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This week’s stories inadvertently illustrate the step-by-step process proponents employ to legalize marijuana for medical and recreational use.

Step 1. Target states with ballot initiatives.
Tell voters patients need marijuana for medical use, despite a lack of supporting evidence. Deny evidence that the drug is addictive, harmful to the developing brain, and is associated with increased traffic fatalities, ER visits, hospitalizations, and mental illnesses. [Of 26 ballot initiative states, 19 have legalized marijuana for medical use since 1996, 4 more have initiatives pending this November, and two have legalized cannabidiol (CBD). Only one initiative state, Nebraska, remains free of “medical” or “recreational” pot.]

Tired of the legislature’s refusal to legalize marijuana for medical use, the Marijuana Policy Project from Washington DC, has brought 72 percent of the $267,000 raised to place a ballot initiative on the state’s November ballot, contributing 44 percent — $118,000 – on its own. MPP, along with the Drug Policy Alliance and NORML, are the three organizations most responsible for the legalization of marijuana in the US.

Read The Salt Lake Tribune’s “From Legalizing Medical Marijuana to Raising Taxes for Schools, Utah Voters Will Have a Lot of Decisions to Make in November” here.

Step 2. Expand eligible conditions.
Once you’ve got marijuana legalized for medical use, expand the number of conditions that are eligible for its use.

Regulators in Michigan are thinking about adding 22 more conditions to the list of 14 that are currently eligible for “medical” marijuana use. (States have “approved” marijuana to treat more than 70 different conditions thus far.)

Read WXYZ.com “Michigan Considering Expanding Conditions Covered under Medical Marijuana Law” here.

Step 3. With a little help from the media . . .
Conduct research with pharmaceutical-grade marijuana components, but always illustrate news articles about the research with a marijuana plant.

Two new, privately funded studies were announced today. One, a $740,000 grant, is to the University of Utah to study how THC and CBD interact with the brain. The other, a $4.7 million grant, is to the University of San Diego School of Medicine’s Center for Medicinal Cannabis Research to study childhood autism. The latter study (and presumably the former) will administer pharmaceutical-grade synthesized CBD manufactured by INSYS Therapeutics. Its CBD product is in Phase 2 clinical trials seeking FDA approval. It looks nothing like the picture above that accompanies The Salt Lake Tribune’s story or the picture below that accompanies the Newswise.com story.

One caveat: The gifts to the two universities come from the Rae and Tye Noorda Foundation of Utah in partnership with the Wholistic Research and Education Foundation of California. Andy Noorda, who serves as a board member of his deceased parents’ foundation, co-founded the Wholistic Research and Education Foundation along with Mana Artisan Botanics of Hawaii. The company makes CBD products from hemp grown in Colorado. We have learned from alcohol and tobacco that industry-funded research is not always trustworthy.

Read The Salt Lake Tribune’s “University of Utah Launches $740,000 Study on How Marijuana Interacts with the Human Brain” here and Newswise.com’s “Philanthropic Gift will Fund Multidisciplinary Investigation of Mechanisms and Potential Therapeutic Benefits of Cannabidiol for Treating Neurodevelopmental Disorder” here.
Visit the Wholistic Research and Education Foundation here and Mana Artisan Botanics here.

Step 4. Join marijuana Industry to legalize recreational pot.
Link up with the marijuana industry that makes medicines, not one of which has been approved by FDA. Join forces to legalize marijuana for recreational use. (All 8 states that have done this legalized pot for medicine first.)

Proponents have succeeded in placing an initiative on Michigan’s November 2018 ballot that would legalize marijuana for recreational use. Among other provisions, the initiative calls for a 10 percent excise tax and a 6 percent sales tax. While allowing communities to ban marijuana businesses within their boundaries, 15 percent of those revenues would go to “communities that allow marijuana businesses within their borders and 15 percent would go to counties where marijuana business are located.”

Read the Detroit Free Press article, “Michigan Approves Marijuana Legalization Vote for November” here.

Step 5. Deny the consequences of legalization.
Colorado legalized marijuana for medical use in 2000, legalized cultivation and dispensaries in 2009, and legalized recreational use in 2012, effective 2014. Drug-related deaths have nearly tripled since legalization began.

Read KOAA’s “Overdose Fatalities Continue to Reach New Record Highs in Colorado” here.

See Step 5.
More than 3,400 marijuana violations occurred in Colorado elementary, middle, and high schools last academic year, up more than 18 percent from two years before.

Read Fox 31’s “Marijuana Violations in Colorado K-12 Schools Up 18 Percent” here.

Source: nfia@nationalfamilies.org

The Marijuana Report is a weekly e-newsletter published by National Families in Action in partnership with SAM (Smart Approaches to Marijuana).

May 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

By Jason Schwartz

British Columbia has long been cited as a model for North American drug policy and harm reduction implementation.

BC has established a Death Review Panel in response to the overdose crisis. The panel recently issued a report with 3 recommendations. The first recommendation to regulate recovery homes, which currently require only a simple inspection of the facility. (The other 2 were for more maintenance treatments and more harm reduction.)

The chair of the panel cited the abstinence orientation of houses as a concern.

A columnist at the Vancouver Sun pushes back against the argument that BC is suffering from insufficient harm reduction:

This is, after all, a city and a province that for nearly 20 years has been at the forefront of harm-reduction with needle exchange programs, safe injection sites, methadone and suboxone treatment programs, a prescription heroin program and, more recently, free naloxone kits, free-standing naloxone stations and training for first-responders and even teachers in how to use it as an antidote for fentanyl overdoses.

We’ve gone from crisis to crisis, each one sucking up incredible resources. Currently, a quarter of a million dollars a day goes into the Downtown Eastside alone for methadone treatment. This year, the B.C. government expects the number of British Columbians receiving replacement drug therapy to rise to 30,000 and then nearly double to 58,000 by 2020-21.

In 2006 when Vancouver updated its four pillars approach, it noted that there were 8,319 British Columbians being treated with methadone.

By 2020-21, the province also expects to be supplying 55,000 “free” take-home naloxone kits, up from 45,000 this year.

We keep hearing about an overdose crisis, but what we have is an addictions crisis. Solving it will require a lot more than simply reducing harm.

What’s needed is a recovery orientation. (Which does not rule out harm reduction.)

Source: https://addictionandrecoverynews.wordpress.com/2018/04/12/overdose-crisis-or-addiction-crisis/

April 2018

It is no accident that in almost the same week both Australia and UK have decided that cannabis is to be recommended for a host of medical disorders mostly in advance of gold standard clinical trials. This is a direct product of the organized transnational global drug liberalization movement orchestrated from New York.

I wish to most respectfully disagree with the points made by BMJ editor Dr. Godlee. Diarrhoea and colic occur in cannabis withdrawal; Crohn’s disease has a prominent immune aspect, and cannabinoids are likely acting partly as immune modulators. Statements from patients are uninterpretable without understanding the treatments tried, their withdrawal symptomatology and their personal preferences.

Most importantly, as Dr Godlee states, cannabis is a mixture of 104 cannabinoids. The tide cannot be both out and in at the same time. Medicines in western nations are universally pure substances. This comprises a fundamental difficulty.

Medical research has confirmed that the body’s endocannabinoid system is a finely regulated and highly complex system which is involved in the detailed regulation of essentially all body systems including the brain and cardiovascular systems and stem cell niches.

Studies have shown that the rate of use of cannabis by expecting mothers closely parallels that in the wider community. In fact given the long half-life of cannabis in tissues even were a maternal habitual smoker to stop when she discovered her pregnancy, her infant would continue to be exposed to her on-board cannabinoid load for several months afterwards during critical periods of organogenesis. And other studies show that the father’s cannabis use is even more damaging than the mothers’.

Whilst much research has focussed on the effects of endocannabinoids in the adult brain relatively little research has looked at the impact of these same effects in the developing brain of the foetus and neonate. Whilst the brain stem is almost devoid of type 1 cannabinoid receptors (CB1Rs) they are in high concentration in many parts of the midbrain, limbic system, subcortical regions and cerebral and cerebellar cortices. Foetal CB1Rs have been shown to play key roles in virtually all aspects of brain development including neural stem cell function, determining the ratio of glial v neuronal differentiation, brain inflammation, axonal growth cone guidance, stem cell niche function and signalling, blood flow signalling, white matter and CNS tract formation, glial cell differentiation, myelination, dendrite formation, neural migration into the developing cortex, synapse formation and integration of newly formed neurons into the neural network. They are also found in high density on endoplasmic reticulum and mitochondria from which latter they indirectly control major issues including cognition, DNA maintenance and repair systems both by supplying energy and by metabolite shuttle and RNA signalling.

Hence it is not surprising that gestational cannabis has been linked with a clear continuum of defects, including in protracted longitudinal studies from Pittsburgh, Ottawa and Netherlands impaired cortical and executive functioning; reduced spatial judgement; the need to recruit more brain to perform similar computational tasks; microcephaly; lifelong smaller heads and smaller brains; anencephaly (in two CDC studies), and increased foetal death. This progression clearly reflects a spectrum of congenital neurological impairment which is quite consistent with the known distribution of CB1Rs mainly across the foetal and adult forebrain and midbrain and its derivatives.

It is also consistent with a recent explosion of autism in Colorado, California, New Jersey and many other sites in USA and internationally in recent years. Moreover cannabis induced synpatopathy closely mimics that seen in autism, as do similar white matter disconnection endophenotypes.

A similar scenario plays out in the cardiovasculature. The American Heart Association and American Academy of Pediatrics issued a joint statement as long ago as 2007 noting that foetal cannabis exposure was linked with increased rates of ventricular septal defect and Ebstein’s anomaly (complex tricuspid valvopathy). This is consistent with recent Colorado experience where ventricular septal defect has risen from 43.9 to 59.4 / 10,000 live births, or 35.3% 2000-2013. Both of these structures are derivatives of the endocardial cushions which are rich in CB1Rs. Concerningly Colorado has also seen a 262% rise in atrial septal defects over the same period. Exposure to other drugs does not explain this change as they were falling across this period. It has also been reported that the father’s use of cannabis is the strongest environmental factor implicated in cardiovascular defects, here involving transposition of the great arteries, which is a derivative of the conoventricular ridges immediately distal and continuous with embryonic endocardial cushions, and also rich in CB1Rs.

Similar findings play out in gastroschisis. There is an impressive concordance amongst the larger studies of the relationship of gastroschisis and congenital cannabis exposure where senior Canadian authors concluded that cannabis caused a three-fold rise in gastroschisis, consistent with a high density of CB1Rs on the umbilical vessels.

And cannabis has also been implicated as an indirect chromosomal clastogen and indirect genotoxin through its effect to disrupt the mitotic spindle by microtubule inhibition, and likely DNA maintenance and repair by its effect on nuclear actin filaments.

Moreover cannabidiol has been shown to alter the epigenome, to be genotoxic, and to bind to CB1Rs at high doses, so the simplistic case that “Cannabidiol is good” – fails.

These considerations imply that if clinical trials continue to show efficacy for additional indications for cannabinoids, their genotoxic and teratogenic potential, from both mother and father, will need to be carefully balanced with their clinical utility. They also imply that these issues will need to be more widely canvassed and discussed in order to introduce more balance into the heavily biased present global media coverage of the highly misleading misnomer “medical cannabis”.

Only once before has a known teratogen been marketed globally: the thalidomide disaster is the proximate reason for modern pharmaceutical laws. With its widespread uptake, rising concentrations, asymptotic genotoxic dose-response curves and actions through the paternal line cannabis could be much worse.

Albert S Reece
Doctor
University of Western Australia and Edith Cowan University at Joondalup in Western Australia
Brisbane

Source: https://www.bmj.com/content/362/bmj.k3357/rr-0

 

Source:

https://jamanetwork.com/journals/jamasurgery/article-abstract/2689028

Childhood adversity permanently alters the peripheral and central immune systems, increasing the sensitivity of the body’s immune response to cocaine, reports a study by researchers at the IRCCS Santa Lucia Foundation and University of Rome “La Sapienza,” Italy.

The study, published in Biological Psychiatry, showed that exposure to psychosocial stress early in life altered the structure of immune cells and inflammatory signals in mice and led to increased drug-seeking behavior. Exposure to early psychosocial stress in mice, or a difficult childhood in humans, increased the immune response to cocaine in adulthood, revealing a shared mechanism in the role of immune response in the effects of early life stress on cocaine sensitivity in mice and humans.

The findings help explain why as many as 50 percent of people who experience childhood maltreatment develop addiction problems. The results in mice and humans suggest that exposure to adversity during childhood triggers activation of the immune system, leading to permanent changes that sensitize the immune system and increase susceptibility to the effects of cocaine in adulthood.

“This paper suggests the existence of an extraordinary degree of interplay between the neural and immune systems related to the impact of early life stress on later risk for cocaine misuse. It both highlights the complex impact of early life stress and suggests an immune-related mechanism for reducing later addiction risk,” said John Krystal, MD, Editor of Biological Psychiatry.

After inducing psychosocial stress in 2-week-old mice by exposing them to a threatening male, first author Luisa Lo Iacono, PhD, and colleagues examined brain immune cells, called microglia, in adulthood. Early social stress altered the structure of microglia in the ventral tegmental area, a brain region important for the reward system and drug-seeking, and increased the response of microglia to cocaine. In the peripheral immune system, early social stress increased the release of inflammatory molecules from white blood cells, which was further amplified by exposure to cocaine, compared with control mice.

“Remarkably, pharmacologically blocking this immune activation during early life stress prevents the development of the susceptibility to cocaine in adulthood,” said senior author Valeria Carola, PhD. Mice who received an antibiotic to prevent activation of immune cells during social stress did not have cellular changes or drug-seeking behavior.

The study also compared immune system function of 38 cocaine addicts and 20 healthy volunteers. Those who experienced childhood maltreatment had increased expression levels of genes important for immune system function. And the highest levels were found in cocaine addicts who had experienced a difficult childhood.

The findings add to the growing collection of evidence from the research group for the negative effects of early life trauma on brain development. “Our work emphasizes once again the importance of the emotional environment where our children are raised and how much a serene and stimulating environment can provide them with an extra ‘weapon’ against the development of psychopathologies,” said Dr. Carola.

Source:  https://medkit.info/2018/07/17/childhood-adversity-increases-susceptibility-to-addiction-via-immune-response/

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:

http://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:

http://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/

A fall in the price of cocaine has led to the highest number of young people using class A drugs in more than a decade, experts say.

Cocaine prices are at their lowest levels in more than 25 years and young people are finding Class A drugs easily accessible, charities warned.  The drug is more widely available thanks to mobile phones and is being distributed to users outside city centres thanks to “county lines” in which gangs use children to export their trade to suburban and rural areas.

Figures released by the Home Office from the Crime Survey of England and Wales for 2017/18 show that 8.4 per cent of 16 to 24 year-olds had used Class A drugs in the last year, compared to seven per cent in 2016/17.

The proportion is the highest since 2005/6 and a significant rise from the recent low of 4.8 per cent, seen in 2012/13.  Six per cent had used powder cocaine, up from 4.8 per cent in the previous year and the highest figure since 2008/2009.

Figures from the UN’s 2018 World Drug Report show that in 2016 the street price of a gram of cocaine in the UK was $54 (£41), the cheapest at any point since 1990, when the time series begins. In 2007 the price was $91 (£69), and prices climbed as high as $128 (£97) in 1998.

Yasmin Batliwala, chair of London-based drug and alcohol treatment charity WDP, said young people were paying as little as £30 for a gram.

“Our young people’s services have seen a significant rise in the use of Class A drugs. The primary drug of choice has always been alcohol, as well as cannabis, but certainly in the last two or more years the use of Class A drugs has increased substantially.  “Class A drugs such as cocaine are extremely easily available. It’s actually very difficult to avoid drugs these days.In terms of price the cost has come down, so they’re not that expensive,” she said.

Harry Shapiro, of DrugWise, said the lower price of the drug meant users no longer had to be “city boys with lots of money”.  Mobile phones also made it easier for people to “hook into a regular supply,” he said. “You’ve got a broader network of distribution making it available in places where it wasn’t before, and they don’t have to hang around on street corners waiting for a bloke any more.

“Some people have got their dealer on speed dial and it’s a bit like home delivery of pizza.  All of that allows for a more discreet, wider network of distribution.”

Earlier this month addiction charity Addaction said its drug workers were dealing with children as young as 13 who were addicted to cocaine.  The organisation said the issue was a particular problem in Scotland, where its South Lanarkshire service has lowered the age threshold of its services from 14 to 13.

One of the charity’s workers Jacqueline Baker-Whyte said: “In the past, cocaine was a drug for people with money. That’s no longer the case. It’s cheap, plentiful and easy to get. The ‘quality’ is usually poor and the side effects can be horrendous.”

A spokeswoman for drugs charity Release said the figures showed that “criminalisation does not deter drug use”.
“The reported increase in recent powder cocaine use could be attributed to the drug’s reduced street-level price, and its higher purity,” she added.

Source: https://www.telegraph.co.uk/news/2018/07/26/class-drug-use-among-young-people-highest-decade-price-cocaine

Filed under: Cocaine,Latest News,Youth :

These are very shocking videos with information about some of the effects of drug legalisation in the USA.

 

 

 

In an era when 24% of teenage Californian mothers test cannabis-positive it is unfortunate that the vast and conflicting literature on cannabis teratology has created professional confusion on the important subject of cannabis teratology.  An appreciation of overarching patterns can contribute to clarity in this field.

There is considerable agreement in the literature that cannabis interferes with foetal development including earlier birth, higher rates of prematurity, and lifelong smaller heads – which obviously necessarily implies lifelong smaller brains as well 1.  Moreover the National Birth Defects Prevention Network coordinated by CDC have issued two papers documenting increased rates of anencephaly with R.R. = 1.7 (95%C.I. 0.9-3.4) and RR=1.9 (95% C.I. 1.1-3.2) respectively 2.   And there is very close agreement from the three major longitudinal studies from Ottawa, Pittsburgh and Netherlands of brain growth and intellectual development in children after prenatal cannabis exposure (PCE) which clearly document impaired executive functioning, poorer attention, difficulty in school work increased rates of addiction, persisting through all grades of school and into young adult life as long as the early 20’s 3.   Other studies have shown reduced frontal cortical thickness and increased white matter tract disconnections approaching 90% in key executive and computational cortical areas.  It is known that the foetal brain stem is low in cannabinoid type 1 receptors (CB1R’s) but many parts of the rest of the brain, including cerebral, hippocampal, orbitofrontal and cerebellar cortices, the limbic system and parts of the midbrain have moderate to high density CB1R’s.

This pattern of CB1R distribution forms both the greatest strength of cannabis and also its greatest weakness.  It is often – although clearly wrongly – said that cannabis cannot kill patients because the brain stem is low in CB1R’s so direct respiratory depression cannot occur as occurs from opioids.  The tag line about cannabis not causing death, though thoroughly deserving of “urban myth” status is demonstrably erroneous as cannabis is now well linked with cardiac arrest, psychosis, testicular cancer, chronic lung disease and unemployment – amongst many others – all of which are greatly elevate mortality.  As in adult life, so in foetal life the largely supratentorial distribution of CB1R’s implies that perturbation of the endogenous endocannabinoid system could conceivably interfere with the development of the supratentorial brain.  This pattern is well displayed by anencephaly in which the brain stem is often more or less intact.  It can be argued that the remainder of the neuroteratological manifestations of PCE reflect the pattern of distribution and expression of CB1R’s which occur with development.   This implies that cannabis neuroteratology actually reflects a continuum with subtle forms of neurobehavioral teratology at one end of the spectrum, microcephaly and smaller heads in an intermediate position and anencephaly at the most severe end.  This continuum can be further extended to include neurologically induced foetal loss and spontaneous and therapeutically induced terminations.

Moreover high density CB1R’s have been demonstrated on brain mitochondria where they subserve numerous key brain functions including thinking, attention, memory and wakefulness 4.  Their inhibition is directly linked with stimulating aging processes via mitonuclear crosstalk, induction of the mitochondrial stress response and impaired DNA repair.  The implications of accelerated molecular and neuronal aging at the foetal stage have not been properly considered.

The American Heart Association and the American Academy of Pediatrics issued a statement as long ago as 2007 that found two heart defects, ventricular septal defect (VSD) and Ebsteins anomaly, were known to be related to cannabis use on the basis of two studies 5.  Importantly both the atrioventricular valves and parts of the membranous interventricular septum are derived from the endocardial cushions which are known to be high in CB1R’s from as early as 9 weeks of gestation.  The Colorado experience also fits here with a 35% increase in VSD rates and a 262% increase in atrial septal defect rates 2000-2013 (Figure 1).  This early appearance of cardiovascular CB1R’s is important as many women are unsure of their pregnancy at this time; and given the very long half-life of cannabis in fat stores of several months immediate cessation would not protect a developing foetus during critical periods of organogenesis.  Studies show that paternal exposure is more significant than maternal exposure for several defects including transposition of the great arteries.  CB1R is a key regulator of the neurovascular neural stem cell niche.

Gastroschisis incidence has also risen, and reflects vasoactive drug exposure.  High density CB1R’s on foetal arteries, CB1R-mediated vasospasm and cannabis arteritis imply that the demonstrated vasoactive properties of cannabis have been largely overlooked 6.  Seven studies uniformly document on univariate testing increased incidence of gastroschisis after cannabis exposure and a further two studies show increased severity.  Carefully adjusted Canadian studies show a threefold elevation of gastroschisis risk.

Δ9-Tetrahydrocannabinol also interferes with nuclear actin and tubulin polymerization directly interfering with the processes of DNA repair and cell division respectively 7.  Hence Down’s syndrome, which is one of the chromosomal mis-segregation disorders has been linked with PCE.

Government reports from Canada show a clear association of high congenital anomaly rates for total defects, cardiovascular defects, orofacial clefts and gastroschisis with areas of high cannabis consumption.  Similar evidence is also available for high cannabis use areas in Northern New South Wales in Australia.  USA state level epidemiology replicates these same patterns.

As the second most common cannabinoid present in cannabis it is important to appreciate that the above-cited neonatal epidemiology also implicates cannabidiol which also binds to CB1R’s at high doses and has demonstrated genotoxicity, epigenotoxicity and mitochondrial toxicity.

These observations show that the CB1R, the dominant cannabinoid endoreceptor, well explains much of the neurobehavioural and cardiovascular teratology which is now relatively well described.

Importantly such an understanding, together with the non-linear asymptotic cannabinoid-genotoxic dose-response curve, predicts that increased community exposure to cannabis both by prevalence and by the high concentrations widely available will necessarily imply severe brain damage which can safely be said to approach 100% for significant in utero or paternal exposure, a congenital defect from which recovery is not possible as brain growth is permanently compromised.

Source:  Paper by Prof. Dr. Stuart Reece to DrugWatch International  July 2018

References

Volkow ND, Compton WM, Wargo EM. The Risks of Marijuana Use During Pregnancy. JAMA. 2017;317(2):129-130.Van Gelder MMHJ, Donders ART, Devine O, Roeleveld N, Reefhuis J.

Using bayesian models to assess the effects of under-reporting of cannabis use on the association with birth defects, national birth defects prevention study, 1997-2005. Paediatric and perinatal epidemiology. 2014;28(5):424-433.

Brents L. Correlates and consequences of Prenatal Cannabis Exposure (PCE): Identifying and Characterizing Vulnerable Maternal Populations and Determining Outcomes in Exposed Offspring In: Preedy V.R., ed. Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis and Treatment. Vol 1. London: Academic Press; 2017:160-170.

Hebert-Chatelain E, Desprez T, Serrat R, et al. A cannabinoid link between mitochondria and memory. Nature. 2016;539(7630):555-559.

 

Jenkins KJ, Correa A, Feinstein JA, et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007;115(23):2995-3014.

Pacher P, Steffens S, Hasko G, Schindler TH, Kunos G. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol. 2018;15(3):151-166.

Reece AS, Hulse GK. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Mutat Res. 2016;789:15-25.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Key Points

Question  Are changes in population-level alcohol and tobacco consumption associated with changes in overall cancer mortality?

Findings  In this population-based cohort study, temporal associations of alcohol and tobacco consumption with cancer mortality overall were found using Australian time series data (1935-2014). An estimated 1-L decrease in alcohol consumption per capita and a 1-kg decrease in tobacco consumption per capita were associated with a decline of 3.9% and 16%, respectively, in overall cancer mortality across a 20-year period.

Meaning  Health policy interventions that can decrease population alcohol and tobacco consumption may lead to a reduction in cancer mortality over a 20-year period.

Abstract

Importance  Understanding whether the population-level consumption of alcohol and tobacco is associated with cancer mortality is a crucial question for public health policy that has not been answered by previous studies.

Objective  To examine temporal associations of alcohol and tobacco consumption with overall cancer mortality in the Australian population, looking across different sex and age groups.

Design, Setting, and Participants  This population-based cohort study conducted a time series analysis (autoregressive integrated moving average models) using aggregate-level annual time series data from multiple sources. Data on alcohol consumption and tobacco consumption per capita between 1935 and 2014 among the Australian population aged 15 years and older were collected from the Australian Bureau of Statistics and Cancer Council Victoria. Analysis was conducted from June 1, 2017, to October 30, 2017.

Exposures  Sex- and age-specific cancer mortality rates from 1968 to 2014 were collected from the Australian Institute Health and Welfare.

Main Outcomes and Measures  Population-level cancer mortality in different sex and age groups in Australia, controlling for the effects of health expenditure.

Results  Among the Australian total population aged 15 years and older in this study, 50.5% were women. Cancer death rates per 100 000 persons increased from 199 in 1968 to 214 in 1989 and then decreased steadily to 162 in 2014. Taking into account lagged effects, 1-L decreases in alcohol consumption per capita were associated with a decline of 3.9% in overall cancer mortality over a 20-year period, and 1-kg decreases in tobacco consumption per capita were associated with a 16% reduction. Alcohol consumption per capita was significantly associated with overall cancer mortality among men aged 50 to 69 years and women aged 50 years and older. Tobacco consumption per capita was found to be significantly associated with overall cancer mortality only among men aged 50 years and older.

Conclusions and Relevance  In this study, alcohol consumption per capita was positively associated with overall cancer mortality among older men and women, and tobacco consumption per capita was positively associated with overall cancer mortality among older men over a 20-year period. This study provides evidence that a decrease in population-level drinking and tobacco smoking could lead to a reduction in cancer mortality.

Source:  JAMA Network Open. 2018;1(3):e180713. doi:10.1001/jamanetworkopen.2018.0713

Filed under: Alcohol,Latest News :

Report by prominent marijuana policy group finds costs would outweigh any tax revenue under legalization; Healthy and Productive Illinois coalition urges rejection of legalization

Today, the day before the unofficial “marijuana holiday,” Healthy and Productive Illinois (HPIL) – a project of Smart Approaches to Marijuana Action (SAM Action) – released a comprehensive working paper on the projected costs of legalization in Illinois, finding that legalization would cost the state $670.5 million, far outweighing estimated tax revenue projections of approximately $566 million. The report will be released today at 9:30 am in Room N505 of the Thompson State Building in Chicago, during a press conference by HPIL to announce opposition to legalization.

This report uses data from states like Colorado that have legalized marijuana to debunk the myth that taxed marijuana sales will be a boon to the state’s well-reported fiscal crisis. A conservative approximation of quantifiable data such as administrative and regulatory enforcement, increased drugged driving fatalities and other vehicle related property damages, short term health costs, and increased workplace absenteeism and accidents would cost the state $670.5 million in 2020.

“This study clearly demonstrates that the only people who will make money from marijuana commercialization are those in the industry that grow and sell it, at the direct expense of public health and safety,” said Dr. Aaron Weiner Director of Addiction Services at Linden Oaks Behavioral Health. “This industry is actively lobbying in Springfield to move their agenda forward, misleading our leaders and the general public. We have to speak up about the truth to protect the health of our State,” continued Dr. Weiner.

Healthy and Productive Illinois is a coalition formed to spread science-based awareness on marijuana harms and push back against the movement to legalize marijuana. The group believes the marijuana industry is mimicking the tactics of the Big Tobacco industry.

“We know that when citizens of Illinois are informed that marijuana is already decriminalized, only 23% want to fully legalize it,” said Andy Duran, Executive Director of Linking Efforts Against Drugs (LEAD). “Lack of knowledge and confusion is the fuel that drives the commercial marijuana market forward, just like tobacco before it. Imagine what would happen if everyone was aware that the State will lose money, too,” continued Duran.

There is sufficient information available to suggest that marijuana legalization could incur additional costly side effects, but at this time data is not robust enough to quantify their long-term impact. One of these additional costs would be controlling an expanded black market.

“In Oregon and Colorado, we are seeing thriving black markets and illegal grow operations hiding amongst legal growers,” said Chief James Black, Vice President of the Illinois Association of Chiefs of Police. “This expanded black market creates a real problem for law enforcement who now have to work even harder and allocate more precious resources to weed out illegal grow ops,” continued Chief Black.

Additional costs include:

* Additional workplace injuries among part-time employees

* Increases in alcohol use and abuse

* Increases in tobacco use

* More opioid abuse

* Increases in short-term/long-term recovery for marijuana use disorders

* Greater marijuana use among underage students

* Property and other economic damage from marijuana extraction lab explosions

* Controlling an expanded black market, sales to minors, and public intoxication

* Other administrative burdens of most state legalization programs, such as:

– money for drugged driving awareness campaigns;

– drug prevention programs; and

– pesticide control and other agricultural oversight mechanisms

* Long-term health impacts of marijuana use

“Cost reports such as this are the dirty truth that the pot industry doesn’t want law makers and the general public to see,” said Dr. Kevin Sabet, Founder and President of SAMA and former senior drug policy advisor to President Obama. “The pot industry is dead set on becoming the next Big Tobacco. The men in suits behind Big Pot will become rich while communities of color continue to suffer with addiction, black markets thrive, and states are left to foot the bill,” continued Dr. Sabet.

Source: Email from SAM (Smart Approaches to Marijuana) <info@learnaboutsam.org>

April 2018

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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42. Fowler CJ. Delta9-tetrahydrocannabinol and cannabidiol as potential curative agents for cancer: a critical examination of the preclinical literaturePharmacol Ther. 2015;97:587–596 [PubMed]
43. Aviello G, Romano B, Borrelli F, et al. Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancerJ Mol Med. 2012;90:925–934 [PubMed]
44. Jadoon KA, Ratcliffe SH, Barrett DA. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot studyDiabetes Care. 2016;39:1777–1786 [PubMed]
45. Watanabe K, Motoya E, Matsuzawa N, et al. Marijuana extracts possess the effects like the endocrine disrupting chemicalsToxicology. 2005;206:471–478 [PubMed]
46. Narimatsu S, Watanabe K, Yamamoto I. Inhibition of hepatic microsomal cytochrome P450 by cannabidiol in adult male ratsChem Pharm Bull. 1990;38:1365–1368 [PubMed]
47. Jones NA, Hill AJ, Smith I, et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivoJ Pharm Ex Ther. 2010;332:569–577 [PMC free article] [PubMed]
48. Jones NA, Glyn SE, Akiyama S, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizuresSeizure. 2012;21:344–352 [PubMed]
49. Fasinu PS, Phillips S, ElSohly MA, et al. Current status and prospects for cannabidiol preparations as new therapeutic agentsPharmacotherapy. 2016;36:781–796 [PubMed]
50. Persson A, Ingelman-Sundberg M. Pharmacogenomics of cytochrome P450 dependent metabolism of endogenous compounds: implications for behavior, psychopathology and treatmentJ Pharmacogenomics Pharmacoproteomics 2014;5:12–7.
51. Ghosh C, Hossain M, Solanki J, et al. Pathophysiological implications of neurovascular P450 in brain disordersDrug Discov Today. 2016;21:1609–1619 [PMC free article] [PubMed]
52. Brunt TM, van Genugten M, Höner-Snoeken K, et al.Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabisJ Clin Psychopharmacol. 2014;34:344–349 [PubMed]
53. Das RK, Kamboj SK, Ramadas M, et al. Cannabidiol enhances consolidation of explicit fear extinction in humansPsychopharmacology. 2013;226:781–792 [PubMed]
54. Bhattacharyya S, Morrison PD, Fusar-Poli P, et al. Opposite effects of Δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathologyNeuropsychopharmacology. 2010;35:764–774 [PMC free article] [PubMed]
55. Martin-Santos R, Crippa J, Batalla A. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) administration in healthy volunteersCurr Pharm Des. 2012;18:4966–4979 [PubMed]
56. Crippa JAS, Hallak JEC, Machado-de-Sousa JP, et al.Cannabidiol for the treatment of cannabis withdrawal syndrome: a case reportJ Clin Pharm Ther. 2013;38:162–164 [PubMed]
57. Morgan CJ, Freeman TP, Schafer GL. Cannabidiol attenuates the appetitive effects of Δ9-tetrahydrocannabinol in humans smoking their chosen cannabisNeuropsychopharmacology. 2010;35:1879–1885 [PMC free article] [PubMed]
58. Hurd YL, Yoon M, Manini AF. Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stageNeurotherapeutics. 2015;12:807–815 [PMC free article] [PubMed]
59. Morgan CJ, Das RK, Joye A, et al. Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findingsAddictive Behav. 2013;38:2433–2436 [PubMed]
60. Zuardi AW, Guimaraes FS, Moreira AC. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteersBraz J Med Biol Res. 1993;26:213–217 [PubMed]
61. Appiah-Kusi E, Mondelli V, McGuire P, et al. Effects of cannabidiol treatment on cortisol response to social stress in subjects at high risk of developing psychosisPsychoneuroendocrinology. 2016;7(Supplement):23–24
62. Geffrey AL, Pollack SF, Bruno PL, et al. Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsyEpilepsia. 2015;56:1246–1251 [PubMed]
63. Grotenhermen F, Gebhardt K, Berger M. Cannabidiol. Nachtschatten Verlag: Solothurn, Switzerland, 2016
64. Mincis M, Pfeferman A, Guimarães RX. Chronic administration of cannabidiol in man. Pilot studyAMB Rev Assoc Med Bras.1973;19:185–190 [PubMed]
65. Cunha J, Carlini EA, Pereira AE, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patientsPharmacology. 1980;21:175–185 [PubMed]
66. Zuardi AW, Crippa JAS, Hallak JEC, et al. Cannabidiol for the treatment of psychosis in Parkinson’s diseaseJ Psychopharmacol. 2009;3:979–983 [PubMed]
67. Leweke FM, Piomelli D, Pahlisch F. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophreniaTransl psychiatry. 2012;2:e9–4. [PMC free article][PubMed]
68. Leweke F, Koethe D, Gerth C. Cannabidiol as an antipsychotic: a double-blind, controlled clinical trial of cannabidiol versus amisulpiride in acute schizophrenia. In: 15th annual symposium on cannabinoids Cannabinoid Research Society: Clearwater Beach, FL, 2005
69. Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humansSchizophr Res. 2015;162:153–161 [PubMed]
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

There was big news in Congress today that I wanted you to know about. A proposed government spending bill released today eliminated a provision that has protected the marijuana industry from federal prosecution for violating the Controlled Substances Act.

The Rohrabacher-Farr language was eliminated from the Commerce, Justice, Science bill that funds the Department of Justice, even though the language had previously been included in the 2017 base text. In addition, the Financial Services bill retained language preventing Washington, DC from implementing full retail sales and commercialization of recreational marijuana.

Smart Approaches to Marijuana (SAM) submitted testimony to the Appropriations Committee to push back against this provision, which has allowed unsafe and untested products to masquerade as medicine. Rather than submit their products to the FDA for approval as safe and effective medicines, the marijuana industry has instead been using medical marijuana laws as a guise to increase demand for marijuana consumption and service the black market with large amounts of high-potency marijuana.

“If I were an investor, I would sell my marijuana stocks short,” said Kevin Sabet, President of SAM. “The marijuana industry has lost in every state in which they were pushing legislation in 2017, the industry’s largest lobbying group is losing its bank account , and now they are losing protection that has helped them thrive despite marijuana’s illegal status. Although the debate over Rohrbacher-Farr is far from over, the bad news just keeps coming for the pot industry. But it’s great news for parents, prevention groups, law enforcement, medical professionals, victims’ rights advocates and everyone who cares about putting public health before profits.”

Evidence demonstrates that marijuana – which has skyrocketed in average potency over the past decade – is addictive and harmful to the human brain, especially when used by adolescents. Moreover, in states that have already legalized the drug, there has been an increase in drugged driving crashes and youth marijuana use. States that have legalized marijuana have also failed to shore up state budget shortfalls with marijuana taxes, continue to see a thriving black market, and are experiencing a continued rise in alcohol sales.

Thank you for the work that you are doing to help with these big wins for public health and safety!  

Source: Email from Smart Approaches to Marijuana (SAM) June 2017

There was big news in Congress yesterday that I wanted you to know about. We are pleased to report that the House has not included any pro-pot riders in its spending bills this year! Thank you for all of your efforts, including calls and emails. Congress has heard your voice and acted to preserve the public health and safety of our kids and communities.

Pro-pot advocates filed more than ten amendments to protect the marijuana industry and increase marijuana investment opportunities, but none of the amendments were allowed to proceed. The lessons of legalization are getting out, and it’s clear the experiment has failed, as our recent Cole Memo Report has shown. The black market is thriving, kids are ending up in emergency rooms, and drugged driving fatalities are soaring .

The fight isn’t over, though. Even though the House bill is clear, the Senate version of the spending bill still contains key marijuana industry protections. Those differences will be resolved in the coming months. We will continue to send out alerts to let you know when it’s time to come together and act.

Thank you again for all your work over the past years. You’ve made a difference, and we are grateful for your partnership. Please consider a donation to help with our efforts as we continue this battle in the coming months.

Source: Email SAM Action <info@samaction.net> from Kevin Sabet September 2017

The opioid crisis is unlike any drug epidemic America has ever known. It’s claiming lives at an almost unimaginable rate.

But to get an idea of why these drugs are taking such a toll, you have to look at the people who are dying.

This is not just the curse of the stereotypical addict.

Many of those admitted to the country’s fast swelling mortuaries were middle class professionals whose first fix was dealt to them by a doctor.

Back in the 90s and early 2000s, pharmaceutical firms began a major lobbying exercise, persuading doctors to prescribe their synthetic forms of heroin for pain relief.

Soon GPs across the country were handing out powerful prescriptions for relatively minor ailments.

The drugs worked, but they proved highly addictive and when patients’ prescriptions ran out, many took to the streets to feed what had fast become a habit.

That’s where the problem really starts. In pill form, this medication could be controlled, but by going to “street chemists” for their fix, people were taking a huge risk.

They’d buy the drugs, illegally imported from China, ready mixed with harmless powders. Just a few grains of opioid in each capsule, which they’d either snort, smoke or inject.

Most of the powders are phenomenally potent. One, Carfentanil, is said to be 10,000 times stronger than heroin.

Originally created as an elephant tranquiliser, a couple of grains could be enough to kill.

Others are less powerful but still deadly, and here’s the real issue – most addicts have no idea which kind of opioid they’re taking.

Yet across America people are seeking out dealers and buying this stuff for as little as two dollars per fix.

Some have reached a truly hopeless stage.

Ian Blackburn, a long-time addict, told me he’s never known anything like it. He’s felt in control of his drug habit in the past. Not any more.

“Three hits, that’s all it takes”, he told me: “You take this stuff three times and it’s forever”.

He explained how he doesn’t get a buzz from the drug any more, he simply takes it to feel normal, to take the pain of withdrawal away. Without it, his legs start to cramp, his stomach wrenches and he loses control of his functions.

“Every couple of hours you need a hit”, he says “no ifs ands or buts, you’re going to find it and you’re going to get money to get it, no matter what”.

Source: http://www.itv.com/news/2017-06-27/opioid-crisis-claiming-record-number-of-addicts-lives-in-the-us/

September 2017

I was just learning this morning that CBD is well documented to trigger and act via PPAR gamma receptors which are well known to physicians as used in a class of diabetes drugs called the thiazolidinediones (pioglitazone and its congeners).

So I thought I should just check if this was involved in pregnancy and gestation.

Sure enough – BINGO!!!

Another strike of GOLD!!!

So I wrote this to add in the references…

Cannabidiol is known to interact with the (Peroxisome Proliferation Activated Receptor) PPARγ pathway 1-8.

PPARγ is known to be a very important transcription factor in metabolic regulation and is also the master regulator of the adipogenic differentiation pathway.

It also plays a key role in the reproductive tract with actions on the corpus luteum and developing gametes.

It has been documented in a rich literature to have a major effect on developing embryos and the reproductive tract 9-32.

References

1 De Filippis, D. et al. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS One 6, e28159, doi:10.1371/journal.pone.0028159 (2011).
2 Esposito, G. et al. Cannabidiol reduces Abeta-induced neuroinflammation and promotes hippocampal neurogenesis through PPARgamma involvement. PLoS One 6, e28668, doi:10.1371/journal.pone.0028668 (2011).
3 Hegde, V. L., Singh, U. P., Nagarkatti, P. S. & Nagarkatti, M. Critical Role of Mast Cells and Peroxisome Proliferator-Activated Receptor gamma in the Induction of Myeloid-Derived Suppressor Cells by Marijuana Cannabidiol In Vivo. J Immunol 194, 5211-5222, doi:10.4049/jimmunol.1401844 (2015).
4 Hind, W. H., England, T. J. & O’Sullivan, S. E. Cannabidiol protects an in vitro model of the blood-brain barrier from oxygen-glucose deprivation via PPARgamma and 5-HT1A receptors. Br J Pharmacol 173, 815-825, doi:10.1111/bph.13368 (2016).
5 O’Sullivan, S. E. & Kendall, D. A. Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology 215, 611-616, doi:10.1016/j.imbio.2009.09.007 (2010).
6 O’Sullivan, S. E., Sun, Y., Bennett, A. J., Randall, M. D. & Kendall, D. A. Time-dependent vascular actions of cannabidiol in the rat aorta. European journal of pharmacology 612, 61-68, doi:10.1016/j.ejphar.2009.03.010 (2009).
7 Ramer, R. et al. COX-2 and PPAR-gamma confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther 12, 69-82, doi:10.1158/1535-7163.MCT-12-0335 (2013).
8 Scuderi, C., Steardo, L. & Esposito, G. Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARgamma involvement. Phytother Res 28, 1007-1013, doi:10.1002/ptr.5095 (2014).
9 Adaikalakoteswari, A. et al. Low Vitamin B12 in Pregnancy Is Associated With Adipose-Derived Circulating miRs Targeting PPARgamma and Insulin Resistance. The Journal of clinical endocrinology and metabolism 102, 4200-4209, doi:10.1210/jc.2017-01155 (2017).
10 Anghebem-Oliveira, M. I. et al. Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population. Arch Endocrinol Metab 61, 238-248, doi:10.1590/2359-3997000000258 (2017).
11 Casamadrid, V., Amaya, C. A. & Mendieta, Z. H. Body Mass Index in Pregnancy Does Not Affect Peroxisome Proliferator-activated Receptor Gamma Promoter Region (-359 to -260) Methylation in the Neonate. Ann Med Health Sci Res 6, 38-43, doi:10.4103/2141-9248.180272 (2016).
12 Cawyer, C. et al. Attenuation of hyperglycemia-induced apoptotic signaling and anti-angiogenic milieu in cultured cytotrophoblast cells. Hypertens Pregnancy 35, 159-169, doi:10.3109/10641955.2015.1122035 (2016).
13 Drew, P. D. & Kane, C. J. Peroxisome Proliferator-Activated Receptor-gamma Agonists: Potential Therapeutics for Neuropathology Associated with Fetal Alcohol Spectrum Disorders. J Clin Cell Immunol 7, doi:10.4172/2155-9899.1000469 (2016).
14 Gao, F., Hu, W., Li, Y., Shen, H. & Hu, J. Mono-2-ethylhexyl phthalate inhibits human extravillous trophoblast invasion via the PPARgamma pathway. Toxicology and applied pharmacology 327, 23-29, doi:10.1016/j.taap.2017.04.014 (2017).
15 Hasby Saad, M., El-Anwar, N., Lotfy, S., Fouda, M. & Hasby, E. Human placental PPAR-gamma & SOX2 expression in serologically proved toxoplasmosis. Parasite Immunol, e12529, doi:10.1111/pim.12529 (2018).
16 Hu, W. et al. Activation of Peroxisome Proliferator-Activated Receptor Gamma and Disruption of Progesterone Synthesis of 2-Ethylhexyl Diphenyl Phosphate in Human Placental Choriocarcinoma Cells: Comparison with Triphenyl Phosphate. Environ Sci Technol 51, 4061-4068, doi:10.1021/acs.est.7b00872 (2017).
17 Kurzynska, A., Chojnowska, K., Bogacki, M. & Bogacka, I. PPAR ligand association with prostaglandin F2alpha and E2 synthesis in the pig corpus luteum-An in vitro study. Anim Reprod Sci 172, 157-163, doi:10.1016/j.anireprosci.2016.07.014 (2016).
18 Lecoutre, S. et al. Depot- and sex-specific effects of maternal obesity in offspring’s adipose tissue. The Journal of endocrinology 230, 39-53, doi:10.1530/JOE-16-0037 (2016).
19 Lendvai, A., Deutsch, M. J., Plosch, T. & Ensenauer, R. The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development. Am J Physiol Endocrinol Metab 310, E797-810, doi:10.1152/ajpendo.00372.2015 (2016).
20 Lin, Y., Bircsak, K. M., Gorczyca, L., Wen, X. & Aleksunes, L. M. Regulation of the placental BCRP transporter by PPAR gamma. J Biochem Mol Toxicol 31, doi:10.1002/jbt.21880 (2017).
21 Maekawa, M. et al. Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes. Transl Psychiatry 7, e1229, doi:10.1038/tp.2017.182 (2017).
22 Mahendra, J. et al. Evidence Linking the Role of Placental Expressions of Peroxisome Proliferator-Activated Receptor-gamma and Nuclear Factor-Kappa B in the Pathogenesis of Preeclampsia Associated With Periodontitis. J Periodontol 87, 962-970, doi:10.1902/jop.2016.150677 (2016).
23 Marginean, C. et al. The role of TGF-beta1 869 T > C and PPAR gamma2 34 C > G polymorphisms, fat mass, and anthropometric characteristics in predicting childhood obesity at birth: A cross-sectional study according the parental characteristics and newborn’s risk for child obesity (the newborns obesity’s risk) NOR study. Medicine (Baltimore) 95, e4265, doi:10.1097/MD.0000000000004265 (2016).
24 Meher, A. P. et al. Placental DHA and mRNA levels of PPARgamma and LXRalpha and their relationship to birth weight. J Clin Lipidol 10, 767-774, doi:10.1016/j.jacl.2016.02.004 (2016).
25 Papamitsou, T., Toskas, A., Papadopoulou, K., Economou, Z. & Sioga, A. Expression of peroxisome proliferator activation receptors (PPARs) and TNFalpha in placenta tissues in unexplained recurrent pregnancy loss: an immunohistochemical study. Histology and histopathology 31, 1029-1036, doi:10.14670/HH-11-734 (2016).
26 Roberti, S. L. et al. Critical role of mTOR, PPARgamma and PPARdelta signaling in regulating early pregnancy decidual function, embryo viability and feto-placental growth. Molecular human reproduction, doi:10.1093/molehr/gay013 (2018).
27 Shapiro, A. L. et al. Nicotinamide Promotes Adipogenesis in Umbilical Cord-Derived Mesenchymal Stem Cells and Is Associated with Neonatal Adiposity: The Healthy Start BabyBUMP Project. PLoS One 11, e0159575, doi:10.1371/journal.pone.0159575 (2016).
28 Singh, S. P. et al. Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia. J Immunol 198, 3815-3822, doi:10.4049/jimmunol.1700014 (2017).
29 Sonanez-Organis, J. G. et al. HIF-1alpha and PPARgamma during physiological cardiac hypertrophy induced by pregnancy: Transcriptional activities and effects on target genes. Gene 591, 376-381, doi:10.1016/j.gene.2016.06.025 (2016).
30 Wang, L. L., Yu, Y., Guan, H. B. & Qiao, C. Effect of Human Umbilical Cord Mesenchymal Stem Cell Transplantation in a Rat Model of Preeclampsia. Reprod Sci 23, 1058-1070, doi:10.1177/1933719116630417 (2016).
31 Wu, Y., Ruan, Y., Shen, L. & Gong, Q. Protective effects of PPAR-gamma against pregnancy-induced hypertension by differential ETR expression in rat models. J Cell Biochem 119, 3118-3128, doi:10.1002/jcb.26454 (2018).
32 Xu, Y. et al. An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment. J Immunol 196, 2476-2491, doi:10.4049/jimmunol.1502055 (2016).

Source: Email to www.drugwatch.org from Stuart Reece April 2018

The Oregon Health Authority also issued this month a baseline report titled Marijuana Report: Use, Attitudes, and Health Effects in Oregon. This comprehensive report includes several key findings.
 
Pictured above, for example, is a state map showing the 40 cities and 11 counties that have banned marijuana businesses within their boundaries. However, the Oregon Medical Marijuana Dispensary Program shows those numbers to be higher. Some 80 of the state’s 242 cities and 17 of its 36 counties have banned marijuana processing businesses and marijuana dispensaries from conducting business within their boundaries.
 
Oregon legalized marijuana for medical use in 1998 and for recreational use in 2014. Possession of up to eight ounces became legal for those age 21 or older July 1, 2015. Because recreational dispensaries will not open until late this year, the state allowed dispensaries selling pot for medical use to begin selling pot for recreational use as well October 1, 2015.
 
In just three months, however, some changes are already being seen. Marijuana-related calls to the state’s Poison Control Center increased in the last half of 2015, for example, from 105 in 2014 to 158 in 2015.
 
Other data include:

  • One in ten 8th-graders and one in five 11th-graders used marijuana in the past month, about the same as national levels.
  • Approximately 90% of marijuana users smoke the drug.
  • Some 62% of 11th-graders report marijuana is easy to get, some say easier than cigarettes.
  • Nearly half of current marijuana using 11th-graders who drive say they drove within three hours of using the drug.
  • Half (51%) of Oregon adults have seen marijuana store or product advertising, but less than one-third (29%) have seen information about marijuana health effects.
  • Nearly two-thirds (63%) of Oregon adults say they don’t know when it is legal to drive after using marijuana.

Read this report here.

The Oregon Health Authority has issued two new reports on marijuana. Oregon’s Medical Marijuana Program: Statistical Snapshot, January 2016 finds that 22 physicians have recommended marijuana for medical use to 85% of the state’s registered patients.
 
Some 1,700 physicians serve between 1 and 449 patients and account for a total of 19,087 patients, while 22 physicians account for a total of 60,908 patients, an average of 2,769 patients each.
 
Oregon now has registered:

  • 77,155 patients
  • 35,736 caregivers
  • 46,812 growers
  • 32,171 grow sites

Patients are 59% male, 41% female. Conditions they registered for (they may register for more than one condition) include:

  • Severe pain, 71,533 (92%)
  • Spasms, 22,501 (28.9%)
  • Nausea, 10,680 (13.7%)
  • PTSD, 5,527 (7.1%)
  • Cancer, 4,460 (5.7%)
  • Seizures, 2,122 (2.7%)

Those listing cachexia, HIV/AIDS, glaucoma, and Alzheimer’s disease are less than 1.5% each.
 
Read this report here.

Source:

https://www.oregon.gov/oha/ph/DiseasesConditions/ChronicDisease/MedicalMarijuanaProgram/Documents/OMMP%20Statistic%20Snapshot%20-%2001-2016.pdf

Cannabis oil has come under scrutiny

RUNGROJ YONGRIT/EPA-EFE/REX/Shutterstock

By Alison George

Cannabis is in the headlines for its potential medical benefits after the recent confiscation of cannabis oil medication from the mother of a 12-year-old British boy with severe epilepsy. The furore that ensued is shining a light on campaigns for cannabis oils to be made legal for medical reasons, and the UK government has now announced a review into the use of medicinal cannabis. Here’s what you need to know.

What is cannabis oil?

Cannabis oil is extracted from the cannabis plant Cannabis sativa. The plants medicinal properties have been touted for more than 3,000 years. It was described in the ancient Eygyptian Ebers papyrus around 1550BC, and it was likely used as a medicine in China before that. Some varieties of the plant contain high levels of the psychoactive substance tetrahydrocannabinol (THC), which is responsible for the “high” that comes from smoking or eating cannabis leaves or resin. The plant’s other major chemical component is cannabidiol, which has no psychoactive effect. Both act on the body’s natural cannabinoid receptors which are involved in many processes such as memory, pain and appetite. The cannabis plant also contains more than 100 other different cannabinoid compounds at lower concentrations.

So can cannabis oil make you high?

It depends on the THC content. Some types of Cannabis sativa plant, known as hemp, contain very little THC. The extracts from these plants contain mainly cannabidiol, so will not get anyone stoned.

Is it legal?

That’s a complicated question. In the UK cannabidiol is legal. Cannabis plant extracts (known as hemp or CBD oils) are available in high-street stores but the THC content must be below 0.2 per cent. “THC is not psychoactive at this level,” says David Nutt, a neuropsychopharmacologist at Imperial College London. But cannabidiol is illegal in many other countries.

In the USA for example, cannabidiol is classed as a schedule 1 controlled substance, and can only be sold in states where cannabis use is legal.

However, the tide may turn in favour of cannabidiol after a recent World Health Organisation review. This concluded that cannabidiol “exhibits no effects indicative of any abuse or dependence potential” but “has been demonstrated as an effective treatment of epilepsy … and may be a useful treatment for a number of other medical conditions.”

What is the evidence that cannabis oils can help treat epilepsy?

Although there is some scientific evidence that THC has potential to control convulsions, its mind-altering effects mean that much of the focus has turned to cannabidiol – particularly for childhood epilepsies that conventional drugs fail to control.

Two recent high quality randomised and placebo controlled trials showed that cannabidiol is an effective treatment for Lennox-Gastaut syndrome and Dravet syndrome, severe forms of epilepsy. The mechanism of action is unknown, but it may be due to a combination of effects, such as inhibiting the activity of neurons and dampening inflammation in the brain.

The situation is less clear when it comes to the use of commercial cannabis oils to control seizures, where the evidence is mainly anecdotal, and the oils can contain differing concentrations of cannabidiol and THC.

The UK government announced on 19 June that it would review the use of medical cannabis.

Are there any cannabis-based epilepsy drugs on the market?

Not yet. In April the US Food and Drug Administration recommended the approval of a drug called Epidiolex for Lennox-Gastaut syndrome and Dravet syndrome. Its active ingredient is cannabidiol, and final approval is due at the end of this month.

However, it is possible the drug is not as effective as cannabis oil containing THC, says Nutt. For example, the cannabis oil used to treat Billy Caldwell, the boy at the centre of the recent cannabis oil confiscation furore, contained cannabidiol and a low dose of THC, because cannabidiol alone did not stop all his seizures.

This is one of the big unknowns. “It is important to remember that there is currently very little scientific evidence to support cannabis oil containing both THC and cannabidiol as a treatment for epilepsy,” said the charity Epilepsy Action, in a statement issued this month.

Are cannabis-based medications available for other conditions?

Yes. A synthetic version of THC called Nabilone has been used since the 1980s to treat nausea after chemotherapy and to help people put on weight. A drug called Sativex is also approved for the treatment of pain and spasms associated with multiple sclerosis. It contains an equal mix of THC and cannabidiol, but would not be suitable for the treatment of children with epilepsy such as Billy. “If you used that to treat epilepsy, the kids would be stoned off their heads,” says Nutt.

What is the aim of the UK government’s review of medical cannabis? 

The first part of the review will look at the evidence for the therapeutic value of cannabis-based products. It can recommend any promising ones for the second part of the review. This will be carried out by the government’s Advisory Council for the Misuse of Drugs, which can recommend a change to the legal medical status of cannabis and cannabinoids.

This will hopefully lead to a relaxation of the rules surrounding research into cannabis-based medicines says Tom Freeman, a clinical psychopharmacologist at King’s College London.

In the UK cannabis currently has Schedule 1 status, the most restrictive category, which is for drugs which are not used medicinally such as LSD. “This creates a Catch 22 situation,” says Freeman. “You can’t show that cannabis and cannabis-based products have medicinal value because of restrictions on medical research.”  If cannabis is moved to the Schedule 2 category, it will join substances such as morphine and diamorphine (heroin) which can be prescribed by doctors if there is a clinical need. 

Source: https://www.newscientist.com/article/2172415-cannabis-oil-what-is-it-and-does-it-really-work-as-medicine/  June 2018

Watch Here and Share!

As the legal status of marijuana changes its perceived dangers are lessening while the potency of the drug is increasing.

This video covers marijuana as a psychoactive substance that induces its effects by manipulation of natural brain chemicals known as  the endocannabinoids.The toxic and addictive impact that results from the drug’s disruption of natural endocannibinoids is characterized in this video by the testimony of those impacted by the drug and by the scientists who are studying its effects.

This video is 26 minutes and will help to clarify the many myths and misconceptions regarding the effects of marijuana.

Source: Email from SAM (Smart Approaches to Marijuana) <info@learnaboutsam.org>

March 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

There will never be fundamental change in west Belfast’s drug problem without addressing the poverty and conflict legacies affecting it, a new report has found.

Launched on Monday, the West Belfast Community Drugs Panel’s report examined all aspects of drugs misuse in the area and provided a series of recommendations.

The panel was set up in October last year in reaction to a spate of drug-related deaths in the west of the city and is made up of representatives from several government departments, including the Belfast Trust and the Public Health Agency.

Families in the area affected by drugs, including bereaved parents, were also invited to give their views through community representatives on the panel, which was chaired by Noel Rooney, former head of the Probation Board for NI.

Funding for the report was provided by the Belfast Policing and Community Safety Partnership, which is made up of councillors and representatives from statutory agencies.

The report found significant issues relating to drugs misuse in west Belfast, many related to chronic under-funding by successive governments and the lack of a coherent, multi-agency strategy to deal with the problem.

It also identified significant contributing factors relating to the area’s social housing provision.

Several of the root causes detailed in the report, however, are generational and systemic.

“The West Belfast drugs issue is directly related to the area being affected by systemic poverty and the legacy of the NI Conflict and, unfortunately, this looks set to worsen over time,” the report reads.

“There will never be a fundamental change for west Belfast without addressing the poverty and conflict legacies.”

Elsewhere, the panel found addiction to prescription medications to be disproportionately high in the area.

“Evidence shows the level of prescribing medication in west Belfast is higher than in most other parts of Belfast, the north of Ireland and Great Britain,” the document states.

The report recommends several measures that public agencies could take to try and tackle the problem, including:

– An anti-poverty plan aligned with appropriate, long-term funding (10-15 year minimum)

– A multi-layered education strategy with a focus on early intervention

– A co-designed pilot social housing model, specifically for the area

– A zero-tolerance drugs policy from the PSNI, with a stronger focus on small level dealing

In addition, the report includes a ‘What We Heard’ section summarising key information providing to the panel by members of the public, community representatives and others.

“Criminal gangs, some claiming to have paramilitary connections, are controlling the supply of cocaine and heroin in some streets to children as young as 12-years-old,” the report reads.

“They decide what to provide and how much it will cost local people.”

Prescription medications being reported as being currently misused in west Belfast include: Tramadol, an opiate-based painkiller, and Fentanyl, a tranquiliser 100 times stronger than heroin.

It is now in the hands of government agencies to decide which, if any, of the report’s recommendations they might adopt.

Source:  https://www.belfasttelegraph.co.uk/news/northern-ireland/children-as-young-as-12-taking-drugs   11th June 2018

 

Submitted by Livia Edegger

Strengthening Families Programme, a family-focused prevention programme used in 26 countries around the world, was found to be nine times more effective than individually-targeted programmes and yielded a $10 return for every dollar spent on it. The programme, designed for youth and their families, aims to improve parent-child interactions, parenting skills and strengthen young people’s social and problem-solving skills.

Submitted by Livia Edegger 

As support for decriminalising and legalising marijuana is growing, several new studies highlight the potentially harmful effects of the drug on its user’s brain and heart. The findings are particularly revealing in the field of recreational cannabis use. While studying the brains of a group of twenty occasional cannabis smokers, researchers from Harvard University found that as few as one or two uses a week can change the brain. Smoking marijuana was found to primarily affect the areas involved in decision making, emotions and motivations. Along the same lines, a group of French researchers found that marijuana use ups the risk of developing heart problems (i.e. strokes, heart attacks and circulation problems). More research is needed to better understand the health risks associated with marijuana.

Links:

Source:

http://preventionhub.org/en/prevention-update/even-casual-cannabis-use-can-affect-health

Submitted by Andy Travis 

Those who first used alcohol at or before the age of 14 were nearly four times more likely to meet the criteria for past year alcohol abuse or dependence than those who started using alcohol between the ages of 18 and 20 (16.5% vs. 4.4%) and more than six times more likely than those who started using alcohol at or after age 21 (16.5% vs. 2.5%).

These findings illustrate the need for alcohol education and prevention efforts as early as middle school.

Percentage of Adults (Ages 21 or Older) Who Abused or Were Dependent on Alcohol in the Past Year, by Age of First Alcohol Use, 2009.

 

Similarly, adults who first started using marijuana at or before the age of 14 are most likely to have abused or been dependent on illicit drugs in the past year. Adults who first used marijuana at age 14 or younger were six times more likely to meet the criteria for past year illicit drug abuse or dependence than those who first used marijuana when they were 18 or older (12.6% vs. 2.1%) and almost twice as likely as those who started between the ages of 15 and 17 (12.6% vs. 6.6%).

Percentage of Adults (Ages 21 or Older) Who Abused or Were Dependent on Illicit Drugs in the Past Year, by Age of First Marijuana Use, 2009.

 

Links:
• Adults Who Initiate Alcohol Use Before Age 21 More Likely to Abuse or Become Dependent on Alcohol(link is external) – CESAR FAX, University of Maryland, USA.
• Early Marijuana Use Related to Later Illicit Drug Abuse and Dependence(link is external) – CESAR FAX, University of Maryland, USA.

Source:

http://preventionhub.org/en/prevention-update/adults-who-initiate-alcohol-and-marijuana-use-age-21-are-much-more-likely-abuse-or-become-d

Submitted by Andy Travis

This forthright editorial in the journal ‘Addiction’ joins over 500 public health leaders and 27 organisations in questioning the role of the global alcohol industry in making alcohol policy. Conflict with the tobacco industry is well documented, where vested interests have fought an aggressive rearguard action against efforts to reduce tobacco harm. Alcohol interests are now seen to be moving intensively into areas of policy making. Addiction’s editorial raises the strong suspicion that these moves are designed mainly to impede effective control and protect commercial interests. The WHO’s Global Strategy on the Harmful Use of Alcohol was endorsed unanimously in 2010, but in 2012 the alcohol producers issued their own strategy and claimed that the adoption of the WHO strategy, ‘…has legitimated industry’s ongoing efforts and has opened the door to the inclusion of producers as equal stakeholders’. Leading health professionals responded with dismay, arguing that the producer’s actions are weak, mostly lacking an appropriate evidence base and unlikely to reduce harm. Dr Chan, Director General of WHO, recently commented on the role of big business.

As the new publication makes clear, it is not just Big Tobacco anymore. Public health must also contend with Big Food, Big Soda, and Big Alcohol. All of these industries fear regulation, and protect themselves by using the same tactics. Research has documented these tactics well. They include front groups, lobbies, promises of self-regulation, lawsuits, and industry-funded research that confuses the evidence and keeps the public in doubt. Tactics also include gifts, grants, and contributions to worthy causes that cast these industries as respectable corporate citizens in the eyes of politicians and the public.

Concern has also been expressed over ‘aggressive marketing strategies’ in areas of the world with minimum alcohol and tobacco policies in place, such as many countries with emerging economies in Asia, Africa and Latin America (see Prevention Hub link below). The ‘Addiction’ editorial highlights the marketing of alcohol to young people and promotion of products such as alcopops.

Links:

Source:

http://preventionhub.org/en/prevention-update/international-outcry-grows-over-alcohol-industry-role-policy-making

Filed under: Alcohol,Economic,Latest News :

An effective drug-free workplace policy is one of the best ways for employers to protect their businesses. An effective program does not end with pre-employment screening, since any drug user can count up to three days before the test and then begin to use again after being hired.

Drug-free workplace policies reduce the amount of sick time, absenteeism, workman’s comp claims, insurance premiums, and protects against civil lawsuits because of an employee who inflicts damage on others because of impairment.

Communities that emphasize and encourage drug-free workplace practices can have an impact on overall drug use in the community. When combined with effective education and prevention, and by increasing the incentive of users to seek treatment, we can promote a drug-free culture and a thriving business environment that protects individuals, families and the community.

While some might think they don’t need a drug-free workplace policy, as we discussed last week, that’s really not true. Small businesses, not just large companies, need firm drug testing policies.

One new form of marijuana that’s growing in popularity nationwide underscores the need for workplace drug testing programs. This dangerous drug, wax marijuana, can easily be used in the workplace because it doesn’t look like regular marijuana — and frighteningly, it’s the most powerful form of the drug.

Here’s what employers need to know about wax marijuana, and why it shows the need to participate in Drug Free Work Week.

The 411 on Wax Marijuana – and What it Means for Drug Free Workplace Programs

With aliases like butter and honeycomb because of its waxy texture, wax is the most powerful form of marijuana.

According to wax marijuana users, a single hit can leave a high lasting all day. One dosage is equal to 20 marijuana cigarettes and can produce powerful hallucinations and psychotic effects. This potency is because wax marijuana is more than 80% pure THC.

Manufacturers produce wax by extracting the main psychoactive compound, Tetrahydrocannabinol (THC), from marijuana. They use flammable substances like butane in the process, which makes it quite dangerous, but renders the wax marijuana very strong.

While wax marijuana is legal in states like Colorado and Washington, it’s illegal under federal law and in most states.

Employers should take note – due to its appearance, wax marijuana can be passed off as lip balm.

This means that your employees could bring the most powerful form of marijuana into the workplace and use it right under your nose.

Remember, any on-the-clock substance abuse has lasting effects on your workplace, particularly when it comes to the safety of your employees. Just one hit of wax marijuana can result in an extremely powerful, daylong high — rendering your worker a serious danger to everyone around them.

Your workplace needs a drug testing policy to combat new trends in substance use, like wax marijuana.

Drug Free Work Week is a great opportunity for you to take stock of your existing drug testing policy or create a new workplace drug testing program. If you don’t take the time now to create or revise a policy, you may pay for it down the line as your employees try new drugs, such as wax marijuana, and end up causing injuries or financial damage to your workplace.

Partner With ARCpoint Labs for Workplace Drug Testing Policies.

Located nationwide, ARCpoint Labs provides workplace drug testing assistance. We can work with you to create and implement a drug testing policy that fits your unique needs, considering desired detection windows, new and emerging drugs, and your community’s particular substance abuse issues. Let us work with you to carry out a custom drug testing program.

Source: http://sober-work-place.com/drug-testing-2/with-wax-marijuana-use-on-the-rise-make-sure-you-celebrate-drug-free-work-week/  Introduction from Monte Stiles from DWI

This is a very powerful and heartbreaking story –  let us hope many young people will take notice and never ‘try’ drugs offered by ‘a friend’

Connor Reid Eckhardt added a new video.

“THIS IS SO IMPORTANT TO SHARE….THIS IS NOT A MOVIE!! OUR 19 YEAR OLD SON CONNOR IS NOT WAKING UP FROM THE SINGLE HIT OF “SPICE, K2,” HE TOOK. It has over 600 names. The credits are not going to roll. He is not going surfing this morning. He is GETTING “THAT HAIR CUT” we never wanted to give before he goes into surgery to donate 4 of his organs to SAVE FOUR OTHER LIVES. Connor died. Our son, our only son died from a legal high purchased at the corner market. No drugs or alcohol in his system. Most, not all legal highs are made in CHINA and sold to our youth. Millions are being affected by these legal highs. Please help us get the attention of presidential candidates. We must get this stopped. An entire generation of children and youth are at risk. Please get educated. The Connor Project Foundation is about Education, Awareness, and Prevention. Doit4connor. Do it for your kids and for your communities.

OUR 19 OLD SON CONNOR IS DEAD FROM ONE HIT OF A SYNTHETIC DRUG called spice. WHERE DOES MOST OF THIS POISON COME FROM??? CHINA!!! Who sells this poison to our kids? Go check out these shop owners. WE LET THESE CHEMICALS INTO THE USA?? Why?? Connor made a decision that night that changed our lives forever. He chose to try legal high offered to him “by a friend”. It is sold over the counter in gas stations, mini marts, smoke shops, etc. Targeted at our youth. Stop the madness and share with at least one person. We must take a stand for Connor and all the others who have died or are institutionalized because of these killer legal highs.”

Source:

https://www.facebook.com/270455916494386/videos/436695296537113/

Researchers at the Centre for Addiction and Mental Health (CAMH) have identified 428 distinct disease conditions that co-occur in people with Fetal Alcohol Spectrum Disorders (FASD), in the most comprehensive review of its kind.

The results were published today in The Lancet.

“We’ve systematically identified numerous disease conditions co-occurring with FASD, which underscores the fact that it isn’t safe to drink any amount or type of alcohol at any stage of pregnancy, despite the conflicting messages the public may hear,” says Dr. Lana Popova, Senior Scientist in Social and Epidemiological Research at CAMH, and lead author on the paper. “Alcohol can affect any organ or system in the developing fetus.”

FASD is a broad term describing the range of disabilities that can occur in individuals as a result of alcohol exposure before birth. The severity and symptoms vary, based on how much and when alcohol was consumed, as well as other factors in the mother’s life such as stress levels, nutrition and environmental influences. The effects are also influenced by genetic factors and the body’s ability to break down alcohol, in both the mother and fetus.

Different Canadian surveys suggest that between six and 14 per cent of women drink during pregnancy.

The 428 co-occurring conditions were identified from 127 studies included in The Lancet review. These disease conditions, coded in the International Classification of Disease (ICD-10), affected nearly every system of the body, including the central nervous system (brain), vision, hearing, cardiac, circulation, digestion, and musculoskeletal and respiratory systems, among others.

While some of these disorders are known to be caused by alcohol exposure – such as developmental and cognitive problems, and certain facial anomalies – for others, the association with FASD does not necessarily represent a cause-and-effect link.

Problems range from communications disorders to hearing loss

However, many disorders occurred more often among those with FASD than the general population. Based on 33 studies representing 1,728 individuals with Fetal Alcohol Syndrome (FAS), the most severe form of FASD, the researchers were able to conduct a series of meta-analyses to establish the frequency with which 183 disease conditions occurred.

More than 90 per cent of those with FAS had co-occurring problems with conduct. About eight in 10 had communications disorders, related to either understanding or expressing language. Seven in 10 had developmental/cognitive disorders, and more than half had problems with attention and hyperactivity.

Because most studies were from the U.S., the frequency of certain co-occurring conditions was compared with the general U.S. population. Among people with FAS, the frequency of hearing loss was estimated to be up to 129 times higher than the general U.S. population, and blindness and low vision were 31 and 71 times higher, respectively.

“Some of these other co-occurring problems may lead people to seek professional help,” says Dr. Popova. “The issue is that the underlying cause of the problem, alcohol exposure before birth, may be overlooked by the clinician and not addressed.”

The benefits of screening and diagnosis

Improving the screening and diagnosis of FASD has numerous benefits. Earlier access to programs or resources may prevent or reduce secondary outcomes that can occur among those with FASD, such as problems with relationships, schooling, employment, mental health and addictions, or with the law.

“We can prevent these issues at many stages,” says Dr. Popova. “Eliminating alcohol consumption during pregnancy or reducing it among alcohol-dependent women is extremely important. Newborns should be screened for prenatal alcohol exposure, especially among populations at high risk. And alerting clinicians to these co-occurring conditions should trigger questions about prenatal alcohol exposure.”

“It is important that the public receive a consistent and clear message – if you want to have a healthy child, stay away from alcohol when you’re planning a pregnancy and throughout your whole pregnancy,” she says.

It’s estimated that FASD costs $1.8 billion annually in Canada, due largely to productivity losses, corrections and health care costs, among others.

In addition to this review, Dr. Popova has been part of an expert group of leading FASD researchers and clinicians working with the Ontario Ministry of Children and Youth Services on its new FASD strategy. Her team is also undertaking a study to determine how common FASD is in Canada, as well as in other countries in Eastern and Central Europe and Africa.

Source:

https://m.medicalxpress.com/news/2016-01-conditions-co-occur-fetal-alcohol-spectrum.html

January 2016

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