PAPERS

January 2019 • Volume 48, Number 1 • Alex Berenson
Alex Berenson Author, Tell Your Children: The Truth About Marijuana, Mental Illness, and Violence

The following is adapted from a speech delivered on January 15, 2019, at Hillsdale College’s Allan P. Kirby, Jr. Center for Constitutional Studies and Citizenship in Washington, D.C.

Seventy miles northwest of New York City is a hospital that looks like a prison, its drab brick buildings wrapped in layers of fencing and barbed wire. This grim facility is called the Mid-Hudson Forensic Psychiatric Institute. It’s one of three places the state of New York sends the criminally mentally ill—defendants judged not guilty by reason of insanity.
Until recently, my wife Jackie—Dr. Jacqueline Berenson—was a senior psychiatrist there. Many of Mid-Hudson’s 300 patients are killers and arsonists. At least one is a cannibal. Most have been diagnosed with psychotic disorders like schizophrenia that provoked them to violence against family members or strangers.
A couple of years ago, Jackie was telling me about a patient. In passing, she said something like, Of course he’d been smoking pot his whole life.
Of course? I said.
Yes, they all smoke.

So marijuana causes schizophrenia?
I was surprised, to say the least. I tended to be a libertarian on drugs. Years before, I’d covered the pharmaceutical industry for The New York Times. I was aware of the claims about marijuana as medicine, and I’d watched the slow spread of legalized cannabis without much interest.
Jackie would have been within her rights to say, I know what I’m talking about, unlike you. Instead she offered something neutral like, I think that’s what the big studies say. You should read them.
So I did. The big studies, the little ones, and all the rest. I read everything I could find. I talked to every psychiatrist and brain scientist who would talk to me. And I soon realized that in all my years as a journalist I had never seen a story where the gap between insider and outsider knowledge was so great, or the stakes so high.

I began to wonder why—with the stocks of cannabis companies soaring and politicians promoting legalization as a low-risk way to raise tax revenue and reduce crime—I had never heard the truth about marijuana, mental illness, and violence.
***
Over the last 30 years, psychiatrists and epidemiologists have turned speculation about marijuana’s dangers into science. Yet over the same period, a shrewd and expensive lobbying campaign has pushed public attitudes about marijuana the other way. And the effects are now becoming apparent.
Almost everything you think you know about the health effects of cannabis, almost everything advocates and the media have told you for a generation, is wrong.
They’ve told you marijuana has many different medical uses. In reality marijuana and THC, its active ingredient, have been shown to work only in a few narrow conditions. They are most commonly prescribed for pain relief. But they are rarely tested against other pain relief drugs like ibuprofen—and in July, a large four-year study of patients with chronic pain in Australia showed cannabis use was associated with greater pain over time.
They’ve told you cannabis can stem opioid use—“Two new studies show how marijuana can help fight the opioid epidemic,” according to Wonkblog, a Washington Post website, in April 2018— and that marijuana’s effects as a painkiller make it a potential substitute for opiates. In reality, like alcohol, marijuana is too weak as a painkiller to work for most people who truly need opiates, such as terminal cancer patients. Even cannabis advocates, like Rob Kampia, the co-founder of the Marijuana Policy Project, acknowledge that they have always viewed medical marijuana laws primarily as a way to protect recreational users.

As for the marijuana-reduces-opiate-use theory, it is based largely on a single paper comparing overdose deaths by state before 2010 to the spread of medical marijuana laws— and the paper’s finding is probably a result of simple geographic coincidence. The opiate epidemic began in Appalachia, while the first states to legalize medical marijuana were in the West. Since 2010, as both the epidemic and medical marijuana laws have spread nationally, the finding has vanished. And the United States, the Western country with the most cannabis use, also has by far the worst problem with opioids.
Research on individual users—a better way to trace cause and effect than looking at aggregate state-level data—consistently shows that marijuana use leads to other drug use. For example, a January 2018 paper in the American Journal of Psychiatry showed that people who used cannabis in 2001 were almost three times as likely to use opiates three years later, even after adjusting for other potential risks.
Most of all, advocates have told you that marijuana is not just safe for people with psychiatric problems like depression, but that it is a potential treatment for those patients. On its website, the cannabis delivery service Eaze offers the “Best Marijuana Strains and Products for Treating Anxiety.” “How Does Cannabis Help Depression?” is the topic of an article on Leafly, the largest cannabis website. But a mountain of peer-reviewed research in top medical journals shows that marijuana can cause or worsen severe mental illness, especially psychosis, the medical term for a break from reality. Teenagers who smoke marijuana regularly are about three times as likely to develop schizophrenia, the most devastating psychotic disorder.

After an exhaustive review, the National Academy of Medicine found in 2017 that “cannabis use is likely to increase the risk of developing schizophrenia and other psychoses; the higher the use, the greater the risk.” Also that “regular cannabis use is likely to increase the risk for developing social anxiety disorder.”
***
Over the past decade, as legalization has spread, patterns of marijuana use—and the drug itself—have changed in dangerous ways.
Legalization has not led to a huge increase in people using the drug casually. About 15 percent of Americans used cannabis at least once in 2017, up from ten percent in 2006, according to a large federal study called the National Survey on Drug Use and Health. (By contrast, about 65 percent of Americans had a drink in the last year.) But the number of Americans who use cannabis heavily is soaring. In 2006, about three million Americans reported using cannabis at least 300 times a year, the standard for daily use. By 2017, that number had nearly tripled, to eight million, approaching the twelve million Americans who drank alcohol every day. Put another way, one in 15 drinkers consumed alcohol daily; about one in five marijuana users used cannabis that often.
Cannabis users today are also consuming a drug that is far more potent than ever before, as measured by the amount of THC—delta-9-tetrahydrocannabinol, the chemical in cannabis responsible for its psychoactive effects—it contains. In the 1970s, the last time this many Americans used cannabis, most marijuana contained less than two percent THC. Today, marijuana routinely contains 20 to 25 percent THC, thanks to sophisticated farming and cloning techniques—as well as to a demand by users for cannabis that produces a stronger high more quickly. In states where cannabis is legal, many users prefer extracts that are nearly pure THC. Think of the difference between near-beer and a martini, or even grain alcohol, to understand the difference.

These new patterns of use have caused problems with the drug to soar. In 2014, people who had diagnosable cannabis use disorder, the medical term for marijuana abuse or addiction, made up about 1.5 percent of Americans. But they accounted for eleven percent of all the psychosis cases in emergency rooms—90,000 cases, 250 a day, triple the number in 2006. In states like Colorado, emergency room physicians have become experts on dealing with cannabis-induced psychosis.
Cannabis advocates often argue that the drug can’t be as neurotoxic as studies suggest, because otherwise Western countries would have seen population-wide increases in psychosis alongside rising use. In reality, accurately tracking psychosis cases is impossible in the United States. The government carefully tracks diseases like cancer with central registries, but no such registry exists for schizophrenia or other severe mental illnesses.

On the other hand, research from Finland and Denmark, two countries that track mental illness more comprehensively, shows a significant increase in psychosis since 2000, following an increase in cannabis use. And in September of last year, a large federal survey found a rise in serious mental illness in the United States as well, especially among young adults, the heaviest users of cannabis.
According to this latter study, 7.5 percent of adults age 18-25 met the criteria for serious mental illness in 2017, double the rate in 2008. What’s especially striking is that adolescents age 12-17 don’t show these increases in cannabis use and severe mental illness.

A caveat: this federal survey doesn’t count individual cases, and it lumps psychosis with other severe mental illness. So it isn’t as accurate as the Finnish or Danish studies. Nor do any of these studies prove that rising cannabis use has caused population-wide increases in psychosis or other mental illness. The most that can be said is that they offer intriguing evidence of a link.
Advocates for people with mental illness do not like discussing the link between schizophrenia and crime. They fear it will stigmatize people with the disease. “Most people with mental illness are not violent,” the National Alliance on Mental Illness (NAMI) explains on its website. But wishing away the link can’t make it disappear. In truth, psychosis is a shockingly high risk factor for violence. The best analysis came in a 2009 paper in PLOS Medicine by Dr.Seena Fazel, an Oxford University psychiatrist and epidemiologist. Drawing on earlier studies, the paper found that people with schizophrenia are five times as likely to commit violent crimes as healthy people, and almost 20 times as likely to commit homicide.

NAMI’s statement that most people with mental illness are not violent is of course accurate, given that “most” simply means “more than half”; but it is deeply misleading. Schizophrenia is rare. But people with the disorder commit an appreciable fraction of all murders, in the range of six to nine percent.
“The best way to deal with the stigma is to reduce the violence,” says Dr. Sheilagh Hodgins, a professor at the University of Montreal who has studied mental illness and violence for more than 30 years.

The marijuana-psychosis-violence connection is even stronger than those figures suggest. People with schizophrenia are only moderately more likely to become violent than healthy people when they are taking antipsychotic medicine and avoiding recreational drugs. But when they use drugs, their risk of violence skyrockets. “You don’t just have an increased risk of one thing—these things occur in clusters,” Dr. Fazel told me.

Along with alcohol, the drug that psychotic patients use more than any other is cannabis: a 2010 review of earlier studies in Schizophrenia Bulletin found that 27 percent of people with schizophrenia had been diagnosed with cannabis use disorder in their lives. And unfortunately—despite its reputation for making users relaxed and calm—cannabis appears to provoke many of them to violence.
A Swiss study of 265 psychotic patients published in Frontiers of Forensic Psychiatry last June found that over a three-year period, young men with psychosis who used cannabis had a 50 percent chance of becoming violent. That risk was four times higher than for those with psychosis who didn’t use, even after adjusting for factors such as alcohol use. Other researchers have produced similar findings. A 2013 paper in an Italian psychiatric journal examined almost 1,600 psychiatric patients in southern Italy and found that cannabis use was associated with a ten-fold increase in violence.

The most obvious way that cannabis fuels violence in psychotic people is through its tendency to cause paranoia—something even cannabis advocates acknowledge the drug can cause. The risk is so obvious that users joke about it and dispensaries advertise certain strains as less likely to induce paranoia. And for people with psychotic disorders, paranoia can fuel extreme violence. A 2007 paper in the Medical Journal of Australia on 88 defendants who had committed homicide during psychotic episodes found that most believed they were in danger from the victim, and almost two-thirds reported misusing cannabis—more than alcohol and amphetamines combined.

Yet the link between marijuana and violence doesn’t appear limited to people with pre-existing psychosis. Researchers have studied alcohol and violence for generations, proving that alcohol is a risk factor for domestic abuse, assault, and even murder. Far less work has been done on marijuana, in part because advocates have stigmatized anyone who raises the issue. But studies showing that marijuana use is a significant risk factor for violence have quietly piled up. Many of them weren’t even designed to catch the link, but they did. Dozens of such studies exist, covering everything from bullying by high school students to fighting among vacationers in Spain.

In most cases, studies find that the risk is at least as significant as with alcohol. A 2012 paper in the Journal of Interpersonal Violence examined a federal survey of more than 9,000 adolescents and found that marijuana use was associated with a doubling of domestic violence; a 2017 paper in Social Psychiatry and Psychiatric Epidemiology examined drivers of violence among 6,000 British and Chinese men and found that drug use—the drug nearly always being cannabis—translated into a five-fold increase in violence.

Today that risk is translating into real-world impacts. Before states legalized recreational cannabis, advocates said that legalization would let police focus on hardened criminals rather than marijuana smokers and thus reduce violent crime. Some advocates go so far as to claim that legalization has reduced violent crime. In a 2017 speech calling for federal legalization, U.S. Senator Cory Booker said that “states [that have legalized marijuana] are seeing decreases in violent crime.” He was wrong.

The first four states to legalize marijuana for recreational use were Colorado and Washington in 2014 and Alaska and Oregon in 2015. Combined, those four states had about 450 murders and 30,300 aggravated assaults in 2013. Last year, they had almost 620 murders and 38,000 aggravated assaults—an increase of 37 percent for murders and 25 percent for aggravated assaults, far greater than the national increase, even after accounting for differences in population growth.

Knowing exactly how much of the increase is related to cannabis is impossible without researching every crime. But police reports, news stories, and arrest warrants suggest a close link in many cases. For example, last September, police in Longmont, Colorado, arrested Daniel Lopez for stabbing his brother Thomas to death as a neighbour watched. Daniel Lopez had been diagnosed with schizophrenia and was “self-medicating” with marijuana, according to an arrest affidavit.

In every state, not just those where marijuana is legal, cases like Lopez’s are far more common than either cannabis or mental illness advocates acknowledge. Cannabis is also associated with a disturbing number of child deaths from abuse and neglect—many more than alcohol, and more than cocaine, methamphetamines, and opioids combined—according to reports from Texas, one of the few states to provide detailed information on drug use by perpetrators.

These crimes rarely receive more than local attention. Psychosis-induced violence takes particularly ugly forms and is frequently directed at helpless family members. The elite national media prefers to ignore the crimes as tabloid fodder. Even police departments, which see this violence up close, have been slow to recognize the trend, in part because the epidemic of opioid overdose deaths has overwhelmed them.
So the black tide of psychosis and the red tide of violence are rising steadily, almost unnoticed, on a slow green wave.
***
For centuries, people worldwide have understood that cannabis causes mental illness and violence—just as they’ve known that opiates cause addiction and overdose. Hard data on the relationship between marijuana and madness dates back 150 years, to British asylum registers in India. Yet 20 years ago, the United States moved to encourage wider use of cannabis and opiates.
In both cases, we decided we could outsmart these drugs—that we could have their benefits without their costs. And in both cases we were wrong. Opiates are riskier, and the overdose deaths they cause a more imminent crisis, so we have focused on those. But soon enough the mental illness and violence that follow cannabis use will also be too widespread to ignore.

Whether to use cannabis, or any drug, is a personal decision. Whether cannabis should be legal is a political issue. But its precise legal status is far less important than making sure that anyone who uses it is aware of its risks. Most cigarette smokers don’t die of lung cancer. But we have made it widely known that cigarettes cause cancer, full stop. Most people who drink and drive don’t have fatal accidents. But we have highlighted the cases of those who do.
We need equally unambiguous and well-funded advertising campaigns on the risks of cannabis. Instead, we are now in the worst of all worlds. Marijuana is legal in some states, illegal in others, dangerously potent, and sold without warnings everywhere.

But before we can do anything, we—especially cannabis advocates and those in the elite media who have for too long credulously accepted their claims—need to come to terms with the truth about the science on marijuana. That adjustment may be painful. But the alternative is far worse, as the patients at Mid-Hudson Forensic Psychiatric Institute—and their victims—know.

Source: Imprimis January 2019 • Volume 48, Number 1

You’re aware America is under siege, fighting an opioid crisis that has exploded into a public-health emergency. You’ve heard of OxyContin, the pain medication to which countless patients have become addicted. But do you know that the company that makes Oxy and reaps the billions of dollars in profits it generates is owned by one family?

The newly installed Sackler Courtyard at London’s Victoria and Albert Museum is one of the most glittering places in the developed world. Eleven thousand white porcelain tiles, inlaid like a shattered backgammon board, cover a surface the size of six tennis courts. According to the V&A;’s director, the regal setting is intended to serve as a “living room for London,” by which he presumably means a living room for Kensington, the museum’s neighborhood, which is among the world’s wealthiest. In late June, Kate Middleton, the Duchess of Cambridge, was summoned to consecrate the courtyard, said to be the earth’s first outdoor space made of porcelain; stepping onto the ceramic expanse, she silently mouthed, “Wow.”

The Sackler Courtyard is the latest addition to an impressive portfolio. There’s the Sackler Wing at New York’s Metropolitan Museum of Art, which houses the majestic Temple of Dendur, a sandstone shrine from ancient Egypt; additional Sackler wings at the Louvre and the Royal Academy; stand-alone Sackler museums at Harvard and Peking Universities; and named Sackler galleries at the Smithsonian, the Serpentine, and Oxford’s Ashmolean. The Guggenheim in New York has a Sackler Center, and the American Museum of Natural History has a Sackler Educational Lab. Members of the family, legendary in museum circles for their pursuit of naming rights, have also underwritten projects of a more modest caliber—a Sackler Staircase at Berlin’s Jewish Museum; a Sackler Escalator at the Tate Modern; a Sackler Crossing in Kew Gardens. A popular species of pink rose is named after a Sackler. So is an asteroid.

The Sackler name is no less prominent among the emerald quads of higher education, where it’s possible to receive degrees from Sackler schools, participate in Sackler colloquiums, take courses from professors with endowed Sackler chairs, and attend annual Sackler lectures on topics such as theoretical astrophysics and human rights. The Sackler Institute for Nutrition Science supports research on obesity and micronutrient deficiencies. Meanwhile, the Sackler institutes at Cornell, Columbia, McGill, Edinburgh, Glasgow, Sussex, and King’s College London tackle psychobiology, with an emphasis on early childhood development.

The Sacklers’ philanthropy differs from that of civic populists like Andrew Carnegie, who built hundreds of libraries in small towns, and Bill Gates, whose foundation ministers to global masses. Instead, the family has donated its fortune to blue-chip brands, braiding the family name into the patronage network of the world’s most prestigious, well-endowed institutions. The Sackler name is everywhere, evoking automatic reverence; the Sacklers themselves, however, are rarely seen.

The descendants of Mortimer and Raymond Sackler, a pair of psychiatrist brothers from Brooklyn, are members of a billionaire clan with homes scattered across Connecticut, London, Utah, Gstaad, the Hamptons, and, especially, New York City. It was not until 2015 that they were noticed by Forbes, which added them to the list of America’s richest families. The magazine pegged their wealth, shared among twenty heirs, at a conservative $14 billion. (Descendants of Arthur Sackler, Mortimer and Raymond’s older brother, split off decades ago and are mere multi-millionaires.) To a remarkable degree, those who share in the billions appear to have abided by an oath of omertà: Never comment publicly on the source of the family’s wealth.

That may be because the greatest part of that $14 billion fortune tallied by Forbes came from OxyContin, the narcotic painkiller regarded by many public-health experts as among the most dangerous products ever sold on a mass scale. Since 1996, when the drug was brought to market by Purdue Pharma, the American branch of the Sacklers’ pharmaceutical empire, more than two hundred thousand people in the United States have died from overdoses of OxyContin and other prescription painkillers. Thousands more have died after starting on a prescription opioid and then switching to a drug with a cheaper street price, such as heroin. Not all of these deaths are related to OxyContin—dozens of other painkillers, including generics, have flooded the market in the past thirty years. Nevertheless, Purdue Pharma was the first to achieve a dominant share of the market for long-acting opioids, accounting for more than half of prescriptions by 2001.

According to the Centers for Disease Control, fifty-three thousand Americans died from opioid overdoses in 2016, more than the thirty-six thousand who died in car crashes in 2015 or the thirty-five thousand who died from gun violence that year. This past July, Donald Trump’s Commission on Combating Drug Addiction and the Opioid Crisis, led by New Jersey governor Chris Christie, declared that opioids were killing roughly 142 Americans each day, a tally vividly described as “September 11th every three weeks.” The epidemic has also exacted a crushing financial toll: According to a study published by the American Public Health Association, using data from 2013—before the epidemic entered its current, more virulent phase—the total economic burden from opioid use stood at about $80 billion, adding together health costs, criminal-justice costs, and GDP loss from drug-dependent Americans leaving the workforce. Tobacco remains, by a significant multiple, the country’s most lethal product, responsible for some 480,000 deaths per year. But although billions have been made from tobacco, cars, and firearms, it’s not clear that any of those enterprises has generated a family fortune from a single product that approaches the Sacklers’ haul from OxyContin.

Even so, hardly anyone associates the Sackler name with their company’s lone blockbuster drug. “The Fords, Hewletts, Packards, Johnsons—all those families put their name on their product because they were proud,” said Keith Humphreys, a professor of psychiatry at Stanford University School of Medicine who has written extensively about the opioid crisis. “The Sacklers have hidden their connection to their product. They don’t call it ‘Sackler Pharma.’ They don’t call their pills ‘Sackler pills.’ And when they’re questioned, they say, ‘Well, it’s a privately held firm, we’re a family, we like to keep our privacy, you understand.’ ”

The family’s leaders have pulled off three of the great marketing triumphs of the modern era: The first is selling OxyContin; the second is promoting the Sackler name; and the third is ensuring that, as far as the public is aware, the first and the second have nothing to do with one another.

To the extent that the Sacklers have cultivated a reputation, it’s for being earnest healers, judicious stewards of scientific progress, and connoisseurs of old and beautiful things. Few are aware that during the crucial period of OxyContin’s development and promotion, Sackler family members actively led Purdue’s day-to-day affairs, filling the majority of its board slots and supplying top executives. By any assessment, the family’s leaders have pulled off three of the great marketing triumphs of the modern era: The first is selling OxyContin; the second is promoting the Sackler name; and the third is ensuring that, as far as the public is aware, the first and the second have nothing to do with one another.


If you head north on I-95 through Stamford, Connecticut, you will spot, on the left, a giant misshapen glass cube. Along the building’s top edge, white lettering spells out ONE STAMFORD FORUM. No markings visible from the highway indicate the presence of the building’s owner and chief occupant, Purdue Pharma.

Originally known as Purdue Frederick, the first iteration of the company was founded in 1892 on New York’s Lower East Side as a peddler of patent medicines. For decades, it sustained itself with sales of Gray’s Glycerine Tonic, a sherry-based liquid of “broad application” marketed as a remedy for everything from anemia to tuberculosis. The company was purchased in 1952 by Arthur Sackler, thirty-nine, and was run by his brothers, Mortimer, thirty- six, and Raymond, thirty-two. The Sackler brothers came from a family of Jewish immigrants in Flatbush, Brooklyn. Arthur was a headstrong and ambitious provider, setting the tone—and often choosing the path—for his younger brothers. After attending medical school on Arthur’s dime, Mortimer and Raymond followed him to jobs at the Creedmoor psychiatric hospital in Queens. There, they coauthored more than one hundred studies on the biochemical roots of mental illness. The brothers’ research was promising—they were among the first to identify a link between psychosis and the hormone cortisone—but their findings were mostly ignored by their professional peers, who, in keeping with the era, favored a Freudian model of mental illness.

Concurrent with his psychiatric work, Arthur Sackler made his name in pharmaceutical advertising, which at the time consisted almost exclusively of pitches from so-called “detail men” who sold drugs to doctors door-to-door. Arthur intuited that print ads in medical journals could have a revolutionary effect on pharmaceutical sales, especially given the excitement surrounding the “miracle drugs” of the 1950s—steroids, antibiotics, antihistamines, and psychotropics. In 1952, the same year that he and his brothers acquired Purdue, Arthur became the first adman to convince The Journal of the American Medical Association, one of the profession’s most august publications, to include a color advertorial brochure.

In the 1960s, Arthur was contracted by Roche to develop an advertising strategy for a new antianxiety medication called Valium. This posed a challenge, because the effects of the medication were nearly indistinguishable from those of Librium, another Roche tranquilizer that was already on the market. Arthur differentiated Valium by audaciously inflating its range of indications. Whereas Librium was sold as a treatment for garden- variety anxiety, Valium was positioned as an elixir for a problem Arthur christened “psychic tension.” According to his ads, psychic tension, the forebear of today’s “stress,” was the secret culprit behind a host of somatic conditions, including heartburn, gastrointestinal issues, insomnia, and restless-leg syndrome. The campaign was such a success that for a time Valium became America’s most widely prescribed medication—the first to reach more than $100 million in sales. Arthur, whose compensation depended on the volume of pills sold, was richly rewarded, and he later became one of the first inductees into the Medical Advertising Hall of Fame.

As Arthur’s fortune grew, he turned his acquisitive instincts to the art market, quickly amassing the world’s largest private collection of ancient Chinese artifacts. According to a memoir by Marietta Lutze, his second wife, collecting, exhibiting, owning, and donating art fed Arthur’s “driving necessity for prestige and recognition.” Rewarding at first, collecting soon became a mania that took over his life. “Boxes of artifacts of tremendous value piled up in numerous storage locations,” she wrote, “there was too much to open, too much to appreciate; some objects known only by a packing list.” Under an avalanche of “ritual bronzes and weapons, mirrors and ceramics, inscribed bones and archaic jades,” their lives were “often in chaos.” “Addiction is a curse,” Lutze noted, “be it drugs, women, or collecting.”

When Arthur donated his art and money to museums, he often imposed onerous terms. According to a memoir written by Thomas Hoving, the Met director from 1967 to 1977, when Arthur established the Sackler Gallery at the Metropolitan Museum of Art to house Chinese antiquities, in 1963, he required the museum to collaborate on a byzantine tax-avoidance maneuver. In accordance with the scheme, the museum first soldArthur a large quantity of ancient artifacts at the deflated 1920s prices for which they had originally been acquired. Arthur then donated back the artifacts at 1960s prices, in the process taking a tax deduction so hefty that it likely exceeded the value of his initial donation. Three years later, in connection with another donation, Arthur negotiated an even more unusual arrangement. This time, the Met opened a secret chamber above the museum’s auditorium to provide Arthur with free storage for some five thousand objects from his private collection, relieving him of the substantial burden of fire protection and other insurance costs. (In an email exchange, Jillian Sackler, Arthur’s third wife, called Hoving’s tax-deduction story “fake news.” She also noted that New York’s attorney general conducted an investigation into Arthur’s dealings with the Met and cleared him of wrongdoing.)

In 1974, when Arthur and his brothers made a large gift to the Met—$3.5 million, to erect the Temple of Dendur—they stipulated that all museum signage, catalog entries, and bulletins referring to objects in the newly opened Sackler Wing had to include the names of all three brothers, each followed by “M.D.” (One museum official quipped, “All that was missing was a note of their office hours.”)

Hoving said that the Met hoped that Arthur would eventually donate his collection to the museum, but over time Arthur grew disgruntled over a series of rankling slights. For one, the Temple of Dendur was being rented out for parties, including a dinner for the designer Valentino, which Arthur called “disgusting.” According to Met chronicler Michael Gross, he was also denied that coveted ticket of arrival, a board seat. (Jillian Sackler said it was Arthur who rejected the board seat, after repeated offers by the museum.) In 1982, in a bad breakup with the Met, Arthur donated the best parts of his collection, plus $4 million, to the Smithsonian in Washington, D. C.


Arthur’s younger brothers, Mortimer and Raymond, looked so much alike that when they worked together at Creedmoor, they fooled the staff by pretending to be one another. Their physical similarities did not extend to their personalities, however. Tage Honore, Purdue’s vice-president of discovery of research from 2000 to 2005, described them as “like day and night.” Mortimer, said Honore, was “extroverted—a ‘world man,’ I would call it.” He acquired a reputation as a big-spending, transatlantic playboy, living most of the year in opulent homes in England, Switzerland, and France. (In 1974, he renounced his U. S. citizenship to become a citizen of Austria, which infuriated his patriotic older brother.) Like Arthur, Mortimer became a major museum donor and married three wives over the course of his life.

Mortimer had his own feuds with the Met. On his seventieth birthday, in 1986, the museum agreed to make the Temple of Dendur available to him for a party but refused to allow him to redecorate the ancient shrine: Together with other improvements, Mortimer and his interior designer, flown in from Europe, had hoped to spiff up the temple by adding extra pillars. Also galling to Mortimer was the sale of naming rights for one of the Sackler Wing’s balconies to a donor from Japan. “They sold it twice,” Mortimer fumed to a reporter from New York magazine. Raymond, the youngest brother, cut a different figure—“a family man,” said Honore. Kind and mild-mannered, he stayed with the same woman his entire life. Lutze concluded that Raymond owed his comparatively serene nature to having missed the worst years of the Depression. “He had summer vacations in camp, which Arthur never had,” she wrote. “The feeling of the two older brothers about the youngest was, ‘Let the kid enjoy himself.’ ”

Raymond led Purdue Frederick as its top executive for several decades, while Mortimer led Napp Pharmaceuticals, the family’s drug company in the UK. (In practice, a family spokesperson said, “the brothers worked closely together leading both companies.”) Arthur, the adman, had no official role in the family’s pharmaceutical operations. According to Barry Meier’s Pain Killer, a prescient account of the rise of OxyContin published in 2003, Raymond and Mortimer bought Arthur’s share in Purdue from his estate for $22.4 million after he died in 1987. In an email exchange, Arthur’s daughter Elizabeth Sackler, a historian of feminist art who sits on the board of the Brooklyn Museum and supports a variety of progressive causes, emphatically distanced her branch of the family from her cousins’ businesses. “Neither I, nor my siblings, nor my children have ever had ownership in or any benefit whatsoever from Purdue Pharma or OxyContin,” she wrote, while also praising “the breadth of my father’s brilliance and important works.” Jillian, Arthur’s widow, said her husband had died too soon: “His enemies have gotten the last word.”


The Sacklers have been millionaires for decades, but their real money—the painkiller money—is of comparatively recent vintage. The vehicle of that fortune was OxyContin, but its engine, the driving power that made them so many billions, was not so much the drug itself as it was Arthur’s original marketing insight, rehabbed for the era of chronic-pain management. That simple but profitable idea was to take a substance with addictive properties—in Arthur’s case, a benzo; in Raymond and Mortimer’s case, an opioid—and market it as a salve for a vast range of indications.

In the years before it swooped into the pain-management business, Purdue had been a small industry player, specializing in over-the-counter remedies like ear-wax remover and laxatives. Its most successful product, acquired in 1966, was Betadine, a powerful antiseptic purchased in industrial quantities by the U. S. government to prevent infection among wounded soldiers in Vietnam. The turning point, according to company lore, came in 1972, when a London doctor working for Cicely Saunders, the Florence Nightingale of the modern hospice movement, approached Napp with the idea of creating a timed-release morphine pill. A long-acting morphine pill, the doctor reasoned, would allow dying cancer patients to sleep through the night without an IV. At the time, treatment with opioids was stigmatized in the United States, owing in part to a heroin epidemic fueled by returning Vietnam veterans. “Opiophobia,” as it came to be called, prevented skittish doctors from treating most patients, including nearly all infants, with strong pain medication of any kind. In hospice care, though, addiction was not a concern: It didn’t matter whether terminal patients became hooked in their final days. Over the course of the seventies, building on a slow-release technology the company had already developed for an asthma medication, Napp created what came to be known as the “Contin” system. In 1981, Napp introduced a timed-release morphine pill in the UK; six years later, Purdue brought the same drug to market in the U. S. as MS Contin.

“The Sacklers have hidden their connection to their product,” said Keith Humphreys, a professor of psychiatry at Stanford University School of Medicine. “They don’t call it ‘Sackler Pharma.’ They don’t call their pills ‘Sackler pills.’”

MS Contin quickly became the gold standard for pain relief in cancer care. At the same time, a number of clinicians associated with the burgeoning chronic-pain movement started advocating the use of powerful opioids for noncancer conditions like back pain and neuropathic pain, afflictions that at their worst could be debilitating. In 1986, two doctors from Memorial Sloan Kettering hospital in New York published a fateful article in a medical journal that purported to show, based on a study of thirty-eight patients, that long-term opioid treatment was safe and effective so long as patients had no history of drug abuse. Soon enough, opioid advocates dredged up a letter to the editor published in The New England Journal of Medicine in 1980 that suggested, based on a highly unrepresentative cohort, that the risk of addiction from long-term opioid use was less than 1 percent. Though ultimately disavowed by its author, the letter ended up getting cited in medical journals more than six hundred times.

As the country was reexamining pain, Raymond’s eldest son, Richard Sackler, was searching for new applications for Purdue’s timed-release Contin system. “At all the meetings, that was a constant source of discussion—‘What else can we use the Contin system for?’ ” said Peter Lacouture, a senior director of clinical research at Purdue from 1991 to 2001. “And that’s where Richard would fire some ideas—maybe antibiotics, maybe chemotherapy—he was always out there digging.” Richard’s spitballing wasn’t idle blather. A trained physician, he treasured his role as a research scientist and appeared as an inventor on dozens of the company’s patents (though not on the patents for OxyContin). In the tradition of his uncle Arthur, Richard was also fascinated by sales messaging. “He was very interested in the commercial side and also very interested in marketing approaches,” said Sally Allen Riddle, Purdue’s former executive director for product management. “He didn’t always wait for the research results.” (A Purdue spokesperson said that Richard “always considered relevant scientific information when making decisions.”)

Perhaps the most private member of a generally secretive family, Richard appears nowhere on Purdue’s website. From public records and conversations with former employees, though, a rough portrait emerges of a testy eccentric with ardent, relentless ambitions. Born in 1945, he holds degrees from Columbia University and NYU Medical School. According to a bio on the website of the Koch Institute for Integrative Cancer Research at MIT, where Richard serves on the advisory board, he started working at Purdue as his father’s assistant at age twenty-six before eventually leading the firm’s R&D; division and, separately, its sales and marketing division. In 1999, while Mortimer and Raymond remained Purdue’s co-CEOs, Richard joined them at the top of the company as president, a position he relinquished in 2003 to become cochairman of the board. The few publicly available pictures of him are generic and sphinxlike—a white guy with a receding hairline. He is one of the few Sacklers to consistently smile for the camera. In a photo on what appears to be his Facebook profile, Richard is wearing a tan suit and a pink tie, his right hand casually scrunched into his pocket, projecting a jaunty charm. Divorced in 2013, he lists his relationship status on the profile as “It’s complicated.”

When Purdue eventually pleaded guilty to felony charges in 2007 for criminally “misbranding” OxyContin, it acknowledged exploiting doctors’ misconceptions about oxycodone’s strength.

Richard’s political contributions have gone mostly to Republicans—including Strom Thurmond and Herman Cain—though at times he has also given to Democrats. (His ex-wife, Beth Sackler, has given almost exclusively to Democrats.) In 2008, he wrote a letter to the editor of The Wall Street Journaldenouncing Muslim support for suicide bombing, a concern that seems to persist: Since 2014, his charitable organization, the Richard and Beth Sackler Foundation, has donated to several anti-Muslim groups, including three organizations classified as hate groups by the Southern Poverty Law Center. (The family spokesperson said, “It was never Richard Sackler’s intention to donate to an anti-Muslim or hate group.”) The foundation has also donated to True the Vote, the “voter-fraud watchdog” that was the original source for Donald Trump’s inaccurate claim that three million illegal immigrants voted in the 2016 election.

Former employees describe Richard as a man with an unnerving intelligence, alternately detached and pouncing. In meetings, his face was often glued to his laptop. “This was pre-smartphone days,” said Riddle. “He’d be typing away and you would think he wasn’t even listening, and then all of the sudden his head would pop up and he’d be asking a very pointed question.” He was notorious for peppering subordinates with unexpected, rapid-fire queries, sometimes in the middle of the night. “Richard had the mind of someone who’s going two hundred miles an hour,” said Lacouture. “He could be a little bit disconnected in the way he would communicate. Whether it was on the weekend or a holiday or a Christmas party, you could always expect the unexpected.”

Richard also had an appetite for micromanagement. “I remember one time he mailed out a rambling sales bulletin,” said Shelby Sherman, a Purdue sales rep from 1974 to 1998. “And right in the middle, he put in, ‘If you’re reading this, then you must call my secretary at this number and give her this secret password.’ He wanted to check and see if the reps were reading this shit. We called it ‘Playin’ Passwords.’ ” According to Sherman, Richard started taking a more prominent role in the company during the early 1980s. “The shift was abrupt,” he said. “Raymond was just so nice and down-to-earth and calm and gentle.” When Richard came, “things got a lot harder. Richard really wanted Purdue to be big—I mean really big.”

To effectively capitalize on the chronic-pain movement, Purdue knew it needed to move beyond MS Contin. “Morphine had a stigma,” said Riddle. “People hear the word and say, ‘Wait a minute, I’m not dying or anything.’ ” Aside from its terminal aura, MS Contin had a further handicap: Its patent was set to expire in the late nineties. In a 1990 memo addressed to Richard and other executives, Purdue’s VP of clinical research, Robert Kaiko, suggested that the company work on a pill containing oxycodone, a chemical similar to morphine that was also derived from the opium poppy. When it came to branding, oxycodone had a key advantage: Although it was 50 percent stronger than morphine, many doctors believed—wrongly—that it was substantially less powerful. They were deceived about its potency in part because oxycodone was widely known as one of the active ingredients in Percocet, a relatively weak opioid- acetaminophen combination that doctors often prescribed for painful injuries. “It really didn’t have the same connotation that morphine did in people’s minds,” said Riddle.

A common malapropism led to further advantage for Purdue. “Some people would call it oxy-codeine” instead of oxycodone, recalled Lacouture. “Codeine is very weak.” When Purdue eventually pleaded guilty to felony charges in 2007 for criminally “misbranding” OxyContin, it acknowledged exploiting doctors’ misconceptions about oxycodone’s strength. In court documents, the company said it was “well aware of the incorrect view held by many physicians that oxycodone was weaker than morphine” and “did not want to do anything ‘to make physicians think that oxycodone was stronger or equal to morphine’ or to ‘take any steps . . . that would affect the unique position that OxyContin’ ” held among physicians.

Purdue did not merely neglect to clear up confusion about the strength of OxyContin. As the company later admitted, it misleadingly promoted OxyContin as less addictive than older opioids on the market. In this deception, Purdue had a big assist from the FDA, which allowed the company to include an astonishing labeling claim in OxyContin’s package insert: “Delayed absorption, as provided by OxyContin tablets, is believed to reduce the abuse liability of a drug.”

The theory was that addicts would shy away from timed-released drugs, preferring an immediate rush. In practice, OxyContin, which crammed a huge amount of pure narcotic into a single pill, became a lusted-after target for addicts, who quickly discovered that the timed-release mechanism in OxyContin was easy to circumvent—you could simply crush a pill and snort it to get most of the narcotic payload in a single inhalation. This wasn’t exactly news to the manufacturer: OxyContin’s own packaging warned that consuming broken pills would thwart the timed-release system and subject patients to a potentially fatal overdose. MS Contin had contended with similar vulnerabilities, and as a result commanded a hefty premium on the street. But the “reduced abuse liability” claim that added wings to the sales of OxyContin had not been approved for MS Contin. It was removed from OxyContin in 2001 and would never be approved again for any other opioid.

The year after OxyContin’s release, Curtis Wright, the FDA examiner who approved the pharmaceutical’s original application, quit. After a stint at another pharmaceutical company, he began working for Purdue. In an interview with Esquire, Wright defended his work at the FDA and at Purdue. “At the time, it was believed that extended-release formulations were intrinsically less abusable,” he insisted. “It came as a rather big shock to everybody—the government and Purdue—that people found ways to grind up, chew up, snort, dissolve, and inject the pills.” Preventing abuse, he said, had to be balanced against providing relief to chronic-pain sufferers. “In the mid-nineties,” he recalled, “the very best pain specialists told the medical community they were not prescribing opioids enough. That was not something generated by Purdue—that was not a secret plan, that was not a plot, that was not a clever marketing ploy. Chronic pain is horrible. In the right circumstances, opioid therapy is nothing short of miraculous; you give people their lives back.” In Wright’s account, the Sacklers were not just great employers, they were great people. “No company in the history of pharmaceuticals,” he said, “has worked harder to try to prevent abuse of their product than Purdue.”


Purdue did not invent the chronic-pain movement, but it used that movement to engineer a crucial shift. Wright is correct that in the nineties patients suffering from chronic pain often received inadequate treatment. But the call for clinical reforms also became a flexible alibi for overly aggressive prescribing practices. By the end of the decade, clinical proponents of opioid treatment, supported by millions in funding from Purdue and other pharmaceutical companies, had organized themselves into advocacy groups with names like the American Pain Society and the American Academy of Pain Medicine. (Purdue also launched its own group, called Partners Against Pain.) As the decade wore on, these organizations, which critics have characterized as front groups for the pharmaceutical industry, began pressuring health regulators to make pain “the fifth vital sign”—a number, measured on a subjective ten-point scale, to be asked and recorded at every doctor’s visit. As an internal strategy document put it, Purdue’s ambition was to “attach an emotional aspect to noncancer pain” so that doctors would feel pressure to “treat it more seriously and aggressively.” The company rebranded pain relief as a sacred right: a universal narcotic entitlement available not only to the terminally ill but to every American.

The company rebranded pain relief as a sacred right: a universal narcotic entitlement available not only to the terminally ill but to every American. By 2001, annual OxyContin sales had surged past $1 billion.

OxyContin’s sales started out small in 1996, in part because Purdue first focused on the cancer market to gain formulary acceptance from HMOs and state Medicaid programs. Over the next several years, though, the company doubled its sales force to six hundred—equal to the total number of DEA diversion agents employed to combat the sale of prescription drugs on the black market—and began targeting general practitioners, dentists, OB/GYNs, physician assistants, nurses, and residents. By 2001, annual OxyContin sales had surged past $1 billion. Sales reps were encouraged to downplay addiction risks. “It was sell, sell, sell,” recalled Sherman. “We were directed to lie. Why mince words about it? Greed took hold and overruled everything. They saw that potential for billions of dollars and just went after it.” Flush with cash, Purdue pioneered a high-cost promotion strategy, effectively providing kickbacks—which were legal under American law—to each part of the distribution chain. Wholesalers got rebates in exchange for keeping OxyContin off prior authorization lists. Pharmacists got refunds on their initial orders. Patients got coupons for thirty- day starter supplies. Academics got grants. Medical journals got millions in advertising. Senators and members of Congress on key committees got donations from Purdue and from members of the Sackler family.

It was doctors, though, who received the most attention. “We used to fly doctors to these ‘seminars,’ ” said Sherman, which were, in practice, “just golf trips to Pebble Beach. It was graft.” Though offering perks and freebies to doctors was hardly uncommon in the industry, it was unprecedented in the marketing of a Schedule II narcotic. For some physicians, the junkets to sunny locales weren’t enough to persuade them to prescribe. To entice the holdouts—a group the company referred to internally as “problem doctors”—the reps would dangle the lure of Purdue’s lucrative speakers’ bureau. “Everybody was automatically approved,” said Sherman. “We would set up these little dinners, and they’d make their little fifteen-minute talk, and they’d get $500.”

Between 1996 and 2001, the number of OxyContin prescriptions in the United States surged from about three hundred thousand to nearly six million, and reports of abuse started to bubble up in places like West Virginia, Florida, and Maine. (Research would later show a direct correlation between prescription volume in an area and rates of abuse and overdose.) Hundreds of doctors were eventually arrested for running pill mills. According to an investigation in the Los Angeles Times, even though Purdue kept an internal list of doctors it suspected of criminal diversion, it didn’t volunteer this information to law enforcement until years later.

As criticism of OxyContin mounted through the aughts, Purdue responded with symbolic concessions while retaining its volume-driven business model. To prevent addicts from forging prescriptions, the company gave doctors tamper-resistant prescription pads; to mollify pharmacists worried about robberies, Purdue offered to replace, free of charge, any stolen drugs; to gather data on drug abuse and diversion, the company launched a national monitoring program called RADARS.

Critics were not impressed. In a letter to Richard Sackler in July 2001, Richard Blumenthal, then Connecticut’s attorney general and now a U. S. senator, called the company’s efforts “cosmetic.” As Blumenthal had deduced, the root problem of the prescription-opioid epidemic was the high volume of prescriptions written for powerful opioids. “It is time for Purdue Pharma to change its practices,” Blumenthal warned Richard, “not just its public-relations strategy.”

It wasn’t just that doctors were writing huge numbers of prescriptions; it was also that the prescriptions were often for extraordinarily high doses. A single dose of Percocet contains between 2.5 and 10mg of oxycodone. OxyContin came in 10-, 20-, 30-, 40-, and 80mg formulations and, for a time, even 160mg. Purdue’s greatest competitive advantage in dominating the pain market, it had determined early on, was that OxyContin lasted twelve hours, enough to sleep through the night. But for many patients, the drug lasted only six or eight hours, creating a cycle of crash and euphoria that one academic called “a perfect recipe for addiction.” When confronted with complaints about “breakthrough pain”—meaning that the pills weren’t working as long as advertised—Purdue’s sales reps were given strict instructions to tell doctors to strengthen the dose rather than increase dosing frequency.

Sales reps were encouraged to downplay addiction risks. “It was sell, sell, sell,” recalled Sherman. “We were directed to lie. Why mince words about it?”

Over the next several years, dozens of class-action lawsuits were brought against Purdue. Many were dismissed, but in some cases Purdue wrote big checks to avoid going to trial. Several plaintiffs’ lawyers found that the company was willing to go to great lengths to prevent Richard Sackler from having to testify under oath. “They didn’t want him deposed, I can tell you that much,” recalled Marvin Masters, a lawyer who brought a class-action suit against Purdue in the early 2000s in West Virginia. “They were willing to sit down and settle the case to keep from doing that.” Purdue tried to get Richard removed from the suit, but when that didn’t work, the company settled with the plaintiffs for more than $20 million. Paul Hanly, a New York class-action lawyer who won a large settlement from Purdue in 2007, had a similar recollection. “We were attempting to take Richard Sackler’s deposition,” he said, “around the time that they agreed to a settlement.” (A spokesperson for the company said, “Purdue did not settle any cases to avoid the deposition of Dr. Richard Sackler, or any other individual.”)

When the federal government finally stepped in, in 2007, it extracted historic terms of surrender from the company. Purdue pleaded guilty to felony charges, admitting that it had lied to doctors about OxyContin’s abuse potential. (The technical charge was “misbranding a drug with intent to defraud or mislead.”) Under the agreement, the company paid $600 million in fines and its three top executives at the time—its medical director, general counsel, and Richard’s successor as president—pleaded guilty to misdemeanor charges. The executives paid $34.5 million out of their own pockets and performed four hundred hours of community service. It was one of the harshest penalties ever imposed on a pharmaceutical company. (In a statement to Esquire, Purdue said that it “abides by the highest ethical standards and legal requirements.” The statement went on: “We want physicians to use their professional judgment, and we were not trying to pressure them.”)

Fifty-three thousand Americans died from opioid overdoses in 2016, more than the thirty-six thousand who died in car crashes in 2015 or the thirty-five thousand who died from gun violence that year.

No Sacklers were named in the 2007 suit. Indeed, the Sackler name appeared nowhere in the plea agreement, even though Richard had been one of the company’s top executives during most of the period covered by the settlement. He did eventually have to give a deposition in 2015, in a case brought by Kentucky’s attorney general. Richard’s testimony—the only known record of a Sackler speaking about the crisis the family’s company helped create—was promptly sealed. (In 2016, STAT, an online magazine owned by Boston Globe Media that covers health and medicine, asked a court in Kentucky to unseal the deposition, which is said to have lasted several hours. STAT won a lower-court ruling in May 2016. As of press time, the matter was before an appeals court.)

In 2010, Purdue executed a breathtaking pivot: Embracing the arguments critics had been making for years about OxyContin’s susceptibility to abuse, the company released a new formulation of the medication that was harder to snort or inject. Purdue seized the occasion to rebrand itself as an industry leader in abuse-deterrent technology. The change of heart coincided with two developments: First, an increasing number of addicts, unable to afford OxyContin’s high street price, were turning to cheaper alternatives like heroin; second, OxyContin was nearing the end of its patents. Purdue suddenly argued that the drug it had been selling for nearly fifteen years was so prone to abuse that generic manufacturers should not be allowed to copy it.

On April 16, 2013, the day some of the key patents for OxyContin were scheduled to expire, the FDA followed Purdue’s lead, declaring that no generic versions of the original OxyContin formulation could be sold. The company had effectively won several additional years of patent protection for its golden goose.


Opioid withdrawal, which causes aches, vomiting, and restless anxiety, is a gruesome process to experience as an adult. It’s considerably worse for the twenty thousand or so American babies who emerge each year from opioid-soaked wombs. These infants, suddenly cut off from their supply, cry uncontrollably. Their skin is mottled. They cannot fall asleep. Their bodies are shaken by tremors and, in the worst cases, seizures. Bottles of milk leave them distraught, because they cannot maneuver their lips with enough precision to create suction. Treatment comes in the form of drops of morphine pushed from a syringe into the babies’ mouths. Weaning sometimes takes a week but can last as long as twelve. It’s a heartrending, expensive process, typically carried out in the neonatal ICU, where newborns have limited access to their mothers.

But the children of OxyContin, its heirs and legatees, are many and various. The second- and third-generation descendants of Raymond and Mortimer Sackler spend their money in the ways we have come to expect from the not-so-idle rich. Notably, several have made children a focus of their business and philanthropic endeavors. One Sackler heir helped start an iPhone app called RedRover, which generates ideas for child-friendly activities for urban parents; another runs a child- development center near Central Park; another is a donor to charter-school causes, as well as an investor in an education start-up called AltSchool. Yet another is the founder of Beespace, an “incubator for emerging nonprofits,” which provides resources and mentoring for initiatives like the Malala Fund, which invests in education programs for women in the developing world, and Yoga Foster, whose objective is to bring “accessible, sustainable yoga programs into schools across the country.” Other Sackler heirs get to do the fun stuff: One helps finance small, interesting films like The Witch; a second married a famous cricket player; a third is a sound artist; a fourth started a production company with Boyd Holbrook, star of the Netflix series Narcos; a fifth founded a small chain of gastropubs in New York called the Smith.

Holding fast to family tradition, Raymond’s and Mortimer’s heirs declined to be interviewed for this article. Instead, through a spokesperson, they put forward two decorated academics who have been on the receiving end of the family’s largesse: Phillip Sharp, the Nobel-prize-winning MIT geneticist, and Herbert Pardes, formerly the dean of faculty at Columbia University’s medical school and CEO of New York-Presbyterian Hospital. Both men effusively praised the Sacklers’ donations to the arts and sciences, marveling at their loyalty to academic excellence. “Once you were on that exalted list of philanthropic projects,” Pardes told Esquire, “you were there and you were in a position to secure additional philanthropy. It was like a family acquisition.” Pardes called the Sacklers “the nicest, most gentle people you could imagine.” As for the family’s connection to OxyContin, he said that it had never come up as an issue in the faculty lounge or the hospital break room. “I have never heard one inch about that,” he said.

Pardes’s ostrichlike avoidance is not unusual. In 2008, Raymond and his wife donated an undisclosed amount to Yale to start the Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences. Lynne Regan, its current director, told me that neither students nor faculty have ever brought up the OxyContin connection. “Most people don’t know about that,” she said. “I think people are mainly oblivious.” A spokesperson for the university added, “Yale does not vet donors for controversies that may or may not arise.”

In May, a dozen lawmakers in Congress sent a bipartisan letter to the World Health Organization warning that Sackler-owned companies were preparing to flood foreign countries with legal narcotics.

The controversy surrounding OxyContin shows little sign of receding. In 2016, the CDC issued a startling warning: There was no good evidence that opioids were an effective treatment for chronic pain beyond six weeks. There was, on the other hand, an abundance of evidence that long-term treatment with opioids had harmful effects. (A recent paper by Princeton economist Alan Krueger suggests that chronic opioid use may account for more than 20 percent of the decline in American labor-force participation from 1999 to 2015.) Millions of opioid prescriptions for chronic pain had been written in the preceding two decades, and the CDC was calling into question whether many of them should have been written at all. At least twenty-five government entities, ranging from states to small cities, have recently filed lawsuits against Purdue to recover damages associated with the opioid epidemic.

The Sacklers, though, will likely emerge untouched: Because of a sweeping non-prosecution agreement negotiated during the 2007 settlement, most new criminal litigation against Purdue can only address activity that occurred after that date. Neither Richard nor any other family members have occupied an executive position at the company since 2003.

The American market for OxyContin is dwindling. According to Purdue, prescriptions fell 33 percent between 2012 and 2016. But while the company’s primary product may be in eclipse in the United States, international markets for pain medications are expanding. According to an investigation last year in the Los Angeles Times, Mundipharma, the Sackler-owned company charged with developing new markets, is employing a suite of familiar tactics in countries like Mexico, Brazil, and China to stoke concern for as-yet-unheralded “silent epidemics” of untreated pain. In Colombia, according to the L.A. Times, the company went so far as to circulate a press release suggesting that 47 percent of the population suffered from chronic pain.

Napp is the family’s drug company in the UK. Mundipharma is their company charged with developing new markets.

In May, a dozen lawmakers in Congress, inspired by the L.A. Timesinvestigation, sent a bipartisan letter to the World Health Organization warning that Sackler-owned companies were preparing to flood foreign countries with legal narcotics. “Purdue began the opioid crisis that has devastated American communities,” the letter reads. “Today, Mundipharma is using many of the same deceptive and reckless practices to sell OxyContin abroad.” Significantly, the letter calls out the Sackler family by name, leaving no room for the public to wonder about the identities of the people who stood behind Mundipharma.

The final assessment of the Sacklers’ global impact will take years to work out. In some places, though, they have already left their mark. In July, Raymond, the last remaining of the original Sackler brothers, died at ninety-seven. Over the years, he had won a British knighthood, been made an Officer of France’s Légion d’Honneur, and received one of the highest possible honors from the royal house of the Netherlands. One of his final accolades came in June 2013, when Anthony Monaco, the president of Tufts University, traveled to Purdue Pharma’s headquarters in Stamford to bestow an honorary doctorate. The Sacklers had made a number of transformational donations to the university over the years—endowing, among other things, the Sackler School of Graduate Biomedical Sciences. At Tufts, as at most schools, honorary degrees are traditionally awarded on campus during commencement, but in consideration of Raymond’s advanced age, Monaco trekked to Purdue for a special ceremony. The audience that day was limited to family members, select university officials, and a scrum of employees. Addressing the crowd of intimates, Monaco praised his benefactor. “It would be impossible to calculate how many lives you have saved, how many scientific fields you have redefined, and how many new physicians, scientists, mathematicians, and engineers are doing important work as a result of your entrepreneurial spirit.” He concluded, “You are a world changer.”

Source: https://www.esquire.com/news-politics/a12775932/sackler-family-oxycontin/ October 2017

For those who are still concerned about ‘evidence based science’ and ‘best medical and pharmaceutical practice’…the following ‘open letter’ with attachments was sent to all Federal Senators, NSW and Victorian Premiers last week. 

Dear Senator,
 
In the coming weeks/months, you will no doubt be presented with a Bill to consider changing both law and process to permit a new version of ‘medical marijuana’. On behalf of our Institute and a concerned public I would like you to carefully consider the following.

Firstly I write with some concerns about the consultation conducted on behalf of Victorian State government by the VLRC in Melbourne on May 6th this year and the now subsequent recommendations that have emerged from this very small Melbourne meeting (Less than 60 people in attendance! – This issue was directly raised with Victorian Health Minister earlier this year).

Whilst we gleaned from radio interviews with VLRC representatives prior to the consultation that the public discussions on the potential introduction of a new form ‘medical marijuana’ (different to existing medicinal forms of cannabis derived pharmaceuticals already in the Australian market) were not for changing laws to suit a particular agenda. It was instead implied that the purpose was to look at potential redundancies that might hinder best practice.  It was to be, for all intents and purposes an unbiased mechanism to: glean evidence, perspectives, opinions and ideas from the general public for consideration in the higher and more important discussion of wise, evidence based, best healthcare practice before making any move on the release of another version of therapeutic cannabis.

Conversely, our affiliate/colleagues experience of the very small Melbourne consultation did not reflect any of the above expectation. Rather those of our affiliates who attended observed the following:

  1. A seemingly deliberately emotively charged atmosphere, in favour of getting cannabis legalised for medical purposes. The tone seemed to be set to that end from the outset.
  2. The meeting was facilitated by representatives of the VLRC who appeared to have a bias toward the legalisation of ‘medical marijuana’ in manner that suited the self-medicating option, regardless of evidence based science.
  3. When attempts were made to present evidence contrary to the seemingly predetermined agenda of these facilitators, they were either quickly shut down (if they dared to speak in the first place) or continually ignored; apparently, dissenting opinions were not welcome. Whilst at the same time, proponents for ‘self-medication’ use of cannabis were given complete and unfettered access to the floor, producing statements such as:“Many, many people have been cured – from just about anything and everything.”
    “What would you rather have – infertility or 35 seizures a day?”
    “Random workplace drug testing is wrong.”Not only are these statements (now on record) outrageous, they are also utterly unsubstantiated by any legitimate clinical trial. This very small contingent of pro-cannabis lobbyists were permitted to simply spruik anecdotes with no evidence based presentation yet also had their evidenced-deprived opinions affirmed and validated by the facilitators.
  4. The facilitators appeared to infer that the Government (of Victoria, at least) already has legislation in place with this current ‘consultation’ process simply in play to validate those changes and therefore it is in essence a forgone conclusion. There was also a strong indication that either the A.M.A. or T.G.A. recommendations or processes would be ignored and negated wherever possible by simple legal changes.

Senator, it is a concern that if this particular experience of ours was repeated in other consultations with the same consensus manufacturing agenda, then this consultative process is a travesty.

If a government negates not only good evidence based science, but also established protective, best practice medical processes to enable a legal rite of passage for self-medication, it is placing itself at an extremely high risk of litigation. Future law-suits are likely, from the ‘victims’ of self-medicating regimes who will cite the changes in law that were NOT based on proper clinical trial or TGA and AMA recommendations and protocols.  When emotionally charged vitriol combines with vote chasing and misguided sympathies, it is the recipients of these untested substances that will be the final casualties – especially children! Compassion and wisdom dictate that all fair and democratic processes be engaged to maximise help and minimise harm, especially to children who will be the ones at greatest risk of an ill-advised self-medicating regime.

Senator, for purposes of clarification about the possible national legalisation of ‘another’ route/process/protocol for medicines are you able to confirm or deny that:

  1. The representations by the facilitators at the Melbourne consultation are in fact reflective of the pre-ordained intent of the public consultation documented above in not only Victoria, but other States and Territories?
  2. If not, will a review of the practice/method/behaviours be made into this particular process and subsequently the clearly questionable recommendations that have emerged from such narrow, non-evidence based and seemingly biased processes?
  3. A fair and proper representation of all views on this matter be gleaned from these meetings/consultations and interpreted and represented fairly without prejudice?
  4. A.M.A. and T.G.A. processes and protocols for best practice on medicines will be upheld and engaged, or simply ignored and by-passed?

Finally Senator, it is of grave concern that a pattern seems to be emerging from this ‘populist’ process, that best practice, evidence based protocols may simply be ignored and by passed.  If this is indeed the plan and the use of VLRC type agencies is the vehicle to do so, then the following must be raised.

The Dalgarno Institute ask:

  • Do you want your government and your ministerial role to be linked with a poorly considered and non-evidenced based process that enables a self-medicating policy – particularly for the ones the State has greatest responsibility to protect – the children?
  • Will your government and ministerial role be the ones who in so ignoring proper clinical processes facilitate a quasi-health regime that will precipitate immediate and long term unwanted side effects that can then be later subject to litigation and class-actions?
  • If an unqualified and unproven self-medicating mechanism is sanctioned and approved by government, and the inevitable damage (particularly to children) emerges, will the taxpayers of Australia have to fund the damages of an ill-conceived and non-TGA/AMA approved medical practice? Or will there be iron-clad caveats in place that ensure those who chose to use their own version of ‘medicine’ be the only ones liable for the outcomes of it, and not place further healthcare and monetary burden on the vast majority of tax-payers who have sought to follow best evidence-based and prescriptive practices?
  • If proper clinical trials and T.G.A and A.M.A. processes and protocols are negated or circumvented and a ‘new’ or ‘alternative’ process for registering, manufacturing, prescribing and dispensing marijuana as medicine be put in place, then how will you/your government  address the following important questions.
    • Who will be ‘growing’ and preparing this ‘medicine’?
    • Who will monitor content and quality of ‘medicine’?
    • Who will determine dosage rates and quantities?
    • What mechanisms will be in place to ensure quality control is followed?
    • What mechanisms will be in place to ensure, movement, dispensing and use of this ‘medicine’ is done without risk to non-patients?
    • Who will be able to prescribe this ‘medicine’ – Doctors, pharmacists, naturopaths, nurses, and counsellors? Who will monitor this process and ensure total safety?
    • What community safe-guards will be in place to ensure this new ‘medicine’ will not be misused?
    • Will the ‘medicine’ come in edible or smoked form and what safeguards will be in play around such a ‘medicine delivery’ system?
    • Will there be advertising and public promotion of this new form of ‘medicine’? Will that be strictly monitored to ensure no misinformation will mislead the public?
    • Which government department will oversee this process and how many more new protocols, processes, staff and finance will be required to set up this new vehicle for ‘medicine’ identification and management?
    • Who will be paying for this new and added cost?

We at Dalgarno Institute and its growing coalition remain very concerned for the overwhelming majority of Australians who are being kept in the dark about this new and illegitimate push to change evidence based processes and the laws that ensure those processes are protected. We are looking to you, in your role, to ensure that there is a genuine and robust pursuit of best medical and health practice outcomes for all Australians, particularly the most vulnerable – the young, very sick and disadvantaged – and that any mechanism that seeks to undermine that platform not be permitted to emerge under any circumstance.  Science and best health practice, NOT lawyers should determine pharmaceutical best practice.

I have also attached just a very small sample of the volumes of evidence-based data currently in the scientific space that raise clear warnings about a ‘new’ and untested version of cannabis as medicine. Please avail yourself of them and consult the people who do know better, compassion and good government demands it.
We look forward to receiving your response.

Sincerely Yours, 

Shane Varcoe
Executive Director
Dalgarno Institute

You can read our compassionate policy stance on M.M titled ‘CANNABIS AS MEDICINE? CAUTION NEEDED’!

https://dalgarnoinstitute.org.au/index.php/advocacy/dalgarno-aod-policy/86-open-letter-to-all-australian-politicians-regarding-new-version-of-medicinal-cannabis

Source: Email from Dalgarno Institute

September 2017

Thomas M. Nappe, DO* and Christopher O. Hoyte, MD

Abstract

Since marijuana legalization, pediatric exposures to cannabis have increased. To date, pediatric deaths from cannabis exposure have not been reported. The authors report an 11-month-old male who, following cannabis exposure, presented with central nervous system depression after seizure, and progressed to cardiac arrest and died. Myocarditis was diagnosed post-mortem and cannabis exposure was confirmed.

Given the temporal relationship of these two rare occurrences – cannabis exposure and sudden death secondary to myocarditis in an 11-month-old – as well as histological consistency with drug-induced myocarditis without confirmed alternate causes, and prior reported cases of cannabis-associated myocarditis, a possible relationship exists between cannabis exposure in this child and myocarditis leading to death. In areas where marijuana is commercially available or decriminalized, the authors urge clinicians to preventively counsel parents and to include cannabis exposure in the differential diagnosis of patients presenting with myocarditis.

INTRODUCTION

Since marijuana legalization, pediatric exposures to cannabis have increased, resulting in increased pediatric emergency department (ED) visits. Neurologic toxicity is most common after pediatric exposure; however, gastrointestinal and cardiopulmonary toxicity are reported. According to a retrospective review of 986 pediatric cannabis ingestions from 2005 to 2011, pediatric exposure has been specifically linked to a multitude of symptoms including, but not limited to, drowsiness, lethargy, irritability, seizures, nausea and vomiting, respiratory depression, bradycardia and hypotension.Prognosis is often reassuring. 

Specific myocardial complications related to cannabis toxicity that are well documented in adolescence through older adulthood include acute coronary syndrome, cardiomyopathy, myocarditis, pericarditis, dysrhythmias and cardiac arrest. To date, there are no reported pediatric deaths from myocarditis after confirmed, recent cannabis exposure. The authors report an 11-month-old male who, following cannabis exposure, presented in cardiac arrest after seizure and died. Myocarditis was diagnosed post-mortem and cannabis exposure was confirmed. Analyses of serum cannabis metabolites, post-mortem infectious testing, cardiac histopathology, as well as clinical course, support a potential link between the cannabis exposure and myocarditis that would justify preventive parental counseling and consideration of urine drug screening in this reported setting.

CASE REPORT

An 11-month-old male with no known past medical history presented to the ED with central nervous system (CNS) depression and then went into cardiac arrest. The patient was lethargic for two hours after awakening that morning and then had a seizure. During the prior 24–48 hours, he was irritable with decreased activity and was later retching. He was noted to be healthy before developing these symptoms. Upon arrival in the ED, he was unresponsive with no gag reflex. Vital signs were temperature 36.1° Celsius, heart rate 156 beats per minute, respiratory rate 8 breaths per minute, oxygen saturation 80% on room air.

Physical exam revealed a well-nourished, 20.5 lb., 11-month-old male, with normal development, no trauma, normal oropharynx, normal tympanic membranes, no lymphadenopathy, tachycardia, clear lungs, normal abdomen and Glasgow Coma Scale rating of 4. He was intubated for significant CNS depression and required no medications for induction or paralysis. Post-intubation chest radiograph is shown in Image 2. He subsequently became bradycardic with a heart rate in the 40s with a wide complex rhythm. Initial electrocardiogram (ECG) was performed and is shown in Image 1.

He then became pulseless, and cardiopulmonary resuscitation was initiated. Laboratory analysis revealed sodium 136 mmol/L, potassium 7.7 mmol/L, chloride 115 mmol/L, bicarbonate 8.0 mmol/L, blood urea nitrogen 24 mg/dL, creatinine 0.9 mg/dL, and glucose 175 mg/dL Venous blood gas pH was 6.77. An ECG was repeated (Image 3). He received intravenous fluid resuscitation, sodium bicarbonate infusion, calcium chloride, insulin, glucose, ceftriaxone and four doses of epinephrine. Resuscitation continued for approximately one hour but the patient ultimately died.

Initial electrocardiogram demonstrating wide-complex tachycardia.

Post-intubation chest radiograph. Measurement indicates distance of endotracheal tube tip above carina.

Repeat electrocardiogram showing disorganized rhythm, peri-arrest.

Further laboratory findings in the ED included a complete blood count (CBC) with differential, liver function tests (LFTs), one blood culture and toxicology screen. CBC demonstrated white blood cell count 13.8 K/mcL with absolute neutrophil count of 2.5 K/mcL and absolute lymphocyte count of 10.7 K/mcL, hemoglobin 10.0 gm/dL, hematocrit 34.7%, and platelet count 321 K/mcL. LFTs showed total bilirubin 0.6 mg/dL, aspartate aminotransferase 77 IU/L, and alanine transferase 97 IU/U. A single blood culture from the right external jugular vein revealed aerobic gram-positive rods that were reported two days later as Bacillus species (not Bacillus anthracis). Toxicology screening revealed urine enzyme-linked immunosorbent assay positive for tetrahydrocannabinol-carboxylic acid (THC-COOH) and undetectable serum acetaminophen and salicylate concentrations. Route and timing of exposure to cannabis were unknown.

Autopsy revealed a non-dilated heart with normal coronary arteries. Microscopic examination showed a severe, diffuse, primarily lymphocytic myocarditis, with a mixed cellular infiltrate in some areas consisting of histiocytes, plasma cells, and eosinophils. Myocyte necrosis was also observed. There was no evidence of concomitant bacterial or viral infection based on post-mortem cultures obtained from cardiac and peripheral blood, lung pleura, nasopharynx and cerebrospinal fluid. Post-mortem cardiac blood analysis confirmed the presence of Δ-9-carboxy-tetrahydrocannabinol (Δ-9-carboxy-THC) at a concentration of 7.8 ng/mL. Additional history disclosed an unstable motel-living situation and parental admission of drug possession, including cannabis.

DISCUSSION

As of this writing, this is the first reported pediatric death associated with cannabis exposure. Given the existing relationship between cannabis and cardiovascular (CV) toxicity, as well as the temporal progression of events, post-mortem analysis, and previously reported cases of cannabis-induced myocarditis, the authors propose a relationship between cannabis exposure in this patient and myocarditis, leading to cardiac arrest and ultimately death. This occurrence should justify consideration of urine drug screening for cannabis in pediatric patients presenting with myocarditis of unknown etiology in areas where cannabis is widely used. In addition, parents should be counseled regarding measures to prevent such exposures.

The progressive clinical presentation of this patient during the prior 24–48 hours, including symptoms of somnolence, lethargy, irritability, nausea, seizure and respiratory depression are consistent with previously documented, known complications of recent cannabis exposure in the pediatric population. It is well known that common CV effects of cannabis exposure include tachycardia and decreased vascular resistance with acute use and bradycardia in more chronic use. These effects are believed to be multifactorial, and evidence suggests that cannabinoid effect on the autonomic nervous system, peripheral vasculature, cardiac microvasculature, and myocardial tissue and Purkinje fibers are all likely contributory. The pathogenesis of myocarditis is not fully understood. In general, myocarditis results from direct damage to myocytes from an offending agent such as a virus, or in this case, potentially a toxin. The resulting cellular injury leads to a local inflammatory response. Destruction of cardiac tissue may result in myocyte necrosis and arrhythmogenic activity, or cellular remodeling in chronic myocarditis.

Autopsy findings in this patient were consistent with noninfectious myocarditis as a cause of death. The histological findings of myocyte necrosis with mature lymphocytic mixed cellular infiltrate are consistent with drug-induced, toxic myocarditis.The presence of THC metabolites in the patient’s urine and serum, most likely secondary to ingestion, is the only uncovered risk factor in the etiology for his myocarditis. This is highly unlikely attributable to passive exposure.

It is difficult to extrapolate a specific time of cannabis ingestion given the unknown dose of THC, the individual variability of metabolism and excretion, as well as the lack of data on this topic in the pediatric population and post-mortem redistribution (PMR) kinetics. However, the THC metabolite detected in the patient’s blood, Δ-9-carboxy-THC, is known to peak in less than six hours and be detectable for at least a day, while the parent compound, tetrahydrocannabinol (THC), is expected to rapidly metabolize and distribute much more quickly, being potentially undetectable six hours after exposure in an infrequent user. 

The parent compound was below threshold for detection in this patient’s blood. In addition, if cannabis ingestion occurred the day of presentation, it would have been more likely that THC would have been detected with its metabolite after PMR. Given this information, the authors deduce that cannabis consumption occurred within the recent two to six days, assuming this was a single, acute high-potency ingestion. This time frame would overlap with the patient’s symptomatology and allow time for the development of myocarditis, thus supporting cannabis as the etiology.

The link between cannabis use and myocarditis has been documented in multiple teenagers and young adults. In 2008 Leontiadis reported a 16-year-old with severe heart failure requiring a left ventricular assist device, associated with biopsy-diagnosed myocarditis.The authors attributed the heart failure to cannabis use of unknown chronicity. In 2014 Rodríguez-Castro reported a 29-year-old male who had two episodes of myopericarditis several months apart.Each episode occurred within two days of smoking cannabis.In 2016, Tournebize reported a 15-year-old male diagnosed with myocarditis, clinically and by cardiac magnetic resonance imaging, after initiating regular cannabis use eight months earlier. There were no other causes for myocarditis, including infectious, uncovered by these authors, and no adulterants were identified in these patients’ consumed marijuana.Unlike our patient, all three of these previously reported patients recovered.

In the age of legalized marijuana, children are at increased risk of exposure, mainly through ingestion of food products, or “edibles.”These products are attractive in appearance and have very high concentrations of THC, which can make small exposures exceptionally more toxic in small children.

Limitations in this report include the case study design, the limitations on interpreting an exact time, dose and route of cannabis exposure, the specificity of histopathology being used to classify etiology of myocarditis, and inconsistent blood culture results. The inconsistency in blood culture results also raises concern of a contributing bacterial etiology in the development of myocarditis, lending to the possibility that cannabis may have potentially induced the fatal symptomatology in an already-developing silent myocarditis. However, due to high contaminant rates associated with bacillus species and negative subsequent blood cultures, the authors believe this was more likely a contaminant. In addition, the patient had no source of infection on exam or recent history and was afebrile without leukocytosis. All of his subsequent cultures from multiple sites were negative.

CONCLUSION

Of all the previously reported cases of cannabis-induced myocarditis, patients were previously healthy and no evidence was found for other etiologies. All of the prior reported cases were associated with full recovery. In this reported case, however, the patient died after myocarditis-associated cardiac arrest. Given two rare occurrences with a clear temporal relationship – the recent exposure to cannabis and the myocarditis-associated cardiac arrest – we believe there exists a plausible relationship that justifies further research into cannabis-associated cardiotoxicity and related practice adjustments. In states where cannabis is legalized, it is important that physicians not only counsel parents on preventing exposure to cannabis, but to also consider cannabis toxicity in unexplained pediatric myocarditis and cardiac deaths as a basis for urine drug screening in this setting.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965161/ March 2017

The medical marijuana market is in a downward spiral as businesses, lured by big money, shift to recreational

At the height of the medical marijuana industry there were 420 dispensaries in Oregon. Now there are only eight.

In 2015, Erich Berkovitz opened his medical marijuana processing company, PharmEx, with the intention of getting sick people their medicine. His passion stemmed from his own illness. Berkovitz has Tourette syndrome, which triggers ticks in his shoulder that causes chronic pain. Cannabis takes that away.

Yet in the rapidly changing marijuana landscape, PharmEx is now one of three medical-only processors left in the entire state of Oregon.

On the retail end, it’s also grim. At the height of the medical marijuana industry in 2016, there were 420 dispensaries in Oregon available to medical cardholders. Today, only eight are left standing and only one of these medical dispensaries carries Berkovitz’s products.

Ironically, Oregon’s medical marijuana market has been on a downward spiral since the state legalized cannabis for recreational use in 2014. The option of making big money inspired many medical businesses to go recreational, dramatically shifting the focus away from patients to consumers. In 2015, the Oregon Liquor Control Commission (OLCC) took over the recreational industry. Between 2016 and 2018, nine bills were passed that expanded consumer access to marijuana while changing regulatory procedures on growing, processing and packaging.

In the shuffle, recreational marijuana turned into a million-dollar industry in Oregon, while the personalized patient-grower network of the medical program quietly dried up.

Now, sick people are suffering.

“For those patients that would need their medicine in an area that’s opted out of recreational sales, and they don’t have a grower or they’re not growing on their own, it does present a real access issue for those individuals,” said André Ourso, an administrator for the Center for Health Protection at the Oregon Health Authority. The woes of the Oregon Medical Marijuana Program (OMMP) were outlined in a recently published report by the Oregon Health Authority. The analysis found the program suffers from “insufficient and inaccurate reporting and tracking,” “inspections that did not keep pace with applications”, and “insufficient funding and staffing”.

Operating outside of Salem, Oregon, PharmEx primarily makes extracts – a solid or liquid form of concentrated cannabinoids. Through his OMMP-licensed supply chain, he gets his high dose medicine to people who suffer from cancer, Crohn’s, HIV and other autoimmune diseases. Many are end-of-life patients.

These days, most recreational dispensaries sell both consumer and medical products, which are tax-free for cardholders. The problem for Berkovitz is that he’s only medically licensed. This means recreational dispensaries can’t carry his exacts. Legally, they can

only sell products from companies with an OLCC license. Since issuing almost 1,900 licenses, the OLCC has paused on accepting new applications until further notice.

Limits on THC – a powerful active ingredient in cannabis products – are also an issue, according to Berkovitz. With the dawn of recreational dispensaries, the Oregon Health Authority began regulating THC content. A medical edible, typically in the form of a sweet treat, is now capped at 100mg THC, which Berkovitz says is not enough for a really sick person.

“If you need two 3000mg a day orally and you’re capped at a 100mg candy bar, that means you need 20 candy bars, which cost $20 a pop,” he said. “So you’re spending $400 a day to eat 20 candy bars.”

“The dispensaries never worked for high dose patients, even in the medical program,” continued Berkovitz. “What worked was people who grew their own and were able to legally process it themselves, or go to a processor who did it at a reasonable rate.”

But with increased processing and testing costs, and a decrease on the number of plants a medical grower can produce, patients are likely to seek cannabis products in a more shadowy place – the black market.

“All the people that we made these laws for – the ones who are desperately ill – are being screwed right now and are directed to the black market,” said Karla Kay, the chief of operations at PharmEx.

Kay, who also holds a medical marijuana card for her kidney disease, said some patients she knows have resorted to buying high dose medical marijuana products illegally from local farmers markets – in a state that was one of the first to legally establish a medical cannabis industry back in 1998.

Moreover, the networks between medical patients, growers and processors have diminished.

The OMMP maintains a record of processors and the few remaining dispensaries, but no published list of patients or grow sites – a privacy right protected under Oregon law, much to the chagrin of law enforcement.

According to the Oregon Health Authority’s report, just 58 of more than 20,000 medical growers were inspected last year.

In eastern Oregon’s Deschutes county, the sheriff’s office and the district attorney have repeatedly requested the location of each medical marijuana grower in their county. They’ve been consistently denied by the Oregon Health Authority.

Recently, the sheriff has gone as far as hiring a detective to focus solely on enforcing marijuana operations.

“There is an overproduction of marijuana in Oregon and the state doesn’t have adequate resources to enforce the laws when it comes to recreational marijuana, medical marijuana, as well as ensuring the growth of hemp is within the THC guidelines,” said the Deschutes sheriff, Shane Nelson. As of last February, the state database logged 1.1m pounds of cannabis flower, as reported by the Willamette Week in April. That’s three times what residents buy in a year, which means the excess is slipping out of the regulated market. To help curb the trend, senate bill 1544 was passed this year to funnel part of the state’s marijuana tax revenues into the Criminal Justice Commission and provide the funding needed to go after the black market, especially when it comes to illicit Oregon weed being smuggled to other states. The program’s priority is “placed on rural areas with lots of production and diversion, and little law enforcement”, said Rob Bovett, the legal counsel with the Association of Oregon Counties, who crafted the bill.

In a May 2018 memo on his marijuana enforcement priorities, Billy J Williams, a US attorney for the district of Oregon, noted that “since broader legalization took effect in 2015, large quantities of marijuana from Oregon have been seized in 30 states, most of which continue to prohibit marijuana.”

As of 1 July, however, all medical growers that produce plants for three or more patients – about 2,000 growers in Oregon – must track their marijuana from seed-to-sale using the OLCC’s Cannabis Tracking System.

Berkovitz, however, is looking to cut out the middle man (namely dispensaries) to keep PharmEx afloat. “The only way the patients are going to have large, high doses of medicine is if we revive the patient-grower networks. They need to communicate with each other. No one’s going to get rich, but everybody involved will get clean medicine from the people they trust at a more affordable rate.”

Source: https://www.theguardian.com/society/2018/jul/31/oregon-cannabis-medical-marijuana-problems-sick-people

There are several principal pathways to inheritable genotoxicity, mutagenicity and teratogenes is induced by cannabis which are known and well established at this time including the following.
These three papers discuss different aspects of these effects.

1) Stops Brain Waves and Thinking The brain has both stimulatory and inhibitory pathways.  GABA is the main brain inhibitory pathway. Brain centres talk to each other on gamma (about 40 cycles/sec) and theta frequencies (about 5 cycles/sec), where the theta waves are  used as the carrier waves for the gamma wave which then interacts like harmonics in music.
The degree to which the waves are in and out of phase carries information which can be  monitored externally. GABA (γ-aminobutyric acid) inhibition is key to the generation of the synchronized firing which underpins these various brain oscillations. These GABA transmissions are controlled presynaptically by type 1 cannabinoid receptors (CB1R’s) and CB1R stimulation shuts them down. This is why cannabis users forget and fall asleep.

2) Blocks GABA Pathway and Brain Formation GABA is also a key neurotransmitter in  brain formation in that it guides and direct neural stem cell formation and transmission and development and growth of the cerebral cortex and other major brain areas. Gamma and theta  brain waves also direct neural stem cell formation, sculpting and connectivity.

Derangements then of GABA physiology imply that the brain will not form properly. Thin frontal cortical  plate measurements have been shown in humans prenatally exposed to cannabis by fMRI.
This implies that their brains can never be structurally normal which then explains the long  lasting and persistent defects identified into adulthood.

3) Epigenetic Damage DNA not only carries the genetic hardware of our genetic code but it also carries the software of the code which works like traffic lights along the sequence of DNA bases to direct when to switch the genes on and off. This is known as the “epigenetic code”.

Fetal alcohol syndrome is believed to be due to damage to the software epigenetic code. The long lasting intellectual, mood regulation, attention and concentration defects which have been described after in utero cannabis exposure in the primary, middle and high schools and as college age young adults are likely due to these defects. Epigenetics “sets in stone” the errors of brain structure made in (2) above.

4) Arterial Damage. Cannabis has a well described effect to damage arteries through (CB1R’s) (American Heart Association 2007) which they carry in high concentration (Nature Reviews Cardiology 2018). In adults this causes heart attack (500% elevation in the first hour after smoking), stroke, severe cardiac arrhythmias including sudden cardiac death; but in developing babies CB1R’s acting on the developing heart tissues can lead to at least six major cardiac defects (Atrial- ventricular- and mixed atrio-ventricular and septal defects, Tetralogy of Fallot, Epstein’s deformity amongst others), whilst constriction of various babies’ arteries can lead to serious side effects such as gastroschisis (bowels hanging out) and possibly absent limbs (in at least one series).

5) Disruption of Mitotic Spindle. When cells divide the separating chromosomes actually slide along “train tracks” which are long chains made of tubulin. The tubulin chains are called “microtubules” and the whole football-shaped structure is called a “mitotic spindle”. Cannabis inhibits tubulin formation, disrupting microtubules and the mitotic spindle causing the separating chromosomes to become cut off in tiny micronuclei, where they eventually become smashed up and pulverized into “genetic junk”, which leads to foetal malformations, cancer and cell death. High rates of Down’s syndrome, chromosomal anomalies and cancers in cannabis exposed babies provide clinical evidence of this.

6) Defective Energy Generation & Downstream DNA Damage DNA is the crown jewel of the cell and its most complex molecule. Maintaining it in good repair is a very energy intensive process. Without energy DNA cannot be properly maintained. Cannabis has been known to reduce cellular energy production by the cell’s power plants, mitochondria, for many decades now. This has now been firmly linked with increased DNA damage, cancer formation and aging of the cells and indeed the whole organism. As it is known to occur in eggs and sperm, this will also damage the quality of the germ cells which go into forming the baby and lead directly to damaged babies and babies lost and wasted through spontaneous miscarriage and therapeutic termination for severe deformities.

7) Cancer induction Cannabis causes 12 cancers and has been identified as a carcinogen by the California Environmental Protection agency (2009). This makes it also a mutagen. 4 of these cancers are inheritable to children; i.e. inheritable carcinogenicity and mutagenicity. All four studies in testicular cancer are strongly positive (elevation by three fold). Carcinogen = mutagen = teratogen.

8) Colorado’s Teratology Profile. From the above described teratological profile we would expect exactly the profile of congenital defects which have been identified in Colorado (higher total defects and heart defects, and chromosomal defects) and Ottawa in Canada (long lasting and persistent brain damage seen on both functional testing and fMRI brain scans in children exposed in utero) where cannabis use has become common.

Gastroschisis was shown to be higher in all seven studies looking at this; and including in Canada, carefully controlled studies. Moreover in Australia, Canada, North Carolina, Colorado, Mexico and New Zealand, gastroschisis and sometimes other major congenital defects cluster where cannabis use is highest. Colorado 2000-2013 has experienced an extra 20,152 severely abnormal births above the rates prior to cannabis liberalization which if applied to the whole USA would equate to more than 83,000 abnormal babies live born annually (and probably about that number again therapeutically aborted); actually much more since both the number of users and concentration of cannabis have risen sharply since 2013, and cannabis has been well proven to be much more severely genotoxic at higher doses.

9) Cannabidiol is also Genotoxic and tests positive in many genotoxicity assays, just as tetrahydrocannabinol does.

10) Births defects registry data needs to be open and transparent and public. At present it is not. This looks too much like a cover up.

Source: Email from Dr Stuart Reece to Drug Watch International members May 2018

Eleonora Patsenker, Ph.D. and Felix Stickel, M.D., Ph.D.

Mounting evidence indicates that the endocannabinoid (EC) system (ECS) plays an important role in various liver diseases including viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, hepatic encephalopathy, and autoimmune hepatitis. The ECS also impacts on involved processes such as hepatic hemodynamics, nutrient intake and turnover, and ischemia/reperfusion (I/R) after liver transplantation. Although this involvement is undisputed, therapeutic implications regarding the ECS are just beginning to emerge; so far, no approved drug
acting specifically on the ECS is available.

Source: https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/cld.527 2016

 

 

Source:

http://www.pnas.org/content/109/40/E2657

July 2012

By William Ross Perlman, Ph.D., CMPP, NIDA Notes Contributing Writer

This research:

  • Identified a gene variant that promotes impulsive behavior and enhanced responses to heroin in rats.
  • Linked the corresponding human gene variant to increased risk for impulsivity and drug use.

People who are highly impulsive and those diagnosed with ADHD are at increased risk for substance use disorders (SUD). Recent research implicates a variant of the gene for a protein called cAMP-response element modulator (CREM) in these associations. Drs. Michael L. Miller and Yasmin L. Hurd from the Icahn School of Medicine at Mount Sinai in New York, with colleagues from several other institutions, showed that the gene variant promotes impulsive and hyperactive behavior in both animals and humans, and can contribute to a person’s risk for developing SUD.

Of Rats…

The Icahn researchers began their investigations with a strain of rats that exhibit impulsive behaviors resembling human attention-deficit/hyperactivity disorder (ADHD). Initial experiments confirmed that, compared with a strain (Western Kyoto) of rats that are not known for impulsivity, these “spontaneously hypertensive” (SH) rats:

  • Were more impatient to receive rewards, fidgeted more while waiting to receive rewards, ran around more, and were more attracted to novel experiences.
  • Self-administered more heroin and, when it was made unavailable, gave up seeking it less readily.  
  • Had enhanced elevation of dopamine levels in response to heroin.

The researchers screened the rats’ DNA for genetic differences that might contribute to these behavioral differences. The results revealed that the two strains carried different variants of the gene for CREM. As a result, the SH rats had lower concentrations of CREM in the core of the nucleus accumbens—a key brain region governing reward and movement.

…And People

 

Figure 1. A CREM Gene Variant Increases HyperactivityHyperactivity scores were higher in ADHD subjects than in control subjects. In addition, ADHD subjects who carried at least one copy of the less highly expressed A variant (i.e., with the G/A or A/A CREM genotype) reported significantly higher hyperactivity than did those carrying only the more highly expressed G variant (i.e., with the G/G genotype). Genotype had no effect on hyperactivity in non-ADHD control subjects

The researchers used genetic and behavioral evidence from previous studies conducted by other researchers to demonstrate that the corresponding variant in the human CREM gene similarly predisposes people to impulsivity. This variant occupies approximately the same position on the human gene that the rodent variant occupies on the rodent gene. At this site, known as rs12765063, the CREM gene exists in two versions—called A and G—and the A variant dials down CREM production. In one study, preschool children with the A variant were found to be more distractible and to engage in more dangerous activities than peers with only the G variant (Figure 1). In another, among adolescents with ADHD, those who carried the A variant reported more symptomatic hyperactivity than those who did not.

The researchers further found that by promoting impulsivity, the variant raises the risk of drug use. Thus, in two studies of adolescents, neither the A variant alone nor ADHD alone increased the risk for drug use, but the two together did. The first analysis looked at adolescents with ADHD, and found higher rates of drug use among those with the A variant than among those with only the G variant. The second analysis looked at adolescents who had the A variant of rs12765063 and histories of childhood ADHD. It found that those whose childhood ADHD still persisted reported more use of alcohol, tobacco, marijuana, and prescription stimulants than those who had outgrown their ADHD (Figure 2). Moreover, those who no longer had ADHD reported no more drug use than a comparison group who did not carry the A variant.

 

Figure 2. The A Variant of the CREM Gene Is Associated With Increased Drug Use in People With Persistent ADHD Among a cohort whose childhood ADHD persisted through adolescence, those with the CREM A variant reported more drug use than those with only the G variant. Genotype was not linked to risk for drug use in people without ADHD (i.e., those who never had ADHD or those with remitted ADHD).

A Key to Prevention and Treatment?

Dr. Hurd suggests that CREM may be a key link between impulsivity and vulnerability to addiction. Understanding these relationships may help identify new ways of treating or preventing SUD. The protein is known to regulate multiple gene networks and their biological functions, and to influence the growth of structures that neurons use to communicate with each other.

Dr. Hurd says, “These results highlight that CREM is a mediating factor between impulsivity and substance abuse vulnerability. It brings attention to CREM in the nucleus accumbens as a regulator of impulsive action and structural plasticity.”

The study was supported by NIH grants DA015446, DA030359, DA006470, DA038954, DA031559, and DA007135.

Source: https://www.drugabuse.gov/news-events/nida-notes/2018/06/gene-links-impulsivity-drug-use-vulnerability June 2018

Introduction by Theodore M. Pinkert, M.D., J.D.

The study of the consequences of maternal drug abuse represents one of the most compelling areas of research in the drug abuse field. The potential victims of this problem have no say in the maternal behaviors, which may place them at risk. Therefore, it is incumbent upon the research community to attempt to delineate the potential hazards to the fetus, the newborn, the infant, and the child, so that deficits may be identified in sufficient time to compensate, where possible, with specific treatment interventions.

The purpose of this volume is to focus attention on recent studies of the effects of maternal substance abuse on offspring. The material presented includes reviews of animal data, as well as the results of large interdisciplinary clinical studies, which were originally presented on September 24th and 25th, 1984, at a National Institute on Drug Abuse Technical Review sponsored by the Divisions of Preclinical and Clinical Research. (The papers presented in the preclinical portion of this meeting will be published in a separate volume, entitled Prenatal Drug Exposure: Kinetics and Dynamics.)

     In the opening chapter of this monograph, Dr. Donald Hutchings defines the field of study known as behavioral teratology and provides a conceptual and historical framework that facilitates an understanding of what inferences may reasonably be drawn from both the animal and clinical literature. His studies in behavioral teratology integrate developmental toxicology and teratology with developmental psychology and focus on a variety of neurobehavioral changes that are crucial to the development and maturation of the individual.

The next chapter, by Dr. Ernest Abel, elaborates on the difficulties inherent in attempting to understand the interactive nature of the maternal and fetoplacental units. Through a careful review of his own work, and that of others, he provides important insights into the limitations and strengths of both epidemiological and clinical studies. He also points out the value of animal studies in providing the methodological rigor necessary (in combination with the human studies) to establish the most convincing demonstration of causality when adverse pregnancy outcomes are suspected from one or more chemical agents. Then he reviews the effects of marijuana (A5—THC) on pregnant animals and their offspring and discusses both the results and the methodological pitfalls to be avoided in these studies.

     In the following chapter, Dr. Nancy Day and her colleagues analyze the problems faced by clinical researchers in obtaining reliable and valid results using the instruments and techniques currently employed in prenatal research. The two major challenges identified are: (1) When questionnaire formats are used, do subjects understand the questions and report accurately? and (2) How does one obtain accurate measures of complex and changing events (substance abuse patterns) for specific time periods which coincide with different stages of fetal vulnerability, so that the prediction of biological effects can be made with a high degree of probability?

In the same chapter, the authors suggest techniques for eliciting accurate patterns of maternal drug intake and describe how these techniques are implemented in their current research on the effects of maternal marijuana and alcohol use during pregnancy. The value of the assessment instruments they have developed is that they measure both the quantity and frequency of drug intake in a manner that more closely resembles the way subjects naturally organize their own memory of substance use——in terms of both language and sequence. The authors also elaborate other techniques which are designed to overcome accuracy problems created either by the patient’s deliberate misrepresentation of past drug intake or by their flawed recall of remote events. These techniques include the bogus pipeline, which attempts to overcome misrepresentation of drug use, and the breakdown of prepregnancy and first trimester events into specific time intervals to aid in more accurate recall of the quantity and frequency of drug use.

     The next chapter, by Katherine Tennes and colleagues, describes the results of a large clinical study on the effects of prenatal marijuana exposure. Participating women responded to structured questionnaires about themselves, their habits (substance abuse, nutritional, etc.), and the habits of the father, if known. After delivery, infants were examined for birth measurements, physical anomalies, and muscle tone, and the Brazelton Neonatal Behavioral Assessment Scale was administered. At 1 year of age, the infant’s physical parameters were reexamined and they were evaluated on the Bayley Infant Scale of Mental and Motor Development and Behavior Checklist. One finding of this study is that maternal marijuana use decreased from previous levels of consumption as the pregnancy advanced. At delivery, no significant differences in 12 indices of obstetrical complications were detected that could not be attributed to parity, or to the amount of pain—relieving medication administered (although users of marijuana required more pain—relieving medication than nonusers). Heavy marijuana use was found to be associated with an increase in male over female offspring, but with a decrease in infant length at birth. No increase in teratogenicity, or decrease in APGAR or Brazelton scores, was associated with prenatal marijuana use. No significant differences were detected in physical measurements or Bayley scores at 1 year. The authors point out that some of their outcome data are in disagreement with previous clinical studies, and they explore possible reasons for the difference in results. In addition, the authors caution that studies examining the effects of maternal marijuana use on more complex cognitive functioning in offspring have yet to be performed.

     In the next chapter, Dr. Peter Fried reports on another major clinical study of maternal marijuana use, but in a population with significantly different demographics than the previous study. Among his findings were that gestation was shortened by maternal marijuana use and that there were neurobehavioral effects, as measured by altered visual responses and changes in state regulation (heightened tremors and startles), in the newborn. Although not yet completed, studies employing neuro- opthalmological and electrophysiological testing suggested that prenatal exposure to marijuana might delay maturation of the visual system. In agreement with the Tennes study, there were no differences in rates of miscarriage, obstetrical complications. APGAR scores, or teratological effects between the marijuana—using population and the comparison group. (Studies of both animal and human populations which suggest different results are presented and discussed.)

In addition, data collected from developmental tests administered to the infants at 6—month intervals after birth failed to discriminate infants of marijuana—using mothers from either matched controls or the general population. Dr. Fried cautions that it is not at all clear whether neurological findings present at birth are transient, or compensated for by maturation. He suggests the possibility that the tests currently used to measure developmental neurological disturbances in the newborn and neonate may not have
sufficient discriminatory sensitivity to detect subtle differences that may remain in the older, marijuana—exposed infant or child.

     In the next chapter, Drs. Rosen and Johnson review their findings on the prenatal effects and postnatal consequences to the offspring of methadone—maintained mothers. Their results include analyses of methadone’s effects upon the neonatal and infant periods of development, and they present recent data from their oldest cohorts of children, who are now in the 4— to 7—year—old age range. Among the effects on offspring of methadone—maintained mothers was a higher incidence of small—for—gestational—age infants, and infants below the third percentile in head circumference.

In addition, the maternal methadone dose and the length of time on methadone had a positive correlation with a higher incidence of obstetrical complications, decreased birth weight, and decreased infant performance on certain Brazelton measures. Neurological and developmental testing continued to reveal significant differences between methadone—exposed children and a comparison group through the 36—month evaluations. These differences included an increased incidence of abnormal reflexes, nystagmus, infections, abnormal muscle tone, and delayed developmental milestones among the methadone—exposed infants. As the children reached school age, those who did poorly neuro— developmentally at earlier evaluations continued to do poorly. A trend toward lower scores in receptive language evaluations was evident among the methadone—exposed children.

Their neurological evaluations demonstrated a higher prevalence of abnormalities of fine and gross motor coordination, poor balance, decreased attention span, hyperactivity, and speech and language delays. There was also a higher incidence of referrals for behavioral and academic problems. However, as the comparison group of children (a population selected from women in a low socioeconomic status similar to that of the methadone—maintained mothers) approached school age, they too began to show poor performance in testing. This raises important questions about the interaction between prenatal environments and the socioeconomic status of the child in the postnatal environment.

     In the following chapter, Dr. Ira Chasnoff compares the effects on offspring of the maternal use of narcotic versus nonnarcotic substances. Unique in this group of reports, his study is an attempt to distinguish the in utero effects of narcotic use (methadone and pentazocine/tripelennamine groups), from non— narcotic drug use (including a small group of women whose primary drug of abuse was phencyclidine EPCPJ, and another group with mixed sedative/hypnotic exposure, including marijuana). Although the number of subjects in each group was small, infants exposed in utero to narcotic substances showed fairly consistent decreases in birth weight, length, and head circumference from both the sedative/hypnotic group and the comparison group.

The methadone—exposed group of neonates also demonstrated deficits in auditory orientation and motor maturity. Infants exposed to both narcotic and nonnarcotic drugs showed decrements in state regulation, and infants exposed to PCP showed increased state liability and poor consolability when compared to all other drug—exposed groups. As was manifested in the preceding Rosen and Johnson material, the scores of the comparison group of infants began to fall away from the normal range toward that of the drug—exposed infants by 24 months of age.

     In the last chapter, Dr. Barry Zuckerman reviews the developmental consequences of maternal drug use. He describes the features compatible with the fetal alcohol syndrome and discusses research which suggests that these features may reflect a final common pathway of numerous agents (Including drugs of abuse), rather than a specific teratogenic effect of alcohol.

In addition, the author stresses the importance to developmental outcome studies of repeated assessments over time, and he suggests the application of newer physiologic techniques such as evoked responses, Brain Electrical Activity Mapping (BEAM),
Positron Emission Tomography (PET Scan), and Nuclear Magnetic Resonance (NMR), to enhance our understanding of the effects of prenatal drug exposure.

     In summary, much remains to be learned about the specific developmental effects of a variety of commonly used and abused drugs. The research community has not yet exhausted the potential for the development and application of new testing techniques and Instruments that will help us to identify the scope of subtle cognitive and motor effects caused by prenatal drug exposure.

Beyond these refinements lies the possibility of understanding the particular mechanisms through which these drugs exert their effects. It is the hope of those who participated in the conference that what lies herein will stimulate research into the many unanswered questions In this area.

Source and link to full articles:

https://archives.drugabuse.gov/sites/default/files/monograph59_0.pdf

Introduction by Cora Lee Wetherington, Vincent L. Smeriglio, and Loretta P. Finnegan

For several years the use of drugs during pregnancy, particularly cocaine, has been a major public health issue because of the concern about possible adverse behavioral effects on the neonate and the developing child. While many popular press publications have warned of the severe adverse effects of prenatal drug exposure, the scientific literature has been less clear on this issue, in part because of complex methodological issues that confront research in this field.
    On July 12 and 13, 1993, the National Institute on Drug Abuse conducted a technical review at which researchers reviewed the state of the art regarding behavioral assessments of offspring prenatally exposed to abused drugs. Presenters identified and addressed the complex methodological issues that abound in both human and animal studies designed to assess behavioral effects of prenatal drug exposure, and they stressed the caveats involved in drawing causal conclusions from associations between maternal drug abuse and adverse behavioral outcomes in the offspring. This research monograph is based upon revisions of presentations made at that technical review. The fundamental aim of this research monograph is to clarify the methodological issues for future research in this field, to provide caution in the interpretation of research findings, and to suggest future research directions.

Link to source and full articles:

https://archives.drugabuse.gov/sites/default/files/monograph164_0.pdf  1996

PHE publications gateway number: 2016490 December 2016

Executive summary

Alcohol is a prominent commodity in the UK marketplace. It is widely used in numerous social situations. For many, alcohol is associated with positive aspects of life; however, there are currently over 10 million people drinking at levels which increase their risk of health harm. Among those aged 15 to 49 in England, alcohol is now the leading risk factor for ill-health, early mortality and disability and the fifth leading risk factor for ill health across all age groups. Since 1980, sales of alcohol in England and Wales have increased by 42%, from roughly 400 million litres in the early 1980s, with a peak at 567 million litres in 2008, and a subsequent decline.

This growth has been driven by increased consumption among women, a shift to higher strength products, and increasing affordability of alcohol, particularly through the 1980s and 1990s. Over this period, the way in which alcohol is sold and consumed also changed. In 2016 there were 210,000 license premises in England and Wales, a 4% increase on 2010. There has been a shift in drinking location such that most alcohol is now bought from shops and drunk at home.

Although consumption has declined in recent years, levels of abstinence have also increased. Consequently, it is unclear how much of the decline is actually related to drinkers consuming less alcohol and how much to an increasing proportion of the population not drinking at all. In recent years, many indicators of alcohol-related harm have increased.

There are now over 1 million hospital admissions relating to alcohol each year, half of which occur in the lowest three socioeconomic deciles. Alcohol-related mortality has also increased, particularly for liver disease which has seen a 400% increase since 1970, and this trend is in stark contrast to much of Western Europe. In England, the average age at death of those dying from an alcohol-specific cause is 54.3 years. The average age of death from all causes is 77.6 years.

More working years of life are lost in England as a result of alcohol-related deaths than from cancer of the lung, bronchus, trachea, colon, rectum, brain, pancreas, skin, ovary, kidney, stomach, bladder and prostate, combined.

Despite this burden of harm, some positive trends have emerged over this period, particularly indicators which relate to alcohol consumption among those aged less than 18 years, and there have been steady reductions in alcohol-related road traffic crashes. The public health burden of alcohol is wide ranging, relating to health, social or economic harms. These can be tangible, direct costs (including costs to the health, criminal justice and welfare systems), or indirect costs (including the costs of lost productivity due to absenteeism, unemployment, decreased output or lost working years due to premature pension or death).

Harms can also be intangible, and difficult to cost, including those assigned to pain and suffering, poor quality of life or the emotional The Public Health Burden of Alcohol and the Effectiveness and Cost-Effectiveness of Alcohol Control Policies: An evidence review 7 distress caused by living with a heavy drinker. The spectrum of harm ranges from those that are relatively mild, such as drinkers loitering near residential streets, through to those that are severe, including death or lifelong disability. Many of these harms

impact upon other people, including relationship partners, children, relatives, friends, co-workers and strangers. In sum, the economic burden of alcohol is substantial, with estimates placing the annual cost to be between 1.3% and 2.7% of annual GDP.

Few studies report costs on the magnitude of harm to people other than the drinker, so the economic burden of alcohol consumption is generally underestimated. Crucially, the financial burden which alcohol-related harm places on society is not reflected in its market price, with taxpayers picking up a larger amount of the overall cost compared to the individual drinkers. This should provide impetus for governments to implement effective policies to reduce the public health impact of alcohol, not only because it is an intrinsically desirable societal goal, but because it is an important aspect of economic growth and competitiveness. Reflecting three key influencers of alcohol consumption – price (affordability), ease of purchase (availability) and the social norms around its consumption (acceptability) – an extensive array of policies have been developed with the primary aim of reducing the public health burden of alcohol. The present review evaluates the effectiveness and cost-effectiveness of each of these policy approaches.

Source: https://assets.publishing.service.gov.uk/government/uploads 2016

Sydney Parliament House, 09.07.2018

Cannabis has been greatly oversold by a left leaning press controlled by globalist and centralist forces while its real and known dangers have not been given appropriate weight in the popular press. In particular its genotoxic and teratogenic potential on an unborn generation for the next hundred years has not been aired or properly weighed in popular forums.

These weighty considerations clearly take cannabis out of the realm of personal choice or individual freedoms and place it squarely in the realm of the public good and a matter with which the whole community is rightly concerned and properly involved.

Cannabinoids are a group of 400 substances which occur only in the leaves of the Cannabis sativa plant where they are used by the plants as toxins and poisons in natural defence against other plants and against herbivores.

Major leading world experts such as Dr Nora Volkow, Director of the National Institute of Drug Abuse at NIH 1, Professor Wayne Hall, Previous Director of the Sydney Based National Drug and Alcohol Research Centre at UNSW 2, and Health Canada 3 – amongst many others – are agreed that cannabis is linked with the following impressive lists of toxicities:

1) Cannabis is addictive, particularly when used by teenagers

2) Cannabis affects brain development

3) Cannabis is a gateway to other harder drug use

4) Cannabis is linked with many mental health disorders including anxiety, depression,

psychosis, schizophrenia and bipolar disorder

5) Cannabis alters and greatly impairs the normal developmental trajectory – getting a

job, finishing a course and forming a long term stable relationship 4-11

6) Cannabis impairs driving ability 12

7) Cannabis damages the lungs

8) Cannabis is immunosuppressive

9) Cannabis is linked with heart attack, stroke and cardiovascular disease

10) Cannabis is commonly more potent in recent years, with forms up to 30% being widely available in many parts of USA, and oils up to 100% THC also widely available.

Serious questions have also been raised about its involvement in 12 different cancers, increased Emergency Room presentations and exposures of developing babies during pregnancy. It is with this latter group that the present address is mainly concerned.

Basic Physiology and Embryology Cells make energy in dedicated organelles called mitochondria. Mitochondrial energy, in the form of ATP, is known to be involved in both DNA protection and control of the immune system. This means that when the cell’s ATP is high DNA maintenance is good and the genome is intact. When cellular ATP drops DNA maintenance is impaired, DNA breaks remain unsealed, and cancers can form. Also immunity is triggered by low ATP.

As organisms age ATP falls by half each 20 years after the age of 20. Mitochondria signal and shuttle to the cell nucleus via several pathways. Not only do cells carry cannabinoid receptors on their surface, but they also exist, along with their signalling machinery, at high density on mitochondria themselves 13-19. Cannabis, and indeed all addictive drugs, are known to impair this cellular energy generation and thus promote the biochemical aging process 14-16,19,20. Most addictions are associated with increased cancers, increased infections and increased clinical signs of ageing 21-34.

The foetal heart forms very early inside the mother with a heartbeat present from day 21 of human gestation. The heart forms by complicated pathways, and arises from more than six groups of cells inside the embryo 35,36. First two arteries come together, they fold, then flex and twist to give the final shape of the adult heart. Structures in the centre of the heart mass called endocardial cushions grow out to form the heart valves between the atria and ventricles and parts of the septum which grows between the two atria and ventricles. These cardiac cushions, and their associated conoventricular ridges which grow into and divide the cardiac outflow tract into left and right halves, all carry high density cannabinoid type 1 receptors (CB1R’s) and cannabis is known to be able to interfere with their growth and development.CB1R’s appear on foetal arteries from week nine of human gestation 37.

The developing brain grows out in a complex way in the head section 35,36. Newborn brain cells are born centrally in the area adjacent to the central ventricles of the brain and then migrate along pathways into the remainder of the brain, and grow to populate the cortex, parietal lobes, olfactory lobes, limbic system, hypothalamus and hippocampus which is an important area deep in the centre of the temporal lobes where memories first form.

Developing bipolar neuroblasts migrate along pathways and then climb out along 200 million guide cells, called radial glia cells, to the cortex of the brain where they sprout dendrites and a major central axon which are then wired in to the electrical network in a “use it or lose it”, “cells that fire together wire together” manner.

The brain continues to grow and mature into the 20’s as new neurons are born and surplus dendrites are pruned by the immune system. Cannabinoids interfere with cellular migration, cellular division, the generation of newborn neurons and all the classes of glia, axonal pathfinding, dendrite sprouting, myelin formation around axons and axon tracts and the firing of both inhibitory and stimulatory synapses 14-16,19,20,38-40. Cannabinoids interfere with gene expression directly, via numerous epigenetic means, and via immune perturbation.

Cannabinoids also disrupt the mechanics of cell division by disrupting the mitotic spindle on which chromosomal separation occurs, causing severe genetic damage and frank chromosomal mis-segregation, disruption, rupture and pulverization 41-43.

Cannabis was found to be a human carcinogen by the California Environmental Protection agency in 2009 44. This makes it a likely human teratogen (deforms babies). Importantly, while discussion continues over some cancers, it bears repeating that a positive association between cannabis and testicular cancer was found in all four studies which investigated this question 45-49.

Cannabis Teratogenesis

The best animal models for human malformations are hamsters and rabbits. In rabbits cannabis exhibits a severe spectrum of foetal abnormalities when applied at high dose including shortened limbs, bowels hanging out, spina bifida and exencephaly (brain hanging out). There is also impaired foetal growth and increased foetal loss and resorption 50,51.

Many of these features have been noted in human studies 52. In 2014 Centres for Disease Control Atlanta Georgia reported increased rates of anencephaly (no brain, usually rapid death) gastroschisis (bowels hanging out), diaphragmatic hernia, and oesophageal narrowing 53,54. The American Heart Association and the American Academy of Pediatrics reported in 2007 an increased rate of ventricular septal defect and an abnormality of the tricuspid valve (Ebstein’s anomaly) 55. Strikingly, a number of studies have shown that cannabis exposure of the father is worse than that of the mother 56. In Colorado atrial septal defect is noted to have risen by over 260% from 2000-2013 (see Figure 1; note close correlation (correlation coefficient R = 0.95, P value = 0.000066) between teenage cannabis use and rising rate of major congenital anomalies in Colorado to 12.7%, or 1 in 8 live births, a rate four times higher than the USA national average !) 57.

And three longitudinal studies following children exposed to cannabis in utero have consistently noted abnormalities of brain growth with smaller brains and heads – persisting into adult life – and deficits of cortical and executive functioning persistent throughout primary, middle and high schools and into young adult life in the early 20’s 58-63. An Australian MRI neuroimaging study noted 88% disconnection of cortical wiring from the splenium to precuneus which are key integrating and computing centres in the cerebral cortex 38,39,64. Chromosomal defects were also found to be elevated in Colorado (rose 30%) 57, in Hawaii 52 in our recent analysis of cannabis use and congenital anomalies across USA, and in infants presenting from Northern New South Wales to Queensland hospitals 65. And gastroschisis shows a uniform pattern of elevation in all recent studies which have examined it (our univariate meta-analysis) 52,54,66-71.

Interestingly the gastroschisis rate doubled in North Carolina in just three years 1997-2001 72, but rose 24 times in Mexico 73 which for a long time formed a principal supply source for Southern USA 74. Within North Carolina gastroschisis and congenital heart defects closely followed cannabis distribution routes 74-76. In Canada a remarkable geographical analysis by the Canadian Government has shown repeatedly that the highest incidence of all anomalies – including chromosomal anomalies – occurs in those northern parts where most cannabis is smoked 77,78.

Congenital anomalies forms the largest cause of death of babies in the first year of life. The biggest group of them is cardiovascular defects. Since cannabis affects several major classes
of congenital defects it is obviously a major human teratogen. Its heavy epigenetic footprint,
by which it controls gene expression by controlling DNA methylation and histone modifications 79-81, imply that its effects will be felt for the next three to four generations – that is the next 100 years 82,83. Equally obviously it is presently being marketed globally as a major commodity apparently for commercial – or ideological – reasons. Since cannabis is clearly contraindicated in several groups of people including:

1) Babies

2) Children

3) Adolescents

4) Car drivers

5) Commercial Drivers – Taxis, Buses, Trains,

6) Pilots of Aeroplanes

7) Workers – Manual Tools, Construction, Concentration Jobs

8) Children

9) Adolescents

10) Males of Reproductive age

11) Females of Reproductive age

12) Pregnancy

13) Lactation

14) Workers

15) Older People – Mental Illness

16) Immunosuppressed

17) Asthmatics – 80% Population after severe chest infection

18) People with Personal History of Cancer

19) People with Family History of Cancer

20) People with Personal History of Mental Illness

21) People with Family History of Mental Illness

22) Anyone or any population concerned about ageing effects 34

… cannabis legalization is not likely to be in the best interests of public health.

Concluding Remarks

In 1854 Dr John Snow achieved lasting public health fame by taking the handle off the Broad Street pump and saving east London from its cholera epidemic, based upon the maps he drew of where the cholera cases were occurring – in the local vicinity of the Broad Street pump.

Looking across the broad spectrum of the above evidence one notices a trulyremarkable concordance of the evidence between:

1) Preclinical studies in

i) Rabbits and

ii) Hamsters

2) Cellular and biological mechanisms, particularly relating to:

i) Brain development

ii) Heart development

iii) Blood vessel development

iv) Genetic development

v) Abnormalities of chromosomal segregation

i. Downs syndrome

ii. Turners syndrome

iii. Trisomy 18

iv. Trisomy 13

vi) Cell division / mitotic poison / micronucleus formation

vii) Epigenetic change

viii) Growth inhibition

3) 84Cross-sectional Epidemiological studies, especially from:

i) Canada 77,85

ii) USA 86,87

iii) Northern New South Wales 65,88 4) Longitudinal studies from 58:

i) Ottawa 59-63

ii) Pittsburgh

iii) Netherlands

Our studies of congenital defects in USA have also shown a close concordance of congenital anomaly rates for 23 defects with the cannabis use rate indexed for the rising cannabis concentration in USA, and mostly in the three major classes of brain defects, cardiovascular defects and chromosomal defects, just as found by previous investigators in Hawaii 52.

Of no other toxin to our knowledge can it be said that it interferes with brain growth and development to the point where the brain is permanently shrunken in size or does not form at all. The demonstration by CDC twice that the incidence of anencephaly (no brain) is doubled by cannabis 53,54 implies that anencephaly is the most severe end of the neurobehavioural teratogenicity of cannabis and forms one end of a continuum with all the other impairments which are implied by the above commentary.

(Actually when blighted ova, foetal resorptions and spontaneous abortion are included in the teratological profile anencephaly is not the most severe end of the teratological spectrum – that is foetal death). It is our view that with the recent advent of high dose potent forms of cannabis reaching the foetus through both maternal and paternal lines major and clinically significant neurobehavioural teratological presentations will become commonplace, and might well become all but universal in infants experiencing significant gestational exposure.

One can only wonder if the community has been prepared for such a holocaust and tsunami amongst its children?

It is the view of myself and my collaborators that these matters are significant and salient and should be achieving greater airplay in the public discussion proceeding around the world at this time on this subject.

Whilst cannabis legalization may line the pockets of the few it will clearly not be in the public interest in any sense; and indeed the public will be picking up the bill for this unpremeditated move for generations to come. Oddly – financial gain seems to be one of the primary drivers of the present transnational push. When the above described public health message gets out amongst ambitious legal fraternities, financial gain and the threat of major medico-legal settlements for congenital defects – will quickly become be the worst reason for cannabis legalization.

Indeed it can be argued that the legalization lobby is well aware of all of the above concerns – and their controlled media pretend debate does not allow such issues to air in the public forum. The awareness of these concerns is then the likely direct reason that cannabis requires its own legislation. As noted in the patient information leaflet for the recently approved Epidiolex (cannabidiol oil for paediatric fits) the US Food and Drug Administration (FDA) is well aware of the genotoxicity of cannabinoids.

The only possible conclusion therefore is that the public is deliberately being duped. To which our only defence will be to publicize the truth.

Source: Summary of Address to Sydney Parliament House, 09.07.2018 by Professor Dr. Stuart Reece, Clinical Associate Professor, UWA Medical School. University of Western Australia

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25 Reece A.S. & G.K., H. Impact of Lifetime Opioid Exposure on Arterial Stiffness and Vascular Age: Cross-sectional and Longitudinal Studies in Men and Women. BMJ Open 4, 1-19, doi:10.1136/bmjopen-2013-004521 (2014).

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Authors: Mücke M, Weier M, Carter C, Copeland J, Degenhardt L, Cuhls H, Radbruch L, Häuser W, Conrad R.

Abstract

We provide a systematic review and meta-analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017.

     Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias.

     In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD]:

0.2 95% confidence interval [CI]: [-0.66, 1.06] P = 0.65),

appetite (SMD: 0.81 95% CI: [-1.14, 2.75]; P = 0.42),

nausea/vomiting (SMD: 0.21 [-0.10, 0.52] P = 0.19),

>30% decrease in pain (risk differences [RD]: 0.07 95% CI: [-0.01, 0.16]; P = 0.07),

or sleep problems (SMD: -0.09 95% CI: [-0.62, 0.43] P = 0.72).

     In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD: 0.20 [-0.15, 0.54]; P = 0.26).

     Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [-0.02; 0.08]; P = 0.23) or poor mental health (RD: -0.01 [-0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05).

     Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer-associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability.

     In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.

Source: https://www.ncbi.nlm.nih.gov/pubmed/29400010  February 2018

Cannabis’ effects on diabetes unclear – by Dr. Elizabeth Ko & Dr. Eve Glazier – Ask the Doctors  column, August 4, 2018 –  Ask the Doctors, c/0 Media Relations, UCLA Health, 924 Westwood Blvd. Suite 350, Los Angeles, CA  90095

Question:  I have Type 1 diabetes and have used marijuana for years to control my blood sugar.  I’ve seen my blood sugar drop 100 points in five minutes with marijuana, faster than my Humalog insulin can manage.  Why is that?  Will medical marijuana ever go mainstream?

Answer:  Marijuana, or cannabis, contains more than 100 active chemical compounds.  Known as cannabinoids, each behaves differently in the body.  As the number of states that allow the use of cannabis for medical purposes continues to grow, so does the body of evidence that many of the compounds found within the plant have therapeutic potential.

     The challenge to investigate medical claims regarding cannabis is that it remains illegal at the federal level.  Research is subject to numerous restrictions.  Even so, various studies and clinical trials are moving forward.

     We found that you’re not alone in noticing its effect on blood sugar.  However, much of what we found is anecdotal evidence, which lacks scientific rigor.  The study of cannabis and its potential effects on diabetes is in the early stages, which much of the work done in mice and on donated tissue samples.

     Until researchers are able to work extensively with human populations, the how and why of the effects of cannabis on the complex physiologic processes encompassed by diabetes will remain educated guesses.

     Preliminary research suggests that certain cannabinoids may help with glucose control.  Some studies have found that cannabis can have a positive effect on insulin resistance.  A study published in 2016 in a journal of the American Diabetes Association found that THCV, one of the cannabinoids that are not psychoactive, improved glycemic control in some individuals with Type 2 diabetes.  Another study that same year drew a link between cannabidiol, a compound in cannabis, and a decrease in inflammation of the pancreas.  In an observational study using data from the federal Centers for Disease Control and Prevention, researchers found the incidence of diabetes among regular cannabis users to be measurably lower than that of the population at large.

     The results of several other recent studies contradict a number of these pro-cannabis findings.  So, basically, the jury is still out.

     Although cannabis shows promise in the area of diabetes, science has yet to catch up with the claims being made.  In the research that has been done, the reason for the effects of cannabis is not yet fully understood.  Interest in the subject is strong, though, and continues to grow.

From “Ask the Doctors” – typed-copied from printed Erie Times-News (Erie, Pa.), August 4, 2018 (www.GoErie.com

Response by Prof. Stuart Reece to FDA

Link to FDA

https://www.federalregister.gov/documents/2018/04/09/2018-07225/international-drug-scheduling-convention-on-psychotropic-substances-single-convention-on-narcotic

Source: Dr Stuart Reece’s original response letter to the FDA:

03 FDA Federal Register Submission for WHO Review and Consideration – Genotoxicity Teratogenicity Concise 2  April 2018

The proliferation of retail boutiques in California did not really bother him, Evan told me, but the billboards did. Advertisements for delivery, advertisements promoting the substance for relaxation, for fun, for health. “Shop. It’s legal.” “Hello marijuana, goodbye hangover.” “It’s not a trigger,” he told me. “But it is in your face.”

When we spoke, he had been sober for a hard-fought seven weeks: seven weeks of sleepless nights, intermittent nausea, irritability, trouble focusing, and psychological turmoil. There were upsides, he said, in terms of reduced mental fog, a fatter wallet, and a growing sense of confidence that he could quit. “I don’t think it’s a ‘can’ as much as a ‘must,'” he said.

Evan, who asked that his full name not be used for fear of the professional repercussions, has a self-described cannabis-use disorder. If not necessarily because of legalization, but alongside legalization, such problems are becoming more common: The share of adults with one has doubled since the early aughts, as the share of cannabis users who consume it daily or near-daily has jumped nearly 50 percent-all “in the context of increasingly permissive cannabis legislation, attitudes, and lower risk perception,” as the National Institutes of Health put it.

Public-health experts worry about the increasingly potent options available, and the striking number of constant users. “Cannabis is potentially a real public-health problem,” said Mark A. R. Kleiman, a professor of public policy at New York University. “It wasn’t obvious to me 25 years ago, when 9 percent of self-reported cannabis users over the last month reported daily or near-daily use. I always was prepared to say, ‘No, it’s not a very abusable drug. Nine percent of anybody will do something stupid.’ But that number is now [something like] 40 percent.” They argue that state and local governments are setting up legal regimes without sufficient public-health protection, with some even warning that the country is replacing one form of reefer madness with another, careening from treating cannabis as if it were as dangerous as heroin to treating it as if it were as benign as kombucha.

But cannabis is not benign, even if it is relatively benign, compared with alcohol, opiates, and cigarettes, among other substances. Thousands of Americans are finding their own use problematic-in a climate where pot products are getting more potent, more socially acceptable to use, and yet easier to come by, not that it was particularly hard before.

For Keith Humphreys, a professor of psychiatry and behavioral sciences at Stanford University, the most compelling evidence of the deleterious effects comes from users themselves. “In large national surveys, about one in 10 people who smoke it say they have a lot of problems. They say things like, ‘I have trouble quitting. I think a lot about quitting and I can’t do it. I smoked more than I intended to. I neglect responsibilities.’ There are plenty of people who have problems with it, in terms of things like concentration, short-term memory, and motivation,” he said. “People will say, ‘Oh, that’s just you fuddy-duddy doctors.’ Actually, no. It’s millions of people who use the drug who say that it causes problems.”

Users or former users I spoke with described lost jobs, lost marriages, lost houses, lost money, lost time. Foreclosures and divorces. Weight gain and mental-health problems. And one other thing: the problem of convincing other people that what they were experiencing was real. A few mentioned jokes about Doritos, and comments implying that the real issue was that they were lazy stoners. Others mentioned the common belief that you can be “psychologically” addicted to pot, but not “physically” or “really” addicted. The condition remains misunderstood, discounted, and strangely invisible, even as legalization and white-marketization pitches ahead.

The country is in the midst of a volte-face on marijuana. The federal government still classifies cannabis as Schedule I drug, with no accepted medical use. (Meth and PCP, among other drugs, are Schedule II.) Politicians still argue it is a gateway to the use of things like heroin and cocaine. The country still spends billions of dollars fighting it in a bloody and futile drug war, and still arrests more people for offenses related to cannabis than it does for all violent crimes combined.

Yet dozens of states have pushed ahead with legalization for medical or recreational purposes, given that for decades physicians have argued that marijuana’s health risks have been overstated and its medical uses overlooked; activists have stressed prohibition’s tremendous fiscal cost and far worse human cost; and researchers have convincingly argued that cannabis is far less dangerous than alcohol. A solid majority of Americans support legalization nowadays.

Academics and public-health officials, though, have raised the concern that cannabis’s real risks have been overlooked or underplayed-perhaps as part of a counter-reaction to federal prohibition, and perhaps because millions and millions cannabis users have no problems controlling their use. “Part of how legalization was sold was with this assumption that there was no harm, in reaction to the message that everyone has smoked marijuana was going to ruin their whole life,” Humphreys told me. It was a point Kleiman agreed with. “I do think that not legalization, but the legalization movement, does have a lot on its conscience now,” he said. “The mantra about how this is a harmless, natural, and non-addictive substance-it’s now known by everybody. And it’s a lie.”

Thousands of businesses, as well as local governments earning tax money off of sales, are now literally invested in that lie. “The liquor companies are salivating,” Matt Karnes of GreenWave Advisors told me. “They can’t wait to come in full force.” He added that Big Pharma was targeting the medical market, with Wall Street, Silicon Valley, food businesses, and tobacco companies aiming at the recreational market.

Sellers are targeting broad swaths of the consumer market-soccer moms, recent retirees, folks looking to replace their nightly glass of chardonnay with a precisely dosed, low-calorie, and hangover-free mint. Many have consciously played up cannabis as a lifestyle product, a gift to give yourself, like a nice crystal or an antioxidant face cream. “This is not about marijuana,” one executive at the California retailer MedMen recently argued. “This is about the people who use cannabis for all the reasons people have used cannabis for hundreds of years. Yes for recreation, just like alcohol, but also for wellness.”

Evan started off smoking with his friends when they were playing sports or video games, lighting up to chill out after his nine-to-five as a paralegal at a law office. But that soon became couch-lock, and he lost interest in working out, going out, doing anything with his roommates. Then came a lack of motivation and the slow erosion of ambition, and law school moving further out of reach. He started smoking before work and after work. Eventually, he realized it was impossible to get through the day without it. “I was smoking anytime I had to do anything boring, and it took a long time before I realized that I wasn’t doing anything without getting stoned,” he said.

His first attempts to reduce his use went miserably, as the consequences on his health and his life piled up. He gained nearly 40 pounds, he said, when he stopped working out and cooking his own food at home. He recognized that he was just barely getting by at work, and was continually worried about getting fired. Worse, his friends were unsympathetic to the idea that he was struggling and needed help. “[You have to] try to convince someone that something that is hurting you is hurting you,” he said.

Other people who found their use problematic or had managed to quit, none of whom wanted to use their names, described similar struggles and consequences. “I was running two companies at the time, and fitting smoking in between running those companies. Then, we sold those companies and I had a whole lot of time on my hands,” one other former cannabis user told me. “I just started sitting around smoking all the time. And things just came to a halt. I was in terrible shape. I was depressed.”

Lax regulatory standards and aggressive commercialization in some states have compounded some existing public-health risks, raised new ones, and failed to tamp down on others, experts argue. In terms of compounding risks, many cite the availability of hyper-potent marijuana products. “We’re seeing these increases in the strength of cannabis, as we are also seeing an emergence of new types of products,” such as edibles, tinctures, vape pens, sublingual sprays, and concentrates, Ziva Cooper, an associate professor of clinical neurobiology in the Department of Psychiatry at Columbia University Medical Center, told me. “A lot of these concentrates can have up to 90 percent THC,” she said, whereas the kind of flower you could get 30 years ago was far, far weaker. Scientists are not sure how such high-octane products affect people’s bodies, she said, but worry that they might have more potential for raising tolerance, introducing brain damage, and inculcating dependence.

As for new risks: In many stores, budtenders are providing medical advice with no licensing or training whatsoever. “I’m most scared of the advice to smoke marijuana during pregnancy for cramps,” said Humphreys, arguing that sellers were providing recommendations with no scientific backing, good or bad, at all.

In terms of long-standing risks, the lack of federal involvement in legalization has meant that marijuana products are not being safety-tested like pharmaceuticals; measured and dosed like food products; subjected to agricultural-safety and pesticide standards like crops; and held to labelling standards like alcohol. (Different states have different rules and testing regimes, complicating things further.)

Health experts also cited an uncomfortable truth about allowing a vice product to be widely available, loosely regulated, and fully commercialized: Heavy users will make up a huge share of sales, with businesses wanting them to buy more and spend more and use more, despite any health consequences.

“The reckless way that we are legalizing marijuana so far is mind-boggling from a public-health perspective,” Kevin Sabet, an Obama administration official and a founder of the non-profit Smart Approaches to Marijuana, told me. “The issue now is that we have lobbyists, special interests, and people whose motivation is to make money that are writing all of these laws and taking control of the conversation.”

This is not to say that prohibition is a more attractive policy, or that legalization has proven a public-health disaster. “The big-picture view is that the vast majority of people who use cannabis are not going to be problematic users,” said Jolene Forman, an attorney at the Drug Policy Alliance. “They’re not going to have a cannabis-use disorder. They’re going to have a healthy relationship with it. And criminalization actually increases the harms related to cannabis, and so having like a strictly regulated market where there can be limits on advertising, where only adults can purchase cannabis, and where you’re going to get a wide variety of products makes sense.”

Still, strictly regulated might mean more strictly regulated than today, at least in some places, drug-policy experts argue. “Here, what we’ve done is we’ve copied the alcohol industry fully formed, and then on steroids with very minimal regulation,” Humphreys said. “The oversight boards of a number of states are the industry themselves. We’ve learned enough about capitalism to know that’s very dangerous.”

A number of policy reforms might tamp down on problem use and protect consumers, without quashing the legal market or pivoting back to prohibition and all its harms. One extreme option would be to require markets to be non-commercial: The District of Columbia, for instance, does not allow recreational sales, but does allow home cultivation and the gifting of marijuana products among adults. “If I got to pick a policy, that would probably be it,” Kleiman told me. “That would be a fine place to be if we were starting from prohibition, but we are starting from patchwork legalization. As the Vermont farmer says, I don’t think you can get there from here. I fear its time has passed. It’s generally true that the drug warriors have never missed an opportunity to miss an opportunity.”

There’s no shortage of other reasonable proposals, many already in place or under consideration in some states. The government could run marijuana stores, as in Canada. States could require budtenders to have some training or to refrain from making medical claims. They could ask users to set a monthly THC purchase cap and remain under it. They could cap the amount of THC in products, and bar producers from making edibles that are attractive to kids, like candies. A ban or limits on marijuana advertising are also options, as is requiring cannabis dispensaries to post public-health information.

Then, there are THC taxes, designed to hit heavy users the hardest. Some drug-policy experts argue that such levies would just push people from marijuana to alcohol, with dangerous health consequences. “It would be like saying, ‘Let’s let the beef and pork industries market and do whatever they wish, but let’s have much tougher restrictions on tofu and seitan,'” said Mason Tvert of the Marijuana Policy Project. “In light of the current system, where alcohol is so prevalent and is a more harmful substance, it is bad policy to steer people toward that.” Yet reducing the commercial appeal of all vice products-cigarettes, alcohol, marijuana-is an option, if not necessarily a popular one.

Perhaps most important might be reintroducing some reasonable skepticism about cannabis, especially until scientists have a better sense of the health effects of high-potency products, used frequently. Until then, listening to and believing the hundreds of thousands of users who argue marijuana is not always benign might be a good start.

Source: info@learnaboutsam.org   20th August 2018

www.learnaboutsam.org

In 2016, Gov. Greg Abbott announced a $9.75 million grant to McKesson Corporation. Now, Texas is among the states investigating the giant drug distributor’s role in a growing opioid crisis

In the early months of 2016, as U.S. overdose deaths were on track to break records and the number of Texas infants born addicted to opioid painkillers climbed steadily higher, Gov. Greg Abbott was courting a massive pharmaceutical company, McKesson, with a multimillion-dollar offer.

At the time, the two stories — Texas public health officials grappling with an overdose epidemic while the governor’s office worked on economic development — seemed unrelated. When Abbott announced he would give McKesson a $9.75 million grant from the state’s Enterprise Fund to woo the pharmaceutical distributor into expanding its operations in North Texas, he mostly received favorable news coverage for promising nearly 1,000 jobs to the local Irving economy.

But as the state and nation’s focus on the opioid crisis has sharpened in recent months, McKesson and other drug companies have come under legal scrutiny and the deal has put Abbott in an uncomfortable position.

Texas has since joined a multistate investigation into pharmaceutical companies, including McKesson, over whether they are responsible for feeding the nation’s opioid crisis and whether they broke any laws in the process. Several Texas counties have moved to sue McKesson and other companies for economic damages, alleging that manufacturers downplayed addiction risks and their distributors failed to track suspicious orders that flooded communities with pills.

The state grant to McKesson, worth about $10,000 for each job it brought to North Texas, is the largest Abbott has doled out from the Enterprise Fund, the controversial deal-closing incentives program created in 2004 under former Gov. Rick Perry. No U.S. state or local government has publicly given McKesson a more generous grant since 2000, according to data compiled by Good Jobs First, a Washington D.C.-based group that tracks government subsidies and other economic incentives.

In statements at the time, Abbott said the company’s expansion would “serve as an invaluable contribution to the Texas economy.”

But if Texas decides to sue McKesson, as several of its counties have, lawyers for the state will likely argue the opposite has happened — at least in the context of the company’s distribution of opioids. Across the country, local and state governments have begun to argue they are bearing the financial burden associated with opioid addiction.

One state lawmaker suggested Abbott’s office should have more closely scrutinized McKesson’s record before issuing the grant — even though the grant happened more than a year before Attorney General Ken Paxton announced Texas was joining the multistate investigation.

“There needs to be better oversight here,” said state Rep. Joe Moody, an El Paso Democrat and member of the new House panel examining the opioid crisis. “You’re in the middle of the opioid crisis, and we’re issuing an enormous grant that comprises a significant amount of grants this company is getting across the country.” 

Abbott’s office did not respond to repeated requests for comment.

Faced with the lawsuits and investigations, McKesson — headquartered in San Francisco but with a sizable Texas footprint — has denied any wrongdoing and insisted it is trying to work toward halting the opioid crisis, not fuel it.

“Our partnership with the state remains strong,” said Kristin Chasen, a company spokeswoman. “We certainly agree that the opioid epidemic is a national public health crisis, and we’re cooperatively having lots of conversations with AG Paxton and the others involved in the multistate investigation.”

A nationwide emergency

Opioids are a family of drugs that include prescription painkillers like hydrocodone as well as illicit drugs like heroin. Last Thursday, President Donald Trump declared a nationwide emergency to address the surging human and financial toll of opioid addiction.

U.S. drug overdose deaths in 2015 far outnumbered deaths from auto accidents or guns, and opioids account for more than 60 percent of overdose deaths — nearly 100 each day, according to the U.S. Centers for Disease Control. That death toll has quadrupled over the past two decades. 

“Beyond the shocking death toll, the terrible measure of the opioid crisis includes the families ripped apart and, for many communities, a generation of lost potential and opportunity,” Trump said Thursday

In Texas, opioids have claimed proportionately fewer lives than in other states, and the growth of opioid-related deaths has been slower, according to U.S. mortality data. Still, the casualties in Texas — 1,107 accidental opioid poisoning deaths in 2016 — have seized the attention of state policymakers.

Last week, Texas House Speaker Joe Straus ordered lawmakers to form a select committee on opioids and substance abuse to examine an issue that he said has had a “devastating impact on many lives.” The announcement came after Paxton joined a 41-state investigation into whether a slew of drug manufacturers and distributors broke any laws in allegedly fueling the crisis.

“This is a public safety and public health issue. Opioid painkiller abuse and related overdoses are devastating families here in Texas and throughout the country,” Paxton said when he announced the probe in June.

Some Texas counties have already taken the drug companies to court.

In late September, Upshur County, population about 40,000, sued a slew of painkiller manufacturers and distributors — including McKesson. Seeking to recoup an unspecified amount in financial damages, the East Texas county argues the drug companies broadly “ignored science and consumer health for profits,” meaning the county “continues to spend large sums combatting the public health crisis created by [a] negligent and fraudulent marketing campaign.”

More specifically, the suit argues McKesson and other distributors “did nothing” to address the “alarming and suspicious” overprescription of drugs.

Bowie County, a rural slice of East Texas nudging Arkansas, has since joined the lawsuit, with other East Texas counties expected to follow. El Paso County isalso mulling legal action, and Bexar County, home to San Antonio, has announced plans to sue.

In an interview last week, Bexar County Judge Nelson Wolff said he couldn’t immediately offer a complete list of companies his county would target, but “I’m sure McKesson is one of them.”

Wolff chuckled when asked about the company’s grant from the state. “That’d give us $10 million more that we could get out of their hides in our lawsuit, if you look at it that way.”

In teaming up to probe drug companies, some experts suggest governments are following a playbook similar to one used during the 1990s to sue tobacco companies for their role in fueling a costly health crisis — an effort that resulted in a settlement yielding more than $15 billion for Texas alone.

“It’s like a polluter externalizing all his risk,” said Mike Papantonio, a Florida-based lawyer with experience in tobacco litigation. 

“He makes a lot of money because he pours the poison right into the river,” said Papantonio, who now organizes a legal conference for groups interested in suing pharmaceutical companies. “The shareholders love it, but then the taxpayers have to come back and fix it.”

“McKesson is a great company”

At the April grand opening of the new McKesson campus in Las Colinas, near Irving, local leaders gathered alongside Abbott and company executives for a ribbon-cutting at the $157 million, 525,000-square foot campus.

“McKesson is a great company,” Abbott said on the stage of a large meeting room at the newly renovated headquarters. 

“I am proud of the work McKesson is doing,” he went on, “and make a commitment of my own to continue to ensure Texas attracts further business and expanding enterprise.”

Beth Van Duyne, then the mayor of Irving, now a U.S. Housing and Urban Development administrator under Trump, defended the city’s decision to give the pharmaceutical company a more than $2 million incentives package on top of the state’s Enterprise Fund gift.

“Having to offer incentives is always a difficult decision to make, but as long as the return on that investment is strong, we can support it,” Van Duyne said in a video recorded from the grand opening.

Even though the promise of taxpayer funds came before Paxton launched his investigation, Moody, the Democratic lawmaker, said Abbott’s office should more carefully vet companies before granting them taxpayer money, and in McKesson’s case, it should have considered the drug company’s alleged role in the opioid crisis.

“We know there’s a problem with drug distribution. These drugs being taken out of the regular route, finding their way into other people’s hands — leading to deaths, leading to overdoses,” he said, later adding, “I don’t think it’s unrealistic to ask that to be part of the evaluation at all. Part of the conversation of growing the economy is what types of companies, businesses do you want?” 

State Rep. Kevin Roberts, a Houston Republican and fellow member of the House panel studying opioids, said he did not know what went into Abbott’s decision making, so he couldn’t comment on the wisdom of the grant. But he agreed that the state should also consider wider issues when deciding which businesses are awarded grants from the enterprise fund.

“I do believe that there is some ethical responsibility in that process as well,” he said. “Just because things look profitable doesn’t mean you do them.”

The fact that McKesson got the state grant doesn’t shield it from liability if Texas ultimately files an opioid lawsuit, Roberts added. “If General Paxton goes forward, the fact that they got a TEF grant does not excuse them.”

Pressure to act

McKesson is also facing legal challenges outside of Texas.

In a recent report to the U.S. Securities and Exchange Commission, the company noted an opioid-related lawsuit brought by the State of West Virginia and nine similar complaints filed in state and federal courts in West Virginia against McKesson and other large distributors. McKesson also listed a federal lawsuit in which the Cherokee Nation alleges the company oversupplied drugs to its population.

In January, McKesson agreed to pay $150 million and revamp its compliance procedures to settle a lawsuit brought by the U.S. Department of Justice after prosecutors alleged the company failed to detect and report “suspicious orders” of opioids.

The company paid $13.25 million to settle a similar Justice Department suit in 2008. McKesson did not admit wrongdoing in either case.

Chasen, the spokeswoman, said McKesson is “really proud of our controlled substances monitoring program today,” and the recent scrutiny addresses conduct “that was really far in the past at this point.”

Chasen added that the company reports all orders “in real time” to the U.S. Drug Enforcement Agency, flagging suspicious ones. 

Mark Kinzly, a co-founder of the Texas Overdose Naloxone Initiative, which educates police officers and the public on overdose prevention, has been critical of the state’s mixed response to the opioid epidemic. In 2015, for example, Abbott drew the ire of Kinzly and other advocates when he vetoed a “Good Samaritan” bill that would have protected someone from prosecution, even if they possessed a small amount of drugs, when they called 911 to help a friend in the throes of overdose.

Abbott said at the time that the bill had an admirable goal but did not include “adequate protections to prevent its misuse by habitual drug abusers and drug dealers.”

Kinzly said Trump’s declaration of a national opioid emergency may lead more politicians to demonstrate support for expanding drug treatment programs. “That will put some pressure on Republican governors, I would imagine,” he said.

Trump, for his part, suggested Thursday that pharmaceutical companies remained in the federal government’s crosshairs.

“What they have and what they’re doing to our people is unheard of,” he said. “We will be bringing some very major lawsuits against people and against companies that are hurting our people.” 

Source: https://www.texastribune.org/2017/10/31/during-opioid-crisis-texas-subsidized-drug-company-its-now-investigati/

October 2017

By Christopher Ingraham

Drug overdose deaths surpassed 72,000 in 2017, according to provisional estimates recently released by the Centers for Disease Control and Prevention. That represents an increase of more than 6,000 deaths, or 9.5 percent, over the estimate for the previous 12-month period.

That staggering sum works out to about 200 drug overdose deaths every single day, or one every eight minutes.

The increase was driven primarily by a continued surge in deaths involving synthetic opioids, a category that includes fentanyl. There were nearly 30,000 deaths involving those drugs in 2017, according to the preliminary data, an increase of more than 9,000 over the prior year.

Deaths involving cocaine also shot up significantly, putting the stimulant on par with drugs such as heroin and the category of natural opiates that includes painkillers such as oxycodone and hydrocodone. One potential spot of good news is that deaths involving those latter two drug categories appear to have flattened out, suggesting the possibility that opiate mortality may be at or nearing its peak.


Overdose estimates for selected drug types in 2017.

The CDC cautions that these figures are early estimates based on monthly death records processed by the agency. The CDC adjusts these figures to correct for underreporting, because some recorded deaths are still pending full investigation. Final mortality figures are typically released at the end of the following calendar year.

The CDC updates these provisional numbers monthly. The recent inclusion of December 2017 means that a complete, albeit early look at 2017 overdose mortality is now available for the first time.

Geographically the deaths are distributed similarly to how they’ve been in prior years, with parts of Appalachia and New England showing the highest mortality rates. Once again, the highest rates were seen in West Virginia, with 58.7 overdose deaths for every 100,000 residents. The District of Columbia (50.4), Pennsylvania (44.1), Ohio (44.0) and Maryland (37.9) rounded out the top five.

At the other end of the spectrum, states in the Great Plains had some of the lowest death rates. Nebraska had the fewest with just 8.2 deaths per 100,000, a rate less than one-seventh the rate in West Virginia.

Despite the nationwide increase, the CDC’s preliminary data also shows overdose rates fell in a number of states, including North Dakota and Wyoming, compared with the prior year. Particularly significant were the decreases in Vermont and Massachusetts, two states with relatively high rates of overdose mortality.

Beyond that, the month-to-month data brings some potentially good news: Nationwide, deaths involving opioids have plateaued and even fallen slightly in recent months, from an estimated high of 49,552 deaths in the 12-month period ending in September 2017 down to 48,612 in the period ending January of this year. While it’s too early to say whether that trend will continue through 2018, those numbers are somewhat encouraging.


Opiate death estimates through January 2018.

A chief concern among substance abuse experts is the ubiquity of fentanyl, a synthetic opioid that’s roughly 50 times more potent than heroin. Because it’s cheap and relatively easy to make, it’s often mixed with other drugs such as heroin and cocaine.

Policymakers have struggled to come up with an adequate response to the opioid crisis. Overdose deaths initially ballooned during the Obama administration, which was criticized by experts for being slow to respond to the problem. Last year, the Trump administration declared the epidemic a “public health emergency” but allocated no new funding for states to address the issue. Former congressman Patrick Kennedy (D-R.I.), a member of the task force that the administration convened to tackle the epidemic, criticized President Trump late last year for being “all talk and no follow-through” on opioids.

https://www.washingtonpost.com/business/2018/08/15/fentanyl-use-drove-drug-overdose-deaths-record-high-cdc-estimates/?utm_term=.9c9d31666886

Abstract
Core deficits in social functioning are associated with various neuropsychiatric and neurodevelopmental disorders, yet biomarker identification and the development of effective pharmacological interventions has been limited. Recent data suggest the intriguing possibility that endogenous cannabinoids, a class of lipid neuromodulators generally implicated in the regulation of neurotransmitter release, may contribute to species-typical social functioning. Systematic study of the endogenous cannabinoid signaling could, therefore, yield novel approaches to understand the neurobiological underpinnings of atypical social functioning.

This article provides a critical review of the major components of the endogenous cannabinoid system (for example, primary receptors and effectors—Δ9-tetrahydrocannabinol, cannabidiol, anandamide and 2-arachidonoylglycerol) and the contributions of cannabinoid signaling to social functioning. Data are evaluated in the context of Research Domain Criteria constructs (for example, anxiety, chronic stress, reward learning, motivation, declarative and working memory, affiliation and attachment, and social communication) to enable interrogation of endogenous cannabinoid signaling in social functioning across diagnostic categories. The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder. Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048207/

Introduction
Synaptic cell-adhesion molecules and their interactions with other molecular pathways affect both synapse formation and its function (Varoqueaux et al., 2006; Sudhof, 2008; Bemben et al., 2015a). Neurexins are presynaptic cell-adhesion molecules that interact with neuroligins and other postsynaptic partners. Neurexins are encoded by three genes, each of which encodes a long and short isoform, termed α- and β-neurexins, respectively (Sudhof, 2008). Interestingly, despite studies linking neurexins to autism and other neuropsychiatric disorders (Leone et al., 2010; Rabaneda et al., 2014), the precise cellular mechanisms underlying the role of neurexins in cognition remain poorly understood.

Since most biochemical studies of neurexins have focused on β-neurexins, investigating the synaptic actions of β-neurexins is particularly imperative. In their timely Cell article, Anderson et al. reported that β-neurexins selectively modulate synaptic strength at excitatory synapses by regulating postsynaptic endocannabinoid synthesis, describing an unexpected trans-synaptic mechanism for β-neurexins to control neural circuits via endocannabinoid signaling. 

Source: https://www.frontiersin.org/articles/10.3389/fnins.2016.00203/full

See also:

https://drugprevent.org.uk/ppp/2018/08/%CE%B2-neurexins-control-neural-circuits-by-regulating-synaptic-endocannabinoid-signaling/

Abstract
α- and β-neurexins are presynaptic cell-adhesion molecules implicated in autism and schizophrenia. We find that although β-neurexins are expressed at much lower levels than α-neurexins, conditional knockout of β-neurexins with continued expression of α-neurexins dramatically decreased neurotransmitter release at excitatory synapses in cultured cortical neurons. The β-neurexin knockout phenotype was attenuated by CB1-receptor inhibition which blocks presynaptic endocannabinoid signaling or by 2-arachidonoylglycerol synthesis inhibition which impairs postsynaptic endocannabinoid release. In synapses formed by CA1-region pyramidal neurons onto burst-firing subiculum neurons, presynaptic in vivo knockout of β-neurexins aggravated endocannabinoid-mediated inhibition of synaptic transmission and blocked LTP; presynaptic CB1-receptor antagonists or postsynaptic 2-arachidonoylglycerol synthesis inhibition again reversed this block. Moreover, conditional knockout of β-neurexins in CA1-region neurons impaired contextual fear memories. Thus, our data suggest that presynaptic β-neurexins control synaptic strength in excitatory synapses by regulating postsynaptic 2-arachidonoylglycerol synthesis, revealing an unexpected role for β-neurexins in the endocannabinoid-dependent regulation of neural circuits.

Source:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709013/

See also:

https://drugprevent.org.uk/ppp/2018/08/endocannabinoid-mediates-excitatory-synaptic-function-of-%ce%b2-neurexins-commentary-%ce%b2-neurexins-control-neural-circuits-by-regulating-synaptic-endocannabinoid-signaling/

Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs.

Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients’ compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam’s side effects.

Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.

Keywords: : cannabidiol, cannabinoids, medical uses, safety, side effects, toxicity

Introduction

Since several years, other pharmacologically relevant constituents of the Cannabis plant, apart from Δ9-THC, have come into the focus of research and legislation. The most prominent of those is cannabidiol (CBD). In contrast to Δ9-THC, it is nonintoxicating, but exerts a number of beneficial pharmacological effects. For instance, it is anxiolytic, anti-inflammatory, antiemetic, and antipsychotic. Moreover, neuroprotective properties have been shown.1,2 Consequently, it could be used at high doses for the treatment of a variety of conditions ranging in psychiatric disorders such as schizophrenia and dementia, as well as diabetes and nausea.1,2

At lower doses, it has physiological effects that promote and maintain health, including antioxidative, anti-inflammatory, and neuroprotection effects. For instance, CBD is more effective than vitamin C and E as a neuroprotective antioxidant and can ameliorate skin conditions such as acne.3,4

The comprehensive review of 132 original studies by Bergamaschi et al. describes the safety profile of CBD, mentioning several properties: catalepsy is not induced and physiological parameters are not altered (heart rate, blood pressure, and body temperature). Moreover, psychological and psychomotor functions are not adversely affected. The same holds true for gastrointestinal transit, food intake, and absence of toxicity for nontransformed cells. Chronic use and high doses of up to 1500 mg per day have been repeatedly shown to be well tolerated by humans.1

Nonetheless, some side effects have been reported for CBD, but mainly in vitro or in animal studies. They include alterations of cell viability, reduced fertilization capacity, and inhibition of hepatic drug metabolism and drug transporters (e.g., p-glycoprotein).1Consequently, more human studies have to be conducted to see if these effects also occur in humans. In these studies, a large enough number of subjects have to be enrolled to analyze long-term safety aspects and CBD possible interactions with other substances.

This review will build on the clinical studies mentioned by Bergamaschi et al. and will update their survey with new studies published until September 2016.

Relevant Preclinical Studies

Before we discuss relevant animal research on CBD possible effects on various parameters, several important differences between route of administration and pharmacokinetics between human and animal studies have to be mentioned. First, CBD has been studied in humans using oral administration or inhalation. Administration in rodents often occures either via intraperitoneal injection or via the oral route. Second, the plasma levels reached via oral administration in rodents and humans can differ. Both these observations can lead to differing active blood concentrations of CBD.1,5,6

In addition, it is possible that CBD targets differ between humans and animals. Therefore, the same blood concentration might still lead to different effects. Even if the targets, to which CBD binds, are the same in both studied animals and humans, for example, the affinity or duration of CBD binding to its targets might differ and consequently alter its effects.

The following study, which showed a positive effect of CBD on obsessive compulsive behavior in mice and reported no side effects, exemplifies the existing pharmacokinetic differences.5 When mice and humans are given the same CBD dose, more of the compound becomes available in the mouse organism. This higher bioavailability, in turn, can cause larger CBD effects.

Deiana et al. administered 120 mg/kg CBD either orally or intraperitoneally and measured peak plasma levels.5 The group of mice, which received oral CBD, had plasma levels of 2.2 μg/ml CBD. In contrast, i.p. injections resulted in peak plasma levels of 14.3 μg/ml. Administering 10 mg/kg oral CBD to humans leads to blood levels of 0.01 μg/ml.6 This corresponds to human blood levels of 0.12 μg/ml, when 120 mg/kg CBD was given to humans. This calculation was performed assuming the pharmacokinetics of a hydrophilic compound, for simplicity’s sake. We are aware that the actual levels of the lipophilic CBD will vary.

A second caveat of preclinical studies is that supraphysiological concentrations of compounds are often used. This means that the observed effects, for instance, are not caused by a specific binding of CBD to one of its receptors but are due to unspecific binding following the high compound concentration, which can inactivate the receptor or transporter.

The following example and calculations will demonstrate this. In vitro studies have shown that CBD inhibits the ABC transporters P-gp (P glycoprotein also referred to as ATP-binding cassette subfamily B member 1=ABCB1; 3–100 μM CBD) and Bcrp (Breast Cancer Resistance Protein; also referred to as ABCG2=ATP-binding cassette subfamily G member 2).7 After 3 days, the P-gp protein expression was altered in leukemia cells. This can have several implications because various anticancer drugs also bind to these membrane-bound, energy-dependent efflux transporters.1 The used CBD concentrations are supraphysiological, however, 3 μM CBD approximately corresponds to plasma concentrations of 1 μg/ml. On the contrary, a 700 mg CBD oral dose reached a plasma level of 10 ng/ml.6 This means that to reach a 1 μg/ml plasma concentration, one would need to administer considerably higher doses of oral CBD. The highest ever applied CBD dose was 1500 mg.1Consequently, more research is warranted, where the CBD effect on ABC transporters is analyzed using CBD concentrations of, for example, 0.03–0.06 μM. The rationale behind suggesting these concentrations is that studies summarized by Bih et al. on CBD effect on ABCC1 and ABCG2 in SF9 human cells showed that a CBD concentration of 0.08 μM elicited the first effect.7

Using the pharmacokinetic relationships mentioned above, one would need to administer an oral CBD dose of 2100 mg CBD to affect ABCC1 and ABCG2. We used 10 ng/ml for these calculations and the ones in Table 1,6,8 based on a 6-week trial using a daily oral administration of 700 mg CBD, leading to mean plasma levels of 6–11 ng/ml, which reflects the most realistic scenario of CBD administration in patients.6 That these levels seem to be reproducible, and that chronic CBD administration does not lead to elevated mean blood concentrations, was shown by another study. A single dose of 600 mg led to reduced anxiety and mean CBD blood concentrations of 4.7–17 ng/ml.9

Table 1.

Inhibition of Human Metabolic Enzymes by Exogenous Cannabinoids In Vitro and the Extrapolated Levels of Oral Daily CBD Administration in Humans Needed to Reach These In Vitro Concentrations (Adapted)6,8

CYP-450 isoform 1A1 1A2 1B1 2A6 2B6 2C9 2D6 3A4 3A5 3A7
CBD (in μM) 0.2 2.7 3.6 55.0 0.7 0.9–9.9 1.2–2.7 1.0 0.2 12.3
aExtrapolated oral daily CBD doses to reach the levels above (in mg) 4900 63,000 84,000 1.28 Mio. Ca. 16,000 21,000–231,000 28,000–63,000 Ca. 23,000 4900 0.29 Mio.
aThe calculations made here are based on the assumption that the CBD distribution in the blood follows the pharmacokinetics of a hydrophilic substance such as alcohol. The reality is more complex, because CBD is lipophilic and, for example, will consequently accumulate in fat tissue. These calculations were made with the intention to give the reader an impression and an approximation of the supraphysiological levels used in in vitro studies.

It also seems warranted to assume that the mean plasma concentration exerts the total of observed CBD effects, compared to using peak plasma levels, which only prevail for a short amount of time. This is not withstanding, that a recent study measured Cmax values for CBD of 221 ng/ml, 3 h after administration of 1 mg/kg fentanyl concomitantly with a single oral dose of 800 mg CBD.10

CBD-drug interactions

Cytochrome P450-complex enzymes

This paragraph describes CBD interaction with general (drug)-metabolizing enzymes, such as those belonging to the cytochrome P450 family. This might have an effect for coadministration of CBD with other drugs.7 For instance, CBD is metabolized, among others, via the CYP3A4 enzyme. Various drugs such as ketoconazol, itraconazol, ritonavir, and clarithromycin inhibit this enzyme.11 This leads to slower CBD degradation and can consequently lead to higher CBD doses that are longer pharmaceutically active. In contrast, phenobarbital, rifampicin, carbamazepine, and phenytoin induce CYP3A4, causing reduced CBD bioavailability.11 Approximately 60% of clinically prescribed drugs are metabolized via CYP3A4.1 Table 1 shows an overview of the cytochrome inhibiting potential of CBD. It has to be pointed out though, that the in vitro studies used supraphysiological CBD concentrations.

Studies in mice have shown that CBD inactivates cytochrome P450 isozymes in the short term, but can induce them after repeated administration. This is similar to their induction by phenobarbital, thereby implying the 2b subfamily of isozymes.1 Another study showed this effect to be mediated by upregulation of mRNA for CYP3A, 2C, and 2B10, after repeated CBD administration.1

Hexobarbital is a CYP2C19 substrate, which is an enzyme that can be inhibited by CBD and can consequently increase hexobarbital availability in the organism.12,13 Studies also propose that this effect might be caused in vivo by one of CBD metabolites.14,15Generally, the metabolite 6a-OH-CBD was already demonstrated to be an inducer of CYP2B10. Recorcinol was also found to be involved in CYP450 induction. The enzymes CYP3A and CYP2B10 were induced after prolonged CBD administration in mice livers, as well as for human CYP1A1 in vitro.14,15 On the contrary, CBD induces CYP1A1, which is responsible for degradation of cancerogenic substances such as benzopyrene. CYP1A1 can be found in the intestine and CBD-induced higher activity could therefore prevent absorption of cancerogenic substances into the bloodstream and thereby help to protect DNA.2

Effects on P-glycoprotein activity and other drug transporters

A recent study with P-gp, Bcrp, and P-gp/Bcrp knockout mice, where 10 mg/kg was injected subcutaneously, showed that CBD is not a substrate of these transporters itself. This means that they do not reduce CBD transport to the brain.16 This phenomenon also occurs with paracetamol and haloperidol, which both inhibit P-gp, but are not actively transported substrates. The same goes for gefitinib inhibition of Bcrp.

These proteins are also expressed at the blood–brain barrier, where they can pump out drugs such as risperidone. This is hypothesized to be a cause of treatment resistance.16 In addition, polymorphisms in these genes, making transport more efficient, have been implied in interindividual differences in pharmacoresistance.10 Moreover, the CBD metabolite 7-COOH CBD might be a potent anticonvulsant itself.14 It will be interesting to see whether it is a P-gp substrate and alters pharmacokinetics of coadministered P-gp-substrate drugs.

An in vitro study using three types of trophoblast cell lines and ex vivo placenta, perfused with 15 μM CBD, found BCRP inhibition leading to accumulation of xenobiotics in the fetal compartment.17BCRP is expressed at the apical side of the syncytiotrophoblast and removes a wide variety of compounds forming a part of the placental barrier. Seventy-two hours of chronic incubation with 25 μM CBD also led to morphological changes in the cell lines, but not to a direct cytotoxic effect. In contrast, 1 μM CBD did not affect cell and placenta viability.17 The authors consider this effect cytostatic. Nicardipine was used as the BCRP substrate in the in vitro studies, where the Jar cell line showed the largest increase in BCRP expression correlating with the highest level of transport.17,and references therein

The ex vivo study used the antidiabetic drug and BCRP substrate glyburide.17 After 2 h of CBD perfusion, the largest difference between the CBD and the placebo placentas (n=8 each) was observed. CBD inhibition of the BCRP efflux function in the placental cotyledon warrants further research of coadministration of CBD with known BCRP substrates such as nitrofurantoin, cimetidine, and sulfasalazine. In this study, a dose–response curve should be established in male and female subjects (CBD absorption was shown to be higher in women) because the concentrations used here are usually not reached by oral or inhaled CBD administration. Nonetheless, CBD could accumulate in organs physiologically restricted via a blood barrier.17

Physiological effects

CBD treatment of up to 14 days (3–30 mg/kg b.w. i.p.) did not affect blood pressure, heart rate, body temperature, glucose levels, pH, pCO2, pO2, hematocrit, K+ or Na+ levels, gastrointestinal transit, emesis, or rectal temperature in a study with rodents.1

Mice treated with 60 mg/kg b.w. CBD i.p. for 12 weeks (three times per week) did not show ataxia, kyphosis, generalized tremor, swaying gait, tail stiffness, changes in vocalization behavior or open-field physiological activity (urination, defecation).1

Neurological and neurospychiatric effects

Anxiety and depression

Some studies indicate that under certain circumstances, CBD acute anxiolytic effects in rats were reversed after repeated 14-day administration of CBD.2 However, this finding might depend on the used animal model of anxiety or depression. This is supported by a study, where CBD was administered in an acute and “chronic” (2 weeks) regimen, which measured anxiolytic/antidepressant effects, using behavioral and operative models (OBX=olfactory bulbectomy as model for depression).18 The only observed side effects were reduced sucrose preference, reduced food consumption and body weight in the nonoperated animals treated with CBD (50 mg/kg). Nonetheless, the behavioral tests (for OBX-induced hyperactivity and anhedonia related to depression and open field test for anxiety) in the CBD-treated OBX animals showed an improved emotional response. Using microdialysis, the researchers could also show elevated 5-HT and glutamate levels in the prefrontal cortex of OBX animals only. This area was previously described to be involved in maladaptive behavioral regulation in depressed patients and is a feature of the OBX animal model of depression. The fact that serotonin levels were only elevated in the OBX mice is similar to CBD differential action under physiological and pathological conditions.

A similar effect was previously described in anxiety experiments, where CBD proved to be only anxiolytic in subjects where stress had been induced before CBD administration. Elevated glutamate levels have been proposed to be responsible for ketamine’s fast antidepressant function and its dysregulation has been described in OBX mice and depressed patients. Chronic CBD treatment did not elicit behavioral changes in the nonoperated mice. In contrast, CBD was able to alleviate the affected functionality of 5HT1A receptors in limbic brain areas of OBX mice.18 and references therein

Schiavon et al. cite three studies that used chronic CBD administration to demonstrate its anxiolytic effects in chronically stressed rats, which were mostly mediated via hippocampal neurogenesis.19 and references therein For instance, animals received daily i.p. injections of 5 mg/kg CBD. Applying a 5HT1A receptor antagonist in the DPAG (dorsal periaqueductal gray area), it was implied that CBD exerts its antipanic effects via these serotonin receptors. No adverse effects were reported in this study.

Psychosis and bipolar disorder

Various studies on CBD and psychosis have been conducted.20 For instance, an animal model of psychosis can be created in mice by using the NMDAR antagonist MK-801. The behavioral changes (tested with the prepulse inhibition [PPI] test) were concomitant with decreased mRNA expression of the NMDAR GluN1 subunit gene (GRN1) in the hippocampus, decreased parvalbumin expression (=a calcium-binding protein expressed in a subclass of GABAergic interneurons), and higher FosB/ΔFosB expression (=markers for neuronal activity). After 6 days of MK-801 treatment, various CBD doses were injected intraperitoneally (15, 30, 60 mg/kg) for 22 days. The two higher CBD doses had beneficial effects comparable to the atypical antipsychotic drug clozapine and also attenuated the MK-801 effects on the three markers mentioned above. The publication did not record any side effects.21

One of the theories trying to explain the etiology of bipolar disorder (BD) is that oxidative stress is crucial in its development. Valvassori et al. therefore used an animal model of amphetamine-induced hyperactivity to model one of the symptoms of mania. Rats were treated for 14 days with various CBD concentrations (15, 30, 60 mg/kg daily i.p.). Whereas CBD did not have an effect on locomotion, it did increase brain-derived neurotrophic factor (BDNF) levels and could protect against amphetamine-induced oxidative damage in proteins of the hippocampus and striatum. No adverse effects were recorded in this study.22

Another model for BD and schizophrenia is PPI of the startle reflex both in humans and animals, which is disrupted in these diseases. Peres et al., list five animal studies, where mostly 30 mg/kg CBD was administered and had a positive effect on PPI.20 Nonetheless, some inconsistencies in explaining CBD effects on PPI as model for BD exist. For example, CBD sometimes did not alter MK-801-induced PPI disruption, but disrupted PPI on its own.20 If this effect can be observed in future experiments, it could be considered to be a possible side effect.

Addiction

CBD, which is nonhedonic, can reduce heroin-seeking behavior after, for example, cue-induced reinstatement. This was shown in an animal heroin self-administration study, where mice received 5 mg/kg CBD i.p. injections. The observed effect lasted for 2 weeks after CBD administration and could normalize the changes seen after stimulus cue-induced heroin seeking (expression of AMPA, GluR1, and CB1R). In addition, the described study was able to replicate previous findings showing no CBD side effects on locomotor behavior.23

Neuroprotection and neurogenesis

There are various mechanisms underlying neuroprotection, for example, energy metabolism (whose alteration has been implied in several psychiatric disorders) and proper mitochondrial functioning.24 An early study from 1976 found no side effects and no effect of 0.3–300 μg/mg protein CBD after 1 h of incubation on mitochondrial monoamine oxidase activity in porcine brains.25 In hypoischemic newborn pigs, CBD elicited a neuroprotective effect, caused no side effects, and even led to beneficial effects on ventilatory, cardiac, and hemodynamic functions.26

A study comparing acute and chronic CBD administration in rats suggests an additional mechanism of CBD neuroprotection: Animals received i.p. CBD (15, 30, 60 mg/kg b.w.) or vehicle daily, for 14 days. Mitochondrial activity was measured in the striatum, hippocampus, and the prefrontal cortex.27 Acute and chronic CBD injections led to increased mitochondrial activity (complexes I-V) and creatine kinase, whereas no side effects were documented. Chronic CBD treatment and the higher CBD doses tended to affect more brain regions. The authors hypothesized that CBD changed the intracellular Ca2+ flux to cause these effects. Since the mitochondrial complexes I and II have been implied in various neurodegenerative diseases and also altered ROS (reactive oxygen species) levels, which have also been shown to be altered by CBD, this might be an additional mechanism of CBD-mediated neuroprotection.1,27

Interestingly, it has recently been shown that the higher ROS levels observed after CBD treatment were concomitant with higher mRNA and protein levels of heat shock proteins (HSPs). In healthy cells, this can be interpreted as a way to protect against the higher ROS levels resulting from more mitochondrial activity. In addition, it was shown that HSP inhibitors increase the CBD anticancer effect in vitro.28 This is in line with the studies described by Bergamaschi et al., which also imply ROS in CBD effect on (cancer) cell viability in addition to, for example, proapoptotic pathways such as via caspase-8/9 and inhibition of the procarcinogenic lipoxygenase pathway.1

Another publication studied the difference of acute and chronic administration of two doses of CBD in nonstressed mice on anxiety. Already an acute i.p. administration of 3 mg/kg was anxiolytic to a degree comparable to 20 mg/kg imipramine (an selective serotonin reuptake inhibitor [SSRI] commonly prescribed for anxiety and depression). Fifteen days of repeated i.p. administration of 3 mg/kg CBD also increased cell proliferation and neurogenesis (using three different markers) in the subventricular zone and the hippocampal dentate gyrus. Interestingly, the repeated administration of 30 mg/kg also led to anxiolytic effects. However, the higher dose caused a decrease in neurogenesis and cell proliferation, indicating dissociation of behavioral and proliferative effects of chronic CBD treatment. The study does not mention adverse effects.19

Immune system

Numerous studies show the CBD immunomodulatory role in various diseases such as multiple sclerosis, arthritis, and diabetes. These animal and human ex vivo studies have been reviewed extensively elsewhere, but studies with pure CBD are still lacking. Often combinations of THC and CBD were used. It would be especially interesting to study when CBD is proinflammatory and under which circumstances it is anti-inflammatory and whether this leads to side effects (Burstein, 2015: Table 1 shows a summary of its anti-inflammatory actions; McAllister et al. give an extensive overview in Table 1 of the interplay between CBD anticancer effects and inflammation signaling).29,30

In case of Alzheimer’s disease (AD), studies in mice and rats showed reduced amyloid beta neuroinflammation (linked to reduced interleukin [IL]-6 and microglial activation) after CBD treatment. This led to amelioration of learning effects in a pharmacological model of AD. The chronic study we want to describe in more detail here used a transgenic mouse model of AD, where 2.5-month-old mice were treated with either placebo or daily oral CBD doses of 20 mg/kg for 8 months (mice are relatively old at this point). CBD was able to prevent the development of a social recognition deficit in the AD transgenic mice.

Moreover, the elevated IL-1 beta and TNF alpha levels observed in the transgenic mice could be reduced to WT (wild-type) levels with CBD treatment. Using statistical analysis by analysis of variance, this was shown to be only a trend. This might have been caused by the high variation in the transgenic mouse group, though. Also, CBD increased cholesterol levels in WT mice but not in CBD-treated transgenic mice. This was probably due to already elevated cholesterol in the transgenic mice. The study observed no side effects.31 and references within

In nonobese diabetes-prone female mice (NOD), CBD was administered i.p. for 4 weeks (5 days a week) at a dose of 5 mg/kg per day. After CBD treatment was stopped, observation continued until the mice were 24 weeks old. CBD treatment lead to considerable reduction of diabetes development (32% developed glucosuria in the CBD group compared to 100% in untreated controls) and to more intact islet of Langerhans cells. CBD increased IL-10 levels, which is thought to act as an anti-inflammatory cytokine in this context. The IL-12 production of splenocytes was reduced in the CBD group and no side effects were recorded.32

After inducing arthritis in rats using Freund’s adjuvant, various CBD doses (0.6, 3.1, 6.2, or 62.3 mg/day) were applied daily in a gel for transdermal administration for 4 days. CBD reduced joint swelling, immune cell infiltration. thickening of the synovial membrane, and nociceptive sensitization/spontaneous pain in a dose-dependent manner, after four consecutive days of CBD treatment. Proinflammatory biomarkers were also reduced in a dose-dependent manner in the dorsal root ganglia (TNF alpha) and spinal cord (CGRP, OX42). No side effects were evident and exploratory behavior was not altered (in contrast to Δ9-THC, which caused hypolocomotion).33

Cell migration

Embryogenesis

CBD was shown to be able to influence migratory behavior in cancer, which is also an important aspect of embryogenesis.1 For instance, it was recently shown that CBD inhibits Id-1. Helix-loop-helix Id proteins play a role in embryogenesis and normal development via regulation of cell differentiation. High Id1-levels were also found in breast, prostate, brain, and head and neck tumor cells, which were highly aggressive. In contrast, Id1 expression was low in noninvasive tumor cells. Id1 seems to influence the tumor cell phenotype by regulation of invasion, epithelial to mesenchymal transition, angiogenesis, and cell proliferation.34

There only seems to exist one study that could not show an adverse CBD effect on embryogenesis. An in vitro study could show that the development of two-cell embryos was not arrested at CBD concentrations of 6.4, 32, and 160 nM.35

Cancer

Various studies have been performed to study CBD anticancer effects. CBD anti-invasive actions seem to be mediated by its TRPV1 stimulation and its action on the CB receptors. Intraperitoneal application of 5 mg/kg b.w. CBD every 3 days for a total of 28 weeks, almost completely reduced the development of metastatic nodules caused by injection of human lung carcinoma cells (A549) in nude mice.36 This effect was mediated by upregulation of ICAM1 and TIMP1. This, in turn, was caused by upstream regulation of p38 and p42/44 MAPK pathways. The typical side effects of traditional anticancer medication, emesis, and collateral toxicity were not described in these studies. Consequently, CBD could be an alternative to other MMP1 inhibitors such as marimastat and prinomastat, which have shown disappointing clinical results due to these drugs’ adverse muscoskeletal effects.37,38

Two studies showed in various cell lines and in tumor-bearing mice that CBD was able to reduce tumor metastasis.34,39 Unfortunately, the in vivo study was only described in a conference abstract and no route of administration or CBD doses were mentioned.36 However, an earlier study used 0.1, 1.0, or 1.5 μmol/L CBD for 3 days in the aggressive breast cancer cells MDA-MB231. CBD downregulated Id1 at promoter level and reduced tumor aggressiveness.40

Another study used xenografts to study the proapoptotic effect of CBD, this time in LNCaP prostate carcinoma cells.36 In this 5-week study, 100 mg/kg CBD was administered daily i.p. Tumor volume was reduced by 60% and no adverse effects of treatment were described in the study. The authors assumed that the observed antitumor effects were mediated via TRPM8 together with ROS release and p53 activation.41 It has to be pointed out though, that xenograft studies only have limited predictive validity to results with humans. Moreover, to carry out these experiments, animals are often immunologically compromised, to avoid immunogenic reactions as a result to implantation of human cells into the animals, which in turn can also affect the results.42

Another approach was chosen by Aviello et al.43 They used the carcinogen azoxymethane to induce colon cancer in mice. Treatment occurred using IP injections of 1 or 5 mg/kg CBD, three times a week for 3 weeks (including 1 week before carcinogen administration). After 3 months, the number of aberrant crypt foci, polyps, and tumors was analyzed. The high CBD concentration led to a significant decrease in polyps and a return to near-normal levels of phosphorylated Akt (elevation caused by the carcinogen).42 No adverse effects were mentioned in the described study.43

Food intake and glycemic effects

Animal studies summarized by Bergamaschi et al. showed inconclusive effects of CBD on food intake1: i.p. administration of 3–100 mg/kg b.w. had no effect on food intake in mice and rats. On the contrary, the induction of hyperphagia by CB1 and 5HT1A agonists in rats could be decreased with CBD (20 mg/kg b.w. i.p.). Chronic administration (14 days, 2.5 or 5 mg/kg i.p.) reduced the weight gain in rats. This effect could be inhibited by coadministration of a CB2R antagonist.1

The positive effects of CBD on hyperglycemia seem to be mainly mediated via CBD anti-inflammatory and antioxidant effects. For instance, in ob/ob mice (an animal model of obesity), 4-week treatment with 3 mg/kg (route of administration was not mentioned) increased the HDL-C concentration by 55% and reduced total cholesterol levels by more than 25%. In addition, treatment increased adiponectin and liver glycogen concentrations.44 and references therein

Endocrine effects

High CBD concentrations (1 mM) inhibited progesterone 17-hydroxylase, which creates precursors for sex steroid and glucocorticoid synthesis, whereas 100 μM CBD did not in an in vitro experiment with primary testis microsomes.45 Rats treated with 10 mg/kg i.p. b.w. CBD showed inhibition of testosterone oxidation in the liver.46

Genotoxicity and mutagenicity

Jones et al. mention that 120 mg/kg CBD delivered intraperetonially to Wistar Kyoto rats showed no mutagenicity and genotoxicity based on personal communication with GW Pharmaceuticals47,48These data are yet to be published. The 2012 study with an epilepsy mouse model could also show that CBD did not influence grip strength, which the study describes as a “putative test for functional neurotoxicity.”48

Motor function was also tested on a rotarod, which was also not affected by CBD administration. Static beam performance, as an indicator of sensorimotor coordination, showed more footslips in the CBD group, but CBD treatment did not interfere with the animals’ speed and ability to complete the test. Compared to other anticonvulsant drugs, this effect was minimal.48 Unfortunately, we could not find more studies solely focusing on genotoxicity by other research groups neither in animals nor in humans.

Acute Clinical Data

Bergamaschi et al. list an impressive number of acute and chronic studies in humans, showing CBD safety for a wide array of side effects.1 They also conclude from their survey, that none of the studies reported tolerance to CBD. Already in the 1970s, it was shown that oral CBD (15–160 mg), iv injection (5–30 mg), and inhalation of 0.15 mg/kg b.w. CBD did not lead to adverse effects. In addition, psychomotor function and psychological functions were not disturbed. Treatment with up to 600 mg CBD neither influenced physiological parameters (blood pressure, heart rate) nor performance on a verbal paired-associate learning test.1

Fasinu et al. created a table with an overview of clinical studies currently underway, registered in Clinical Trials. gov.49 In the following chapter, we highlight recent, acute clinical studies with CBD.

CBD-drug interactions

CBD can inhibit CYP2D6, which is also targeted by omeprazole and risperidone.2,14 There are also indications that CBD inhibits the hepatic enzyme CYP2C9, reducing the metabolization of warfarin and diclofenac.2,14 More clinical studies are needed, to check whether this interaction warrants an adaption of the used doses of the coadministered drugs.

The antibiotic rifampicin induces CYP3A4, leading to reduced CBD peak plasma concentrations.14 In contrast, the CYP3A4 inhibitor ketoconazole, an antifungal drug, almost doubles CBD peak plasma concentration. Interestingly, the CYP2C19 inhibitor omeprazole, used to treat gastroesophageal reflux, could not significantly affect the pharmacokinetics of CBD.14

A study, where a regimen of 6×100 mg CBD daily was coadministered with hexobarbital in 10 subjects, found that CBD increased the bioavailability and elimination half-time of the latter. Unfortunately, it was not mentioned whether this effect was mediated via the cytochrome P450 complex.16

Another aspect, which has not been thoroughly looked at, to our knowledge, is that several cytochrome isozymes are not only expressed in the liver but also in the brain. It might be interesting to research organ-specific differences in the level of CBD inhibition of various isozymes. Apart from altering the bioavailability in the overall plasma of the patient, this interaction might alter therapeutic outcomes on another level. Dopamine and tyramine are metabolized by CYP2D6, and neurosteroid metabolism also occurs via the isozymes of the CYP3A subgroup.50,51 Studying CBD interaction with neurovascular cytochrome P450 enzymes might also offer new mechanisms of action. It could be possible that CBD-mediated CYP2D6 inhibition increases dopamine levels in the brain, which could help to explain the positive CBD effects in addiction/withdrawal scenarios and might support its 5HT (=serotonin) elevating effect in depression.

Also, CBD can be a substrate of UDP glucuronosyltransferase.14Whether this enzyme is indeed involved in the glucuronidation of CBD and also causes clinically relevant drug interactions in humans is yet to be determined in clinical studies. Generally, more human studies, which monitor CBD-drug interactions, are needed.

Physiological effects

In a double-blind, placebo-controlled crossover study, CBD was coadministered with intravenous fentanyl to a total of 17 subjects.10Blood samples were obtained before and after 400 mg CBD (previously demonstrated to decrease blood flow to (para)limbic areas related to drug craving) or 800 mg CBD pretreatment. This was followed by a single 0.5 (Session 1) or 1.0μg/kg (Session 2, after 1 week of first administration to allow for sufficient drug washout) intravenous fentanyl dose. Adverse effects and safety were evaluated with both forms of the Systematic Assessment for Treatment Emergent Events (SAFTEE). This extensive tool tests, for example, 78 adverse effects divided into 23 categories corresponding to organ systems or body parts. The SAFTEE outcomes were similar between groups. No respiratory depression or cardiovascular complications were recorded during any test session.

The results of the evaluation of pharmacokinetics, to see if interaction between the drugs occurred, were as follows. Peak CBD plasma concentrations of the 400 and 800 mg group were measured after 4 h in the first session (CBD administration 2 h after light breakfast). Peak urinary CBD and its metabolite concentrations occurred after 6 h in the low CBD group and after 4 h in the high CBD group. No effect was evident for urinary CBD and metabolite excretion except at the higher fentanyl dose, in which CBD clearance was reduced. Importantly, fentanyl coadministration did not produce respiratory depression or cardiovascular complications during the test sessions and CBD did not potentiate fentanyl’s effects. No correlation was found between CBD dose and plasma cortisol levels.

Various vital signs were also measured (blood pressure, respiratory/heart rate, oxygen saturation, EKG, respiratory function): CBD did not worsen the adverse effects (e.g., cardiovascular compromise, respiratory depression) of iv fentanyl. Coadministration was safe and well tolerated, paving the way to use CBD as a potential treatment for opioid addiction. The validated subjective measures scales Anxiety (visual analog scale [VAS]), PANAS (positive and negative subscores), and OVAS (specific opiate VAS) were administered across eight time points for each session without any significant main effects for CBD for any of the subjective effects on mood.10

A Dutch study compared subjective adverse effects of three different strains of medicinal cannabis, distributed via pharmacies, using VAS. “Visual analog scale is one of the most frequently used psychometric instruments to measure the extent and nature of subjective effects and adverse effects. The 12 adjectives used for this study were as follows: alertness, tranquility, confidence, dejection, dizziness, confusion/disorientation, fatigue, anxiety, irritability, appetite, creative stimulation, and sociability.” The high CBD strain contained the following concentrations: 6% Δ9-THC/7.5% CBD (n=25). This strain showed significantly lower levels of anxiety and dejection. Moreover, appetite increased less in the high CBD strain. The biggest observed adverse effect was “fatigue” with a score of 7 (out of 10), which did not differ between the three strains.52

Neurological and neurospychiatric effects

Anxiety

Forty-eight participants received subanxiolytic levels (32 mg) of CBD, either before or after the extinction phase in a double-blind, placebo-controlled design of a Pavlovian fear-conditioning experiment (recall with conditioned stimulus and context after 48 h and exposure to unconditioned stimulus after reinstatement). Skin conductance (=autonomic response to conditioning) and shock expectancy measures (=explicit aspects) of conditioned responding were recorded throughout. Among other scales, the Mood Rating Scale (MRS) and the Bond and Bodily Symptoms Scale were used to assess anxiety, current mood, and physical symptoms. “CBD given postextinction (active after consolidation phase) enhanced consolidation of extinction learning as assessed by shock expectancy.” Apart from the extinction-enhancing effects of CBD in human aversive conditioned memory, CBD showed a trend toward some protection against reinstatement of contextual memory. No side/adverse effects were reported.53

Psychosis

The review by Bergamaschi et al. mentions three acute human studies that have demonstrated the CBD antipsychotic effect without any adverse effects being observed. This holds especially true for the extrapyramidal motor side effects elicited by classical antipsychotic medication.1

Fifteen male, healthy subjects with minimal prior Δ9-THC exposure (<15 times) were tested for CBD affecting Δ9-THC propsychotic effects using functional magnetic resonance imaging (fMRI) and various questionnaires on three occasions, at 1-month intervals, following administration of 10 mg delta-9-Δ9-THC, 600 mg CBD, or placebo. Order of drug administration was pseudorandomized across subjects, so that an equal number of subjects received any of the drugs during the first, second, or third session in a double-blind, repeated-measures, within-subject design.54 No CBD effect on psychotic symptoms as measured with PANSS positive symptoms subscale, anxiety as indexed by the State Trait Anxiety Inventory (STAI) state, and Visual Analogue Mood Scale (VAMS) tranquilization or calming subscale, compared to the placebo group, was observed. The same is true for a verbal learning task (=behavioral performance of the verbal memory).

Moreover, pretreatment with CBD and subsequent Δ9-THC administration could reduce the latter’s psychotic and anxiety symptoms, as measured using a standardized scale. This effect was caused by opposite neural activation of relevant brain areas. In addition, no effects on peripheral cardiovascular measures such as heart rate and blood pressure were measured.54

A randomized, double-blind, crossover, placebo-controlled trial was conducted in 16 healthy nonanxious subjects using a within-subject design. Oral Δ9-THC=10 mg, CBD=600 mg, or placebo was administered in three consecutive sessions at 1-month intervals. The doses were selected to only evoke neurocognitive effects without causing severe toxic, physical, or psychiatric reactions. The 600 mg CBD corresponded to mean (standard deviation) whole blood levels of 0.36 (0.64), 1.62 (2.98), and 3.4 (6.42) ng/mL, 1, 2, and 3 h after administration, respectively.

Physiological measures and symptomatic effects were assessed before, and at 1, 2, and 3 h postdrug administration using PANSS (a 30-item rating instrument used to assess psychotic symptoms, with ratings based on a semistructured clinical interview yielding subscores for positive, negative, and general psychopathology domains), the self-administered VAMS with 16 items (e.g., mental sedation or intellectual impairment, physical sedation or bodily impairments, anxiety effects and other types of feelings or attitudes), the ARCI (Addiction Research Center Inventory; containing empirically derived drug-induced euphoria; stimulant-like effects; intellectual efficiency and energy; sedation; dysphoria; and somatic effects) to assess drug effects and the STAI-T/S, where subjects were evaluated on their current mood and their feelings in general.

There were no significant differences between the effects of CBD and placebo on positive and negative psychotic symptoms, general psychopathology (PANSS), anxiety (STAI-S), dysphoria (ARCI), sedation (VAMS, ARCI), and the level of subjective intoxication (ASI, ARCI), where Δ9-THC did have a pronounced effect. The physiological parameters, heart rate and blood pressure, were also monitored and no significant difference between the placebo and the CBD group was observed.55

Addiction

A case study describes a patient treated for cannabis withdrawal according to the following CBD regimen: “treated with oral 300 mg on Day 1; CBD 600 mg on Days 2–10 (divided into two doses of 300 mg), and CBD 300 mg on Day 11.” CBD treatment resulted in a fast and progressive reduction in withdrawal, dissociative and anxiety symptoms, as measured with the Withdrawal Discomfort Score, the Marijuana Withdrawal Symptom Checklist, Beck Anxiety Inventory, and Beck Depression Inventory (BDI). Hepatic enzymes were also measured daily, but no effect was reported.56

Naturalistic studies with smokers inhaling cannabis with varying amounts of CBD showed that the CBD levels were not altering psychomimetic symptoms.1 Interestingly, CBD was able to reduce the “wanting/liking”=implicit attentional bias caused by exposure to cannabis and food-related stimuli. CBD might work to alleviate disorders of addiction, by altering the attentive salience of drug cues. The study did not further measure side effects.57

CBD can also reduce heroin-seeking behaviors (e.g., induced by a conditioned cue). This was shown in the preclinical data mentioned earlier and was also replicated in a small double-blind pilot study with individuals addicted to opioids, who have been abstinent for 7 days.52,53 They either received placebo or 400 or 800 mg oral CBD on three consecutive days. Craving was induced with a cue-induced reinstatement paradigm (1 h after CBD administration). One hour after the video session, subjective craving was already reduced after a single CBD administration. The effect persisted for 7 days after the last CBD treatment. Interestingly, anxiety measures were also reduced after treatment, whereas no adverse effects were described.23,58

A pilot study with 24 subjects was conducted in a randomized, double-blind, placebo-controlled design to evaluate the impact of the ad hoc use of CBD in smokers, who wished to stop smoking. Pre- and post-testing for mood and craving of the participants was executed. These tests included the Behaviour Impulsivity Scale, BDI, STAI, and the Severity of Dependence Scale. During the week of CBD inhalator use, subjects used a diary to log their craving (on a scale from 1 to 100=VAS measuring momentary subjective craving), the cigarettes smoked, and the number of times they used the inhaler. Craving was assessed using the Tiffany Craving Questionnaire (11). On day 1 and 7, exhaled CO was measured to test smoking status. Sedation, depression, and anxiety were evaluated with the MRS.

Over the course of 1 week, participants used the inhaler when they felt the urge to smoke and received a dose of 400 μg CBD via the inhaler (leading to >65% bioavailability); this significantly reduced the number of cigarettes smoked by ca. 40%, while craving was not significantly different in the groups post-test. At day 7, the anxiety levels for placebo and CBD group did not differ. CBD did not increase depression (in contract to the selective CB1 antagonist rimonabant). CBD might weaken the attentional bias to smoking cues or could have disrupted reconsolidation, thereby destabilizing drug-related memories.59

Cell migration

According to our literature survey, there currently are no studies about CBD role in embryogenesis/cell migration in humans, even though cell migration does play a role in embryogenesis and CBD was shown to be able to at least influence migratory behavior in cancer.1

Endocrine effects and glycemic (including appetite) effects

To the best of our knowledge, no acute studies were performed that solely concentrated on CBD glycemic effects. Moreover, the only acute study that also measured CBD effect on appetite was the study we described above, comparing different cannabis strains. In this study, the strain high in CBD elicited less appetite increase compared to the THC-only strain.52

Eleven healthy volunteers were treated with 300 mg (seven patients) and 600 mg (four patients) oral CBD in a double-blind, placebo-controlled study. Growth hormone and prolactin levels were unchanged. In contrast, the normal decrease of cortisol levels in the morning (basal measurement=11.0±3.7 μg/dl; 120 min after placebo=7.1±3.9 μg/dl) was inhibited by CBD treatment (basal measurement=10.5±4.9 μg/dl; 120 min after 300 mg CBD=9.9±6.2 μg/dl; 120 min after 600 mg CBD=11.6±11.6 μg/dl).60

A more recent study also used 600 mg oral CBD for a week and compared 24 healthy subjects to people at risk for psychosis (n=32; 16 received placebo and 16 CBD). Serum cortisol levels were taken before the TSST (Trier Social Stress Test), immediately after, as well as 10 and 20 min after the test. Compared to the healthy individuals, the cortisol levels increased less after TSST in the 32 at-risk individuals. The CBD group showed less reduced cortisol levels but differences were not significant.61 It has to be mentioned that these data were presented at a conference and are not yet published (to our knowledge) in a peer-reviewed journal.

Chronic CBD Studies in Humans

Truly chronic studies with CBD are still scarce. One can often argue that what the studies call “chronic” CBD administration only differs to acute treatment, because of repeated administration of CBD. Nonetheless, we also included these studies with repeated CBD treatment, because we think that compared to a one-time dose of CBD, repeated CBD regimens add value and knowledge to the field and therefore should be mentioned here.

CBD-drug interactions

An 8-week-long clinical study, including 13 children who were treated for epilepsy with clobazam (initial average dose of 1 mg/kg b.w.) and CBD (oral; starting dose of 5 mg/kg b.w. raised to maximum of 25 mg/kg b.w.), showed the following. The CBD interaction with isozymes CYP3A4 and CYP2C19 caused increased clobazam bioavailability, making it possible to reduce the dose of the antiepileptic drug, which in turn reduced its side effects.62

These results are supported by another study described in the review by Grotenhermen et al.63 In this study, 33 children were treated with a daily dose of 5 mg/kg CBD, which was increased every week by 5 mg/kg increments, up to a maximum level of 25 mg/kg. CBD was administered on average with three other drugs, including clobazam (54.5%), valproic acid (36.4%), levetiracetam (30.3%), felbamate (21.2%), lamotrigine (18.2%), and zonisamide (18.2%). The coadministration led to an alteration of blood levels of several antiepileptic drugs. In the case of clobazam this led to sedation, and its levels were subsequently lowered in the course of the study.

Physiological effects

A first pilot study in healthy volunteers in 1973 by Mincis et al. administering 10 mg oral CBD for 21 days did not find any neurological and clinical changes (EEG; EKG).64 The same holds true for psychiatry and blood and urine examinations. A similar testing battery was performed in 1980, at weekly intervals for 30 days with daily oral CBD administration of 3 mg/kg b.w., which had the same result.65

Neurological and neuropsychiatric effects

Anxiety

Clinical chronic (lasting longer than a couple of weeks) studies in humans are crucial here but were mostly still lacking at the time of writing this review. They hopefully will shed light on the inconsistencies observerd in animal studies. Chronic studies in humans may, for instance, help to test whether, for example, an anxiolytic effect always prevails after chronic CBD treatment or whether this was an artifact of using different animal models of anxiety or depression.2,18

Psychosis and bipolar disorder

In a 4-week open trial, CBD was tested on Parkinson’s patients with psychotic symptoms. Oral doses of 150–400 mg/day CBD (in the last week) were administered. This led to a reduction of their psychotic symptoms. Moreover, no serious side effects or cognitive and motor symptoms were reported.66

Bergamaschi et al. describe a chronic study, where a teenager with severe side effects of traditional antipsychotics was treated with up to 1500 mg/day of CBD for 4 weeks. No adverse effects were observed and her symptoms improved. The same positive outcome was registered in another study described by Bergamaschi et al., where three patients were treated with a starting dose of CBD of 40 mg, which was ramped up to 1280 mg/day for 4 weeks.1 A double-blind, randomized clinical trial of CBD versus amisulpride, a potent antipsychotic in acute schizophrenia, was performed on a total of 42 subjects, who were treated for 28 days starting with 200 mg CBD per day each.67 The dose was increased stepwise by 200 mg per day to 4×200 mg CBD daily (total 800 mg per day) within the first week. The respective treatment was maintained for three additional weeks. A reduction of each treatment to 600 mg per day was allowed for clinical reasons, such as unwanted side effects after week 2. This was the case for three patients in the CBD group and five patients in the amisulpride group. While both treatments were effective (no significant difference in PANSS total score), CBD showed the better side effect profile. Amisulpride, working as a dopamine D2/D3-receptor antagonist, is one of the most effective treatment options for schizophrenia. CBD treatment was accompanied by a substantial increase in serum anandamide levels, which was significantly associated with clinical improvement, suggesting inhibition of anandamide deactivation via reduced FAAH activity.

In addition, the FAAH substrates palmitoylethanolamide and linoleoyl-ethanolamide (both lipid mediators) were also elevated in the CBD group. CBD showed less serum prolactin increase (predictor of galactorrhoea and sexual dysfunction), fewer extrapyramidal symptoms measured with the Extrapyramidal Symptom Scale, and less weight gain. Moreover, electrocardiograms as well as routine blood parameters were other parameters whose effects were measured but not reported in the study. CBD better safety profile might improve acute compliance and long-term treatment adherence.67,68

A press release by GW Pharmaceuticals of September 15th, 2015, described 88 patients with treatment-resistant schizophrenic psychosis, treated either with CBD (in addition to their regular medication) or placebo. Important clinical parameters improved in the CBD group and the number of mild side effects was comparable to the placebo group.2 Table 2 shows an overview of studies with CBD for the treatment of psychotic symptoms and its positive effect on symptomatology and the absence of side effects.69

Table 2.

Studies with CBD with Patients with Psychotic Symptoms (Adapted)69

Assessment Oral CBD administration Total number of study participants Main findings
BPRS (brief psychiatric rating scale) Up to 1500 mg/day for 26 days 1 Improvement of symptomatology, no side effects
BPRS Up to 1280 mg/day for 4 weeks 3 Mild improvement of symptomatology of 1 patient, no side effects
BPRS, Parkinson Psychosis Questionnaire (PPQ) Up to 600 mg/day for 4 weeks 6 Improvement of symptomatology, no side effects
Stroop Color Word Test, BPRS, PANSS (positive and negative symptom scale) Single doses of 300 or 600 mg 28 Performance after placebo and CBD 300 mg compared to CBD 600 mg; no effects on symptomatology
BPRS, PANSS Up to 800 mg/day for 4 weeks 39 CBD as effective as amisulpride in terms of improvement of symptomatology; CBD displayed superior side effect profile

Treatment of two patients for 24 days with 600–1200 mg/day CBD, who were suffering from BD, did not lead to side effects.70 Apart from the study with two patients mentioned above, CBD has not been tested systematically in acute or chronic administration scenarios in humans for BD according to our own literature search.71

Epilepsy

Epileptic patients were treated for 135 days with 200–300 mg oral CBD daily and evaluated every week for changes in urine and blood. Moreover, neurological and physiological examinations were performed, which neither showed signs of CBD toxicity nor severe side effects. The study also illustrated that CBD was well tolerated.65

A review by Grotenhermen and Müller-Vahl describes several clinical studies with CBD2: 23 patients with therapy-resistant epilepsy (e.g., Dravet syndrome) were treated for 3 months with increasing doses of up to 25 mg/kg b.w. CBD in addition to their regular epilepsy medication. Apart from reducing the seizure frequency in 39% of the patients, the side effects were only mild to moderate and included reduced/increased appetite, weight gain/loss, and tiredness.

Another clinical study lasting at least 3 months with 137 children and young adults with various forms of epilepsy, who were treated with the CBD drug Epidiolex, was presented at the American Academy for Neurology in 2015. The patients were suffering from Dravet syndrome (16%), Lennox–Gastaut syndrome (16%), and 10 other forms of epilepsy (some among them were very rare conditions). In this study, almost 50% of the patients experienced a reduction of seizure frequency. The reported side effects were 21% experienced tiredness, 17% diarrhea, and 16% reduced appetite. In a few cases, severe side effects occurred, but it is not clear, if these were caused by Epidiolex. These were status epilepticus (n=10), diarrhea (n=3), weight loss (n=2), and liver damage in one case.

The largest CBD study conducted thus far was an open-label study with Epidiolex in 261 patients (mainly children, the average age of the participants was 11) suffering from severe epilepsy, who could not be treated sufficiently with standard medication. After 3 months of treatment, where patients received CBD together with their regular medication, a median reduction of seizure frequency of 45% was observed. Ten percent of the patients reported side effects (tiredness, diarrhea, and exhaustion).2

After extensive literature study of the available trials performed until September 2016, CBD side effects were generally mild and infrequent. The only exception seems to be a multicenter open-label study with a total of 162 patients aged 1–30 years, with treatment-resistant epilepsy. Subjects were treated for 1 year with a maximum of 25 mg/kg (in some clinics 50 mg/kg) oral CBD, in addition to their standard medication.

This led to a reduction in seizure frequency. In this study, 79% of the cohort experienced side effects. The three most common adverse effects were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), and diarrhea (n=31 [19%]).72 It has to be pointed out that no control group existed in this study (e.g., placebo or another drug). It is therefore difficult to put the side effect frequency into perspective. Attributing the side effects to CBD is also not straightforward in severely sick patients. Thus, it is not possible to draw reliable conclusions on the causation of the observed side effects in this study.

Parkinson’s disease

In a study with a total of 21 Parkinson’s patients (without comorbid psychiatric conditions or dementia) who were treated with either placebo, 75 mg/day CBD or 300 mg/day CBD in an exploratory double-blind trial for 6 weeks, the higher CBD dose showed significant improvement of quality of life, as measured with PDQ-39. This rating instrument comprised the following factors: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. For the factor, “activities of daily living,” a possible dose-dependent relationship could exist between the low and high CBD group—the two CBD groups scored significantly different here. Side effects were evaluated with the UKU (Udvalg for Kliniske Undersøgelser). This assessment instrument analyzes adverse medication effects, including psychic, neurologic, autonomic, and other manifestations. Using the UKU and verbal reports, no significant side effects were recognized in any of the CBD groups.73

Huntington’s disease

Fifteen neuroleptic-free patients with Huntington’s disease were treated with either placebo or oral CBD (10 mg/kg b.w. per day) for 6 weeks in a double-blind, randomized, crossover study design. Using various safety outcome variables, clinical tests, and the cannabis side effect inventory, it was shown that there were no differences between the placebo group and the CBD group in the observed side effects.6

Immune system

Forty-eight patients were treated with 300 mg/kg oral CBD, 7 days before and until 30 days after the transplantation of allogeneic hematopoietic cells from an unrelated donor to treat acute leukemia or myelodysplastic syndrome in combination with standard measures to avoid GVHD (graft vs. host disease; cyclosporine and short course of MTX). The occurrence of various degrees of GVHD was compared with historical data from 108 patients, who had only received the standard treatment. Patients treated with CBD did not develop acute GVHD. In the 16 months after transplantation, the incidence of GHVD was significantly reduced in the CBD group. Side effects were graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0) classification, which did not detect severe adverse effects.74

Endocrine and glycemic (including appetite, weight gain) effects

In a placebo-controlled, randomized, double-blind study with 62 subjects with noninsulin-treated type 2 diabetes, 13 patients were treated with twice-daily oral doses of 100 mg CBD for 13 weeks. This resulted in lower resistin levels compared to baseline. The hormone resistin is associated with obesity and insulin resistance. Compared to baseline, glucose-dependent insulinotropic peptide levels were elevated after CBD treatment. This incretin hormone is produced in the proximal duodenum by K cells and has insulinotropic and pancreatic b cell preserving effects. CBD was well tolerated in the patients. However, with the comparatively low CBD concentrations used in this phase-2-trial, no overall improvement of glycemic control was observed.40

When weight and appetite were measured as part of a measurement battery for side effects, results were inconclusive. For instance, the study mentioned above, where 23 children with Dravet syndrome were treated, increases as well as decreases in appetite and weight were observed as side effects.2 An open-label trial with 214 patients suffering from treatment-resistant epilepsy showed decreased appetite in 32 cases. However, in the safety analysis group, consisting of 162 subjects, 10 showed decreased weight and 12 had gained weight.52 This could be either due to the fact that CBD only has a small effect on these factors, or appetite and weight are complex endpoints influenced by multiple factors such as diet and genetic predisposition. Both these factors were not controlled for in the reviewed studies.

Conclusion

This review could substantiate and expand the findings of Bergamaschi et al. about CBD favorable safety profile.1Nonetheless, various areas of CBD research should be extended. First, more studies researching CBD side effects after real chronic administration need to be conducted. Many so-called chronic administration studies, cited here were only a couple of weeks long. Second, many trials were conducted with a small number of individuals only. To perform a throrough general safety evaluation, more individuals have to be recruited into future clinical trials. Third, several aspects of a toxicological evaluation of a compound such as genotoxicity studies and research evaluating CBD effect on hormones are still scarce. Especially, chronic studies on CBD effect on, for example, genotoxicity and the immune system are still missing. Last, studies that evaluate whether CBD-drug interactions occur in clinical trials have to be performed.

In conclusion, CBD safety profile is already established in a plethora of ways. However, some knowledge gaps detailed above should be closed by additional clinical trials to have a completely well-tested pharmaceutical compound.

Abbreviations Used

AD Alzheimer’s disease
ARCI Addiction Research Center Inventory
BD bipolar disorder
BDI Beck Depression Inventory
CBD cannabidiol
HSP heat shock protein
IL interleukin
MRS Mood Rating Scale
PPI prepulse inhibition
ROS reactive oxygen species
SAFTEE Systematic Assessment for Treatment Emergent Events
STAI State Trait Anxiety Inventory
TSST Trier Social Stress Test
UKU Udvalg for Kliniske Undersøgelser
VAMS Visual Analogue Mood Scale
VAS Visual Analog Scales

Acknowledgments

The study was commissioned by the European Industrial Hemp Association. The authors thank Michal Carus, Executive Director of the EIHA, for making this review possible, for his encouragement, and helpful hints.

Author Disclosure Statement

EIHA paid nova-Institute for the review. F.G. is Executive Director of IACM.#

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70. Zuardi AW, Crippa JAS, Dursun SM, et al. Cannabidiol was ineffective for manic episode of bipolar affective disorderJ Psychopharmacol. 2010;24:135–137 [PubMed]
71. Braga RJ, Abdelmessih S, Tseng J, et al. Cannabinoids and bipolar disorder. Cannabinoids in neurologic and mental disease. Elsevier, Amsterdam, 2015, p. 205
72. Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trialLancet Neurol. 2016;15:270–278 [PubMed]
73. Chagas MHN, Zuardi AW, Tumas V, et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trialJ Psychopharmacol. 2014;28:1088–1098 [PubMed]
74. Yeshurun M, Shpilberg O, Herscovici C, et al. Cannabidiol for the prevention of graft-versus- host-disease after allogeneic hematopoietic cell transplantation: results of a phase II studyBiol Blood Marrow Transplant. 2015;21:1770–1775 [PubMed]
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/
June 2017

Researchers map out a cellular mechanism that offers a biological explanation for alcoholism, and could lead to treatments

Credit: Getty Images

You can lead a lab rat to sugar water, but you can’t make him drink—especially if there’s booze around.

New research published Thursday in Science may offer insights into why some humans who drink alcohol develop an addiction whereas most do not. After caffeine, alcohol is the most commonly consumed psychoactive substance in the world. For the majority of people the occasional happy hour beer or Bloody Mary brunch is where it stops. Yet we all know that others will drink compulsively, despite whatever consequence or darkness it brings.

The new research confirms earlier work showing this is true for rats; but it takes things a step further and supports a study design that could help scientists better understand addiction biology, and possibly develop more effective therapies for human addictive behaviors. Led by a team at Linköping University in Sweden, the researchers found that when given a choice between alcohol and a tastier, more biologically desirable sugar substitute, a subgroup of rats consistently preferred the alcohol. The authors further identified a specific brain region and molecular dysfunction most likely responsible for these addictive tendencies. They believe their findings and study design could be steps toward developing an effective pharmaceutical therapy for alcohol addiction, a kind of treatment that has eluded researchers for years.

A taste for sweetness is evolutionarily embedded in the mammalian brain; in the wild, sugar translates into fast calories and improved survival odds. For the new study, 32 rats were trained to sip a 20 percent alcohol solution for 10 weeks until it became habit. They were then presented with a daily choice between more alcohol or a solution of the noncaloric sweetener saccharine. (The artificial sweetener provides sugary-tasting enticement without the potential confounding variable of actual calories.) The majority of rats vastly preferred the faux sugar over the alcohol option.

But the fact that four rats—or 12.5 percent of the total—stuck with the alcohol was telling to senior author Markus Heilig, director of the Center for Social and Affective Neuroscience at Linköping, given the rate of alcohol misuse in humans is around 15 percent. So Heilig expanded the study. “There were four rats who went for alcohol despite the more natural reward of sweetness,” he says. “We built on that, and 600 animals later we found that a very stable proportion of the population chose alcohol.” What’s more, the “addicted” rats still chose alcohol even when it meant receiving an unpleasant foot shock.

To get a better sense of what was going on at a molecular level, Heilig and his colleagues analyzed which genes were expressed in the rodent subjects’ brains. The expression of one gene in particular—called GAT-3—was found to be greatly reduced in the brains of those who opted for alcohol rather than saccharine. GAT-3 codes for a protein that normally controls levels of a neurotransmitter called GABA, a common chemical in our brains and one known to be involved in alcohol dependence.

In collaboration with co-author and University of Texas at Austin research scientist Dayne Mayfield, Heilig’s team found that in brain samples from deceased humans who had suffered from alcohol addiction, GAT-3 levels were markedly lower in the amygdala—generally considered the brain’s emotional center. One might assume that any altered gene expression contributing to addictive behaviors would instead manifest in the brain’s reward circuitry—a network of centers involved in pleasurable responses to enticements like food, sex and gambling.

Yet the decrease in GAT-3 expression in both rats and humans was by far strongest in the amygdala. “Figuring out the reward circuitry has been a fantastic success story, but it’s probably of limited relevance to clinical addiction,” Heilig says. “The rewarding effect of drugs happens in everybody. It’s a completely different story in the minority of people who continue to take drugs despite adverse consequences.” He believes altered activity in the amygdala makes perfect sense, given that addiction—in both rats and humans—often brings with it negative emotions and anxiety.

Much previous addiction research has relied on models in which rodents learn to self-administer addictive substances, but without other options that could compete with drug use. It was French neuroscientist Serge Ahmed who recognized this as a major limitation to understanding addition biology given that, in reality, only a minority of humans develops addiction to a particular substance. By offering an alternative reward (that is, sweet water), his team showed only a minority of rats develop a harmful preference for drug use—a finding that has now been confirmed with several other commonly abused drugs.

Building on Ahmed’s concept, Heilig added the element of choice to his research. “You can’t determine the true reward of an addictive drug in isolation; it’s dependent on what other options are available—in our case a sugar substitute.” He says most models that have been used to study addiction, and to seek ways to treat it, were probably too limited in their design. “The availability of choice,” he adds, “is going to be fundamental to studying addiction and developing effective treatments for it.”

Paul Kenny, chair of neuroscience at Icahn School of Medicine at Mount Sinai, agrees. “In order to develop novel therapeutics for alcoholism it is critical to understand not just the actions of alcohol in the brain, but how those actions may differ between individuals who are vulnerable or resilient to the addictive properties of the drug,” he says. “This Herculean effort to impressively map out a cellular mechanism that likely contributes to alcohol dependence susceptibility will likely provide important new leads in the search for more effective therapeutics.” Kenny was not involved in the new research.

Heilig and his team believe they have already identified a promising addiction treatment based on their latest work,  and have teamed up with a pharmaceutical company in hopes of soon testing the compound in humans. The drug suppresses the release of GABA and thus could restore levels of the neurotransmitter to normal in people with a dangerous taste for alcohol. With any luck, one of civilization’s oldest  vices might soon loosen its grip.. Illumination.

Source:  www.scientificamerican.com/article/scientists-pinpoint-brain-region-that-may-be-center-of-alcohol-addiction/   June 21st 2018

TO ALL OUR READERS: THE NDPA WOULD URGE YOU TO READ THE REPORT MENTIONED IN THE ARTICLE BELOW, (Tracking the Money That’s Legalizing Marijuana and Why It Matters), WHICH GIVES A DETAILED DESCRIPTION OF HOW MARIJUANA BECAME THE NUMBER ONE DRUG OF CHOICE FOR MILLIONS OF PEOPLE WORLDWIDE, HOW IT BECAME ‘BIG BUSINESS’ IN THE USA AND WHY WE NEED TO DISSEMINATE THIS INFORMATION WIDELY.

Report by National Families in Action Rips the Veil Off the Medical Marijuana Industry
Research Traces the Money Trail and Reveals the Motivation Behind Marijuana as Medicine

Tracking the Money That’s Legalizing Marijuana and Why It Matters documents state-by-state financial data, exposing the groups and the amount of money used either to fund or oppose ballot initiatives legalizing medical or recreational marijuana in 16 U.S. states.

• NFIA report reveals three billionaires — George Soros, Peter Lewis and John Sperling — who contributed 80 percent of the money to medicalize marijuana through state ballot initiatives during a 13-year period, with the strategy to use medical marijuana as a runway to legalized recreational pot.
• Report shows how billionaires and marijuana legalizers manipulated the ballot initiative process, outspent the people who opposed marijuana and convinced voters that marijuana is medicine, even while most of the scientific and medical communities say marijuana is not medicine and should not be legal.

• Children in Colorado treated with unregulated cannabis oil have had severe dystonic reactions, other movement disorders, developmental regression, intractable vomiting and worsening seizures.

• A medical marijuana industry has emerged to join the billionaires in financing initiatives to legalize recreational pot.

ATLANTA, March 14, 2017 (GLOBE NEWSWIRE) — A new report by National Families in Action (NFIA) uncovers and documents how three billionaires, who favor legal recreational marijuana, manipulated the ballot initiative process in 16 U.S. states for more than a decade, convincing voters to legalize medical marijuana. NFIA is an Atlanta-based non-profit organization, founded in 1977, that has been helping parents prevent children from using alcohol, tobacco, and other drugs. NFIA researched and issued the paper to mark its 40th anniversary.

The NFIA study, Tracking the Money That’s Legalizing Marijuana and Why It Matters, exposes, for the first time, the money trail behind the marijuana legalization effort during a 13-year period. The report lays bare the strategy to use medical marijuana as a runway to legalized recreational pot, describing how financier George Soros, insurance magnate Peter Lewis, and for-profit education baron John Sperling (and groups they and their families fund) systematically chipped away at resistance to marijuana while denying that full legalization was their goal.

The report documents state-by-state financial data, identifying the groups and the amount of money used either to fund or oppose ballot initiatives legalizing medical or recreational marijuana in 16 states. The paper unearths how legalizers fleeced voters and outspent — sometimes by hundreds of times — the people who opposed marijuana.

Tracking the Money That’s Legalizing Marijuana and Why It Matters illustrates that legalizers lied about the health benefits of marijuana, preyed on the hopes of sick people, flouted scientific evidence and advice from the medical community and gutted consumer protections against unsafe, ineffective drugs. And, it proves that once the billionaires achieved their goal of legalizing recreational marijuana (in Colorado and Washington in 2012), they virtually stopped financing medical pot ballot initiatives and switched to financing recreational pot. In 2014 and 2016, they donated $44 million to legalize recreational pot in Alaska, Oregon, California, Arizona, Nevada, Massachusetts and Maine. Only Arizona defeated the onslaught (for recreational marijuana).

Unravelling the Legalization Strategy: Behind the Curtain

In 1992, financier George Soros contributed an estimated $15 million to several groups he advised to stop advocating for outright legalization and start working toward what he called more winnable issues such as medical marijuana. At a press conference in 1993, Richard Cowen, then-director of the National Organization for the Reform of Marijuana Laws, said, “The key to it [full legalization] is medical access. Because, once you have hundreds of thousands of people using marijuana medically, under medical supervision, the whole scam is going to be blown. The consensus here is that medical marijuana is our strongest suit. It is our point of leverage which will move us toward the legalization of marijuana for personal use.”

Between 1996 and 2009, Soros, Lewis and Sperling contributed 80 percent of the money to medicalize marijuana through state ballot initiatives. Their financial contributions, exceeding $15.7 million (of the $19.5 million total funding), enabled their groups to lie to voters in advertising campaigns, cover up marijuana’s harmful effects, and portray pot as medicine — leading people to believe that the drug is safe and should be legal for any use.
Today, polls show how successful the billionaires and their money have been. In 28 U.S. states and the District of Columbia, voters and, later, legislators have shown they believe marijuana is medicine, even though most of the scientific and medical communities say marijuana is not medicine and should not be legal. While the most recent report, issued by the National Academies of Sciences (NAS), finds that marijuana may alleviate certain kinds of pain, it also finds there is no rigorous, medically acceptable documentation that marijuana is effective in treating any other illness. At the same time, science offers irrefutable evidence that marijuana is addictive, harmful and can hinder brain development in adolescents. At the distribution level, there are no controls on the people who sell to consumers. Budtenders (marijuana bartenders) have no medical or pharmaceutical training or qualifications.

One tactic used by legalizers was taking advantage of voter empathy for sick people, along with the confusion about science and how the FDA approves drugs. A positive finding in a test tube or petri dish is merely a first step in a long, rigorous process leading to scientific consensus about the efficacy of a drug. Scientific proof comes after randomized, controlled clinical trials, and many drugs with promising early stage results never make it through the complex sets of hurdles that prove efficacy and safety. But marijuana legalizers use early promise and thin science to persuade and manipulate empathetic legislators and voters into buying the spin that marijuana is a cure-all.

People who are sick already have access to two FDA-approved drugs, dronabinol and nabilone, that are not marijuana, but contain identical copies of some of the components of marijuana. These drugs, available as pills, effectively treat chemotherapy-induced nausea and vomiting and AIDS wasting. The NAS reviewed 10,700 abstracts of marijuana studies conducted since 1999, finding that these two oral drugs are effective in adults for the conditions described above. An extract containing two marijuana chemicals that is approved in other countries, reduces spasticity caused by multiple sclerosis. But there is no evidence that marijuana treats other diseases, including epilepsy and most of the other medical conditions the states have legalized marijuana to treat. These conditions range from Amyotrophic lateral sclerosis (ALS) and Crohn’s disease to Hepatitis-C, post-traumatic stress disorder (PTSD) and even sickle cell disease.

Not So Fast — What about the Regulations?
Legalizers also have convinced Americans that unregulated cannabidiol, a marijuana component branded as cannabis oil, CBD, or Charlotte’s Web, cures intractable seizures in children with epilepsy, and polls show some 90 percent of Americans want medical marijuana legalized, particularly for these sick children. In Colorado, the American Epilepsy Society reports that children with epilepsy are receiving unregulated, highly variable artisanal preparations of cannabis oil recommended, in most cases, by doctors with no training in paediatrics, neurology or epilepsy. Young patients have had severe dystonic reactions and other movement disorders, developmental regression, intractable vomiting and worsening seizures that can be so severe that their physicians have to put the child into a coma to get the seizures to stop. Because of these dangerous side effects, not one paediatric neurologist in Colorado, where unregulated cannabidiol is legal, recommends it for these children.

Dr. Sanjay Gupta further clouded the issue when he produced Weed in 2013, a three-part documentary series for CNN on marijuana as medicine. In all three programs, Dr. Gupta promoted CBD oil, the kind the American Epilepsy Society calls artisanal. This is because not one CBD product sold in legal states has been purified to Food and Drug Administration (FDA) standards, tested, or proven safe and effective. The U.S. Congress and the FDA developed rigid processes to review drugs and prevent medical tragedies such as birth defects caused by thalidomide. These processes have facilitated the greatest advances in medicine in history.

“By end-running the FDA, three billionaires have been willing to wreck the drug approval process that has protected Americans from unsafe, ineffective drugs for more than a century,” said Sue Rusche, president and CEO of National Families in Action and author of the report. “Unsubstantiated claims for the curative powers of marijuana abound.” No one can be sure of the purity, content, side effects or potential of medical marijuana to cause cancer or any other disease. When people get sick from medical marijuana, there are no uniform mechanisms to recall products causing the harm. Some pot medicines contain no active ingredients. Others contain contaminants. “Sick people, especially children, suffer while marijuana medicine men make money at their expense,” added Ms. Rusche.

Marijuana Industry — Taking a Page from the Tobacco Industry
The paper draws a parallel between the marijuana and tobacco industries, both built with the knowledge that a certain percentage of users will become addicted and guaranteed lifetime customers. Like tobacco, legalized marijuana will produce an unprecedented array of new health, safety and financial consequences to Americans and their children.

“Americans learned the hard way about the tragic effects of tobacco and the deceptive practices of the tobacco industry. Making another addictive drug legal unleashes a commercial business that is unable to resist the opportunity to make billions of dollars on the back of human suffering, unattained life goals, disease, and death,” said Ms. Rusche. “If people genuinely understood that marijuana can cause cognitive, safety and mental health problems, is addictive, and that addiction rates may be three times higher than reported, neither voters nor legislators would legalize pot.”
The paper and the supporting data are available at www.nationalfamilies.org.
About National Families in Action

National Families in Action is a 501 (c) (3) nonprofit organization that was founded in Atlanta, Georgia in 1977. The organization helped lead a national parent movement credited with reducing drug use among U.S. adolescents and young adults by two-thirds between 1979 and 1992. For forty years, it has provided complex scientific information in understandable language to help parents and others protect children’s health. It tracks marijuana science and the marijuana legalization movement on its Marijuana Report website and its weekly e-newsletter of the same name.

Source: https://globenewswire.com/news-release/2017/03/14/936283/0/en/New-Report-by-National-Families-in-Action-Rips-the-Veil-Off-the-Medical-Marijuana-Industry.html

The following letter was submitted to the US government Food and Drug Adminstration by Australian Professor Dr. Stuart Reece as evidence against the suggested re-scheduling of cannabinoids in the USA. This item can be found online where a full list of carefully researched references is included. Professor Reece has produced an extraordinary article which should be widely read.

We cannot recommend this article highly enough.

NDPA April 2018

http://GordonDrugAbusePrevention.com

This website has been created as a public service to help address the problem of the use of marijuana and other mood- and mind-altering substances in the United States and around the world. A purpose is help inform the public, the media, and those in positions of public responsibility of the challenges facing the nation as a result of the widespread use of psychoactive and mood-altering substances, particularly marijuana and designer drugs. The harmful effects of these substances have not been well understood. In fact, there is great ignorance of the harmful effects of marijuana and other drugs that are being used for experimental or recreational purposes. The implications that the harmful effects that these drugs have for the health and wellbeing of individuals, families, and society are legion. * * * * * * *

Federal Register Submission
Food and Drug Administration,
10903 New Hampshire Ave.,
Silver Spring,
MD, 20993-0002, USA.

Re: Re-Scheduling of Cannabinoids in USA – Tetrahydrocannabinol and Cannabidiol Related Arteriopathy, Genotoxicity and Teratogenesis

I am very concerned about the potential for increased cannabis availability in USA implied by full drug legalization; however, a comprehensive and authoritative submission of the evidence would take weeks and months to prepare. Knowing what we know now and indeed, what has been available in the scientific literature for a growing number of years concerning a myriad of harmful effects of marijuana, marijuana containing THC should not be reclassified.

These effects that are now well documented in the scientific literature include, alarmingly, harm involving reproductive function and birth anomalies as a result of exposure to or use of marijuana with THC. In addition to all of the usual concerns which you will have heard from many sources including the following I have further particular concerns:

1) Effect on developing brains

2) Effect on driving

3) Effect as a Gateway drug to other drug use including the opioid epidemic

4) Effect on developmental trajectory and failure to attain normal adult goals(stable relationship, work, education)

5) Effect on IQ and IQ regression

6) Effect to increase numerous psychiatric and psychological disorders

7) Effect on respiratory system

8) Effect on reproductive system

9) Effect in relation to immunity and immunosuppression

10) Effect of now very concentrated forms of cannabis, THC and CBD which are widely available

11) Outdated epidemiological studies which apply only to the era before cannabis became so potent and so concentrated

12) Cannabis is now known to have an important arteriopathic effect and cardiovascular toxic effect .

These issues are all well covered by a rich recent literature including reviews from such major international authorities as Dr Nora Volkow Director of NIDA, Professor Wayne Hall and others .

Cannabinoid Therapeutics

In my view the therapeutic effects of cannabinoids have been wildly inflated by the press. Moreover, with over 1,000 studies listed for cannabinoids on clinicaltrials.gov, the chance of a type I experimental error, or studies being falsely reported to be positive when in fact they are not, is at last 25/1,000 at the 0.05 level.

THC as dronabinol is actually a failed drug from USA which has such a high incidence of side effects that it was rarely used as superior agents are readily available for virtually all of its touted and alleged therapeutic applications. My American liaisons advise that dronabinol sales have climbed in recent times as patients use it as a ruse to avoid detection of cannabinoid use at work in states where it is not yet legal. So when I call it a failed therapeutic I mean in a traditional sense, not in the novel way it is now applied for flagrantly flouting the law.

In considering the alleged benefits of cannabis one has to be particularly mindful of cannabis addiction in which cannabinoids will alleviate the effect of drug withdrawal as they do in any other addiction. Moreover, the fact that cannabis itself is known to cause both pain and nausea, greatly complicates the interpretation of many studies.

I also have the following concerns which relate in sum to the arteriopathy and vasculopathy and the genotoxicity of cannabis, tetrahydrocannabinol and likely including cannabidiol and various other cannabinoids:

Cannabinoid Arteriopathy

Particularly noteworthy amongst these various reports are two reports by Dr Nora Volkow in 2014, the Director of the National Institute of Drug Abuse at NIH to the New England Journal of Medicine which together document the adverse cardiovascular and cerebrovascular effects of cannabis at the epidemiological level ; a report from our own increase cardiovascular aging to BMJ Open ; a series of reports showing a fivefold

increase in the rate of heart attack within one hour after cannabis smoking ; several reports of cannabis related arteritis ; other reports of the cerebrovascular actions of cannabis ; documentation that cannabis exposure increases arterial stiffness and cardiovascular and organismal aging ; and a recent report showing that human endothelial vascular function – vasodilation – is substantially inhibited within just one minute of cannabis exposure .

It is also relevant that a synthetic cannabinoid was recently shown to directly induce both thromboxane synthase and lipoxygenase, and so be directly vasoconstrictive, prothrombotic and proinflammatory .

Vascular aging, including both macrovascular and microvascular aging is a major pathological feature not only because most adults in western nations die from myocardial infarction or cerebrovascular accidents, but also because local blood flow and microvascular function is a key determinant of stem cell niche activity in many stem cell beds. This has given rise to the vascular theory of aging which has been produced by some of the leading researchers at the National Health Lung and Blood Institute at NIH, amongst many others .

It can thus be said not only that “You are as old as your (macrovascular) arteries”, but also that “you are as old as your (microvascular) stem cells.” Hence the now compelling evidence for the little known arteriopathic complications of cannabis and cannabinoids, carry very far reaching implications indeed. This was confirmed directly in the clinical study of arterial stiffness from my clinic mentioned above .

Whilst aging, myocardial infarction and cerebrovascular accidents are all highly significant outcomes and major public health endpoints, these effects assume added significance in the context of congenital anomalies. Some congenital defects, such as gastroschisis, are thought to be due to a failure of vascular supply of part of the anterior abdominal wall . Hence in one recent study the unadjusted odds ratio of having a gastroschisis pregnancy amongst cannabis users (O.R.=8.03, 95%C.I. 5.63-11.46) was almost as high as that for heroin, cocaine and amphetamine users (O.R.= 9.35, 95%C.I.
6.64-13.15), and the adjusted odds ratio for any illicit drug use (of which was 84% cannabis) was O.R.=3.54 (95%C.I. 2.22-5.63) and for cannabis alone was said by these Canadian authors to be O.R.=3.0. Hence cannabis related vasculopathy – arteriopathy beyond its very serious implications in adults also carries implications for paediatric and congenital disorders and may also constitute a major teratogenic mechanism.

Cannabinoid Genotoxicity and Teratogenesis

Cannabis is associated with 11 cancers (lung, throat, bladder, airways, testes, prostate,

cervix, larynx) including;

Four congenital and thus inherited cancers (rhabdomyosarcoma, neuroblastoma,ALL,

AML and AMML);

Sativex product insert in many nations carries standard warning against its use by

males or females who might be having a baby.

Cannabis – and likely also CBD – is known to be associated with epigenetic changes

some of which are believed to be inheritable for at least four generations.

Cannabis is known to interfere with tubulin synthesis and binding and it also

acts via Stathmin so that microtubule function is impeded . This leads directly to

micronucleus formation. Cannabis has been known to test positive in the

micronucleus assay for over fifty years. This is a major and standard test for

genotoxicity. Micronucleus formation is known to lead directly to major chromosomal toxicity including chromosomal shattering – so-called chromothripsis –and is known to be associated with cell death, cancerogenesis and major foetal abnormalities.

Cannabis has also been linked definitively with congenital heart disease is a statement

by the American Heart Association and the American Academy of Pediatrics in 2007, on the basis of just three epidemiological studies, all done in the days before cannabis became so concentrated. Congenital heart defects have also been linked with

the father’s cannabis use . Indeed, one study showed that paternal cannabis use was

the strongest risk factor of all for preventable congenital cardiac defects.

Cannabis has also been linked with gastroschisis in at least seven cohort and case

control studies some of which are summarized in a Canadian Government

Report 200. In that report the geographic incidence of most major congenital anomalies

closely paralleled the use of cannabis as described in other major Canadian reports.

The overall adjusted odds ratio for cannabis induction of gastroschisis was

quoted by these authors as 3.0. Moreover, outbreaks of both congenital heart disease and gastroschisis in North Carolina also paralleled the local use of cannabis in that state as described by Department of Justice Reports . The incidence of gastroschisis was noted to double in North Carolina 1999-2001 in the same period the cannabis trade there was rising.

Figures of cannabis use in pregnant women in California by age were also

recently reported to JAMA 229, age group trend lines by age group which closely

approximate those reported by CDC for the age incidence of gastroschisis in the USA

Importantly much of the cannabis coming into both North Carolina and Florida is said to originate in Mexico. An eight-fold rise in the rate of gastroschisis has been reported from Mexico . Gastroschisis has also risen in Washington state. Cannabis has also been associated with 17 other major congenital defects by major Hawaiian epidemiological study reported by Forrester in 2007 when it was used alone

When considered in association with other drug use – which in many cases cannabis leads to – cannabis use was associated with a further 19 major congenital defects. In addition to the effect of cannabinoids on the epigenome and microtubules, cannabinoids have been firmly linked to a reduction of the ability of the cell to produce energy from their mitochondria. An extensive and robust evidence base now links cellular energy generation to the maintenance and care of cellular DNA .

Moreover, as the cellular energy charge falls so too DNA maintenance collapses, and indeed, the cell can spiral where its remaining energy resources, particularly as NAD+, are routed into failing and futile DNA repair, the cell slips into pseudohypoxic metabolism like the Warburg effect well known in cancerogenesis , NAD+ falls below the level required for further energy generation and cellular metabolism collapses. Hence this well-established collapse of the mitochondrial energy charge and transmembrane potential forms a potent engine of continuing and accelerating genotoxicity .

Moreover, the well documented decline in mitochondrial respiration induced by cannabinoids, including tetrahydrocannabinol, cannabidiol and anandamide achieves particular significance in the light of the robustly documented decline in cellular energetics including NAD+ which not only occurs with age but indeed, has now been shown to be one of the primary drivers of cellular and whole organismal aging. It follows therefore that cannabinoid administration (including THC andCBD) necessarily phenocopies cellular aging. This implies of course that cannabinoid dependent patients are old at the cellular level. Indeed, normal human aging is phenocopied in the clinical syndrome of cannabinoid dependence which includes:

1) Neurological deficits in:

i) attention,

ii) learning and

iii) memory;

iv) social withdrawal and disengagement and

v) academic and

vi) occupational underachievement

2) Psychiatric disorders including

i) Anxiety,

ii) Depression,

iii) Mixed Psychosis

iv) Bipolar Affective disorder and

v) Schizophrenia,

3) Respiratory disorders including:

i) Asthma

ii) Chronic Bronchitis (increased sputum production)

iii) Emphysema (Increased residual volume)

iv) Probably increased carcinomas of the aerodigestive tract

4) Immune suppression which generally implies

i) segmental immunostimulation in some parts of the immune system since the innate and adaptive immune systems exert profound homeostatic mechanisms in response to suppression of one of its parts. A Substantial literature on immunostimulation

5) Reproductive effects generally characterized by reduced

i) Male and

ii) Female fertility

6) Cardiovascular toxicity with elevated rates of

i) Myocardial infarction

ii) Cerebrovascular accident

iii) Arteritis

iv) Vascular age – vascular stiffness

7) Genotoxicity in

i) Respiratory epithelium and

ii) Gonadal tissues.

8) Osteoporosis

9) Cancers of the

i) Head and neck

ii) Larynx

iii) Lung

iv) Leukaemia

v) Prostate

vi) Cervix

vii) Testes

viii) Bladder

ix) Childhood neuroblastoma

x) Childhood acute lymphoblastic leukaemia

xi) Childhood Acuter Myeloid and myelomonocytic leukaemia

xii) Childhood rhabdomyosarcoma 201,202.

The issue here of course is that cannabinoid dependence therefore copies without exception all of the major disorders of old age, each of which is also faithfully phenocopied by cannabis dependence.

The most prominent disorders of older age include:

1) Alzheimer’s disease

2) Cardiovascular and cerebrovascular disease

3) Osteoporosis

4) Systemic inflammatory syndrome

5) Changes in lung volume and the mechanics of breathing

6) Cancers

Hence this provides one powerful pathway by which cannabinoid exposure can replicate and phenocopy the disorders of old age. This is not of course to suggest that this is the only such pathway. Obviously changes of the general level of immune activity, or alterations of the level of DNA repair occurring directly or indirectly associated with cannabis use can form similar such pathways: both are well documented in cannabis use and also in the aging literature as major pathways implicated in systemic aging.

Nevertheless, the decline in mitochondrial energetics together with its inherent genotoxic implications does seem to be a particularly well substantiated and robustly demonstrated pathway which must give serious pause to cannabinoid advocates if the sustainability of the health and welfare systems is to be factored in together with any consideration of individual patient, advocate and industrial-complex rights.

The genotoxicity of THC, CBD and CBN has been noted against sperm since at least 1999 (Zimmerman and Zimmerman in Nahas “Marijuana and Medicine” 1999, Springer). This is clearly highly significant as sperm go directly into the formation of the zygote and the new human individual. CB1R receptors are known to exist intracellularly on both the membranes of endoplasmic reticulum and mitochondria. In both locations they can induce organellar stress and major cell toxicity including disruption of DNA maintenance. Interestingly mitochondrial outer membrane CB1R’s signal via a complex signalling chain involving the G-protein transduction machinery, protein kinase A and cyclic-AMP across the intermembrane space to the inner membrane and cristae, in a fashion replicating much of the G-protein signalling occurring at the cell membrane. This machinery is also implicated in mitonuclear signalling, and the mitonuclear DNA balance between mitochondrial DNA and nuclear DNA transcriptional control, which has long been implicated in inducing the mitochondrial unfolded protein cellular stress response cell aging, stem cell behaviour and DNA genotoxic mechanisms.

You are no doubt aware that human sperm are structured like express outboard motors behind DNA packets with layers of mitochondria densely coiled around the rotating flagellum which powers their progress in the female reproductive tract. These mitochondria also carry CB1R’s and are significantly inhibited even at 100 nanomolar THC. The acrosome reaction is also inhibited .

Cannabidiol is known to act via the PPARγ system 101,302-308. PPARγ is known to have a major effect on gene expression, reproductive and embryonic and zygote function during development 309-332 so that significant genotoxic and / or teratogenic effects seem inevitable via this route. Drugs which act in this class, known as the thiazolidinediones, are classed as category B3 in pregnancy and caution is indicated in their use in pregnancy and lactation.

The Report of the Reproductive and Cancer Hazard Assessment Branch of the Office of Environmental Health Hazard Assessment of the Health Department of California was mentioned above in connection with the carcinogenicity of marijuana smoke . Since virtually all mutagens are also teratogens it follows therefore from the basic tenets of mutagenesis that if cannabis is unsafe as a known carcinogen it must also be at the very least a putative teratogen.

CBD has also been noted to be a genotoxic in other studies . All of which points to major teratogenic activity for both THC and CBD. Some of the quotations from Professor James Graham’s classical book on the effects of THC in hamsters and white rabbits, the best animal models for human genotoxicity, bear repeating:

a) “The concentration of THC was relatively low and the malignancy severe.”

b) “40-100μg resin/ml there occurred marked inhibition of cell division.

c) “large total dose, Hamsters, 25-300mg/kg …“oedema,phocomelia,omphalocoele, spina bifida, exencephaly, multiple malformations and myelocoele. This is a formidable list.”

d) “It is to this anti-mitotic action that the authors attribute the embryotoxic action of cannabis.”

e) “By such criteria resin or extract of cannabis would be forbidden to women

during the first three months of pregnancy.”

Indeed, even from the other side of the world I have heard many exceedingly adverse reports from US states in which cannabis has been legalized including Colorado, Washington, Oregon, Florida and California. Taken together the above evidence suggests that these negative reports stem directly from the now known actions of cannabis and cannabinoids, and are by no means incidental epiphenomena somehow related to social constructs surrounding cannabis use or the product forms, dosages, or routes of administration involved.

Cannabis that contains increasingly high levels of THC is now widely available, particularly in the jurisdictions where the use of cannabis has been legalized. This means that another major genotoxin, akin to Thalidomide, is being unleashed on the USA and the world. This is clearly a very grave, and. indeed, an entirely preventable occurrence.

Dr Frances Kelsey of FDA is said to have the public servant based at FDA who saved American from the thalidomide scandal which devastated so many other English-speaking nations including my own . This occurred because the genotoxicity section of the file application with FDA was blank. It was blank because thalidomide tested positive in various white rabbit and guinea pig assays. It is these same tests which cannabis is known to have failed. Dr Kelsey’s photograph has been published in the medical press with President Kennedy for her service to the nation. The challenge to FDA at this time seems whether Science can triumph over agenda driven populism, its primary vehicle, the mass media, and its primary proximate driver the burgeoning cannabis industry. Since FDA is the Federal agency par excellence where Health Science is weighed, commissioned and thoughtfully considered the challenge in our time would appear to be no less.

Evidence to date does not suggest that major congenital malformations are as common after prenatal cannabis exposure as they are after prenatal thalidomide exposure. Nevertheless the qualitative similarities remain and indeed are prominent. It is yet to be seen whether the rate of congenital anomalies after cannabis are quantitatively as common: epidemiological studies in a high potency era have not been undertaken; and even the birth defects rates from most birth defects registers in western nations including that held by CDC, Atlanta appear to be seriously out of date at the time of writing. Moreover the non-linear dose response curve in many cannabis genotoxicity studies which includes a sharp knee bend upwards beyond a certain threshold level which suggests that we could well be in for a very unpleasant quantitative surprise. At the time of writing this remains to be formally determined.

Dr Bertha Madras, Professor of Addiction Psychiatry at Harvard Medical School has recently argued against re-scheduling of cannabis. Her comments include the following:

“Why do nations schedule drugs? …… Nations schedule psychoactive drugs because we revere this three-pound organ (of our brain) differently than any other part of our body. It is the repository of our humanity. It is the place that enables us to write poetry and to do theater, to conjure up calculus and send rockets to Pluto three billion miles away, and to create I Phones and 3 D computer printing. And that is the magnificence of the human brain. Drugs can influence (the brain) adversely. So, this is not a war on drugs. This is a defense of our brains, the ultimate source of our humanity” .

I look forward to seeing the comments that you post concerning the reasons why the classification for marijuana should not be changed and that, indeed, the public should be alerted to the very harmful effects of marijuana with THC, especially in light of the wide range of marijuana’s harmful effects and the high potency of THC in today’s marijuana and in light of the idiosyncratic effects of marijuana of even low doses of THC and owing to the certain risk of harm to progeny and babies born to users of marijuana.

Please feel free to call on me if you would like further information concerning the research to which I have referred herein.

Yours sincerely,

Professor Dr. Stuart Reece, MBBS (Hons.), FRCS(Ed.), FRCS(Glas.), FRACGP, MD(UNSW). School of Psychiatry and Clinical Neurosciences Edith Cowan University and University of Western Australia, Perth, WA stuart.reece@uwa.edu.au

Source: http://GordonDrugAbusePrevention.com.

A small but vocal contingent of drug policy interpreters is attempting again to further the fallacious meme that ‘prohibition’ and ‘supply reduction’ are driving drug deaths in Australia, not poor policy interpretation and use which foster a permission model for the vulnerable and pop-culture informed community – particularly the young, Dalgarno Institute writes.

PRESS RELEASE FROM THE DALGARNO INSTITUTE…

The National Drug Strategy

The latest National Drug Strategy 2017-26, now puts Demand Reduction as the priority! The strategy states that “Harm Minimisation includes a range of approaches to help prevent and reduce drug related problems…including a focus on abstinence-oriented strategies… [Harm minimisation] policy approach does not condone drug use.” (page 6)“Prevention of uptake reduces personal, family and community harms, allow better use of health and law enforcement resources, generates substantial social and economic benefits and produces a healthier workforce. Demand Reduction strategies that prevent drug use are more cost effective than treating established drug-related problems…Strategies that delay the onset of use prevent longer term harms and costs to the community.” (page 8)

The National Drug Strategy segments the drug issue into three main categories:

Tobacco – Alcohol – Illicit drugs

A quick summary of the policy focus/emphasis on each drug can be encapsulated as follows:

Tobacco

QUIT! Cessation, and exit from tobacco use is the ONLY goal for this drug. There is no illusion about the journey to that destination being difficult, and the reality of failure clear, but the goal posts don’t move QUIT is the ONE message ONE focus and ONE voice in all sectors of the media, community, education and legislation arenas. (Remember this is a legal drug, and until about 20 years ago, utterly socially acceptable) We have reduced smoking rates of 75% of Australian Males (not including females) after World War II down to around 14% of total population. According to health data, approximately 100,000 people give up tobacco each year, but about the same take it up. No prizes for guessing that cohort make up? The 16-24-year-old demographic usually engage (research shows us) in tobacco use mostly when drinking alcohol. Of course, learning ‘smoking’ as a delivery mechanism also equips the tobacco user for ‘smoking’ of other drugs.

Alcohol

‘Moderate! Drink Responsibility!’ However, a growing educative and legislative push (due to the rising costs of alcohol harms to community) is seeing attitudes change, with now approx. 21 per cent of Australians of drinking age now abstinent! (Remember this is a legal and completely socially acceptable drug.)

Illicit drugs

The mantra? ‘Use is likely, so use carefully and don’t die!’ And we are perpetually informed by certain vested interests that for the 3.5 – 4% of illicit drug users in this country (Cannabis use excised from stats here) that cessation of, or exiting from, drug use is virtually impossible – well so the mantra educates, and that ‘learned behaviour’ of powerlessness and choice stripped victimhood is now parroted as reason enough to ‘validate’ the notion of intractability.

So, then it is touted, the only answer for this demographic is either legalisation or a suite of policies or policy interpretations that enables, empowers, endorses or equips on going drug use, because, it is believed any ‘prohibition’ messaging will not only fail, but be counterproductive. But apparently NOT so with Tobacco, where such prohibition messaging has worked brilliantly!!The cognitive dissonance in this space continues to be breathtaking!

So, what of Harm Reduction ONLY policy implementation of our three pillar National Drug Strategy?

Harm Reduction.

Let’s be clear – what we have now in Australia’s drug taking public psyche (learned/taught behaviour), is well educated and fully self-aware, (and product aware) young adults determining that any drug use risk is manageable. Why? These purported intelligent, sophisticated ‘buzz’ seeking and cashed up adult party goers, willingly and deliberately seek out illicit drugs, purchase them with disposable income, not because of the tyranny of addiction, but to ‘enhance the party experience’. They then take these substances to public events and consume these psychotropic toxins.

Of course, they are fully aware of the mantra they have been taught, as early as secondary school, that if something happens all you should do is call the ambulance. Not only will these remarkable and brave tax-payer funded public servants attend to your self-inflicted illegally induced harm, but will ferry you, at cost to the public purse, to an already overcrowded and strained public health facility. There they will be treated by caring professionals, who have more regard for their well-being than the hapless drug user does. Once they are discharged from the hospital, there (for the most part) is no cost to them, and complete impunity from the law. Little, if no legal action or facilitated diversion is taken and the illicit drug user goes on their way until next drug taking episode.

Whilst no one wants to see injury, let alone death from these reckless behaviours, the mechanisms to ‘save lives’ are already well in play and consequently risk/responsibility factors are disregarded. What must not happen, but clearly is happening, is this utter carelessness for wellbeing of self and others cannot, must not be endorsed or worse, enabled/empowered by poor policy or policy interpretation/use.

There is little or absolutely no accountability for this costly, dangerous, self-indulgent and illegal behaviour. And the cry from the pro-drug lobby is not to call for best practice demand reduction, prevention and/or recovery/exit from this activity/behaviour – No, it’s to declare ‘inevitability’ of behaviour and then, the careless equipping, enabling or empowering of mechanisms to assist the educated self-harmer to continue to use!

Again, it is this permission, NOT prohibition that is continuing to put young lives (and more of them) at risk. The no-longer tacit, but now abundantly clear message in the cultural market place, is that ‘you can take drugs anytime and anywhere and nothing will be done, other than assistance for you if things go pear shaped!’

It’s this message, and not demand and supply reduction vehicles which is empowering ongoing drug use.

It’s time to change the narrative around this ever-permissive drug culture – if not for the sake of people’s lives, then for the emerging generation who are watching this model set them up for engagement, not avoidance of illegal drug use.

Genuine compassion driven anti-drug Harm Reduction must always be about the cessation and/or exiting from drug use and any policy or policy interpretation that fosters a contrary outcome is not good drug policy. The drug policy/strategy interpretation narrative has meant that the term ‘harm reduction’ and ‘harm minimisation’ are now interchangeable terms. Essentially this ensures that Harm Reduction becomes the only pillar of the three-pillar strategy is in play.

This has worked marvellously at convincing even anti-drug citizens, that there is only one option available. Time will not permit to table every encounter we’ve had, but the following statement reflects numbers we have heard…

“Pity we can’t use your harm prevention education program, because it’s illegal. We are only allowed to teach harm reduction in schools!” Head of a State Government Regional Education group, Victoria.

Of course, this is patently false, as Demand Reduction and prevention are not only best practice models, but mandated in the NDS, particularly for the demographic with the developing brain – 12-28-year-old! The Key questions that must be asked about illicit drug policy, are the following;

* Does the policy (or interpretation – harm reduction only) lead to an exit from or cessation of drug use, or does it enable, endorse, empower or equip on going drug use?

* Does the policy (or interpretation) increase or reduce demand for illicit drugs?

* Does the policy (or interpretation) undermine or support the other two pillars? (i.e. increase or reduce Demand or Supply for drugs)

If the policy use/interpretation is creating cognitive dissonance in implementation and leads to a conflagration, rather than collaboration of all three pillars, then the strategy is going to have difficulty in effectively moving a culture away from drug use.

Well, perhaps that is exactly the agenda of the pro-drug lobbyists who have inordinate and disproportionate influence in drug policy implementation? I hear even genuine and compassionate harm reductionists, who actually want to stop drug use and see people recover, railing against supply reduction pillar as ‘waste of resources’. And staggeringly many of these same good people are silent on Demand Reduction, the key to seeing change. These two modes of thinking are the key elements of ensuring only one ‘pillar’ of the NDS is focused on, for genuine or disingenuous purposes. Again, one must ask, does the drug policy interpretation facilitate:

Reducing – Remediating – Recovery from drug use?

Or does the policy instead facilitate the:

Enabling – Empowering – Equipping of drug use?

This interpretative matrix needs to be applied to all drug categories and types – for example, do the following strategies lend themselves more to Enabling or Reducing on going drug use?

* Injecting rooms

* Needle Syringe Programs

* Pill Testing

* 12 Step Programs

* Therapeutic Communities

THE LOW-DOWN ON ‘DIRTY’ SYRINGES 29/5/17 (Anex)

People who inject drugs in Australia can appear to be well provided for with regard to sterile needles and syringes. Across the country there are 3500 needle and syringe programs (NSPs) which distribute almost 50 million pieces of equipment a year. But the international best practice for injecting drugs of a fresh needle for every injection is far from reality. People who inject drugs reuse syringes, share equipment like spoons, water and tourniquets, and a small proportion continue to share injecting equipment with others

. A 20-year survey by the Australian NSP Survey showed that…. Since 2011 the reuse had hovered around 21-25 per cent. The percentage of people who inject drugs who reported they shared syringes with others was also steady at 15-16 per cent from 2011-2015. And the sharing of equipment other than needles remained stable at 28-31 per cent.

This article in a recent ANEX update – notice the nonchalant manner that ‘best practice’ is used and the blithely mentioned MILLIONS of tax-payers funded syringes being unaccountably handed out, yet having 30% of injecting drug users STILL sharing equipment with 16% still sharing needles!

Of course, this proliferation of unaccountable injecting gear has been a key element in the rabid rise in street use and syringe/needle discarding. So, what may be the answer? Will we need to have 3500 injecting rooms open 24/7 for convenience of use and ease of access? Facilities too, with absolute zero accountability as there is absolutely NO potential ‘stigma bestowing’ process permitted that might challenge the behaviour of the self-harming drug taker!

If every injecting episode for every Intravenous drug user was to take place in an injecting room and a sunset clause on such behaviour, ensuring a transitioning to drug use exiting measures, then this might have some merit, as catastrophically expensive and unmanageable as that would be. However, the data tells us that for every single injecting episode that occurs ‘under supervision’, there are over 90 that happen elsewhere!

The appalling ‘health care’ logic, or lack of, is very concerning! It becomes even more so when policy caveats of ‘non-judgemental’ attitudes (whatever that this subjective descriptor can mean) are foisted upon, even the NSP staff – However, NO SUCH MORAL COMMENTARY can be levelled, what-so-ever, at the person who is the self-harming, law breaking, body destroying, and no doubt, family grieving drug taker! This at best is

‘moral’ hypocrisy – at worst unconsumable! (Of course, that last sentence itself is viewed as counterproductive and stigmatizing and thus not permitted in the discourse!)

“The perpetual permission of harm reduction only policies, NOT prohibition is putting lives at risk!” Dalgarno Institute.

Injecting Rooms

Gary Christian, Secretary for Drug Free Australia, has pointed to the lack of success by the Kings Cross Injecting Centre (MSIC) in reducing overdose deaths in the Kings Cross area. He said, “Tracking of overdose deaths in the Kings Cross area from 5 years before the injecting room opened compared with the 9 years after the injecting room was opened showed no change whatsoever in the percentage of deaths in the area as compared to the rest of NSW. The KPMG review showed that Kings Cross had 12% of NSW opiate deaths before the commencement of the MSIC, and in the 9 years after it remained at 12%, such has been its failure to make any difference.”

Evidence given to the NSW Parliament indicates that overdoses in the Kings Cross injecting room are 32 times higher than the overdose histories of those entering the injecting room, indicating that clients are experimenting with higher doses of opiates and cocktails of drugs knowing that if they should overdose in their experimentation, someone will bring them around. NSW Hansard records testimony from ex-clients of the injecting room who were rehabilitating from drugs that experimentation with higher doses of drugs is the reason for the inordinately high overdose rate in the room.

The question now appears to not be about ‘best practice’, but simply what emotive or socio-political drivers dictate when it comes to drug policy – So, where do you land? If you’re all for drug use, then another conversation and investigation in to the why of that is your priority. However, the disturbing reality for the tens of thousands of ex-users who already know the ultimate outcome of illicit drug use is. The reality is, those conversations and investigations are near impossible for a person using the substance in a culture that passively, no, actively permits it!

Any enterprise that inadvertently enables, empowers or equips ongoing illicit drug use has already breached best health care practice. Harm Reduction can never be about the support of on-going, health diminishing substance use. Caring, responsible and civic minded clinicians and policy makers will always be focused on movement toward exit from, and cessation of drug use. Mechanisms that enable any government agency to send a message to the community that we are not only supporting, but enabling tax payer funded illicit drug use, not only breaches care for the illegal drug user, but breaches international conventions. It also demonstrates a lack of concern for most of the non-drug using community.

I trust a thorough ‘best practice’ consideration of any drug policy ‘strategy’ will always seek to reduce demand for and use of any illicit drug, if not for the sake of the drug user, then for the wider community, who the vast majority of are illicit drug free. Our emerging generation need proactive and protective mechanisms to give them best chance to live drug free lives.

Let us be very clear, we are not conducting a ‘war against drugs’. We are however fighting for the brains, potentials, and in many instances, the very future of an entire emerging generation. (Dr Bertha Madras – Harvard) That for any caring civic minded human being is a fight worth having, and one worth joining!

Source: dbrecoveryresources.com/2018/04/permission-empowered-drug-policy-interpretations-drive-demand-for-drug-use/ Dalgarno Institute

July 2017 Revised January 2018

Injury Prevention Centre: Who we are

The Injury Prevention Centre (IPC) is a provincial organization that focuses on reducing catastrophic injury and death in Alberta. We act as a catalyst for action by supporting communities and decision-makers with knowledge and tools. We raise awareness about preventable injuries as an important component of lifelong health and wellness. We are funded by an operating grant from Alberta Health and we are housed at the School of Public Health, University of Alberta.

Injury in Alberta

Injuries are the leading cause of death for Albertans aged 1 to 44 years. In 2014, injuries resulted in 2,118 deaths, 63,913 hospital admissions and 572,653 emergency department visits. Of all age groups, young adults, 20 to 24 years old had the highest percentage of injury deaths with 84.9%. Youth, 15 to 19 years of age had the second highest percentage of injury deaths with 76.4%.

1. Alberta is spending an estimated $4 billion annually on injury – that amounts to $1,083.00 for every Albertan.

2. Potential impact of cannabis legalization on injury in Alberta In 2018, the Government of Canada will legalize the use of cannabis for recreational purposes. In the United States, some jurisdictions have similarly legalized cannabis for recreational use and have collected data on the changes in injuries due to cannabis use. Jurisdictions that have legalized the use of recreational as well as medical cannabis have experienced increases in injuries due to burns (100%), pediatric ingestion of cannabis (48%), drivers testing positive for cannabis and/or alcohol and drugs (9%), drivers testing positive for THC (6%) and drivers testing positive for the metabolite caboxy-THC (12%) when comparing pre- and post-legalization numbers.

3. (pg. 149) Of greatest concern are the traffic outcomes. “Fatalities substantially increased after legislation in Colorado and Washington, from 49 (in 2010) to 94 (in 2015) in Colorado, and from 40 to 85 in Washington. These outcomes suggest that after legislation, more people are driving while impaired by cannabis.”

4. (pg.155) Alberta can expect to see similar changes in injuries when the new laws take effect. The objective of this document is to recommend policies for inclusion in the Alberta Cannabis Framework that will minimize negative impacts of cannabis legalization on injuries to Albertans. Our focus is on:

* Preventing Cannabis-Impaired Driving

* Preventing Poisoning of Children by Cannabis

* Preventing Burns due to Combustible Solvent Hash Oil Extraction

* Preventing Other Injuries due to Cannabis Impairment

* Developing Surveillance to Identify Trends in Cannabis-Related injury

* Implementing a Comprehensive Public Education Plan

Injuries due to cannabis impairment in Alberta can be expected to rise following the legalization of recreational cannabis use. To mitigate the negative effects of legalization on injuries in Alberta, the Injury Prevention Centre recommends the Government of Alberta take the following actions for:

Preventing Cannabis-Impaired Driving

Impose administrative sanctions at a lower limit than Criminal Code impairment

Mandate a lower per se levels for THC/alcohol co-use

Increase sanctions for co-use of alcohol and cannabis

Separate cannabis and alcohol outlets by the creation of a public retail system for the distribution of cannabis products

Support Research to Improve Enforcement Tools

Apply sufficient resources to training and enforcement

Conduct public education regarding cannabis-impaired driving .

Preventing Poisoning of Children by Cannabis

Uphold federal legislation regarding packaging

Support public education on cannabis poisoning’

Preventing Burns due to Combustible Solvent Hash Oil Extraction

Prohibit the production of cannabis products using combustible solvents if it fails to appear in federal Bill C45.

Implement public education regarding the dangers of producing cannabis products using combustible solvents

Preventing Other Injuries due to Cannabis-Impairment

Inform the public about the risks of other activities when impaired

Develop Surveillance to Identify Trends in Cannabis-Related injury

Collect and analyze emergency department, hospital admission and death data for injuries involving cannabis impairment

Develop and implement a comprehensive public education campaign about the safe use of cannabis

Source: https://injurypreventioncentre.ca/downloads/positions/IPC%20-%20Cannabis%20Legalization Jan. 2018

EXECUTIVE SUMMARY

The objectives of this risk assessment were to:

· ascertain the state of the science in research into the potential health effects of low levels of tetrahydrocannabinol (THC) and other cannabinoids found in Cannabis sativa;

· identify key health hazards that may be associated with the presence of THC and other cannabinoids in consumer products made with industrial hemp (C. sativa cultivars with <0.3% (w/w) THC);

· assess the human health safety of the Canadian limit of 10 ug/g THC for raw materials and products made from industrial hemp; and

· to identify uncertainties and critical data gaps in the risk assessment.

Of the more than 60 cannabinoids identified in C. sativa, the toxicity of THC is the best characterized. Limited toxicity data have been reported for two other cannabinoids, cannabidiol (CBD) and cannabinol (CBN), but there are no toxicity data on the remaining cannabinoids.

Two key hazards of cannabinoid exposure are neuroendocrine disruption and neurological impairment. Neuroendocrine disruption by low levels of cannabinoids during developmental stages (perinatal, prepubertal, pubertal) leads to permanent adverse effects on brain and reproductive system development in animals. The lowest observed effect level (LOEL) for neuroendocrine disruption by THC was 1 ug/kg/d derived from a study in rats (no suitable human studies were available). Such effects could occur in humans. Similarities in the types of adverse effects, the cannabinoid receptor distribution in the brain, and the pharmacokinetics and metabolism of cannabinoids among humans and animal species support the extrapolation from animal data to humans for the purposes of risk assessment. Neurological impairment is manifested as deficits in performance with respect to cognitive and motor skills. The LOEL for neurological impairment by THC was 70 ug/kg based on data from a dose-response study in which human subjects who had a history of marihuana use received a single oral dose of THC, and cognitive and motor skills and perception of psychoactive effects were measured.

It was not deemed possible to develop a tolerable daily intake (TDI) due to the lack of a no observed effect level (NOEL), lack of data on chronic exposure and lack of data on the potential contribution of other cannabinoids to the adverse effects. Potential health risks of foods made with industrial hemp ingredients were characterized by estimating the amount of food from various food categories that would need to be eaten to reach a dose of THC equal to the LOELs for neurological impairment in humans and neuroendocrine effects in animals. Potential health risks from use of cosmetics and personal care products and nutraceuticals made with industrial hemp oil were characterized by comparing exposure to

THC through product use with the LOELs for neurological impairment in humans and neuroendocrine effects in animals. These exposure estimates were based on the assumption that the THC concentration in industrial hemp-based in ingredients was 10 ug/g, the current Canadian guideline.

The direct comparison of exposure results with the LOELs does not address:

· the bioaccumulative potential of THC with repeated dosing or consumer use;

· the lack of an identified NOELfor THC for neuroendocrine disruption or neurological impairment;

· the potential that some individuals may be more sensitive to THC than the adults with a history of marihuana use for which the LOEL of 70 ug/g for neurological impairment was observed;

· the possibility that humans could be more sensitive to THC than the rats in the study used to derive the LOEL of 1 ug/kg for neuroendocrine disruption; and,

· the potential for neuroendocrine disruption or neurological impairment by other cannabinoids (i.e. CBD, CBN and others) that would be present in industrial hemp-based products (concentrations of these have not been measured).

In consideration of the above uncertainties, the conclusions from the risk characterization were as follows:
Food: Risk of neuroendocrine disruption: Likely.

Risk of neurological impairment and psychoactivity: Likely, particularly for children.

With respect to neurological impairment, the amount of each food type that would need to be consumed to deliver a dose of THC equal to the LOEL exceeded the mean daily intake and "serving size" which may suggest an absence of risk. In the case of the child; however, some foods (dairy substitutes and candy) were identified that could be consumed in sufficient quantities on occasion in a single day or a single sitting to cause neurological impairment, or even psychoactive effects. For example 2.3 ice cream bars could deliver a dose of THC of 70 ug/kg (the LOEL for neurological impairment) and 4.6 ice cream bars could deliver a dose of 140 ug/kg (the LOEL for psychoactivity) for a 33.9 kg child.

Cosmetics: Risk of neuroendocrine disruption: Possible

Risk of neurological impairment: Unlikely

The risk of neurological impairment cannot be excluded entirely, particularly in the case of children without further information on the relative sensitivities of children vs adults, the relative sensitivities of marihuana users vs non users, the effects of repeated exposure over a long time period, the effects and concentrations of cannabinoids other than THC and the extent of dermal penetration and systemic exposure of topically applied cannabinoids under conditions of actual product use.

Nutraceuticals: Risk of neuroendocrine disruption: Likely

Risk of neurological impairment: Possible, particularly in children.

Major shortcomings related to key data gaps identified in the assessment that preclude the development of definitive conclusions regarding the degree of potential risk are:

· the inability to consider the potential contribution of cannabinoids other than THC (limited toxicity data for other cannabinoids indicate their ability to cause neuroendocrine disruption) to the overall health risks;

· the inability to consider the long term effects of bioaccumulation of THC over time from repeated low dose exposure due to lack of chronic low level toxicity studies and lack of data on the steady-state pharmacokinetics of THC;

· the inability to consider the effects of THC and other cannabinoids after multi-generation long term exposure;

· the inability to determine the degree of exposure to the developing fetus and nursing infant; and

· the lack of analytical data for THC and other cannabinoid concentrations, at detectable levels, in raw materials and finished products made from industrial hemp.

Abstract

Metabolic and behavioural effects of, and interactions between Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are influenced by dose and administration route.

Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous (sc.) THC, CBD and THC+CBD. Concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and CBD in serum and brain were determined over 24h, locomotor activity (open field) and sensorimotor gating (prepulse inhibition, PPI) were also evaluated.

In line with recent knowledge we expected metabolic and behavioural interactions between THC and CBD. While cannabinoid serum and brain levels rapidly peaked and diminished after pulmonary administration, sc. and oral administration produced long-lasting levels of cannabinoids with oral reaching the highest brain levels.

Except pulmonary administration, CBD inhibited THC metabolism resulting in higher serum/brain levels of THC. Importantly, following sc. and oral CBD alone treatments, THC was also detected in serum and brain. S.c. cannabinoids caused hypolocomotion, oral treatments containing THC almost complete immobility.

In contrast, oral CBD produced mild hyperlocomotion. CBD disrupted, and THC tended to disrupt PPI, however their combination did not.

In conclusion, oral administration yielded the most pronounced behavioural effects which corresponded to the highest brain levels of cannabinoids. Even though CBD potently inhibited THC metabolism after oral and sc. administration, unexpectedly it had minimal impact on THC-induced behaviour.

Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD-only products, might have important legal and forensic ramifications.

Source: Eur Neuropsychopharmacol. 2017 Dec;27(12):1223-1237. doi: 10.1016/j.euroneuro.2017.10.037. Epub 2017 Nov 10.

Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover In Brief

Fall 2014 • Volume 8 • Issue 3 An Introduction To Co-Occurring Borderline Personality Disorder And Substance Use Disorders

This In Brief is for health and human services professionals (e.g., social workers, vocational counselors, case managers, healthcare providers, probation officers). It is intended to introduce such professionals to borderline personality disorder (BPD)—a condition with very high rates of suicide and self-harm that often co-occurs with substance use disorders (SUDs).

This In Brief presents the signs and symptoms of BPD, with or without a co-occurring SUD, alerts professionals to the importance of monitoring clients with BPD for self-harm and suicidal behavior, and encourages professionals to refer such clients for appropriate treatment.

This In Brief is not meant to present detailed information about BPD or treatment guidelines for BPD or SUDs. How Common Is BPD?1 Estimates of BPD prevalence in the U.S. population range from 1.6 percent to 5.9 percent. BPD affects approximately 10 percent of all psychiatric outpatients and up to 20 percent of all inpatients.

What Is Borderline Personality Disorder?

BPD is one among several personality disorders (e.g., narcissistic personality disorder, paranoid personality disorder, antisocial personality disorder). According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),1 personality disorders are generally characterized by:

■ Entrenched patterns of behavior that deviate significantly from the usual expectations of behavior of the individual’s culture.

■ Behavior patterns that are pervasive, inflexible, and resistant to change.

■ Emergence of the disorder’s features no later than early adulthood (unlike depression, for example, which can begin at any age).

■ Lack of awareness that behavior patterns and personality characteristics are problematic or that they differ from those of other individuals.

■ Distress and impairment in one or more areas of a person’s life (often only after other people get upset about his or her behavior).

■ Behavior patterns that are not better accounted for by the effects of substance abuse, medication, or some other mental disorder or medical condition (e.g., head injury).

BPD is a complex and serious mental illness. Individuals with BPD are often misunderstood and misdiagnosed. A history of childhood trauma (e.g., physical or sexual abuse, neglect, early parental loss) is more common for individuals with BPD.1,2 In fact, many individuals with BPD may have developed BPD symptoms as a way to cope with childhood trauma. However, it is important to note that not all individuals with BPD have a history of childhood trauma. It is also important to note that some of the symptoms of BPD overlap with those of several other DSM-5 diagnoses, such as bipolar disorder and posttraumatic stress disorder (PTSD).

Therefore, a diagnosis of BPD should be made only by a licensed and experienced mental health professional (whose scope of practice includes diagnosing mental disorders) and then only after a thorough assessment over time. Individuals with BPD often require considerable attention from their therapists and are generally considered to be challenging clients to treat.3,4,5 However, BPD may not be the chronic disorder it was once thought to be.

In Brief BPD often respond to appropriate treatment and may have a good long-term prognosis,1,5 experiencing a remission of symptoms with a relatively low occurrence of relapse.6,7 The DSM-5 indicates that BPD is diagnosed more often in women than in men (75 percent and 25 percent, respectively).1 Other research, however, has suggested that there may be no gender difference in prevalence in the general population,5,6 but that BPD is associated with a significantly higher level of mental and physical disability for women than it is for men.6 In addition, the types of co-occurring conditions tend to be different for women than for men. In women, the most common co-occurring disorders are major depression, anxiety disorders, eating disorders, and PTSD. Men with BPD are more likely to have co-occurring SUDs and antisocial personality disorder, and they are more likely to experience episodes of intense or explosive anger.8,9

What Are the Symptoms of BPD?

The DSM-5 classifies mental disorders and includes specific diagnostic criteria for all currently recognized mental disorders. It is a tool for diagnosis and treatment, but it is also a tool for communication, providing a common language for clinicians and researchers to discuss symptoms and disorders. According to the DSM-5, the symptoms of BPD include:1

■ Intense fear of abandonment and efforts to avoid abandonment (real or imagined).

■ Turbulent, erratic, and intense relationships that often involve vacillating perceptions of others (from extremely positive to extremely negative).

■ Lack of a sense of self or an unstable sense of self

■ Impulsive acts that can be hurtful to oneself (e.g., excessive spending, reckless driving, risky sex).

■ Repeated suicidal behavior or gestures or self-mutilating behavior. (See the section below on suicide and nonsuicidal self-injury.)

■ Chronic feelings of emptiness

■ Episodes of intense (and sometimes inappropriate) anger or difficulty controlling anger (e.g., repeated physical fights, inappropriate displays of anger)

■ Temporary feelings of paranoia (often stress-related) or severe dissociative symptoms (e.g., feeling detached from oneself, trancelike).

Anyone with some of these symptoms may need to be referred to a licensed mental health professional for a complete assessment. Exhibit 1 presents some examples of how a person with BPD might behave. Suicide and nonsuicidal self-injury BPD is unique in that it is the only mental disorder diagnosis that includes suicide attempts or self-harming behaviors among its diagnostic criteria.3 The risk of suicide is high among individuals with BPD, with as many as 79 percent reporting a history of suicide attempts10 and 8 percent to 10 percent dying by suicide—a rate that may be 50 times greater than the rate among the general population.11 More than 75 percent of individuals with BPD engage in deliberate self-harming behaviors known as nonsuicidal self-injury (NSSI) (e.g., cutting or burning themselves).12 Unlike suicide attempts, NSSI does not usually involve a desire or intent to die. Sometimes the person with BPD does not consider these behaviors harmful.4 One study involving 290 patients with BPD found that 90 percent of patients reported a history of NSSI, and over 70 percent reported the use of multiple methods of NSSI.10 Reasons for NSSI vary from person to person and, for some individuals, there may be more than one reason. The behaviors may be: 4,13,14

■ A way to express anger or pain

■ A way to relieve pain (i.e., shifting from psychic pain to physical pain)

■ A way to “feel” something.

■ A way to “feel real.”

■ An attempt to regulate emotions.

■ A form of self-punishment.

■ An effort to get attention or care from others. NSSI may include: 4,13,14

■ Cutting.

■ Burning.

■ Skin picking or excoriation.

■ Head banging.

■ Hitting.

■ Hair pulling

Exhibit 1. Examples of Symptomatic Behavior (BPD)

■ Patterns of intense and unstable relationships

John comes in to see his case manager, George, and announces that he plans to marry a woman he met at a speed-dating event the night before. George has heard this same story from John at least once a month for the past 4 months.

■ Emotions that seem to change quickly from one extreme to another

Suzie has been working with a vocational rehabilitation counselor, Tony, for 2 weeks to prepare for job retraining. One day, just after Tony gets everything set up for Suzie to begin her training, Suzie storms out of the office screaming at him, “You’re just trying to get rid of me! You don’t understand me at all! I hate you!” Later, when Tony calls to suggest that maybe Suzie would prefer to work with another counselor, Suzie begins to cry and says, “Please don’t drop me, Tony! I need you!”

■ Evidence of self-harm or self-mutilation

José is a probation officer. During his weekly appointment with his client, Annie, José notices a pattern of recent cuts across her left forearm. José asks her about them, and Annie becomes defensive and says, “Okay, I cut myself sometimes, so what? It’s none of your business. I’m not hurting anybody!”

■ Pattern of suicidal thoughts, gestures,* or attempts

Maria is a nurse. As she looks over the health history of her new patient, Sally, she notices that Sally has been hospitalized three times in the past 4 years after suicide attempts, and that she has seen six different therapists. Sally tells her, “Yeah, I get suicidal sometimes. I just can’t seem to find the right therapist who can help me.”

■ Intense displays of emotion that often seem inappropriate or out of proportion to the situation

Regina is a social worker at a domestic violence shelter. She notices one of her clients, Elena, sitting in the living room with a sketchpad in her lap. Regina asks if she can see what Elena is drawing. Elena turns the sketchpad around to reveal a beautiful, detailed drawing of the shelter house. Regina admires it and says how beautiful it is, then says, “That’s funny, I thought that the house number was on the right side of the door.” Elena, who had been smiling, takes the sketchpad from Regina, looks at the drawing, then rips it from the pad and begins tearing it up, saying, “You’re right, it’s all wrong! I’ll have to start all over again!”

*Regarding the word gestures: It is dangerous to dismiss or label any suicidal behavior as a gesture. Anyone who exhibits suicidal thoughts or behaviors of any kind needs to be assessed by a licensed mental health professional.

What Are the Symptoms of SUDs?

SUDs involve patterns of recurrent substance use that result in significant problems, which fall into the following categories:1

■ Impaired control—taking more of the substance than intended, trying unsuccessfully to cut down on use, spending an increasing amount of time obtaining and using the substance, craving or having a strong desire for substance use

■ Social impairment—failing to fulfill obligations at work, school, or home; continuing substance use in spite of the problems it causes; giving up or reducing other activities because of substance use

■ Risky use—using the substance(s) in situations in which it may be physically dangerous to do so (e.g., driving) or in spite of physical or psychological problems that may have been caused or may be made worse by substance use (e.g., liver problems, depression)

■ Pharmacological criteria—displaying symptoms of tolerance (need for increased amounts of the substance to achieve the desired effect) or withdrawal (a constellation of physical symptoms that occurs when the use of the substance has ceased)

What Is the Relationship Between BPD and SUDs?

One study15 found that the prevalence of BPD among individuals seeking buprenorphine treatment for opioid addiction exceeded 40 percent, and another16 found that nearly 50 percent of individuals with BPD were likely to report a history of prescription drug abuse. A large survey6 found that 50.7 percent of individuals with a lifetime diagnosis (i.e., meeting the criteria for a diagnosis at some point during the individual’s life) of BPD also had a diagnosis of an SUD over the previous 12 months. This same survey found that for individuals with a lifetime diagnosis of an SUD, 9.5 percent also had a lifetime diagnosis of BPD. This is a significantly higher incidence of BPD than that in the general public, which ranges from 1.6 percent to 5.9 percent.1

One longitudinal study17 found that 62 percent of patients with BPD met criteria for an SUD at the beginning of the study. However, over 90 percent of patients with BPD and a co-occurring SUD experienced a remission of the SUD by the time of the study’s 10-year follow-up. (Remission was defined as any 2-year period during which the person did not meet criteria for an SUD.) The authors also looked at whether there were recurrences of SUDs after periods of remission and found that the rate of recurrence was 40 percent for alcohol and 35 percent for drugs. The rate of new onsets of SUDs, while lower than expected, was still 21 percent for drugs and 23 percent for alcohol.

Another study18 found that individuals with BPD had higher rates of new SUD onsets even when their BPD symptoms improved (compared with new SUD onsets for individuals with other personality disorders). A client with BPD and a co-occurring SUD presents some particular challenges. BPD is difficult to treat, partly because of the pervasive, intractable nature of personality disorders and partly because clients with BPD often do not adhere to treatment and often drop out of treatment. The impulsivity, suicidality, and self-harm risks associated with BPD may all be exacerbated by the use of alcohol or drugs.19 In addition, the presence of BPD may contribute to the severity of SUD symptoms,20 and the course of SUD treatment may be more complicated for clients who also have BPD.21

Who Can Best Provide Treatment for People With BPD and SUDs?

Individuals who display some of the symptoms of BPD (as described above) should be referred to an experienced licensed mental health professional for a thorough mental health assessment and possible referral to treatment. It is important to know whether referral sources have experience treating clients with BPD. If individuals display symptoms of substance misuse, they should also be assessed for a co-occurring SUD. Individuals with BPD sometimes trigger intense feelings of frustration and even anger in their therapists and other providers.12

Clients with BPD often have difficulty developing good relationships, including productive working relationships with therapists and other providers (e.g., healthcare workers, case managers, vocational counselors). Some individuals with BPD may move from therapist to therapist (or other professionals) in an effort to find “just the right person.” Individuals who have an SUD may receive treatment from an individual counselor or therapist or from an outpatient treatment program. However, a co-occurring diagnosis of BPD may complicate SUD treatment. It is important for the professionals treating the person for either diagnosis to work in consultation with each other.

Treatment for BPD—especially with a co-occurring SUD— sometimes involves a team approach. Depending on the treatment plan, a person may have an individual therapist, a group therapist, a substance abuse counselor, a psychiatrist, and a primary care provider; treatment may need to be planned and managed through the coordinated efforts of all providers. Regular consultation among all providers can ensure that everyone is working toward the same goals from each of their professional perspectives. For example:

■ In individual therapy sessions, a therapist may help the client learn to tolerate gradually increasing levels of uncomfortable emotions (e.g., stress, anxiety) so that the client may begin to have more control over those emotions.

■ A psychiatrist may consider the use of medication for the client or evaluate currently prescribed medications to determine adherence and their effect on the client’s ability to engage in the emotional work of therapy.

■ A substance abuse counselor may work with the client to achieve abstinence, identify relapse triggers that may come up as the client does emotional work in therapy, and identify coping strategies for remaining abstinent.

■ A vocational counselor may need to work with the client on distress tolerance as it relates to employment issues, such as applying for jobs or beginning a new job. This may mean helping the client understand the importance of being at interviews, vocational training classes, or work on time (even if emotional problems make that difficult) and helping the client develop strategies to achieve a pattern of good work habits. Some people with BPD may consciously or unconsciously attempt to sabotage treatment by providing conflicting information to providers or by trying to turn one provider against another. Consultation among all providers can help deter this.

What Treatments Are Available for Individuals With BPD and SUDs?

Many studies have been done on treatment approaches for BPD or SUDs, but very few have involved participants with co-occurring BPD and SUDs.22,23,24 However, based on the studies that have been done on co-occurring BPD and SUDs, a few approaches seem to show promise.

Perhaps the most researched approach is Dialectical Behavior Therapy, which has been adapted for treatment of co-occurring BPD and SUDs (Dialectical Behavior Therapy-S [DBT-S]). It is important to note, however, that DBT-S and other promising approaches involve structured, manualized treatments that are quite intensive and require a significant amount of training and resources (e.g., staffing, space, finances) that may not be available in all areas.25 Many therapists work on their own with individuals who have BPD, using the best techniques that their training and experience have to offer—hopefully in regular consultation with an experienced clinical supervisor. Therapists often adapt psychotherapy to better meet the needs of an individual client, sometimes combining different therapeutic approaches or mixing techniques.4

However, for clients with both BPD and SUDs, the therapist may need to work with an SUD treatment provider to provide comprehensive care. Pharmacotherapy for BPD and SUDs The Food and Drug Administration (FDA) has not approved any medications for the treatment of BPD. However, individuals with BPD may take medications to alleviate some of their symptoms.11,22 For example, selective serotonin reuptake inhibitors may be prescribed for depressed mood, irritability, anger, and impulsivity.11 There are several FDA-approved medications for SUD treatment. For alcohol use disorder, these include acamprosate, disulfiram, and naltrexone.26

For opioid use disorder, approved medications include buprenorphine, a combination of buprenorphine and naloxone, methadone, and naltrexone.27 Some of these medications may be prescribed on a short-term basis (e.g., to ease withdrawal symptoms, lessen cravings), and others may be prescribed for long-term use (e.g., to facilitate longer periods of abstinence).26,27 Individuals may receive their prescriptions and medication management from a psychiatrist, from other types of healthcare providers, or from both (or, in the case of methadone, from an opioid treatment program). Individuals may take medication as one part of a treatment plan that also includes attending individual therapy, group therapy, group skill-building sessions, or a mutual-help group (e.g., 12-step program), or some combination of these.

What Are Some Things To Remember When Working With Someone Who Has Co-Occurring BPD and SUDs?

Some of the same guidelines that have been identified as necessary for mental health professionals who work with clients who have these two diagnoses may also be helpful for all human services professionals. Working with a client who has co-occurring BPD and SUDs requires:

■ Strong (but not rigid) professional boundaries—Be clear with the person about the expectations in the working relationship (e.g., length of appointments, level of support, contact outside regular appointments). Be aware of special requests to make exceptions to the usual rules for working with clients. These requests sometimes escalate over time. If in doubt about making an exception to the rules, discuss the situation with a supervisor who is knowledgeable about working with individuals who have BPD (within applicable confidentiality requirements).11

■ A commitment to self-care—If possible, schedule appointments with someone who has BPD right before lunch or before a break. Avoid scheduling back-to-back appointments with two individuals who have BPD. It is important to have some time between them to see clients with other diagnoses, to work on other tasks, or simply to take a break. Develop the habit of leaving work at work (i.e., don’t “replay” interactions with individuals who have BPD).

■ An awareness of how BPD may affect any kind of work with the individual—For example, fearing abandonment and avoiding abandonment are characteristics of BPD and may manifest in some unexpected ways. For example, if the professional relationship has focused on the person with BPD completing certain goals, that person may thwart his or her own progress to avoid the feelings of abandonment that would result from ending the working relationship.

■ Knowledge about what skills the individual who has BPD is learning in therapy—The person may need assistance applying those new skills to broader life situations. For example, perhaps one skill the person has learned is how to break down a seemingly overwhelming task into a series of small steps. Work with the person to apply that particular skill to the situation at hand.

Conclusions

It is important to remember that:

■ Most human services professionals will encounter clients with BPD in the course of their work.

■ Individuals with BPD often have co-occurring diagnoses (e.g., depression, SUDs). ■ BPD is often characterized by intense emotional displays and impulsive acts (e.g., self-harm, suicide attempts).

■ Working with an individual with BPD (with or without a co-occurring SUD) can be challenging.

■ Individuals with BPD (with or without a co-occurring SUD) deserve to receive appropriate treatment and deserve to be treated with compassion and respect.

■ Individuals with BPD often respond to appropriate treatment and experience a remission of symptoms with a relatively low occurrence of relapse.

■ Individuals with BPD (with or without a co-occurring SUD) may have a team of professionals who provide different aspects of care (e.g., therapist, psychiatrist).

■ It is important for all professionals involved in the care of an individual with BPD to communicate and work together.

Resources

SAMHSA resources

National Registry of Evidence-based Programs and Practices http://nrepp.samhsa.gov

Treatment Improvement Protocols (TIPs) (see back page for electronic access and ordering information)

TIP 36: Substance Abuse Treatment for Persons With Child Abuse and Neglect Issues

TIP 42: Substance Abuse Treatment for Persons With Co-Occurring Disorders

TIP 44: Substance Abuse Treatment for Adults in the Criminal Justice System

TIP 50: Addressing Suicidal Thoughts and Behaviors in Substance Abuse Treatment Web resources

American Psychiatric Association http://www.psych.org

American Psychological Association http://www.apa.org

Borderline Personality Disorder Resource Center http://bpdresourcecenter.org

Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover 7 An Introduction to Co-Occurring Borderline Personality Disorder and Substance Use Disorders Fall 2014, Volume 8, Issue 3

National Education Alliance for Borderline Personality Disorder http://www.borderlinepersonalitydisorder.com

National Institute of Mental Health http://www.nimh.nih.gov

National Institute on Drug Abuse http://www.drugabuse.gov

Notes

1 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

2 Battle, C. L., Shea, M. T., Johnson, D. M., Yen, S., Zlotnick, C., Zanarini, M. C., et al. (2004). Childhood maltreatment associated with adult personality disorders: Findings from the Collaborative Longitudinal Personality Disorders Study. Journal of Personality Disorders, 18(2), 193–211.

3 Dimeff, L. A., Comtois, K. A., & Linehan, M. M. (2009). Cooccurring addiction and borderline personality disorder. In R. K. Ries, D. A. Fiellin, S. C. Miller, & R. Saitz (Eds.), Principles of addiction medicine (4th ed., pp. 1227–1237). Philadelphia: Lippincott Williams & Wilkins.

4 National Institute of Mental Health. (2011). Borderline personality disorder. NIH Publication No. 11‑4928. Bethesda, MD: Author.

5 Substance Abuse and Mental Health Services Administration. (2011). Report to Congress on borderline personality disorder. HHS Publication No. (SMA) 11‑4644. Rockville, MD: Substance Abuse and Mental Health Services Administration.

6 Grant, B. F., Chou, S. P., Goldstein, R. B., Huang, B., Stinson, F. S., Saha, T. D., et al. (2008). Prevalence, correlates, disability, and comorbidity of DSM-IV borderline personality disorder: Results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Journal of Clinical Psychiatry, 69, 533–545.

7 Zanarini, M. C., Frankenburg, F. R., Hennen, J., Reich, D. B., & Silk, K. R. (2005). The McLean Study of Adult Development (MSAD): Overview and implications of the first six years of prospective follow-up. Journal of Personality Disorders, 19(5), 505–523.

8 Sansone, R. A., & Sansone, L. A. (2011). Gender patterns in borderline personality disorder. Innovations in Clinical Neuroscience, 8(5), 16–20.

9 Tadíc, A., Wagner, S., Hoch, J., Başkaya, Ö., von Cube, R., Skaletz, C., et al. (2009). Gender differences in axis I and axis II comorbidity in patients with borderline personality disorder. Psychopathology, 42, 257–263.

10 Zanarini, M. C., Frankenburg, F. R., Reich, D. B., Fitzmaurice, G., Weinberg, I., & Gunderson, J. G. (2008). The 10-year course of physically self-destructive acts reported by borderline patients and axis II comparison subjects. Acta Psychiatrica Scandinavica, 117, 177–184.

11 American Psychiatric Association. (2001). Practice guideline for the treatment of patients with borderline personality disorder. American Journal of Psychiatry, 158, 1–52.

12 Black, D. W., & Andreasen, N. C. (2011). Introductory textbook of psychiatry (5th ed.). Washington, DC: American Psychiatric Publishing.

13 Brown, M. Z., Comtois, K. A., & Linehan, M. M. (2002). Reasons for suicide attempts and nonsuicidal self-injury in women with borderline personality disorder. Journal of Abnormal Psychology, 111(1), 198–202.

14 Kleindienst, N., Bohus, M., Ludäscher, P., Limberger, M. F., Kuenkele, K., Ebner-Priemer, U. W., et al. (2008). Motives for nonsuicidal self-injury among women with borderline personality disorder. Journal of Nervous and Mental Disease, 196(3), 230–236.

15 Sansone, R. A., Whitecar, P., & Wiederman, M. W. (2008). The prevalence of borderline personality among buprenorphine patients. International Journal of Psychiatry in Medicine, 38(2), 217–226.

16 Sansone, R. A., & Wiederman, M. W. (2009). The abuse of prescription medications: Borderline personality patients in psychiatric versus non-psychiatric settings. International Journal of Psychiatry in Medicine, 39(2), 147–154.

17 Zanarini, M. C., Frankenburg, F. R., Weingeroff, J. L., Reich, D. B., Fitzmaurice, G. M., & Weiss, R. D. (2011). The course of substance use disorders in patients with borderline personality disorder and axis II comparison subjects: A 10-year follow-up study. Addiction, 106(2), 342–348.

18 Walter, M., Gunderson, J. G., Zanarini, M. C., Sanislow, C. A., Grilo, C. M., McGlashan, T. H., et al. (2009). New onsets of substance use disorders in borderline personality disorder over 7 years of follow-ups: Findings from the Collaborative Longitudinal Personality Disorders Study. Addiction, 104, 97–103.

19 van den Bosch, L. M. C., Verheul, R., & van den Brink, W. (2001). Substance abuse in borderline personality disorder: Clinical and etiological correlates. Journal of Personality Disorders, 15, 416–424.

20 Morgenstern, J., Langenbucher, J., Labouvie, E., & Miller, K. J. (1997). The comorbidity of alcoholism and personality disorders in a clinical population: Prevalence rates and relation to alcohol typology variables. Journal of Abnormal Psychology, 106(1), 74–84.

21 Center for Substance Abuse Treatment. (2005). Substance abuse treatment for persons with co-occurring disorders. Treatment Improvement Protocol (TIP) Series 42. HHS Publication No. (SMA) 13‑3992. Rockville, MD: Substance Abuse and Mental Health Services Administration.

22 Gianoli, M. O., Jane, J. S., O’Brien, E., & Ralevski, E. (2012). Treatment for comorbid borderline personality disorder and alcohol use disorders: A review of the evidence and future recommendations. Experimental and Clinical Psychopharmacology, 20(4), 333–344.In Brief In Brief, An Introduction to Co-Occurring Borderline Personality Disorder and Substance Use Disorders

23 Kienast, T., & Foerster, J. (2008). Psychotherapy of personality disorders and concomitant substance dependence. Current Opinion in Psychiatry, 21, 619–624.

24 Pennay, A., Cameron, J., Reichert, T., Strickland, H., Lee, N. K., Hall, K., et al. (2011). A systematic review of interventions for co-occurring substance use disorder and borderline personality disorder. Journal of Substance Abuse Treatment, 41(4), 363–373.

25 Zanarini, M. C. (2009). Psychotherapy of borderline personality disorder. Acta Psychiatrica Scandinavica, 120, 373–377.

26 Center for Substance Abuse Treatment. (2009). Incorporating alcohol pharmacotherapies into medical practice. Treatment Improvement Protocol (TIP) Series 49. HHS Publication No. (SMA) 13‑4380. Rockville, MD: Substance Abuse and Mental Health Services Administration.

27 Center for Substance Abuse Treatment. (2005). Medication-assisted treatment for opioid addiction in opioid treatment programs.

Treatment Improvement Protocol (TIP) Series 43. HHS Publication No. (SMA) 12‑4214. Rockville, MD: Substance Abuse and Mental Health Services Administration.

In Brief

This In Brief was written and produced under contract numbers 270-09-0307 and 270-14-0445 by the Knowledge Application Program, a Joint Venture of JBS International, Inc., and The CDM Group, Inc., for the Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human Services (HHS). Christina Currier served as the Contracting Officer’s Representative.

Disclaimer: The views, opinions, and content of this publication are those of the authors and do not necessarily reflect the views, opinions, or policies of SAMHSA or HHS.

Public Domain Notice: All materials appearing in this document except those taken from copyrighted sources are in the public domain and may be reproduced or copied without permission from SAMHSA or the authors. Citation of the source is appreciated. However, this publication may not be reproduced or distributed for a fee without the specific, written authorization of the Office of Communications, SAMHSA, HHS. Electronic Access and Copies of Publication: This publication may be ordered or downloaded from SAMHSA’s Publications Ordering Web page at http://store.samhsa.gov. Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727) (English and Español).

Recommended Citation: Substance Abuse and Mental Health Services Administration. (2014). An Introduction to Co-Occurring Borderline Personality Disorder and Substance Use Disorders. In Brief, Volume 8, Issue 3. Originating Office: Quality Improvement and Workforce Development Branch, Division of Services Improvement, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 1 Choke Cherry Road, Rockville, MD 20857. HHS Publication No. (SMA) 14-4879 Printed 2014

Source:

https://store.samhsa.gov/product/An-Introduction-to-Co-Occurring-Borderline-Personality-Disorder-and-Substance-Use-Disorders/SMA14-4879

Interviewed by Mark Gold, MD

FEATURED ADDICTION EXPERT: Brian Fuehrlein, MD, PhD, Assistant Professor, Yale University Director, Psychiatric Emergency Room, VA Connecticut Healthcare System

If a patient has overdosed on opioid, can you describe your approach to the emergency including the exam, medications, observation and discharge-transfer?

As the director of a psychiatric emergency room at VA Connecticut and Yale, I assume the care of patients after medical stabilization. Medical stabilization often includes Narcan administration and other possible treatments. While I am not generally directly involved in the Narcan administration, I will frequently see patients soon after a Narcan reversal (days to weeks). I have a very clear approach to these patients. My approach to a patient post Narcan reversal is aggressive and assertive. In my mind, I may be the last physician that this patient sees alive. I am very aggressive when discussing the severity of the illness and the critical need for treatment. When developing a treatment plan, I am very assertive. I will spend as much time as I can with the patient attempting to motivate them for treatment. When a patient has already required a Narcan reversal (and hence nearly died) they are high risk for this to occur again. This is as critical of a patient that I care for.

We generally refer to opioid overdoses as accidental, but do you have an idea of what percentage of the patients are depressed, wanted to die, or had passive suicidal ideation? Do you formally evaluate them for concurrent psychiatric illness at some time after you save their lives?

All patients who present to the psychiatric emergency room receive a thorough psychiatric and substance use assessment. The prevalence of co-occurring psychiatric illness with opioid use disorder (OUD) is very high. By the time the OUD has progressed to the point of intravenous use leading to Narcan reversal, there are typically many psychosocial consequences and stressors. In addition, these patients are often young (<30). These severe consequences, which often occur quickly, may lead to feelings of hopelessness, helplessness and passive suicidal ideation (SI). While I do not know firm percentages, in my experience the majority of those with severe opioid use disorder suffer from comorbid anxiety and/or depression. A lower percentage, but still significant amount, experience passive SI and will report things like “I was not trying to kill myself, but if I were to never wake up the world would be better off without me”. I would say that a small but significant percentage is actively suicidal at the time of the overdose with intent to die.

Patients will often have a history of multiple overdoses. What is your approach and ideal post rescue plan? Do you transfer them to a locked unit or give them a follow-up appointment? What happens to a person who is given Narcan and rescued by an EMT?

I tend to be as aggressive and assertive as possible while discussing the severity of the illness and the dire need for intensive treatment, especially in a patient who has had multiple overdoses. I attempt to motivate every patient who has experienced an overdose to be initiated on medication-assisted treatment (MAT). If agreeable, I will start buprenorphine in the VA/Yale psychiatric emergency room. Initiating buprenorphine in an emergency room setting is difficult in practice. Given the resources available at the VA we are able to do it. This practice is based upon a recent study at Yale that showed that initiating buprenorphine in emergency setting results in patients more likely to be connected to treatment. I also educate every patient about the need for a psychosocial support structure. I am a proponent of AA/NA programs and I discuss with all patients the importance of meetings/sponsorship. The goal for all patients who present post overdose is to initiate them on buprenorphine, transfer them to our substance use treatment program (either inpatient or IOP level of care) and then to attend 90 meetings in 90 days.

Unfortunately, many patients request discharge without willingness to engage directly in treatment. While state laws differ, in CT it is often hard to commit patients involuntarily specifically for substance use. If the patient is actively or passively suicidal or manic/psychotic, etc., we can often commit them on a psychiatric commitment. But if the risk stems primarily from ongoing substance use, we are often unable to hold the patient and force treatment upon them. We try very hard to motivate them for treatment. We will also engage their family to help with the motivation. But many patients are discharged home with outpatient follow-up only. We will prescribe a Narcan rescue kit, educate about harm reduction strategies, provide an appointment to see mental health within 7 days and place a follow-up phone call the day after discharge. But we are often unable to do more unless the patient is willing.

What is your suggestion for the role of Vivitrol post Narcan care?

I attempt to motivate all patients with opioid use disorder, particularly those post overdose, to initiate buprenorphine in the psychiatric emergency room. The first line treatment is buprenorphine, unless there is a reason/contraindication. For example, if adequate trials of buprenorphine have demonstrated its lack of efficacy in that patient, or if there was an intolerable side effect or adverse reaction. Methadone is generally the second line agent that is used following a buprenorphine failure. Following a Methadone treatment failure (side effect, etc), then Vivitrol the third line agent. Veterans at the VA will have an assigned outpatient treatment coordinator. We will collaborate with the outpatient team to determine the appropriate management of the opioid use disorder. We are able to initiate buprenorphine or Vivitrol the PER but Methadone initiation is deferred to the opioid treatment program. It is critical that patients with OUD are initiated on maintenance medication (one of the 3 mentioned) AND referred to a treatment program AND AA/NA.

Can you compare patients that you would suggest for Methadone vs. Suboxone vs. Vivitrol? How do you decide the doses? How long do you suggest MAT plus therapy and when to stop?

In general, buprenorphine is the first line, Methadone is second line and Vivitrol is third line, though this depends greatly on the individual patient. At times, Methadone is the first line agent if the patient requires the structure of the opioid treatment program or if the severity of the addiction is such that high dose Methadone is preferred. In general, buprenorphine is appropriate for the majority of the patients that I see in the psychiatric emergency room. Duration of MAT therapy remains debated. It depends on many factors and is an individual decision between the physician and the patient. In my opinion, a very important consideration when deciding whether to stop MAT is the patient’s commitment to a recovery program. If the patient is going to daily meetings, has a sponsor and is completing step work, I am more likely to endorse a plan of tapering down the buprenorphine than the same patient who is relying solely on the buprenorphine for sobriety.

Other considerations include IV use, previous OD with Narcan administration and other high risk behaviors. These would make me more likely to recommend longer term use of buprenorphine. In addition, the decision to stop MAT would depend on factors like cost, side effects, etc. Opioid use disorder is a deadly illness that requires long term treatment. When the illness is severe, high risk behaviors are present and the buprenorphine is not causing problems, I am unlikely to recommend tapering it off.

Are you seeing opioid overdose and addicts concurrently using marijuana, alcohol, cocaine, methamphetamine, other? Can you give us a sense of how many patients just use one drug or are just addicted to one drug? Do you do drug testing on all patients in the ED?

Yes, we perform urine drug screens on all patients who present to the psychiatric emergency room (PER). In my experience there are several groups of patients with opioid use disorder.

The most common group of patients with OUD also have a history of other substance use disorders. Most common would be marijuana, alcohol, cocaine and sedatives. While this group has struggled with an addiction to multiple substances, the opioids are the clear drug of choice. Many patients in this group will set all other drugs aside and only use them occasionally once opioids are discovered.

The second most common group with OUD continues to use other drugs concomitantly with the opioids. They may not identify opioids (or any of the others) as a clear drug of choice. This group will often speedball (mix opioids and cocaine). They also may unfortunately mix alcohol or sedatives with opioids, which is an unfortunate combination.

The least common group has OUD with no other history of substance use.

Methamphetamine is not as common in the northeast and hence for regional considerations I do not see it commonly. As a resident in Dallas, TX, methamphetamine use, with or without opioids, was common.

Do you have a protocol for switching someone from Suboxone to Naltrexone?

In the PER we do not generally complete an opioid detox and hence do not generally switch from buprenorphine to Naltrexone. We either initiate and titrate buprenorphine for maintenance or transfer to a local rehab or detox facility for completing detox.

Do you have an opioid detox protocol that you’d use in the hospital or ED?

First, we try hard to not detox OUD patients. Patients with OUD should be on MAT and we use the psychiatric emergency room (PER) visit as a means to initiate buprenorphine. We aggressively recommend buprenorphine initiation. If agreeable, we generally will start buprenorphine 4mg in the PER once withdrawal symptoms are moderate (COWS >8). We will then repeat the 4mg dose if indicated for a maximum dose of 8mg on day 1. The patient will then spend the night in the PER for observation.

On day 2, we titrate up to a maximum dose of 16mg if indicated. At that point the patient is ready for movement to the next level of care. Occasionally, patients will require a second night in the PER to titrate the buprenorphine up and for complete stabilization of withdrawal symptoms.

Once at a stabilizing dose the patients will generally move to our 21-day substance use treatment program. While in the program the buprenorphine is titrated as necessary. Upon completion of the program the patient is referred to the buprenorphine clinic in conjunction with a psychosocial program.

If the patient is unwilling to attend the 21-day program, and buprenorphine is initiated in the PER, the patient is discharged from the PER and seen daily in the outpatient detox/stabilization clinic until an appointment is available in the buprenorphine clinic. Given the resources at the VA we are able to initiate buprenorphine in the PER with confidence that a plan on the backend is achievable.

If the patient is unwilling to be on maintenance therapy then an opioid detox is completed. This is done with either buprenorphine or symptom-driven. Typically for detox, the patient is transferred to a local detox facility that the VA contracts with.

You have worked in both the inpatient and residential drug free drug programs and now Yale in ED and MAT, can you give me a sense of what lessons you have learned from each and how each might have a role and limitations?

Residential programs are a very important part of the recovery process but are not a cure for addiction. I often encounter patients who have completed our 21-day treatment program multiple times, each time having relapsed almost immediately after completion. When patients and/or families expect that years or decades of use will be cured after 21 days in a program they will naturally be disappointed. “Treatment begins when you leave the program” is a very important tenet of recovery. A good residential program will introduce/reinforce recovery principles and motivate the patient to continue this process after completion of the program. Without a solid aftercare program, residential programs are destined to fail.

Regarding the emergency room, many providers may not see the emergency room as an ideal environment for a discussion about recovery. Every patient that I see in the PER will hear about the importance for long term treatment and the need for a solid recovery program. I will discuss long term strategies including MAT, NA and other treatment options. Even with patients who present to the PER frequently, I always spend time discussing the importance of a solid foundation of recovery and the need for MAT. Even in the context of a busy emergency room, there is always time for a brief motivational interaction which may make a real difference and save a life.

Are you seeing meth or cocaine emergencies and/or overdoses? What is your approach?

Methamphetamine is not a common drug of abuse in this region of the country. Cocaine is incredibly common and it is commonly abused in the powder form or in the form of crack. It is often used in conjunction with opioids (speedballs). When cocaine overdoses occur (rarer than opioid overdoses), the patient is seen and stabilized in the medical ER prior to transfer to the PER. With patients who are using cocaine at levels so dangerous that it leads to overdose, I am aggressive and assertive the way I am with opioids. The difference with stimulants is the lack of MAT. Hence the reliance on a psychosocial treatment becomes more important. Patients are referred to the substance use treatment program to begin the recovery process. They are then referred to AA/NA, contingency management, CBT for addiction or other psychosocial support programs.

Source: https://www.rivermendhealth.com/resources/q-a-with-brian-fuehrlein-md-phd-the-opioid-epidemic-and-emergency-room-visits November 2017

By Christopher Glazek

You’re aware America is under siege, fighting an opioid crisis that has exploded into a public-health emergency. You’ve heard of OxyContin, the pain medication to which countless patients have become addicted. But do you know that the company that makes Oxy and reaps the billions of dollars in profits it generates is owned by one family?

The newly installed Sackler Courtyard at London’s Victoria and Albert Museum is one of the most glittering places in the developed world. Eleven thousand white porcelain tiles, inlaid like a shattered backgammon board, cover a surface the size of six tennis courts. According to the V&A’s director, the regal setting is intended to serve as a “living room for London,” by which he presumably means a living room for Kensington, the museum’s neighborhood, which is among the world’s wealthiest. In late June, Kate Middleton, the Duchess of Cambridge, was summoned to consecrate the courtyard, said to be the earth’s first outdoor space made of porcelain; stepping onto the ceramic expanse, she silently mouthed, “Wow.”

The Sackler Courtyard is the latest addition to an impressive portfolio. There’s the Sackler Wing at New York’s Metropolitan Museum of Art, which houses the majestic Temple of Dendur, a sandstone shrine from ancient Egypt; additional Sackler wings at the Louvre and the Royal Academy; stand-alone Sackler museums at Harvard and Peking Universities; and named Sackler galleries at the Smithsonian, the Serpentine, and Oxford’s Ashmolean. The Guggenheim in New York has a Sackler Center, and the American Museum of Natural History has a Sackler Educational Lab. Members of the family, legendary in museum circles for their pursuit of naming rights, have also underwritten projects of a more modest caliber—a Sackler Staircase at Berlin’s Jewish Museum; a Sackler Escalator at the Tate Modern; a Sackler Crossing in Kew Gardens. A popular species of pink rose is named after a Sackler. So is an asteroid.

The Sackler name is no less prominent among the emerald quads of higher education, where it’s possible to receive degrees from Sackler schools, participate in Sackler colloquiums, take courses from professors with endowed Sackler chairs, and attend annual Sackler lectures on topics such as theoretical astrophysics and human rights. The Sackler Institute for Nutrition Science supports research on obesity and micronutrient deficiencies. Meanwhile, the Sackler institutes at Cornell, Columbia, McGill, Edinburgh, Glasgow, Sussex, and King’s College London tackle psychobiology, with an emphasis on early childhood development.

The Sacklers’ philanthropy differs from that of civic populists like Andrew Carnegie, who built hundreds of libraries in small towns, and Bill Gates, whose foundation ministers to global masses. Instead, the family has donated its fortune to blue-chip brands, braiding the family name into the patronage network of the world’s most prestigious, well-endowed institutions. The Sackler name is everywhere, evoking automatic reverence; the Sacklers themselves, however, are rarely seen. [In 1974, when the Sackler brothers made a large gift to the Met—$3.5 million, to erect the Temple of Dendur—they stipulated that all museum signage, catalog entries, and bulletins referring to objects in the newly opened Sackler Wing had to include the names of all three brothers, each followed by “M.D.”]

The descendants of Mortimer and Raymond Sackler, a pair of psychiatrist brothers from Brooklyn, are members of a billionaire clan with homes scattered across Connecticut, London, Utah, Gstaad, the Hamptons, and, especially, New York City. It was not until 2015 that they were noticed by Forbes, which added them to the list of America’s richest families.

The magazine pegged their wealth, shared among twenty heirs, at a conservative $14 billion. (Descendants of Arthur Sackler, Mortimer and Raymond’s older brother, split off decades ago and are mere multi-millionaires.) To a remarkable degree, those who share in the billions appear to have abided by an oath of omertà: Never comment publicly on the source of the family’s wealth.

That may be because the greatest part of that $14 billion fortune tallied by Forbes came from OxyContin, the narcotic painkiller regarded by many public-health experts as among the most dangerous products ever sold on a mass scale. Since 1996, when the drug was brought to market by Purdue Pharma, the American branch of the Sacklers’ pharmaceutical empire, more than two hundred thousand people in the United States have died from overdoses of OxyContin and other prescription painkillers. Thousands more have died after starting on a prescription opioid and then switching to a drug with a cheaper street price, such as heroin. Not all of these deaths are related to OxyContin—dozens of other painkillers, including generics, have flooded the market in the past thirty years. Nevertheless, Purdue Pharma was the first to achieve a dominant share of the market for long-acting opioids, accounting for more than half of prescriptions by 2001.

According to the Centers for Disease Control, fifty-three thousand Americans died from opioid overdoses in 2016, more than the thirty-six thousand who died in car crashes in 2015 or the thirty-five thousand who died from gun violence that year. This past July, Donald Trump’s Commission on Combating Drug Addiction and the Opioid Crisis, led by New Jersey governor Chris Christie, declared that opioids were killing roughly 142 Americans each day, a tally vividly described as “September 11th every three weeks.” The epidemic has also exacted a crushing financial toll: According to a study published by the American Public Health Association, using data from 2013—before the epidemic entered its current, more virulent phase—the total economic burden from opioid use stood at about $80 billion, adding together health costs, criminal-justice costs, and GDP loss from drug-dependent Americans leaving the workforce. Tobacco remains, by a significant multiple, the country’s most lethal product, responsible for some 480,000 deaths per year. But although billions have been made from tobacco, cars, and firearms, it’s not clear that any of those enterprises has generated a family fortune from a single product that approaches the Sacklers’ haul from OxyContin.

Even so, hardly anyone associates the Sackler name with their company’s lone blockbuster drug. “The Fords, Hewletts, Packards, Johnsons—all those families put their name on their product because they were proud,” said Keith Humphreys, a professor of psychiatry at Stanford University School of Medicine who has written extensively about the opioid crisis. “The Sacklers have hidden their connection to their product. They don’t call it ‘Sackler Pharma.’ They don’t call their pills ‘Sackler pills.’ And when they’re questioned, they say, ‘Well, it’s a privately held firm, we’re a family, we like to keep our privacy, you understand.’ ”

To the extent that the Sacklers have cultivated a reputation, it’s for being earnest healers, judicious stewards of scientific progress, and connoisseurs of old and beautiful things. Few are aware that during the crucial period of OxyContin’s development and promotion, Sackler family members actively led Purdue’s day-to-day affairs, filling the majority of its board slots and supplying top executives. By any assessment, the family’s leaders have pulled off three of the great marketing triumphs of the modern era: The first is selling OxyContin; the second is promoting the Sackler name; and the third is ensuring that, as far as the public is aware, the first and the second have nothing to do with one another.

If you head north on I-95 through Stamford, Connecticut, you will spot, on the left, a giant misshapen glass cube. Along the building’s top edge, white lettering spells out ONE STAMFORD FORUM. No markings visible from the highway indicate the presence of the building’s owner and chief occupant, Purdue Pharma. Originally known as Purdue Frederick, the first iteration of the company was founded in 1892 on New York’s Lower East Side as a peddler of patent medicines. For decades, it sustained itself with sales of Gray’s Glycerine Tonic, a sherry-based liquid of “broad application” marketed as a remedy for everything from anemia to tuberculosis. The company was purchased in 1952 by Arthur Sackler, thirty-nine, and was run by his brothers, Mortimer, thirty- six, and Raymond, thirty-two. The Sackler brothers came from a family of Jewish immigrants in Flatbush, Brooklyn. Arthur was a headstrong and ambitious provider, setting the tone—and often choosing the path—for his younger brothers. After attending medical school on Arthur’s dime, Mortimer and Raymond followed him to jobs at the Creedmoor psychiatric hospital in Queens. There, they coauthored more than one hundred studies on the biochemical roots of mental illness. The brothers’ research was promising—they were among the first to identify a link between psychosis and the hormone cortisone—but their findings were mostly ignored by their professional peers, who, in keeping with the era, favored a Freudian model of mental illness.

Concurrent with his psychiatric work, Arthur Sackler made his name in pharmaceutical advertising, which at the time consisted almost exclusively of pitches from so-called “detail men” who sold drugs to doctors door-to-door. Arthur intuited that print ads in medical journals could have a revolutionary effect on pharmaceutical sales, especially given the excitement surrounding the “miracle drugs” of the 1950s—steroids, antibiotics, antihistamines, and psychotropics. In 1952, the same year that he and his brothers acquired Purdue, Arthur became the first adman to convince The Journal of the American Medical Association, one of the profession’s most august publications, to include a color advertorial brochure.

In the 1960s, Arthur was contracted by Roche to develop an advertising strategy for a new antianxiety medication called Valium. This posed a challenge, because the effects of the medication were nearly indistinguishable from those of Librium, another Roche tranquilizer that was already on the market. Arthur differentiated Valium by audaciously inflating its range of indications. Whereas Librium was sold as a treatment for garden- variety anxiety, Valium was positioned as an elixir for a problem Arthur christened “psychic tension.” According to his ads, psychic tension, the forebear of today’s “stress,” was the secret culprit behind a host of somatic conditions, including heartburn, gastrointestinal issues, insomnia, and restless-leg syndrome. The campaign was such a success that for a time Valium became America’s most widely prescribed medication—the first to reach more than $100 million in sales. Arthur, whose compensation depended on the volume of pills sold, was richly rewarded, and he later became one of the first inductees into the Medical Advertising Hall of Fame.

As Arthur’s fortune grew, he turned his acquisitive instincts to the art market, quickly amassing the world’s largest private collection of ancient Chinese artifacts. According to a memoir by Marietta Lutze, his second wife, collecting, exhibiting, owning, and donating art fed Arthur’s “driving necessity for prestige and recognition.” Rewarding at first, collecting soon became a mania that took over his life. “Boxes of artifacts of tremendous value piled up in numerous storage locations,” she wrote, “there was too much to open, too much to appreciate; some objects known only by a packing list.” Under an avalanche of “ritual bronzes and weapons, mirrors and ceramics, inscribed bones and archaic jades,” their lives were “often in chaos.” “Addiction is a curse,” Lutze noted, “be it drugs, women, or collecting.”

When Arthur donated his art and money to museums, he often imposed onerous terms. According to a memoir written by Thomas Hoving, the Met director from 1967 to 1977, when Arthur established the Sackler Gallery at the Metropolitan Museum of Art to house Chinese antiquities, in 1963, he required the museum to collaborate on a byzantine tax-avoidance maneuver. In accordance with the scheme, the museum first sold Arthur a large quantity of ancient artifacts at the deflated 1920s prices for which they had originally been acquired. Arthur then donated back the artifacts at 1960s prices, in the process taking a tax deduction so hefty that it likely exceeded the value of his initial donation. Three years later, in connection with another donation, Arthur negotiated an even more unusual arrangement. This time, the Met opened a secret chamber above the museum’s auditorium to provide Arthur with free storage for some five thousand objects from his private collection, relieving him of the substantial burden of fire protection and other insurance costs. (In an email exchange, Jillian Sackler, Arthur’s third wife, called Hoving’s tax-deduction story “fake news.” She also noted that New York’s attorney general conducted an investigation into Arthur’s dealings with the Met and cleared him of wrongdoing.)

In 1974, when Arthur and his brothers made a large gift to the Met—$3.5 million, to erect the Temple of Dendur—they stipulated that all museum signage, catalog entries, and bulletins referring to objects in the newly opened Sackler Wing had to include the names of all three brothers, each followed by “M.D.” (One museum official quipped, “All that was missing was a note of their office hours.”)

Hoving said that the Met hoped that Arthur would eventually donate his collection to the museum, but over time Arthur grew disgruntled over a series of rankling slights. For one, the Temple of Dendur was being rented out for parties, including a dinner for the designer Valentino, which Arthur called “disgusting.” According to Met chronicler Michael Gross, he was also denied that coveted ticket of arrival, a board seat. (Jillian Sackler said it was Arthur who rejected the board seat, after repeated offers by the museum.) In 1982, in a bad breakup with the Met, Arthur donated the best parts of his collection, plus $4 million, to the Smithsonian in Washington, D. C.

Arthur’s younger brothers, Mortimer and Raymond, looked so much alike that when they worked together at Creedmoor, they fooled the staff by pretending to be one another. Their physical similarities did not extend to their personalities, however. Tage Honore, Purdue’s vice-president of discovery of research from 2000 to 2005, described them as “like day and night.” Mortimer, said Honore, was “extroverted—a ‘world man,’ I would call it.” He acquired a reputation as a big-spending, transatlantic playboy, living most of the year in opulent homes in England, Switzerland, and France. (In 1974, he renounced his U. S. citizenship to become a citizen of Austria, which infuriated his patriotic older brother.) Like Arthur, Mortimer became a major museum donor and married three wives over the course of his life.

Mortimer had his own feuds with the Met. On his seventieth birthday, in 1986, the museum agreed to make the Temple of Dendur available to him for a party but refused to allow him to redecorate the ancient shrine: Together with other improvements, Mortimer and his interior designer, flown in from Europe, had hoped to spiff up the temple by adding extra pillars. Also galling to Mortimer was the sale of naming rights for one of the Sackler Wing’s balconies to a donor from Japan. “They sold it twice,” Mortimer fumed to a reporter from New York magazine. Raymond, the youngest brother, cut a different figure—“a family man,” said Honore. Kind and mild-mannered, he stayed with the same woman his entire life. Lutze concluded that Raymond owed his comparatively serene nature to having missed the worst years of the Depression. “He had summer vacations in camp, which Arthur never had,” she

wrote. “The feeling of the two older brothers about the youngest was, ‘Let the kid enjoy himself.’ ”

Raymond led Purdue Frederick as its top executive for several decades, while Mortimer led Napp Pharmaceuticals, the family’s drug company in the UK. (In practice, a family spokesperson said, “the brothers worked closely together leading both companies.”) Arthur, the adman, had no official role in the family’s pharmaceutical operations. According to Barry Meier’s Pain Killer, a prescient account of the rise of OxyContin published in 2003, Raymond and Mortimer bought Arthur’s share in Purdue from his estate for $22.4 million after he died in 1987. In an email exchange, Arthur’s daughter Elizabeth Sackler, a historian of feminist art who sits on the board of the Brooklyn Museum and supports a variety of progressive causes, emphatically distanced her branch of the family from her cousins’ businesses. “Neither I, nor my siblings, nor my children have ever had ownership in or any benefit whatsoever from Purdue Pharma or OxyContin,” she wrote, while also praising “the breadth of my father’s brilliance and important works.” Jillian, Arthur’s widow, said her husband had died too soon: “His enemies have gotten the last word.”

The Sacklers have been millionaires for decades, but their real money—the painkiller money—is of comparatively recent vintage. The vehicle of that fortune was OxyContin, but its engine, the driving power that made them so many billions, was not so much the drug itself as it was Arthur’s original marketing insight, rehabbed for the era of chronic-pain management. That simple but profitable idea was to take a substance with addictive properties—in Arthur’s case, a benzo; in Raymond and Mortimer’s case, an opioid—and market it as a salve for a vast range of indications.

In the years before it swooped into the pain-management business, Purdue had been a small industry player, specializing in over-the-counter remedies like ear-wax remover and laxatives. Its most successful product, acquired in 1966, was Betadine, a powerful antiseptic purchased in industrial quantities by the U. S. government to prevent infection among wounded soldiers in Vietnam. The turning point, according to company lore, came in 1972, when a London doctor working for Cicely Saunders, the Florence Nightingale of the modern hospice movement, approached Napp with the idea of creating a timed-release morphine pill. A long-acting morphine pill, the doctor reasoned, would allow dying cancer patients to sleep through the night without an IV. At the time, treatment with opioids was stigmatized in the United States, owing in part to a heroin epidemic fueled by returning Vietnam veterans. “Opiophobia,” as it came to be called, prevented skittish doctors from treating most patients, including nearly all infants, with strong pain medication of any kind. In hospice care, though, addiction was not a concern: It didn’t matter whether terminal patients became hooked in their final days. Over the course of the seventies, building on a slow-release technology the company had already developed for an asthma medication, Napp created what came to be known as the “Contin” system. In 1981, Napp introduced a timed-release morphine pill in the UK; six years later, Purdue brought the same drug to market in the U. S. as MS Contin.

MS Contin quickly became the gold standard for pain relief in cancer care. At the same time, a number of clinicians associated with the burgeoning chronic-pain movement started advocating the use of powerful opioids for noncancer conditions like back pain and neuropathic pain, afflictions that at their worst could be debilitating. In 1986, two doctors from Memorial Sloan Kettering hospital in New York published a fateful article in a medical journal that purported to show, based on a study of thirty-eight patients, that long-term opioid treatment was safe and

effective so long as patients had no history of drug abuse. Soon enough, opioid advocates dredged up a letter to the editor published in The New England Journal of Medicine in 1980 that suggested, based on a highly unrepresentative cohort, that the risk of addiction from long-term opioid use was less than 1 percent. Though ultimately disavowed by its author, the letter ended up getting cited in medical journals more than six hundred times.

As the country was reexamining pain, Raymond’s eldest son, Richard Sackler, was searching for new applications for Purdue’s timed-release Contin system. “At all the meetings, that was a constant source of discussion—‘What else can we use the Contin system for?’ ” said Peter Lacouture, a senior director of clinical research at Purdue from 1991 to 2001. “And that’s where Richard would fire some ideas—maybe antibiotics, maybe chemotherapy—he was always out there digging.” Richard’s spitballing wasn’t idle blather. A trained physician, he treasured his role as a research scientist and appeared as an inventor on dozens of the company’s patents (though not on the patents for OxyContin). In the tradition of his uncle Arthur, Richard was also fascinated by sales messaging. “He was very interested in the commercial side and also very interested in marketing approaches,” said Sally Allen Riddle, Purdue’s former executive director for product management. “He didn’t always wait for the research results.” (A Purdue spokesperson said that Richard “always considered relevant scientific information when making decisions.”)

Perhaps the most private member of a generally secretive family, Richard appears nowhere on Purdue’s website. From public records and conversations with former employees, though, a rough portrait emerges of a testy eccentric with ardent, relentless ambitions. Born in 1945, he holds degrees from Columbia University and NYU Medical School. According to a bio on the website of the Koch Institute for Integrative Cancer Research at MIT, where Richard serves on the advisory board, he started working at Purdue as his father’s assistant at age twenty-six before eventually leading the firm’s R&D division and, separately, its sales and marketing division. In 1999, while Mortimer and Raymond remained Purdue’s co-CEOs, Richard joined them at the top of the company as president, a position he relinquished in 2003 to become cochairman of the board. The few publicly available pictures of him are generic and sphinxlike—a white guy with a receding hairline. He is one of the few Sacklers to consistently smile for the camera. In a photo on what appears to be his Facebook profile, Richard is wearing a tan suit and a pink tie, his right hand casually scrunched into his pocket, projecting a jaunty charm. Divorced in 2013, he lists his relationship status on the profile as “It’s complicated.” WHEN PURDUE EVENTUALLY PLEADED GUILTY TO FELONY CHARGES IN 2007 FOR CRIMINALLY “MISBRANDING” OXYCONTIN, IT ACKNOWLEDGED EXPLOITING DOCTORS’ MISCONCEPTIONS ABOUT OXYCODONE’S STRENGTH.

Richard’s political contributions have gone mostly to Republicans—including Strom Thurmond and Herman Cain—though at times he has also given to Democrats. (His ex-wife, Beth Sackler, has given almost exclusively to Democrats.) In 2008, he wrote a letter to the editor of The Wall Street Journal denouncing Muslim support for suicide bombing, a concern that seems to persist: Since 2014, his charitable organization, the Richard and Beth Sackler Foundation, has donated to several anti-Muslim groups, including three organizations classified as hate groups by the Southern Poverty Law Center. (The family spokesperson said, “It was never Richard Sackler’s intention to donate to an anti-Muslim or hate group.”) The foundation has also donated to True the Vote, the “voter-fraud watchdog” that was the original source for Donald Trump’s inaccurate claim that three million illegal immigrants voted in the 2016 election.

Former employees describe Richard as a man with an unnerving intelligence, alternately detached and pouncing. In meetings, his face was often glued to his laptop. “This was pre-

smartphone days,” said Riddle. “He’d be typing away and you would think he wasn’t even listening, and then all of the sudden his head would pop up and he’d be asking a very pointed question.” He was notorious for peppering subordinates with unexpected, rapid-fire queries, sometimes in the middle of the night. “Richard had the mind of someone who’s going two hundred miles an hour,” said Lacouture. “He could be a little bit disconnected in the way he would communicate. Whether it was on the weekend or a holiday or a Christmas party, you could always expect the unexpected.”

Richard also had an appetite for micromanagement. “I remember one time he mailed out a rambling sales bulletin,” said Shelby Sherman, a Purdue sales rep from 1974 to 1998. “And right in the middle, he put in, ‘If you’re reading this, then you must call my secretary at this number and give her this secret password.’ He wanted to check and see if the reps were reading this shit. We called it ‘Playin’ Passwords.’ ” According to Sherman, Richard started taking a more prominent role in the company during the early 1980s. “The shift was abrupt,” he said. “Raymond was just so nice and down-to-earth and calm and gentle.” When Richard came, “things got a lot harder. Richard really wanted Purdue to be big—I mean really big.”

To effectively capitalize on the chronic-pain movement, Purdue knew it needed to move beyond MS Contin. “Morphine had a stigma,” said Riddle. “People hear the word and say, ‘Wait a minute, I’m not dying or anything.’ ” Aside from its terminal aura, MS Contin had a further handicap: Its patent was set to expire in the late nineties. In a 1990 memo addressed to Richard and other executives, Purdue’s VP of clinical research, Robert Kaiko, suggested that the company work on a pill containing oxycodone, a chemical similar to morphine that was also derived from the opium poppy. When it came to branding, oxycodone had a key advantage: Although it was 50 percent stronger than morphine, many doctors believed—wrongly—that it was substantially less powerful. They were deceived about its potency in part because oxycodone was widely known as one of the active ingredients in Percocet, a relatively weak opioid- acetaminophen combination that doctors often prescribed for painful injuries. “It really didn’t have the same connotation that morphine did in people’s minds,” said Riddle.

A common malapropism led to further advantage for Purdue. “Some people would call it oxy-codeine” instead of oxycodone, recalled Lacouture. “Codeine is very weak.” When Purdue eventually pleaded guilty to felony charges in 2007 for criminally “misbranding” OxyContin, it acknowledged exploiting doctors’ misconceptions about oxycodone’s strength. In court documents, the company said it was “well aware of the incorrect view held by many physicians that oxycodone was weaker than morphine” and “did not want to do anything ‘to make physicians think that oxycodone was stronger or equal to morphine’ or to ‘take any steps . . . that would affect the unique position that OxyContin’ ” held among physicians.

Purdue did not merely neglect to clear up confusion about the strength of OxyContin. As the company later admitted, it misleadingly promoted OxyContin as less addictive than older opioids on the market. In this deception, Purdue had a big assist from the FDA, which allowed the company to include an astonishing labeling claim in OxyContin’s package insert: “Delayed absorption, as provided by OxyContin tablets, is believed to reduce the abuse liability of a drug.”

The theory was that addicts would shy away from timed-released drugs, preferring an immediate rush. In practice, OxyContin, which crammed a huge amount of pure narcotic into a single pill, became a lusted-after target for addicts, who quickly discovered that the timed-release mechanism in OxyContin was easy

to circumvent—you could simply crush a pill and snort it to get most of the narcotic payload in a single inhalation. This wasn’t exactly news to the manufacturer: OxyContin’s own packaging warned that consuming broken pills would thwart the timed-release system and subject patients to a potentially fatal overdose. MS Contin had contended with similar vulnerabilities, and as a result commanded a hefty premium on the street. But the “reduced abuse liability” claim that added wings to the sales of OxyContin had not been approved for MS Contin. It was removed from OxyContin in 2001 and would never be approved again for any other opioid.

The year after OxyContin’s release, Curtis Wright, the FDA examiner who approved the pharmaceutical’s original application, quit. After a stint at another pharmaceutical company, he began working for Purdue. In an interview with Esquire, Wright defended his work at the FDA and at Purdue. “At the time, it was believed that extended-release formulations were intrinsically less abusable,” he insisted. “It came as a rather big shock to everybody—the government and Purdue—that people found ways to grind up, chew up, snort, dissolve, and inject the pills.” Preventing abuse, he said, had to be balanced against providing relief to chronic-pain sufferers. “In the mid-nineties,” he recalled, “the very best pain specialists told the medical community they were not prescribing opioids enough. That was not something generated by Purdue—that was not a secret plan, that was not a plot,that was not a clever marketing ploy. Chronic pain is horrible. In the right circumstances, opioid therapy is nothing short of miraculous; you give people their lives back.” In Wright’s account, the Sacklers were not just great employers, they were great people. “No company in the history of pharmaceuticals,” he said, “has worked harder to try to prevent abuse of their product than Purdue.”

Purdue did not invent the chronic-pain movement, but it used that movement to engineer a crucial shift. Wright is correct that in the nineties patients suffering from chronic pain often received inadequate treatment. But the call for clinical reforms also became a flexible alibi for overly aggressive prescribing practices. By the end of the decade, clinical proponents of opioid treatment, supported by millions in funding from Purdue and other pharmaceutical companies, had organized themselves into advocacy groups with names like the American Pain Society and the American Academy of Pain Medicine. (Purdue also launched its own group, called Partners Against Pain.) As the decade wore on, these organizations, which critics have characterized as front groups for the pharmaceutical industry, began pressuring health regulators to make pain “the fifth vital sign”—a number, measured on a subjective ten-point scale, to be asked and recorded at every doctor’s visit. As an internal strategy document put it, Purdue’s ambition was to “attach an emotional aspect to non cancer pain” so that doctors would feel pressure to “treat it more seriously and aggressively.” The company rebranded pain relief as a sacred right: a universal narcotic entitlement available not only to the terminally ill but to every American.

The company rebranded pain relief as a sacred right: a universal narcotic entitlement available not only to the terminally ill but to every American. By 2001, annual OxyContin sales had surged past $1 billion.

OxyContin’s sales started out small in 1996, in part because Purdue first focused on the cancer market to gain formulary acceptance from HMOs and state Medicaid programs. Over the next several years, though, the company doubled its sales force to six hundred—equal to the total number of DEA diversion agents employed to combat the sale of prescription drugs on the black market—and began targeting general practitioners, dentists, OB/GYNs, physician assistants, nurses, and residents. By 2001, annual OxyContin sales had surged past $1 billion. Sales reps were encouraged to downplay addiction risks. “It was sell, sell,

sell,” recalled Sherman. “We were directed to lie. Why mince words about it? Greed took hold and overruled everything. They saw that potential for billions of dollars and just went after it.” Flush with cash, Purdue pioneered a high-cost promotion strategy, effectively providing kickbacks—which were legal under American law—to each part of the distribution chain. Wholesalers got rebates in exchange for keeping OxyContin off prior authorization lists. Pharmacists got refunds on their initial orders. Patients got coupons for thirty- day starter supplies. Academics got grants. Medical journals got millions in advertising. Senators and members of Congress on key committees got donations from Purdue and from members of the Sackler family.

It was doctors, though, who received the most attention. “We used to fly doctors to these ‘seminars,’ ” said Sherman, which were, in practice, “just golf trips to Pebble Beach. It was graft.” Though offering perks and freebies to doctors was hardly uncommon in the industry, it was unprecedented in the marketing of a Schedule II narcotic. For some physicians, the junkets to sunny locales weren’t enough to persuade them to prescribe. To entice the holdouts—a group the company referred to internally as “problem doctors”—the reps would dangle the lure of Purdue’s lucrative speakers’ bureau. “Everybody was automatically approved,” said Sherman. “We would set up these little dinners, and they’d make their little fifteen-minute talk, and they’d get $500.”

Between 1996 and 2001, the number of OxyContin prescriptions in the United States surged from about three hundred thousand to nearly six million, and reports of abuse started to bubble up in places like West Virginia, Florida, and Maine. (Research would later show a direct correlation between prescription volume in an area and rates of abuse and overdose.) Hundreds of doctors were eventually arrested for running pill mills. According to an investigation in the Los Angeles Times, even though Purdue kept an internal list of doctors it suspected of criminal diversion, it didn’t volunteer this information to law enforcement until years later. As criticism of OxyContin mounted through the aughts, Purdue responded with symbolic concessions while retaining its volume-driven business model. To prevent addicts from forging prescriptions, the company gave doctors tamper-resistant prescription pads; to mollify pharmacists worried about robberies, Purdue offered to replace, free of charge, any stolen drugs; to gather data on drug abuse and diversion, the company launched a national monitoring program called RADARS.

Critics were not impressed. In a letter to Richard Sackler in July 2001, Richard Blumenthal, then Connecticut’s attorney general and now a U. S. senator, called the company’s efforts “cosmetic.” As Blumenthal had deduced, the root problem of the prescription-opioid epidemic was the high volume of prescriptions written for powerful opioids. “It is time for Purdue Pharma to change its practices,” Blumenthal warned Richard, “not just its public-relations strategy.”

It wasn’t just that doctors were writing huge numbers of prescriptions; it was also that the prescriptions were often for extraordinarily high doses. A single dose of Percocet contains between 2.5 and 10mg of oxycodone. OxyContin came in 10-, 20-, 30-, 40-, and 80mg formulations and, for a time, even 160mg. Purdue’s greatest competitive advantage in dominating the pain market, it had determined early on, was that OxyContin lasted twelve hours, enough to sleep through the night. But for many patients, the drug lasted only six or eight hours, creating a cycle of crash and euphoria that one academic called “a perfect recipe for addiction.” When confronted with complaints about “breakthrough pain”—meaning that the pills weren’t working as long as advertised—Purdue’s sales reps were given strict instructions to tell doctors to strengthen the dose rather than increase dosing frequency.

Sales reps were encouraged to downplay addiction risks. “It was sell, sell, sell,” recalled Sherman. “We were directed to lie. Why mince words about it?”

Over the next several years, dozens of class-action lawsuits were brought against Purdue. Many were dismissed, but in some cases Purdue wrote big checks to avoid going to trial. Several plaintiffs’ lawyers found that the company was willing to go to great lengths to prevent Richard Sackler from having to testify under oath. “They didn’t want him deposed, I can tell you that much,” recalled Marvin Masters, a lawyer who brought a class-action suit against Purdue in the early 2000s in West Virginia. “They were willing to sit down and settle the case to keep from doing that.” Purdue tried to get Richard removed from the suit, but when that didn’t work, the company settled with the plaintiffs for more than $20 million. Paul Hanly, a New York class-action lawyer who won a large settlement from Purdue in 2007, had a similar recollection. “We were attempting to take Richard Sackler’s deposition,” he said, “around the time that they agreed to a settlement.” (A spokesperson for the company said, “Purdue did not settle any cases to avoid the deposition of Dr. Richard Sackler, or any other individual.”)

When the federal government finally stepped in, in 2007, it extracted historic terms of surrender from the company. Purdue pleaded guilty to felony charges, admitting that it had lied to doctors about OxyContin’s abuse potential. (The technical charge was “misbranding a drug with intent to defraud or mislead.”) Under the agreement, the company paid $600 million in fines and its three top executives at the time—its medical director, general counsel, and Richard’s successor as president—pleaded guilty to misdemeanor charges. The executives paid $34.5 million out of their own pockets and performed four hundred hours of community service. It was one of the harshest penalties ever imposed on a pharmaceutical company. (In a statement to Esquire, Purdue said that it “abides by the highest ethical standards and legal requirements.” The statement went on: “We want physicians to use their professional judgment, and we were not trying to pressure them.”)

Fifty-three thousand Americans died from opioid overdoses in 2016, more than the thirty-six thousand who died in car crashes in 2015 or the thirty-five thousand who died from gun violence that year.

No Sacklers were named in the 2007 suit. Indeed, the Sackler name appeared nowhere in the plea agreement, even though Richard had been one of the company’s top executives during most of the period covered by the settlement. He did eventually have to give a deposition in 2015, in a case brought by Kentucky’s attorney general. Richard’s testimony—the only known record of a Sackler speaking about the crisis the family’s company helped create—was promptly sealed. (In 2016, STAT, an online magazine owned by Boston Globe Media that covers health and medicine, asked a court in Kentucky to unseal the deposition, which is said to have lasted several hours. STAT won a lower-court ruling in May 2016. As of press time, the matter was before an appeals court.)

In 2010, Purdue executed a breathtaking pivot: Embracing the arguments critics had been making for years about OxyContin’s susceptibility to abuse, the company released a new formulation of the medication that was harder to snort or inject. Purdue seized the occasion to rebrand itself as an industry leader in abuse-deterrent technology. The change of heart coincided with two developments: First, an increasing number of addicts, unable to afford OxyContin’s high street price, were turning to cheaper alternatives like heroin; second, OxyContin was nearing the end of its patents. Purdue suddenly argued that the drug it had been selling for nearly fifteen years was so prone to abuse that generic manufacturers should not be allowed to copy it.

On April 16, 2013, the day some of the key patents for OxyContin were scheduled to expire, the FDA followed Purdue’s lead, declaring that no generic versions of the original OxyContin formulation could be sold. The company had effectively won several additional years of patent protection for its golden goose.

Opioid withdrawal, which causes aches, vomiting, and restless anxiety, is a gruesome process to experience as an adult. It’s considerably worse for the twenty thousand or so American babies who emerge each year from opioid-soaked wombs. These infants, suddenly cut off from their supply, cry uncontrollably. Their skin is mottled. They cannot fall asleep. Their bodies are shaken by tremors and, in the worst cases, seizures. Bottles of milk leave them distraught, because they cannot maneuver their lips with enough precision to create suction. Treatment comes in the form of drops of morphine pushed from a syringe into the babies’ mouths. Weaning sometimes takes a week but can last as long as twelve. It’s a heartrending, expensive process, typically carried out in the neonatal ICU, where newborns have limited access to their mothers.

But the children of OxyContin, its heirs and legatees, are many and various. The second- and third-generation descendants of Raymond and Mortimer Sackler spend their money in the ways we have come to expect from the not-so-idle rich. Notably, several have made children a focus of their business and philanthropic endeavors. One Sackler heir helped start an iPhone app called Red Rover, which generates ideas for child-friendly activities for urban parents; another runs a child- development center near Central Park; another is a donor to charter-school causes, as well as an investor in an education start-up called AltSchool. Yet another is the founder of Beespace, an “incubator for emerging nonprofits,” which provides resources and mentoring for initiatives like the Malala Fund, which invests in education programs for women in the developing world, and Yoga Foster, whose objective is to bring “accessible, sustainable yoga programs into schools across the country.” Other Sackler heirs get to do the fun stuff: One helps finance small, interesting films like The Witch; a second married a famous cricket player; a third is a sound artist; a fourth started a production company with Boyd Holbrook, star of the Netflix series Narcos; a fifth founded a small chain of gastropubs in New York called the Smith.

Holding fast to family tradition, Raymond’s and Mortimer’s heirs declined to be interviewed for this article. Instead, through a spokesperson, they put forward two decorated academics who have been on the receiving end of the family’s largesse: Phillip Sharp, the Nobel-prize-winning MIT geneticist, and Herbert Pardes, formerly the dean of faculty at Columbia University’s medical school and CEO of New York-Presbyterian Hospital. Both men effusively praised the Sacklers’ donations to the arts and sciences, marveling at their loyalty to academic excellence. “Once you were on that exalted list of philanthropic projects,” Pardes told Esquire, “you were there and you were in a position to secure additional philanthropy. It was like a family acquisition.” Pardes called the Sacklers “the nicest, most gentle people you could imagine.” As for the family’s connection to OxyContin, he said that it had never come up as an issue in the faculty lounge or the hospital break room. “I have never heard one inch about that,” he said.

Pardes’s ostrich like avoidance is not unusual. In 2008, Raymond and his wife donated an undisclosed amount to Yale to start the Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences. Lynne Regan, its current director, told me that neither students nor faculty have ever brought up the OxyContin connection. “Most people don’t know about that,” she said. “I think people are mainly oblivious.” A spokesperson for the university added, “Yale does not vet donors for controversies that may or may not arise.”

In May, a dozen lawmakers in Congress sent a bipartisan letter to the World Health Organization warning that Sackler-owned companies were preparing to flood foreign countries with legal narcotics.

The controversy surrounding OxyContin shows little sign of receding. In 2016, the CDC issued a startling warning: There was no good evidence that opioids were an effective treatment for chronic pain beyond six weeks. There was, on the other hand, an abundance of evidence that long-term treatment with opioids had harmful effects. (A recent paper by Princeton economist Alan Krueger suggests that chronic opioid use may account for more than 20 percent of the decline in American labor-force participation from 1999 to 2015.) Millions of opioid prescriptions for chronic pain had been written in the preceding two decades, and the CDC was calling into question whether many of them should have been written at all. At least twenty-five government entities, ranging from states to small cities, have recently filed lawsuits against Purdue to recover damages associated with the opioid epidemic.

The Sacklers, though, will likely emerge untouched: Because of a sweeping non-prosecution agreement negotiated during the 2007 settlement, most new criminal litigation against Purdue can only address activity that occurred after that date. Neither Richard nor any other family members have occupied an executive position at the company since 2003.

The American market for OxyContin is dwindling. According to Purdue, prescriptions fell 33 percent between 2012 and 2016. But while the company’s primary product may be in eclipse in the United States, international markets for pain medications are expanding. According to an investigation last year in the Los Angeles Times, Mundipharma, the Sackler-owned company charged with developing new markets, is employing a suite of familiar tactics in countries like Mexico, Brazil, and China to stoke concern for as-yet-unheralded “silent epidemics” of untreated pain. In Colombia, according to the L.A. Times, the company went so far as to circulate a press release suggesting that 47 percent of the population suffered from chronic pain. [Napp is the family’s drug company in the UK. Mundipharma is their company charged with developing new markets.]

In May, a dozen lawmakers in Congress, inspired by the L.A. Times investigation, sent a bipartisan letter to the World Health Organization warning that Sackler-owned companies were preparing to flood foreign countries with legal narcotics. “Purdue began the opioid crisis that has devastated American communities,” the letter reads. “Today, Mundipharma is using many of the same deceptive and reckless practices to sell OxyContin abroad.” Significantly, the letter calls out the Sackler family by name, leaving no room for the public to wonder about the identities of the people who stood behind Mundipharma.

The final assessment of the Sacklers’ global impact will take years to work out. In some places, though, they have already left their mark. In July, Raymond, the last remaining of the original Sackler brothers, died at ninety-seven. Over the years, he had won a British knighthood, been made an Officer of France’s Légion d’Honneur, and received one of the highest possible honors from the royal house of the Netherlands. One of his final accolades came in June 2013, when Anthony Monaco, the president of Tufts University, traveled to Purdue Pharma’s headquarters in Stamford to bestow an honorary doctorate. The Sacklers had made a number of transformational donations to the university over the years—endowing, among other things, the Sackler School of Graduate Biomedical Sciences. At

Tufts, as at most schools, honorary degrees are traditionally awarded on campus during commencement, but in consideration of Raymond’s advanced age, Monaco trekked to Purdue for a special ceremony. The audience that day was limited to family members, select university officials, and a scrum of employees. Addressing the crowd of intimates, Monaco praised his benefactor. “It would be impossible to calculate how many lives you have saved, how many scientific fields you have redefined, and how many new physicians, scientists, mathematicians, and engineers are doing important work as a result of your entrepreneurial spirit.” He concluded, “You are a world changer.”

Source: This article appears in the November ’17 issue of Esquire.

Executive Summary

Purpose

Rocky Mountain High Intensity Drug Trafficking Area (RMHIDTA) is tracking the impact of marijuana legalization in the state of Colorado. This report will utilize, whenever possible, a comparison of three different eras in Colorado’s legalization history:

· 2006 – 2008: Medical marijuana pre-commercialization era

· 2009 – Present: Medical marijuana commercialization and expansion era

· 2013 – Present: Recreational marijuana era

Rocky Mountain HIDTA will collect and report comparative data in a variety of areas, including but not limited to:

· Impaired driving and fatalities

· Youth marijuana use

· Adult marijuana use

· Emergency room admissions

· Marijuana-related exposure cases

· Diversion of Colorado marijuana

This is the fifth annual report on the impact of legalized marijuana in Colorado. It is divided into ten sections, each providing information on the impact of marijuana legalization. The sections are as follows:

Section 1 – Impaired Driving and Fatalities:

· Marijuana-related traffic deaths when a driver was positive for marijuana more than doubled from 55 deaths in 2013 to 123 deaths in 2016.

· Marijuana-related traffic deaths increased 66 percent in the four-year average (2013-2016) since Colorado legalized recreational marijuana compared to the four-year average (2009-2012) prior to legalization.

o During the same time period, all traffic deaths increased 16 percent.

· In 2009, Colorado marijuana-related traffic deaths involving drivers testing positive for marijuana represented 9 percent of all traffic deaths. By 2016, that number has more than doubled to 20 percent.

Section 2 – Youth Marijuana Use:

· Youth past month marijuana use increased 12 percent in the three-year average (2013-2015) since Colorado legalized recreational marijuana compared to the three-year average prior to legalization (2010-2012).

· The latest 2014/2015 results show Colorado youth ranked #1 in the nation for past month marijuana use, up from #4 in 2011/2012 and #14 in 2005/2006.

· Colorado youth past month marijuana use for 2014/2015 was 55 percent higher than the national average compared to 39 percent higher in 2011/2012.

Section 3 – Adult Marijuana Use:

· College age past month marijuana use increased 16 percent in the three-year average (2013-2015) since Colorado legalized recreational marijuana compared to the three-year average prior to legalization (2010-2012).

· The latest 2014/2015 results show Colorado college-age adults ranked #2 in the nation for past-month marijuana use, up from #3 in 2011/2012 and #8 in 2005/2006.

· Colorado college age past month marijuana use for 2014/2015 was 61 percent higher than the national average compared to 42 percent higher in 2011/2012.

· Adult past-month marijuana use increased 71 percent in the three-year average (2013-2015) since Colorado legalized recreational marijuana compared to the three-year average prior to legalization (2010-2012).

· The latest 2014/2015 results show Colorado adults ranked #1 in the nation for past month marijuana use, up from #7 in 2011/2012 and #8 in 2005/2006.

· Colorado adult past month marijuana use for 2014/2015 was 124 percent higher than the national average compared to 51 percent higher in 2011/2012.

Section 4 – Emergency Department and Hospital Marijuana-Related Admissions:

· The yearly rate of emergency department visits related to marijuana increased 35 percent after the legalization of recreational marijuana (2011-2012 vs. 2013-2015).

· Number of hospitalizations related to marijuana:

o 2011 – 6,305

o 2012 – 6,715

o 2013 – 8,272

o 2014 – 11,439

o Jan-Sept 2015 – 10,901

· The yearly number of marijuana-related hospitalizations increased 72 percent after the legalization of recreational marijuana (2009-2012 vs. 2013-2015).

Section 5 – Marijuana-Related Exposure:

· Marijuana-related exposures increased 139 percent in the four-year average (2013-2016) since Colorado legalized recreational marijuana compared to the four-year average (2009-2012) prior to legalization.

· Marijuana-Only exposures more than doubled (increased 210 percent) in the four-year average (2013-2016) since Colorado legalized recreational marijuana compared to the four-year average (2009-2012) prior to legalization.

Section 6 – Treatment:

· Marijuana treatment data from Colorado in years 2006 – 2016 does not appear to demonstrate a definitive trend. Colorado averages 6,683 treatment admissions annually for marijuana abuse.

· Over the last ten years, the top four drugs involved in treatment admissions were alcohol (average 13,551), marijuana (average 6,712), methamphetamine (average 5,578), and heroin (average 3,024).

Section 7 – Diversion of Colorado Marijuana:

· In 2016, RMHIDTA Colorado drug task forces completed 163 investigations of individuals or organizations involved in illegally selling Colorado marijuana both in and out of state.

o These cases led to:

§ 252 felony arrests

§ 7,116 (3.5 tons) pounds of marijuana seized

§ 47,108 marijuana plants seized

§ 2,111 marijuana edibles seized

§ 232 pounds of concentrate seized

§ 29 different states to which marijuana was destined

· Highway interdiction seizures of Colorado marijuana increased 43 percent in the four-year average (2013-2016) since Colorado legalized recreational marijuana compared to the four-year average (2009-2012) prior to legalization.

· Of the 346 highway interdiction seizures in 2016, there were 36 different states destined to receive marijuana from Colorado.

o The most common destinations identified were Illinois, Missouri, Texas, Kansas and Florida.

Section 8 – Diversion by Parcel:

· Seizures of Colorado marijuana in the U.S. mail has increased 844 percent from an average of 52 parcels (2009-2012) to 491 parcels (2013-2016) in the four-year average that recreational marijuana has been legal.

· Seizures of Colorado marijuana in the U.S. mail has increased 914 percent from an average of 97 pounds (2009-2012) to 984 pounds (2013-2016) in the four-year average that recreational marijuana has been legal.

Section 9 – Related Data:

· Crime in Denver increased 17 percent and crime in Colorado increased 11 percent from 2013 to 2016.

· Colorado annual tax revenue from the sale of recreational and medical marijuana was 0.8 percent of Colorado’s total statewide budget (FY 2016).

· As of June 2017, there were 491 retail marijuana stores in the state of Colorado compared to 392 Starbucks and 208 McDonald’s.

· 66 percent of local jurisdictions have banned medical and recreational marijuana businesses.

Section 10 – Reference Materials:

This section lists various studies and reports regarding marijuana.

THERE IS MUCH MORE DATA IN EACH OF THE TEN SECTIONS. THIS PUBLICATION MAY BE FOUND ON THE ROCKY MOUNTAIN HIDTA WEBSITE; GO TO WWW.RMHIDTA.ORG AND SELECT REPORTS.

Source: WWW.RMHIDTA.ORG October 2017

Drug trafficking is now the most murderous criminal activity in American history. Overdose deaths from illegal drugs passed 50,000 in 2015 — many times the number of Americans killed by all Islamic terrorists over almost 20 years. Yet stopping the skyrocketing body count will require overcoming a pervasive misunderstanding of how drug abuse and addiction are caused.

Blaming the victim has created confusion and policy failure. No one starts using drugs intending to become an addict. While addiction may seem like slow-motion suicide, most addicts do not want to die — the poison hooks them, taking over their life. Media reports of addiction are mixed with entertainment and social media that present drug use as commonplace. More and more Americans are drawn to the flame, many introduced to substance abuse by a friend or family member. “Just say no” is dead. Yes, encouraging young people not to use drugs can save individual lives, but personal morality is not the right battleground.

There are multiple factors that may be contributing to this crisis. Does expanding supply trigger drug experimentation? Does human biology simply include a dangerous susceptibly to runaway addiction? Or is cultural confusion about freedom and self-destruction enabling and normalizing drug addiction? All these factors (and possibly more) likely play a part. But what causes an epidemic is the addictive poison itself, spread in sufficient quantities. Ultimately, America’s addiction catastrophe is properly understood as a mass poisoning.

As a result, cutting the drug supply — and only cutting supply — will reduce deaths and addiction. The evidence for this conclusion is manifest; ignoring it will cost countless more lives.

Curtailing Supply

There was no demand for crack before it was created and distributed by Colombian traffickers. There was no demand for meth before it was created by criminal gangs and then “cooked” by users. Similarly, there was no massive abuse of prescription opioids until they were irresponsibly marketed by some manufacturers and prescribed by physicians contrary to sound medical practice.

The increase in heroin and fentanyl use, addiction, and deaths followed the increase in the supply from Mexico and China. Conversely, during the George W. Bush Administration, when the supply of cocaine, crack, and meth began declining, use declined. Now, as cocaine production in Colombia has grown again, use and overdose deaths are climbing. Finally, the leveling trend in the abuse of prescription opioids has followed enforcement actions against pill mills and criminal physicians — that is, it follows an apparent reduction in supply. Americans have long accepted the claim that it is impossible to stop drug trafficking, even in the face of extensive evidence to the contrary. Anti-terrorism efforts must stop just a few dedicated individuals. This is a tough problem that Americans see solved every day. Yet the poisoning of millions is supposedly unstoppable. It isn’t.

Moreover, misunderstanding the cause of drug epidemics has shifted the policy debate away from the right goals: reducing the supply of drugs and returning addicts to sobriety. With deaths at historic levels, some still maintain that drug use is a right or otherwise not worth the cost of controlling. This harm reduction position is at odds with both supply control and all forms of prevention education — and increasingly at odds with treatment understood as having the goal of abstinence.

Many drug policy progressives now insist on medically supervised addiction. Such medication assisted treatment (MAT) amounts to government-supervised facilities for drug use (injection sites) or even government-supplied drugs for the addicted. The model here is the Netherlands, where endless, government-supported drug use is treated as a means of treating addiction. These addicts continue to be victimized by their own country, fostering a separate and profoundly dysfunctional underclass.

In the face of expanding supply, prevention and treatment efforts cannot be strategic — they can save individual lives, but new lives will be put at risk. This is merely squeezing an uncontained balloon. Moreover, if supply is reduced significantly, use and addiction will necessarily fall without respect to prevention and treatment efforts. The evidence of almost 50 years indicates that prevention and treatment efforts only contribute to strategic results when supply is reduced.

Prevention and treatment save lives, but their strategic effect is overwhelmed if supply and trafficking are not curtailed.

Policy proposals placing emphasis on reviving drug overdose victims mistake cause and effect. In the case of opioid addiction, the cause is the opioids themselves and increasingly, fentanyl. Revived addicts are still victims, and, sadly, many treated for opioid addiction will relapse in the face of burgeoning supply. Fentanyl and its variants are now driving the rapid rise in opioid deaths and drug overdoses in general. Information, albeit inadequate, suggests China is the source for these substances and the precursors to produce them. It seems there is no large-scale legitimate use for these chemicals outside of what is supposed to be controlled production for limited medical use — thus, industrial diversion is not a primary issue. Unfortunately, however, this means U.S. officials cannot attack fentanyl directly, but only via Chinese enforcement action.

China is likely to be sensitive to sustained pressure by authoritative American voices, whether from federal officials or prominent private individuals. America should ramp up this pressure soon. If executive branch officials cannot lead the charge, individuals from outside the executive, including members of Congress, should take the lead.

The Chinese are likely to act only in response to threats to their political or economic interests. Spurring them to act may require frequent confrontations over their performance in stopping fentanyl trafficking to the U.S. and Mexico. But sustained, genuine pressure works.

It is also possible that fentanyl and precursors are being trafficked from other Asian countries. Hence further — and swift — investigation is needed.

Bolstering Intelligence Resources

It is reasonable to anticipate that traffickers will seek to move production in response to pressure. If that happens, other Asian nations can be pressured by a range of escalating sanctions. Identification, especially public charging of foreign criminals, can be particularly helpful in disrupting trafficking operations, along with attacks on criminal funds and individuals through U.S. law.

An attack of sufficient power to collapse trafficking networks requires detailed intelligence. Such intelligence is also needed to prod foreign governments to act within their authority. Greater intelligence resources are also crucial for attacking trafficker finance, corruption operations, and measuring policy effectiveness. Attacking networks and responding to the drug epidemic requires comprehensive, real-time data. This data — from foreign intelligence services, domestic law enforcement agencies, and public health reports — should be fused into a strategic whole.

Fortunately, American intelligence has developed tools to attack such networked terrorist threats. At over 50,000 overdose deaths a year, the mass poisoning of drug trafficking is the most profound attack on America today. It is time to fully unleash intelligence tools on trafficking networks.

Without adequate intelligence, the magnitude of trafficking on the internet and “dark web” is unknown. Available information suggests it is significant, however. Federal drug enforcement has generally made electronic investigations a low priority, rejecting proposals to disrupt such markets by means of false sites, service denials, and cross-referencing data from multiple sources. All national security capacities are not yet deployed against opioid trafficking on the internet; this should change immediately. Past efforts to mount internet attacks by federal drug enforcement agencies have been crippled by ignorance, lack of experience, lack of vision, and complacency. The primary strategic goal should not just be to make future cases, but permanent market disruption; make it difficult to use the internet for trafficking by destroying the ability of buyers to connect with sellers.

Even the incomplete information on the opioid epidemic suggests that enforcement actions against pill mills and criminal physicians have reduced addiction and death driven by U.S. pharmaceutical sources. This has been a “supply control” success. Nonetheless, there is evidence of lower, but continued diversion. The pharmaceutical industry, the health insurance industry, and the federal government (the largest single health-care payer) all have information that should be brought together to identify and stop criminal diversion. The key point should be to focus attention on the biggest threat and its biggest components. There are regular reports of misuse of federal health-care funds to support addiction; some reports suggest areas where such practices are concentrated, which may serve as a starting point for enforcement actions.

Disrupting Networks Colombia is now back to producing more cocaine than it did prior to the dramatic drop in coca cultivation through Plan Colombia, which was largely due to the cooperation of former President Alvaro Uribe. Aside from a corresponding rise in cocaine overdose deaths, there are now reports of deaths resulting from cocaine-fentanyl mixtures. This deadly combination was seen about 10 years ago and may now be poised to cause harm on a greater scale. Much more fentanyl is available to Mexican traffickers carrying opioids and cocaine into the U.S. The Obama administration downplayed drug control in Colombia to pursue other goals. Colombian institutions are, again, put at risk by narcoterrorism. The previous security partnership needs reinvigoration, but the U.S. should make clear that the current trends are unacceptable for an ally and trading partner. A first step might be to have a government official or prominent private citizen warn the Colombian president that “if he doesn’t stop sending the cocaine, perhaps it is time to ask him to stop sending the coffee and the flowers.” Fortunately, former-president Uribe remains politically active and he knows how to attack the cocaine problem — Colombians would be wise to give him the job.

Contrary to the widespread belief that prescription diversion is driving the opioid crisis, available evidence indicates that most opioids and other illegal are produced outside the U.S. Further, these drugs seem to be arriving from Mexico. It is likely that most of them pass within six feet of a uniformed federal officer at our southern border. This is an unacceptable failure. Additional personnel will be useful, but the most important missing element is access to intelligence about trafficker operations. Enforcement agencies need to “see” into Mexico, and they need to see the structure of foreign and domestic trafficking networks.

Drug enforcement agencies and prosecutors need to treat individual cases as a means of network disruption, not as ends in themselves. In fact, it is likely that many smaller cases involving lesser charges that can be brought quickly will damage street-level trafficking networks more effectively than larger cases requiring longer investigations. In short, enforcement efforts need to become urgent and strategic.

Moreover, traffickers deserve stiff prison sentences. Such sentences are important leverage for turning traffickers against each other. Prison capacity for these death merchants must be made available to save lives. Enforcement pressure needs to be scaled to the threat.

Overall, drug enforcement management is insufficiently threat-based and seldom shifts resources rapidly to the greatest threats. While drug trafficking is killing more Americans than all other criminal activity combined, drug enforcement does not receive resources remotely proportional to the threat. The criminal-justice system is merely trying (and failing) to cope with the drug threat. It must come to see its mission as systematically destroying the threat — and plan, budget, and staff accordingly.

A Counter-Drug Strategy

An effective counter-drug strategy must attack at three points: source, distribution, and retail. If any one point of attack is particularly effective, it will substantially reduce use. It is probable, however, that the different points of attack will be effective in different degrees, while results will be cumulative and reinforcing.

At the retail level of street sales and use, the targets are whole communities, large geographic areas. Local and state efforts will be most important because there are insufficient federal resources to create the magnitude of the response required at the retail level. Local and state elements can be “enlisted” in a more unified national effort. That means encouraging and offering supplementary, strategic support with national personnel and resources.

Nevertheless, it may be critical to begin with willing state and local partners — those who commit their personnel and resources to the new strategy. These initial sites will also refine the elements of the strategy and demonstrate the effectiveness of more controversial components. Sites should be in priority areas and on as wide a scale as circumstances permit, but they should also be understood as points from which localized effort will flow outward — as ink spots on paper. Taking back individual communities in this way is an application of counterinsurgency concepts — it is also an established means of fighting epidemics.

At the retail level, the dealer and user are the center of gravity. Street-level enforcement needs to respond to opioid distribution as an immediate threat to life. Every sale can bring an overdose and every overdose can result in death. Each dealer is more like an active shooter than a house thief. Yet police response is frequently more focused on victim than on victimizer. The low-level dealer is also a low priority for enforcement personnel and prosecutors. This misguided policy is feeding the epidemic at the local level.

Accordingly, street-level enforcement should be reconceived in two ways. First, much greater urgency should be given to finding and incapacitating the dealer. Second, arresting users should be seen as a public health measure to screen for and treat addiction, as with the successful drug court model. Drug courts and diversion programs are already a major source of treatment admissions in the U.S. But this has been understood as a means of reducing the burden on the criminal-justice system. It should be seen as a necessary means of getting addicts who are in denial (as the vast majority are) into treatment and keeping them there through detoxification and stable sobriety. Street-level enforcement should be targeted to collapse dealer networks and should be tuned to become an intake channel for treatment.

All this will mean more arrests and more resources devoted to creating appropriate responses for users and dealers after arrest. Occasional, non-addicted users have a much lower probability of arrest at the point of drug sales because their purchases are infrequent. The risk to addicts is greater because they commonly need multiple doses per day. Thus, the normal pressure of street-level enforcement will tend to involve the larger dealers and the heavier users. Arrest and referral to treatment will save the lives of the addicted and even the arrest and warning of occasional users could be a potentially life-saving deterrent.

Such enforcement effort needs to be targeted, however. The obvious way to locate addicts and their dealers is to follow the reports of overdose victims. These reports provide a painful — but clear — geographic map of the epidemic. That map should be the basis for identifying priority areas nationally.

Currently, national information on overdose deaths lags by more than a year. This is unacceptable, and public health officials should be held accountable for creating a local, state, and national, real-time map of the epidemic. Preventing death means stopping traffickers and bringing effective outreach to the addicted in real time.

Finally, while attacking the source and border interdiction take the form of “outside-in” efforts, street enforcement and treatment involves an “inside-out” movement. Is this possible? Can individual communities make progress in the absence of full national success against the drug supply? Can a neighborhood-by-neighborhood strategy work?

Certainly, there is a risk of the epidemic moving back into improved areas from nearby trafficker enclaves. But, in fact, there are many law enforcement examples demonstrating that crime and drug trafficking is displaceable and containable with sustained, effective effort. The pace of the attack matters, and must run ahead of criminal replacement efforts. Local law enforcement agencies successfully contain certain crimes within specific geographic areas, and respond aggressively if criminals overstep boundaries. As in other matters, overwhelming the problem requires capable leadership with the authority, resources, and determination to prevail. For each part of the strategy above, it is important that one individual receive overall responsibility and that this individual understand that they will be removed in the absence of rapid progress. There is no accountability if there is no individual accountability.

The future of addiction in America rests on whether the supply of addictive drugs is dramatically reduced. The drug policy of the Trump administration will determine whether use and addiction are diminished or if they are more deeply embedded in American life — further expanding the underclass of addicted individuals living in misery and dying too young.

John P. Walters, chief operating officer of the Hudson Institute, was Director of National Drug Control Policy (2001–09).

Source: http://www.realclearpolicy.com/articles/2017/09/21/stopping_the_drug_epidemic_110362.html

Comment from Carla Lowe in the USA:

Hello from California,

A most informative article on the opioid epidemic from our friend John Walters. But I wonder how he would justify not addressing marijuana as a key link to this problem.

Perhaps he, like others far from California, is not aware of our 50,000 illegal marijuana grows, a 35 billion dollar business supplying 60% of the nation’s pot. And this is all in the name of so-called “medical” marijuana.

This situation will become significantly worse after January 1st when marijuana will be available just for fun for those over 21. Only Fools would think that kids’ use won’t rise in our formally golden state, now tragically turning green.

Please help us call on President Trump to enforce federal drug laws. It is absolutely our only hope in turning back this madness.

Carla Lowe CALMca.org

Comment from Dr. Stuart Reece in Australia

Yes John. The above is correct but only a partial analysis. Addiction is often based on the gateway drugs cannabis, alcohol and tobacco. Not only is this addictive basis not being addressed by current policies and practice but it is actively being sponsored by many US state Governments in the extremely false belief that reimbursement through taxation with compensate the community for the virtually endless destruction wrecked by drugs at all levels. Up till now the Feds have not addressed this issue either.

Worse still is what is being done to the next generation. It is not rocket science to observe that the children of these addicted patients are mostly not normal. This is very different to the rest of the community. Not only so but cannabis almost certainly underlies the international “gastroschisis epidemic” (where babies are born with their bowels hanging outside of their body) which no one is talking about, and is commonest in the youngest parents – because they smoke the most weed.

If we don’t start telling the truth about addiction in its totality the web of lies will engulf and enslave us all. The hardest hit will be the children and the poor. And, just as has happened in every single community across the globe in developed and developing nations, social decay and distress will become rampant and profligate.

Freedom begins with the truth – and showing a way out of our seductive mess – and breaking the spell of those who cannot wait to cash in on the collapse of the West.

[As illustrated in the Obituary of pioneering FDA scientist, Frances Oldham Kelsey in The Washington Post 8/8/15.]

THIS POST OBITUARY WAS A GODSEND, COMING JUST AS MANY POLITICAL LEADERS ARE BEGINNING A HEADLONG RUSH TO USURP FDA’S AUTHORITY TO APPROVE MARIJUANA-BASED MEDICINES IN FAVOR Of MONEY-CORRUPTED POLITICAL APPROVAL. THE ENDANGERED CITIZENRY, THEIR HEALTH PROFESSIONALS,POLITICAL LEADERS AND OBJECTIVE NEWS MEDIA JOURNALISTS , MUST STRONGLY RESIST THIS MISGUIDED ACTION BY POLTICIANS WHO ARE BLINDLY IGNORING THE HORRIFIC THALIDOMIDE PRECEDENT.

Edited excerpts with commentary follow: The full article is available at the following link:

http://www.washingtonpost.com/national/health-science/frances-oldham-kelsey-heroine-of-thalidomide-tragedy-dies-at-101/2015/08/07/ae57335e-c5da-11df-94e1-c5afa35a9e59_story.html

Frances Oldham Kelsey, FDA scientist who kept thalidomide off U.S. market, dies at 101

In the annals of modern medicine, it was a horror story of international scope: thousands of babies dead in the womb and at least 10,000 others in 46 countries born with severe deformities… The cause, scientists discovered by late 1961, was thalidomide, a drug that, during four years of commercial sales… was marketed to pregnant women as a miracle cure for morning sickness and insomnia.

The tragedy was largely averted in the United States, with much credit due to Frances Oldham Kelsey, a medical officer at the Food and Drug Administration in Washington, who raised concerns about thalidomide before its effects were conclusively known. For a critical 19-month period, she fastidiously blocked its approval while drug company officials maligned her as a bureaucratic nitpicker…

The global thalidomide calamity precipitated legislation…in October 1962 that substantially strengthened the FDA’s authority over drug testing. The new regulations, still in force, required pharmaceutical companies to conduct phased clinical trials, obtain informed consent from participants in drug testing, and warn the FDA of adverse effects, and granted the FDA with important controls over prescription-drug advertising…

In Washington, (Kelsey) joined a corps of reform-minded scientists who, although not yet empowered by the 1962 law that required affirmative FDA approval of any new drug, demanded strong evidence of effectiveness before giving their imprimatur.

At the time, a drug could go on the market 60 days after the manufacturer filed an application with the FDA… Meanwhile, pharmaceutical drug companies commonly supplied doctors with new drugs and encouraged them to test the product on patients, an uncontrolled and dangerous practice that relied almost entirely on anecdotal evidence. NICAP note: Much like today’s treatment of “medical marijuana.”

Thalidomide, which was widely marketed as a sedative as well as a treatment for pregnancy-related nausea during the first trimester of pregnancy, had proven wildly popular in Europe and a boon for its German manufacturer. NICAP note: Much like pro-pot propaganda today has created “wildly popular” support among a fact-deprived public, and boom-times for the Big Marijuana industry.

By the fall of 1960, a Cincinnati-based drug company, William S. Merrell, had licensed the drug and began to distribute it under the trade name Kevadon to 1,200 U.S. doctors in advance of what executives anticipated would be its quick approval by the FDA. NICAP note: Today, illegal drug companies produce and market hundreds of uncontrolled marijuana products and distribute them to corrupt doctors willing to “recommend” such unapproved marijuana “medicines.”

The Merrell application landed on Dr. Kelsey’s desk within weeks of her arrival at the agency…Immediately the application alarmed her. Despite what she called the company’s “quite fulsome” claims, the absorption and toxicity studies were so incomplete as to be almost meaningless. NICAP note: Much like the “quite fulsome claims” for pot medicines are legion today, as is the dearth of valid

studies verifying those claims. For the true documented scientific case against smoking weed as “medicine” see “The DEA Position on Marijuana” at link:

www.justice.gov/dea/docs/marijuana_position_2011.pdf

Dr. Kelsey rejected the application numerous times and requested more data. Merrell representatives, who had large potential profits riding on the application, began to complain to her bosses and show up at her office, with respected clinical investigators in tow, to protest the hold-up. NICAP note: Much as the Pot Legalization Lobbyists and ACLU show up at any attempts to limit sales and use of marijuana—and for the same reason: “large potential profits.”

Another reason for her concern was that the company had apparently done no studies on pregnant animals. At the time, a prevailing view among doctors held that the placental barrier protected the fetus from (harms from) what Dr. Kelsey once called “the indiscretions of the mother,” such as abuse of alcohol, tobacco or illegal drugs. Earlier in her career, however, she had investigated the ways in which drugs did in fact pass through the placenta from mother to baby… NICAP note: Today there are numerous valid studies showing that both mental and physical defects in children can be caused by a pregnant mother’s use of marijuana and other illegal drugs.

While Dr. Kelsey stood her ground on Kevadon, infant deaths and deformities were occurring at an alarming rate in places where thalidomide had been sold… NICAP note: Today, drug addiction, drug-related permanent disabilities and overdose deaths are “occurring at an alarming rate,” nearly all of which began with a shared joint of marijuana from a schoolmate or friend.

Dr. Kelsey might have remained an anonymous bureaucrat if not for a (previous) front-page story in The Post. The newspaper had received a tip about her from staffers working for Sen. Estes Kefauver, a Tennessee Democrat who had been stalled in his years-long battle with the pharmaceutical industry to bolster the country’s drug laws.

The coverage of Dr. Kelsey gave her — and Kefauver — a lift. As thousands of grateful letters flowed in to Dr. Kelsey from the public, the proposed legislation became hard to ignore or to water down. The new law was widely known as the Kefauver-Harris Amendments.

“She had a huge effect on the regulations adopted in the 1960s to help create the modern clinical trial system,” said Daniel Carpenter, a professor of government at Harvard University and the author of “Reputation and Power,” a definitive history of the FDA. “She may have had a bigger effect after thalidomide than before.”…

For decades, Dr. Kelsey played a critical role at the agency in enforcing federal regulations for drug development — protocols that were credited with forcing more rigorous standards around the world…

In Chicago, she helped Geiling investigate the 107 deaths that occurred nationwide in 1937 from the newly marketed liquid form of sulfanilamide, a synthetic antibacterial drug used to treat streptococcal infections. In tablet form, it had been heralded as a wonder-drug of the age, but it tasted unpleasant.

Because the drug was not soluble in water or alcohol, the chief chemist of its manufacturer, S.E. Massengill Co. of Bristol, Tenn., dissolved the sulfanilamide with an industrial substance that was a chemical relative of antifreeze. He then added cherry flavoring and pink coloring to remedy the taste and appearance.

Massengill rushed the new elixir to market without adequately testing its safety. Many who took the medicine — including a high number of children — suffered an agonizing death.

At the time, the FDA’s chief mandate, stemming from an obsolete 1906 law, was food safety. At the agency’s request, Geiling joined the Elixir Sulfanilamide investigation and put Dr. Kelsey to work on animal testing of the drug. She recalled observing rats as they “shriveled up and died.”

Amid national outrage over Elixir Sulfanilamide, Congress passed the Federal Food, Drug and Cosmetic Act of 1938, legislation that vastly expanded federal regulatory oversight over drugs and set a new benchmark for drug safety before marketing… NICAP note: Today, pro-pot politicians are rushing headlong into a massive campaign to block that objective FDA approval process for drugs and instead substitute a money-driven political process that will create a new “Thalidomide” out of marijuana and destroy many more American lives and futures.

Babies who suffered from the effects of thalidomide and survived grew up with a range of impairments. Some required lifelong home care… NICAP note: Is this to be the legacy of current politicians whose corrupt abandonment of the nation’s premier drug approval system will create generations of children “who suffered from the effects of POLITICAL APPROVED “medical” marijuana and survived with a range of impairments, some requiring lifelong home care?”

—————————————————————————————————————

Source: National Institute of Citizen Anti-drug Policy (NICAP)

NICAP COMMENTARY BY: DeForest Rathbone, Chairman.NICAP 8/9/15, Rev. 8/26/15

There is current research into the probable genotoxicity of marijuana and this has been likened to the harm to the foetus in the womb from the drug Thalidomide in the 1960’s.

In the annals of modern medicine, it was a horror story of international scope: thousands of babies dead in the womb and at least 10,000 others in 46 countries born with severe deformities. Some of the children were missing limbs. Others had arms and legs that resembled a seal’s flippers. In many cases, eyes, ears and other organs and tissues failed to develop properly. The cause, scientists discovered by late 1961, was thalidomide, a drug that, during four years of commercial sales in countries from Germany to Australia, was marketed to pregnant women as a miracle cure for morning sickness and insomnia.

The tragedy was largely averted in the United States, with much credit due to Frances Oldham Kelsey, a medical officer at the Food and Drug Administration in Washington, who raised concerns about thalidomide before its effects were conclusively known. For a critical 19-month period, she fastidiously blocked its approval while drug company officials maligned her as a bureaucratic nitpicker. Dr. Kelsey, a physician and pharmacologist later lauded as a heroine of the federal workforce, died Aug. 7 at her daughter’s home in London, Ontario. She was 101. Her daughter, Christine Kelsey, confirmed her death but did not cite a specific cause.

Dr. Kelsey did not single-handedly uncover thalidomide’s hazards. Clinical investigators and health authorities around the world played an important role, as did several of her FDA peers. But because of her tenacity and clinical training, she became the central figure in the thalidomide episode.

In July 1962, The Washington Post directed national attention on the matter — and on Dr. Kelsey — with a front-page article reporting that her “scepticism and stubbornness … prevented what could have been an appalling American tragedy.” [From 1962: ‘Heroine’ of FDA keeps bad drug off the market].

 

The global thalidomide calamity precipitated legislation signed by President John F. Kennedy in October 1962 that substantially strengthened the FDA’s authority over drug testing. The new regulations, still in force, required pharmaceutical companies to conduct phased clinical trials, obtain informed consent from participants in drug testing, and warn the FDA of adverse effects, and granted the FDA with important controls over prescription-drug advertising.

As the new federal law was being hammered out, Kennedy rushed to include Dr. Kelsey in a previously scheduled White House award ceremony honouring influential civil servants, including an architect of NASA’s manned spaceflight program.“In a way, they tied her to the moonshot in showing what government scientists were capable of,” said Stephen Fried, a journalist who investigated the drug industry in the book “Bitter Pills.” “It was an act of incredible daring and bravery to say we need to wait longer before we expose the American people to this drug.”

Dr. Kelsey became, Fried said, “the most famous government regulator in American history.”

‘I was the newest person there and pretty green’

Dr. Kelsey had landed at the FDA in August 1960, one of seven full-time medical officers hired to review about 300 human drug applications per year.The number of women pursuing careers in science was minuscule, but Dr. Kelsey had long been comfortable in male-dominated environments. Growing up in Canada, she spent part of her childhood in an otherwise all-boys private school. She had two daughters while shouldering the demands of medical school in the late 1940s.

In Washington, she joined a corps of reform-minded scientists who, although not yet empowered by the 1962 law that required affirmative FDA approval of any new drug, demanded strong evidence of effectiveness before giving their imprimatur.At the time, a drug could go on the market 60 days after the manufacturer filed an application with the FDA. If the medical officer determined that the submission was incomplete, the drug company could provide additional information, and the clock would start anew.

Meanwhile, pharmaceutical drug companies commonly supplied doctors with new drugs and encouraged them to test the product on patients, an uncontrolled and dangerous practice that relied almost entirely on anecdotal evidence. Thalidomide, which was widely marketed as a sedative as well as a treatment for pregnancy-related nausea during the first trimester of pregnancy, had proven wildly popular in Europe and a boon for its German manufacturer, Chemie Grünenthal.

By the fall of 1960, a Cincinnati-based drug company, William S. Merrell, had licensed the drug and began to distribute it under the trade name Kevadon to 1,200 U.S. doctors in advance of what executives anticipated would be its quick approval by the FDA.The government later estimated that more than 2.5 million tablets were given to about 20,000 patients, several hundred of whom were pregnant.

The Merrell application landed on Dr. Kelsey’s desk within weeks of her arrival at the agency. “I was the newest person there and pretty green,” she later said in an FDA oral history, “so my supervisors decided, ‘Well, this is a very easy one. There will be no problems with sleeping pills.’ ” Immediately the application alarmed her. Despite what she called the company’s “quite fulsome” claims, the absorption and toxicity studies were so incomplete as to be almost meaningless.

Dr. Kelsey rejected the application numerous times and requested more data. Merrell representatives, who had large potential profits riding on the application, began to complain to her bosses and show up at her office, with respected clinical investigators in tow, to protest the hold-up. Dr. Kelsey’s FDA superiors backed her as she conducted her research. By February 1961, she had found more evidence to support her suspicions, including a letter in the British Medical Journal by an English doctor who reported that his patients on thalidomide experienced a painful “tingling” in the arms and feet.

 

Dr. Kelsey also discovered that, despite warnings of side effects printed on British and German drug labels, Merrell had not notified the FDA of any adverse reactions.  Another reason for her concern was that the company had apparently done no studies on pregnant animals. At the time, a prevailing view among doctors held that the placental barrier protected the foetus from what Dr. Kelsey once called “the indiscretions of the mother,” such as abuse of alcohol, tobacco or illegal drugs. Earlier in her career, however, she had investigated the ways in which drugs did in fact pass through the placenta from mother to baby.

While Dr. Kelsey stood her ground on Kevadon, infant deaths and deformities were occurring at an alarming rate in places where thalidomide had been sold. The development of seal-like flippers, a condition known as phocomelia that previously affected an estimated 1 in 4 million infants, began to crop up by the dozens in many countries.

Clinical investigators, because of a variety of complications including spotty tracking systems, only belatedly made the link to thalidomide.  Grünenthal began pulling the drug from the market in Germany in late 1961. Health authorities in other countries issued warnings. Merrell waited until March 1962 to withdraw its U.S. application. By then, at least 17 babies were born in the United States with thalidomide-related defects, according to the FDA

Influence beyond thalidomide

Dr. Kelsey might have remained an anonymous bureaucrat if not for the front-page story in The Post. The newspaper had received a tip about her from staffers working for Sen. Estes Kefauver, a Tennessee Democrat who had been stalled in his years-long battle with the pharmaceutical industry to bolster the country’s drug laws. The coverage of Dr. Kelsey gave her — and Kefauver — a lift. As thousands of grateful letters flowed in to Dr. Kelsey from the public, the proposed legislation became hard to ignore or to water down. The new law was widely known as the Kefauver-Harris Amendments.

“She had a huge effect on the regulations adopted in the 1960s to help create the modern clinical trial system,” said Daniel Carpenter, a professor of government at Harvard University and the author of “Reputation and Power,” a definitive history of the FDA. “She may have had a bigger effect after thalidomide than before.”

In 1963, Dr. Kelsey was named chief of the FDA’s investigational drug branch. Four years later, she was named director of the new Office of Scientific Investigations, a position she held until 1995.  She spent another decade, until her retirement at 90, working at the FDA’s Center for Drug Evaluation and Research. In that role, she advised the director of its compliance office on scientific and medical issues and analyzed historical drug review issues.

According to historians of the FDA, she was instrumental in establishing the institutional review boards — a cornerstone of modern clinical drug development — that were created after abusive drug testing trials were exposed in prisons, hospitals and nursing homes. For decades, Dr. Kelsey played a critical role at the agency in enforcing federal regulations for drug development — protocols that were credited with forcing more rigorous standards around the world.

Name mistaken for a man’s

Frances Kathleen Oldham was born near Cobble Hill, on Vancouver Island, British Columbia, on July 24, 1914. Her father was a retired British army officer, and her mother came from a prosperous Scottish family.  The young “Frankie,” as she was called, grew up exploring the woods and shorelines, sometimes bringing home frogs for dissection. At McGill University in Montreal, she studied pharmacology — the effects of drugs on people — and received a bachelor’s degree in 1934 and a master’s degree in 1935.

A McGill professor urged her to apply for a research assistant job at the University of Chicago, where pharmacology professor Eugene Geiling accepted her without an interview. Geiling, who had mistaken the names Frances for the masculine Francis, addressed her by mail as “Mr. Oldham.”

“When a woman took a job in those days, she was made to feel as if she was depriving a man of the ability to support his wife and child,” Dr. Kelsey told the New York Times in 2010. “But my professor said: ‘Don’t be stupid. Accept the job, sign your name and put “Miss” in brackets afterward.’ ”

In Chicago, she helped Geiling investigate the 107 deaths that occurred nationwide in 1937 from the newly marketed liquid form of sulfanilamide, a synthetic antibacterial drug used to treat streptococcal infections. In tablet form, it had been heralded as a wonder-drug of the age, but it tasted unpleasant.Because the drug was not soluble in water or alcohol, the chief chemist of its manufacturer, S.E. Massengill Co. of Bristol, Tenn., dissolved the sulfanilamide with an industrial substance that was a chemical relative of antifreeze. He then added cherry flavouring and pink colouring to remedy the taste and appearance.

Massengill rushed the new elixir to market without adequately testing its safety. Many who took the medicine — including a high number of children — suffered an agonizing death.  At the time, the FDA’s chief mandate, stemming from an obsolete 1906 law, was food safety. At the agency’s request, Geiling joined the Elixir Sulfanilamide investigation and put Dr. Kelsey to work on animal testing of the drug. She recalled observing rats as they “shrivelled up and died.”

Amid national outrage over Elixir Sulfanilamide, Congress passed the Federal Food, Drug and Cosmetic Act of 1938, legislation that vastly expanded federal regulatory oversight over drugs and set a new benchmark for drug safety before marketing. Massengill’s owner ultimately was fined a maximum penalty of $26,000 for mislabelling and misbranding; by technical definition, an elixir contains alcohol.

‘We need to take precautions’

Dr. Kelsey received a doctorate from Chicago in 1938, then joined the faculty. In 1943, she wed a pharmacology colleague, Fremont Ellis Kelsey.  After graduating from Chicago’s medical school in 1950, Frances Kelsey taught pharmacology at the University of South Dakota medical school and was a fill-in doctor at practices throughout the state. She also became a U.S. citizen before arriving in Washington in 1960 when her husband was hired by the National Institutes of Health. He died in 1966 after a heart attack.

Survivors include their daughters, Susan Duffield of Shelton, Wash., and Christine Kelsey of London, Ontario; a sister; and two grandchildren. Dr. Kelsey moved to Ontario from suburban Maryland in 2014.

Babies who suffered from the effects of thalidomide and survived grew up with a range of impairment. Some required lifelong home care. Others held jobs and were not severely hindered by their disabilities. Many legal settlements were reached between drug companies and the victims of thalidomide, and new claims continue to surface. Grünenthal formally apologized to victims of thalidomide in 2012.

The drug, however, never disappeared entirely. Researchers have investigated thalidomide’s effects on H.I.V. and Crohn’s disease and have conducted clinical trials for on its use for rheumatoid arthritis and macular degeneration, a leading cause of blindness.

In 1998, the FDA approved the drug for the treatment of lesions from leprosy. In 2006, thalidomide was cleared for use with the medicine dexamethasone for certain cases of multiple myeloma, a cancer of the bone marrow.

The agency enforced strict safeguards, including pregnancy testing, for such new uses. “We need to take precautions,” Dr. Kelsey told an interviewer in in 2001, “because people forget very soon.”

Source:https://www.washingtonpost.com/national/health-science/frances-            oldham-kelsey-heroine-of-thalidomide-tragedy-dies-at-101/2015/08/07

Louise Stanger is a speaker, educator, licensed clinician, social worker, certified daring way facilitator and interventionist who uses an invitational intervention approach to work with complicated mental health, substance abuse, chronic pain and process addiction clients.

In the mid-to-late 2000s, Red Bull, an energy drink high on energy and low on nutritional value, made its North American debut with the famous “Red Bull gives you wings” campaign. The tag line, a nod to the “pick me up” qualities it gives to drinkers of the product, set the stage for the way in which teens and young adults relate to the nascent product category.

In essence, advertising birthed energy drinks as the way to find uplift, fight fatigue, and give that extra boost. Regrettably, no one was paying attention to the drinks’ negative side effects.

Red Bull has since spawned its own grocery store aisle of knock-offs – Monster, Rockstar, Full Throttle, Amp – to name a few. In 2016, U.S. retail sales of energy drinks topped $11 billion (Red Bull generated $5.1B in revenue in 2010). By comparison, that number is roughly how much Hollywood makes on movie tickets in a year.

Paradoxically, energy drinks’ meteoric rise in popularity and consumption has coincided with major health risks and the onslaught of addiction to other harmful substances. How did a drink that tastes like cough syrup land with such a huge impact?

Long before Red Bull “gave us wings,” Chaleo Yoovidhya, a Southeast Asian pharmacist, developed energy “tonics” aimed at labourers and truck drivers in the 1960s, according to The Dragonfly Effect, a book that looks at successful branding campaigns for products like energy drinks.

Then in the 1980s, an Austrian billionaire businessman named Dietrich Mateschitz discovered the tonics and married them with innovative guerrilla marketing to launch in North America. The aim was to put cans of Red Bull, the syrupy concoction of sugar and caffeine, in the hands of their target market: young adult males and teens who are oblivious to the drinks’ ingredients. The ad campaign struck like a lightning bolt and a multibillion dollar industry took ro

The key ingredient in energy drinks that gives the consumer energizing effects is caffeine. Though caffeine, found in commonly consumed drinks like coffee, tea and sodas, isn’t outright bad for you, the serving size, frequency and consumption patterns are cause for alarm.

Most energy drinks contain 70-200 milligrams of caffeine; for example, Rockstar 2X has 250 mg per 12 ounces, a 12 ounce can of Red Bull has 111 mg, and a 5-Hour Energy shot, a variation of the energy drink craze, is a whopping 207 mg of caffeine in just 2 ounces.

To put these concentration levels into perspective, the American Academy of Paediatrics maintains adolescents must not consume more than 100 mg of caffeine per day (it’s 500 mg for adults).

And more alarming than the serving sizes are the rates at which teens consume energy drinks. When young adults and teenagers get with their friends, they’ll consume 3-4 drinks in a short period of time or even chug (i.e. “shotgun”) whole cans in an instant. Despite this binge-style consumption, teens remain oblivious to the high caffeine content and unaware of the effects energy drinks have on the body. Other studies and researchers have observed energy drinks become the chaser for alcohol consumption in certain situations.

At these high levels of consumption, the Journal of the American Medical Association (JAMA) reports serious health risks associated with energy drinks. These include:

· Increased heart rate, irregularities and palpitations

· Increased blood pressure

· Sleep disturbances, insomnia

· Diuresis or increased urine production

· Hyperglycaemia (increased blood sugar), due to the high levels of sugar content, which may be harmful for people at risk for diabetes or already diabetic

Perhaps most dangerous are the serious side effects caused when energy drinks are consumed with alcohol. According to University Health News Daily, “the dangers of energy drinks mixed with alcohol are related to reduced sensation of intoxication and impaired judgment.”

Here’s how it goes: the user gets a burst of energy and alertness (increased heart rate and dilated blood vessels) from the high content of caffeine in the energy drink, prompting the person to feel less intoxicated and therefore drinking more alcohol and putting themselves at risk for alcohol poisoning and severely impaired judgment.

Teens, young adults and college-aged students who play drinking games or drink in high-risk environments such as parties, boating, swimming, beach days, etc. put themselves at greater risk of injury and bodily harm with these combinations.

In addition to high-risk environments and dangerous situations, energy drink and alcohol mixing lowers inhibitions, making room for engaging in high-risk behaviours such as unwanted sexual encounters, driving vehicles, boats and jet skis under the influence, and other behaviours that may lead to hospitalization or encounters with law enforcement.

We need look no further than the case of Four Loko, an energy drink that comes ready made with alcohol and caffeine for proof that mixing the two is dangerous. The drink gets its name from its four signature ingredients: alcohol, caffeine, taurine and guarana.

According to a report in The Week, the company that produced Four Loko, Phusion Projects of Chicago aka Drink Four Brewing Company, came under ethical fire for marketing to adolescents under the age of 21 (as most energy drink companies do – though this was the first to pre-mix alcohol and caffeine).

Four Loko also caught fire with college students and it didn’t take long for reports of blackouts and other alcohol overdose related incidents to take hold of its users. University campuses across the nation including the University of Rhode Island, Central Washington University and Worcester State University began to ban the beverage and companies with similar beverages have since reformulated its drinks and reduced its marketing toward underage students and young adults. In 2014, the company reached a settlement to stop production and distribution of Four Loko in the United States, according to a report in The Atlantic.

Moreover, the University of Maryland’s research on the topic has found a link between high energy drink consumption and developing addiction to other harmful substances later on. Researchers looked at the health and risk-taking habits of 1,099 college students over a four year period.

Their analysis of the study found that participants who consumed highly caffeinated drinks (energy drinks, sodas, etc.) are more likely to develop an addiction to cocaine, alcohol, or other substances when compared to students who did not consume such beverages. “The results suggest that energy drink users might be at heightened risk for other substance use, particularly stimulants,” says Amelia Arria, an associate professor and lead author of the study.

New research from Purdue University found that mixing alcohol and highly caffeinated drinks could significantly change the brain activity of a teenager. Dr. Richard van Rijn, the lead researcher, says “it seems the two substances (energy drinks and alcohol) together push [teenagers] over a limit that causes changes in their behaviour and changes the neurochemistry in their brains.”

Although energy drinks are regulated by the Food and Drug Administration, little oversight is given to labelling cans and packages with the risks related to consumption. As an educator, I believe the FDA must first do a better job of labelling. Just as cigarettes and alcohol have warning labels, so too must energy drinks.

Grocery stores should move energy drink products to areas where alcohol is sold – away from wandering young eyes. Public health discussions in high schools and middle schools need to take place. Youth and young adult sports teams must reconsider energy drink sponsorships and greater oversight concerning marketing practices toward under-aged youth.

As a young adult, if you do choose to consume these beverages, be sure to read the labels for serving sizes, caffeine content, and try to avoid mixing with alcohol. Parents, teachers, sports coaches, and community leaders must communicate to teenagers and young adults the harm energy drinks may cause. Together we must work together to be educated and informed against aggressive advertising to keep our teens and young adults healthy and engaged.

To learn more about Louise Stanger and her interventions and other resources, visit her website.

Source: http://www.huffingtonpost.com/entry/red-bull-monster-four-loko-rockstar-the-downside_us_59b021cce4b0bef3378cdcee    6th Sept.2017

 

 

 

Mathias B. Forrester and Ruth D. Merz

Hawaii Birth Defects Program, Honolulu, Hawaii, USA

Extracts from Study 

The literature on the association between prenatal illicit drug use and birth defects is inconsistent. The objective of this study was to determine the risk of a variety of birth defects with prenatal illicit drug use.

Data were derived from an active, population based adverse pregnancy outcome registry. Cases were all infants and foetuses with any of 54 selected birth defects delivered during 1986–2002.

The prenatal methamphetamine, cocaine, or marijuana use rates were calculated for each birth defect and compared to the prenatal use rates among all deliveries.

Among all deliveries, the prenatal use rate was 0.52% for methamphetamine,0.18% for cocaine, and 0.26% for marijuana.

Methamphetamine rates were significantly higher than expected for 14 (26%) of the birth defects.

Cocaine rates were significantly higher than expected for 13 (24%) of the birth defects.

Marijuana rates were significantly higher than expected for 21 (39%) of the birth defects. Increased risk for the three drugs occurred predominantly among birth defects associated with the central nervous system, cardiovascular system, oral clefts, and limbs. There was also increased risk of marijuana use among a variety of birth defects associated with the gastrointestinal system. Prenatal uses of methamphetamine, cocaine, and marijuana are all associated with increased risk of a variety of birth defects.

The affected birth defects are primarily associated with particular organ systems.

DISCUSSION

Using data from a Statewide, population-based registry that covered over 300,000 births and a 17-yr period, this investigation examined the association between over 50 selected birth defects and maternal use of methamphetamine, cocaine, or marijuana during pregnancy. Much of the literature on prenatal illicit drug use and birth defects involved case reports, involved a small number of cases, were not population-based, or focused on only one or a few particular birth defects.

There are various limitations to this investigation. The number of cases for many of the birth defects categories was relatively small, limiting the ability to identify statistically significant differences and resulting in large confidence intervals.

In spite of this, a number of statistically significant analyses were identified. Some statistically significant results might be expected to occur by chance. If 1 in every 20 analyses is expected to result in statistically significant differences solely by chance, then among the 162 analyses performed in this study, 8 would be expected to be statistically significant by chance. However, 48 statistically significant differences were identified. Thus, not all of the statistically significant results are likely to be due to chance.

This study included all pregnancies where methamphetamine, cocaine, or marijuana use was identified through either report in the medical record or positive toxicology test. This was done because neither self-report nor toxicology testing is likely to identify all instances of prenatal illicit drug use (Christmas et al., 1992).

In spite of using both methods for determining prenatal illicit drug use, all pregnancies involving methamphetamine, cocaine, or marijuana were not likely to have been identified. The degree of under ascertainment is unknown. A previous study examined the maternal drug use rate around the time of delivery in Hawaii during 1999 (Derauf et al., 2003). This study found 1.4% of the pregnancies involved methamphetamine use and 0.2% involved marijuana use. Among 1999 deliveries, the HBDP identified a prenatal methamphetamine use rate of 0.7% and a marijuana use rate of 0.4%. However, comparisons between the 2 studies should be made with caution because the previous study collected data from a single hospital during only a 2-mo period.

Another limitation is that the present study did not control for potential confounding factors such as maternal demographic characteristics, health behaviors, and prenatal care. Increased risk of birth defects has been associated with inadequate prenatal care (Carmichael et al., 2002), maternal smoking (Honein et al., 2001), and maternal alcohol use (Martinez-Frias et al., 2004).

These factors are also found with maternal illicit drug use (Cosden et al., 1997; Hutchins, 1997; Norton-Hawk, 1997). Thus the increased risk of selected birth defects with illicit drug use in this study might actually be due to one of these other underlying factors. Unfortunately, informationon some of the potential confounding factors such as socioeconomic status are not collected by the HBDP. Information collected on some other factors such as smoking and alcohol use is suspect because of negative attitudes toward their use during pregnancy. Moreover, the small number of cases among many of the birth defects groups would make controlling for these factors difficult.

Finally, this investigation included use of the illicit drugs at any time during the pregnancy. Most birth defects are believed to occur at 3–8 wk after conception (Makri et al., 2004; Sadler, 2000). In a portion of the cases, the drug use might have occurred at a time when it could not have caused the birth defect. Furthermore, this study does not include information on dose; however, teratogenicity of a substance may depend on its dose (Werler et al., 1990). In spite of the various potential concerns of the present study, data may suggest future areas of investigation where the limitations inherent in the present one are excluded.

This investigation found significantly higher than expected rates for prenatal use of methamphetamine, cocaine, and marijuana among a number of specific birth defects. Although not identical, there were general similarities between the three illicit drugs and the birth defects with which they were associated. Increased rates for methamphetamine, cocaine, and marijuana occurred predominantly among birth defects affecting the central nervous system, cardiovascular system, oral clefts, and limbs. There were also increased rates of marijuana use with a variety of birth defects associated with the gastrointestinal  system. With the exception of marijuana and encephalocele, none of illicit drugs were associated with neural-tube defects (anencephaly, spina bifida, encephalocele). The rates of use for the three illicit drugs were not significantly elevated with eye defects other than anophthalmia/microphthalmia, genitourinary defects, and musculoskeletal defects aside from limb defects.

In the majority of instances, the associations between particular illicit drugs and birth defects were found whether or not those cases involving use of multiple types of drugs were included.

Of the 14 significant associations between methamphetamine and specific birth defects, 10 (71.4%) remained once multiple drug cases were excluded. Corresponding rates were 61.5% (8 of 13) for cocaine and 81.0% (17 of 21) for marijuana.

The similarities in the patterns of birth defects with which methamphetamine, cocaine, and marijuana are associated might suggest that the three drugs exert similar effects on embryonic and foetal development. This might not be expected, considering that the three illicit drugs differ in their mechanisms of action and clinical effects (Leiken & Paloucek, 1998).

Some of the associations between methamphetamine, cocaine, and marijuana observed in the present investigation were previously reported. Other studies observed similar associations, or lack thereof, of methamphetamine or amphetamine with neural-tube defects (Shaw et al., 1996) and cardiovascular and musculoskeletal defects (McElhatton et al., 2000); cocaine with neural-tube defects (Shaw et al., 1996), cardiovascular defects (Lipshultz et al., 1991), ventricular septal defect and atrial septal defect (Ferencz et al., 1997c; Martin & Edmonds, 1991), tricuspid atresia (Ferencz et al., 1997d), craniosynostosis (Gardner et al., 1998), and situs inversus (Kuehl & Loffredo, 2002); and marijuana with neural-tube defects (Shaw et al., 1996), single ventricle (Steinberger et al., 2002), ventricular septal defect (Williams et al., 2004), tricuspid atresia (Ferencz et al., 1997d), and gastroschisis (Torfs et al., 1994).

In contrast, this study differed from other research with respect to their findings regarding methamphetamine or amphetamine and gastroschisis (Torfs et al., 1994); cocaine and microcephaly (Martin & Edmonds, 1991), conotruncal defects (Adams et al., 1989), endocardial cushion defect (Ferencz et al., 1997b), situs inversus (Ferencz et al., 1997a), oral clefts (Beatyet al., 2001), and genitourinary defects (Abe et al., 2003; Battin et al., 1995; Martin & Edmonds, 1991); and marijuana and conotruncal defects (Adams et al., 1989), Ebstein anomaly (Ferencz et al., 1997e; Correa-Villasenor et al., 1994), and oral clefts (Beaty et al., 2001).

The inconsistent findings between this and the other studies could be due to differences in study methodology, case classification, or number of cases. The mechanisms by which methamphetamine, cocaine, and marijuana might contribute to the rates for birth defects is currently unknown. Any potential explanation would have to take into account the observation that each of the illicit drugs was associated with a variety of specific birth defects affecting different organ systems. This might suggest that these three drugs would need to influence a basic, common factor involved in embryonic development.

Folic acid is involved in nucleic acid synthesis and cellular division (Scholl & Johnson, 2000) and thus would play an important role in the early growth and cellular proliferation of the embryo. Folic acid has been found to prevent a variety of birth defects (Forrester & Merz, 2005). Thus, anything that interferes with the activity of folic acid might be expected to increase the risk for these birth defects. Many of these birth defects were associated with methamphetamine, cocaine, and/or marijuana in the present study.

However, two of the birth defects most closely affected by folic acid—anencephaly and spina bifida—were not associated with any of the three illicit drugs. Vascular disruption has been suggested as a potential cause for a variety of different birth defects such as intestinal atresia/stenosis, limb reduction defects, and gastroschisis.

Since cocaine is a vasoconstrictor, it has been hypothesized that cocaine use could increase the risk of these vascular disruption defects (Hume et al., 1997; Martin et al., 1992; Hoyme et al., 1983; de Vries, 1980). Although this investigation found an association between cocaine and limb reduction deformities, no association was found with intestinal atresia/stenosis or gastroschisis.

In conclusion, this study found that prenatal use of methamphetamine, cocaine, or marijuana were associated with increased risk of a variety of birth defects. The affected birth defects were primarily associated with particular organ systems. Because of various limitations of the study, further research is recommended.

Source:  Journal of Toxicology and Environmental Health, Part A, 70: 7–18, 2007

MS Society says there is sufficient evidence of drug’s effectiveness to relax ban for patients with no other options

Ten thousand people with multiple sclerosis in the UK should be allowed to use cannabis legally in order to relieve their “relentless and exhausting” symptoms, experts in the disease have told ministers.

The MS Society claims the one in 10 sufferers of the condition whose pain and spasticity cannot be treated by medication available on the NHS should be able to take the drug without fear of prosecution.

The evidence on cannabis’s effectiveness, while not conclusive, is now strong enough that the government should relax the ban on the drug for MS patients who have no other treatment options, the society says in a report.

Doctors who treat MS patients have backed the society’s call, as have the Liberal Democrats and the Green party. Legalisation would ease “the extremely difficult situation in which many people with MS find themselves”, the charity said.

The society is calling for the first time for the 10,000 patients – one in 10 of the 100,000 people in Britain with MS – to be able to access cannabis without fear of arrest. It has changed its position after reviewing the evidence, consulting its medical advisers and seeking the views of 3,994 people who have the condition.

“We think cannabis should be legalised for medicinal use for people with MS to relieve their pain and muscle spasms when other treatments haven’t worked,” said Genevieve Edwards, the MS Society’s director of external affairs.

“The level of clinical evidence to support cannabis’s use for medicinal purposes is not conclusive. But there is sufficient evidence for our medical advisers to say that on the balance of probability, cannabis could benefit many people with MS experiencing pain and muscle spasms.” The charity is also urging NHS bosses to make Sativex, a cannabis-based drug used by some people with MS, available on prescription across the UK so that patients who can afford it no longer have to acquire it privately, at a cost of about £2,000 a year. Wales is the only home nation to provide the mouth spray through the NHS.

Patients’ inability to access Sativex on the NHS in England, Scotland and Northern Ireland “has resulted in many people with MS turning to illegal forms of cannabis as an alternative. It’s simply not right that some people are being driven to break the law to relieve their pain and spasticity. It’s also really risky when you’re not sure about the quality or dosage of what you’re buying,” Edwards said.

Norman Lamb, the Lib Dem health spokesman, said: “This is the strongest proof yet that the existing law on cannabis is a huge injustice that makes criminals of people whose only crime is to be in acute pain. This draconian law is potentially opening anything up to 10,000 MS sufferers to prosecution, and underlines why the Liberal Democrats have braved a tabloid backlash to campaign for the legalisation of cannabis. It is about time the government listened to the science.”

One in five (22%) MS patients who took part in a survey by the society said they had used cannabis to help manage their symptoms, but only 7% were still doing so. A quarter (26%) of those who had stopped taking it said they had done so out of fear of

prosecution. Another 26% of respondents had considered trying cannabis but had not done so for the same reason and also because they were concerned about the drug’s safety.

Doctors are divided over cannabis’s potential role in treating MS. Some are supportive while others are anxious about endorsing the use of a drug that can cause psychiatric problems. The Royal College of GPs said it was currently drawing up policy on the issue and could not comment. The Royal College of Physicians, which represents hospital doctors, said it had no policy on the issue.

Dr Willy Notcutt, a pain management specialist at the James Paget hospital in Norfolk, who has been treating MS patients for more than 20 years, said: “Every week I come across patients wishing to use cannabis to control their symptoms but who are unable to get proven drugs like Sativex from the NHS. Many patients seek illegal cannabis to get help. They can’t be sure of its origin but are being forced to commit a criminal act in order to obtain relief.”

Dr Waqar Rashid, a consultant neurologist at Brighton and Sussex University Hospitals NHS trust, said: “[Cannabis is] not a cure-all, and there are other treatments that should be tried first. But it makes sense for criminality not be a barrier to a treatment which could reduce the debilitating impact of symptoms and transform someone’s quality of life.”

Caroline Lucas, the Green party co-leader and its sole MP, said: “The MS Society’s new position is a big step forward, and recognises the fact that thousands of people with MS could benefit from the the use of medicinal cannabis. By rigidly sticking to criminalising cannabis the government drives MS sufferers to illegally acquire the drugs, thus putting themselves as risk of prosecution simply for searching for pain relief.” The National Institute for Health and Clinical Excellence (Nice), which advises the government, has told the NHS not to prescribe Sativex for spasticity because it is not cost-effective. The Home Office said: “This government has no plans to legalise cannabis. Cannabis is controlled as a Class B drug under the Misuse of Drugs Act 1971 and, in its raw form, currently has no recognised medicinal benefits in the UK.”

Case study: Steven Colborn, 55, from Seaham, County Durham

Imagine running a marathon while sharp pain darts up and down your legs. This is what multiple sclerosis feel like for me. When muscle spasticity kicks in my legs just twist and turn and bend back on themselves and it’s excruciatingly painful.

But three years ago I was offered a treatment that could help. During a regular appointment, a specialist nurse said they had managed to get a month’s supply of Sativex, a drug derived from cannabis, from the manufacturer.

The results were incredible. My muscle tension eased and I started to feel my legs moving better. I was able to get a good night’s sleep. I could exercise without getting as tired as quickly. For the first time in a long time I felt that I was managing my condition.

My month’s supply ran out and the drug wasn’t available free on the NHS. I was offered a muscle relaxer called Baclofen which hadn’t worked for me in the past.

I have been forced to pay for this drug myself. I can’t work any more so I rely on disability benefits. I have to save up a lot of money to be able to afford it – it costs £412 a month. Over the past four years I’ve only managed to buy about seven months’ worth.

I take Sativex but other people get similar relief from cannabis in its pure form. I don’t like taking this myself because of the narcotic effect, which you don’t get with Sativex. But for those it helps, it should be made legal.

I have had this illness for 36 years and every day I wake up and think ‘maybe there has been a breakthrough’. I know there will never be a cure, but I am just looking for a way to make things easier. Now I have been presented with something that offers me hope and the NHS say they cannot afford it. My question is: can you afford people like me getting worse?

Source:  https://www.theguardian.com/society/2017/jul/27/legalise-cannabis-as-treatment-of-last-resort-for-multiple-sclerosis-says-charity

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Comments by  NDPA:

UK  is 1st world nation with 1st world medicine approval system, even then we get things wrong e.g Thalidomide.

Cannabis based medicine is no problem if it goes through that system.

Sadly, ill people have been and are being exploited by the drug legalisation lobby, in furtherance of their nirvana of recreational cannabis for all.

Cannabis is a very harmful psychoactive drug, it induces dependency in around 1 in 9 or 10 users. It has numerous bad effects.

Smoking is obviously not a sensible delivery system for medication, yet a lot of those complaining want to smoke cannabis.

Cannabis based drugs like Sativex are in the pharmacopeia thanks to the wise licensing of the research on them by successive UK governments.

The mechanisms by which those cannabis based drugs are made available to  specific MS sufferers are a matter for the relevant authorities who deal with all pharmaceutical drugs. They must show efficacy and they must satisfy NICE.

There are no grounds at all for making cannabis any sort of special case, in fact the recreational user base and the legalisation lobby distort the arguments and would be better remaining silent.

Introduction  

On 31 July 2017 a court case commences in the Pretoria High Court about the constitutional legality of South Africa’s dagga legislation. The media is calling it the “Trial of the Plant”.

What is the “Trial of the Plant” about?

It is about the dagga plant and its prohibition in our society. Scientists have long since proven that the dagga plant is highly complex and dangerous and must be prohibited, but some believe it is not dangerous and even medicinal.

What does the law in SA say about dagga?

Except for medical and research exemptions, the possession, use, cultivation, transportation and distribution of dagga is criminalised in terms of the Drugs and drug trafficking act as well as the Medicines and related substances act.

Was the law not settled by the Constitutional court in 2002?

In 2002 a Rastafarian brought a case to the Constitutional Court about Dagga where he complained that the law prevented him smoking dagga as a religious observance and this violated his rights to religious freedom.

The court accepted that a Rastafarian’s religious rights were violated but dismissed the case as there is no objective way for law enforcement officials to distinguish between the possession or use of cannabis for religious or for recreational purposes.

The trial of the plant will in all likelihood be the final decider.

Why is that?

Because the Trial of the Plant will be the first and only case where there will be oral evidence given and tested, in the witness stand.

These other cases were fought and decided on affidavit evidence in a day or two.

The trial of the plant is very different and will take many days in court starting on 31 July and continuing through the month of August.

There are three legal teams comprising 6 attorneys, 11 advocates, 16 expert witnesses and as many as 12 other witnesses.  The trial will probably be recorded by the media and will also probably go all the way to the Constitutional Court to be finally decided.

DFL’s lead counsel is Adv Reg Willis instructed by the University of Pretoria Law Clinic.

How did this case start?

In 2010 a couple were arrested with approximately R500 000.00 worth of dagga in their home. They became known as the dagga couple.

To avoid prosecution they obtained an interdict in the Pretoria High Court against their prosecution, pending the outcome of a case to declare that all the SA dagga legislation is unconstitutional.

The case is against various government departments and against Doctors for Life International.

DFL joined this case to be of assistance to the State.

So for example DFL will lead the evidence of Harvard Professor Bertha Madras who is one of the foremost authorities on cannabis in the world. She contends that the legalisation of cannabis has to be resisted in the interests of the human brain.

Who is Doctors for Life and what does it do?

DFL is a non-profit relief and civil society organisation of doctors who care and give voluntarily of their own time and money to the many needs of the poor.

DFL serve the needs of the underprivileged communities they serve in South Africa and Southern Africa.  DFL also has an extensive track record of being involved in public interest cases predominantly as a friend of the court, especially to assist with scientific and similar evidence.

So then how is the dagga couple funding their case?

The dagga couple dragged the case out for some years, while they raised money.  They started an organisation called “Fields of Green for All” “FOGFA” which now has over 45000 supporters who are funding the case.

How important is this case for South Africa?

Given the role of dagga in crime, women and child abuse and the future of our youth, this trial is one of the most important to ever reach our courts.  If the dagga couple win their case as they want to, there will be no restriction on the possession, consumption, cultivation, transportation and distribution of cannabis.  A free for all.

Read our dagga court case press releases and more info on cannabis Media Release: High Court Blunders into Dagga Minefield

Source:  Letter from Johan Claassen  www.doctorsforlife.co.za) sent to Drugwatch International  27th July 2017

A new study provides credible evidence that marijuana legalization will lead to decreased academic success. (Elaine Thompson/AP)

The most rigorous study yet of the effects of marijuana legalization has identified a disturbing result: College students with access to recreational cannabis on average earn worse grades and fail classes at a higher rate. Economists Olivier Marie and Ulf Zölitz took advantage of a decision by Maastricht, a city in the Netherlands, to change the rules for “cannabis cafes,” which legally sell recreational marijuana. Because Maastricht is very close to the border of multiple European countries (Belgium, France and Germany), drug tourism was posing difficulties for the city. Hoping to address this, the city barred noncitizens of the Netherlands from buying from the cafes.

This policy change created an intriguing natural experiment at Maastricht University, because students there from neighboring countries suddenly were unable to access legal pot, while students from the Netherlands continued.

The research on more than 4,000 students, published in the Review of Economic Studies, found that those who lost access to legal marijuana showed substantial improvement in their grades. Specifically, those banned from cannabis cafes had a more than 5 percent increase in their odds of passing their courses. Low performing students benefited even more, which the researchers noted is particularly important because these students are at high-risk of dropping out. The researchers attribute their results to the students who were denied legal access to marijuana being less likely to use it and to suffer cognitive impairments (e.g., in concentration and memory) as a result.

Other studies have tried to estimate the impact of marijuana legalization by studying those U.S. states that legalized medicinal or recreational marijuana. But marijuana policy researcher Rosalie Pacula of RAND Corporation noted that the Maastricht study provide evidence that “is much better than anything done so far in the United States.”

States differ in countless ways that are hard for researchers to adjust for in their data analysis, but the Maastricht study examined similar people in the same location — some of them even side by side in the same classrooms — making it easier to isolate the effect of marijuana legalization. Also, Pacula pointed out that since voters in U.S. states are the ones who approve marijuana legalization, it creates a chicken and egg problem for researchers (i.e. does legalization make people smoke more pot, or do pot smokers tend to vote for legalization?). This methodological problem was resolved in the Maastricht study because the marijuana policy change was imposed without input from those whom it affected.

Although this is the strongest study to date on how people are affected by marijuana legalization, no research can ultimately tell us whether legalization is a good or bad decision: That’s a political question and not a scientific one. But what the Maastricht study can do is provides highly credible evidence that marijuana legalization will lead to decreased academic success — perhaps particularly so for struggling students — and that is a concern that both proponents and opponents of legalization should keep in mind.

Source:https://www.washingtonpost.com/news/wonk/wp/2017/07/25/these-       college-students-lost-access-to-legal-pot-and-started-getting-better-grades/?   

In his last article for Pro Talk, Renaming and Rethinking Drug Treatment, psychologist Robert Schwebel, Ph.D., author and developer of The Seven Challenges program, expressed his views about problems in typical drug and alcohol treatment. In this interview, he focuses on changes that he thinks would better meet the needs of individuals with substance problems.

The Seven Challenges Program

The Seven Challenges is described as “a comprehensive counselling program for teens and young adults that incorporates work on alcohol and other drug problems.” The program addresses much more than substance issues because it also helps young people develop better life skills, as well as manage their situational and psychological problems. Although there is an established structure for each session and a framework for decision-making (see website for the youth version of “The Seven Challenges”), it is not pre-scripted as in many traditional programs. Rather it is “exceptionally flexible, in response to the immediate needs of the clients.”

Independent studies funded by The Center for Substance Abuse Treatment and published in peer-reviewed journals have provided evidence that The Seven Challenges significantly decreases substance use of adolescents and greatly improves their overall mental health status. The program has been shown to be especially effective for the many young people with drug problems who also have trauma issues.

Just recently, a new version of The Seven Challenges program was introduced for adults and is being piloted in a research project. Soon, a book geared toward the general public by Dr. Schwebel that incorporates much of the philosophy of the program, as well as many of the decision-making and behavior change strategies, will be available.

Q&A: What Should Treatment Look Like?

Q: In your last article for Pro Talk, you argued strongly against the word “treatment” and suggested that we use the word “counselling” instead. Will you reiterate why you prefer using “counselling” when talking about professional help for people with substance problems?

Dr. S.: Counselling is an active and interactive process that’s responsive to the needs of individuals. It may include education, but it’s more than that because the information is personalized and offered in the context of a discussion about what’s happening in a person’s life. Effective counsellors help clients become aware of their options, expand those options, and make their own informed choices.

Treatment, on the other hand, sounds like something imposed and passive that an authority (say a doctor) does to someone else or tells them to do. It also implies recipients receive a standardized protocol or regime with a preconceived goal, usually abstinence when we’re talking about addiction. It doesn’t suggest autonomy of choice or collaboration.

 

Q: You stress the importance of choice and collaboration, suggesting both are important in addiction counselling. Please tell us more.

Dr. S.: In collaborative counselling that allows choices, clients get to identify the issues they want to work on. They make the decisions. We make it clear that we’re not there to make them quit using drugs…and couldn’t even if we tried. We tell them, “We’re here to support you in working on your issues, things that are important to you; things that are not going well in your life or as well you would like them to be going.”

We also support clients in decision-making about drugs. They set their own goals about using. One person might want to quit using, while another might want to set new limits. For those who want to change their drug use behavior, we check in with them about how they’re doing regarding their decision on a session-by-session basis. If they have setbacks, we’ll provide individualized support to help them figure out why, We’re not doubting them or trying to “catch” them. Rather, we’re helping them succeed with their own decisions to change. This type of check-in would not apply to individuals who have not yet decided to make changes.

 

Q: Many addiction programs feel that dealing with addiction should be the first priority and that other issues are secondary. What are your thoughts about this?

Dr. S.: I’ll start by saying that they have equal importance. Drug problems have everything to do with what is going on in a person’s life. And, a person’s life is very much affected by drug problems. I do want to say, however, that not everyone who winds up in an addiction program has an addiction. That’s a ridiculous generalization. They may be having problems with binge drinking, issues with family or jobs because of substance misuse, or legal problems because they were unlucky and got caught. (For instance they got arrested for another crime and tested positive for drugs.) They often wind up in places that require abstinence and wonder, “What am I doing here?” Then they’re told they’re “in denial.”

Traditional treatment tends to focus narrowly on drug problems, usually pushing an agenda of immediate abstinence. However, drug problems – whether or not they qualify as “addiction,” are very much connected to the rest of life. Therefore, clients need comprehensive counselling that addresses what’s happening in their overall lives and helps clients make their lives better. So it’s not all about use of substances and making the individual quit. The goal is to support clients and to help them make their own decisions about life and substance use.

We use the term “issues” – not “problems.” Whatever is most important to the individual that day is what we work on. A client might say, “I have an issue with my mother.” We don’t just want to have a discussion about the issue; we want to set a session goal so that a client gets practical help with an issue each time. Ideally we try to facilitate a next step, some sort of action that can be taken between sessions. We want to support our clients in making their own lives better. We like to reassure clients that we won’t be harping on drugs all the time: At least half of what we do is about everything else besides drugs. This means that counsellors need to know how to help people with their other problems. Unfortunately, many have a narrow background in drug treatment and don’t yet know how to do that.

 

Q: How do you address the issue of “powerlessness” which a number of young people have told me they struggled with in12-step treatment programs they’ve attended? Don’t adolescents by nature resist anything that threatens to take away their autonomy?

Dr. S.: One of our main messages is “You are powerful; people do take control over their drug use. You have that power within you.” We also say, “You don’t need to do it alone. You are entitled to support. We’re behind you. We’re not saying it’s easy and

there won’t be setbacks along the way. If there are, we’ll help you figure out why and how to handle it differently the next time. At the same time we’ll help you with other issues in your life so you’ll have less need for drugs.”

I think there is great harm in the all-or-nothing approach to drug and alcohol problems and that more people would come for help if they were not told that they’re powerless. Also, many more would come if they felt they could make a choice about drugs and did not expect to be coerced.

 

A New Version of The Seven Challenges

Following is the new adult version of Dr. Schwebel’s The Seven Challenges program:

· Challenging Yourself to Make Thoughtful Decisions About Your Life, Including Your Use of Alcohol and Other Drugs

· Challenging Yourself to Look at Your Responsibility and the Responsibility of Others for Your Problems

· Challenging Yourself to Look at What You Like About Alcohol and Other Drugs, and Why You Use Them

· Challenging Yourself to Honestly Look at Your Life, Including Your Use of Alcohol and Other Drugs

· Challenging Yourself to Look at Harm That Has Happened or Could Happen From Your Use of Alcohol and Other Drugs

· Challenging Yourself to Look at Where You Are Headed, Where You Would Like to Go, and What You Would Like to Accomplish

· Challenging Yourself to Take Action and Succeed With Your Decisions About Your Life and Use of Alcohol and Other Drugs

Source:  http://www.rehabs.com/pro-talk-articles/what-drug-and-alcohol-treatment-should-look-like-an-interview-with-dr-robert-schwebel/     17th July 2017

Medication-assisted treatment is often called the gold standard of addiction care. But much of the country has resisted it.

If you ask Jordan Hansen why he changed his mind on medication-assisted treatment for opioid addiction, this is the bottom line.

Several years ago, Hansen was against the form of treatment. If you asked him back then what he thought about it, he would have told you that it’s ineffective — and even harmful — for drug users. Like other critics, to Hansen, medication-assisted treatment was nothing more than substituting one drug (say, heroin) with another (methadone).

Today, not only does Hansen think this form of treatment is effective, but he readily argues — as the scientific evidence overwhelmingly shows — that it’s the best form of treatment for opioid addiction. He believes this so strongly, in fact, that he now often leads training sessions for medication-assisted treatment across the country.

“It almost hurts to say it out loud now, but it’s the truth,” Hansen told me, describing his previous beliefs. “I was kind of absorbing the collective fear and ignorance from the culture at large within the recovery community.” Hansen is far from alone. Over the past few years, America’s harrowing opioid epidemic — now the deadliest drug overdose crisis in the country’s history — has led to a lot of rethinking about how to deal with addiction. For addiction treatment providers, that’s led to new debates about the merits of the abstinence-only model — many of which essentially consider addiction a failure of willpower — so long supported in the US.

The case for prescription heroin

The Hazelden Betty Ford Foundation, which Hansen works for, exemplifies the debate. As one of the top drug treatment providers in the country, it used to subscribe almost exclusively to the abstinence-only model, based on an interpretation of the 12 steps of Alcoholics Anonymous and Narcotics Anonymous popularized in American addiction treatment in the past several decades. But in 2012, Hazelden announced a big switch: It would provide medication-assisted treatment.

“This is a huge shift for our culture and organization,” Marvin Seppala, chief medical officer of Hazelden, said at the time. “We believe it’s the responsible thing to do.”

From the outside, this might seem like a bizarre debate: Okay, so addiction treatment providers are supporting a form of treatment that has a lot of evidence behind it. So what?

But the growing embrace of medication-assisted treatment is demonstrative of how the opioid epidemic is forcing the country to take another look at its inadequate drug treatment system. With so many people dying from drug overdoses — tens of thousands a year — and hundreds of thousands more expected to die in the next decade, America is finally considering how its response to addiction can be better rooted in science instead of the moralistic stigmatization that’s existed for so long.

The problem is that the moralistic stigmatization is still fairly entrenched in how the US thinks about addiction. But the embrace of medication-assisted treatment shows that may be finally changing — and America may be finally looking at addiction as a medical condition instead of a moral failure.

The research is clear: Medication-assisted treatment works

One of the reasons opioid addiction is so powerful is that users feel like they must keep using the drugs in order to stave off withdrawal. Once a person’s body grows used to opioids but doesn’t get enough of the drugs to satisfy what it’s used to, withdrawal can pop up, causing, among other symptoms, severe nausea and full-body aches. So to avoid suffering through it, drug users often seek out drugs like heroin and opioid painkillers — not necessarily to get a euphoric high, but to feel normal and avoid withdrawal. (In the heroin world, this is often referred to as “getting straight.”)

Medications like methadone and buprenorphine (also known as Suboxone) can stop this cycle. Since they are opioids themselves, they can fulfil a person’s cravings and stop withdrawal symptoms. The key is that they do this in a safe medical setting, and when taken as prescribed do not produce the euphoric high that opioids do when they are misused. By doing this, an opioid user significantly reduces the risk of relapse, since he doesn’t have to worry about avoiding withdrawal anymore. Users can take this for the rest of their lives, or in some cases, doses may be reduced; it varies from patient to patient.

The research backs this up: Various studies, including systemic reviews of the research, have found that medication-assisted treatment can cut the all-cause mortality rate among addiction patients by half or more. Just imagine if a medication came out for any other disease — and, yes, health experts consider addiction a disease — that cuts mortality by half; it would be a momentous discovery.

“That is shown repeatedly,” Maia Szalavitz, a long time addiction journalist and author of Unbroken Brain: A Revolutionary New Way of Understanding Addiction, told me. “There’s so much data from so many different places that if you add methadone or Suboxone in, deaths go down, and if you take it away, deaths go up.” That’s why the biggest public health organizations — including the Centers for Disease Control and Prevention, the National Institute on Drug Abuse, and the World Health Organization — all acknowledge medication-assisted treatment’s medical value. And experts often describe it to me as “the gold standard” for opioid addiction care.

The data is what drove Hansen’s change in perspective. “If I wanted to view myself as an ethical practitioner and doing the best that I could for the people I served, I needed to make this change based on the overwhelming evidence,” he said. “And I needed to separate that from my personal recovery experience.”

Medication-assisted treatment is different from traditional forms of dealing with addiction in America, which tend to demand abstinence. The standards in this field are 12-step programs, which combine spiritual and moralistic ideals into a support group for people suffering from addiction. While some 12-step programs allow medication-assisted treatment, others prohibit it as part of their demand for total abstinence. The research shows this is a particularly bad idea for opioids, for which medications are considered the standard of care.

There are different kinds of medications for opioids, which will work better or worse depending on a patient’s circumstances. Methadone, for example, is only administered in a clinic, typically one to four times a day — but that means patients will have to make the trip to a clinic on a fairly regular basis. Buprenorphine is a take-home drug that’s taken once or twice a day, but the at-home access also means it might be easier to misuse and divert to the black market.

One rising medication, known as naltrexone or its brand name Vivitrol, isn’t an opioid — making it less prone to misuse — and only needs to be injected once a month. But it doesn’t work in the same way as methadone or buprenorphine. It requires full detoxification to use (usually three to 10 days of no opioid use), while buprenorphine, for example, only requires a partial detoxification process (usually 12 hours to two days). And instead of preventing withdrawal — indeed, the detox process requires going through withdrawal — it blocks the effects of opioids up to certain doses, making it much harder to get high or overdose on the drugs. It’s also relatively new, so there’s less evidence for its real-world effectiveness.

One catch is that even these medications, though the best forms of opioid treatment, do not work for as much as 40 percent of opioid users. Some patients may prefer not to take any medications because they see any drug use whatsoever as getting in the way of their recovery, in which case total abstinence may be the right answer for them. Others may not respond well physically to the medications, or the medications may for whatever reason fail to keep them from misusing drugs.

This isn’t atypical in medicine. What works for some people, even the majority, isn’t always going to work for everyone. So these are really first-line treatments, but in some cases patients may need alternative therapies if medication-assisted treatment doesn’t work. (That might even involve prescription heroin — which, while it’s perhaps counterintuitive, the research shows it works to mitigate the problems of addiction when provided in tightly controlled, supervised medical settings.)

Medication can also be paired with other kinds of treatment to better results. It can be used in tandem with cognitive behavioral therapy or similar approaches, which teach drug users how to deal with problems or settings that can lead to relapse. All of that can also be paired with 12-step programs like AA and NA or other support groups in which people work together and hold each other accountable in the fight against addiction. It all varies from patient to patient.

It is substituting one drug for another, but that’s okay

The main criticism of medication-assisted treatment is that it’s merely replacing one drug with another. Health and Human Services Secretary Tom Price recently echoed this criticism, saying, “If we’re just substituting one opioid for another, we’re not moving the dial much. Folks need to be cured so they can be productive members of society and realize their dreams.” (A spokesperson for Price later walked back the statement, saying Price supports all kinds of drug treatment.)

On its face, this argument is true. Medication-assisted treatment is replacing one drug, whether it’s opioid painkillers or heroin, with another, such as methadone or buprenorphine.

But this isn’t by itself a bad thing. Under the Diagnostic and Statistical Manual of Mental Disorders, it’s not enough for someone to be using or even physically dependent on drugs to qualify for a substance use disorder, the technical name for addiction. After all, most US adults use drugs — some every day or multiple times a day — without any problems whatsoever. Just think about that next time you sip a beer, glass of wine, coffee, tea, or any other beverage with alcohol or caffeine in it, or any time you use a drug to treat a medical condition.

The qualification for a substance use disorder is that someone is using drugs in a dangerous or risky manner, putting himself or others in danger. So someone with a substance use disorder would not just be using opioids but potentially using these drugs in a way that puts him in danger — perhaps by feeling the need to commit crimes to obtain the drugs or using the drugs so much that he puts himself at risk of overdose and inhibits his day-to-day functioning. Basically, the drug use has to hinder someone from being a healthy, functioning member of society to qualify as addiction.

The key with medication-assisted treatment is that while it does involve continued drug use, it turns that drug use into a much safer habit. So instead of stealing to get heroin or using painkillers so much that he puts his life at risk, a patient on medication-assisted treatment can simply use methadone or buprenorphine to meet his physical cravings and otherwise go about his day — going to school, work, or any other obligations.

Yet this myth of the dangers of medication-assisted treatment remains prevalent — to deadly results.

In 2013, Judge Frank Gulotta Jr. in New York ordered an opioid user arrested for drugs, Robert Lepolszki, off methadone treatment, which he began after his arrest. In January 2014, Lepolszki died of a drug overdose at 28 years old — a direct result, Lepolszki’s parents say, of failing to get the medicine he needed. In his defense,  Gulotta has continued to argue that methadone programs “are crutches — they are substitutes for drugs and drug cravings without enabling the participant to actually rid him or herself of the addiction.”

This is just one case, but it shows the real risk of denying opioid users medication: It can literally get them killed by depriving them of lifesaving medical care.

The myth is also a big reason why there are still restrictions on medication-assisted treatment. For example, the federal government still caps how many patients doctors can prescribe buprenorphine to, with strict rules about raising the cap. This limits how accessible the treatment is. A Huff Post analysis found that even if every doctor who can prescribe buprenorphine did so at the maximum rate in 2012, more than half of Americans with opioid use disorders could not get the medication. That’s on top of barriers to addiction treatment in general. According to a 2016 report by the surgeon general, just 10 percent of Americans with a drug use disorder obtain specialty treatment. The report attributed the low rate to severe shortages in the supply of care, with some areas of the country, particularly rural counties, lacking affordable options for treatment — which can lead to waiting periods of weeks or even months. Only recently has there been a broader push to fix this gap in care.

The medications used in treatment do carry some risks

None of this is to say that the medications used in these treatments are without any problems whatsoever. Methadone is tied to thousands of deadly overdoses a year, although almost entirely when it’s used for pain, not addiction, treatment — since it’s much more regulated in addiction care. Buprenorphine is safer in that, unlike common painkillers, heroin, and methadone, its effect has a ceiling — meaning it has no significant effect after a certain dose level. But it’s still possible to misuse, particularly for people with lower tolerance levels. And there are some reports of buprenorphine mills, where patients can get buprenorphine for misuse from unscrupulous doctors — similar to how pill mills popped up during the beginning of the opioid epidemic and provided patients easy access to painkillers.

Naltrexone, meanwhile, can heighten the risk of overdose and death in case of full relapse. Overdose and death are risks in any case of relapse, but they’re particularly acute for naltrexone because it requires a full detox process that eliminates prior tolerance. (Although this would typically require someone to stop taking naltrexone, since otherwise it blocks the effects of opioids up to certain doses.)

But when taken as prescribed, the medications are broadly safe and effective for addiction treatment. For regulators, it’s a matter of making sure the drugs aren’t diverted into misuse, while also providing good access to people who genuinely need them.

The fight over medication-assisted treatment is really about how we see addiction

Behind the arguments about medication-assisted treatment is a simple reality of how Americans view addiction: Many still don’t see it, as public health officials and experts do, as a disease.

With other diseases, there is no question that medication can be a legitimate answer. That medication is not viewed as a proper answer by many to addiction shows that people believe addiction is unique in some way — particularly, they view addiction as at least partly a moral failing instead of just a disease.

I get emails all the time to this effect. Here, for example, is a fairly representative reader message: “Darwin’s Theory says ‘survival of the fittest.’ Let these lost souls pay the price of their criminal choices and criminal actions. Society does not owe them multiple medical resuscitations from their own bad judgment, criminal activity, and self-inflicted wounds.”

This contradicts what addiction experts broadly agree on. As Stanford psychiatrist and Drug Dealer, MD author Anna Lembke put it, “If you see somebody who continues to use despite their lives being totally destroyed — losing their jobs, losing loved ones, ending up in jail — nobody would choose that. Nobody anywhere would ever choose that life. So clearly it is beyond this individual’s control on some level.”

Many Americans may understand this with, say, depression and anxiety. We know that people with these types of mental health problems are not in full control of their thoughts and emotions. But many don’t realize that addiction functions in a similar way — only that the thoughts and emotions drive someone to seek out drugs at just about any cost.

Some of the sentiment against medications, as Hansen can testify, is propagated by people suffering from addiction. Some of them believe that any drug use, even to treat addiction, goes against the goal of full sobriety. They may believe that if they got sober without medications, perhaps others should too. Many of them also don’t trust the health care system: If they got addicted to drugs because a doctor prescribed them opioid painkillers, they have a good reason to distrust doctors who are now trying to get them to take another medication — this time for their addiction.

The opioid epidemic, however, has gotten a lot of people in the addiction recovery world to reconsider their past beliefs. Funeral after funeral and awful statistic after awful statistic, there is a sense that there has to be a better way — and by looking at the evidence, many have come to support medication-assisted treatment.

“I remember sitting there,” Hansen said, speaking to his experience at a funeral, as a mother sang her dead son a lullaby, “thinking that we have to do better.”

Source:  German Lopez@germanrlopezgerman.lopez@vox.com  Jul 20, 2017

 

Medical Illness Model:

Near the end of the Second World War researchers and leaders in the recovery community jointly formulated the problem of uncontrolled drinking into what is now known as the Disease Model of alcoholism. This model postulates that, like medical illnesses, alcoholism–more specifically alcohol dependence, or addiction—can be diagnosed, its course observed, and its physical causes understood.

Further, scientific trials can be undertaken to identify the best treatments for those who suffer from it. The diagnosis of Alcohol Dependence, in this model, rested on four symptoms: 1) a tolerance to alcohol in which a person needs to drink ever greater amounts to reach a desired effect, 2) withdrawal symptoms, such as “the shakes” and others, on stopping use, 3) the Loss of Control phenomenon in which affected persons lose the ability to control how much they drink at a sitting and thereby can no longer predict how much they will drink from one episode to the next, and 4) social or physical impairment resulting from combinations of the first three symptom categories1.

This model pictures a condition from which many alcohol dependent people emerge every year, and into which many others return. View as a disease, alcoholism takes on the characteristics of a remitting-relapsing illness with primary symptoms that direct us to brain functioning. And, because ethyl alcohol is a very small molecule with easy access to most parts of the body, moderate to heavy alcohol use often injures other organs, such as the liver and heart among others.

Uncontrolled, or dependent, alcohol use also affects the social network setting of family as well as work activities, friendships, and legal involvement. Last, however, the Disease model brings with it the possibilities of treatment and of hope. At this date, effective medicinal agents against alcoholism are very few. But hope, that necessary ingredient for recovery, waxes strong in the illness model. In the words of the alcoholic patient quoted in the Part 2, “It is much easier to think of myself as an ill person working to become well, rather than a bad person trying to become good.”

Genetic Models:

From the Disease model has come another, that of genetic influence. The observation that alcoholism often runs in families for many years meant that family cultures or mores determined who would become alcoholic and who would not. While it is clear that cultural and family life influences are very powerful, more recent studies have noted that an underlying genetic disposition may be at play in some genealogical lines2. If so, the evidence suggests a confluence of many gene effects rather than the dominant/recessive results of inheritance in Mendelian models of genetic death, as for example, in Huntington’s Disease.

Instead, the gene effects seem to have more to do with the vulnerability towards alcoholism. One form appears in those who have a genetically-based insensitivity to alcohol—an “inborn tolerance,” and develop alcohol dependence at much higher rates than alcohol sensitive comparison groups. Another form may require a combination of

gene influences and environment conditions to come together to result in alcohol-plus-multiple drug dependence, sometimes referred to as Type 2 or Type B alcoholics.

Unexpectedly, the news of gene involvement was greeted with enthusiasm among some quarters of the actively drinking alcoholic public: “Since alcoholism is genetic, we can’t escape our genes and may as well keep drinking.” As with older models however, the element of choice remains present in the sober periods between drinking episodes. As some of the other models suggest, healing from alcoholism remains an individual process.

Psychological Adaptation Models in Illness and Recovery:

Further modern research asks that we look at individuals and their abilities to adapt to the stresses of life. Careful observation has established that individual humans have the ability to adapt creatively to the painful thoughts and feelings of living and to do so in ways that connect us together rather than drive us apart3. This model of Mature human psychological adaptation, however, emphasizes that the brain function at its healthy best. Heavy, continuous use of alcohol carries often subtle, if severe, effects on the brain that are as yet poorly understood.

But we know they exist because of their effects in driving down the ability to adapt, from psychological Maturity to much more rigid Primitive mechanisms of coping, such as when an alcoholic “denies” that an obvious problem exists at all. This kind of Denial can occur in the actively drinking alcoholic who understands that resolving his or her ambivalence toward drinking is too painful to contemplate; therefore, a failure to perceive the problem seems preferable than facing it.

So it is that the Adaptation model views the First of the Twelve Steps as addressing primitive Denial in coming to recognize that the individual’s alcoholism exists. Progressing along the continuum of the Steps leads finally to the Twelfth: helping others who have the same problem. In the Psychological Adaptation model, this exemplifies the Mature mechanism of Altruism: selflessly helping others. The occurrence of brain healing as abstinence continues—along with the progression towards psychological maturity, whether viewed in the Psychological Adaptation or the Twelve Step models—suggests that brain recovery process are at work. We can only recognize their existence at this point, and need to understand their biology if we are to improve treatments in the Disease model.

Many Models, More Questions:

With this overview of the different model formulations of the problem of alcoholism and what to do about it, we are now ready to look as specific questions from a scientific point of view. As this series unfolds, we will have recourse to use all of the models mentioned—now adding the crucial ingredient of evidence, systematically gathered. In future Updates, the discussion will focus on specific problems and what we can learn about them.

Source:  https://www.ncadd.org/blogs/research-update/models-of-alcoholism-medical-physiological-causes  14th Jan. 2014

Cannabis is the most widely used illicit drug in the United States, and trends show increasing use in the general population. As cannabis consumption rises, there has been significant emerging evidence for cannabis-related risks to health.1

Numerous lines of evidence suggest a correlation between cannabis consumption and a variety of psychiatric conditions, including cannabis-induced psychosis (CIP). While it can be difficult to differentiate CIP from other psychoses, CIP holds distinguishing characteristics, which may aid in its diagnosis. Given the increasing push toward cannabis legalization, assessing CIP and employing timely treatments is critical.

Specifically in youth, there is a direct relationship between cannabis use and its risks. The lack of knowledge surrounding its detrimental effects, combined with misunderstandings related to its therapeutic effects, has potential for catastrophic results.

CASE VIGNETTE

Ms. J, a 19-year-old college sophomore, was admitted to the Early Psychosis Unit at the Centre for Addiction and Mental Health (CAMH) displaying signs of agitation and acute psychosis. Her roommates had noted that her behavior had become increasingly bizarre, and she had isolated herself over the past month. She began smoking marijuana at the age of 17 and since starting college used it daily.

Ms. J exhibited signs of paranoia, believing other students in her dorm were stealing from her and trying to poison her. She remained adamant that all her problems were rooted in the competitive environment of the university and that smoking marijuana aided in keeping her sanity. In a sense, she was self-medicating. Her clinical presentation was consistent with a diagnosis of CIP.

After the hospitalization, she received outpatient case management services in the Early Psychosis Program at CAMH, which included motivational interviewing to raise her awareness about the importance of abstaining from cannabis use. She has been abstinent from cannabis for more than a year with no evidence of psychosis; she recently returned to school to finish her degree.

Epidemiology of CIP

Reports have shown a staggering increase in cannabis-related emergency department (ED) visits in recent years. In 2011, the Substance Abuse and Mental Health Services Administration (SAMHSA) and Drug Abuse Warning Network (DAWN) estimated a total of 1.25 million illicit-drug–related ED visits across the US, of which 455,668 were marijuana related.2 A similar report published in 2015 by the Washington Poison Center Toxic Trends Report showed a dramatic increase in cannabis-related ED visits.3 In states with recent legalization of recreational cannabis, similar trends were seen.4

States with medicinal marijuana have also shown a dramatic rise in cannabis-related ED visits. Moreover, states where marijuana is still illegal also showed increases.5 This widespread increase is postulated to be in part due to the easy accessibility of the drug, which contributes to over-intoxication and subsequent symptoms. Overall, from 2005 to 2011, there has been a dramatic rise in cannabis-related ED visits among all age groups and genders.

Neurobiology of CIP

Cannabis is considered an environmental risk factor that increases the odds of psychotic episodes, and longer exposure is associated with greater risk of psychosis in a dose-

dependent fashion. The drug acts as a stressor that leads to the emergence and persistence of psychosis. While a number of factors play a role in the mechanism by which consumption produces psychosis, the primary psychoactive ingredient is considered to be delta 9-tetrahydrocannabinol (delta9-THC). Properties of delta9-THC include a long half-life (up to 30 days to eliminate the long-acting THC metabolite carboxy-THC from urine) and high lipophilicity, which may contribute to CIP.

During acute consumption, cannabis causes an increase in the synthesis and release of dopamine as well as increased reuptake inhibition, similar to the process that occurs during stimulant use. Consequently, patients with CIP are found to have elevated peripheral dopamine metabolite products.

Findings from a study that examined presynaptic dopaminergic function in patients who have experienced CIP indicate that dopamine synthesis in the striatum has an inverse relationship with cannabis use. Long-term users had reduced dopamine synthesis, although no association was seen between dopaminergic function and CIP.6 This observation may provide insight into a future treatment hypothesis for CIP because it implies a different mechanism of psychosis compared with schizophrenia. As cannabis may not induce the same dopaminergic alterations seen in schizophrenia, CIP may require alternative approaches—most notably addressing associated cannabis use disorder.

Polymorphisms at several genes linked to dopamine metabolism may moderate the effects of CIP. The catechol-o-methyltransferase (COMT Val 158Met) genotype has been linked to increased hallucinations in cannabis users.7Homozygous and heterozygous genetic compositions (Met/Met, Val/Met, Val/Val) for COMT Val 158Met have been studied in patients with CIP and suggest that the presence of Val/Val and Val/Met genotypes produces a substantial increase in psychosis in relation to cannabis use. This suggests that carriers of the Val allele are most vulnerable to CIP attacks.

There has been much controversy surrounding the validity of a CIP diagnosis and whether it is a distinct clinical entity or an early manifestation of schizophrenia. In patients being treated for schizophrenia, those with a history of CIP had an earlier onset of schizophrenia than patients who never used cannabis.8Evidence suggests an association between patients who have received treatment for CIP and later development of schizophrenia spectrum disorder. However, it has been difficult to distinguish whether CIP is an early manifestation of schizophrenia or a catalyst. Nonetheless, there is a clear association between the 2 disorders.

Assessment of CIP

DSM-5 categorizes cannabis-induced psychotic disorder as a substance-induced psychotic disorder. However, there are distinguishing characteristics of CIP that differentiate it from other psychotic disorders such as schizophrenia. Clear features of CIP are sudden onset of mood lability and paranoid symptoms, within 1 week of use but as early as 24 hours after use. CIP is commonly precipitated by a sudden increase in potency (eg, percent of THC content or quantity of cannabis consumption; typically, heavy users of cannabis consume more than 2 g/d). Criteria for CIP must exclude primary psychosis, and symptoms should be in excess of expected intoxication and withdrawal effects. A comparison of the clinical features of idiopathic psychosis versus CIP is provided in the Table.

When assessing for CIP, careful history taking is critical. Time of last drug ingestion will indicate if a patient’s psychotic symptoms are closely related to cannabis intoxication/withdrawal effects. While acute cannabis intoxication presents with a range of transient positive symptoms (paranoia, grandiosity, perceptual alterations), mood symptoms (anxiety), and cognitive deficits (working memory, verbal recall, attention), symptoms that persist beyond the effects of intoxication and withdrawal are better categorized as CIP, regardless of the route of administration (smoke inhalation, oral, intravenous). CIP has historically been associated with fewer negative symptoms than schizophrenia; however, without a clear timeline of use, distinguishing schizophrenia from CIP may prove difficult.

A diagnosis of primary psychosis (eg, schizophrenia) is warranted in the absence of heavy cannabis use or withdrawal (for at least 4 weeks), or if symptoms preceded onset of heavy use. The age at which psychotic symptoms emerge has not proved to be a helpful indicator; different studies show a conflicting median age of onset.

Clinical features of schizophrenia and CIP share many overlapping characteristics. However, compared with primary psychoses with concurrent cannabis abuse, CIP has been established to show more mood symptoms than primary psychosis. The mood symptom profile includes obsessive ideation, interpersonal sensitivity, depression, and anxiety. Of significance is the presence of social phobia: 20% of patients with CIP demonstrate phobic anxiety compared with only 3.8% of patients with primary psychosis with cannabis abuse.

Hypomania and agitation have also been found to be more pronounced in cases of CIP.9 Visual hallucinations are more common and more distinct in CIP than in other psychoses such as schizophrenia. Perhaps the most discriminating characteristic of CIP is awareness of the clinical condition, greater disease insight, and the ability to identify symptoms as a manifestation of a mental disorder or substance use. The presence of much more rapidly declining positive symptoms is another distinctive factor of CIP.

Finally, family history may help distinguish CIP from primary psychosis. Primary psychosis has a strong association with schizophrenia and other psychotic disorders in first- or second-degree relatives, whereas CIP has a weaker family association with psychosis.

Treatment of CIP

As with all substance-induced psychotic states, abstinence from cannabis may be the definitive measure to prevent recurrence. With limited research surrounding CIP, achieving symptomatic treatment during acute phases of CIP has proved to be difficult. The Figure suggests possible treatment progression for CIP.

Pharmacotherapeutic interventions include the second-generation antipsychotic drug olanzapine and haloperidol. While both are equally effective, their different adverse- effect profiles should be taken into consideration when treating a patient; olanzapine is associated with significantly fewer extrapyramidal adverse effects.

One report indicates that antipsychotics worsened the condition in some patients.10 Conventional antipsychotics failed to abate the symptoms of CIP in one 20-year old man. Trials of olanzapine, lithium, and haloperidol had little to no effect on his psychosis. Risperidone was tried but elicited temporal lobe epilepsy with auditory, somatic, and olfactory hallucinations. However, the use of valproate sodium markedly improved his symptoms and cognition, returning him to baseline.

Carbamazepine has also been shown to have rapid effects when used as an adjunct to antipsychotics.11 Use of anti-seizure medication in CIP treatment has been hypothesized to reduce neuroleptic adverse effects, resulting in better tolerance of antipsychotics.10,11 These results suggest the use of adjunctive anti-epileptics should be considered in CIP treatment strategies, although further studies in a broad range of patients with CIP are needed.

Abstaining from cannabis is the most beneficial and effective measure for preventing future CIP events; however, it is likely to be the most difficult to implement.

Psychosocial intervention has a significant impact on early-phase psychosis, and when the intervention is initiated plays a role in disease outcomes. A delay in providing intensive psychosocial treatment has been associated with more negative symptoms compared with a delay in administrating antipsychotic medication.12 Employing cannabis- focused interventions with dependent patients who present with first-episode psychosis can decrease use in a clinically meaningful way and subjectively improve patient quality of life.

Compared with the standard of care, motivational interviewing significantly increases number of days abstinent from cannabis and aids in decreasing short-term consumption.13 Patients who are treated with motivational interviewing in addition to standard of care (combination of antipsychotic medication, regular office-based psychiatric contact, psychoeducation) are reported to also have more confidence and willingness to reduce cannabis use.

Patients with CIP who are unwilling or unable to decrease cannabis consumption may be protected from psychotic relapse with aripiprazole (10 mg/d). Its use suppresses the re-emergence of psychosis without altering cannabis levels. However, no direct comparison has been made with aripiprazole and other antipsychotics in treating CIP. Clearly, well-controlled large studies of putative treatments for CIP are needed.

Conclusions

As more countries and states approve legalization, and marijuana becomes more accessible, CIP and other cannabis-related disorders are expected to increase. Efforts should be made by physicians to educate patients and discourage cannabis use. Just as there was an era of ignorance concerning the damaging effects of tobacco, today’s conceptions about cannabis may in fact be judged similarly in the future. The onus is on psychiatrists to take an evidence-based approach to this increasing problem.

Source:  http://www.psychiatrictimes.com/substance-use-disorder/cannabis-induced-psychosis-review  14th July

New Hampshire has the second-highest rate of drug overdoses in the country. Eric Adams in Laconia (population 16,000) has been assigned one task to stop them.

Eric Adams is a handsome, clean-shaven man, almost 41, with a booming voice and hair clipped short enough for the military, which once was an ambition of his. After high school, he tried to join the Marines but was turned away because of his asthma. He needed three different inhalers then, plus injections. Today he has outgrown the problem. He is 5-foot-10, weighs 215 pounds and can dead lift 350.

Adams has worked in law enforcement for almost two decades.

He began as a guard at the New Hampshire state prison, where he asked to work in maximum security, then left to become a police officer in Tilton and was soon recommended for the Drug Task Force, a statewide operation against narcotics dealers. Adams grew his hair long and arranged undercover buys, a Glock 27 concealed in a holster beneath his jeans. Later he would return wearing a bulletproof vest, surrounded by fellow officers, to kick in the door with his pistol drawn.

Eric Adams in his office at the Laconia Police Department.
CreditNatalie Keyssar for The New York Times

Laconia, where Adams works today, is a former mill town in central New Hampshire surrounded by lakes. In midwinter, Laconia is home to 16,000 residents, though in summer that number swells to 30,000. Those are gleaming, sun-dappled days. Then winter falls on New England like a gavel.

A blight in the region is especially acute. Of the 13 states with the highest death rates from drug overdoses, five are in New England. New Hampshire in particular has more per capita overdose deaths than anywhere but West Virginia. In 2012, the state had 163 such deaths, a majority of them (as elsewhere in the country) from heroin and prescription opioids. In 2015, the state had nearly 500 deaths, the most in its history. In Manchester, its largest city, the police seized more than 27,000 grams of heroin that year, up from 1,314 grams a year earlier. In certain neighborhoods, a single dose of heroin can cost less than a six pack of Budweiser. Waiting lists for treatment programs stretch as long as eight weeks.

Those years spent guarding prisoners, and later kicking down doors, changed Adams’s thinking. So many of the drug users he saw had made one bad decision and then became chained to it, Adams realized. Or they had begun on a valid prescription for pain medication, after an injury, and then grew addicted. When refills grew scarce, they turned to alternatives. Many were no longer even using to get high, only to avoid the agony of withdrawal.

They were teenaged, middle-aged and elderly; they were students, bankers and grocery clerks. They were businesswomen with six-figure salaries and homeless men with shopping carts. Arresting a person like this did no good, because there was always another to replace him or her — and regardless, any jail sentence had limits. Afterward, Adams saw, everyone landed right back where they started.

‘‘We’re not getting anywhere,’’ he told his chief, Christopher Adams (the two men are not related), and his lieutenant. It turned out that they had already reached a similar conclusion. Until recently, Christopher Adams told me, he couldn’t recall ever hearing of a heroin case. ‘‘Now it’s every day,’’ he said. ‘‘It’s a majority. Not just in Laconia. It’s all over.’’ He and his lieutenant sat down to consider what their department might do. It seemed that there were three conceivable approaches to a drug problem: prevention, enforcement and treatment. To accomplish all three would mean regarding drug users, and misusers, as not only criminals. They were also customers who were being targeted and sold to; they were also victims who needed medical treatment. To coordinate all those approaches would require a particular sort of officer.

In September 2014, Eric Adams became the first person in New England — to his knowledge, the only person in the country — whose job title is prevention, enforcement and treatment coordinator. ‘‘I never thought I’d be doing something like this,’’ he told me. ‘‘I learned fast.’’ The department printed him new business cards: ‘‘The Laconia Police Department recognizes that substance misuse is a disease,’’ they read. ‘‘We understand you can’t fight this alone.’’ On the reverse, Adams’s cell phone number and email address were listed. He distributed these to every officer on patrol and answered his phone any time it rang, seven days a week. Strangers called him at 3 a.m., and Adams spoke with them for hours.

The department assigned him an unmarked Crown Victoria, and in it he followed the blips and squawks of a police scanner, driving to the scene of any overdose it reported and introducing himself to the victim, as well as any friends or family he could locate. Residents like these often shrank from the police or stiffened defensively. But when Adams told them that they weren’t under arrest, that he had only come to help, they seemed to sag in relief.

People who work with addicts generally agree that this moment, immediately after an overdose, offers the greatest chance to sway an addict, when he or she feels most vulnerable. ‘‘You’re at a crossroads right then and there,’’ a local paramedic told me. If an addict agreed to Adams’s help, Adams drove him to a treatment facility, sat beside him in waiting rooms, ferried his parents or siblings to visit him there or at the jail or hospital. He added the names of everyone he encountered to a spreadsheet, and he kept in touch even with those who relapsed. Were they feeling safe? Attending support meetings? Did they have a job? A place to sleep?

In the nearly three years since, as overdose rates have climbed across New Hampshire, those in Laconia have fallen. In 2014, the year Adams began, the town had 10 opioid fatalities. In 2016, the number was five. Fifty-one of its residents volunteered for treatment last year, up from 46 a year before and 14 a year before that. The county as a whole, Belknap, had fewer opioid-related emergency-room visits than any other New Hampshire county but one. Of the 204 addicts Adams has crossed paths with, 123 of them, or 60 percent, have agreed to keep in touch with him. Adams calls them at least weekly. Ninety-two have entered clinical treatment. Eighty-four, or just over 40 percent of all those he has met, are in recovery, having kept sober for two months or longer. Zero have died.

On most mornings, Adams arrives at his office well before 9 to answer email. By then, his phone is already chiming. ‘‘I thought when I got this position: Monday through Friday, day shifts, weekends off. I’m going to see my kids and wife more,’’ Adams said, laughing. ‘‘That’s not the case.’’ Pinned to the walls of his office, a windowless room on the second floor of the department, are pamphlets and resource guides for homelessness, peer-support groups and addiction hotlines, as well as a dry-erase board listing drug-treatment centers statewide. In December, when I visited one morning, the floor was cluttered with toys for local families in preparation for Christmas: doll sets, wireless headphones, a pillow the color of sorbet.

As soon as he began the job, Adams researched what social-service organizations the region had to offer and drove to their offices to introduce himself. A few employees at places like these knew one another from previous referrals, but many didn’t, so Adams went about acquainting them. At health conferences, he arrived to the quizzical frowns of social workers and realized that, of some 200 attendees, he was the only police officer. A network gradually sprouted around him. One morning in December, his first call was from Daisy Pierce, the director of a non-profit organization whose doors opened two weeks earlier; Adams is its chairman. Might Adams help her get a teenager into the Farnum Center, a treatment facility in Manchester, an hour south? Adams dialled a pastor he knew, who phoned a recovery coach. ‘‘For the first year and a half, I was the only transportation around here,’’ he told me when he hung up. ‘‘I would drive people down to Farnum all the time.’’

Next, Adams turned to a matter unresolved from the day before: a woman the county prosecutor had phoned about, asking if Adams could find her housing. Until recently, the woman had been staying at a homeless shelter, but that stay had ended and, because she was on probation, with nowhere else to sleep, Adams’s fellow officers had taken her to jail, though they could hold her for only one night. She would be released that day, still with nowhere else to stay. The next 48 hours would be critical, Adams felt. Here was a person who wanted to get sober but for whom the local authorities had little to offer.

From his desk, he dialled a treatment center, then various landlords and non-profit directors he knew. ‘‘Hi, this is Eric Adams over at the Laconia Police Department. I’m calling to see if you have anything. . . . ’’ Then he tried calling back the county prosecutor, tapping his fingers impatiently as the phone rang. When no one answered, he pulled a cellphone from his pocket and looked through it for numbers to dial on his office phone, while scribbling notes on two different legal pads. A cup from Dunkin’ Donuts sat on his desk, but he hadn’t had time to sip from it. After a half-dozen calls, he hung up the phone and sighed. ‘‘This is the biggest problem in the area,’’ he said. ‘‘It’s housing. There are only a handful of landlords that own so many properties.’’ Adams tried to be up front with landlords, and he didn’t blame them for sometimes rebuffing him, because they had to look out for their other tenants. But it meant limited options for a woman like the one he was trying to help.

He swivelled toward his computer and began scrolling through notes. Finding nothing, he rubbed his eyes with frustration, propped his elbows onto his desk and rested his chin on his hands to think. ‘‘Oh! Let me try — I haven’t talked with her in a while.’’ He dialled another number. ‘‘Hi, this is Eric Adams over at the Laconia Police Department. . . . ’’ A moment later, he hung up. ‘‘All right, this is the last one I can think of.’’ He dialled again. ‘‘I was wondering if you had any rentals available for a female. Oh, really? That’d be great.’’ He recited his email address. ‘‘Thank you!’’

Good news?  Adams shook his head. ‘‘Not for a couple weeks.’’ He stood, pushing back his chair, and cursed. Out of the office he strode to make a lap around the building to clear his head, then returned and looked at the clock — 9:40 a.m. He had a meeting at 10 at the local branch of the Bank of New Hampshire to help Pierce, the nonprofit director, apply for a new line of credit for their organization. Halfway to the door, he backtracked to pluck the Dunkin’ Donuts cup from his desk and sipped. ‘‘My coffee’s cold.’’

On a glass table in the bank lobby lay that morning’s copy of The Laconia Daily Sun. ‘‘Drug Sweep in Laconia Results in 17 Arrests,’’ its front page read. Headlines like that had become increasingly common, especially as the drugs themselves changed — first to opiates, then to opioids. They weren’t the same thing, Adams had learned. Opiates are derived from nature, and there are only so many, drugs like morphine, heroin and codeine. By contrast, opioids — though the word is now often used as an umbrella term for all these substances — technically means synthetic drugs like Vicodin, Percocet, fentanyl and OxyContin, all of which were invented in a laboratory.

This is why detectives sometimes encountered new opioids that were 20, 50, 100 times as potent as heroin. In a lab, you can do nearly anything. A dealer, even if he or she knows the difference, rarely bothers labelling, so a dose of so-called heroin might include fractions of nearly anything — meaning, of course, that the potency might be nearly anything. Overdoses happen not just when a person knowingly ingests a large dose but also when he or she ingests a dose of unknown composition.

After the meeting at the bank, Adams’s phone rang, and he vanished briefly. The call was from a woman whose son was arrested on charges of dealing meth. She wanted an intervention and hoped Adams might help. Steering toward the Belknap County jail, past homes spangled with Christmas lights, Adams admitted that he felt wary. He had already met this young man, who wanted nothing to do with him. Still, Adams would try. He never knew when an addict might begin saying ‘‘yes’’ to him. Sometimes this happened quickly: Adams’s phone would ring, and it was someone he met the previous day. ‘‘I’m exhausted,’’ the person would confess. Others waited a year or longer. All that time, they had hung onto his card. ‘‘I think I’m ready now,’’ they said.

Occasionally an addict used similar words even in rebuffing him — ‘‘I don’t think I’m ready yet’’ — a phrase that implicitly acknowledged a problem even as he or she denied one. It was the kind of sign Adams kept on the lookout for. Possibly this moment had come for the young man in jail.

When we arrived, Adams hustled through the drably carpeted lobby, hardly slowing before a receptionist and a guard waved him inside. A half-hour later, he returned, his face tight with frustration, and strode past me to the car without speaking. ‘‘He doesn’t have a problem,’’ he told me. ‘‘That’s what he said. He doesn’t have a problem.’’

Inside, he told me, guards had brought the young man from his cell into a windowed conference room, where he recognized Adams, as Adams predicted. ‘‘You know why I’m here,’’ Adams began gently.  ‘‘You’re trying to be nosy,’’ the man replied.

‘‘If you want to think of it that way, that’s fine.’’ Adams glanced at the young man’s file and explained that the man’s mother had called. ‘‘So I wanted to talk to you a little bit. This is an opportunity for you to get some help.’’ The young man went silent. ‘‘I mean, you got arrested,’’ Adams added, gesturing toward the file.  The man told him that he didn’t do the stuff, just sold it. He didn’t need help.

‘‘O.K.,’’ Adams told him, crossing his arms and leaning forward. Was the young man on any weight-loss program, then? ‘‘Because when I saw you before, to now, you’ve lost a lot of weight.’’ He nodded toward the young man, who was twitching uncomfortably in his chair. ‘‘And you’re all over the place, just sitting there.’’

When the man told Adams he was innocent, Adams reminded him that he was always available and slid him another one of his cards. Adams wished him well, then he asked guards to briefly fetch the woman they were holding overnight — the one for whom Adams was searching for housing — to check in and promise that he was trying.

Even as Adams nosed the Crown Vic out of the parking lot, he couldn’t get the episode out of his head. ‘‘Why won’t you just say, ‘I need this’?’’ he asked aloud, thinking of the young man. ‘‘Your life is going this way. You’ve been arrested. You’re homeless. It’s all drug-related.’’ He sighed. ‘‘The thing I had the hardest time learning was you’re not going to save everyone. That was very hard for me to accept.’’

A common sentiment among the police was that officers interacted with just 5 percent or so of the residents they served. In certain communities, that fraction was smaller. Laconia wasn’t a large town. ‘‘You think, mathematically,’’ Adams began, before pausing, ‘‘why can’t I? Why can’t I fix this?’’

For several miles he steered quietly, past muddied snowbanks. ‘‘It bothers me, but I’ve done what I can do right now. I can’t force him to want help.’’ He turned into the lot of the department and slowed into a parking spot.

‘‘Is there such a thing as an addict you have no sympathy for?’’ I wondered.  Adams considered this, letting the engine idle, and dropped his hands into his lap. Eleven seconds passed in silence. ‘‘I don’t think so,’’ he said finally. ‘‘There are reasons they are the way they are.’’

A kit with Narcan, a nasal spray that blocks the effect of opioids on the central nervous system. CreditNatalie Keyssar for The New York Times

Adams could list, from memory, addicts who had opened their lives to him, had volunteered for treatment, had wept in relief and gratitude. Already I had met two young adults who were newly in recovery and partly credited Adams for the lives they had regained. But those weren’t the names that tormented him.

Inside his office, he noticed two new voice-mail messages. The first was from a woman who read of Adams in the newspaper. ‘‘If you could tell me what to do? I’m more than willing to do whatever I need.’’ Adams scribbled something on a legal pad, then played the second voice mail. The same voice filled the room again, but now it broke into tears. Could Adams please tell her what to do?

Adams jotted another note, then checked his watch. Just past noon. Because he knew the work schedule of the mother of the young man he visited in jail, he knew she would be off soon and expecting his call. ‘‘She’s not going to be happy,’’ he said, mostly to himself. Rubbing his forehead, he sat down and dialed.

In so many towns all across the country, it is difficult to talk about an issue like heroin, not only because there is a stigma or because people worry about sounding impolite, but because everyone calibrates differently, based on neighbors and co-workers they see all day, how much of a problem it is or whether it is a problem at all. There were towns near Laconia — diplomatically, Adams declined to name them — that denied they had any drug crisis, even as the numbers they had showed otherwise. When presented with those numbers, some officials found alternative explanations.

Those were residents from other towns who just happened to cross the border, they argued. This reasoning just contributed to the problem, Adams said. Between 2004 and 2013, the number of New Hampshire residents receiving state-funded treatment for heroin addiction climbed by 90 percent. The number receiving treatment for prescription-opiate abuse climbed by 500 percent. But in terms of availability of beds, New Hampshire ranks second to last in New England in access to drug-treatment programs, ahead of only Vermont. The number who still need treatment is probably much higher. In October 2014, New Hampshire became the second-to-last state in the country to begin a prescription-drug-monitoring program, leaving only Missouri without one.

Engler, who was cautious and businesslike, with slicked hair and a graying goatee, had been mayor for three years, though he had lived in Laconia for almost 17 and owned The Laconia Daily Sun. Over his dress shirt he wore a fleece vest embroidered with the paper’s logo. Engler referred to what was happening in Laconia as ‘‘this so-called heroin epidemic,’’ his tone melodramatic, raising his hands defensively above his head.

‘‘We’re the county seat,’’ Engler told me. ‘‘We’re also the home of the regional hospital. Towns in New Hampshire are extremely close together. I think we tend to get credit for more things than are directly attributable to our residents.’’ Though he thought highly of Eric Adams, he also felt sceptical that heroin deserved to be considered an epidemic, regardless of the statistics. ‘‘When I go to a Rotary Club meeting, I don’t hear people sitting around talking about, ‘Woe is us, everybody’s dying of heroin.’ ’’

Might that be because, in a setting like the Rotary Club, heroin was not a topic of polite conversation?

‘‘There could be something to that,’’ Engler admitted. Still, an overdose death was an overdose death — it would appear in the news that way, and Engler would have heard of it. ‘‘I don’t believe there has been a huge, communitywide reaction to this. There’s not 100 people showing up at City Council meetings saying: ‘You have to do something about this. This is terrible.’ The papers aren’t full of letters to the editor. Not at all. And I think there’s a reason for that. The reason for that is’’ — Engler paused and crossed his arms — ‘‘since we have been in the so-called heroin epidemic in New Hampshire, I don’t believe there has been an instance in the Lakes Region, in Belknap County, where we have had a tragic story involving the son or daughter of someone from a prominent family. All it takes is one, usually. Somebody in Londonderry, some girl who was valedictorian of her class, her dad was a doctor or a lawyer or something like that, overdoses and dies, and suddenly it’s a crisis to everyone in town.’’

That very week, I told Engler, while tagging along with Adams for a meeting at the high school, I’d heard teachers mention a current student, a well-liked senior athlete, a team captain, whose sister had struggled with addiction and who had been open about the experience. Another member of the same graduating class, a girl whose grades ranked her in the top 10, had been walking with a friend in 2012 when a local mother, high while driving to pick up her own child from the middle school, swerved and struck them on the sidewalk. The girl survived. Her friend was killed.

The mayor was unmoved. ‘‘That was oxycodone,’’ Engler said dismissively. ‘‘Here, locally, the heroin epidemic, whatever you want to call it, has not crossed over in any obvious way from the underclass to the middle, middle–upper class.’’

Chadwick Boucher, a former addict and an early client of Eric Adams’s, with his work truck in his father’s yard. CreditNatalie Keyssar for The New York Times

Later that week, another prospective client phoned Adams. ‘‘I’m at wits’ end,’’ the man said. For the woman who needed housing, Adams helped track down a relative, at whose home she could stay until an apartment opened. On Friday evening, two more residents overdosed. Adams intended to visit them. Whether either one would accept Adams’s card, would call him, would enter treatment, would achieve recovery, would some day relapse, Adams couldn’t predict. There were no guarantees in this sort of work.

Early in his tenure, Adams made a presentation to ‘‘some prominent people in the community’’ — he didn’t want to name anyone — and afterward, as much of the room applauded, a man approached to shake Adams’s hand. As he reached out, the man said: ‘‘It’s a really good job you’re doing. I think it’s great. But my opinion is, if they stick a needle in their arm, they should die.’’

‘‘I’m sorry you feel that way,’’ Adams said, startled. ‘‘I’d hope you would feel differently if it was your own family member.’’  But the man shook his head. ‘‘That will never happen.’’

This sort of thing happened all the time when Adams began. Today it happened far less frequently. So many others had grown into Adams’s approach: fellow officers, downtown business owners, the captain at the Belknap County jail. Police officers from around New England and even farther away had phoned or travelled to Laconia to learn what Adams was doing, and whether the model could be replicated. Other towns, independently, had been pressed by the crisis to conceive approaches of their own. Manchester had turned its firehouses into safe stations. Gloucester, across the border in Massachusetts, had a network of community volunteers.

A city as large as Philadelphia or Boston could sensibly implement a PET approach too, Adams’s supervisors argued; a community like that would simply need more than one officer, with each assigned to a geographical area. But the shift this required would be profound, asking departments that for so long had thought mainly of enforcement to think differently. In Adams’s daily work, it was unavoidable that certain values competed. A client might divulge a crime to him, and he would be forced to interrupt her to give a Miranda warning. ‘‘If there is a crime, that individual needs to be held accountable,’’ he said. ‘‘But this is where our prosecutor, our judges, come into play.’’ Some attorneys had expressed discomfort with him and had insisted on being present when he met their clients. ‘‘I’m totally fine with that,’’ he said, ‘‘because it’s an opportunity for me to educate the attorney, to let them know what I do, how I do it, what the processes are.’’ In a role so complicated, with so much at stake, clearly it was vital that the right officer held the job.

In an empty conference room on the first floor of the department, I met a young man named Chadwick Boucher, an early client of Adams’s. The two men hugged when they saw each other, and then Adams disappeared upstairs to make calls while Boucher and I spoke. He was 27, though he had the calm demeanour of someone two or three times as old. As early as middle school, Boucher began sneaking his parents’ liquor, partly to fit in with older boys he admired, he told me. Soon he added marijuana. He played hockey then, and played well — invitations came from showcases in Boston and scouts from Division I colleges, including the University of New Hampshire, a national power. Instead, Boucher quit. It was too much pressure. He finished high school and moved in with a friend, who introduced him to OxyContin.

What followed was difficult to align into a neat chronology. He bounced from one friend’s apartment to another, from Oxy to Percocet and finally, when pills grew scarce, to heroin. There was a criminal distribution charge, probation, two treatment programs that he abandoned, feeling as though he didn’t belong. There were short-term jobs tending bar or waiting tables, collecting pay-checks before inevitably being fired. Suddenly he was high behind the wheel of his father’s Cutlass — not in the road, but in a driveway — startling awake to the police rapping on his window. Then he was at the Laconia police station, in a room with a plainclothes officer named Eric Adams.

‘‘He opened his arms to me,’’ Boucher recalled. It had felt bizarre, sharing the truth with a cop. But things had changed so quickly. Most of his family had stopped returning his calls, and all his friends had vanished. The only people around him now were strangers who shared his addiction, and he didn’t like or trust them. The difference in meeting someone like Adams was obvious. ‘‘He cares about my well-being,’’ Boucher said. ‘‘I needed that.’’

Adams wanted him to call every day, so Boucher called every day. Then every week. He entered another treatment program, and this time he graduated. He was now nearing a year sober. He owned a business and was caught up on his bills. He lived up the road in an apartment and had friends again, some of whom were in recovery, too. They made a point to talk openly about it, to keep an eye out for one another. Some he referred to Adams. He knew that recovery demanded his full attention, that it probably always would. If he lost anything else in his life — an apartment, a business — he lost that one thing only and could do without it. If he lost his recovery, he would lose everything, all at once.

I asked Boucher how he preferred to be named in this article — by only ‘‘Chad’’? Or would he prefer anonymity? But he shook his head. It was important to him to be honest about who he was. He hoped this would send a message to other addicts and to those who encountered them. ‘‘It’s important that people know there’s a way out.’’ Recovery from addiction was an achievable thing and, having discovered this fact, having discovered Eric Adams, Boucher intended to share it. The news might save lives. He knew it was possible that a business client might discover his unflattering past, that he might lose an account or two. ‘‘I’ve come way too far for that,’’ he said.

Source:  https://www.nytimes.com/2017/07/12/magazine/a-small-town-police-officers-war-on-drugs 

 

 

 

LOWELL, Mass. — They hide in weeds along hiking trails and in playground grass. They wash into rivers and float downstream to land on beaches. They pepper baseball dugouts, sidewalks and streets. Syringes left by drug users amid the heroin crisis are turning up everywhere.

In Portland, Maine, officials have collected more than 700 needles so far this year, putting them on track to handily exceed the nearly 900 gathered in all of 2016. In March alone, San Francisco collected more than 13,000 syringes, compared with only about 2,900 the same month in 2016. People, often children, risk getting stuck by discarded needles, raising the prospect they could contract blood-borne diseases such as hepatitis or HIV or be exposed to remnants of heroin or other drugs.

Activist Rocky Morrison, of the “Clean River Project,” holds up a fish bowl filled with hypodermic needles, that were recovered during 2016, on the Merrimack River. Charles Krupa / AP

It’s unclear whether anyone has gotten sick, but the reports of children finding the needles can be sickening in their own right. One 6-year-old girl in California mistook a discarded syringe for a thermometer and put it in her mouth; she was unharmed.

“I just want more awareness that this is happening,” said Nancy Holmes, whose 11-year-old daughter stepped on a needle in Santa Cruz, California, while swimming. “You would hear stories about finding needles at the beach or being poked at the beach. But you think that it wouldn’t happen to you. Sure enough.”

They are a growing problem in New Hampshire and Massachusetts — two states that have seen many overdose deaths in recent years.  “We would certainly characterize this as a health hazard,” said Tim Soucy, health director in Manchester, New Hampshire’s largest city, which collected 570 needles in 2016, the first year it began tracking the problem. It has found 247 needles so far this year.

Needles turn up in places like parks, baseball diamonds, trails and beaches — isolated spots where drug users can gather and attract little attention, and often the same spots used by the public for recreation. The needles are tossed out of carelessness or the fear of being prosecuted for possessing them.

One child was poked by a needle left on the grounds of a Utah elementary school. Another youngster stepped on one while playing on a beach in New Hampshire.

Even if adults or children don’t get sick, they still must endure an unsettling battery of tests to make sure they didn’t catch anything. The girl who put a syringe in her mouth was not poked but had to be tested for hepatitis B and C, her mother said.

Some community advocates are trying to sweep up the pollution. Rocky Morrison leads a clean-up effort along the Merrimack River, which winds through the old milling city of Lowell, and has recovered hundreds of needles in abandoned homeless camps that dot the banks, as well as in piles of debris that collect in floating booms he recently started setting.

He has a collection of several hundred needles in a fishbowl, a prop he uses to illustrate that the problem is real and that towns must do more to combat it.

“We started seeing it last year here and there. But now, it’s just raining needles everywhere we go,” said Morrison, a burly, tattooed construction worker whose Clean River Project has six boats working parts of the 117-mile river.

Among the oldest tracking programs is in Santa Cruz, California, where the community group Take Back Santa Cruz has reported finding more than 14,500 needles in the county over the past 4 1/2 years. It says it has gotten reports of 12 people getting stuck, half of them children.

“It’s become pretty commonplace to find them. We call it a rite of passage for a child to find their first needle,” said Gabrielle Korte, a member of the group’s needle team. “It’s very depressing. It’s infuriating. It’s just gross.”

Some experts say the problem will ease only when more users get treatment and more funding is directed to treatment programs.  Others are counting on needle exchange programs, now present in more than 30 states, or the creation of safe spaces to shoot up — already introduced in Canada and proposed by U.S. state and city officials from New York to Seattle.  Studies have found that needle exchange programs can reduce pollution, said Don Des Jarlais, a researcher at the Icahn School of Medicine at Mount Sinai hospital in New York.

But Morrison and Korte complain poor supervision at needle exchanges will simply put more syringes in the hands of people who may not dispose of them properly.

After complaints of discarded needles, Santa Cruz County took over its exchange from a non-profit in 2013 and implemented changes. It did away with mobile exchanges and stopped allowing drug users to get needles without turning in an equal number of used ones, said Jason Hoppin, a spokesman for the Santa Cruz County.

Along the Merrimack, nearly three dozen riverfront towns are debating how to stem the flow of needles. Two regional planning commissions are drafting a request for proposals for a clean-up plan. They hope to have it ready by the end of July.

“We are all trying to get a grip on the problem,” said Haverhill Mayor James Fiorentini. “The stuff comes from somewhere. If we can work together to stop it at the source, I am all for it.”

Source:  http://www.nbcnews.com/storyline/americas-heroin-epidemic/discarded-syringes-heroin-crisis-create-health-environmental-problems-n783671  July 2017

 

Blue Cross Blue Shield issued a report on the opioid crisis with their data from all members in their commercial plans.  Early in the document, they report a pair of striking numbers.

First, that 21% of members filled a prescription for an opioid in 2015. I’ve heard these kinds of numbers before, but I never get numb. That’s 1 in 5 members, despite growing attention to excessive prescribing of opioids.

Second, a 493% increase in diagnosis of opioid use disorders over 7 years. My reaction is that this has to reflect changes in coding or diagnostic practices rather than the population. It’s implausible that there was an increase this large in the number of people with an opioid use disorder.

The document then devotes a great deal of attention to opioid prescribing.

Toward the end, there are a couple of graphics that caught my attention.

First, a map showing rates of opioid use disorders.

 

Then, this:

Though critical to treating opioid use disorder, the use of medication-assisted treatments (e.g., methadone) does not always track with rates of opioid use disorder (compare Exhibits 10 and 11). For example, New England leads the nation in use of medication-assisted treatments but it has lower levels of opioid use disorder than other parts of the country

 

So . . . they note that New England has average rates of opioid use disorders, yet they have high rates of utilization of medication-assisted treatment. This caught my attention because New England has higher rates of overdose, as depicted in the CDC graphics below.

Number and age-adjusted rates of drug overdose deaths by state, US 2015

 

Statistically significant drug overdose death rate increase from 2014 to 2015, US states

(It’s worth noting that BCBS is not among the top 3 insurers in Maine or New Hampshire, but they are the biggest in Massachusetts and Vermont.)

It begs questions about what the story is, doesn’t it?

I don’t presume to know the answers.

§ What was the sequence of events for the high OD rates and the utilization of MAT? And, what impact, if any, has the expansion of MAT had on overdose rates?

§ Is the BCBS data representative? (This brand new SAMHSA report suggest that the data about use is representative.)

§ We know that opioid maintenance meds reduce risk of OD, but we also know that people stop taking these meds at high rates. Does this imply that, in the real world, these meds end up providing less OD protection than hoped?

§ What are the policies and practices of the other insurers in the state?  (For example, we know that Anthem [the largest insurer in Maine and Vermont] recently ended prior authorization requirements for MAT. It’s not clear how restrictive they had been. They also are attempting to institute reformsto address the fact that, “only about 16 to 19 percent of the members taking the medications for opioid use disorder also were getting the recommended in-person counseling.”)

§ Are there regional differences in drug potency that explain this?

Let’s hope that more insurers follow suit and share their data.

Source:   https://addictionandrecoverynews.wordpress.com/2017/07/16/blue-cross-blue-shield-publishes-major-opioid-report/

It is vital that physicians—particularly psychiatrists who are on the frontlines with patients who struggle with cannabis use—are able to identify and characterize cannabis use disorders; provide education; and offer effective, evidence-based treatments. This article provides a brief overview of each of these topics by walking through clinical decision-making with a case vignette that touches on common experiences in treating a patient with cannabis use disorder.

A separate and important issue is screening for emerging drugs of abuse, including synthetic “marijuana” products such as K2 and spice. Although these products are chemically distinct from the psychoactive compounds in the traditional cannabis plant, some cannabis users have tried synthetic “marijuana” products because of their gross physical similarity to cannabis plant matter.

CASE VIGNETTE

Mr. M is a 43-year-old legal clerk who has been working in the same office for 20 years. He presents as a referral from his primary care physician to your outpatient psychiatry office for an initial evaluation regarding “managing some mid-life issues.” He states that while he likes his job, it is the only job he has had since graduating college and he finds the work boring, noting that most of his co-workers have gone on to law school or more senior positions in the firm. When asked what factors have prevented him from seeking different career opportunities, he states that he would “fail a drug test.” Upon further inquiry, Mr. M says he has been smoking 2 or 3 “joints” or taking a few hits off of his “vaping pen” of cannabis daily for many years, for which he spends approximately $70 to $100 a week.

He first used cannabis in college and initially only smoked “a couple hits” in social settings. Over time, he has needed more cannabis to “take the edge off” and has strong cravings to use daily. He reports liking how cannabis decreases his anxiety and helps him fall asleep, although he thinks the cannabis sometimes makes him “paranoid,” which results in his avoidance of family and friends.

More recently, he identifies conflict and regular arguments with his wife over his cannabis use—she feels it prevents him from being present with his family and is a financial burden. He admits missing an important awards ceremony for her work and sporting events for his children, for which he had to “come up with excuses,” but the truth is that he ended up smoking more than he had intended and lost track of the time.

Mr. M reports multiple previous unsuccessful attempts to reduce his use and 2 days when he stopped completely, which resulted in “terrible dreams,” poor sleep, sweating, no appetite, anxiety, irritability, and strong cravings for cannabis. Resumption of his cannabis use relieved these symptoms. He denies tobacco or other drug use, including use of synthetic marijuana products such as K2 or spice, and reports having a glass of wine or champagne once or twice a year for special occasions.

The diagnosis

In the transition from DSM IV-TR to DSM-5, cannabis use disorders, along with all substance use disorders, have been redefined in line with characterizing a spectrum of

pathology and impairment. The criteria to qualify for a cannabis use disorder remain the same except for the following:

1. The criterion for recurrent legal problems has been removed.

2. A new criterion for craving or a strong desire or urge to use cannabis has been added, and the terms abuse and dependence were eliminated.

To qualify as having a cannabis use disorder, a threshold of 2 criteria must be met. Severity of the disorder is characterized as “mild” if 2 or 3 criteria are met, “moderate” if 4 or 5 criteria are met, and “severe” if 6 or more criteria are met. Mr. M demonstrates 3 symptoms of impaired control: using longer than intended, unsuccessful efforts to cut back, and craving; 3 symptoms of social impairment: failure to fulfil home obligations, persistent problems with his wife, and reduced pursuit of occupational opportunities; 1 symptom of risky use: continued use despite paranoia; and 2 symptoms of pharmacological properties: tolerance and withdrawal. As such, he meets 9 criteria, which qualify him for a diagnosis of severe cannabis use disorder.

You summarize Mr. M’s 9 symptoms and counsel him about severe cannabis use disorder. He becomes upset and states that he was not aware one could develop an “addiction” to cannabis. He expresses an interest in treatment and asks what options are available.

Treatment options

Psychotherapeutic treatments, including motivational enhancement treatment (MET), cognitive behavioral therapy (CBT), and contingency management (CM), have demonstrated effectiveness in reducing frequency and quantity of cannabis use, but abstinence rates remain modest and decline after treatment. Generally, MET is effective at engaging individuals who are ambivalent about treatment; CM can lead to longer periods of abstinence during treatment by incentivizing abstinence; and CBT can work to enhance abstinence following treatment (preventing relapse). Longer duration of psychotherapy is associated with better outcomes. However, access to evidence-based psychotherapy is frequently limited, and poor adherence to evidence-based psychotherapy is common.

In conjunction with psychotherapy, medication strategies should be considered. Because there are no FDA-approved pharmacological agents for cannabis use disorder, patients should understand during the informed consent process that all pharmacotherapies used to treat this disorder are off-label. A number of clinical trials provide evidence for the off-label use of medications in the treatment of cannabis use disorder. The current strategies for the off-label treatment of cannabis use disorder target withdrawal symptoms, aim to initiate abstinence and prevent relapse or reduce use depending on the patient’s goals, and treat psychiatric comorbidity and symptoms that may be driving cannabis use. Here we focus on the evidence supporting these key strategies.

Targeting withdrawal and craving

Cannabis withdrawal is defined by DSM-5 as having 3 or more of the following signs and symptoms that develop after the cessation of prolonged cannabis use:

• Irritability, anger, or aggression

• Nervousness or anxiety

• Sleep difficulty

• Decreased appetite or weight loss

• Restlessness

• Depressed mood

• At least one of the following physical symptoms that causes discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache

Withdrawal symptoms may be present within the first 24 hours. Overall, they peak within the first week and persist up to 1 month following the last use of cannabis. In the case of Mr. M, insomnia, poor appetite, and irritability as well as sweating are identified, which meet DSM-5 criteria for cannabis withdrawal during the 2 days he abstained from use. He also identifies strong craving and vivid dreams, which are additional withdrawal symptoms included on marijuana withdrawal checklists in research studies, although not included in DSM-5 criteria. These and other symptoms should be considered in clinical treatment.

Medication treatment studies for cannabis withdrawal have hypothesized that if withdrawal symptoms can be reduced or alleviated during cessation from regular cannabis use, people will be less likely to resume cannabis use and will have better treatment outcomes. Studies have shown that dronabinol and nabilone improved multiple withdrawal symptoms, including craving; and quetiapine, zolpidem, and mirtazapine help with withdrawal-induced sleep disturbances.1-5

Combining dronabinol and lofexidine (an alpha-2 agonist) was superior to placebo in reducing craving, withdrawal, and self-administration during abstinence in a laboratory model. However, in a subsequent treatment trial, the combined medication treatment was not superior to placebo in reducing cannabis use or promoting abstinence.6

Six double-blind placebo-controlled pharmacotherapy trials in adults with cannabis use disorder have looked at withdrawal as an outcome.7 Of these studies, only dronabinol, bupropion, and gabapentin reduced withdrawal symptoms.8-10 In addition to reducing withdrawal symptoms, nabiximols/Sativex (a combination tetrahydrocannabinol [THC] and cannabidiol nasal spray not available in the US) increased retention (while actively on the medication in an inpatient setting) but did not reduce outpatient cannabis use at follow-up.11

All of the medications available for prescription in the US can be monitored reliably with urine drug screening to assess for illicit cannabis use except dronabinol, which will result in a positive screen for cannabis. When using urine drug screening, remember that for heavy cannabis users the qualitative urine drug screen can be positive for cannabis up to a month following cessation. When selecting a medication, take into account the cost of the medication, particularly since insurance will likely not cover THC agonists such as dronabinol for this indication, and possible misuse or diversion of scheduled substances (eg, dronabinol, nabilone). In addition, monitoring for reductions in substance use and withdrawal symptoms is key.

Abstinence initiation and relapse prevention

Other clinical trials have looked at medications to promote abstinence by reducing stress-induced relapse, craving (not as a component of withdrawal), and the reinforcing aspects of cannabis. Of these trials, the following results show potential promise with positive findings: gabapentin reduced quantitative THC urine levels and improved cognitive functioning (in addition to decreasing withdrawal), and buspirone led to more negative urine drug screens for cannabis (although the difference was not significant compared with placebo).10,12 However, in a follow-up larger study, no differences were seen compared with placebo and women had worse cannabis use outcomes on buspirone.13

N-acetylcysteine resulted in twice the odds of a negative urine drug screen in young adults and adolescents (although there was no difference between adolescent groups in self-report of cannabis use).14 Gray and colleagues15 reported that no differences were seen between N-acetylcysteine and placebo (results of the trial are soon to be published). Topiramate resulted in significantly decreased grams of cannabis used but no difference in percent days used or proportion of positive urine drug screens.16 In a recent small clinical trial, reductions in cannabis use were seen with oxytocin in combination with MET.17 Studies with nabilone and long-term naltrexone administration reduced relapse and cannabis self-administration and subjective effects, respectively, which suggests promising avenues yet to be explored by clinical trials.2,18

Treatment of psychiatric comorbidity

Other studies have looked at the effects of treating common comorbid psychiatric disorders in adults with cannabis use disorder, postulating that if the psychiatric disorder is treated, the individual may be more likely to abstain or reduce his or her cannabis use. For example, if a person is less depressed, he may better engage in CBT for relapse prevention.

Fluoxetine for depression and cannabis use disorder in adolescents decreased cannabis use and depression, although there was no difference compared with placebo.19 A trial of venlafaxine for adults with depression and cannabis use disorder demonstrated less abstinence with greater withdrawal-like symptoms compared with placebo.20,21 These findings suggest that this antidepressant might not be beneficial for treatment-seeking individuals with cannabis use disorder and may actually negatively affect outcomes.

CASE VIGNETTE CONT’D

After discussing and presenting the different psychotherapy and medication treatment options to Mr. M, you and he decide to start CBT to help with abstinence initiation. In addition, you prescribe 20 mg of dronabinol up to 2 times daily in combination with 50 mg of naltrexone daily, to help globally target Mr. M’s withdrawal symptoms and prevent relapse once abstinence is achieved. However, a few days later, Mr. M calls to say that his insurance will not cover the prescription for dronabinol and he cannot afford the high cost. Given his main concerns of cannabis withdrawal symptoms, you select gabapentin up to 400 mg 3 times daily and continue weekly individual CBT.

Mr. M calls back several days later and reports that he has made some improvements in reducing the frequency of his cannabis use, which he attributes to the medication, but he thinks he needs additional assistance. After reviewing the treatment options again, he gives informed consent to start 1200 mg of N-acetylcysteine twice daily. After 10 weeks of this medication, his urine screens are negative.

You continue to provide relapse prevention CBT. He reports to you that his anxiety and insomnia are almost resolved, and you suspect that withdrawal was the cause of these symptoms. He reports significant improvement in his relationship with his family and recently received a promotion at work for “going above and beyond” on a project he was given the lead.

Over the next 6 months, he has 2 relapses that in functional analysis with you are determined to be triggered by unsolicited contact from his former drug dealer. Together, you develop a plan to block any further contact from the drug dealer. After several months, both the gabapentin and N-acetylcysteine are tapered and discontinued. Mr. M continues to see you for biweekly therapy sessions with random drug screens every 4 to 6 weeks.

Conclusion

Based on the available evidence, gabapentin, THC agonists, naltrexone, and possibly N-acetylcysteine show the greatest promise in the off-label treatment of cannabis use disorders. System considerations, such as medication cost, need to be factored into the decision-making as well as combination medication and psychotherapy approaches, which—as demonstrated in the case of Mr. M—may ultimately work best. Until further research elucidates the standard of medication practices for cannabis use disorder, the best off-label medication strategy should target any co-occurring disorders as well as any identified problematic symptoms related to cannabis use and cessation of use. When available, referral for evidence-based psychotherapy should be made.

Source:  (http://www.psychiatrictimes.com)  30th June 201

Investigating the proposition that cannabis is worth bothering with, this hot topic looks at reports that stronger cannabis on the market is increasing harms to users, prospects of recovery from disorders and dependence, and the emerging response to synthetic forms of cannabis like ‘spice’.

CANNABIS IN THE LAW

A controlled ‘Class B’ substance, cannabis carries legal penalties for possession, supply, and production. Between 2004–2009 cannabis was reclassified as a ‘Class C’ substance, meaning for a brief period of time it carried lesser penalties for possession. In 2009, the Association of Chief Police Officers issued new guidance, advising officers to take an escalating approach to the policing of cannabis possession for personal use: • A warning • A penalty notice for disorder (PND) • Arrest

This three-tiered approach was designed to be “ethical and non-discriminatory”, but also reinforce the “national message that cannabis is harmful and remains illegal”.

In 1990s Britain a common reaction to allocating resources to treating cannabis users was, ‘Why bother? We have more than enough patients with problems with serious drugs like heroin.’ The typically calming use of the drug by adults was seen as preferable to the main alternative – alcohol and its associated violence and disorder. Calls for a treatment response were seen as pathologising what in many societies is both normal and in some ways desirable youth development: trying new experiences, challenging conventions, and exposing the hypocrisy of alcohol-drinking adults. In 1997 the Independent on Sunday launched a campaign to decriminalise cannabis, culminating in a mass ‘roll-up’, and 16,000-strong pro-cannabis march from Hyde Park to Trafalgar Square. Its Editor Rosie Boycott wrote in the paper about her own coming-of-age experience smoking cannabis, telling readers:

“I Rolled my first joint on a hot June day in Hyde Park. Summer of ’68. Just 17. Desperate to be grown-up. … My first smoke, a mildly giggly intoxication, was wholly anti-climatic. The soggy joint fell apart. I didn’t feel changed. But that act turned me – literally – into an outlaw. I was on the other side of the fence from the police – or the fuzz, as we used to call them. So were a great many of my generation.”

The campaign was explosive, but short-lived, apparently subsiding when Boycott left to take up her role as Editor of the Daily Express. A decade later, the Independent issued an apology for the campaign. ‘If only they had known then, what they knew now’, was the message of the article, referring to the reportedly damaging impact of the more potent strains of cannabis and its links to “mental health problems and psychosis for thousands of teenagers”.

Are stronger strains creating more problems?

There has been a long-standing, but controversial, association between cannabis strength and harm. Reading newspaper articles on the subject, it wouldn’t be unusual to see a headline drawing a straight line between ‘super-strength skunk’ and addiction, violence, deaths, or psychosis. In 2008, then Prime Minister Gordon Brown spoke in a similar vein, telling a breakfast-television viewing audience:

I have always been worried about cannabis, with this new skunk, this more lethal part of cannabis.

I don’t think that the previous studies took into account that so much of the cannabis on the streets is now of a lethal quality and we really have got to send out a message to young people – this is not acceptable.

Brown was warning of a dangerous new strain of cannabis on the market, that caused very severe harms to users – contrasting starkly with the common perception of cannabis as a ‘low harm’ or ‘no harm’ drug. The strength or potency of cannabis is determined by the amount of ‘THC’ it contains. THC produces the ‘high’ associated with cannabis, and another major component ‘CBD’ produces the sedative and anti-anxiety effects. As well as potency, the relative amounts of THC and CBD are important for understanding the effects of cannabis – something explored in a University College London study during the programme Drugs Live: Cannabis on Trial. The research team compared two different types of cannabis: the first had high levels of THC (approx. 13%) but virtually no CBD; and the second had a lower level of THC (approx. 6.5%) and substantial amounts of CBD (approx. 8%). They found that CBD had a moderating or protective effect on some of the negative effects of THC, and that “many of the effects that people enjoy are still present in low-potency varieties without some of the harms associated with the high-potency varieties”. At least in the US over the last two decades (between 1995–2014), potency has increased from around 4% to 12%, and the protective CBD content of cannabis has decreased, from around 28% to less than 15%, significantly affecting the ratio of THC to CBD, and with it, the nature and strength of the psychoactive effect of cannabis. Until the 1990s, herbal cannabis sold in the UK was predominantly imported from the Caribbean, West Africa, and Asia. After this time, it was increasingly produced in the UK, being grown indoors using intensive means (artificial lighting, heating, and control of day-length). A study funded by the Home Office analysed samples of cannabis confiscated by 23 police forces in England and Wales in 2008, and found that over 97% of herbal cannabis had been grown by intensive methods; its average potency of 16% compared with just 8% for traditional imported herbal cannabis. This matched other reports of home-grown cannabis being consistently (around 2–3 times) stronger than imported herbal cannabis and cannabis resin.

In 2015, observing a decrease in the use of cannabis in England and Wales, but parallel increase in demand for treatment, a UK study examined whether the trend could be explained by an increase in the availability of higher-potency cannabis. Over 2500 adults were surveyed about their use of different types of cannabis, severity of dependence, and cannabis-related concerns. The researchers found that higher potency cannabis was associated with a greater severity of dependence, especially in young people, and was rated by participants as causing more memory impairment and paranoia than lower potency types. However at the same time, it was reported to produce the best ‘high’, and to be the preferred type.

By definition cannabis is a psychoactive substance, which means it can change people’s perceptions, mood, and behaviour. Higher potency cannabis contains more of the psychoactive component, so it makes sense that higher potency cannabis could increase the risk of temporary or longer-term (adverse) problems with perceptions, mood, and behaviour. However, there is a particular concern that cannabis use could be linked to ‘psychosis’, a term describing a mental illness where a person perceives or interprets reality in a very different way to those around them, which can include hallucinations or delusions.

Whether cannabis causes psychosis, precipitates an existing predisposition, aggravates an existing condition, or has no impact at all on psychotic symptoms, has for decades been hotly contested. With our focus on evaluations of interventions, Drug and Alcohol Findings is in no position to pronounce on this issue, nor on the possibility that the drug might sometimes improve mental health, but some examples of research informing this debate are included below. A 2009 UK study examined whether daily use of high-potency cannabis was linked to an elevated risk of psychosis, comparing 280 patients in London presenting with a first episode of psychosis with a healthy control group. The patients were found to be more likely to smoke cannabis on a daily basis than the control group, and to have smoked for more than five years. Among those who used cannabis, 78% of the patients who had experienced psychosis used higher-potency cannabis, compared with 37% of those in the control group. The findings indicated that the risk of psychosis was indeed greater among the people who were using high potency cannabis on a frequent basis, but couldn’t show that the cannabis use caused the psychosis, or even that the cannabis use made the group more susceptible to psychosis. The wider literature on mental health and substance use would suggest that the association is more complex than this. A recently published paper from the University of York has demonstrated the complications of attributing any association between cannabis use and psychosis to a causal effect of cannabis use rather than other factors or a reverse causal effect. A calculation based on data from England and Wales helped to put this into perspective, indicating that even if cannabis did cause psychosis more than 20,000 people would need to be stopped using cannabis to prevent just one case of psychosis. The apparent steady increase in cannabis potency in the UK since the 1990s is important context for further research. Where higher potency cannabis is increasingly becoming the norm, and is the preference for cannabis users, it would be relevant to generate more evidence of the health-related problems with high potency cannabis, and the treatment and harm reduction solutions based around these health-related problems.

Cannabis accounts for half of all new drug treatment patients

The most widely used illegal drug in Europe, many seemingly enjoy cannabis without it leading to any significant negative social or health effects. However, numbers entering treatment for cannabis use problems have been on the rise (both in the UK, and the rest of Europe), while heroin treatment numbers have fallen  chart. According to Public Health England, this is not because more people are using cannabis, but perhaps because services relieved of some of the recent pressure of opiate user numbers are giving more priority to cannabis, because they are making themselves more amenable to cannabis users, and because of emerging issues with stronger strains of the drug. Whatever the causes, across the UK figures submitted to the European drug misuse monitoring centre show that the proportion of patients starting treatment for drug problems who did so primarily due to their cannabis use rose steadily from 11% in 2003/04 to 22% in 2011/12. With the caveat that data from 2013 onwards is not directly comparabledue to changes in methodology, in 2014 and 2015 the proportion of patients who entered treatment primarily because of a cannabis issue hovered above previous years at 26% (25,278 and 26,295 respectively). Among first ever treatment presentations, the increase from 2003/04 was more pronounced, from 19% to 37%. By 2013, cannabis use had become the main prompt for half the patients who sought treatment for the first time (at 49%), and stayed relatively constant at 47% in 2014, and 48% in 2015.

Showing that more users was not the reason for more starting treatment, over about the same period, in England and Wales the proportion of 16–59-year-olds who in a survey said they had used cannabis in the past year fell from about 11% to 7% in 2013/14, then stayed at that level in 2014/15 and 2015/16. The treatment figures largely reflect trends in England, where in 2013/14 the number of patients starting treatment with cannabis use problems had risen to 30,422, 21% of all treatment starters, up from 23,018 and 19% in 2005/06. Subsequently the number dropped to 27,965 in 2015/16, still around a fifth of all treatment starters. Among the total treatment population – starting or continuing in treatment – cannabis numbers rose from 40,240 in 2005/06 to peak at 64,407 in 2013/14 before falling back to 59,918 in 2015/16; corresponding proportions again hovered around a fifth. As a primary problem substance among under-18s cannabis dominated, accounting for three-quarters of all patients in treatment in 2015/16 and in numbers, 12,863. The dominance of cannabis increased from 2008/09 as numbers primarily in treatment for drinking problems fell.

‘All treatments appear to work’

According to the two main diagnostic manuals used in Europe and the USA, problem cannabis use can develop into a cannabis use disorder or cannabis dependence, identifiable by a cluster of symptoms including: loss of control; inability to cut down or stop; preoccupation with use; neglecting activities unrelated to use; continued use despite experiencing problems; and the development of tolerance and withdrawal. This level of clinical appreciation for cannabis use problems didn’t exist when researcher and writer William L. White entered the addictions field half a century ago:

“When I first entered the rising addiction treatment system in the United States nearly half a century ago, there existed no clinical concept of cannabis dependence and thus no concept of recovery from this condition. In early treatment settings, cannabis was not consider[ed] a “real” drug, the idea of cannabis addiction was scoffed at as remnants of “Reefer Madness,” and casual cannabis use was not uncommon among early staff working in addiction treatment programs of the 1960s. Many in the field remain sceptical of the idea of cannabis dependence, specifically whether problem users at the severe end experience physiological withdrawal. However, reviewing what they believe is mounting evidence, these authors suggest there can be confidence in the existence of a “true withdrawal syndrome” – albeit one that differs qualitatively from the “significant medical or psychiatric problems as observed in some cases of opioid, alcohol, or benzodiazepine withdrawals”. In the case of cannabis, the main symptoms are primarily emotional and behavioural, although appetite change, weight loss, and some physical discomfort are reported. A brief review aimed at practitioners in UK primary care provides guidance on how to manage symptoms of withdrawal among patients trying to stop or reduce their cannabis use.

Research has come a long way, says William L. White, with now “clear data supporting the dependency producing properties of cannabis, a clear conceptualization of cannabis use disorders (CUD) and cannabis dependence (CD)”, but until recently, very little evidence about the prospects of long-term recovery. Yet, key papers – found here and here – indicate that:

• Full remission from cannabis use disorders is not only possible, but probable.

• Stable remission takes time – an average of 33 months.

• Abstinence may not be initially realistic for heavy cannabis users – but those in  remission are usually able to reduce the intensity of their use and its  consequences.

At least in the United States, it seems dependence is more quickly overcome from cannabis than the main legal drugs. A survey of the US general adult population found that within a year of first becoming dependent, 3% each of smokers and drinkers were in remission and remained so until they were surveyed. For cannabis the figure was nearly 5% and for cocaine, nearly 9%. After ten years the proportions in remission had risen to 18% for nicotine, 37% for alcohol, 66% for cannabis and 76% for cocaine. About 26 years after first becoming dependent, half the people at some time dependent on nicotine were in remission, a milestone reached for alcohol after 14 years, for cannabis six years, and for cocaine, five.

Specialised treatment programmes for cannabis users in European countries

Generally for people with cannabis use problems, the European Monitoring Centre for Drugs and Drug Addiction concluded in 2015, and before that in 2008, that “all treatments appear to work”. For adults, effective treatments include motivational interviewing, motivational enhancement therapy and cognitive-behavioural therapy, and for younger people, family-based therapies seem most beneficial. Less important than the type of treatment is the treatment context and the individual’s determination to overcome their problems through treatment. And there is “no firm basis for a conclusion” that cannabis-specific interventions (designed around the risks and harms associated with cannabis) are more effective than general substance use treatment tailored to the individual needs of the cannabis user seeking treatment chart. In some studies brief interventions have been found to work just as well as more intensive treatment, but when the patients are heavily dependent, and the most difficult cases are not filtered out by the research, longer and more individualised therapies can have the advantage. When the World Health Organization trialled its ASSIST substance use screening and brief advice programme in Australia, India, the United States, and Brazil, just over half the identified patients (all had to be at moderate risk of harm but probably not dependent) were primarily problem cannabis users. Among these, risk reduction in relation to this drug was significantly greater among patients allocated to a brief advice session than among those placed on a three-month waiting list for advice. In each country too, risk reduction was greater among intervention patients, except for the USA, where the order was reversed. Suggesting that severity of use was not a barrier to reacting well to brief intervention, only patients at the higher end of the moderate risk spectrum further reduced their cannabis use/risk scores following intervention. The ASSIST study was confined to adults, but young people in secondary schools in the USA whose problem substance use focused mainly on cannabis also reacted well to brief advice.

The relative persistence of opiate use problems versus the transitory nature of those primarily related to cannabis seemed reflected in an analysis of treatment entrants in England from 1 April 2005 to the end of 2013/14, the last time this particular analysis was published. At the end of this period just 7% of primary cannabis users were still in or back in treatment compared to the 30% overall figure and 36% for primary opiate users. The figure peaked at 43% for users of opiates and crack. Over half – 53% – of primary cannabis users had left treatment as planned, apparently having overcome their cannabis problems, compared to 27% of primary opiate users and just 20% with dual opiates and crack use problems. Another 40% of cannabis users had left treatment in an unplanned manner, a slightly higher proportion than among opiate users. The figures tell a tale of relatively high level of success which enables cannabis users to leave treatment, though even in the absence of recorded success, few stay long-term.

However, the forms patients in England complete with their keyworkers while in treatment seem to tell a different story. Compared to how they started treatment, around six months later 45% of primary cannabis users were assessed as using just as often (including a few using more), compared to 30% of opiate users and 42% whose main problem drugs were both opiates and crack, suggesting more rapid and/or more complete remission for opiate users than for cannabis users. One interpretation is that the widespread use of substitute drugs like methadone more reliably reduced the illegal opiate use of opiate users and also helped retain them in treatment, while cannabis users tended quickly to leave treatment, having done well or not. However, these figures relate only to patients who completed the forms at their six-month review, which in practice could have happened anywhere from about one to six months after their assessment for treatment. What proportion of primary cannabis users were still in treatment at that point and available to complete the forms is not clear, but they may have been the patients whose problems were deep seated enough to require extended treatment.

Enjoyable and trouble-free for many, but not without harms Harm reduction – the “set of practical strategies and ideas aimed at reducing negative consequences associated with drug use” – is mostly associated with ‘harder’ drugs like heroin, for which blood-borne viruses and drug-related deaths are clear and severe risks. Yet while “many people experience cannabis as enjoyable and trouble free”, there are also varying degrees of harm with this drug depending on the characteristics of the person using, the type of the cannabis, and the way they consume it. Many formal cannabis harm reduction programmes borrow from the fields of alcohol and tobacco. Advice includes:

• safer modes of administration (eg, on the use of vaporisers, on rolling safer joints, on less risky modes of inhaling) Many people experience cannabis as enjoyable and trouble free … some people require help to reduce or stop

• skills to prevent confrontation with those who disapprove of use

• encouraging users to moderate their use

 

• discouraging mixing cannabis with other drugs

• drug driving prevention and controls

• reducing third-party exposure to second-hand smoke

• education about spotting signs of problematic use

• self-screening for problematic use

In some parts of the UK, National Health Service tobacco smoking cessation services incorporated cannabis into their interventions with adults; and Health Scotland, also addressing the risks of tobacco and cannabis smoking, published a booklet for young people titled Fags ‘n’ Hash: the essential guide to cutting down the risks of using tobacco and cannabis.

Vaporising or swallowing cannabis offers a way to avoid respiratory risks, but only a minority of cannabis do this, most choosing to smoke cannabis joints (or cannabis and tobacco joints). While not all will know about the different health risks, cannabis users may choose against safer consumption methods anyway for a range of reasons (including their own thoughts about safe use):

• Users may find it easier to control the effects (eg, severity, length of effect) of cannabis when inhaling in the form of a joint or spliff

• Preparing and sharing joints can be an enjoyable part of the routine, or part of a person’s social activities

• Alternative methods of smoking (eg, bongs and vaporisers) may be inconvenient to use, or expensive to buy

 

Most harm reduction advice is delivered informally long before users come into contact with drugs professionals – for example through cannabis magazines, websites, and headshops – highlighting the importance of official sources engaging with non-official sources to promote the delivery of accurate, evidence-based harm reduction messages.

A new high

In May 2016 the Psychoactive Substances Act placed a ‘blanket ban’ on new psychoactive substances (previously known as ‘legal highs’), including synthetic cannabinoids (synthetic forms of cannabis). Prior to this, in 2014, there had been 163 reported deaths from new psychoactive substances in the UK, and 204 the year after. The average age was around 28, younger than the average age for other drug misuse deaths of around 38. The fact that these psychoactive substances – which produced similar effects to illicit drugs like cannabis, cocaine, and ecstasy – could be bought so easily online or on the high street, appeared inconsistent; and each fatality prompted “an outcry for something to be done to prevent further tragedies”. This was the context (and arguably the political trigger) for the introduction of the Psychoactive Substances Act. While possession of a psychoactive substance as such wasn’t criminalised;, production, supply, offer to supply, possession with intent to supply, import or export were – with a maximum penalty of seven years’ imprisonment.

Just seven months after the Act came into effect, the Home Office labelled it a success, with a press release stating that nearly 500 people had been arrested, 332 shops around the UK had been stopped from selling the substances, and four people had been sent to prison. But did the Psychoactive Substances Act have the presumably desired effect of limiting access to psychoactive substances (and reducing deaths), or did it just push the drugs the way of dealers? It is perhaps too early to tell, but former chair of the Advisory Council on the Misuse of Drugs Professor Nutt had warned before the Act came into effect that the ‘blanket ban’ would make it harder (not easier) to control drugs. And while Chief executive of DrugWise Harry Shapiro had said the new law would make new psychoactive substances harder to obtain, he also agreed that sale of the drugs would not cease, but merely be diverted to the illicit market: “The same people selling heroin and crack will simply add this to their repertoire.” The paper “From niche to stigma” examined the changing face of the new psychoactive substance user between 2009 and 2016, focusing on people using the synthetic cannabis known as ‘spice’. It looked at the transition of (then) ‘legal highs’ from an “experimental and recreational” scene associated with a “niche middle class demographic”, to “those with degrees of stigma”, especially homeless, prison, and socially vulnerable youth populations (including looked after children, those involved in or at risk of offending, and those excluded or at risk of exclusion from mainstream education). In 2014, the DrugScope Street Drug Survey also observed a problem among these particular groups, recording a “rapid rise in the use of synthetic cannabinoids such as Black Mamba and Exodus Damnation by opiate users, the street homeless, socially excluded teenagers and by people in prison”.

‘SPICE’ AND OTHER SYNTHETICS

Cannabis contains two key components:

• ‘THC’ (tetrahydrocannabinol), which produces the ‘high’

• ‘CBD’ (cannabidiol), which produces the sedative and anti-anxiety effects

Synthetic forms of cannabis contain chemicals that aim to copy the effects of ‘THC’ in cannabis. But the effects of synthetic cannabis can be quite different (and often stronger): firstly, because synthetic production makes it easier to manipulate the amount of the THC-like chemical; and secondly, because of the absence of the moderating equivalent of ‘CBD’. Some synthetics are purposely designed to resemble herbal cannabis, and can be consumed in the same ways (eg, smoked or inhaled). The names also often have deliberate cannabis connotations. The risk of this is that people wishing to take cannabis may be initially unaware that they have been sold the synthetic form, or may believe from the look of it that it will produce similar sought-after effects. The greater intensity of synthetic cannabis at lower dose levels ( box) ensures that it has an appeal in terms of potency and affordability, but may put those with fewer resources at greater harm.

In 2014, the prison inspectorate for England and Wales raised concerns about the rise in the use of psychoactive substances in prisons, in particular synthetic cannabis. A study set in an English adult male prison found that the nature of the market was posing significant challenges to the management of offenders. There, the primary motivation for consumption was being able to take a substance without it being detected. Given this motivation, and the greater likelihood of harms from synthetic versus natural cannabis, the researchers concluded that it was imperative for mandatory drug-testing policies to be revised, and instead rooted in harm reduction – something which would also apply to people on probation subject to mandatory drug-testing.

Cannabis throws up a range of issues rather different from those associated with the drugs treatment in the UK has normally focused on. If current trends continue, understanding the findings will become yet more important to British treatment services.

Source:   http://findings.org.uk/PHP/dl.php?file=cannabis_treat.    Last revised 10 July 2017. 

Legalizing recreational marijuana use in Colorado, Oregon and Washington has resulted in collision claim frequencies that are about three percent higher overall than would have been expected without legalization, a new insurance report has found.

The Highway Loss Data Institute (HLDI) report says that more drivers admit to using marijuana, and the substance is showing up more frequently among people involved in crashes.

The HLDI report authors note that although there is evidence from simulator and on-road studies that marijuana can degrade some aspects of driving performance, researchers haven’t been able to definitively connect marijuana use with more frequent real-world crashes.

Some studies have found that using the drug could more than double crash risk, while others, including a large-scale federal case-control study, have failed to find a link between marijuana use and crashes. Studies on the effects of legalizing marijuana for medical use also have been inconclusive.

Colorado and Washington were the first states to legalize recreational marijuana for adults age 21 and older with voter approval in November 2012. Retail sales began in January 2014 in Colorado and in July 2014 in Washington. Oregon voters approved legalized recreational marijuana in November 2014, and sales started in October 2015.

HLDI conducted a combined analysis using neighbouring states as additional controls to examine the collision claims experience of Colorado, Oregon and Washington before and after law changes. Control states included Idaho, Montana, Nevada, Utah and Wyoming, plus Colorado, Oregon and Washington prior to legalization of recreational use.

During the study period, Nevada and Montana permitted medical use of marijuana, Wyoming and Utah allowed only limited use for medical purposes, and Idaho didn’t permit any use. Oregon and Washington authorized medical marijuana use in 1998, and Colorado authorized it in 2000.

HLDI also looked at loss results for each state individually compared with loss results for adjacent states without legalized recreational marijuana use prior to November 2016.  “The combined-state analysis shows that the first three states to legalize recreational marijuana have experienced more crashes,” says Matt Moore, senior vice president of HLDI. “The individual state analyses suggest that the size of the effect varies by state.”

Colorado saw the biggest estimated increase in claim frequency compared with its control states. After retail marijuana sales began in Colorado, the increase in collision claim frequency was 14 percent higher than in nearby Nebraska, Utah and Wyoming. Washington’s estimated increase in claim frequency was 6 percent higher than in Montana and Idaho, and Oregon’s estimated increase in claim frequency was 4 percent higher than in Idaho, Montana and Nevada.

“The combined effect for the three states was smaller but still significant at 3 percent,” Moore says. “The combined analysis uses a bigger control group and is a good representation of the effect of marijuana legalization overall. The single-state analyses show how the effect differs by state.”

Each of the individual state analyses also showed that the estimated effect of legalizing recreational use of marijuana varies depending on the comparison state examined. For example, results for Colorado vary from a 3 percent increase in claim frequency when compared with Wyoming to a 21 percent increase when compared with Utah.

Data spanned collision claims filed between January 2012 and October 2016 for 1981 to 2017 model vehicles. Analysts controlled for differences in the rated driver population, insured vehicle fleet, the mix of urban versus rural exposure, unemployment, weather and seasonality.

Collision claims are the most frequent kind of claims insurers receive. Collision coverage insures against physical damage to a driver’s vehicle in a crash with an object or other vehicle, generally when the driver is at fault. Collision claim frequency is the number of collision claims divided by the number of insured vehicle years.

HLDI said it will continue to examine insurance claims in states that allow recreational use of marijuana. Meanwhile, IIHS has begun a large-scale case-control study in Oregon to assess how legalized marijuana use may be changing the risk of crashes with injuries. Preliminary results are expected in 2020.

In addition to Colorado, Oregon and Washington, five other states and Washington, D.C., have legalized marijuana for all uses, and 21 states have comprehensive medical marijuana programs as of June. An additional 17 states permit limited access for medical use. Marijuana is still an illegal controlled substance under federal law.

“Worry that legalized marijuana is increasing crash rates isn’t misplaced,” says David Zuby, executive vice president and chief research officer of the Insurance Institute for Highway Safety. “HLDI’s findings on the early experience of Colorado, Oregon and Washington should give other states eyeing legalization pause.”

The Highway Loss Data Institute (HLDI) conducts studies of insurance data on vehicle losses and by publishes insurance loss results by vehicle make and model. Its sister research organization, the Insurance Institute for Highway Safety (IIHS), is focused reducing the losses from motor vehicle crashes. Both organizations are wholly supported by auto insurers and insurance associations.

State Efforts

The Governors Highway Safety Association (GHSA) has urged states to equip themselves with the latest research and recommends that they increase drug testing, bolster laboratory resources, track alcohol (DUI) and drugged (DUID) related driving data separately in state records, use surveys to gauge public attitudes, and evaluate the effects of any law or program changes.

The group has issued a guide, Drug Impaired Driving: A Guide for States, for states. Chief among the report’s recommendations is increased training for law enforcement officers to help them identify and arrest drugged drivers.

“As states across the country continue to struggle with drug-impaired driving, it’s critical that we help them understand the current landscape and provide examples of best practices so they can craft the most effective countermeasures,” said Jonathan Adkins, executive director of GHSA.

GHSA said this year five states are getting grants totalling $100,000 to implement Advanced Roadside Impaired Driving Enforcement (ARIDE) training and Drug Recognition Expert (DRE) programs. The states are Illinois, Montana, Washington, West Virginia and Wisconsin.

Related Research

The HLDI authors cite other research into drugs and driving including a 2016 IIHS survey that found that drivers in Colorado, Oregon and Washington were more likely to view marijuana as a highway safety problem than drivers in states without legalized use (Drivers say alcohol is bigger threat than pot).

A 2016 Columbia University study looked at traffic fatalities in 19 states before and after they enacted legalized medical marijuana laws. On average there was an 11 percent reduction in fatality rates, although the results varied across states. Seven states saw a reduction, while two had an increase, and the other 10 didn’t change.

Researchers using the National Advanced Driving Simulator found that while drivers under the influence of marijuana had trouble maintaining constant lane position, they drove more slowly and with more headway than drivers not under the influence.

About 1 in 5 weekend night-time drivers tested positive for at least one legal or illegal drug in the 2013-14 National Roadside Survey of Alcohol and Drug Use by Drivers conducted by the National Highway Traffic Safety Administration (NHTSA) (More drivers use marijuana, but link to crashes is murky).

A 2016 AAA Foundation study in Washington since legalization estimated that the prevalence of drivers in fatal crashes with marijuana in their blood roughly doubled from 8.3 percent in 2013 to 17 percent in 2014.

The National Highway and Traffic Safety Administration (NHTSA) examined the crash risk associated with driver drug use and found that drivers who tested positive for marijuana were overrepresented in the crash-involved population (More drivers use marijuana, but link to crashes is murky). However, they found no link between marijuana use and driver crash risk. The study, published in 2016, included 2011-12 data on police-reported crashes in Virginia Beach, Virginia, where it is illegal to use marijuana.

Source:  http://www.insurancejournal.com/news/

INTRODUCTION

Drug addiction is a chronic and relapsing disease that often begins during adolescence.

Epidemiological evidence documents an association between marijuana use during adolescence and subsequent abuse of drugs such as heroin and cocaine (1, 2). While many factors including societal pressures, family, culture, and drug availability can contribute to this apparent `gateway’ association, little is known about the neurobiological basis underlying such potential vulnerability.

Of the neural substrates that have been investigated, the enkephalinergic opioid system is  consistently altered by developmental marijuana exposure (3–5), perhaps reflecting neuroanatomical interactions between cannabinoid receptor type 1 and the enkephalinergic system (6, 7).

Debates exist, however, regarding the relationship between proenkephalin (Penk) dysregulation and opiate susceptibility. We previously reported that adult rats exposed to Δ9-tetrahydrocannabinol (THC; primary psychoactive component of marijuana) during adolescence exhibit increased heroin self administration (SA) as well as increased expression of Penk, the gene encoding the opioid neuropeptide enkephalin, in the nucleus accumbens shell (NAcsh), a mesolimbic structure critically involved in reward-related behaviors (3).

Although these data suggest that increased NAcsh Penk expression and heroin SA behavior are independent consequences of adolescent THC exposure, they do not address a possible causal relationship between THCinduced  Penk upregulation in NAcsh and enhanced behavioral susceptibility to opiates.

Moreover, insights regarding the neurobiological mechanisms by which adolescent THC exposure maintains upregulation of Penk into adulthood remain unknown.

Here, we take advantage of viral-mediated gene transfer strategies to show that adulthood addiction-like behaviors induced by adolescent THC exposure are dependent on discrete regulation of NAcsh Penk gene expression. A number of recent studies have demonstrated an important role for histone methylation in the regulation of drug-induced behaviors and transcriptional plasticity, particularly alteration of repressive histone H3 lysine 9 (H3K9) methylation at NAc gene promotors (8, 9).

We report here that one mechanism by which adolescent THC exposure may mediate Penk upregulation in adult NAcsh is through reduction of H3K9 di- and trimethylation, a functional consequence of which may be decreased transcriptional repression of Penk.

ABSTRACT

Background

Marijuana use by teenagers often predates the use of harder drugs, but the neurobiological underpinnings of such vulnerability are unknown. Animal studies suggest enhanced heroin self-administration (SA) and dysregulation of the endogenous opioid system in the nucleus accumbens shell (NAcsh) of adults following adolescent Δ9-tetrahydrocannabinol (THC) exposure. However, a causal link between Penk expression and vulnerability to heroin has yet to be established.

Methods

To investigate the functional significance of NAcsh  Penk tone, selective viral mediated knockdown and overexpression of Penk was performed, followed by analysis of subsequent heroin SA behavior. To determine whether adolescent THC exposure was associated with chromatin alteration, we analyzed levels of histone H3 methylation in the NAcsh via ChIP atfive sites flanking the Penk gene transcription start site.

Results

Here, we show that regulation of the proenkephalin (Penk) opioid neuropeptide gene in NAcsh directly regulates heroin SA behavior. Selective viral-mediated knockdown of Penk in striatopallidal neurons attenuates heroin SA in adolescent THC-exposed rats, whereas Penk overexpression potentiates heroin SA in THC-naïve rats. Furthermore, we report that adolescent THC exposure mediates Penk upregulation through reduction of histone H3 lysine 9 (H3K9) methylation in the NAcsh, thereby disrupting the normal developmental pattern of H3K9 methylation.

Conclusions

These data establish a direct association between THC-induced NAcsh Penk upregulation and heroin SA and indicate that epigenetic dysregulation of Penk underlies the long term effects of THC.

Source:  Biol Psychiatry. 2012 November 15; 72(10): 803–810. doi:10.1016/j.biopsych.2012.04.026.

Findings From A UK Birth Cohort

ABSTRACT

Background

Evidence on the role of cannabis as a gateway drug is inconsistent. We characterise patterns of cannabis use among UK teenagers aged 13–18 years, and assess their influence on problematic substance use at age 21 years.

Methods

We used longitudinal latent class analysis to derive trajectories of cannabis use from self-report measures in a UK birth cohort. We investigated (1) factors associated with latent class membership and (2) whether latent class membership predicted subsequent nicotine dependence, harmful alcohol use and recent use of other illicit drugs at age 21 years.

Results

5315 adolescents had three or more measures of cannabis use from age 13 to 18 years. Cannabis use patterns were captured as four latent classes corresponding to ‘non-users’ (80.1%), ‘late-onset occasional’ (14.2%), ‘early-onset occasional’ (2.3%) and ‘regular’ users (3.4%).

Sex, mother’s substance use, and child’s tobacco use, alcohol consumption and conduct problems were strongly associated with cannabis use.

At age 21 years, compared with the non-user class, late-onset occasional, early-onset occasional and regular cannabis user classes had higher odds of nicotine dependence (OR=3.5, 95% CI 0.7 to 17.9; OR=12.1, 95% CI 1.0 to 150.3; and OR=37.2, 95% CI 9.5 to 144.8, respectively); harmful alcohol consumption (OR=2.6, 95% CI 1.5 to 4.3; OR=5.0, 95% CI 2.1 to 12.1; and OR=2.6, 95% CI 1.0 to 7.1, respectively); and other illicit drug use (OR=22.7, 95% CI 11.3 to 45.7; OR=15.9, 95% CI 3.9 to 64.4; and OR=47.9, 95% CI 47.9 to 337.0, respectively).

Conclusions

One-fifth of the adolescents in our sample followed a pattern of occasional or regular cannabis use, and these young people were more likely to progress to harmful substance use behaviours in early adulthood.

Source:  http://dx.doi.org/10.1136/jech-2016-208503

ABSTRACT

PURPOSE:

Nationwide data have been lacking on drug abuse (DA)-associated mortality. We do not know the degree to which this excess mortality results from the characteristics of drug-abusing individuals or from the effects of DA itself.

METHOD:

DA was assessed from medical, criminal, and prescribed drug registries. Relative pairs discordant for DA were obtained from the Multi-Generation and Twin Registers. Mortality was obtained from the Swedish Mortality registry.

RESULTS:

We examined all individuals born in Sweden 1955-1980 (n = 2,696,253), 75,061 of whom developed DA. The mortality hazard ratio (mHR) (95% CIs) for DA was 11.36 (95% CIs, 11.07-11.66), substantially higher in non-medical (18.15, 17.51-18.82) than medical causes (8.05, 7.77-8.35) and stronger in women (12.13, 11.52-12.77) than in men (11.14, 10.82-11.47). Comorbid smoking and alcohol use disorder explained only a small proportion of the excess DA-associated mortality.

Co-relative analyses demonstrated substantial familial confounding in the DA-mortality association with the strongest direct effects seen in middle and late-middle ages. The mHR was highest for opiate abusers (24.57, 23.46-25.73), followed by sedatives (14.19, 13.11-15.36), cocaine/stimulants (12.01, 11.36-12.69), and cannabis (10.93, 9.94-12.03).

CONCLUSION:

The association between registry-ascertained DA and premature mortality is very strong and results from both non-medical and medical causes. This excess mortality arises both indirectly-from characteristics of drug-abusing persons-and directly from the effects of DA. Excess mortality of opiate abuse was substantially higher than that observed for all other drug classes. These results have implications for interventions seeking to reduce the large burden of DA-associated premature mortality.

Source:  https://www.ncbi.nlm.nih.gov/pubmed/28550519   May 2017

Ketamine Continues to Impress and Confound Researchers

A novel glutamatergic hypothesis of depression, using a 50-year-old anaesthesia medicine, has had a remarkable run as of late. First an anaesthetic, then a popular club drug in the 90s known as “Special K” (and currently still popular in Hong Kong as a “Rave Drug”), and now a novel, fast acting antidepressant, ketamine is a N-Methyl D-Aspartame (NMDA) receptor antagonist. Ketamine was FDA-approved in the U.S. as an anaesthetic nearly 50 years ago. It is used primarily by anaesthesiologists in both hospital and surgical settings. As an N-Methyl D-Aspartame (NMDA) receptor antagonist with dissociative properties, NMDA receptors possess high calcium permeability, which allows ketamine to reach its target quickly. Increasing clinical evidence has shown that a single sub-anaesthetic dose (0.5 mg/kg) of IV-infused ketamine exerts impressive antidepressant effects within hours of administration. These effects have stabilized suicidality in severely depressed, treatment-resistant individuals. The effects of low-dose ketamine infusion therapy can last up to seven days, although the dosing and patient characteristics regarding its optimal effectiveness have not been established.

In my book, “The Good News About Depression: Cures And Treatments In The New Age of Psychiatry”–Revised (1996), I said there was never a better time to be depressed, due in part to recent breakthroughs in understanding of the underlying biology of depression, plus the discovery of novel therapeutics e.g., the SSRIs. Today that book might be called the “Better News About Depression” as a result of the effectiveness of novel treatments such as Transcranial Magnetic Stimulation (TMS) and now ketamine, which has illuminated and broadened our understanding and view of treating depression.

Why Is This Better News?

New clinical and preclinical studies suggest that dysfunction of the glutamatergic system is perhaps more relevant and important than the current catecholamine hypothesis and therapy that targets serotonin, norepinephrine and sometimes dopamine. These medications often take four to six weeks to exert any therapeutic benefit, whereas rapid reductions in depressive symptoms have been observed in response to a single dose of ketamine. This is a vast departure from the SSRIs and SSNRIs that have occupied the mainstream of pharmacological therapy for depression and anxiety disorders for more than 30 years.

Lastly, the mechanism of action of NDMA antagonists are comparatively underexplored but vitally important to our understanding of depression, reversal of suicidality, as well as the debilitating, depressive symptoms induced by abuse of alcohol and other drugs. This review highlights the current evidence supporting the antidepressant effects of ketamine as well as other glutamatergic modulators, such as D-cycloserine, riluzole, CP-101,606, CERC-301 (previously known as MK-0657), basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide, GLYX-13, and esketamine. This all adds up to some very good news for depressed persons and especially those who do not respond to previous SSRI or SSNRI treatments.

Source: http://www.rivermendhealth.com/resources/ketamine-fast-acting-antidepressant/  June2017

 

One in 5 adolescents at risk of tobacco dependency, harmful alcohol consumption and illicit drug use

Researchers from the University of Bristol have found regular and occasional cannabis use as a teen is associated with a greater risk of other illicit drug taking in early adulthood.   The study by Bristol’s Population Health Science Institute, published online in the Journal of Epidemiology & Community Health, also found cannabis use was associated with harmful drinking and smoking.

Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), the researchers looked at levels of cannabis use during adolescence to determine whether these might predict other problematic substance misuse in early adulthood — by the age of 21.

The researchers looked at data about cannabis use among 5,315 teens between the ages of 13 and 18. At five time points approximately one year apart cannabis use was categorised as none; occasional (typically less than once a week); or frequent (typically once a week or more).

When the teens reached the age of 21, they were asked to say whether and how much they smoked and drank, and whether they had taken other illicit drugs during the previous three months. Some 462 reported recent illicit drug use: 176 (38%) had used cocaine; 278 (60%) had used ‘speed’ (amphetamines); 136 (30%) had used inhalants; 72 (16%) had used sedatives; 105 (23%) had used hallucinogens; and 25 (6%) had used opioids.

The study’s lead author, Dr Michelle Taylor from the School of Social and Community Medicine said:

“We tend to see clusters of different forms of substance misuse in adolescents and young people, and it has been argued that cannabis acts as a gateway to other drug use. However, historically the evidence has been inconsistent.

“I think the most important findings from this study are that one in five adolescents follow a pattern of occasional or regular cannabis use and that those individuals are more likely to be tobacco dependant, have harmful levels of alcohol consumption or use other illicit drugs in early adulthood.”

In all, complete data were available for 1571 people. Male sex, mother’s substance misuse and the child’s smoking, drinking, and behavioural problems before the age of 13 were all strongly associated with cannabis use during adolescence. Other potentially influential factors were also considered: housing tenure; mum’s education and number of children she had; her drinking and drug use; behavioural problems when the child was 11 and whether s/he had started smoking and/or drinking before the age of 13.

After taking account of other influential factors, those who used cannabis in their teens were at greater risk of problematic substance misuse by the age of 21 than those who didn’t.

Teens who regularly used cannabis were 37 times more likely to be nicotine dependent and three times more likely to have a harmful drinking pattern than non-users by the time they were 21. And they were 26 times more likely to use other illicit drugs.

Both those who used cannabis occasionally early in adolescence and those who starting using it much later during the teenage years had a heightened risk of nicotine dependence, harmful drinking, and other illicit drug use. And the more cannabis they used the greater was the likelihood of nicotine dependence by the age of 21.

This study used observational methods and therefore presents evidence for correlation but not does not determine clear cause and effect — whether the results observed are because cannabis use actually causes the use of other illicit drugs. Furthermore, it does not identify what the underlying mechanisms for this might be. Nevertheless, clear categories of use emerged.

Dr Taylor concludes:

“We have added further evidence that suggests adolescent cannabis use does predict later problematic substance use in early adulthood. From our study, we cannot say why this might be, and it is important that future research focuses on this question, as this will enable us to identify groups of individuals that might as risk and develop policy to advise people of the harms.

“Our study does not support or refute arguments for altering the legal status of cannabis use — especially since two of the outcomes are legal in the UK. This study and others do, however, lend support to public health strategies and interventions that aim to reduce cannabis exposure in young people.”

Journal Reference:

1. Michelle Taylor, Simon M Collin, Marcus R Munafò, John MacLeod, Matthew Hickman, Jon Heron. Patterns of cannabis use during adolescence and their association with harmful substance use behaviour: findings from a UK birth cohort. Journal of Epidemiology and Community Health, 2017; jech-2016-208503 DOI: 10.1136/jech-2016-208503

Source:   www.sciencedaily.com/releases/2017/06/170607222448<.htm>. 7 June 2017.

Patterns of illicit drug use in each UK country analysed in annual report

An overview of illicit drug use across the whole of the UK in 2016 has been published by the Home Office.

The ‘United Kingdom Drug Situation: Focal Point Annual Report 2016’ has collated data across all four home nations and includes specific analysis of policy, prevention, treatment, drug-related deaths, infectious diseases and drug markets.

Key points relating to the UK as a whole:

· Prevalence in the general population is lower now than ten years ago, with cannabis being the main driver of that reduction. However, there has been little change in recent years.

· Seizures data suggests that herbal cannabis has come to dominate the market. While resin was involved in around two-thirds of cannabis seizures in 2000, it was involved in only five per cent in 2015/16.

· Using the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) definition, which refers to deaths caused directly by the consumption of at least one illicit drug, the total number of drug-related deaths in the UK during 2014 was 2,655; a five per cent increase from 2013 and the highest number reported to date.

· Over the last decade the average age of death has increased from 37.6 years in 2004 to 41.6 in 2014, with males being younger than females (40.3 years and 44.6 years respectively). The largest proportion of deaths in the UK in 2014 was in the 40–44 years age group.

· There were 124,234 treatment presentations in the UK in 2015. This total includes for the first time, data from individuals presenting to treatment services in prisons in England.

· Benzodiazepines were cited as a primary problem substance in far greater proportion of cases in Scotland and Northern Ireland than in England or Wales, whereas Wales had a far higher proportion of clients citing amphetamines/methamphetamines than in any of the other countries.

· National Take-Home Naloxone programmes continue to supply naloxone to those exiting prison in Scotland and Wales: there were 932 kits issued by NHS staff in prisons in Scotland, and 146 in Wales, in 2015/16.

· There were 50 new diagnoses of HIV among people who inject drugs reported from Scotland, compared with 17 in 2014. This increase was due to an outbreak of HIV in people who inject drugs in Glasgow.

Source:  http://www.sdf.org.uk/patterns-illicit-drug-use-uk-country-analysed-annual-report/

Sirs,

I believe that a state’s Attorney General and Secretary of State have the obligation to reject any petition that is obviously in violation of any law.

Whether a ballot initiative is properly worded or not, if it proposes, facilitates or allows the violation of any law – it is illegal.

EXCERPT:  “In an opinion dated Tuesday and released Wednesday, Rutledge said the ballot title of the proposal is ambiguous and “that a number of additions or changes” are needed “to more fully and correctly summarize” the proposal.

“The proposal [to legalize recreational marijuana use in the state] by Larry Morris of West Fork would allow for the cultivation, production, distribution, sale and possession of marijuana for recreational use in Arkansas.”:

As you can readily see, Mr. Morris’ proposal would violate federal law and place persons who engage in any of those activities at risk of federal prosecution or other liability.

I draw to your attention a  LEGAL PRIMER(BELOW) ON: ENFORCING THE CONTROLLED SUBSTANCE ACT IN STATES THAT HAVE COMMERCIALIZED MARIJUANA by Mr. David Evans, Esq. in which he concludes that: “Anyone who participates in the growing, possession, manufacturing, distribution, or sales of marijuana under state law or aids or facilitates or finances such actions is at risk of federal prosecution or other liability.”

I ask that you continue to reject these illegal proposals to legalize marijuana in any form in our state of Arkansas.

I reiterate, it is your job to UPHOLD the LAW, not facilitate LAWBREAKING.

Jeanette McDougal

Board Member, Drug Watch, Intl.

Director, NAHAS – National Alliance of Health and Safety dems8692@aol.com

HUNTINGTON, W.Va. — Officer Sean Brinegar arrived at the house first — “People are coming here and dying,” the 911 caller had said — and found a man and a woman panicking. Two people were dead inside, they told him.

Brinegar, 25, has been on the force in this Appalachian city for less than three years, but as heroin use has surged, he has seen more than his fair share of overdoses. So last Monday, he grabbed a double pack of naloxone from his gear bag and headed inside.

A man was on the dining room floor, his thin body bluish-purple and skin abscesses betraying a history of drug use. He was dead, Brinegar thought, so the officer turned his attention to the woman on a bed. He could see her chest rising but didn’t get a response when he dug his knuckle into her sternum.

Brinegar gave the woman a dose of injected naloxone, the antidote that can jumpstart the breathing of someone who has overdosed on opioids, and returned to the man. The man sat up in response to Brinegar’s knuckle in his sternum — he was alive after all — but started to pass out again. Brinegar gave him the second dose of naloxone.

Maybe on an average day, when this Ohio River city of about 50,000 people sees two or three overdoses, that would have been it. But on this day, the calls kept coming.

Two more heroin overdoses at that house, three people found in surrounding yards. Three overdoses at the nearby public housing complex, another two up the hill from the complex.

From about 3:30 p.m. to 7 p.m., 26 people overdosed in Huntington, half of them in and around the Marcum Terrace apartment complex. The barrage occupied all the ambulances in the city and more than a shift’s worth of police officers.

By the end of it, though, all 26 people were alive. Authorities attributed that success to the cooperation among local agencies and the sad reality that they are well-practiced at responding to overdoses. Many officials did not seem surprised by the concentrated spike.

“It was kind of like any other day, just more of it,” said Dr. Clay Young, an emergency medicine doctor at Cabell Huntington Hospital.

But tragic news was coming. Around 8 p.m., paramedics responded to a report of cardiac arrest. The man later died at the hospital, and only then were officials told he had overdosed. On Wednesday, authorities found a person dead of an overdose elsewhere in Cabell County and think the death could have happened Monday. They are investigating whether those overdoses are tied to the others, potentially making them Nos. 27 and 28.

It’s possible that the rash of overdoses was caused by a particularly powerful batch of heroin or that a dearth of the drug in the days beforehand weakened people’s tolerance. But police suspect the heroin here was mixed with fentanyl, a synthetic opioid that is many times more potent than heroin. A wave of fatal overdoses signaled fentanyl’s arrival in Huntington in early 2015, and now some stashes aren’t heroin laced with fentanyl, but “fentanyl laced with heroin,” said Police Chief Joe Ciccarelli. Another possibility is carfentanil, another synthetic opioid, this one used to sedate elephants. Police didn’t recover drugs from any of the overdoses, but toxicology tests from the deaths could provide answers.

A battle-scarred city

In some ways, what happened in Huntington was as unremarkable as the spurts in overdoses that have occurred in other cities. This year, fentanyl or carfentanil killed a dozen people in Sacramento, nine people in Florida, and 23 people in about a month in Akron, Ohio. The list of cities goes on: New Haven, Conn.; Columbus, Ohio; Barre, Vt.

But what happened in Huntington stands out in other ways. It underlines the potential of a mysterious substance to unleash wide-scale trauma and overwhelm a city’s emergency response. And it suggests that a community that is doing all the right things to combat a worsening scourge can still get knocked back by it.

“From a policy perspective, we’re throwing everything we know at the problem,” said Dr. James Becker, the vice dean for governmental affairs and health care policy at the medical school at Marshall University here. “And yet the problem is one of those that takes a long time to change, and probably isn’t going to change for quite a while.”

Surrounded by rolling hills packed with lush trees, Huntington is one of the many fronts in the fight against an opioid epidemic that is killing almost 30,000 Americans a year. But this city, state, and region are among the most battle-scarred. West Virginia has the highest rate of fatal drug overdoses of any state and the highest rate of babies born dependent on opioids among the 28 states that report data. But even compared with other communities in West Virginia, Huntington sees above-average rates of heroin use, overdose deaths, and drug-dependent newborns. Local officials estimate up to 10 percent of residents use opioids improperly.

The heroin problem emerged about five years ago when authorities around the country cracked down on “pill mills” that sent pain medications into communities; officials here specifically point to a 2011 Florida law that arrested the flow of pills into the Huntington area.

As the pills became harder to obtain and harder to abuse, people turned to heroin. It has devoured many communities in Appalachia and beyond.

In Huntington, law enforcement initially took the lead, with police arresting hundreds of people. They seized thousands of grams of heroin. But it wasn’t making a dent. So in November 2014, local leaders established an office of drug control policy.

“As far as numbers of arrests and seizures, we were ahead of the game, but our problem was getting worse,” said Jim Johnson, director of the office and a former Huntington police officer. “It became very obvious that if we did not work on the demand side just as hard as the supply side, we were never going to see any success.”

The office brought together law enforcement, health officials, community and faith leaders, and experts from Marshall to try to tackle the problem together.

Changes in state law have opened naloxone dissemination to the public and protected people who report overdoses. But the city and its partners have gone further, rolling out programs through the municipal court system to encourage people to seek treatment. One program is designed to help women who work as prostitutes to feed their addiction. Huntington has eight of the state’s 28 medically assisted detox beds, and they’re always full.

Also, in 2014, a center called Lily’s Place opened in Huntington to wean babies from drugs. Last year, the local health department launched this conservative state’s first syringe exchange. The county, health officials know, is at risk for outbreaks of HIV and hepatitis C because of shared needles, so they are trying to get ahead of crises seen in other communities afflicted by addiction.

“Huntington just happens to have taken ownership of the problem, and very courageously started some programs … that have been models for the rest of the state,” said Kenneth Burner, the West Virginia coordinator for the Appalachia High Intensity Drug Trafficking Areas program.

‘A revolving door’

While paramedics in the area have carried naloxone for years, it was this spring that Huntington police officers were equipped with it. Just a few officers have administered it, but Monday was Brinegar’s third time reviving overdose victims with naloxone.

Paramedics, who first try reviving victims by pumping air with a bag through a mask, had to administer another 10 doses of naloxone Monday. Three doses went to one person, said Gordon Merry, the director of Cabell County Emergency Services. During the response, ambulances from stations outside Huntington were called into the city to assist the eight or so response teams already deployed.

Merry was clearly proud of the response, but also frustrated. He was tired, he said, of people whom emergency crews revived going back to drugs. Because of the power of their disease, saving their lives didn’t get at the root of their addiction.

“It’s a revolving door. We’re not solving the problem past reviving them,” he said. “We gave 26 people another chance on life, and hopefully one of those 26 will seek help.”

In the part of town where half the overdoses happened, some homes are well-kept, with gardens, bird feeders, and American flags billowing. “Home Sweet Home,” read an engraved piece of wood above one front door; in another front yard, a wooden sculpture presented a bear holding a fish with “WELCOME” written across its body.

But many structures are decrepit and have their windows blacked out with cardboard and sheets. At one boarded-up house, the metal slats that once made up an overhang for the front porch split apart and warped as they collapsed, like gnarled teeth. On the plywood that covered a window frame was a message spelled out in green dots: GIRL SCOUTS RULE.

In and around the public housing complex, which is made up of squat two-story brick buildings sloping up a hill, people either said they did not know what had happened Monday, or that “lowlifes” in another part of the complex sparked the problem. Even as paramedics were responding to the overdoses, police started raiding residences as part of their investigation, including apartments at the complex, the chief said.

Just up the hill, a man named Bill was sitting on a recliner on his front porch with his cat. He said he saw the police out in the area Monday, but doesn’t pay much attention to overdoses anymore. They are so frequent.

Bill, who is retired, asked to be identified only by his first name because he said he has a son in law enforcement. He has lived in that house for five decades and started locking his door only in recent years. His neighbors’ house had been broken into, and he had seen people using drugs in cars across the street from his house. He called the police sometimes, he said, but the users were always gone by the time the police arrived.

“I hate to say this, but you know, I’d let them die,” Bill said. “If they knew that no one was going to revive them, maybe they wouldn’t overdose.”

Even here, where addiction had touched so many lives, it’s not an uncommon sentiment. Addiction is still viewed by some as a bad personal choice made by bad people.

“Some folks in the community just didn’t care” that 26 of their fellow residents almost died, said Matt Boggs, the executive director of Recovery Point.  Recovery Point is a long-term recovery program that teaches “clients” to live a life without drugs or alcohol. Boggs himself is a graduate of the program, funded by the state and donations and grants.

The clients live in bunk rooms at the facility for an average of more than seven months before graduating. The program says that about two-thirds of graduates stay sober in the first year after graduation, and about 85 percent of those people are sober after two years.

Local officials praise Recovery Point, but like many other recovery programs, it is limited in what it can do. It has 100 beds for men at its location in Huntington, and is expanding at other sites in the state, but Boggs said there’s a waiting list of a couple hundred people.

Mike Thomas, 30, graduated from the main part of the program a month ago and is working as a peer mentor there as he transitions out of the facility. Thomas has been clean since Oct. 15, 2015, but has dreams about getting high or catches himself thinking he could spare $100 from his bank account for drugs.

Thomas hopes to find a full-time job helping addicts. His own recovery will be a lifelong process, one that can be torn apart by a single bad decision, he said. He will always be in recovery, never recovered.    “I’m not cured,” he said.

 

A killer that doesn’t discriminate

As heroin has bled into communities across the country, it has spread beyond the regular drug hotbeds in cities. On a 2004 map of drug use in Huntington — back then, mostly crack cocaine — a few blocks of the city glow red. Almost the entire city glows in yellows and reds on the 2014 map.

In 2015, there were more than 700 drug overdose calls in Huntington, ranging from kids in their early teens to seniors in their late 70s. In 2014, it was 272 calls; in 2012, 146. One bright spot: fatal overdoses, which stood at 58 in 2015, have ticked down so far this year.

“I used to be able to say, ‘We need to focus here,’” said Scott Lemley, a criminal intelligence analyst at the police department. “I can’t do that anymore.”

Heroin hasn’t just dismantled geographic barriers. It has infiltrated every demographic “It doesn’t discriminate.   Prominent businessmen, their child. Police officers, their child. Doctors, their child,” Merry said. “The businessman and police officer do not have their child anymore.”

The businessman is Teddy Johnson. His son, Adam, died in 2007 when he was 22, one of a dozen people who died in a five-month period because of an influx of black-tar heroin. The drug hadn’t made its full resurgence into the region yet, but now, Johnson sees the drug that killed his son everywhere.

 

Teddy Johnson lost his son, Adam, in 2007 to a heroin overdose. He has several tattoos dedicated to Adam’s memory.  He runs a plumbing, heating, and kitchen fixture and remodelling business. From his storefront, he has witnessed deals across the street.

Adam, who was a student at Marshall, was a musician and artist who hosted radio shows. He was the life of any party, his dad said.

Johnson was describing Adam as he sat at the marble countertop of a model kitchen in his business last week. With the photos of his kids on the counter, it felt like a family’s home. Johnson explained how he still kept Adam’s bed made, how he kept his son’s room the same, and then he began to cry.

“The biggest star in the sky we say is Adam’s star,” he said. “When we’re in the car — and it can’t be this way — but it always seems to be in front of us, guiding us.”

Adam’s grave is at the top of a hill near the memorial to the 75 people — Marshall football players, staff, and fans — who died in a 1970 plane crash. It’s a beautiful spot that Johnson visits a few times each week, bringing flowers and cutting the grass around his son’s grave himself. Recently a note was left there from a couple Johnson knows who

just lost their son to an overdose; they were asking Adam to look out for their son in heaven.

But even here, at what should be a respite, Johnson can’t escape what took his son. He said he has seen deals happen in the cemetery, and he recently found a burnt spoon not more than 20 feet from his son’s grave.

Johnson keeps fresh flowers on his son’s grave and cuts the grass around the grave himself.

“I’ve just seen too much of it,” he said.

If Huntington doesn’t have a handle on heroin, at least the initiatives are helping officials understand the scale of the problem. More than 1,700 people have come through the syringe exchange since it opened, where they receive a medical assessment and learn about recovery options. The exchange is open one day a week, and in less than a year, it has distributed 150,000 clean syringes and received 125,000 used syringes.

But to grow and sustain its programs, Huntington needs money, officials say. The community has received federal grants, and state officials know they have a problem. But economic losses and the collapse of the coal industry that fueled the drug epidemic have also depleted state coffers.

“We have programs ready to launch, and we have no resources to launch them with,” said Dr. Michael Kilkenny, the physician director of the Cabell-Huntington Health Department. “We’re launching them without resources, because our people are dying, and we can’t tolerate that.”

In some ways, Huntington is fortunate. It has a university with medical and pharmacy schools enlisted to help, and a mayor’s office and police department collaborating with public health officials. But what does that herald then for other communities?

“If I feel anxious about what happens in Huntington and in Cabell County, I cannot imagine what it must be like to live in one of these other at-risk counties in the United States, where they don’t have all those resources, they don’t have people thinking about it,” said Dr. Kevin Yingling, the dean of the Marshall University School of Pharmacy.

Yingling, Kilkenny, and others were gathered on Friday afternoon to talk about the situation in Huntington, including the rash of overdoses. But by then, there was already a different incident to discuss.

A car had crashed into a tree earlier that afternoon in Huntington. A man in the driver seat and a woman in the passenger seat had both overdosed and needed naloxone to be revived. A preschool-age girl was in the back seat.

Source:    https://www.statnews.com/2016/08/22/heroin-huntington-west-virginia-overdoses/ 22.08.16

In this guest blog, Kate Fleming, Senior Lecturer, Public Health Institute, Liverpool John Moores University, and Raja Mukherjee, Consultant Psychiatrist, Lead Clinician UK National FASD clinic, Surrey and Borders Partnership NHS Foundation Trust consider the context and future for Foetal Alcohol Spectrum Disorders in the UK.

A recent opinion piece in The Guardian entitled Nothing prepared me for pregnancy- apart from the never ending hangover of my 20s took a, presumably, humorous take on the tiredness, vomiting, dehydration, and secrecy that so many women live through in early pregnancy, likening this to days spent hungover after excessive drinking in the author’s early 20s.

In an article that was entirely about alcohol and pregnancy there was reassuringly no mention of the author consuming alcohol during pregnancy, indeed quite the reverse “I don’t actually want booze in my body”.  But neither was there explicit reference to the harms that alcohol can cause in pregnancy.

The harms caused by consuming alcohol in pregnancy

Foetal Alcohol Spectrum Disorders (FASD) is an umbrella term that encompasses the broad range of conditions that are related to maternal alcohol consumption.  The most severe end of the spectrum is Foetal Alcohol Syndrome (FAS) associated with distinct facial characteristics, growth restriction and permanent brain damage.  However, the spectrum includes conditions displaying mental, behavioural and physical effects on a child which can be difficult to diagnose.  Confusingly, these conditions also go under several other names including Neuro-developmental Disorder associated with Prenatal Alcohol Exposure (ND-PAE) the preferred term by the American Psychiatric Association’s fifth version of its Diagnostic and Statistical Manual (APA DSM-V), alcohol-related birth defects, alcohol-related neuro-developmental disorder, and partial foetal alcohol syndrome.

How common is FASD? A recent study which brought together information from over 300 studies estimates the prevalence of drinking in pregnancy to be close to 10%, and around 1 in 4 women in Europe drinking during pregnancy. Their estimates of FAS (the most severe end of the spectrum) were 14.6 per 10000 people worldwide or 37.4 per 10000 people in Europe, corresponding to 1 child in every 67 women who drank being born with FAS.

Given the figure for alcohol consumption in pregnancy is even higher in the UK, with some studies suggesting up to 75% of women drink at some point in their pregnancy, conservatively in the UK we might expect a prevalence of FASD of at least 1%.  We also know that it is highly unlikely that anything close to this number of individuals have formally had a diagnosis.  This lack of knowledge of the prevalence in the UK is hampering efforts to ensure the required multi-sector support for those affected by FASD and their families.

Current policy

For some time a significant focus of alcohol in pregnancy research was to try and identify a safe threshold of consumption, without demonstrable success.  No evidence of harm at low levels does not however equate to evidence of no harm and as such in 2016 the Chief Medical Officer revised guidance on alcohol consumption in pregnancy to recommend that women should avoid alcohol when trying to conceive or when pregnant.  Though this clarity of guidelines has been well received by the overwhelming majority of health professionals there are barriers to its implementation with few professionals “very prepared to deal with the subject”.  In addition, knowledge of the guideline amongst the general public has yet to be evaluated.

As part of the 2011 public health responsibility deal a commitment to 80% of products having labels which include warnings about drinking when pregnant forms part of the alcohol pledges. A study in 2014 showed that 90% of all labels did indeed include this information. However, it has also been shown that this form of education is amongst the least effective in terms of alcohol interventions, and the pledge is no longer in effect.

Pregnancy is recognised as a good time for the initiation of behaviour change yet in the context of alcohol consumption it is arguably too late. An estimated half of all pregnancies are unplanned and there remains therefore a window of early pregnancy before a woman is likely to have had contact with a health professional and before the guidelines can be explained during which unintentional damage to her unborn baby could occur.  The same argument can be used when considering the suggestion of banning the sale of alcohol to pregnant women – visible identification of pregnancy tends only to be possible at the very latest stages.

How then to address consumption of alcohol during pregnancy? 

Consumption of alcohol is doubtless shaped by the culture and context of the society in which one is living.  Highest levels of alcohol consumption in pregnancy are, unsurprisingly, seen in countries where the population consumption of alcohol is also highest.  Current UK policy that is directed to reducing population consumption of alcohol will likely have a knock-on effect of reducing alcohol consumption in pregnancy.

Many women will however be familiar with the barrage of questions that they encounter when not drinking on a night out.  From the not-so-subtle “Not drinking, eh… Wonder why that is? <nudge, nudge, wink, wink>” to the more overt “Are you pregnant?”.  The road to conception and pregnancy is littered with enough stumbling blocks and pressures that the additional unintentional announcement of either fact of conception or intention to conceive is an unnecessary cause of potential further anxiety. Until society accepts that not drinking is an acceptable choice, without any need for clarification or explanation, then pregnant women or those hoping to conceive who are adhering to guidelines will continue to identify themselves, perhaps before they want to.

What next?

The UK’s All Party Parliamentary Group for FASD had its inaugural meeting in June 2015.  This group calls for an increased awareness of FASD particularly regarding looked

after children and individuals within the criminal justice system, sectors where the prevalence of FASD is particularly high. Concerted efforts need to be made to identify children with FASD to ensure that the appropriate support pathways are in place. Alongside this, efforts to ensure the best mechanisms for education of the dangers of alcohol consumption in pregnancy need to be increased, including training for midwives, and other health professionals who may be able to offer brief intervention and advice to women both before and after conception.

The views expressed by the authors are theirs alone and do not represent the views of Liverpool John Moores University, the UK National FASD clinic at Surrey and Borders Partnership NHS Foundation Trust. NOFAS run a national FASD helpline on on 020 8458 5951 as do the FASD Trust on 01608 811 599.

Source:  http://www.alcoholpolicy.net/2017/05/drinking-in-pregnancy-where-next-for-fasd-in-the-uk.html

Addiction Advocacy Needs A Bill Gates, David Geffen, Warren Buffett, Or Tom Steyer

Addiction doesn’t need someone to put their name on a building, or name a research institute. Addiction desperately needs bold philanthropists who want to leverage the people power of the grassroots. Addiction and drug overdoses claim one life every four minutes in America. In the time it takes to order a latte, someone dies—from an illness that is highly treatable. The addiction crisis is the result of social prejudice; criminal justice policies that incarcerate people with addiction instead of giving them treatment; health care policies that make it difficult or impossible to get medical help for substance use disorders; ignorance; and “abstinence-only” drug policies that are ineffective and backwards.

The fact is, people who struggle with substance use disorder are treated like second-class citizens. Admitting there’s a problem can mean losing your job, home, and custody of your children. That makes addiction a civil rights issue. And, thanks to the work of advocates across the nation, it’s finally being recognized as a moral issue, as well. Thought leaders like Tom Steyer are helping to drive this message home. I first met Tom during the Democratic National Convention. I had just shared my experience with addiction and recovery when Tom approached me. I was taken aback by the story he shared. He, too, lost someone very dear to him due to addiction: his best friend, who struggled with addiction for decades. His friend contracted HIV and Hepatitis C through drug use, and died of medical complications due to his illnesses. A few months later, Tom joined me at the Facing Addiction in America summit in Los Angeles, where we invited him to share his story on stage with the U.S. Surgeon General. As Tom talked, tears filled my eyes. He said, “We must embrace our shared humanity and recognize that addiction is a deadly, chronic illness, not a personal failing.” I’d lost friends, too. I was at risk, too. It was time to bridge the gap between policies and public awareness.

People like Tom Steyer and other pioneering philanthropists, who give tens of millions to progressive causes such as medical research, environmental causes, and water quality, must also step up to end the addiction crisis in America. Our fight is America’s fight. The sooner they do, the quicker we can heal this nation from our generation’s most urgent public health crisis.

Working alongside lobbyists, nonprofit groups, social organizers, and peer recovery groups, they can help fill the gaps left by policies and laws that omit or punish people with substance use disorder. As the current administration takes steps toward a health care bill that will leave people suffering from addiction without medical care, these philanthropic giants are in a unique position to help. Why? Because their involvement would not be tied to political party or personal gain. Rather, they would focus on the solution, plain and simple.

Addiction should be one of the issues on the list of social problems we urgently address, next to finding a cure for cancer and ending childhood hunger. Addiction permeates the social fabric of America. Nobody is exempt. As many people suffer from addiction as diabetes; more people use pain medications than tobacco products. For every person who’s developed full blown substance use disorder, another dozen are on the road to addiction. Substance use disorder affects every corner of society, including our collective health, family unity, the economy, workplace productivity, and our reliance on social programs. It also keeps jails full of people who may struggle to find jobs to support their families once they’re released, and will never be able to vote again.

The recovery advocacy movement has been built slowly, through the efforts of individuals and highly fragmented groups. We have an incredible grassroots movement that addresses an issue that directly impacts one in every three families in America, and indirectly touches all of us. But fundraising for recovery advocacy has been largely through family and friend donations—which, although heartfelt, aren’t sufficient to fund serious research, create desperately needed social infrastructure, or provide education about the true nature of addiction. While organizations dedicated to battling cancer, heart disease, and diabetes raise hundreds of millions of dollars annually, the “addiction field,” such as it is, raises perhaps $25 million from private sources. This is unconscionable.

Gates, Geffen, Buffett, Steyer, and other philanthropic giants have the potential to be visionaries in this space. They could quickly stem the addiction epidemic without waiting for policy makers to hammer out yet another law that places people’s recovery at risk. They could find the solution that keeps families intact. With their help, nobody will lose another friend to this disease or the health problems that come with it. Bob and Suzanne Wright demonstrated the power and possibility of this kind of giving when they funded Autism Speaks. Their philanthropy helped move autism front and center: why not do the same for addiction?

What will our society, our culture, be like when we finally take addiction out of the equation? For many people, and their families, the answer is coming much too slowly.

It’s time to apply our knowledge, build a coalition, and offer the solutions our country so desperately needs. It’s time to change the framework of this crisis and confront our deepest values. Instead of punishment, we need to help the people who are sick—dying from this illness. It’s time to work together and end America’s addiction crisis for good.

What we need now is for America’s philanthropic visionaries to step up to help us dramatically accelerate the pace of progress in this urgent effort. Addiction doesn’t need someone to put their name on a building, or name a research institute. Addiction desperately needs bold philanthropists who want to leverage the people power of the grassroots. Ryan Hampton is an outreach lead and recovery advocate at Facing Addiction, a leading nonprofit dedicated to ending the addiction crisis in the United States.

Source:  http://www.huffingtonpost.com/entry/addiction-advocacy-needs-a-bill-gates-david-geffen_us_592ddfaae4b075342b52c0f5   30th May 20127

SAN FRANCISCO – Visits by teens to a Colorado children’s hospital emergency department and its satellite urgent care centers increased rapidly after legalization of marijuana for commercialized medical and recreational use, according to new research being presented at the 2017 Paediatric Academic Societies Meeting in San Francisco.

The study abstract, “Impact of Marijuana Legalization in Colorado on Adolescent Emergency Visits” on Monday, May 8 at the Moscone West Convention Center in San Francisco.

Colorado legalized the commercialization of medical marijuana in 2010 and recreational marijuana use in 2014. For the study, researchers reviewed the hospital system’s emergency department and urgent care records for 13- to 21-year-olds seen between January 2005 and June 2015.

They found that the annual number of visits with a cannabis related diagnostic code or positive for marijuana from a urine drug screen more than quadrupled during the decade, from 146 in 2005 to 639 in 2014.

Adolescents with symptoms of mental illness accounted for a large proportion (66%) of the 3,443 marijuana-related visits during the study period, said lead author George Sam Wang, M.D., FAAP, with psychiatry consultations increasing from 65 to 442. More than half also had positive urine drug screen tests for other drugs. Ethanol, amphetamines, benzodiazepines, opiates and cocaine were the most commonly detected.

Dr. Wang, an assistant professor of paediatrics at the University of Colorado Anschutz Medical Campus, said national data on teen marijuana use suggest rates remained roughly the same (about 7%) in 2015 as they’d been for a decade prior, with many concluding no significant impact from legalization. Based on the findings of his study, however, he said he suspects these national surveys do not entirely reflect the effect legalization may be having on teen usage.

“The state-level effect of marijuana legalization on adolescent use has only begun to be evaluated,” he said. “As our results suggest, targeted marijuana education and prevention strategies are necessary to reduce the significant public health impact of the drug can have on adolescent populations, particularly on mental health.”

Dr. Wang will present the abstract, “Impact of Marijuana Legalization in Colorado on Adolescent Emergency Department (ED) Visits,” from 8 a.m. to 10 a.m. Numbers in this news release reflect updated information provided by the researchers. The abstract is available at https://registration.pas-meeting.org/2017/reports/rptPAS17_abstract.asp?abstract_final_id=3160.11.

The Paediatric Academic Societies (PAS) Meeting brings together thousands of individuals united by a common mission: to improve child health and well-being worldwide. This international gathering includes paediatric researchers, leaders in academic paediatrics, experts in child health, and practitioners. The PAS Meeting is produced through a partnership of four organizations leading the advancement of paediatric research and child advocacy: Academic Paediatric Association, American Academy of Paediatrics, American Paediatric Society, and Society for Paediatric Research. For more information, visit the PAS Meeting online at www.pas-meeting.org, follow us on Twitter @PASMeeting and #pasm17, or like us on Facebook. For additional AAP News coverage, visit http://www.aappublications.org/collection/pas-meeting-updates.

Source:   http://www.aappublications.org/news/2017/05/04/PASMarijuana050417

 A New Agenda to  Turn Back the Drug Epidemic

Robert L. DuPont, MD, President , Institute for Behavior and Health, Inc.

A. Thomas McLellan, PhD, Senior Strategy Advisor , Institute for Behavior and Health, Inc.  May 2017

Institute for Behavior and Health, Inc. , 6191 Executive Blvd , Rockville, MD 20852 , www.IBHinc.org 1

Background 

The Institute for Behavior and Health, Inc. (IBH) is a 501(c)3 non-profit substance use policy and research organization that was founded in 1978. Non-partisan and non-political, IBH develops new ideas and serves as a force for change.

Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs and Health was published in November 2016. Four months later, in March 2017, IBH held a meeting of 25 leaders in addiction treatment, health care, insurance, government and research to discuss the scope and implications of this historic document. The US Surgeon General, VADM Vivek H. Murthy, MD, was an active participant in the meeting. The significance of this new Surgeon General’s Report is analogous to the historic 1964 Surgeon General’s report, Smoking and Health, a document that inspired an extraordinarily successful public health response in the United States that has reduced the rates of cigarette smoking by over 64% and continues its impact even today, more than 50 years following its release.

The following is a summary of the discussion at the March 2017 meeting and the conclusions and recommendations that were developed.

Introduction: The 2016 Surgeon General’s Report 

The two primary objectives of the US Surgeon General’s Report of 2016 are first to provide scientific evidence that shows that in addition to nicotine, other substance misuse and addiction issues (e.g., alcohol, opioids, marijuana, etc.) also are best understood and addressed as public health problems; and second to encourage the inclusion of addiction – its prevention, early recognition and intervention, treatment and active long-term recovery management – into the mainstream of American health care. At present these elements are not integrated either as a stand-alone continuum or within the general medical system. As is true for other widespread illnesses, addiction to nicotine, alcohol, marijuana, opioids, cocaine and other substances is a serious chronic illness. This perspective is contrary to the common perception that addiction reflects a moral failing, a personal weakness or poor parenting. Such opinions have stigmatized individuals who are suffering from these often deadly substance use disorders and have led to expensive and ineffective public policies that segregate prevention and treatment outside of mainstream medical care. A better public health approach encourages afflicted individuals and their family members to seek and receive help within the current health care system for these serious health problems.

An informed public health approach to reducing the prevalence and the harms associated with substance use disorders requires more than the brief treatment of serious cases. Particularly important are substance use prevention programs in schools, healthcare and in all other parts of the community to protect adolescents (ages 12 – 21), the group most at risk for the initiation of substance-related harms and substance use disorders.  Importantly, abundant tragic experience and accumulating science show that substance use disorders are not effectively treated with only short-term care. Because substance use disorders produce 2 significant long-lasting changes in the brain circuits responsible for memory, motivation, inhibition, reward sensitivity and stress tolerance, addicted individuals remain vulnerable to relapse years following specialized treatment.1, 2, 3 Thus, as is true for all other chronic illnesses, long periods of personalized treatment and monitoring are necessary to assure compliance with care, continued sobriety, and improved health and social function. In combination, science-based prevention, early intervention, continuing care and monitoring comprise a modern continuum of public health care. The overall goals of this continuum comport well with those of other chronic illnesses:

1 US Department of Health and Human Services (HHS), Office of the Surgeon General. (2016). Chapter 2. The Neurobiology of Substance Use, Misuse, and Addiction. In: Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS. Available: https://addiction.surgeongeneral.gov/

2 US Department of Health and Human Services (HHS), Office of the Surgeon General. (2016). Chapter 5. Recovery: The Many Paths to Wellness. In: Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS. Available: https://addiction.surgeongeneral.gov/

3 Betty Ford Institute Consensus Panel. (2007). What is recovery? A working definition from the Betty Ford Institute. Journal of Substance Abuse Treatment, 33(3), 221-228.

4 White, W. L. (2012). Recovery/remission from substance use disorders: An analysis of reported outcomes in 415 scientific reports, 1868-2011. Philadelphia, PA: Philadelphia Department of Behavioral Health and Intellectual Disability Services.

· sustained reduction of the cardinal symptom of the illness, i.e., substance use;

· improved general health and function; and,

· education and training of the patient and the family to self-manage the illness and avoid relapses.

In the addiction field achieving these goals is called “recovery.” This word is used to describe abstention from the use of alcohol, marijuana and other non-prescribed drugs as well as improved personal health and social responsibility.3,4 Over 25 million formerly addicted Americans are in stable, long-term recovery of a year or longer.4 Understanding how to consistently accomplish the life-saving goal of recovery must inform health care decisions.

The 2016 Surgeon General’s Report offers a science-informed vision and path to recovery in response to the nation’s serious addiction problem, including specifically the opioid overdose epidemic. Research shows that it is possible to prevent or delay most cases of substance misuse; and to effectively treat even the most serious substance use disorders with recovery as an expectable result of comprehensive, continuous care and sustained monitoring. To do this, substance use disorders must be recognized as serious, chronic health conditions that are both preventable and treatable. The nation must integrate the short-term siloed episodes of specialty treatment that now are isolated from mainstream healthcare into a fully integrated continuum of care comparable to that currently available to those with other chronic illnesses such as diabetes, hypertension, asthma and chronic pain.

Meeting Discussion and Conclusions 

The Surgeon General’s Report and the meeting convened by the Institute for Behavior and Health, Inc. (IBH) to promote its recommendations are significant responses to the expanding epidemic of opioid 3 and other substance use disorders, an epidemic that struck nearly 21 million Americans aged 12 and older in 2015 alone.5 That year saw more than 52,000 overdose deaths.6 This drug epidemic has devastated countless families and communities throughout the US. Unlike earlier and smaller drug epidemics, the current opioid epidemic is not limited to a few regions or communities or a narrow range of ethnicities or incomes in the United States. Instead it afflicts all communities and all socioeconomic groups; its impacts include smaller communities and rural areas as well as suburban areas and inner cities. Fuelled by the suffering of countless grieving families, the nation is in the early stages of confronting the new epidemic. A growing national determination to turn back this deadly epidemic has opened the door to innovation that is sustained by strong bipartisan political support for new and improved efforts in both prevention and treatment of substance use disorders.

5 Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15-4927, NSDUH Series H-50). Available: http://www.samhsa.gov/data/

6 Rudd, R. A., Seth, P., David, F., & Scholl, L. (2016, December 30). Increases in drug and opioid-involved overdose deaths – United States. Morbidity and Mortality Weekly Report, 65(50-51), 1445-1452. Available: https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm

7 Levy, S. J., Williams, J. F., & AAP Committee on Substance Use and Prevention. (2016). Substance use screening, brief intervention, and referral to treatment. Pediatrics, 138(1), e20161211. Available: http://pediatrics.aappublications.org/content/138/1/e20161211

8 US Department of Health and Human Services (HHS), Office of the Surgeon General. (2016). Chapter 3. Prevention Programs and Policies. In: Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS. Available: https://addiction.surgeongeneral.gov/

Abstinence is an Achievable Goal, both for Prevention and for Treatment 

Embracing and synthesizing the 30 years of science supporting the findings of the 2016 Surgeon General’s Report, the group discussed a single goal for the prevention of addiction: no use of alcohol, nicotine, marijuana or other non-prescribed drugs by youth for reasons of health. This goal should be the core prevention message to all children from a very young age. Health care professionals, educators and parents should understand the importance of this simple, clear health message. They should continue to reinforce this message of no-use for health as children grow to adulthood. Even when prevention fails, it is possible for parents, other family members, friends, primary care clinicians, educators and others to identify and to intervene quickly to stop youth substance use from becoming addiction.7

The science behind this ambitious but attainable prevention goal is clear. Alcohol, nicotine products, marijuana and other non-prescribed drug use is uniquely harmful to the still-developing brains of adolescents. Thus any substance “use” among youth must be considered “misuse” – use that may harm self or others. The goal of no substance use is not just for the purpose of preventing addiction, though that is one clear and important by product of successful prevention. Addiction is a biological process that can take years to develop. In contrast, even a single episode of high-dose use of alcohol or other substance could immediately produce an injury, accident or even death. While it is true that most episodes of substance misuse among adults do not produce serious problems, it is also true that substance misuse is associated with 70% or more of the injuries, disabilities and deaths of young people.8 These figures are even higher for minority youth. Many adolescent deaths are preventable 4 because most are related to substance use – including substance-related motor vehicle crashes and overdose.9

9 Subramaniam, G. A., & Volkow, N. D. (2014). Substance misuse among adolescents. To screen or not to screen? JAMA Pediatrics, 168(9), 798-799. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827336/

10 Data analyzed by the Center for Behavioral Health Statistics and Quality. CBHS. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15- 4927, NSDUH Series H-50).

11 2014 data obtained by IBH from the Monitoring the Future study. For discussion of data through 2013 see DuPont, R. L. (2015, July 1). It’s time to re-think prevention; increasing percentages of adolescents understand they should not use any addicting substances. Rockville, MD: Institute for Behavior and Health, Inc. Available: https://www.ibhinc.org/s/IBH_Commentary_Adolescents_No_Use_of_Substances_7-1-15.pdf

Youth who use any one of the three most common “gateway” substances, i.e., alcohol, nicotine and marijuana, are many times more likely than those who do not use that single drug to use the other two substances as well as other illegal drugs.10 The use of any drug opens the door to an endless series of highly risky decisions about which drugs to use, how much to use, and when to use them. This perspective validates the public health goal for youth of no use of any drug.

Complete abstinence from the use of alcohol or any other drug among adolescents is not simply an idealistic goal – it is a goal that can be achieved. Data were presented at the meeting from the nationally representative Monitoring the Future study showing that 26% of American high school seniors in 2014 reported no use of alcohol, cigarettes, marijuana or other non-prescribed drugs in their lifetimes. 11 This is a remarkable increase from only 3% reported by American high school seniors in 1983. Moreover, in the same survey, 50% of high school seniors had not used any alcohol, cigarettes, marijuana or other non-prescribed substance in the past 30 days, up from 16% in 1982. These largely overlooked and important findings show that youth abstinence from any substance use is already widespread and steadily increasing.

In parallel with the goal of abstinence for prevention, the recommended goal for the treatment of those who are addicted is sustained abstinence from the use of alcohol and other drugs, with the caveat, explicitly acknowledged by the group, that individuals who are taking medications as-prescribed in the treatment of substance use disorders (e.g., buprenorphine, methadone and naltrexone) and who do not use alcohol or other non-prescribed addictive substances – are considered to be abstinent and ”in recovery.” Abstinence from all non-prescribed substance use is the scientifically-informed goal for individuals in addiction treatment. This treatment goal is widely accepted in the large national recovery community. The long-lasting effects of addiction to drugs are easily seen among cigarette smokers: smoking only a single cigarette is a serious threat to the former smoker, even decades after smoking the last cigarette. There is incontrovertible evidence from brain and genetic research showing the long-term effects of substance misuse on critical brain regions.2 It is unknown when or if these brain changes will return to being entirely normal following cessation of substance use; however, it is known that the recovering brain is particularly vulnerable to the effects of return to any substance use, often leading to overdose or rapid re-addiction. 5

Participants in the IBH meeting supported the idea that abstinence is the high-value outcome in addiction treatment; and that while any duration of abstinence is valuable, longer-term, stable abstinence of 5 years is analogous to the widely-used standard in cancer treatment of 5-year survival. The scientific basis for the value of sustained recovery is validated by the experience of the estimated 25 million Americans now in recovery. This increasingly visible recovery community is a remarkable and very positive new force in the country.

Measuring and Attaining these Goals 

The mantra from the IBH meeting was, if you don’t measure it, it won’t happen. The group of leaders recognized the paucity of current models for systematic integration of addiction treatment and general healthcare. The group encouraged the identification of promising models and the promotion of innovation to achieve the goal of sustained recovery. Even programs that include fully integrated care of other diseases, managed care and other comprehensive health programs do not reliably achieve the goal of sustained or even temporary recovery for substance use disorders. The meeting participants noted the absence of long-term outcome studies of the treatment of substance use disorders and encouraged all treatment programs not only to extend the care of discharged patients but also to systematically study the trajectories of discharged patients to improve their long-term treatment outcomes. The increasing range of recovery support services after treatment is an important and promising new trend that is now actively promoting sustained recovery.

Meeting participants noted one particularly promising model of public health goal measurement and attainment – the 90-90-90 goals for the treatment of HIV/AIDS: 90% of people with HIV will be screened to know their infection status; 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy; and 90% of all patients receiving antiretroviral therapy will have viral suppression (i.e., zero viral load).12 These measurable goals provide an operational definition of public health success for the country, states and individual healthcare organizations.

12 UNAIDS. (2014). 90-90-90: An Ambitious Treatment Target to Help End the AIDS epidemic. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS. Available: http://www.unaids.org/sites/default/files/media_asset/90-90-90_en_0.pdf

With this model as background, the IBH group concluded that a similar public health approach and similarly specific numeric goals should be established for preventing and treating substance use disorders. Examples of parallel national prevention goals could include 90% rates of screening for substance misuse among adolescents; 90% provision of interventions and follow-up for those screening positive; and 90% total abstinence rates among youth aged 12-21. While these are admittedly ambitious prevention goals, adoption of them could incentivize families, schools and communities to increase the percentage of youth who do not use any alcohol, nicotine, marijuana or other drugs every year.

A similar approach was adopted by the IBH group to improve the impact of addiction treatment. Again, there would be significant public health value if the US adopted the following goals: 90% of individuals aged 12 or older receive annual screening for substance misuse and substance use disorders; 90% of those who receive a diagnosis of a substance use disorder are referred and meaningfully engaged (at 6 least three sessions) in some form of addiction treatment; and 90% of those engaged in treatment achieve sustained abstinence as measured by drug testing, during and for six months following treatment.

Source:  IBH-Report-A-New-Agenda-to-Turn-Back-the-Drug-Epidemic  May 2017

In Southern Ohio, the number of drug-exposed babies in child protection custody has jumped over 200%.  The problem is so dire that workers agreed to break protocol to invite a reporter to hear their stories.  Foster care placements are at record levels, and the number of drug-exposed newborns in their custody has jumped over 200% in the past decade

Inside the Clinton County child protection office, the week has been tougher than most.

Caseworkers in this thinly populated region of southern Ohio, east of Cincinnati, have grown battle-weary from an opioid epidemic that’s leaving behind a generation of traumatized children. Drugs now account for nearly 80% of their cases. Foster-care placements are at record levels, and the number of drug-exposed newborns in their custody has jumped over 200% in the past decade. Funding, meanwhile, hasn’t budged in years.

“Many of our children have experienced such high levels of trauma that they can’t go into traditional foster homes,” said Kathi Spirk, director of Clinton County job and family services. “They need more specialized care, which is very expensive.”

The problem is so dire that workers agreed to break protocol and invite a reporter to camp out in a conference room and hear their stories. For three days, they relived their worst cases and unloaded their frustrations, in scenes that played out like marathon group therapy, for which they have no time. Many agreed that talking about it only made them feel worse, yet still they continued, one after another.

Hence the bad week.

Given the small size of their community, they asked that their names be changed out of concern for their own safety and the privacy of the children.

The caseworkers, like most, are seasoned in despair. Many worked in the 1990s when crack cocaine first arrived, followed by crystal meth in the early 2000s. In 2008, after the shipping giant DHL shuttered its domestic hub here in Wilmington and shed more than 7,000 jobs, prescription pill mills flourished while the economy staggered. Back then, a typical month saw 30 open cases, only a few of them drug-related. But the flood of cheap heroin and fentanyl, now at its highest point yet, has changed everything. A typical month now brings four times as many cases, while institutional knowledge has been flipped on its head.

“At least with meth and cocaine, there was a fight,” said Laura, a supervisor with over 20 years of experience. “Parents used to challenge you to not take their kids. And now you have them say: ‘Here’s their stuff. Here’s their formula and clothes.’ They’re just done. They’re not going to fight you any more.”

Heroin has changed how they approach every step of their jobs, they said, from the first intake calls to that painstaking decision to place a child into temporary foster care or permanent custody. Intake workers now fear what used to be routine.

“Occasionally, we’d get thrown a dirty house, something easy to close and with little trauma to the child,” said Leslie, another worker. “We’re not getting those any more.

Now they’re all serious, and most of them have a drug component. So you may get a dirty house, but it’s never just a dirty house.”

‘I had a four-year old whose mom had died in front of her and she described it like it was nothing’ Children come into the system in two ways. The first is through a court order after caseworkers deem their environment unsafe, and if no friends or family can be found.

Because of the added trauma, removing a child is always the last option, caseworkers said. But in a county with only 42,000 people spread out over 400 square miles, the magnitude of the epidemic has compromised an already delicate safety net. Relatives are overwhelmed financially. Multiple generations are now addicted, along with cousins, uncles, and neighbors. In many cases, a safe house with a grandparent or other relative will eventually attract drug activity.

Law enforcement will also bring children in, usually after parents overdose. These cases often reveal the most horrendous neglect: a three-year old who needed every tooth pulled because he’d never been made to brush them, or kids found sleeping on bug-infested mattresses, going to the toilet in buckets because the water had been shut off. Children are coming in more hardened, they said, older than their years.

“I had a four-year-old whose mom had died in front of her and she described it like it was nothing,” said Bridgette, another caseworker. “She knew how to roll up a dollar bill and snort white powder off the counter. That’s what she thought dollar bills were for.” She added that many of the children could detail how to cook heroin. One foster family had a five-year-old boy who put his medicine dropper in his shoe. “Because that’s where daddy hid his needles,” she said.

“The kids are used to surviving in that mess,” added Carole, another veteran. “Now all the sudden the system is going in and saying it’s not safe. All their survival instincts are taken away and they go ballistic. They don’t know what to do.”

During the first weeks of foster care, meltdowns, tantrums, and violence are common as children navigate new landscapes and begin to process what they’ve experienced.

One afternoon, the caseworkers brought in a foster couple who’d taken in two sisters, an infant born drug-exposed, and her four-year old sister. The baby had to be weaned off opioids and now suffered chronic respiratory problems. Part of her withdrawal had included non-stop hiccups. The older girl had lived with her parents in a drug house and displayed clear signs of post-traumatic stress. Once, a family friend sitting next to her in a car had overdosed and turned purple. She’d witnessed domestic abuse, and one day a neighbor shot and killed her dog while she watched (she’d let the dog out). After a meltdown at a classmate’s pool party, over a year after entering foster care, she revealed having seen a toddler drown in a pond while adults got high. Through therapy, she’d also revealed sexual assault. The foster mother described how the girl suffered flashbacks, triggered by stress and certain anniversaries, like the day of her removal, and other seemingly random events. When this happened, she slipped into catatonic seizures.

“Her eyes are closed and you can’t wake her,” she said. “It’s like narcolepsy, a deep, unconscious sleep. We later discovered it was a coping mechanism she’d developed in order to survive.”

Despite what they’ve endured, most children wish desperately to return to their parents. Many come to see themselves as their parents’ caretakers and feel guilty for being taken away, especially if they were the ones to report an overdose, as in the case of a four-year-old girl who climbed out of a window to alert a neighbor. “She asked me: if I took her away, who was going to take care of mommy?” Bridgette remembered.

For caseworkers, reunification is the endgame. After children enter temporary foster care, the agency spends up to two years working closely with the family while the parents try to stay sober. The only contact with their children comes in the form of twice-weekly visits held in designated rooms here at the office. Each contains a tattered sofa and some second-hand toys. Currently, the agency runs about 200 visits each week. The encounters are monitored through closed-circuit cameras. For everyone involved, it can be the most trying period.

Many parents use the time to build trust and re-establish bonds. “During those first four years, a child gets such good stuff from their parents,” said Sherry, the caseworker who monitors the visits. “The kids are just trying to get that back.” Some parents bring doughnuts and pictures, while others need more guidance. Caseworkers hold parenting classes. Some moms lost newborns at the hospital after they tested positive for drugs; workers teach them how to feed and hold the child, and encourage them to bring outfits to dress their babies.

For other children, the visits trigger a storm of emotion that churns up the trauma of removal. “We had one girl who’d scream and wail at the end of every visit,” Laura, the supervisor, remembered. “Each time she thought she’d never see her mother again. We’d have to pry her out of mom’s arms and carry her down the hallway.”

“We’d sit in our offices and just sob,” added another worker. “But that girl’s cries weren’t enough to keep Mom off heroin.”

The number of available foster families is dwindling, while the cost of supporting them has never been higher

Perhaps the greatest difference with heroin and opioids, caseworkers said, is their iron grasp. Staying sober is a herculean task, especially in this rural community short on resources, where the nearest treatment facilities are over 30 miles away in Dayton, Cincinnati, or Columbus. At some point, nearly every parent falls off the wagon. They disappear and miss visits, leaving children to wait. One of the hardest parts of the job is telling a child that mom or dad isn’t coming, or that they can’t even be found.

“You see the hurt in their eyes,” Sherry said. “It’s a look of defeat, and it just breaks your heart.” She remembered a mother who’d failed to show up for months, then made it for her twin boys’ birthday. “The next day she overdosed and died.”

A tally sheet is used to track how many times prospective clients waiting to enter the program call a detox center, in Huntington, West Virginia. Photograph: Brendan Smialowski/AFP/Getty Images

When parents fail drug screenings during the 18-month period, caseworkers use discretion. Parents might be doing better in other areas like landing a job, or finding secure housing, so workers help them to get back on the wagon. “It’s all about showing progress,” Laura said. Some parents make it 16, 17 months sober and fully engaged. “And they’re the toughest cases, because we’ve been rooting for them this whole time and helping them. We’re giving kids pep talks, saying: ‘Mom’s doing great, she’s getting it together!’ They’re so happy to be going home. And then it all falls apart.”

With heroin, defeat is something the workers have learned to reckon with. Lately they’ve started snapping photos of parents and children during their first visit together, getting medical histories and other vital information – something they used to do much later. “Because we know the parents probably aren’t going to make it,” Laura admitted. “And if we never see them again, this is the info we need.” When asked how many opioid cases had ended in reunification, only two workers raised their hands.

The repeated disappointments come as resources and morale have reached their tipping point. The number of available foster families is dwindling, they said, while the cost of supporting them – over $1.5m a year – has never been higher.

Spirk, the agency’s director, said that all the agency’s budget was paid for with federal dollars and a county tax levy, although they’ve been flat-funded for nearly 10 years. The state contributes just 10%. When it comes to investing in child protection, Ohio ranks last in the country – despite having spent nearly $1bn fighting its opioid problem in 2016 alone.

The Ohio house of representatives recently passed a new state budget with an additional $15m for child protective services, but the state senate has yet to pass its own version. The only bit of hope came in March, when the Ohio attorney general’s office announced a pilot program that will give Clinton County, along with others, additional resources to help treat children for trauma, and to assist with drug treatment. It starts in October.

The epidemic’s unrelenting barrage has also taken a toll on mental health. “Our caseworkers are experiencing secondary trauma and frustration at not being able to reunify children with their parents because of relapses,” Spirk said.

Almost every caseworker said they had experienced depression or some form of PTSD, although no one had sought professional help. The privacy of their cases also means that few can speak openly with friends or family members. Some chose to drink, while others leaned on their faiths. But most said coping mechanisms they once relied on had failed.

“I used to have a routine on my drive home,” Laura said. “I’d stop in front of a church, roll down my window, and throw out all the day’s problems. The next morning I’d pick them back up. These days, I can’t do that anymore.”

“There’s no more outlet,” added Shelly, another supervisor. “You think you’re able to separate but you can’t let it go anymore. You try to eat healthy, do yoga, whatever they tell you to do. But it’s just so horrific now, and it keeps getting worse.”

At some point, the inevitable happens. When a parent can’t stay sober, or stops showing progress, the decision is made to place the child into permanent custody and put them up for adoption. For everyone, including caseworkers, it’s the most wrenching day.

The final act of every case is the “goodbye visit”, held in one of the nicer conference rooms. It’s a chance for parents to let their children know they love them and will miss them, and that it’s time to move on. Adoptive parents can choose to stay in contact, but it isn’t mandatory.

To make the time less stressful, Sherry, the worker who monitors the visits, has them draw pictures together, which she scans and gives to them as mementoes. She also tapes the meetings for them to keep. Watching from her tiny room full of TV screens, she can’t help but cry. “What people don’t realize is that when a baby comes into our custody, they’re still in a carrier seat. By the time the case is over, we’ve helped to potty train them. Two years is a very long time with a child. So in a way, it’s like my goodbye visit, too.”

Caseworkers have started making “life books” for kids once they come into the system. It’s where they put the photos they’ve taken, plus any pictures of birth parents or relatives they can find, report cards, ribbons and medals – the souvenirs of any childhood.  “It’s their history,” Sherry said, “so that one day they can make sense of their lives.”   She noted that one kid, after turning 18, tore his to pieces, taking with him only the good memories.

Source:  https://www.theguardian.com/us-news/2017/may/17/ohio-drugs-child-protection-workers

Abstract

Childhood maltreatment increases the risk of subsequent depression, anxiety and alcohol abuse, but the rate of resilient victims is unknown. Here, we investigated the rate of victims that do not suffer from clinical levels of these problems after severe maltreatment in a population-based sample of 10980 adult participants.

Compared to men, women reported more severe emotional and sexual abuse, as well as more severe emotional neglect. For both genders, severe emotional abuse (OR = 3.80 [2.22, 6.52]); severe physical abuse (OR = 3.97 [1.72, 9.16]); severe emotional neglect (OR = 3.36 [1.73, 6.54]); and severe physical neglect (OR = 11.90 [2.66, 53.22]) were associated with depression and anxiety while only severe physical abuse (OR = 3.40 [1.28, 9.03]) was associated with alcohol abuse.

Looking at men and women separately, severe emotional abuse (OR = 6.05 [1.62, 22.60] in men; OR = 3.74 [2.06, 6.81] in women) and severe physical abuse (OR = 6.05 [1.62, 22.60] in men; OR = 3.03 [0.99, 9.33] in women) were associated with clinical levels of depression and anxiety. In addition, in women, severe sexual abuse (OR = 2.40 [1.10, 5.21]), emotional neglect (OR = 4.78 [2.40, 9.56]), and severe physical neglect (OR = 9.86 [1.99, 48.93]) were associated with clinical levels of depression and anxiety.

Severe emotional abuse in men (OR = 3.86 [0.96, 15.48]) and severe physical abuse in women (OR = 5.18 [1.48, 18.12]) were associated with alcohol abuse. Concerning resilience, the majority of severely maltreated participants did not report clinically significant levels of depression or anxiety (72%), or alcohol abuse (93%) in adulthood. Although the majority of severely abused or neglected individuals did not show clinical levels of depression, anxiety or alcohol use, severe childhood maltreatment increased the risk for showing clinical levels of psychopathology in adulthood.

Introduction

Severe child maltreatment is conventionally defined within child protection practice as severe physical, emotional, sexual abuse and/or severe physical and emotional neglect by adults [1]. Severity can be defined on the basis of the type of maltreatment, its frequency, if the child was subjected to multiple forms of maltreatment, if a weapon had been used, if the maltreatment resulted in an injury, and if the abuse was considered severe by the victim. For sexual abuse, even a single experience is often considered to be severe [1].

Childhood maltreatment and its psychosocial consequences

There are annually over one million victims of childhood maltreatment in the USA alone and childhood maltreatment has a large public health impact [2]. Several studies show that childhood physical, emotional, and sexual abuse are all related to an increased risk of depression and anxiety disorders in adulthood [3–9]. Other studies have found that the severity of abuse and neglect is associated with increased depression and anxiety symptoms in adulthood [10–12]. This means that as a general rule, the more severe the abuse and neglect, the more likely the abused individuals are to show symptoms of depression and anxiety.

There is also a robust relationship between childhood maltreatment and later alcohol abuse [13–16]. For example, Young-Wolff et al. [17] found that men who had experienced childhood maltreatment were 1.7 times more likely to suffer from alcohol abuse in adulthood than men who did not report experiences of childhood maltreatment. Similar findings have been made when investigating the consequences of abuse and neglect in women (e.g., [18]). Findings from a study by Schwandt et al. [19] suggested that the severity of emotional and physical abuse plays a prominent role in the development of alcohol abuse. In line with these results suggesting a role of the severity of childhood abuse on later substance misuse, Hyman et al. [20] found that the severity of abuse was predictive of cocaine use after having been discharged from an inpatient treatment for cocaine addiction.  This was true for women but not for men. Kendler et al. [21] showed that women who had experienced child sexual abuse reported higher incidences of alcohol abuse. Twin studies have also shown that childhood sexual abuse increases the risk of alcohol abuse and addiction later in life [21–24]. To summarize, there is a strong, robust relationship between childhood maltreatment and mental disorders in adulthood. These associations include associations between childhood experiences of physical abuse, emotional abuse, and neglect, respectively, and mental disorders such as depression and anxiety disorders, and alcohol abuse [25–26]. Moreover, multi-type maltreatment in childhood is associated with greater impairment in adulthood, and this association also includes a range of psychological and behavioral problems, such as depression, anxiety, and alcohol abuse [27].

However, not all victims of childhood maltreatment develop symptoms of substance abuse or psychopathology in adulthood. Meta-analyses suggest that many (but not all) children who have experienced abuse succeed in overcoming some of the possible negative outcomes [28]. For example, Klika and Herrenkohl [28] found that some individuals who have experiences of abuse in childhood do not suffer long-term negative sequelae. Collishaw et al. [29] reported that despite serious experiences of childhood sexual or physical abuse, some individuals did not develop psychiatric problems during adulthood. Moreover, Hamilton et al. [30] reported that emotional neglect did not significantly predict increases in depressive or anxiety symptoms later in life. It has been estimated that 12–22% of maltreated individuals are functioning well despite experiencing childhood maltreatment [31].

The current study

Several studies have focused on only experiencing one type of maltreatment (e.g., sexual abuse) or one type of outcome (e.g., depression). Moreover, most previous studies have relied on either convenience samples or samples from health care services, and especially samples of the latter kind might bias the results and show less resilience than is actually the case.

In the present study, we used a large, population-based sample of Finnish men and women. The types of maltreatment included emotional, physical, and sexual abuse as well as emotional and physical neglect.   Thus, the aims of the present study were to:

1. Investigate gender differences in severe experiences of different types of childhood abuse;

2. Compare if and how individuals reporting severe experiences of different types of childhood abuse differ from individuals who did not report experiencing childhood abuse, in terms of presence of clinically significant symptoms of depression and anxiety in adulthood; and

3. Compare if and how individuals reporting severe experiences of different types of childhood abuse differ from individuals who did not report experiencing childhood abuse in terms of presence of alcohol abuse symptoms in adulthood.

Results

Descriptive results

The proportion of participants with severe experiences of emotional abuse was 0.6% (n = 64). The corresponding proportion for severe experiences of physical abuse was 0.2% (n = 26) while the proportions for severe experiences of sexual abuse was 0.4% (n = 43). For severe experiences of emotional neglect, the proportion was 0.4% (n = 44) and for severe experiences of physical neglect 0.1% (n = 7).  With regard to gender differences in the different types of severe experiences of abuse, Table 2 shows that there were statistically signi