Drug use-various effects on foetus, babies, children and youth

Source: Email from Ed Moses to Drug Watch International drug-watch-international@googlegroups.com August 2017

The use of psychoactive substances among children and young people is one of today’s challenges. In order to solve this problem by acting in a coordinated manner, this academic year Vilnius city municipality, in cooperation with the Ministry of the Interior of the Republic of Lithuania, implemented a pilot model for the prevention of drug use and distribution by minors in schools. The project was implemented in three schools of the capital – Antakalnis, Vasilijaus Kačialovos and Vilnius Jesuit high schools.

“Initiating this project, we aimed to increase the safety of students in educational institutions and their entrances, to include in the project all persons participating in the student’s life and, most importantly, to respond to the needs of minors. The problem of psychoactive substance use among young people is not only in Vilnius, so we paid a lot of attention to the sharing of good practices between municipalities,” said Agneta Ladek, Deputy Minister of the Ministry of the Interior of the Republic of Lithuania.

In implementing the project, the Vilnius City Municipality relied on the international primary prevention model Planet Youth, based on scientific and practical evidence, which was implemented in the capital in 2020. One of the key aspects of the model is a community-based approach that fosters positive relationships between children and their families, peers, educators and other adults.

“Building a strong community—of children, parents, or teachers—is the healthiest and wisest way to promote children’s well-being and help them grow into mature individuals who make healthy choices.” It has been scientifically proven that children and teenagers who are surrounded by a positive environment, who have good relations with teachers and parents, use or consider using legal and illegal psychoactive substances much less often,” said Simona Bieliūnė, the vice-mayor of the city of Vilnius.

It is planned that the activities tested during the project will continue to be implemented in other schools of the capital. This will contribute to the consistent implementation of prevention of the use and distribution of psychoactive substances and will help to form healthy lifestyle habits.

Implementation of projects to strengthen school communities

The pilot model project was implemented in three schools of the capital – Antakalnis, Vasilijaus Kačialovos and Vilnius Jesuit high schools. Realizing the extent of the problem of the use and distribution of psychoactive substances among schoolchildren, the heads of educational institutions do not shy away from talking about it publicly and looking for solutions.

“Every year, students from about 30 different educational institutions come to the first classes of the high school, so it is natural that attitudes and attitudes differ. With the start of the new academic year, we face great challenges in order to familiarize students and their parents with the rules in force at our school, and their observance,” said Anželika Keršinskienė, director of Vilnius Antakalnis Gymnasium.

When planning the preventive measures for the implementation of the project, we were guided by the data of each school’s “Planet Youth” study on the extent of psychoactive substance use, children’s psychological resilience, trends in relations with parents, peers, teachers and other factors related to the use of psychoactive substances – common goals are achieved by adapting to unique school situations. After the initiation of the project, data-based individual prevention plans were created and the conditions for their implementation were created, as well as preventive activity planning, financing and implementation practices suitable for the entire municipality were tested.

All the schools that participated in the project note that the project allowed the school communities – administration, teachers, students and their parents – to focus, helped to become more active and strengthen mutual relations.

“During the project, the funds allocated by the municipality allowed our school to expand and renovate the student’s leisure spaces, install smoke detectors, partially covered the costs of fencing the school’s territory. We are happy that the students willingly got involved in the activities, initiated and created social advertisements themselves, but our most important achievement is that our school community started to speak “one language”, said Roza Dimentova, director of Vilnius V. Kačialovos Gymnasium.

“As part of the project, we established 6 student clubs according to their interests on the initiative of the students. Parents and teachers were involved in the activities. Such clubs, such as astronomy, politics or games, bring all participants together and encourage increased student engagement in extracurricular activities. We plan to continue these activities and expand them next year as well,” said Vilnius Jesuit High School director S. Edita Šicaite.

In the pilot model discussion – insights from the professionals

During the implementation of the pilot model for the prevention of underage drug use and distribution in schools, the Vilnius Public Health Office, police representatives, as well as experts from the Icelandic “Planet Youth” model joined the project activities together with the Vilnius City Municipality.

In the discussion of the pilot model, representatives of the municipality for the first time presented footage of the network of free services for the use of psychoactive substances in the city of Vilnius, which will be distributed to doctors and teachers. An informational publication has been created so far, which can be accessed at the address paslaugosjaunimui.lt.

The coordinator of the Vilnius Public Health Office presented the project activities implemented in pilot schools and the importance of student research results in planning targeted prevention measures at different levels of the community.

In the discussion of the pilot model, a tool for assessing the security of school infrastructure was also presented, as well as additional measures for the prevention of the use and distribution of psychoactive substances.

Source: https://madeinvilnius.lt/en/news/city/pilot-model-of-prevention-of-drug-use-and-distribution-by-minors-in-schools-was-implemented-in-Vilnius

Bertha Madras, a leading expert on weed, outlines the science linking it to psychiatric disorders, permanent brain damage, and other serious harms.

Young people who smoked marijuana in the 1960s were seen as part of the counterculture. Now the cannabis culture is mainstream. A 2022 survey sponsored by the National Institutes of Health found that 28.8% of Americans age 19 to 30 had used marijuana in the preceding 30 days—more than three times as many as smoked cigarettes. Among those 35 to 50, 17.3% had used weed in the previous month, versus 12.2% for cigarettes.

While marijuana use remains a federal crime, 24 states have legalized it and another 14 permit it for medical purposes. Last week media outlets reported that the Biden administration is moving to reclassify marijuana as a less dangerous Schedule III drug—on par with anabolic steroids and Tylenol with codeine— which would provide tax benefits and a financial boon to the pot industry.

Bertha Madras thinks this would be a colossal mistake. Ms. Madras, 81, is a psychobiology professor at Harvard Medical School and one of the foremost experts on marijuana. “It’s a political decision, not a scientific one,” she says. “And it’s a tragic one.” In 2024, that is a countercultural view.

Ms. Madras has spent 60 years studying drugs, starting with LSD when she was a graduate student at Allan Memorial Institute of Psychiatry, an affiliate of Montreal’s McGill University, in the 1960s. “I was interested in psychoactive drugs because I thought they could not only give us some insight into how the brain works, but also on how the brain undergoes dysfunction and disease states,” she says.

In 2015 the World Health Organization asked her to do a detailed review of cannabis and its medical uses. The 41-page report documented scant evidence of marijuana’s medicinal benefits and reams of research on its harms, from  cognitive impairment and psychosis to car accidents.

She continued to study marijuana, including at the addiction neurobiology lab she directs at Mass General Brigham McLean Hospital. In a phone interview this week, she walked me through the scientific literature on marijuana, which runs counter to much of what Americans hear in the media.

For starters, she says, the “addiction potential of marijuana is as high or higher than some other drug,” especially for young people. About 30% of those who use cannabis have some degree of a use disorder. By comparison, only 13.5% of drinkers are estimated to be dependent on alcohol. Sure, alcohol can also cause harm if consumed in excess. But Ms. Madras sees several other distinctions.

One or two drinks will cause only mild inebriation, while “most people who use marijuana are using it to become intoxicated and to get high.” Academic outcomes and college completion rates for young people are much worse for those who use marijuana than for those who drink, though there’s a caveat: “It’s still a chicken and egg whether or not these kids are more susceptible to the effects of marijuana or they’re using marijuana for self medication or what have you.”

Marijuana and alcohol both interfere with driving, but with the former there are no medical “cutoff points” to determine whether it’s safe to get behind the wheel. As a result, prohibitions against driving under the influence are less likely to be enforced for people who are high. States where marijuana is legal have seen increases in car accidents.

One of the biggest differences between the two substances is how the body metabolizes them. A drink will clear your system within a couple of hours. “You may wake up after binge drinking in the morning with a headache, but the alcohol is gone.” By contrast, “marijuana just sits there and sits there and promotes brain adaptation.”

That’s worse than it sounds. “We always think of the brain as gray matter,” Ms. Madras says. “But the brain uses fat to insulate its electrical activity, so it has a massive amount of fat called white matter, which is fatty. And that’s where marijuana gets soaked up. . . . My lab showed unequivocally that blood levels and brain levels don’t correspond at all—that brain levels are much higher than blood levels. They’re two to three times higher, and they persist once blood levels go way down.” Even if people quit using pot, “it can persist in their brain for a while.”

Thus marijuana does more lasting damage to the brain than alcohol, especially at the high potencies being consumed today. Levels of THC—the main psychoactive ingredient in pot—are four or more times as high as they were 30 years ago. That heightens the risks, which range from anxiety and depression to impaired memory and cannabis hyperemesis syndrome—cycles of severe vomiting caused by long-term use.

There’s mounting evidence that cannabis can cause schizophrenia. A large-scale study last year that examined health histories of some 6.9 million Danes between 1972 and 2021 estimated that up to 30% of young men’s schizophrenia diagnoses could have been prevented had they not become dependent on pot. Marijuana is  worse in this regard than many drugs usually perceived as more dangerous.

“Users of other potent recreational drugs develop chronic psychosis at much lower rates,” Ms. Madras says. When healthy volunteers in research experiments are given THC—as has been done in 15 studies—they develop transient symptoms of psychosis. “And if you treat them with an antipsychotic drug such as haloperidol, those symptoms will go away.”

Marijuana has also been associated with violent behavior, including in a study published this week in the International Journal of Drug Policy. Data from observational studies are inadequate to demonstrate causal relationships, but Ms. Madras says that the link between marijuana and schizophrenia fits all six criteria that scientists use to determine causality, including the strength of the association and its consistency.

Ms. Madras says at the beginning of the interview that she was operating on three hours of sleep after crashing on scientific projects. Yet she is impressively lucid and energized. She peppers her explanations with citations of studies and is generous in crediting other researchers’ work.

Another cause for concern, she notes, is that more pregnant women are using pot, which has been linked to increased preterm deliveries, admissions of newborns into neonatal intensive care units, lower birth weights and smaller head circumferences. THC crosses the placenta and mimics molecules that our bodies naturally produce that regulate brain development.

“What happens when you examine kids who have been exposed during that critical period?” Ms. Madras asks. During adolescence, she answers, they show an increased incidence of aggressive behavior, cognitive dysfunction, and symptoms of ADHD and obsessive-compulsive disorders. They have reduced white and gray matter.

A drug that carries so many serious side effects would be required by the Food and Drug Administration to carry a black-box warning, the highest-level alert for drugs with severe safety risks. Marijuana doesn’t—but only because the FDA hasn’t cleared it.

The agency has selectively approved cannabis compounds for the treatment of seizures associated with Lennox-Gastaut or Dravet syndrome, nausea associated with chemotherapy for cancer, and anorexia associated with weight loss in AIDS patients. But these approved products are prescribed at significantly less potent doses than the pot being sold in dispensaries that are legal under state law.

What about medicinal benefits? Ms. Madras says she has reviewed “every single case of therapeutic indication for marijuana—and there are over 100 now that people have claimed—and I frankly found that the only one that came close to having some evidence from randomized controlled trials was the neuropathic pain studies.” That’s “a very specific type of pain, which involves damage to nerve endings like in diabetes or where there’s poor blood supply,” she explains.

For other types of pain, and for all other conditions, there is no strong evidence from high-quality randomized trials to support its use. When researchers did a “challenge test on normal people where they induce pain and tried to see whether or not marijuana reduces the pain, it was ineffective.”

Ms. Madras sees parallels between the marketing of pot now and of opioids a few decades ago. “The benefits have been exaggerated, the risks have been minimized, and skeptics in the scientific community have been ignored,” she says. “The playbook is always to say it’s safe and effective and nonaddictive in people.”

Advocates of legalization assert that cannabis can’t be properly studied unless the federal government removes it from Schedule I. Bunk, Ms. Madras says: “I have been able to study THC in my research program.” It requires more paperwork, but “I did all the paperwork. . . . It’s not too difficult.”

Instead of bankrolling ballot initiatives to legalize pot, she says, George Soros and other wealthy donors who “catalyzed this whole movement” should be funding rigorous research: “If these folks, these billionaires, had just taken that money and put it into clinical trials, I would have been at peace.”

It’s a travesty, Ms. Madras adds, that the “FDA has decided that they’re going to listen to that movement rather than to what the science says.” While the reclassification wouldn’t make recreational marijuana legal under federal law, dispensaries and growers would be able to deduct their business expenses on their taxes. The rescheduling would also send a cultural signal that marijuana use is normal.

Ms. Madras worries that “it sets a precedent for the future.” She points to the movement in states to legalize psychedelic substances, for whose medicinal benefits there also isn’t strong scientific evidence. Meantime, she says it makes no sense that politicians continuously urge more spending on addiction treatment and harm reduction while weakening laws that prevent people from becoming addicted in the first place.
Her rejoinder to critics who say the war on drugs was a failure? “This is not a war on drugs. It’s a defense of the human brain at every possible age from in utero to old age.”

Ms. Finley is a member of the Journal’s editorial board.

Source: https://www.wsj.com/articles/what-you-arent-reading-about-marijuana-permanent-brain-damage-biden-schedule-iii-9660395e May 2024

 

A Research Letter published in the Journal of the American Medical Association (JAMA) raises alarms about administering melatonin gummies to children. Between 2012 and 2021, reports to U.S. poison control centers regarding pediatric melatonin ingestions surged 530% and were linked with 27,795 emergency department and clinic visits, 4,097 hospitalizations, 287 intensive care admissions, and tragically, 2 fatalities. Investigation into melatonin products’ labels revealed widespread inaccuracies relating to the presence of both melatonin and cannabidiol (CBD).

 

An examination of 25 melatonin gummy products obtained from the National Institutes of Health’s Dietary Supplement Label Database revealed that a staggering 88 percent of these products had inaccurate labels, ranging from one product containing no melatonin to the others containing anywhere from 74 percent to 347 percent of the stated amount. Among the five products containing CBD, the measured CBD amounts varied from 104 percent to 118 percent of the labeled quantity.

 

This is extremely concerning as administering melatonin gummies to children can expose them to enormously high amounts of melatonin and CBD. Combining melatonin and CBD can lead to potential moderate interactions, intensifying effects like dizziness, drowsiness, confusion, and difficulty concentrating. These products often claim to aid in sleep, stress, and relaxation, making it imperative to inform parents and caregivers that despite product claims, neither melatonin nor CBD has received approval from the U.S. Food and Drug Administration (FDA) for use in healthy children.

 

Source: https://jamanetwork.com/journals/jama/fullarticle/2804077

https://www.drugs.com/interactions-check.php?drug_list=1548-0,3919-0

Appointing Jeff Sessions as US Attorney General infused new life into those of us who know that marijuana is destroying our nation from within. But were we premature in believing that Donald Trump would put an end to what Barack Obama and George Soros inflicted on this nation in the last eight years? After eight months, we still don’t have federal drug policy flowing from the President.

The pattern of past presidents is familiar. Bill Clinton moved the Office of National Drug Control Policy (ONDCP) to a backwater, and reduced its size by about 75 per cent. In 1996, with help from Hillary Clinton and investor George Soros, Clinton allowed California to violate federal laws and become the first victim of the ‘medical marijuana’ hoax. Soros, Peter Lewis and John Sperling, all out-of-state billionaires, financed that campaign with close to $7million (£5.3million).

Obama downgraded the position of Drug Czar from cabinet level to reporting to the Vice President. He then allowed, or directed, Attorney General Eric Holder to ignore the inherent responsibility of the Executive Branch to enforce federal law. Drug strategy in ONDCP was changed to focus on ‘harm reduction’, the subversive ploy of Soros to focus on treatment and rehabilitation, at the expense of primary prevention. The President espoused the claim that ‘marijuana is no worse than alcohol’, leaving most people with a flawed impression. Federal agencies such as the Substance Abuse and Mental Health Services Administration (SAMHSA) spent their fortunes on anything other than marijuana. Congress passed the Rohrabacher/Farr Bill which withheld federal dollars from the Drug Enforcement Administration (DEA) so they couldn’t even enforce the law. The result? Twenty-nine states now have some form of legalised pot. Marijuana users had increased from about 15million to 22.3million Americans at the last count.

Now comes President Trump. During the campaign he indicated he felt legalising marijuana should be a state’s right. He is wrong, but could be forgiven if he took the time to learn why. He was building a hotel empire while many of us have been fighting the drug problem for 40 years. The truth about marijuana has been so misrepresented and suppressed for the last 20 years that he, like most people, doesn’t know what to believe. He has the best scientific information in the world available to him, but the question is: who is giving him advice? Anyone? Or drug legalisers such as Rohrabacher, Peter Theil, Trump confidant Roger Stone? Or even George Soros?

The truth is, marijuana was a dangerous drug 50 years ago, when the potency was only 0.5 per cent to 2 per cent. Today’s highly potent pot, with an advertised range of 25 per cent (+/-) of the active ingredient THC, and up to 98 per cent as wax or oils used in edibles, dabbing and vaping, has the potential to destroy the country by ruining our collective health and intellectual capacity.

Experts such as Dr Stuart Reece from Australia or Dr Bertha Madras of Harvard will attest that marijuana use by either parent can cause congenital abnormalities in a foetus. What’s worse, these abnormalities can affect the next four generations.

Psychotic breaks, mental illness and addiction caused by marijuana have led to a substantial increase in crime, homelessness, erosion of the quality of our inner cities, academic failure, traffic fatalities and public health costs. The combined economic impact in the US is well over $1trillion per annum.

Only the federal government has the resources to combat billionaire-backed legalisation campaigns and the illicit drug trade; the enforcement of federal laws is the only thing that will save California and the nation. Hopefully the President will step up and get us back on track without further delay.

Roger Morgan

RogerMorgan is the Chairman of the Take Back America Campaign http://www.tbac.us

Source: https://www.conservativewoman.co.uk/roger-morgan-trump-must-clamp-marijuana-america-doomed/ October 2017

Abstract

We tested whether cannabinoids (CBs) potentiate alcohol-induced birth defects in mice and zebrafish, and explored the underlying pathogenic mechanisms on Sonic Hedgehog (Shh) signaling. The CBs, Δ9-THC, cannabidiol, HU-210, and CP 55,940 caused alcohol-like effects on craniofacial and brain development, phenocopying Shh mutations. Combined exposure to even low doses of alcohol with THC, HU-210, or CP 55,940 caused a greater incidence of birth defects, particularly of the eyes, than did either treatment alone. Consistent with the hypothesis that these defects are caused by deficient Shh, we found that CBs reduced Shh signaling by inhibiting Smoothened (Smo), while Shh mRNA or a CB1 receptor antagonist attenuated CB-induced birth defects. Proximity ligation experiments identified novel CB1-Smo heteromers, suggesting allosteric CB1-Smo interactions. In addition to raising concerns about the safety of cannabinoid and alcohol exposure during early embryonic development, this study establishes a novel link between two distinct signaling pathways and has widespread implications for development, as well as diseases such as addiction and cancer.

Source: https://www.nature.com/articles/s41598-019-52336-w November 2019

Historically speaking, it’s not a bad time to be the liver of a teenager. Or the lungs.

Regular use of alcohol, tobacco and drugs among high school students has been on a long downward trend.

In 2023, 46% of seniors said they had had a drink in the year before being interviewed; that is a precipitous drop from 88% in 1979, when the behavior peaked, according to the annual Monitoring the Future survey, a closely watched national poll of youth substance use. A similar downward trend was observed among eighth and 10th graders, and for those three age groups when it came to cigarette smoking. In 2023, just 15% of seniors said that they had smoked a cigarette in their life, down from a peak of 76% in 1977.

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Illicit drug use among teens has remained low and fairly steady for the past three decades, with some notable declines during the COVID-19 pandemic.

In 2023, 29% of high school seniors reported using marijuana in the previous year — down from 37% in 2017, and from a peak of 51% in 1979.

There are some sobering caveats to the good news. One is that teen overdose deaths have sharply risen, with fentanyl-involved deaths among adolescents doubling from 2019 to 2020 and remaining at that level in the subsequent years.

Dr. Nora Volkow has devoted her career to studying use of drugs and alcohol. She has been director of the National Institute on Drug Abuse since 2003. She sat down with The New York Times to discuss changing patterns and the reasons behind shifting drug-use trends.

Q: What’s the big picture on teens and drug use?

A: People don’t really realize that among young people, particularly teenagers, the rate of drug use is at the lowest risk that we have seen in decades. And that’s worth saying, too, for legal alcohol and tobacco.

Q: What do you credit for the change?

A: One major factor is education and prevention campaigns. Certainly, the prevention campaign for cigarette smoking has been one of the most effective we’ve ever seen.

Some of the policies that were implemented also significantly helped, not just making the legal age for alcohol and tobacco 21 years, but enforcing those laws. Then you stop the progression from drugs that are more accessible, like tobacco and alcohol, to the illicit ones. And teenagers don’t get exposed to advertisements of legal drugs like they did in the past. All of these policies and interventions have had a downstream impact on the use of illicit drugs.

Q: Does social media use among teens play a role?

A: Absolutely. Social media has shifted the opportunity of being in the physical space with other teenagers. That reduces the likelihood that they will take drugs. And this became dramatically evident when they closed schools because of COVID-19. You saw a big jump downward in the prevalence of use of many substances during the pandemic. That might be because teenagers could not be with one another.

The issue that’s interesting is that despite the fact schools are back, the prevalence of substance use has not gone up to the pre-pandemic period. It has remained stable or continued to go down. It was a big jump downward, a shift, and some drug use trends continue to slowly go down.

Q: Is there any thought that the stimulation that comes from using a digital device may satisfy some of the same neurochemical experiences of drugs, or provide some of the escapism?

A: Yes, that’s possible. There has been a shift in the types of reinforcers available to teenagers. It’s not just social media, it’s video gaming, for example. Video gaming can be very reinforcing, and you can produce patterns of compulsive use. So, you are shifting one reinforcer, one way of escaping, with another one. That may be another factor.

Q: Is it too simplistic to see the decline in drug use as a good news story?

A: If you look at it in an objective way, yes, it’s very good news. Why? Because we know that the earlier you are using these drugs, the greater the risk of becoming addicted to them. It lowers the risk these drugs will interfere with your mental health, your general health, your ability to complete an education and your future job opportunities. That is absolutely good news.

But we don’t want to become complacent.

The supply of drugs is more dangerous, leading to an increase in overdose deaths. We’re not exaggerating. I mean, taking one of these drugs can kill you.

Q: What about vaping? It has been falling, but use is still considerably higher than for cigarettes: In 2021, about one-quarter of high school seniors said that they had vaped nicotine in the preceding year. Why would teens resist cigarettes and flock to vaping?

A: Most of the toxicity associated with tobacco has been ascribed to the burning of the leaf. The burning of that tobacco was responsible for cancer and for most of the other adverse effects, even though nicotine is the addictive element.

What we’ve come to understand is that nicotine vaping has harms of its own, but this has not been as well understood as was the case with tobacco. The other aspect that made vaping so appealing to teenagers was that it was associated with all sorts of flavors — candy flavors. It was not until the FDA made those flavors illegal that vaping became less accessible.

My argument would be there’s no reason we should be exposing teenagers to nicotine. Because nicotine is very, very addictive.

Q: Anything else you want to add?

A: We also have all of this interest in cannabis and psychedelic drugs. And there’s a lot of interest in the idea that psychedelic drugs may have therapeutic benefits. To prevent these new trends in drug use among teens requires different strategies than those we’ve used for alcohol or nicotine.

For example, we can say that if you take drugs like alcohol or nicotine, that can lead to addiction. That’s supported by extensive research. But warning about addiction for drugs like cannabis and psychedelics may not be as effective.

While cannabis can also be addictive, it’s perhaps less so than nicotine or alcohol, and more research is needed in this area, especially on newer, higher-potency products. Psychedelics don’t usually lead to addiction, but they can produce adverse mental experiences that can put you at risk of psychosis.

c.2024 The New York Times Company

Source: https://uk.news.yahoo.com/teen-drug-habits-changing-good-142032071.html?

 

A groundbreaking study presented at the European Psychiatric Association Congress 2024, unveiled disturbing findings relating to the impacts of marijuana use by pregnant mothers. This research linked such usage to various neurodevelopmental disorders, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) in kids. Unlike previous studies reliant on self-reported data, this study dived into health registries examining confirmed diagnoses of prenatal marijuana addiction (otherwise known as cannabis use disorder or CUD) and the specified neurodevelopmental disorders using diagnostic tools based on the ISD-10-AM to capture a more reliable assessment of the risks associated with marijuana use during pregnancy.

 

Conducted by researchers at Curtin University in Australia, they scrutinized over 222,000 mother-child pairs in New South Wales, Australia and found that children born to mothers with diagnosed marijuana addiction during pregnancy exhibit a:

 

·    98 percent increased risk of ADHD,

·    94 percent increased risk of autism, and

·    46 percent increased risk of intellectual disability compared to children whose mothers did not have a CUD during pregnancy.

 

Researchers noted a stronger risk for these neurodevelopmental conditions when mothers also smoked during pregnancy. They also found a combined impact between prenatal CUD and other pregnancy complications such as low birth weight and premature birth, amplifying the risk of neurodevelopmental disorders in kids.

 

Dr. Julian Beezhold, the Secretary General of the European Psychiatric Association, emphasized the study’s uniqueness, offering a more comprehensive understanding of the potential risks associated with prenatal marijuana use. He also stressed the need for public health education campaigns and clinical interventions.

Recognizing the growing prevalence of marijuana use among pregnant women and the heightened potency of THC, which escalates the risks associated with its use during pregnancy, Drug Free America Foundation has launched an educational project dedicated to marijuana and pregnancy. For comprehensive resources, we invite you to explore our dedicated webpage for this project: https://www.marijuanaknowthetruth.org/marijuana-and-pregnancy/. This website provides access to downloadable resources, fact-based research, videos from subject matter experts, shareable social media content, and more available in multiple languages.

Source:  Drug Free America Foundation 

Cannabis and cannabinoids are implicated in multiple genotoxic, epigenotoxic and chromosomal-toxic mechanisms and interact with several morphogenic pathways, likely underpinning previous reports of links between cannabis and congenital anomalies and heritable tumours. However the effects of cannabinoid genotoxicity have not been assessed on whole populations and formal consideration of effects as a broadly acting genotoxin remain unexplored. Our study addressed these knowledge gaps in USA datasets. Cancer data from CDC, drug exposure data from National Survey of Drug Use and Health 2003–2017 and congenital anomaly data from National Birth Defects Prevention Network were used. We show that cannabis, THC cannabigerol and cannabichromene exposure fulfill causal criteria towards first Principal Components of both: (A) Down syndrome, Trisomies 18 and 13, Turner syndrome, Deletion 22q11.2, and (B) thyroid, liver, breast and pancreatic cancers and acute myeloid leukaemia, have mostly medium to large effect sizes, are robust to adjustment for ethnicity, other drugs and income in inverse probability-weighted models, show prominent non-linear effects, have 55/56 e-Values > 1.25, and are exacerbated by cannabis liberalization (P = 9.67 × 10 –43 ,2.66 × 10 –15 ). The results confirm experimental studies showing that cannabinoids are an important cause of community-wide genotoxicity impacting both birth defect and cancer epidemiology at the chromosomal hundred-megabase level.

Source: https://www.nature.com/articles/s41598-021-93411-5.epdf July 2021

Abstract

Background:

Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure.

Objectives / Hypotheses:

Is cannabis associated with ASDI in USA? Is this relationship causal?

Methods:

Geospatio/temporal cohort study, 1991–2016. Census populations of adults, babies, congenital anomalies, income and ethnicity.

Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse probability weighted (ipw) regressions.

Analysis conducted in R.

Results:

 ASDI rose nationally three-fold from 27.4 to 82.8 / 10,000 births 1991–2014 during a period when tobacco and alcohol abuse were falling but cannabis was rising. States including Nevada, Kentucky, Mississippi and Tennessee had steeply rising epidemics (Time: Status β-estimate = 10.72 (95%C.I. 8.39–13.05), P < 2.0 × 10 − 16). ASDI was positively related to exposure to cannabis and most cannabinoids.

Drug exposure data was near-complete from 2006 thus restricting spatial modelling from 2006 to 2014, N = 282. In geospatial regression models cannabis: alcohol abuse term was significant (β-estimate = 19.44 (9.11, 29.77), P = 2.2 × 10 − 4 ); no ethnic or income factors survived model reduction.

Cannabis legalization was associated with a higher ASDI (Time: Status β-estimate = 0.03 (0.01, 0.05), P = 1.1 × 10 -3). Weighted panel regression interactive terms including cannabis significant (from β-estimate = 1418, (1080.6, 1755.4), P = 7.3 × 10 -15). Robust generalized linear models utilizing inverse probability weighting interactive terms including cannabis appear (from β-estimate = 78.88, (64.38, 93.38), P = 1.1 × 10 -8).

Marginal structural models with machine-aided Super Learning association of ASDI with high v. low cannabis exposure R.R. = 1.32 (1.28, 1.36). Model e-values mostly > 1.5.

Conclusions:

ASDI is associated with cannabis use, frequency, intensity and legalization in a spatiotemporally significant manner, robust to socioeconomic demographic adjustment and fulfilled causal criteria, consistent with multiple biological mechanisms and similar reports from Hawaii, Colorado, Canada and Australia. Not only are these results of concern in themselves, but they further imply that our list of the congenital teratology of cannabis is as yet incomplete, and highlight in particular cardiovascular toxicology of prenatal cannabinoid and drug exposure.

Albert Stuart Reece and Gary Kenneth Hulse

Source:  BMC Pediatrics volume 20, Article number: 539 (2020) https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-020-02431-z November 2020

Just one or two joints seem to change the structure of the brain, say researchers from universities around the world, led by senior author and University of Vermont professor of psychiatry Hugh Garavan, PhD, and first author and former UVM postdoctoral fellow Catherine Orr, PhD.
 
The study is part of a long-term European effort called IMAGEN, which has collected brain images from 2,000 children in Ireland, France, and Germany, starting when they were age 14 and continuing through age 23.
 
Researchers compared the brain images of 46 children age 14 who reported having used marijuana once or twice with those of children that age who had not used the drug. The images of the marijuana triers showed greater brain volume in areas with cannabinoid receptors. The biggest differences were in the amygdala, involved in fear and other emotions, and the hippocampus, the site of memory development and spatial abilities.
 
“You’re changing your brain with just one or two joints. Most people would likely assume that one or two joints would have no impact on the brain,” says Dr. Garavan.
 
It is unclear what the extra gray matter in these brain areas means. Normally at age 14, the brain is refining its synaptic connections to make it thinner, not thicker. Dr. Garavan says one possibility is that initial marijuana use in this age group may be disrupting that “pruning” process.
 
The new findings open a new area of focus for future research.
 
Read study abstract here.

Source:  The Marijuana Report  16.01.2019

Abstract

Little attention has been paid to the potential impact of paternal marijuana use on offspring brain development. We administered Δ9-tetrahydrocannabinol (THC, 0, 2, or 4 mg/kg/day) to male rats for 28 days. Two days after the last THC treatment, the males were mated to drug-naïve females. We then assessed the impact on development of acetylcholine (ACh) systems in the offspring, encompassing the period from the onset of adolescence (postnatal day 30) through middle age (postnatal day 150), and including brain regions encompassing the majority of ACh terminals and cell bodies. Δ9-Tetrahydrocannabinol produced a dose-dependent deficit in hemicholinium-3 binding, an index of presynaptic ACh activity, superimposed on regionally selective increases in choline acetyltransferase activity, a biomarker for numbers of ACh terminals. The combined effects produced a persistent decrement in the hemicholinium-3/choline acetyltransferase ratio, an index of impulse activity per nerve terminal. At the low THC dose, the decreased presynaptic activity was partially compensated by upregulation of nicotinic ACh receptors, whereas at the high dose, receptors were subnormal, an effect that would exacerbate the presynaptic defect. Superimposed on these effects, either dose of THC also accelerated the age-related decline in nicotinic ACh receptors. Our studies provide evidence for adverse effects of paternal THC administration on neurodevelopment in the offspring and further demonstrate that adverse impacts of drug exposure on brain development are not limited to effects mediated by the embryonic or fetal chemical environment, but rather that vulnerability is engendered by exposures occurring prior to conception, involving the father as well as the mother.

The increasing use of marijuana by women of childbearing age raises a concern for potential adverse outcomes in the offspring (Ryan et al., 2018). There have been numerous studies of the consequences of maternal cannabis use in humans or Δ9-tetrahydrocannabinol (THC) administration during pregnancy in animals (Abel, 1980Fried, 2002Huizink, 2014Trezza et al., 2008), but little or no attention has been paid to the role of paternal exposure for adverse consequences to the developing fetus or child. Animal studies where both males and females were exposed to THC in adolescence identified persistent changes in gene methylation in association with neurobehavioral anomalies in the offspring (Szutorisz and Hurd, 2018) ; however, these did not distinguish whether there was a specific paternal contribution, which would presumably involve epigenetic changes in sperm. Indeed, recent work found that cannabis exposure in humans, or THC exposure in rats, produces persistent changes in sperm DNA methylation, including the genes that were affected by combined paternal and maternal exposure, as well as genes associated with risk of autism spectrum disorder (Murphy et al., 2018Schrott et al., 2020). The effects in rats were associated with long-lasting attentional impairment in the offspring (Levin et al., 2019).

In the present study, we provide one of the first demonstrations that paternal THC administration, prior to mating, results in abnormalities of offspring brain development, specifically targeting acetylcholine (ACh) systems, which provide essential inputs for learning, memory, reward, and mood. We exposed male rats for 28 days to THC at doses commensurate with moderate cannabis use in humans, mated them to drug-naïve females, and then assessed biomarkers of ACh synaptic function in the offspring. We conducted our evaluations longitudinally from adolescence through adulthood, so as to capture early and late stages of brain development and function, and made our assessments in brain regions comprising all the major ACh projections and their corresponding cell bodies. We evaluated the concentration of presynaptic high-affinity choline transporters (hemicholinium-3 [HC3] binding), the activity of choline acetyltransferase (ChAT), and the concentration of α4β2 nicotinic ACh receptors (nAChRs). High-affinity choline transporters and ChAT are both constitutive components of ACh nerve terminals but they differ in their regulatory mechanisms and hence in their functional significance. Choline acetyltransferase is the enzyme that synthesizes ACh, but is not regulated by nerve impulse activity, so that its presence provides an index of the density of ACh innervation (Slotkin, 2008). In contrast, HC3 binding to the choline transporter is directly responsive to neuronal activity (Klemm and Kuhar, 1979), so that comparative effects on HC3 binding and ChAT enable the characterization of both the concentration of ACh terminals and presynaptic impulse activity. We then calculated the HC3/ChAT ratio as an index of presynaptic activity relative to the number of cholinergic nerve terminals (Slotkin, 2008). Finally, the α4β2 nAChR is the most abundant subtype in the mammalian brain and regulates the ability of ACh systems to release other neurotransmitters involved in reward, cognition, and mood (Dani and De Biasi, 2001). These indices have been used successfully to characterize the impact of diverse neurotoxicants and diseases on ACh systems: neuroactive pesticides (Slotkin et al., 20132019b), nicotine or tobacco smoke (Slotkin et al., 2015), polycyclic aromatic hydrocarbons (Slotkin et al., 2019a), and glucocorticoids (Slotkin et al., 2013); and terminal stages of Alzheimer’s disease (Slotkin et al., 1994).

Source: https://doi.org/10.1093/toxsci/kfaa004 February 2020

  • Neither the cause of autism nor the effects of cannabis on a developing fetus are entirely clear 
  • Researchers at the Ottawa Hospital and University of Ottawa studied 2,200 Canadian women who reported using marijuana while pregnant 
  • The rate of autism among their children was four per 1,000 person-years, compared to 2.42 among children whose mothers did not use marijuana  

Pregnant women who smoke cannabis almost double the risk of their baby being born autistic, warns a new study.

In the largest ever study of its kind, researchers found that children whose mothers reported using cannabis during pregnancy were at greater risk of autism.

The incidence of autism was four per 1,000 person-years among children exposed to cannabis in pregnancy, compared to 2.42 among unexposed children.

‘There is evidence that more people are using cannabis during pregnancy,’ said senior study author Professor Mark Walker, of the University of Ottawa in Canada.

‘This is concerning, because we know so little about how cannabis affects pregnant women and their babies.

‘Parents-to-be should inform themselves of the possible risks, and we hope studies like ours can help.’

A Canadian study found that rates of autism were twice as high among the children of women who used marijuana during pregnancy, compared to rates among children of mothers  who did not use the drug (file)

The researchers reviewed data from every birth in Ontario between 2007 and 2012, before recreational cannabis was legalised in Canada.

Of the half a million women in the study, about 3,000 (0.6 per cent) reported using cannabis during pregnancy.

Importantly, these women reported using only cannabis.

The team had previously found that cannabis use in pregnancy was linked to an increased risk of premature birth.

In that study, they found that women who used cannabis during pregnancy often used other substances including tobacco, alcohol and opioids.

The findings, published in the medical journal Nature Medicine. showed that babies born to this group still had an increased risk of autism compared to those who didn’t use cannabis.

The researchers do not know exactly how much cannabis the women were using, how often, at what time during their pregnancy, or how it was consumed.

But as cannabis becomes more socially acceptable, doctors are concerned that some parents-to-be might think it can be used to treat morning sickness.

Dr Daniel Corsi, an epidemiologist at The Ottawa Hospital, said: ‘In the past, we haven’t had good data on the effect of cannabis on pregnancies.’

He added: ‘This is one of the largest studies on this topic to date.

‘We hope our findings will help women and their health-care providers make informed decisions.’

Autism is fairly common, but still poorly understood.

In the US, about one in every 59 children born will fall somewhere on the autism spectrum.

About one in every 66 children in Canada are autistic and, globally, the rate is approximately one in every 160 children.

Research suggests that there is likely some genetic basis for autism,  which is about four-times more common among boys than girls.

But scientists believe exposures in the womb likely play a role as well.

The effects of cannabis are similarly poorly understood to the origins of autism.

Although doctors caution against it, cannabis use has not been linked to miscarriages in humans (though animal studies have suggested an increased risk) and evidence on the link between weed and low birth-weight is mixed.

Marijuana use during pregnancy has been linked, however, to up to 2.3 times greater risks of stillbirth.

The Ottawa Hospital study did not investigate how exactly marijuana use in pregnancy might lead to autism in a child, but scientists believe that the drug’s interaction with the so-called endocannabinoid system within the nervous system could play a role in the development of the behavioral condition.

Source: Autism is twice as common in children whose mothers used cannabis in pregnancy | Daily Mail Online

Cannabis use during pregnancy is associated with a host of negative outcomes.

Sondem/AdobeStock

The recent paper by Stanciu discussing cannabis use in pregnancy1 makes several useful and highly salient points. With a more complete understanding of the published literature further important patterns in the data emerge. They aid our understanding of the pathobiology of in utero cannabis exposure and thereby powerfully inform the community on the most appropriate manner in which to regulate cannabis and cannabinoids from an improved evidence base.

It is well known that cannabis use has been liberalized across the United States as a result of well-financed and orchestrated campaigns.2 Stanciu is correct that most epidemiological studies point towards harmful associations, that cannabis use in pregnancy is becoming more common, that it is widely recommended in pregnancy by cannabis dispensaries, and that increased rates of low birth weight, premature and stillbirths, and increased neonatal intensive care admission are well recognized associations. It is correct that all 4 longitudinal studies of children born after prenatal cannabis exposure (PCE) show increased adverse neurodevelopmental outcomes including impaired executive function, visuomotor processing deficits, heightened startle responses, impulse control, heightened susceptibility to addiction in later life, emotional behaviors, and motor defects.3-5 Well-documented impacts on the glutamatergic, GABAergic and dopaminergic signaling in the brain are of concern as they represents major neurotransmitters in the central nervous system [CNS]. Well-established links between cannabis use and schizophrenia, bipolar disorder, anxiety, depression, and suicidal ideation are also correctly described. It is true that ACOG have made both historical and recent recommendations against its use in pregnancy, and these recommendations are relevant to practice in all medical specialties.

Conceptual and epidemiological extensions

While it is correct to observe that there is no described phenotype following PCE, it is also important to note that many of these neurodevelopmental deficits have been noted to overlap the ADHD and autism spectrum disorders. This is likely epidemiologically highly significant for the US, where autistic spectrum disorders have been shown to be growing exponentially.6 Cannabis use across the US was shown to be independently associated with autism rates across both time and space, to be dose-related6, and, based on conservative projections, has been predicted to be at least 60% higher in cannabis-legal states than in states where cannabis was illegal by 2030.7

A large Hawaiian study found an increased incidence of microcephaly (R.R. = 12.80, 95%C.I. 4.13-36.17)8 and the CDC have twice reported elevated rates of anencephalus (adjusted O.R. 1.7, C.I. 0.9-3.4) and (posterior O.R. 1.9 (C.I. 1.1, 3.2).9,10 This sets up a clear spectrum of severity from mild neurodevelopmental impairment, to microcephaly, to anencephalus and then fetal death. In the context of dose-response relationships and strong geotemporospatial associations issues of causality necessarily arise.

Stanciu’s observation that preclinical studies in experimental animals are important to understand the likely effects of PCE in individuals, not least due to the problem of the frequent exposure to multiple substances clinically, is also correct. This issue was studied in detail long ago in the 1960s and 1970s, and succinctly summarized by Graham’s telling observation: “oedema, phocomelia, omphalocoele, spina bifida, exencephaly, multiple malformations including myelocoele. This is a formidable list.”11

However, a reasonable question might be: “Why don’t we see such a broad teratological spectrum clinically?”

Stanciu’s remark that there are “no overt birth defects” is an oft-repeated myth and is in error, as well as obviously being at odds with several preclinical studies, especially in the most predictive species for human teratology (ie, hamsters and white rabbits).12,13

A recent paper from the Centers for Disease Control (CDC) noted that 4 defects, anencephalus, gastroschisis, diaphragmatic hernia and esophageal atresia were more common following PCE.9 The American Academy of Pediatrics (AAP) and the American Heart Association (AHA) issued a joint position statement that both ventricular septal defect (VSD) and Ebsteins anomaly were also elevated by PCE.14

The review of 17 years of birth defects from Hawaii found 21 defects to be elevated after PCE and featured prominently cardiovascular defects (atrial septal defect (ASD), VSD, hypoplastic left heart syndrome, tetralogy of Fallot (ToF) and pulmonary valve atresia or stenosis), chromosomal defects such as Downs syndrome, body wall defects such as gastroschisis, limb defects including syndactyly and upper limb reduction defects, facial, bowel and genitourinary system defects with calculated rate ratios ranging from 5.26 (C.I. 1.08-15.46) to 39.98 (C.I. 9.03-122.29).8

In September and October 2018 Colorado released 2 datasets of congenital anomalies across the period of its cannabis legalization program from 2000 to 2013 and 2000 to 2014 and reported 87,772 and 64,463 major defects respectively (which are obviously contradictory).15 Based on 4830 and 4026 major anomalies in the year 2000 this represents a case excess of 20,152 (29.80%) or 11,753 anomalies (22.30%) respectively. During this period the use of tobacco and alcohol was declining and other drug use was not rising. Only cannabis use rose. Importantly, models quartic in time indicated a non-linear response of total birth defects to rising cannabinoid exposure. Estimated exposure to several cannabinoids including cannabinol, THC, and tetrahydrocannabivarin was shown to be positively associated with major defect rates and to be robust to adjustment for other drug use. CNS defects (microcephalus, neural tube defects), cardiovascular defects (ASD, VSD, patent ductus arteriosus (PDA)), total chromosomal anomalies including Downs syndrome, musculoskeletal, respiratory and genitourinary anomalies all rose dramatically.

Defects described as being cannabis-related (by the Hawaiian, CDC, AAP and AHA investigators) rose more quickly than cannabis-unrelated defects (P<0.003). As fetal cardiac tissue and the central great vessels have high numbers of cannabinoid receptors from early in fetal life it is easy to understand why this pattern might emerge. Since ASD, VSD and PDA are the most common cardiovascular congenital anomalies it is understandable that total cardiovascular anomalies increased in Colorado.

recent review of total congenital anomalies in Canada showed that they were 3 times more common in the northern territories which consume more cannabis, and that these effects were robust to adjustment for other drug exposure and for socioeconomic variables.16 Total cardiovascular defects, Downs syndrome and gastroschisis were noted prominently in this series. Neural tube defects including anencephalus and spinal bifida and meningomyelocoele were falling across Canada from 1991 to 2007, although it was not clear whether the decline was due to dietary folate supplementation or increased antenatal early termination of pregnancy for anomalies (ETOPFA).17 Notwithstanding this it was recently shown that within each of 3 periods (the pre-folate period, the transitional period and the post-folate period) neural tube defects across Canada were becoming more common.17

An Australian dataset found greatly elevated relative rates of cardiovascular (PDA, ASD, VSD, ToF, transposition of great vessels), body wall (gastroschisis, exomphalos, diaphragmatic hernia), chromosomal (Downs syndrome, Turners syndrome, Edwards Syndrome (trisomy 18)), genitourinary, hydrocephalus, neural tube defects, and bowel defects with borderline results for anencephalus (ETOPFA data unavailable) in a high cannabis use area in Northern New South Wales compared to Queensland state-wide data.18

Transposition of the great vessels was previously linked with paternal cannabis exposure.19

The presence of Downs syndrome on the list of cannabis-associated anomalies in Hawaii, Colorado, Canada and Australia is important as it necessarily implies megabase-scale genetic damage.8,15,16,18 Since cannabis interferes with tubulin metabolism and thus the separation of the chromosomes which occurs in mitotic anaphase it is easy to see how PCE-induced chromosomal mis-segregation errors might occur.20 Studies of PCE in rodents show that cannabis induces major alterations of gene expression widely with 8% alteration in DNA sperm methylation patterns, changes which are transmissible to subsequent F1 generations.21

Stanciu’s comment about a so-called “cannabis phenotype” is provocative. It is true that a “fetal cannabis syndrome” (FCS) has not been described in the way that a “fetal alcohol syndrome” (FAS) has. Fetal alcohol syndrome of course is a very diverse and pleomorphic group of clinical presentations and a wide spectrum of presentations is described. Importantly the fetal alcohol has been described as being mediated by the cannabinoid type 1 receptor (CB1R’s) and is mediated epigenetically.22-26 The suggestion that alcohol can work epigenetically via CB1Rs but cannabinoids cannot defies the bounds of credulity. Moreover, as noted above, there is as yet no objective marker of gestational cannabinoid exposure. Once such a biomarker has been derived (say epigenetically and / or glycomically27) then an objective measure will exist to allow genotype-epigenotype-phenotype correlative studies to be performed so that we can usefully investigate if a fetal cannabis syndrome phenotype spectrum might exist. However, if researchers do not believe it might exist then it is clear that one will not be described. It is our view that once an objective biomarker is established it will only be a matter of time before a diverse and highly variable FCS is also defined and enters the clinical diagnostic compendium.

Recent US data and analysis

CDC publish 5-year averaged birth defect data for many states as part of the National Birth Defects Prevention Network (NBDPN) annual reports which can be combined with Substance Abuse and Mental Health Services Administration (SAMHSA) state and substate data to examine nationwide drug-related trends. ETOPFA rates are taken from historical time series.

Figure 1A charts Downs syndrome rates corrected for estimated ETOPFA rates against cannabis exposure. Both rates are elevated (shown as pink and purple) in Colorado, Oregon, Washington, Alaska, Maine and Massachusetts.

Downs Syndrome By Cannibas Use

Figure 1B shows the relationship of Downs syndrome to cigarette use for this year which is very different.

Downs Syndrome By Cigarette Use

The Figure also shows the Downs syndrome rates by cannabis use quintile for both the raw Downs syndrome rates (Figure 1C) and the ETOPFA-corrected data (Figure 1D). One notes not only a rising trend with cannabis use, but also an abrupt jump from the fourth to the fifth quintile.

Downs Syndrome Rate by Quintiles of Cannabis Use

This jump is seen when many defects are analyzed in this manner. A list of defects would include, but would not be limited to: atrial septal defect, atrioventricular septal defect, cleft lip and / or palate (all forms combined), trisomy 21 (Downs syndrome), Turners syndrome and ventricular septal defect.

Downs Syndrome by Quintiles of Cannabis Use (ETOPFA-CORRECTED)

Figure 2 lists the prevalence ratio of 62 congenital anomalies tracked by the National Birth Defect Prevention Network (NBDPN) in quintile 5 versus lower quintiles and notes that 44 of them are significantly elevated in the highest quintile of cannabis using states.

Prevalence Ratios

Literature-wide limitations

It should be noted in passing that most of these studies suffer from several major common limitations. Many of the defects described are disorders for which ETOPFA is commonly practiced and frequently recommended to pregnant patients. ETOPFA data was generally not available to investigators. It is beyond question that were such data included the findings would be of greater magnitude and of even greater concern. Secondly many studies rely on self-report which is subject to recall-bias and may be misled. Patients who use cannabis early in pregnancy but stop after they are informed of their pregnant status might answer “no” to questions of PCE, but in fact their fetus is exposed prenatally due to the prolonged terminal half-life of excretion of cannabinoids from body fat stores. Hence a reliable biomarker is required to properly define the denominator in these studies, but it is not thought to exist at present. It could however easily be derived from epigenomic and/or glycomic studies.27

Thirdly there are major analytical limitations of the described series. Advanced analytical methods that allow data analysis simultaneously across both space and time exist and are called geospatial or spatiotemporal techniques. The CDC has demonstrated ability to track congenital anomalies by county. Application of geospatial techniques to county data is therefore possible and would be well assisted by the provision of cannabis-exposure data from the SAMHSA 395 substate areas. Methods which allow the investigation of apparently causal relationships, including inverse probability weighting and the calculation of E-values to quantify unmeasured confounding have similarly not been deployed in this field.

These deficits in the literature represent major gaps in our knowledge which may readily be addressed by the application of available techniques to currently extant data and thus vastly augment the evidence base for well-informed policy formulation. Our group is presently addressing this major knowledge gap with a series of papers on these and related subjects utilizing geospatiotemporal regression, the formal techniques of causal inference, and multiple imputation of chained equations to complete CDC data for various congential anomalies and heritable childhood cancers where such data is missing or withheld for specific ethnic minorities.

Extensive presently unpublished analyses from our group extend the United States analyses presented in preliminary and embryonic form in Figure 1 and Figure 2 using geotemporospatial and causal inference techniques with strongly confirmatory results for both state-based spatiotemporal association and in several cases causal links.

Concluding thoughts

In broad overview the patterns which emerge from these major population-based studies of cannabis-related human teratology indicate several findings that are remarkable for their consistency across series originating from Hawaii, Colorado, Canada, and Australia and for their exact and precise concordance with very worrying data in experimental animals. Prominent amongst affected organ systems includes the CNS, CVS and chromosomal disorders. Body wall and limb defects also likely follow the endovascular cannabinoid receptor distribution pattern, and this is consistent with current understandings related to the pathogenesis of gastroschisis and limb embryogenesis which are both thought to be primarily vasculocentric. Similarly, in the genitourinary and gastrointestinal systems, peripheral cannabinoid receptors are widely distributed and appear from as early as 12 weeks of fetal life. Dose-response effects are seen in many of the above analyses which is one of the major criteria of Hill’s causal algorithm. The sequence of severity of CNS defects (neurodevelopmental impairments/autism-microcephaly-anencephaly-foetal death) also implies a gradation of phenotypic effects of PCE.

The PCE literature has widespread limitations including its reliance on self-report data, the general non-availability of ETOPFA data, the lack of reliable biomarkers to define exposure, and the pointed absence of state-of-the-art analytical techniques including high-resolution geotemporospatial analysis and the formal techniques of causal inference assessment.

Given these limitations the concordance with preclinical and mechanistic data and the positive and highly consistent associations that have been demonstrated in several jurisdictions are particularly concerning. They carry far-reaching genotoxic and intergenerational implications and argue powerfully against cannabis legalization.

Dr Reece is practice principal at Southcity Family Medical Centre and Professor of Medicine at University of Western Australia and Edith Cowan UniversityDr Hulse is Professor of Addiction Medicine within the Division of Psychiatry at The University of Western Australia and the Faculty of Health Sciences at the Edith Cowan UniversityNeither author has any conflicts of interest to declare.

Source:  https://www.psychiatrictimes.com/view/cannabis-pregnancy-rejoinder-exposition-cautionary-tales   October 2020

Abstract

Accidental paediatric cannabis poisonings are an incidental effect of cannabis use. The average THC content of cannabis resin and the number of consumers are rising sharply in the USA and in most European countries. The objective is to study the evolution of prevalence and severity of paediatric exposures to cannabis in France.

Method

This is a retrospective observational study of cases detected by French poison centers between January 1st 2010 and December 31st 2017 of cannabis exposure by ingestion in children aged ten or younger. The clinical severity was assessed using the Poisoning Severity Score (PSS). The criteria used for assessing the overall severity were as follows: PSS ≥ 2, admission to paediatric intensive care, coma and respiratory depression (univariate and multivariate logistic regression).

Results

A total of 965 cases of poisoning were covered. The annual average number of cases was 93 between 2010 and 2014 and 167 between 2015 and 2017. The median age was 15 months (range, 6 months–10 years) and the sex ratio was 1:1. The form of cannabis ingested was mainly resin (75%). During the period covered by the study, 26.1% of children (n = 252) presented with a PSS ≥ 2, 4.5% (n = 43) coma, 4.6% (n = 44) with respiratory depression and 11.7% (n = 113) were admitted into paediatric intensive care (out of 819 hospitalizations). No fatal cases were reported. In comparison to the 2010–2014 period, the length of hospital stays was significantly higher (p < 0.0001) and the comas were significantly deeper (lower score on the Glasgow coma scale, p < 0.005) in 2015–2017. Following adjustments made for the sex, age and weight of the children, the data show that the severity of the poisonings was significantly greater in 2015–2017 in terms of PSS score, the number of comas and monitoring in intensive care (p < 0.001).

Conclusion

The data indicates a significant increase in the number of cases of paediatric exposure to cannabis and a rise in the seriousness of poisonings between 2010 and 2017.

Source:  https://www.tandfonline.com/doi/abs/10.1080/15563650.2020.1806295 June 2020

ABSTRACT

Parental cannabis use has been associated with adverse neurodevelopmental outcomes in offspring, but how such phenotypes are transmitted is largely unknown. Using reduced representation bisulphite sequencing (RRBS), we recently demonstrated that cannabis use is associated with widespread DNA methylation changes in human and rat sperm. Discs-Large Associated Protein 2 (DLGAP2), involved in synapse organization, neuronal signaling, and strongly implicated in autism, exhibited significant hypomethylation (p < 0.05) at 17 CpG sites in human sperm. We successfully validated the differential methylation present in DLGAP2 for nine CpG sites located in intron seven (p < 0.05) using quantitative bisulphite pyrosequencing. Intron 7 DNA methylation and DLGAP2 expression in human conceptal brain tissue were inversely correlated (p < 0.01). Adult male rats exposed to delta-9-tetrahydrocannabinol (THC) showed differential DNA methylation at Dlgap2 in sperm (p < 0.03), as did the nucleus accumbens of rats whose fathers were exposed to THC prior to conception (p < 0.05). Altogether, these results warrant further investigation into the effects of preconception cannabis use in males and the potential effects on subsequent generations.

KEYWORDS: Cannabis, sperm, DNA methylation, autism, heritability

Introduction

Cannabis sativa is the most commonly used illicit psychoactive drug in the United States (U.S.) and Europe [1]. In the U.S., 11 states and Washington D.C. have legalized the recreational use of cannabis and 33 states have legalized the use of medicinal cannabis [2,3]. Since 1995, cannabis potency (defined as the concentration of the psychoactive cannabis component delta-9-tetrahydrocannabinol, or THC, in the sample [4]) has consistently risen from ~4% to as high as 32% in some states [2,5,6]. Changes in cannabis potency have been accompanied by changes in attitudes about cannabis and patterns of cannabis use. Between 2002 and 2014, the percentage of adults in the U.S. who perceived cannabis use as risky declined from 50% to 33% [6]. During this same period, the percentage of U.S. adults who believed cannabis to have no risk rose from 6% to 15% [6]. According to a 2015 Survey on Drug Use and Health, 52.5% of men in the U.S. of reproductive age (≥18) have reported cannabis use at some point in their lives, making cannabis exposure especially relevant for potential future fathers [711].

Given the increased prevalence of cannabis use in the U.S., studies are beginning to focus on the effects of use on the health and development of offspring. Prenatal cannabis exposure via maternal use during pregnancy is associated with decreased infant birth weight, an increased likelihood to require the neonatal intensive care unit, and the potential for an impaired fetal immune system compared to those infants who are not exposed during gestation [1,12]. In rodent studies, rat pups born to parents who were both exposed to THC during adolescence had increased heroin-seeking behaviour later in life, a phenotype that was accompanied by epigenetic changes in the nucleus accumbens [1315]. These studies and others have begun to highlight the potential for intergenerational consequences of cannabis exposure [16]. Identifying the mechanism that underlies these changes is critical as cannabis use continues to increase across the U.S.

The environment impacts the integrity and maintenance of the epigenome such that it is now viewed as a molecular archive of past exposures [17]. While the majority of environmental epigenetic studies are focused on the impact of the inutero environment on the epigenome and health of the child, it has become apparent that the exposure history of the father must also be considered – specifically the impact of his exposures on the sperm epigenome. Studies have shown that exposure to phthalates, pesticides, nutritional deficiencies, and obesity can all induce potentially heritable changes in the sperm epigenome [1824]. It is likely that other common and emerging exposures, including cannabis, may also contribute to disruption of sperm DNA methylation in a similar fashion, and that such changes could be transmitted to the subsequent generation.

Using reduced representation bisulphite sequencing (RRBS) our group recently demonstrated that cannabis use in humans, and THC exposure in rats, is associated with decreased sperm concentrations and widespread changes in sperm DNA methylation [25]. Of the regions identified in humans, Discs-Large Associated Protein 2 (DLGAP2) exhibited significant hypomethylation in the sperm of cannabis-exposed men compared to controls (p < 0.05). DLGAP2, a membrane-associated protein located in the post-synaptic density of neurons, plays a key role in synapse organization and neuronal signaling [26]. Dysregulation of DLGAP2 is associated with various neurological and psychiatric disorders, such as autism spectrum disorder (ASD) and schizophrenia [2629]. In our prior screen, we identified 17 differentially methylated CpG sites within DLGAP2 in the sperm of cannabis-exposed men compared to controls. DLGAP2 was just one of 46 genes with greater than 10 CpG sites showing significantly altered DNA methylation in the sperm of cannabis users compared to controls, out of the 2,077 genes we identified as having altered DNA methylation. The first objective of this study was to validate our preliminary RRBS findings for DLGAP2 using quantitative bisulphite pyrosequencing. Our second objective was to determine the functional association between DNA methylation and gene expression of DLGAP2 to better understand how cannabis use might affect this relationship. To determine the possible intergenerational effects of paternal cannabis use, our third objective was to determine if Dlgap2 was differentially methylated in the sperm of rats exposed to THC versus controls, and if so, whether or not these changes were intergenerationally heritable.

Results

DLGAP2 is hypomethylated in sperm from cannabis users versus controls by Reduced Representation Bisulphite Sequencing (RRBS)

Our prior study [25] revealed 17 differentially methylated sites by RRBS in the sperm of cannabis users compared to controls for the DLGAP2 gene. Table S1 lists all 17 of these sites and their genomic coordinates. Figure 1a graphically demonstrates the significant hypomethylation of nine of these sites that are clustered together in the seventh intron of this gene. DLGAP2 is schematically shown in Figure 1b, including the exon-intron structure, position of CpG islands, transcription start site and the region of interest in intron 7 within the context of the gene body, with an inset showing the nucleotide sequence analysed in this study.

Validation of DLGAP2 RRBS methylation data

To confirm the methylation differences that were initially detected using RRBS, we designed a bisulphite pyrosequencing assay for the DLGAP2 intron 7 region (see Figure 1b) which captures 10 CpG sites, nine of which were identified as significantly differentially methylated using RRBS. We first validated pyrosequencing assay performance using defined mixtures of fully methylated and unmethylated human genomic DNAs. The measured levels of methylation by pyrosequencing showed good agreement between the amount of input methylation levels and the amount of methylation detected (r2 = 0.99 and p = 0.0003) (Figure 1c). These results confirmed the linearity of the assay in the ability to detect increasing amounts of DNA methylation at this region across the full range of possible methylation values, and indicate that the assay is suitable for use with biological specimens.

The DLGAP2 intron 7 region is not an imprinting control region (ICR)

DLGAP2 is paternally expressed in the testis, biallelically expressed in the brain, and has low expression elsewhere in the body [30]. Since DLGAP2 is known to be genomically imprinted in testis [30], and since the imprint control region for this gene has not yet been defined, we sought to determine if the region of interest in intron 7 is part of the DLGAP2 imprint control region (ICR). The methylation at ICRs is established during epigenome reprogramming in the primordial germ cells in embryonic development. Male and female gametes exhibit divergent methylation at ICRs, and this methylation profile is maintained through subsequent post-fertilization epigenetic reprogramming and in somatic cells throughout the life course. Therefore, we expected that if the DLGAP2 intron 7 region is an ICR, the diploid testis tissues from human conceptuses would exhibit approximately 50% methylation due to the complete methylation of one allele at this region and the complete lack of methylation at the other allele. Human conceptal testes tissues (n = 3) showed an average of 72.5% methylation at the DLGAP2 intron 7 region (Figure 1d). This finding, of higher than anticipated and variable levels of methylation, is inconsistent with ICR status.

Bisulphite pyrosequencing validates the RRBS methylation data in human sperm

We next performed quantitative bisulphite pyrosequencing on the same sperm DNA samples from cannabis users and controls as those used to generate the RRBS data to confirm the loss of methylation present at the intron 7 region of DLGAP2. All nine CpG sites that were hypomethylated in the cannabis users by RRBS were also found to be hypomethylated by bisulphite pyrosequencing, as well as an additional CpG site that was captured in the assay design (p < 0.05 for all 10 sites) (Figure 2). Following Bonferroni correction of the p value to adjust for multiple comparisons (p < 0.005), CpG sites 1,2,3,5,7,8,9, and 10 remained significant. From this pyrosequencing assay we observed methylation differences of 7–15% between the sperm of the cannabis users (n = 8) compared to controls (n = 7). Correlation of the RRBS and pyrosequencing data for each individual CpG site showed significant agreement at all sites analysed (p < 0.02 for all sites; Figure S1). All CpG sites showed a significant loss of methylation in accordance with the direction of change observed by RRBS for these same CpG sites.

Methylation of DLGAP2 intron 7 is inversely correlated with DLGAP2 expression

Given that we observed significant loss of intron 7 DLGAP2 DNA methylation in sperm of cannabis users relative to non-users, we next examined the relationship between DNA methylation and gene expression in the brain, where this gene’s function is critical. We used 28 conceptal brain tissues to examine the relationship between DNA methylation and mRNA expression. Expression levels were normalized to the lowest expressing sample, and the relationship between DNA methylation and mRNA expression was calculated with a Pearson correlation. We found that as methylation increased in this region, mRNA expression decreased significantly (p < 0.05) (Figure 3a). Knowing that there are sex differences in autism spectrum disorder (ASD), and that dysregulation of DLGAP2 is associated with ASD [26], we sought to determine if there were any sex differences in the methylation-expression relationship in these tissues. To investigate this, we ran the correlation for males (n = 15) and females (n = 13) independently. The inverse relationship between methylation and expression was evident for both males and females, but this relationship was significant only in females (p = 0.006) (Figure 3b, c).

Intergenerational inheritance of altered Dlgap2 DNA methylation

We next sought to investigate Dlgap2 using data obtained from our prior study [25] to determine if there was any differential methylation of Dlgap2 in THC versus control rats that was not initially identified using the imposed thresholds of that study. We were particularly interested in the potential for intergenerational transmission and to determine if route of THC exposure affected DNA methylation at this gene. The pilot study rats [25] were given THC via oral gavage (to mimic oral ingestion of drug) while subsequent studies dosed rats via intraperitoneal injection (to mimic inhalation of drug). From the rats administered THC via oral gavage versus controls, we identified a region of Dlgap2 that showed differential methylation by the RRBS analysis that contains eight CpG sites. This region is in the first intron of Dlgap2, in a CpG island that spans the first exon of this gene as well (schematic of the gene structure and sequence of this region shown in Figure 4a). We validated the rat Dlgap2 pyrosequencing assay using commercially available rat DNA of defined methylation status. The results showed good agreement between the input methylation and the amount of methylation detected by pyrosequencing (r2 = 0.92, p = 0.01) (Figure 4b).

We were able to demonstrate intergenerational inheritance of an altered DNA methylation pattern in Dlgap2. Comparing the average methylation for exposed and unexposed sperm for each CpG site revealed that sites 2,3,4 and 6 of the eight CpG sites analysed were significantly hypomethylated in the sperm of rats exposed via injection to 4mg/kg THC compared to controls (p = 0.03 to p = 0.005) (Figure 4c). CpG site 6 remained significant after Bonferroni correction (p < 0.006). The same region of Dlgap2 was then analysed in the hippocampus and nucleus accumbens of rats whose fathers were exposed to control or 4mg/kg THC. While CpG site 7 was significantly hypomethylated (p < 0.05) in the hippocampus of the offspring (Figure 5a), this site was not identified as differentially methylated in the sperm of THC exposed rats, and therefore we could not conclude that this change was transmitted as the result of changes present in the exposed sperm. In the nucleus accumbens, however, significant hypomethylation (p = 0.02) at CpG site 2 was detected in the offspring (Figure 5b), one of the same sites identified in the sperm of THC exposed rats. We also found that there was an inverse relationship between DNA methylation and expression of Dlgap2 in the nucleus accumbens, though not statistically significant likely due to the small sample size available in this study (n = 6 exposed, n = 8 unexposed; Figure S2).

Discussion

In this study, we examined the effects of regular male cannabis use on human sperm DNA methylation, at DLGAP2. Our RRBS study initially identified 17 CpG sites in DLGAP2 that were differentially methylated in the sperm of cannabis users compared to controls. Of the sites that were initially identified, nine of them all reside together in the seventh intron of this gene, though not in a defined CpG island. To first confirm the RRBS data, we performed quantitative bisulphite pyrosequencing for the nine clustered CpG sites. We were able to capture an additional CpG site with careful assay design for a total of ten CpG sites analysed via bisulphite pyrosequencing. We successfully validated the RRBS findings, confirming that there was significant hypomethylation among these ten sites with cannabis use. We confirmed a significant inverse correlation between methylation and expression at this region in human conceptal brain tissues.

To begin to determine whether or not the effects of cannabis on sperm are heritable, we analysed sperm from THC exposed and control male rats, as well as the hippocampus and nucleus accumbens from offspring of THC exposed and control males for changes in DNA methylation at Dlgap2. Rats exposed to THC were given a dose (4mg/kg THC for 28 days) that is pharmacodynamically equivalent to daily cannabis use to resemble frequent use in humans. We identified significant hypomethylation at Dlgap2 in the sperm of exposed rats as compared to controls. This hypomethylated state was also detected in the nucleus accumbens of rats born to THC exposed fathers compared to controls, supporting the potential for intergenerational inheritance of an altered sperm DNA methylation pattern. While the changes in the degree of methylation are small in the rats (0.5–0.7%), we previously reported that fractional changes in methylation can significantly influence the degree to which the gene’s expression is altered [31].

DLGAP2 is a member of the DLGAP family of scaffolding proteins located in the post-synaptic density (PSD) of neurons. The PSD is a protein-dense web that lies under the postsynaptic membrane of neurons and facilitates excitatory glutamatergic signaling in the central nervous system [26,32]. DLGAP2 functions to transmit neuronal signals across synaptic junctions and helps control downstream signaling events [26,32]. Due to its important role in PSD signaling, even small changes in the expression of DLGAP2 can have severe consequences [26,32]. Of particular relevance, DLGAP2 has been linked to schizophrenia and importantly, has been identified as an autism candidate gene [27,28,33,34]. Differential methylation of DLGAP2 is reported in the brain of individuals with autism, and has been linked to post-traumatic stress disorder in rats [27,35]. Knockout of Dlgap2 in mice results in abnormal social behaviour, increased aggressive behaviour, and learning deficits [36].

Studies are increasingly showing associations between cannabis use and various neuropsychiatric and behavioural disorders including anxiety, depression, cognitive deficits, autism, psychosis, and addiction [2,6,7,9,14,3739]. Research looking into the effects of THC exposure found that rat pups born to parents who were exposed to THC during adolescence showed increased effort to self-administer heroin compared to those born to unexposed parents [13]. This increase in addictive behaviour was driven by THC-induced changes in DNA methylation, occurring in the striatum, including the nucleus accumbens [14,15]. One of the genes whose methylation was altered by parental THC exposure was Dlgap2 [15]. Recently, a group from Australia analysed datasets from two independent cohorts to examine the relationship between cannabis legalization in the U.S. and ASD incidence. They determined there was a strikingly significant positive association between cannabis legalization and increased ASD incidence. Further, the study authors predicted that there will be a 60% increase in excess ASD cases in states with legal cannabis by 2030, and deemed ASD the most common form of cannabis-associated clinical teratology [40].

It is estimated that the ratio of boys with ASD to girls with ASD is 4:1 which led us to stratify our analysis looking at the relationship between DNA methylation and gene expression by sex [41,42]. The results of our methylation-expression analyses demonstrated a significant association in females but not males. While we don’t know the ASD status of these samples, there are several reasons why this may be the case. First, there are certain genes that confer a stronger ASD phenotype in girls compared to boys [41,42]. Thus, while we see the trend in both sexes, it is possible that dysregulation of this gene may manifest phenotypically more in girls. Alternatively, it may be that the regulatory relationship between methylation and expression is retained in females while altered methylation further exacerbates an already fragile relationship in males. Overall, this data confirms that the region of DNA methylation within DLGAP2 that was differentially methylated in the sperm of cannabis users compared to controls is functionally important in the brain.

DLGAP2 is an imprinted gene that exhibits paternal expression in the testis, biallelic expression in the brain, and low expression elsewhere in the body [30]. Because the methylation established at imprinted genes resists post-fertilization epigenetic reprogramming [4345], this supports the possibility that changes in methylation at DLGAP2 in sperm could be transmitted to the next generation. However, given that the region in intron 7 is not an ICR, it is unlikely that this would be a potential mechanism for intergenerational inheritance of an altered methylation pattern at this region. However, it has recently been discovered that a subset of genes termed ‘escapees’ are able to escape primordial germ cell (PGC) and post-fertilization reprogramming events [46,47], providing a mechanism for epigenetic changes incurred by sperm to be passed on to the subsequent generation.

Processes in the PSD are sensitive to endocannabinoids [26,4851], which suggests that these processes are potentially sensitive to exogenous cannabinoids, such as THC and cannabis. This is especially important as cannabis legalization and use are increasing dramatically across the U.S. It is estimated that 22% of American adults currently use cannabis, of which 63% are regular users (≥1–2 times per month) [710]. Among regular users 55% are males and over half of all men over 18 have reported cannabis use in their lifetime [710]. Importantly, this age range includes individuals of reproductive age. Since almost half of all pregnancies in the U.S. are unplanned, there is concern that many pregnancies may occur during a time when one, or both, parents are using or are exposed to cannabis [52].

Our results provide novel findings about the effects of paternal cannabis use on the methylation status of an ASD candidate gene, a disorder whose rates continue to climb, but whose precise aetiologies remain unknown. Studies are beginning to show that there is a potential for paternal intergenerational inheritance. In particular, epigenetic changes in umbilical cord blood of babies born to obese fathers were also found in the sperm of obese men. This study is the first to demonstrate that there are changes present in the sperm epigenome of cannabis users at a gene involved in ASD.

The results of this study have several limitations. The sample size was small, which might limit generalization of the study findings. However, even though our sample size was small, we were able to identify common pathways that were differentially methylated in both human and rat sperm, highlighting the potential specificity of these effects [25]. We did not account for a wide variety of potential confounders such as various lifestyle habits, sleep, diet/nutrition, exercise, etc, given that their influence on the sperm DNA methylome is largely unknown. Larger studies are required to confirm these findings. In the conceptal tissues we were only able to analyse whole brain, rather than the areas where DLGAP2 is most highly expressed such as the hippocampus and the striatum, which could have diluted the strength of the results.

Strengths of the study included that we used a highly quantitative method to confirm the methylation status that was measured by RRBS. This study was the first demonstration of the association between cannabis use and substantial hypomethylation of DLGAP2 in human sperm. Additionally, we are able to confirm a functional relationship between methylation and expression in a relevant target tissue, and have shown that the relationship between methylation and expression is weakened in males, which could bear relevance to the sexual dimorphism in the prevalence of autism. This is the first demonstration of potential heritability of altered methylation resulting from preconceptional paternal THC exposure. Given the increasing legalization and use of cannabis in the U.S., our results underscore a need for larger studies to determine the potential for heritability of DLGAP2 methylation changes in the human F1 generation and beyond. It will also be important to examine how cannabis-associated methylation changes relate to neurobehavioral phenotypes

Source:   Epigenetics. 2020; 15(1-2): 161–173.

Published online 2019 Aug 26. doi: 10.1080/15592294.2019.1656158

To Whom it may concern

On behalf of Drug Free Australia and our coalition of drug prevention researchers, we wish to commend to you, research that could well be a game-changer in informing and preventing a large proportion of Australia’s substance use issues.

The research is in various stages of development and a synopsis of current and emerging research, being done by Dr Stuart Reece and Professor Gary Hulse should be of genuine interest for all Australian Health Professionals. However, it appears that, to date, too many of the world’s researchers have placed this important research in the ‘too hard’ basket, similar to the way the NHS in the United Kingdom did with research into Pandemics.

At present the COVID-19 pandemic and how it is being addressed, should be a ‘wakeup call’ to Australian health authorities that prevention is the single most important goal. A ‘Harm Minimisation’ only approach, fails to achieve best-practice primary prevention outcomes. The passive discounting of the primary pillar of the National Drug Strategy – Demand Reduction over the last 30 years (and particularly the last 10) has seen a very large increase in illegal drug use in this nation.

The only exception to this has been seen in the correct and full use of both demand and supply reduction on the drug Tobacco. There has been little or no use of harm reduction mechanisms and a relentless and unified approach to abstinent/cessation modelling and it has worked spectacularly well, seeing Australia with, arguably, the lowest daily tobacco use in the world.

The research, that we now summarise, should not be placed in Australia’s ‘too hard’ basket. Rather, it warrants recognition by all Australian Health authorities for the world break-through that it is. Such evidence-based data offers timely insights that should promote and resource primary prevention and demand reduction.

Synopsis of the research:
1. Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis Albert Stuart Reece, MBBS(Hons), FRCS(Ed), FRCS(Glas), FRACGP, MD(UNSW), and Gary Kenneth Hulse, BBSc(Hons), MBSc, PhD
https://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Canadian_Cannabis_Consumption_and_Patterns_of.99248.aspx

Status
Mapping showed cannabis use was more common in the northern Territories of Canada in the Second National Survey of Cannabis Use 2018. Total congenital anomalies, all cardiovascular defects, orofacial clefts, Downs syndrome and gastroschisis were all found to be more common in these same regions and rose as a function of cannabis exposure.

When Canada was dichotomized into high and low cannabis use zones by Provinces v Territories the Territories had a higher rate of total congenital anomalies 450.026 v 390.413 (O.R.=1.16 95%C.I. 1.08-1.25, P=0.000058; attributable fraction in exposed 13.25%, 95%C.I. 7.04–19.04%). In geospatial analysis in a spreml spatial error model cannabis was significant both alone as a main effect (P<2.0×10-16) and in all its first and second order interactions with both tobacco and opioids from P<2.0×10-16.

Conclusion:

These results show that the northern Territories of Canada share a higher rate of cannabis use together with elevated rates of total congenital anomalies, all cardiovascular defects, Down’s syndrome and gastroschisis. This is the second report of a significant association between cannabis use and both total defects and all cardiovascular anomalies and the fourth published report of a link with Downs syndrome and thereby direct major genotoxicity.

The correlative relationships described in this paper are confounded by many features of social disadvantage in Canada’s northern territories. However, in the context of a similar broad spectrum of defects described both in animals and in epidemiological reports from Hawaii, Colorado, USA and Australia they are cause for particular concern and indicate further research.

139 References – click on this link to access.
https://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Canadian_Cannabis_Consumption_and_Patterns_of.99248.aspx

2. Cannabis Consumption Patterns Parallel the East-West Gradient in Canadian Neural Tube Defect Incidence – An Ecological Study
https://www.researchgate.net/publication/337911618_Cannabis_Consumption_Patterns_Explain_the_East-West_Gradient_in_Canadian_Neural_Tube_Defect_Incidence_An_Ecological_Study

Status:
Whilst a known link between prenatal cannabis exposure (PCE) and anencephaly exists, the relationship of PCE with neural tube defects (NTD’s) generally has not been defined. Published data from Canada Health and Statistics Canada was used to assess this relationship. Both cannabis use and NTDs were shown to follow an east-west and north-south gradient. Last year cannabis consumption was significantly associated (P<0.0001; Cannabis use: time interaction P<0.0001). These results were confirmed when estimates of termination for anomaly were used. Canada Health population data allowed the calculation of an NTD O.R.=1.27 (95%C.I. 1.19-1.37; P<10-11) for high risk provinces v. the remainder with an attributable fraction in exposed populations of 16.52% (95%C.I. 12.22-20.62). Data show a robust positive statistical association between cannabis consumption as both a qualitative and quantitative variable and NTDs on a background of declining NTD incidence. In the context of multiple mechanistic pathways these strong statistical findings implicate causal mechanisms.

82 References – click on this link to access.
https://www.researchgate.net/publication/337911618_Cannabis_Consumption_Patterns_Explain_the_East-West_Gradient_in_Canadian_Neural_Tube_Defect_Incidence_An_Ecological_Study

3. Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study. Response to Lane
https://bmjopen.bmj.com/content/6/11/e011891.responses

Status:
We wish to thank Dr Lane for his interest in our study. We are pleased to see statistical input to the issues of cannabis medicine as we feel that sophisticated statistical methodologies have much to offer this field.

Most of the concerns raised are addressed in our very detailed report. As described our research question was whether, in our sizeable body of evidence (N=13,657 RAPWA studies), we could find evidence for the now well-described cannabis vasculopathy and what such implications might be. As this was the first study of its type to apply formal quantitative measures of vascular stiffness to these questions it was not clear at study outset if there would be any effect, much less an estimate of effect size. In the absence of this information power calculations would be mere guesswork. Nor indeed are they mandatory in an exploratory study of this type. Similarly the primary focus of our work was on whether cannabis exposure was an absolute cardiovascular risk factor in its own right, and how it compared to established risk factors. Hence Table 2 contains our main results. The role of Table 1 is to illustrate the bivariate (uncorrected) comparisons which can be made, show the various groups involved, and compare the matching of the groups. It is not intended to be a springboard for effect-size-power calculations which are of merely esoteric interest.
Calculations detailing the observed effect size are clearly described in our text being 11.84% and 8.35% age advance in males and females respectively.

Mixed-effects models are the canonical way to investigate longitudinal data given a usual random error structure 1. We agree with Lane that unusual error structures can affect significance conclusions. Diagnostic tests run on our models confirm that the residuals had the usual spheroidal error structure so that the application of mixed-effects models in the classical way is quite satisfactory. Another way to investigate this issue is that of incremental model building comparing models with and without cannabis exposure terms. If one considers regression equations from our data with cannabis use treated either as a categorical (RA/CA ~ Days_Post-Cannabis * BMI + * Cannabis_Category) or a continuous (RA/(CA*BMI) ~ Cigs*SP + * Cannabis_Use +Chol+DP+HDL+HR+CRH) variable one notes firstly that terms including cannabis use remain significant in final models (after model reduction) and secondly that models which include cannabis exposure are significantly better than ones without (Categorical: AIC = 1088.56 v. 1090.22, Log.Ratio = 19.62, P = 0.0204; Continuous: AIC = 412.33 v. 419.73, Log.Ratio = 9.37, P = 0.0022). Unfortunately formatting rules for BMJ Rapid Responses do not allow us to include a detailed table of regression results in each model in the present reply. We also note that AIC’s are little used in our report, and simply indicate the direction of the ANOVA results comparing models linear, quadratic and cubic in chronological age. They also appear routinely in the display of mixed-effects model results. Their use in such contexts is methodologically unremarkable. Control groups are also spelled out in fine detail in Table 1, in all our Figures and in the text.

We are aware that various algorithms for vascular age have been reported in the literature. The list proposed by Lane is correct but non-exhaustive. Such algorithms are generally derived from known cardiovascular risk factors. As clearly stated in our report the algorithm for vascular age we employed is derived from the proprietary software used. As such its details have not been publicized and indeed are commercially protected information.

We have however been assured by AtCor on many occasions that it includes measures of chronological age, sex, arterial stiffness and height (which is important as it dictates distance and thus speed parameters for the reflected and augmented central arterial pressure waves) and is very well validated and tested. AtCor recently advised that their algorithm is based on a very large series of studies done with arterial stiffness published in 2005 2. As such it has distinct advantages over algorithms which do not include indices of arterial stiffness. The AtCor website includes a very interesting, informative and educative animated loop which clearly illustrates the complex relationship between chronological and vascular age as a function of arterial stiffness and vascular tone 3

We are keen to see advanced statistical methods applied to such questions. We are becoming interested in geospatial and spacetime analyses and its application to the important questions of cannabis epidemiology 4. We find the very breadth of the organ systems impacted by cannabis to be quite remarkable with effects on the brain, cardiovasculature, liver, lungs, testes, ovaries, gastrointestinal, endocrine, reproductive and immune systems being well described and constituting most of the body’s major systems 5 6. Testicular and several pediatric cancers have also been described as being cannabis-associated 5. Such a multisystem generality of toxicity suggests to us that some basic cellular functions may be deleteriously affected – as implied by its well described mitochondriopathy 7, its heavy epigenetic footprint 8, accelerated aging as described in our present report 9 or some multi-way interaction between these and other processes. Given that the cannabis industry is presently entering a major commercialization growth phase, and given the multigenerational implications of mitochondriopathy-epigenotoxicity (by direct: substrate supply including ATP, NAD+ and acetate; and indirect: RNA transfer and malate-aspartate and glycerol-3-phosphate shuttle; pathways 10) further study and elucidation of these points is becoming an increasingly imperative international research priority.

Apropos of the recent Covid-19 pandemic emergency it is also worth noting that since cannabis is immunosuppressive, is known to be damaging to lungs and airways and often carries chemical, microbial and fungal contaminants cannabis use and cannabis vaping is also likely to have a deleterious effect on the coronavirus epidemic. Such data implies an untoward convergence of two public health epidemics. Appropriate controls on cannabis use imply improved public health management of SARS-CoV-2.

10 References – click on this link to access. https://bmjopen.bmj.com/content/6/11/e011891.responses

4. Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends.
https://www.researchgate.net/publication/334368364_Cannabis_Teratology_Explains_Current_Patterns_of_Coloradan_Congenital_Defects_The_Contribution_of_Increased_Cannabinoid_Exposure_to_Rising_Teratological_Trends/link/5d2d4d39a6fdcc2462e3097c/download

Status
Rising Δ9-tetrahydrocannabinol concentrations in modern cannabis invites investigation of the teratological implications of prenatal cannabis exposure.

Data from Colorado Responds to Children with Special Needs (CRCSN), National Survey of Drug Use and Health, and Drug Enforcement Agency was analyzed. Seven, 40, and 2 defects were rising, flat, and falling, respectively, and 10/12 summary indices rose. Atrial septal defect, spina bifida, microcephalus, Down’s syndrome, ventricular septal defect, and patent ductus arteriosus rose, and along with central nervous system, cardiovascular, genitourinary, respiratory, chromosomal, and musculoskeletal defects rose 5 to 37 times faster than the birth rate (3.3%) to generate an excess of 11 753 (22%) major anomalies. Cannabis was the only drug whose use grew from 2000 to 2014 while pain relievers, cocaine, alcohol, and tobacco did not. The correlation of cannabis use with major defects in 2014 (2019 dataset) was R = .77, P = .0011. Multiple cannabinoids were linked with summary measures of congenital anomalies and were robust to multivariate adjustment.

66 References – click on this link to access
https://www.researchgate.net/publication/334368364_Cannabis_Teratology_Explains_Current_Patterns_of_Coloradan_Congenital_Defects_The_Contribution_of_Increased_Cannabinoid_Exposure_to_Rising_Teratological_Trends/link/5d2d4d39a6fdcc2462e3097c/download

5. Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. ‘cannabinoid exposure and altered DNA methylation in rat and human sperm’ epigenetics 2018; 13: 1208-1221.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773386/pdf/kepi-14-11-1633868.pdf
Status

ABSTRACT Recent data from the Kollins lab (‘Cannabinoid exposure and altered DNA methylation in rat and human sperm’ Epigenetics 2018; 13: 1208–1221) indicated epigenetic effects of cannabis use on sperm in man parallel those in rats and showed substantial shifts in both hypo- and hyper-DNA methylation with the latter predominating. This provides one likely mechanism for the transgenerational transmission of epigenomic instability with sperm as the vector. It therefore contributes important pathophysiological insights into the probable mechanisms underlying the epidemiology of prenatal cannabis exposure potentially explaining diverse features of cannabis-related teratology including effects on the neuraxis, cardiovasculature, immune stimulation, secondary genomic instability and carcinogenesis related to both adult and pediatric cancers. The potentially inheritable and therefore multigenerational nature of these defects needs to be carefully considered in the light of recent teratological and neurobehavioural trends in diverse jurisdictions such as the USA nationally, Hawaii, Colorado, Canada, France and Australia, particularly relating to mental retardation, age-related morbidity and oncogenesis including inheritable cancerogenesis.

Increasing demonstrations that the epigenome can respond directly and in real time and retain memories of environmental exposures of many kinds implies that the genome-epigenome is much more sensitive to environmental toxicants than has been generally realized. Issues of long-term multigenerational inheritance amplify these concerns. Further research particularly on the epigenomic toxicology of many cannabinoids is also required. 

206 References – click on this link to access

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773386/pdf/kepi-14-11-1633868.pdf

6. Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis.
https://www.ncbi.nlm.nih.gov/pubmed/32187114

Status:
These results show that the northern Territories of Canada share a higher rate of cannabis use together with elevated rates of total congenital anomalies, all cardiovascular defects, Down’s syndrome and gastroschisis. This is the second report of a significant association between cannabis use and both total defects and all cardiovascular anomalies and the fourth published report of a link with Downs syndrome and thereby direct major genotoxicity. The correlative relationships described in this paper are confounded by many features of social disadvantage in Canada’s northern territories. However, in the context of a similar broad spectrum of defects described both in animals and in epidemiological reports from Hawaii, Colorado, USA and Australia they are cause for particular concern and indicate
further.

139 references – click on this link to access https://www.ncbi.nlm.nih.gov/pubmed/32187114

7. The Potential Association Between Prenatal Cannabis use and Congenital Anomalies
https://journals.lww.com/journaladdictionmedicine/Citation/9000/The_Potential_Association_Between_Prenatal.99243.aspx

Status:
Rates of prenatal cannabis use are likely to rise with legalization, increasing social tolerability, and promotion in social media. Cannabis consumption does not appear to be a benign activity, and there may be significant risk factors to the developing fetus when used in pregnancy. Even as epidemiological data continue to emerge, The American College of Obstetricians and Gynecologists and The Society of Obstetricians and Gynecologists of Canada recommend that women avoid the use of cannabis during pregnancy.14 Whether we will definitively establish the risk of prenatal cannabis use on congenital anomalies using epidemiological approaches remains unclear; however, combing data from ecological and patient-level approaches will be crucial. Patient engagement and increasing awareness of the health implications of cannabis are critical first steps to highlight the potential risks of cannabis use in pregnancy.

14. References – click on this link to access
https://journals.lww.com/journaladdictionmedicine/Citation/9000/The_Potential_Association_Between_Prenatal.99243.aspx

8. America Addresses Two Epidemics – Cannabis and Coronavirus and their Interactions: An Ecological Geospatial Study
Status: Embargoed until publication.

Question: Since cannabis is immunosuppressive and is frequently variously contaminated, is its use associated epidemiologically with coronavirus infection rates?

Findings: Geospatial analytical techniques were used to combine coronavirus incidence, drug and cannabinoid use, population, ethnicity, international flight and income data. Cannabis use and daily cannabis use were associated with coronavirus incidence on both bivariate regression and after multivariable spatial regression with high levels of statistical significance. Cannabis use quintiles and cannabis legal status were also highly significant.

Meaning: Significant geospatial statistical associations were shown between cannabis use and coronavirus infection rates consistent with mechanistic reports and environmental exposure concerns.

Extracts from Abstract:

Results. Significant associations of daily cannabis use quintile with CVIR were identified with the highest quintile having a prevalence ratio 5.11 (95%C.I. 4.90-5.33), an attributable fraction in the exposed (AFE) 80.45% (79.61-81.25%) and an attributable fraction in the population of 77.80% (76.88-78.68%) with Chi-squared-for-trend (14,782, df=4) significant at P<10-500. Similarly when cannabis legalization was considered decriminalization was associated with an elevated CVIR prevalence ratio 4.51 (95%C.I. 4.45-4.58), AFE 77.84% (77.50-78.17%) and Chi-squared-for-trend (56,679, df=2) significant at P<10-500. Monthly and daily use were linked with CVIR in bivariate geospatial regression models (P=0.0027, P=0.0059). In multivariable additive models number of flight origins and population density were significant. In interactive geospatial models adjusted for international travel, ethnicity, income, population, population density and drug use, terms including last month cannabis were significant from P=7.3×10-15, daily cannabis use from P=7.3×10-11 and last month cannabis was independently associated (P=0.0365).

Conclusions and Relevance. Data indicate CVIR demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation. Recent cannabis use is independently predictive of CVIR in both bivariate and multivariable adjusted models and intensity of use is significant in several interactions. Cannabis thus joins tobacco as a SARS2-CoV-2 risk factor.

Summary and Conclusions

The above research clearly shows the links with substance use and Mental illness, Autism, Congenital anomalies and Paediatric cancer including testicular cancer with marijuana use and abuse. Drug Free Australia respectfully and urgently requests a Position Statement and proposed actions from your Department regarding this research and how it can be further promoted and supported within Australia. We look forward to your timely response.

You can find a list of list of Ngo’s and Medical Professional who written support for Drug Free Australia’s Response to the commercialization of Cannabis/Marijuana/CBD in Australia

https://drugfree.org.au/images/pdf-files/homepagepdf/DRReeceSupport2020_updated6May2020.pdf.

Yours sincerely
Major Brian Watters AO B.A.
President
Drug Free Australia
PO Box 379
Seaford, SA 516

 

Highlights

  • Population-based longitudinal cohort study over 30 years spanning age 19/20 to 49/50
  • Cannabis use in adolescence predicted the occurrence of depression and suicidality in adulthood
  • Association between adolescent cannabis use and adult depression/suicidality hold when adjusted for various covariates, including time-varying pattern of substance abuse in adulthood
  • Younger age at first cannabis use and more frequent use in adolescence related to an particularly increased risk of adult depression

Abstract

  • Objective

    To examine the association between cannabis use in adolescence and the occurrence of depression, suicidality and anxiety disorders during adulthood.

  • Methods

    A stratified population-based cohort of young adults (n = 591) from Zurich, Switzerland, was retrospectively assessed at age 19/20 for cannabis use in adolescence. The occurrence of depression, suicidality and anxiety disorders was repeatedly assessed via semi-structured clinical interviews at the ages of 20/21, 22/23, 27/28, 29/30, 34/35, 40/41, and 49/50. Associations were controlled for various covariates, including socio-economic deprivation in adolescence as well as repeated time-varying measures of substance abuse during adulthood.

  • Results

    About a quarter (24%) reported cannabis use during adolescence; 11% started at age 15/16 or younger and 13% between the ages of 16/17 and 19/20. In the adjusted multivariable model, cannabis use during adolescence was associated with adult depression (aOR = 1.70, 95%-CI = 1.24–2.32) and suicidality (aOR = 1.65, 95%-CI = 1.11–2.47), but not anxiety disorders (aOR = 1.10, 95%-CI = 0.82–1.48). First use at age 15/16 and younger (as against first use between age 16/17 and 19/20 and no use) and frequent use in adolescence (as against less frequent use and no use) were associated with a higher risk of depression in adult life.

  • Conclusions

    In this longitudinal cohort study over 30-years, cannabis use during adolescence was associated with depression and suicidality in adult life. Young age at first use and high frequency of use in adolescence may particularly increase the risk of depression in adulthood. All associations were independent of cannabis abuse and other substance abuse during adulthood.

Introduction

An extensive body of evidence suggests that cannabis use in adolescence increases the risk of adult psychotic disorders (Arseneault et al., 2002, Moore et al., 2007, Rossler et al., 2012); based on Mendelian randomization studies it appears that this association may at least partly be causal (Gage et al., 2017, Vaucher et al., 2018). However, it is less clear whether adolescent cannabis use also predicts depression and other affective disorders (Moore et al., 2007). For instance, a recent 35-year longitudinal cohort study of male conscripts found a weak association between cannabis use and an increased risk for depression, but this association disappeared after adjustment for covariates (Manrique-Garcia et al., 2012).

Another prospective population-based study over 3 years including both male and female adults likewise found that cannabis use at baseline weakly increased the risk of depression and anxiety, but once again these associations disappeared after controlling for covariates (comprising alcohol and drug use, education level, and family climate) (Danielsson et al., 2016). In contrast, a longitudinal cohort study of 14-15 year-old students followed over seven years reported a remarkably strong association between early cannabis use and later depression and anxiety that persisted after adjustment for baseline covariates (Patton et al., 2002). Finally, a recent meta-analysis of longitudinal studies found that adolescent cannabis use predicts the development of depression (OR = 1.4), suicidal ideation (OR = 1.5) and suicide attempts (OR = 3.5), but not anxiety (OR = 1.2), in young adulthood (Gobbi et al., 2019).

The aim of the present work was to re-address the association between adolescent cannabis use and later mood and anxiety disorders. We extended previous research by focusing separately on mood disorders, anxiety disorders and suicidality. Moreover, we did not only control for baseline covariates, such as family climate and socio-economic background, but also for concomitant abuse of both alcohol and illicit drugs (including both cannabis and other substances) across the participants’ adult lives. Finally, with a total observation period of 30 years, the present longitudinal study is much longer than most research conducted thus far.

Section snippets

Participants and sampling procedure

The Zurich Study comprised a cohort of 4547 subjects (m = 2201; f = 2346) representative of the canton of Zurich in Switzerland, who were screened in 1978 with the Symptom Checklist 90-Revised (SCL-90-R) (Derogatis, 1977) when males were 19 and females 20 years old. Male and female participants were sampled with different approaches. In Switzerland, every man of Swiss nationality must undertake a military screening test at the age of 19. With the consent of the military authorities, but…

Results

Comprehensive dropout analyses of this cohort have been presented elsewhere (Eich et al., 2003, Hengartner et al., 2016). In short, dropouts appeared to be either extremely low or extremely high scorers on the SCL GSI, but except for a weak gender bias (men were more likely to drop out) there were no baseline characteristics that predicted early study termination. The frequencies of adolescent cannabis use and baseline socio-demographic characteristics are shown in Table 1. In total 143 of 586…

Discussion

In this 30-year longitudinal cohort-study we examined the associations between cannabis use in adolescence (i.e. before the age of 19/20 years) and the development of depressive disorders, severe suicidality and anxiety disorder during adulthood (i.e. between the ages of 20/21 and 49/50). Our results show that cannabis use in adolescence, independently of substance abuse in adulthood, is significantly related to the occurrence of depressive disorders and severe suicidality, but not to anxiety…

Funding

The Zurich Cohort Study was supported by the Swiss National Science Foundation (Grant number 32-50881.97). The donator/sponsor had no further role in the experimental design, the collection, analysis, and interpretation of data, the writing of this report, or the decision to submit this paper for publication…

Author contributions

MPH drafted the manuscript and conducted all statistical analyses; JA and WR contributed to design and conduct of the study, interpretation of the data and critical revision of the manuscript; VAG contributed to interpretation of the data and critical revision. All authors approved the final version of this manuscript…

Source: https://www.sciencedirect.com/science/article/abs/pii/S0165032719320919 May 2020

Alex Azar
Secretary of Health and Human Services
US Department of Health and Human Services
200 Independence Avenue SW
Washington D.C, 20201
November 5, 2019

Dear Secretary Azar:
This letter is to bring to your attention a study underway at the University of Washington referred to as the “Moms and Marijuana Study” and granted under the title: “Olfactory Activation and Brain Development in Infants with Prenatal Cannabis Exposure.” The Office of Human Research Protections issued a decision against opening a case on this research, and we are asking you, as the Secretary of Health and Human Services, to overturn that decision based on the scientific concerns we outline in this letter.

Women who are in their first trimester of a pregnancy, who are frequent users of marijuana for morning sickness, are being recruited. The study seeks to assess the damage marijuana prenatal exposure may have on the babies by means of various testing, including an MRI scan of the infants at six months of age. The recruited women will receive $300.00 + for their participation. The study is solely funded by NIDA. This study calls into question serious issues over human rights and raises ethical questions, including mandatory reporting pertaining to substance abuse in pregnancy. This open letter seeks to gather support from you in seeing that this study is re-evaluated at the federal level. The study’s website is at the following link: https://depts.washington.edu/klab/infoMM.html

We are of the view that the Kleinhans study does not meet the requirements set forth by the Office of Human Research Protections (https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr46/ ): “Subpart B presumption that pregnant women may be included in research, provided certain conditions are met. According to Subpart B, the permissibility of research with pregnant women hinges on a judgment of the potential benefits and risks of the research. Approval of proposed research carrying no “prospect of direct benefit” to the woman or fetus requires that the risk to the fetus be judged “not greater than minimal”. Fetal risk that exceeds that standard is permissible only when the proposed research offers a prospect of direct benefit to the pregnant woman, the fetus, or both.

Notably, if the proposed research does not fit within either of those two parameters, Subpart B offers an additional mechanism at the national level for approval by the Secretary of Health and Human Services.”

The federal definition of minimum risk reads: “That the magnitude and probability of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.” Although the primary harm at issue is exposure to marijuana, the use of MRI or fMRI has not yet been proven safe for otherwise healthy infants, where an unknown risk would come with no benefit, as there is no diagnosis being sought. The UW study consent form reads on page 3:“There are no known side effects associated with MRI or fMRI when earphones are used to protect your hearing.” …. “There may be risks associated with the use of magnetic resonance which are not known at this time.” It is precisely questions about the potential for MRI risks that should be investigated in an animal model first. In principle, any study that recruits subjects and then tracks the consequences of drug transfer to a developing fetus should be carried out in animal models first, and not in humans until the animal results point towards safety. The evidence of decades of research on marijuana in pregnancy does not point to safety but rather to risk and harm.

Two basic principles in bioethics are relied upon to determine the merit of research that involves human subjects: Is the study necessary and can the research be done without the use of human subjects? There now exists a significant body of scientific evidence that warrants and justifies warning women not to use marijuana products at pre-conception, while pregnant, or breast-feeding. The University of Washington study is not necessary to conclude that marijuana use is associated with risk to the child (and also the mother). The National Academies, a lead authority, concluded in a scientific literature review in 2017: There is substantial evidence of a statistical association between maternal cannabis smoking and lower birth weight of the offspring. Studies have already shown that prenatal use is associated with a 50 percent increased likelihood of low birth weight. The Surgeon General’s advisory of August 29, 2019 is also relied upon here. What is the “necessity” that this study addresses? The conclusion has already been made by the findings of science – pregnant women should refrain from marijuana use in order to protect the life and health of their child.

Yet, in spite of existing scientific literature of concern, a highly misleading recruitment statement appears on the University of Washington study’s website introductory page: “We do not expect to find anything of medical concern during the infant MRI scans…If you’re interested in helping us learn more about whether cannabis is safe to use for morning sickness, click the Sign Up button and let us know!” Their lack of concern about the potential for adverse medical outcomes directly contradicts the findings of Grewen et al. (2015) which similarly evaluated postnatal outcomes using MRI scans on infants that had been exposed to marijuana in utero. As compared to controls, the exposed infants showed hypoconnectivity between brain regions: ” Marijuana-specific differences were observed in insula and three striatal connections: anterior insula–cerebellum, right caudate–cerebellum, right caudate–right fusiform gyrus/inferior occipital, left caudate–cerebellum. +MJ neonates had hypo-connectivity in all clusters compared with −MJ and CTR groups.” While an imperfect study because the cases included a proportion of women in the case group who used not only marijuana but also alcohol, tobacco, opiates and SSRIs, one of the two control groups was matched to the cases for use of those drugs, while the other was completely drug free. Notably, work in an animal model by Tortoriello et al. (2014) presents a plausible mechanism for the observed effect of marijuana seen between cases and controls. The combined evidence points towards harm, and confirmation could easily be sought in an animal model that parallels the intent of the University of Washington study.

Furthermore, the ethics are clearly different between the Kleinhans et al. and Grewen et al. studies, because unlike the protocol for the former, the study of Grewen et al. did not recruit women while the fetus was developing but recruited shortly before or after the time of birth. Being unaware of marijuana use until the time of birth, the researchers could not intervene to encourage abstinence for the sake of the fetus, whereas the University of Washington team could intervene, but their protocols do not allow them to. As a further point of distinction, the University of Washington protocol states that infants enrolled in the study will be screened and excluded if they have been in an NICU for 24 hours. This will, for obvious reasons, result in a biased outcome in reporting overall harm from marijuana use during pregnancy.

Typical morning sickness affects up to 91% of pregnancies (Castillo and Phillippi, 2015), and is regarded by many medical practitioners as being a reflex protecting against consumption of dangerous foods or beverages, as well as a sign of a healthy pregnancy because the absence of morning sickness is associated with a higher rate of miscarriage (reviewed by Sherman and Flaxman, 2002). The rare condition when morning sickness becomes pathologic, hyperemesis gravidarum, affects on average 1.1% of pregnancies, and is defined as a loss of 5% or more of the pre-pregnancy weight (Castillo and Phillippi, 2015). Maintenance of fluid and electrolyte balance may become problematic in this situation and pharmacologic intervention may become necessary, both for the health of the mother and the baby. To date, the serious documented outcomes include an increased risk for preterm births and low birth weight (Dodds et al., 2006).

Thus, if the Kleinhans study were to be proposing to recruit only those with hyperemesis gravidarum, the ethics might be more favorable. They would, however, have to exclude women whose marijuana use may have triggered the hyperemesis, which may occur in a subset of pregnant users (Alaniz et al., 2015). The study recruitment website is definitely remiss in not making that possibility clear to those interested in enrolling, and the research protocol describes no effort to ascertain if marijuana might be triggering hyperemesis in their study subjects.

In summary, there is already sufficient scientific evidence to answer the question as to whether or not marijuana is safe to use for typical morning sickness. That answer is no. Please see additional references for numerous research publications showing harm at the end of this letter.
Complaints have been filed with NIDA, The University of Washington, The World Medical Association regarding the Helsinki Declaration, The Office of Human Research Protections, and two doctors have filed a human rights complaint on behalf of the children involved. Complaint documents will be forwarded on request.

Thank you for your time in reviewing this serious situation.

Best regards,
Pamela McColl
Child Rights Activist
pjmccoll@shaw.ca

and

Christine L. Miller, Ph.D.
Neuroscientist
MillerBio
6508 Beverly Rd
Baltimore, Maryland 21239
cmiller@millerbio.com

et al.

Correspondence with the OHRP in regards to the University of Washington study began in September
of 2019. On October an email was received from the OHRP to Pamela McColl:
October 25, 2019

Hello,
OHRP has reviewed the study and will not be opening a case.
Sincerely,
Division of Compliance Oversight OHRP

September 25, 2019
“OHRP is now reviewing your complaint and this study. We are currently gathering the information about the research being conducted before a full review is started. Once OHRP completes a full review of the study, the research conducted and the study’s approval process, we will contact you with our findings. Please remember, this does not mean you can’t contact OHRP again before we finish the full review. You can contact us using this email address to update your complaint at any time.
Thank-you,
Division of Compliance Oversight (OHRP)

September 17, 2019
Thank you for contacting the Office for Human Research Protections (OHRP). OHRP has responsibility for oversight of compliance with the U.S. Department of Health and Human Services (HHS) regulations for the protection of human research subjects (see 45 CFR Part 46 at
www.hhs.gov/ohrp/regulations-and-policy/guidance/index.html

In carrying out this responsibility, OHRP reviews allegations of noncompliance involving human subject research projects conducted or supported by HHS or that are otherwise subject to the regulations, and determines whether to conduct a for-cause compliance evaluation. For further details see OHRP’s guidance, “Compliance Oversight Procedures for Evaluating Institutions,” at www.hhs.gov/ohrp/compliance-and-reporting/evaluating-institutions/index.html.

OHRP has jurisdiction only if the allegations involve human subject research (a) conducted or supported by HHS, or (b) conducted at an institution that voluntarily applies its Assurance of Compliance to all research regardless of source of support. Since this requirement appears to be met by the circumstances described in your email, OHRP appears to have jurisdiction.
Sincerely,
Division of Compliance Oversight
cc. Surgeon General Jerome Adams
cc. Director NIDA Dr. Nora Volkow

In-text citations:
Alaniz VI, Liss J, Metz TD, Stickrath E. Cannabinoid hyperemesis syndrome: a cause of refractory nausea and vomiting in pregnancy. Obstet Gynecol. 2015 Jun;125(6):1484-6.
Castillo MJ, Phillippi JC. Hyperemesis gravidarum: a holistic overview and approach to clinical assessment and management. J Perinat Neonatal Nurs. 2015;29(1):12-22.
Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol. 2006;107(2, pt 1):285–292.
Grewen K, Salzwedel AP, Gao W. Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure. Front Hum Neurosci. 2015;9:601.
Sherman PW, Flaxman SM. Nausea and vomiting of pregnancy in an evolutionary perspective. Am J Obstet Gynecol. 2002;186(5 Suppl Understanding):S190-7.
The National Academies of Sciences, Engineering, and Medicine, 2017, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. National Academies Press, Washington, D.C. 20001
Tortoriello G, et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 2014;33(7):668-85.

Additional references on specific neonatal outcomes:
Lower birth weight, animal studies
Benevenuto SG et al., Recreational use of marijuana during pregnancy and negative gestational and fetal outcomes: An experimental study in mice. Toxicology. 2017;376:94-101.
“Five minutes of daily (low dose) exposure during pregnancy resulted in reduced birthweight…..females from the Cannabis group presented reduced maternal net body weight gain, despite a slight increase in their daily food intake compared to the control group”

Lower birth weight, human studies
Gunn,JKL, Rosales CB, Center KE, Nunez A, Gibson SJ, Christ C, and Ehiri EJ. Prenatal exposure to cannabis and maternal and child health outcomes: A systematic review and meta-analysis. BMJ Open 2016; 6(4):e009986.
“Infants exposed to cannabis in utero had a decrease in birth weight (low birth weight pOR=1.77: 95% CI 1.04 to 3.01; pooled mean difference (pMD) for birth weight=109.42 g: 38.72 to 180.12) compared with infants whose mothers did not use cannabis during pregnancy. Infants exposed to cannabis in utero were also more likely to need placement in the neonatal intensive care unit compared with infants whose mothers did not use cannabis during pregnancy (pOR=2.02: 1.27 to 3.21).”
Brown SJ, Mensah FK, Ah Kit J, Stuart-Butler D, Glover K, Leane C, Weetra D, Gartland D, Newbury J, Yelland J. Use of cannabis during pregnancy and birth outcomes in an Aboriginal birth cohort: a crosssectional, population-based study. BMJ Open. 2016;6(2):e010286.
“Controlling for education and other social characteristics, including stressful events/social health issues did not alter the conclusion that mothers using cannabis experience a higher risk of negative birth outcomes (adjusted OR for odds of low birth weight 3.9, 95% CI 1.4 to 11.2).”
Fergusson, D. M., L. J. Horwood, and K. Northstone. 2002. Maternal use of cannabis and pregnancy outcome. British Journal of Obstetrics and Gynaecology 109(1):21–27.
“Over 12,000 women expecting singletons at 18 to 20 weeks of gestation who were enrolled in the Avon Longitudinal Study of Pregnancy and Childhood……the babies of women who used cannabis at least once per week before and throughout pregnancy were 216g lighter than those of non-users.”

Preterm birth, animal studies
Wang H, Xie H, Dey SK. Loss of cannabinoid receptor CB1 induces preterm birth. PLoS One. 2008;3(10):e3320.
“CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice…. CB1 regulates labor by interacting with the corticotrophin-releasing hormone-driven endocrine axis.”

Preterm birth, human studies
Luke S, Hutcheon J, Kendall T. Cannabis Use in Pregnancy in British Columbia and Selected Birth Outcomes. J Obstet Gynaecol Can. 2019;41(9):1311-1317.
“Using cannabis in pregnancy was associated with a 47% increased risk of SGA (adjusted OR 1.47; 95% CI 1.33–1.61), a 27% increased risk of spontaneous preterm birth (adjusted OR 1.27; 95% CI 1.14–1.42), and a 184% increased risk of intrapartum stillbirth (adjusted HR [aHR] 2.84; 95% CI 1.18–6.82).”
Corsi DJ, Walsh L, Weiss D, Hsu H, El-Chaar D, Hawken S, Fell DB, Walker M. Association Between Selfreported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes. JAMA. 2019;322(2):145-152.
“In a cohort of 661 617 women…. The crude rate of preterm birth less than 37 weeks’ gestation was 6.1%among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95%CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98%(95%CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95%CI, 1.45-1.61]), placental abruption (1.6%vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3%vs 13.8%; RR, 1.40 [95%CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95%CI, 1.13-1.45]).”
Saurel-Cubizolles MJ, Prunet C, Blondel B. Cannabis use during pregnancy in France in 2010. BJOG. 2014;121(8):971-7.
“Cannabis users had higher rates of spontaneous preterm births: 6.4 versus 2.8%, for an adjusted odds ratio (aOR) of 2.15 (95% CI 1.10–4.18).”
Leemaqz SY, Dekker GA, McCowan LM, Kenny LC, Myers JE, Simpson NA, Poston L, Roberts CT;

SCOPE Consortium. Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications. Reprod Toxicol. 2016;62:77-86. “continued maternal marijuana use at 20 weeks’ gestation was associated with” spontaneous preterm birth “independent of cigarette smoking status [adj OR2.28 (95% CI:1.45–3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41–3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks’ gestation had a greater effect size [adj OR 5.44 (95% CI 2.44–12.11)].”

Impacts on the neonatal immune system, animal study
Zumbrun EE et al. Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring. J Neuroimmune Pharmacol. 2015; 10(2):245-54.
“Data from various animal models suggests that in utero exposure to cannabinoids results in profound T cell dysfunction and a greatly reduced immune response to viral antigens

Impacts on cortical wiring and development, animal studies
Tortoriello G, et al. Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J. 2014;33(7):668-85.
“Here, we show that repeated THC exposure disrupts endocannabinoid signaling, particularly the temporal dynamics of CB1 cannabinoid receptor, to rewire the fetal cortical circuitry….these data highlight the maintenance of cytoskeletal dynamics as a molecular target for cannabis”
DiNieri JA, Wang X, Szutorisz H, Spano SM, Kaur J, Casaccia P, Dow-Edwards D, Hurd YL. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry. 2011 Oct 15;70(8):763-9.
“we exposed pregnant rats to THC and examined the epigenetic regulation of the NAc Drd2 gene in their offspring at postnatal day 2, comparable to the human fetal period studied, and in adulthood…. Decreased Drd2 expression was accompanied by reduced D2R binding sites and increased sensitivity to opiate reward in adulthood”
Rodríguez de Fonseca F, Cebeira M, Fernández-Ruiz JJ, Navarro M, Ramos JA. Effects of pre- and perinatal exposure to hashish extracts on the ontogeny of brain dopaminergic neurons. Neuroscience. 1991;43(2-3):713-23.
“Perinatal exposure to cannabinoids altered the normal development of nigrostriatal, mesolimbic and tuberoinfundibular dopaminergic neurons, as reflected by changes in several indices of their activity”.

Impacts on cortical wiring and development, human studies
Grewen K, Salzwedel AP, Gao W. Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure. Front Hum Neurosci. 2015;9:601.

“+MJ (marijuana-exposed) neonates had hypo-connectivity in all clusters compared with –MJ (marijuana unexposed) and CTR (control) groups. Altered striatal connectivity to areas involved in visual spatial and motor learning, attention, and in fine-tuning of motor outputs
involved in movement and language production may contribute to neurobehavioral deficits reported in this at-risk group. Disrupted anterior insula connectivity may contribute to altered integration of interoceptive signals with salience estimates, motivation, decision-making, and later drug use.”
El Marroun H, Tiemeier H, Franken IH, Jaddoe VW, van der Lugt A, Verhulst FC, Lahey BB, White T. Prenatal Cannabis and Tobacco Exposure in Relation to Brain Morphology: A Prospective Neuroimaging Study in Young Children. Biol Psychiatry. 2016;79(12):971-9.
“prenatal cannabis exposure was associated with differences in cortical thickness….. it may be possible that the frontal cortex in cannabis-exposed children undergoes altered neurodevelopmental maturation (i.e., having differences in cortical trajectories) as compared with
nonexposed control subjects”
Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd YL. In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus. Biol Psychiatry. 2004; 56:909–915.
“Adjusting for various covariates, we found a specific reduction, particularly in male fetuses, of the D(2) mRNA expression levels in the amygdala basal nucleus in association with maternal marijuana use. The reduction was positively correlated with the amount of maternal marijuana intake during pregnancy.”

Received by email

I, Surgeon General VADM Jerome Adams, am emphasizing the importance of protecting our Nation from the health risks of marijuana use in adolescence and during pregnancy. Recent increases in access to marijuana and in its potency, along with misperceptions of safety of marijuana endanger our most precious resource, our nation’s youth.

BE PREPARED. GET NALOXONE. SAVE A LIFE.

Background

Marijuana, or cannabis, is the most commonly used illicit drug in the United States. It acts by binding to cannabinoid receptors in the brain to produce a variety of effects, including euphoria, intoxication, and memory and motor impairments. These same cannabinoid receptors are also critical for brain development. They are part of the endocannabinoid system, which impacts the formation of brain circuits important for decision making, mood and responding to stress.

Marijuana and its related products are widely available in multiple forms. These products can be eaten, drunk, smoked, and vaped. Marijuana contains varying levels of delta-9-tetrahydrocannabinol (THC), the component responsible for euphoria and intoxication, and cannabidiol (CBD). While CBD is not intoxicating and does not lead to addiction, its long-term effects are largely unknown, and most CBD products are untested and of uncertain purity.

Marijuana has changed over time. The marijuana available today is much stronger than previous versions. The THC concentration in commonly cultivated marijuana plants has increased three-fold between 1995 and 2014 (4% and 12% respectively). Marijuana available in dispensaries in some states has average concentrations of THC between 17.7% and 23.2%. Concentrated products, commonly known as dabs or waxes, are far more widely available to recreational users today and may contain between 23.7% and 75.9% THC.

The risks of physical dependence, addiction, and other negative consequences increase with exposure to high concentrations of THC and the younger the age of initiation. Higher doses of THC are more likely to produce anxiety, agitation, paranoia, and psychosis. Edible marijuana takes time to absorb and to produce its effects, increasing the risk of unintentional overdose, as well as accidental ingestion by children and adolescents. In addition, chronic users of marijuana with a high THC content are at risk for developing a condition known as cannabinoid hyperemesis syndrome, which is marked by severe cycles of nausea and vomiting.

This advisory is intended to raise awareness of the known and potential harms to developing brains, posed by the increasing availability of highly potent marijuana in multiple, concentrated forms. These harms are costly to individuals and to our society, impacting mental health and educational achievement and raising the risks of addiction and misuse of other substances.  Additionally, marijuana use remains illegal for youth under state law in all states; normalization of its use raises the potential for criminal consequences in this population. In addition to the health risks posed by marijuana use, sale or possession of marijuana remains illegal under federal law notwithstanding some state laws to the contrary.

Watch the Surgeon General Answer FAQs on Marijuana

Marijuana Use during Pregnancy

Pregnant women use marijuana more than any other illicit drug. In a national survey, marijuana use in the past month among pregnant women doubled (3.4% to 7%) between 2002 and 2017. In a study conducted in a large health system, marijuana use rose by 69% (4.2% to 7.1%) between 2009 and 2016 among pregnant women. Alarmingly, many retail dispensaries recommend marijuana to pregnant women for morning sickness.

Marijuana use during pregnancy can affect the developing fetus.

  • THC can enter the fetal brain from the mother’s bloodstream.
  • It may disrupt the endocannabinoid system, which is important for a healthy pregnancy and fetal brain development
  • Studies have shown that marijuana use in pregnancy is associated with adverse outcomes, including lower birth weight.
  • The Colorado Pregnancy Risk Assessment Monitoring System reported that maternal marijuana use was associated with a 50% increased risk of low birth weight regardless of maternal age, race, ethnicity, education, and tobacco use.

The American College of Obstetricians and Gynecologists holds that “[w]omen who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Women reporting marijuana use should be counseled about concerns regarding potential adverse health consequences of continued use during pregnancy”. In 2018, the American Academy of Pediatrics recommended that “…it is important to advise all adolescents and young women that if they become pregnant, marijuana should not be used during pregnancy”.

Maternal marijuana use may still be dangerous to the baby after birth. THC has been found in breast milk for up to six days after the last recorded use. It may affect the newborn’s brain development and result in hyperactivity, poor cognitive function, and other long-term consequences. Additionally, marijuana smoke contains many of the same harmful components as tobacco smoke. No one should smoke marijuana or tobacco around a baby.

Marijuana Use during Adolescence

Marijuana is also commonly used by adolescents, second only to alcohol. In 2017, approximately 9.2 million youth aged 12 to 25 reported marijuana use in the past month and 29% more young adults aged 18-25 started using marijuana. In addition, high school students’ perception of the harm from regular marijuana use has been steadily declining over the last decade. During this same period, a number of states have legalized adult use of marijuana for medicinal or recreational purposes, while it remains illegal under federal law. The legalization movement may be impacting youth perception of harm from marijuana. 

The human brain continues to develop from before birth into the mid-20s and is vulnerable to the effects of addictive substances. Frequent marijuana use during adolescence is associated with:

  • Changes in the areas of the brain involved in attention, memory, decision-making, and motivation. Deficits in attention and memory have been detected in marijuana-using teens even after a month of abstinence.
  • Impaired learning in adolescents. Chronic use is linked to declines in IQ, school performance that jeopardizes professional and social achievements, and life satisfaction.
  • Increased rates of school absence and drop-out, as well as suicide attempts.

Risk for and early onset of psychotic disorders, such as schizophrenia. The risk for psychotic disorders increases with frequency of use, potency of the marijuana product, and as the age at first use decreases. 

  • Other substance use. In 2017, teens 12-17 reporting frequent use of marijuana showed a 130% greater likelihood of misusing opioids23.

Marijuana’s increasingly widespread availability in multiple and highly potent forms, coupled with a false and dangerous perception of safety among youth, merits a nationwide call to action. 

You Can Take Action

No amount of marijuana use during pregnancy or adolescence is known to be safe. Until and unless more is known about the long-term impact, the safest choice for pregnant women and adolescents is not to use marijuana.  Pregnant women and youth–and those who love them–need the facts and resources to support healthy decisions. It is critical to educate women and youth, as well as family members, school officials, state and local leaders, and health professionals, about the risks of marijuana, particularly as more states contemplate legalization.

Science-based messaging campaigns and targeted prevention programming are urgently needed to ensure that risks are clearly communicated and amplified by local, state, and national organizations. Clinicians can help by asking about marijuana use, informing mothers-to-be, new mothers, young people, and those vulnerable to psychotic disorders, of the risks. Clinicians can also prescribe safe, effective, and FDA-approved treatments for nausea, depression, and pain during pregnancy. Further research is needed to understand all the impacts of THC on the developing brain, but we know enough now to warrant concern and action. Everyone has a role in protecting our young people from the risks of marijuana.

Information for Parents and Parents-to-be

You have an important role to play for a healthy next generation.

Information for Youth:

You have an important role to play for a healthy next generation.

Information for States, Communities, Tribes, and Territories:

You have an important role to play for a healthy next generation.

Information for Health Professionals:

You have an important role to play for a healthy next generation.

Source: Surgeon General’s Advisory: Marijuana Use & the Developing Brain | HHS.gov August 2019

Understanding motives for cannabis use is important for addiction prevention and intervention

(SACRAMENTO)  A study in Psychology of Addictive Behaviors by researchers at UC Davis Health and the University of Washington surveyed teens over a six-month period to better understand their motives for using cannabis. The researchers found that teens who have more “demand” for cannabis (meaning they are willing to consume more when it is free and spend more overall to obtain it) are likely to use it for enjoyment.

Using cannabis for enjoyment (“to enjoy the effects of it”) was linked to using more of it and experiencing more negative consequences.

Teens who have more demand for cannabis were also likely to use it to cope (“to forget your problems”). Using cannabis to cope was linked to experiencing more negative consequences, as identified by the Marijuana Consequences Checklist. Examples of negative effects include having trouble remembering things, difficulty concentrating and acting foolish or goofy.

Cannabis — also called marijuana, pot or weed — is the most used federally illegal drug in the United States. As of November 2023, 24 states and the District of Columbia have legalized cannabis for medicinal and recreational use. At the federal level, marijuana remains a Schedule One substance under the Controlled Substances Act.

“Understanding why adolescents use marijuana is important for prevention and intervention,” said Nicole Schultz, first author of the study and an assistant professor in the UC Davis Department of Psychiatry and Behavioral Sciences. “We know that earlier onset of cannabis use is associated with the likelihood of developing a cannabis use disorder. It is important we understand what variables contribute to their use so that we can develop effective strategies to intervene early,” Schultz said.

We know that earlier onset of cannabis use is associated with the likelihood of developing a cannabis use disorder. It is important we understand what variables contribute to their use so that we can develop effective strategies to intervene early.”Nicole Schultz, assistant professor, Department of Psychiatry and Behavioral Sciences

Cannabis a public health concern

Cannabis is the most used psychoactive substance among adolescents. In 2022, 30.7% of twelfth graders reported using cannabis in the past year, and 6.3% reported using cannabis daily in the past 30 days.

The increased use is a public health concern, as cannabis can have significant impacts on teen health. A study earlier this year from Columbia University found teens who use cannabis recreationally are two to four times as likely to develop psychiatric disorders, such as depression and suicidality, than teens who do not use cannabis. Teens are also at risk for addiction or cannabis use disorder, where they try but cannot quit using cannabis.

When talking about prevention and intervention with addictive substances, it is essential to know why people use the substances, according to Schultz.

“The reasons often change over time. At the beginning, someone might use a substance for recreational reasons but have different motives later when the substance has become a problem for them,” she said.

For the study, the researchers used mediation analysis to focus on two motives: enjoyment and coping. They examined how these two motives explained the relationship between cannabis demand — a measure of how important or “reinforcing” cannabis is to the user — and cannabis-related outcomes, which included negative consequences and use.

Study participants were between the ages of 15 and 18. Participants completed an initial survey and follow-up surveys at three months and six months. High school students comprised 60.7% of the participants, and four-year college students comprised 24.7%. All lived in the greater metropolitan area of Seattle, where the legalized age for recreational cannabis use is 21 and older.

Of these participants, 87.6% identified as white, 19.1% as Asian or Asian American, 16.9% identified as Hispanic or Latinx, 4.5% as Black or African American, 3.4% as American Indian or Alaska Native and 3.4% identified with another race. Participants could choose more than one selection for race.

The researchers found that greater cannabis demand was significantly associated with using cannabis for enjoyment. Using for enjoyment was also significantly associated with cannabis use for the young study participants.

“This finding makes sense because using for enjoyment is typically related to the initiation of use versus problematic use. And given the age of the participants in this study, they may have short histories of use,” Schultz said.

Being willing to consume more cannabis at no cost, spend more money on cannabis overall, and continue spending at higher costs was positively associated with using cannabis for coping reasons.

Participants who used cannabis for coping and enjoyment both reported experiencing negative consequences from cannabis use. These included feeling increased anxiety, making decisions that were later regretted and getting in trouble with school or an employer.

The researchers noted several limitations of the study, including a lack of diversity, with nearly 88% of the survey participants identifying as white. Another limitation was that the participants’ cannabis usage was self-reported. The study results may also be specific to regions like Seattle, where cannabis has been legalized for adults.

“The current study suggests that encouraging substance-free activities that are fun for adolescents and help adolescents cope with negative feelings may help them use less cannabis and experience fewer negative consequences from use,” said Jason J. Ramirez senior author of the study. Ramirez is an assistant professor in the Department of Psychiatry and Behavioral Sciences at the University of Washington and a faculty member of the Center for the Study of Health and Risk Behaviors.

By Lisa Howard

Additional authors include Tessa Frohe from the University of Washington and Christopher J. Correia from Auburn University.

The Substance Abuse and Mental Health Services Administration has a website and a national hotline, at 1-800-662-4357, for individuals and families facing substance use disorders. Information about cannabis use disorder is available on the Centers for Disease Control webpage.

This research was supported by the National Institute on Drug Abuse (R21DA045092) and the National Institute on Alcohol Abuse and Alcoholism (F32AA028667, T32AA007455, K01AA030053)

Resources

 

A Research Letter published in the Journal of the American Medical Association (JAMA) raises alarms about administering melatonin gummies to children. Between 2012 and 2021, reports to U.S. poison control centers regarding pediatric melatonin ingestions surged 530% and were linked with 27,795 emergency department and clinic visits, 4,097 hospitalizations, 287 intensive care admissions, and tragically, 2 fatalities. Investigation into melatonin products’ labels revealed widespread inaccuracies relating to the presence of both melatonin and cannabidiol (CBD).

 

An examination of 25 melatonin gummy products obtained from the National Institutes of Health’s Dietary Supplement Label Database revealed that a staggering 88 percent of these products had inaccurate labels, ranging from one product containing no melatonin to the others containing anywhere from 74 percent to 347 percent of the stated amount. Among the five products containing CBD, the measured CBD amounts varied from 104 percent to 118 percent of the labeled quantity.

 

This is extremely concerning as administering melatonin gummies to children can expose them to enormously high amounts of melatonin and CBD. Combining melatonin and CBD can lead to potential moderate interactions, intensifying effects like dizziness, drowsiness, confusion, and difficulty concentrating. These products often claim to aid in sleep, stress, and relaxation, making it imperative to inform parents and caregivers that despite product claims, neither melatonin nor CBD has received approval from the U.S. Food and Drug Administration (FDA) for use in healthy children.

Source:  https://www.drugs.com/interactions-check.php?drug_list=1548-0,3919-0

https://jamanetwork.com/journals/jama/fullarticle/2804077

Nearly 10% of cannabis users in the United States report using it for medicinal purposes.
As of August 2019, 33 states and the District of Columbia have initiated policies allowing the use of cannabis or cannabinoids for the management of specific medical conditions.
Yet, the federal government still classifies cannabis as illegal, complicating its medical use and research into its effectiveness as a treatment for the various conditions purported to benefit from cannabis pharmacotherapy. Because of this conflict and restrictions on cannabis research, evidence of the efficacy of cannabis to manage various diseases is often lacking.

This article updates a review published in the June 23, 2015, issue of JAMA2 and describes newer evidence regarding what is known and not known about the efficacy of cannabis and cannabinoids for managing various conditions.

Indications for Therapeutic Use Approved by the US Food and Drug Administration
Cannabis has numerous cannabinoids, the most notable being tetrahydrocannabinol, which accounts for its psychoactive effects. Individual cannabinoids have unique pharmacologic profiles enabling drug development to manage various conditions without having the cognitive effects typically associated with cannabis.

Only a few cannabinoids have high-quality evidence to support their use and are approved for medicinal use by the US Food and Drug Administration (FDA). The cannabinoids dronabinol and nabilone were approved by the FDA for chemotherapy-induced nausea and vomiting in 1985, with dronabinol gaining an additional indication for appetite stimulation in conditions that cause weight loss, such as AIDS, in 1992. Recently, a third cannabinoid, cannabidiol (CBD), was approved by the FDA for the management of 2 forms of pediatric epilepsy, Dravet syndrome and Lennox-Gastaut syndrome, based on the strength of positive randomized clinical trials (RCTs).

Other Medical Indications
Cannabinoids are often cited as being effective for managing chronic pain. The National Academies of Science, Engineering, and Medicine examined this issue and found that there was conclusive or substantial evidence that cannabis or cannabinoids effectively managed chronic pain, based on their expert committee’s assessment that the literature on this topic had many supportive findings from good-quality studies with no credible opposing findings.

The panel relied on a single meta-analysis of 28 studies, few of which were from the United States, that assessed a variety of diseases and compounds. Although they concluded that cannabinoids effectively managed pain, the CIs associated with these findings were large, suggesting unreliability in the meta-analysis results.
A more recent meta-analysis of 91 publications found cannabinoids to reduce pain 30% more than placebo (odds ratio, 1.46 [95% CI, 1.16 1.84]), but had a number needed to treat for chronic pain of 24 (95% CI, 15-61) and a number needed to harm of 6 (95% CI, 5-8).While a moderate level of evidence supports these recommendations, most studies of the efficacy of cannabinoids on pain are for neuropathic pain, with relatively few high-quality studies examining other types of pain. Taken together, at best, there is only inconclusive evidence that cannabinoids effectively manage chronic pain, and large numbers of patients must receive treatment with cannabinoids for a few to benefit, while not many need to receive treatment to result in harm.
There is strong evidence to support relief of symptoms of muscle spasticity resulting from multiple sclerosis from cannabinoids as reported by patients, but the association is much weaker when outcomes are measured by physicians. There is insufficient evidence to support or refute claims that cannabinoids provide relief for spinal cord injury–related muscle spasms.

Recent Clinical Trials
Two multicenter, international trials with substantial numbers of patients (n = 120 and n = 171) demonstrated the efficacy of CBD as an add-on drug to manage some seizure disorders. Over 14 weeks, 20mg/kg of CBD significantly reduced the median frequency of convulsive seizures in children and young adults with Dravet syndrome as well as the estimated median difference in monthly drop seizures between CBD and placebo in patients with Lennox-Gastaut syndrome. Although promising, these results were found in relatively uncommon disorders and the studies were limited by the use of subjective end points and incomplete blinding that is typical of cannabinoid studies because these drugs have readily identifiable side effects.
Numerous other medical conditions, including Parkinson disease, posttraumatic stress disorder, and Tourette syndrome, have a hypothetical rationale for the use of cannabis or cannabinoids as pharmacotherapy based on cannabinoid effects on spasticity, anxiety, and density of cannabinoid receptors in areas implicated in development of tics, such as the basal ganglia and cerebellum. The strength of the evidence supporting the use of cannabinoids for these diseases is weak because most studies of patients with these diseases have been small, often uncontrolled, or crossover studies.

Few pharmaceutical companies are conducting cannabinoid trials. Thus, it is not likely that additional cannabinoids will be approved by the FDA in the near future. Public interest in cannabis and cannabinoids as pharmacotherapy continues to increase, as does the number of medical conditions for which patients are utilizing cannabis and CBD, despite insufficient evidence to support this trend.

Neurologic Adverse Effects Are Better Defined Than Physical Adverse Effects
Acute cannabis use is associated with impaired learning, memory, attention, and motor coordination, areas that can affect important activities of daily living, such as driving. Acute cannabis use can also affect judgment, potentially resulting in users making risky decisions that they would not otherwise make. While there is consensus that acute cannabis use results in cognitive deficits, residual cognitive effects persisting after acute intoxication are still debated, especially for individuals who used cannabis regularly as adolescents.

Chronic cannabis use is associated with an increased risk of psychiatric illness and addiction. There is a significant association— possibly a causal relationship—between cannabis use and the development of psychotic disorders, such as schizophrenia, particularly among heavy users. Chronic cannabis use can lead to cannabis use disorder (CUD) and contributes to impairment in work, school, and relationships in up to 31% of adult users.  Regular cannabis use at levels associated with CUD (near-daily use of more than one eighth ounce of cannabis per week) is associated with worsening functional status, including lower income, greater need for socio-economic assistance, criminal behavior, unemployment, and decreased life satisfaction.

Cannabis use is associated with adverse perinatal outcomes as well; a 2019 study showed the crude rate of preterm birth was 12.0% among cannabis users and 6.1% among nonusers (risk difference, 5.88% [95% CI, 5.22%-6.54%]).

Inadequate Evidence Supporting the Use of Cannabinoids for Many Medical Conditions
The quality of the evidence supporting the use of cannabinoids is suboptimal. First, studies assessing pain and spasticity are difficult to conduct, in part because of heterogeneity of the outcome measures used in these studies. Second, most RCTs that have evaluated cannabinoid clinical outcomes were small, with fewer than 100 participants in each, and small trials may overestimate treatment effects. Third, the timeframe for most studies is too short to assess the long-term effects of these medications. Fourth, tolerance, withdrawal, and potential for drug-drug interactions may affect the usefulness of cannabis, and these phenomena are not well understood for cannabinoids.

The lack of high-quality evidence results in outsized claims of the efficacy of cannabinoids for numerous medical conditions. There is a need for well-designed, large, multisite RCTs of cannabis or cannabinoids to resolve claims of efficacy for conditions for which there are claims of efficacy not supported by high quality evidence, such as pain and spasticity.

Conclusions
Insufficient evidence exists for the use of medical cannabis for most conditions for which its use is advocated. Despite the lack of evidence, various US state governments have recommended cannabis for the management of more than 50 medical conditions. Physicians may be appropriately reticent to recommend medical cannabis for their patients because of the limited scientific evidence supporting its use or because cannabis remains illegal in federal law. Cannabis is useful for some conditions, but patients who might benefit may not get appropriate treatment because of insufficient awareness regarding the evidence supporting its use or confusion from federal law deeming cannabis illegal.

Source: Medical Use of Cannabis in 2019 | Clinical Pharmacy and Pharmacology | JAMA | JAMA Network August 2019

As states have begun to legalize marijuana, its use has been more openly discussed. While the effects of other commonly used drugs, such as alcohol, have been studied extensively, the effects of marijuana – especially on developing babies during pregnancy – have been much less studied and less widely publicized. This relative silence from the scientific community has affected the public’s opinion on the safety of marijuana: 70 percent of U.S. women think there is “slight or no risk of harm” to the baby from using marijuana during pregnancy. Expectant mothers may use marijuana rather than prescription drugs during pregnancy to relieve pain because they feel “natural” or home remedies are a safer option than prescription drugs. However, just because something is “natural” doesn’t mean it is any safer or a better alternative to well-studied prescription drugs. This seems to be the case for marijuana. Given that marijuana is the most commonly used illicit drug during pregnancy, understanding its risks and impacts on the developing fetus is important.

Three large-scale longitudinal studies tracked how maternal cannabis use affected their child’s development, and they have had surprisingly consistent results. The Ottawa Prenatal Prospective Study surveyed 700 pregnant women who used marijuana in 1978 and has followed about 200 of those children into adulthood. The U.S.-based Maternal Health Practices and Child Development Study has studied 580 children of marijuana users from pregnancy through age 14. The Generation R study is tracking almost 8,000 children in the Netherlands.

Children of marijuana users were more impulsive and hyperactive, and exhibited behavioral issues, lower IQ scores, and memory problems when compared to children of non-users. These mental health problems persisted through their teenage years, where they were significantly more likely to have attention problems and depression. Marijuana-exposed children were also almost twice as likely to display delinquent behavior, such as drug use, by the age of 14 and were more than twice as likely to regularly use marijuana and tobacco as adults. The very consistent results between mice and human studies (summarized in the infographic from The Scientist below) highlights an increasing understanding of the impacts of marijuana use on development.

 

© LAURIE O’KEEFE

It’s important to note that some behavioral outcomes may not be completely related to fetal marijuana exposure. Children of marijuana users may have grown up in a different social environment with more lax views on drugs, contributing to their increased drug use.

As marijuana continues to be legalized, we should expect to see more studies on its health effects and safety.

 

Source: https://sitn.hms.harvard.edu/flash/2019/marijuana-exposure-affects-developing-babies-brains/

Abstract

Importance: As the overall prevalence of prenatal cannabis use rises, it is vital to also monitor trends in the frequency of cannabis use in the period leading up to and during pregnancy because more frequent use may confer greater health risks for mothers and their children.

Objective: To examine trends in the frequency of self-reported cannabis use among pregnant women in the year before and during pregnancy.

Design, setting, and participants: Cross-sectional study using data from 367 403 pregnancies among 276 991 women 11 years or older who completed a self-administered questionnaire on cannabis use during standard prenatal care in Kaiser Permanente Northern California from January 1, 2009, to December 31, 2017. The annual prevalence of self-reported daily, weekly, and monthly cannabis use among women before and during pregnancy was estimated using Poisson regression with a log link function, adjusting for sociodemographics. Data analyses were conducted from February to May 2019.

Exposures: Calendar year.

Main outcomes and measures: Self-reported frequency of cannabis use in the year before pregnancy and during pregnancy assessed as part of standard prenatal care (at approximately 8 weeks’ gestation).

Results: Among the overall sample of 367 403 pregnancies among 276 991 women, 35.9% of the women self-reported white race/ethnicity; 28.0%, Hispanic; 16.6%, Asian; 6.0%, African American; and 13.5%, other. In the sample, 1.2% of the women were aged 11 to 17 years; 15.3%, 18 to 24 years; 61.4%, 25 to 34 years; and 22.0%, older than 34 years. Median (interquartile range) neighborhood household income was $70 472 ($51 583-$92 643). From 2009 to 2017, the adjusted prevalence of cannabis use in the year before pregnancy increased from 6.80% (95% CI, 6.42%-7.18%) to 12.50% (95% CI, 12.01%-12.99%), and the adjusted prevalence of cannabis use during pregnancy increased from 1.95% (95% CI, 1.78%-2.13%) to 3.38% (95% CI, 3.15%-3.60%). Annual relative rates of change in self-reported daily cannabis use (1.115; 95% CI, 1.103-1.128), weekly cannabis use (1.083; 95% CI, 1.071-1.095), and monthly or less cannabis use (1.050; 95% CI, 1.043-1.057) in the year before pregnancy increased significantly, with daily use increasing most rapidly (from 1.17% to 3.05%). Similarly, annual relative rates of change in self-reported daily cannabis use (1.110; 95% CI, 1.089-1.132), weekly cannabis use (1.075; 95% CI, 1.059-1.092) and monthly or less cannabis use (1.044; 95% CI, 1.032-1.057) during pregnancy increased significantly from 2009 to 2017, with daily use increasing most rapidly (from 0.28% to 0.69%).

Conclusions and relevance: Results of this study demonstrate that frequency of cannabis use in the year before pregnancy and during pregnancy has increased in recent years among pregnant women in Northern California, potentially associated with increasing acceptance of cannabis use and decreasing perceptions of cannabis-associated harms.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Young-Wolff, Mr Tucker, Dr Alexeeff, and Ms Armstrong report receiving grants from National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA) during the conduct of the study. No other disclosures were reported.

Figures

 

Adjusted Prevalence of Cannabis Use Among 367 403 Pregnancies During Pregnancy by Frequency of Use, 2009-2017 

Adjusted prevalence estimates (dots) and 95% CIs (error bars) were estimated from Poisson regression models controlling for age group, race/ethnicity, and median neighborhood household income (extracted from the electronic health record [Table 2]). Self-reported cannabis use during pregnancy was assessed via a questionnaire as part of standard prenatal care (at approximately 8 weeks’ gestation).

Abstract
Cannabis has been shown to be teratogenic in cells, animals and humans. Particular targets of prenatal exposure include brain, heart and blood vessels and chromosomal segregation. Three longitudinal clinical studies report concerning cortical dysfunction persisting into adolescence and beyond, which are pertinent to the autism epidemic.
Increased rates of congenital heart defects, gastroschisis, anencephaly and others have been reported. The pattern of neuroteratology seen after cannabis exposure strongly suggests a spectrum of dysfunction from mild to moderate to very severe. Downs syndrome, atrial septal defect (secundum type), ventricular septal defect and anotia / microtia were noted to be more common in prenatally cannabis exposed children in a large US epidemiological study which would appear to have been confirmed by recent experience in Colorado and other USA states.

Studies in cells, together with the above mentioned epidemiology, implicate cannabidiol, cannabichromene, cannabidivarin and other
cannabinoids in significant genotoxicity and / or epigenotoxicity. Notch signalling has recently been shown to be altered by cannabinoids, which is highly pertinent to morphogenesis of the neuraxis and cardiovasculature, and also to congenital and inheritable cancer induction. It is felt that subtle neurobehavioural psychosocial and educational deficits will likely be the most common expression of cannabinoid teratology at the population level. The far reaching implications of this wide spectrum of neuroteratological, pediatric cardiological and other defects and deficits should be carefully considered in increasingly liberal paradigms. Hence it is shown that the disparate presentations of cannabis teratology relate directly and closely to the distribution of CB1R’s across the developing embryo and account for the polymorphous clinical presentations.

Introduction
At a time when up to 24% of Californian teenage mothers test positive for cannabis, it is of concern that the complex literature relating to the teratology of cannabis seems to have created mixed messages in both professional and popular fora, leading the teratogenic effects of cannabis to be overlooked and the impact of increasing cannabis consumption to be underestimated. It is therefore important to reiterate that a number of independent and well-designed studies have similarly indicated major teratogenic effects associated with both maternal and paternal cannabis use.
In reviewing the teratology of prenatal cannabis exposure (PCE) this paper will concisely consider neurobehavioural effects cardiovascular effects including gastroschisis (which is thought to have a vascular aetiopathology), immune effects, chromosomal effects, genetic and epigenetic effects, mitochondrial effects, the effects of the various different exogenous cannabinoids, and notch signalling.

Source: Explaining Contemporary Patterns of Cannabis Teratology (dalgarnoinstitute.org.au) January 2019

In the September/October 2020 Missouri Medicine, Polocaro and Vettraino raise the important issue of the transgenerational effects of prenatal cannabinoid exposure (PCE) on subsequent generations.1 The implications of multigenerational toxicity of cannabinoids is very far-reaching with major policy implications.

The picture presented by Polcaro and Vettraino relating to the mental health implications of PCE is correct if too conservative. As they observe the subject is deeply confounded with multiple other factors impacting post-natal neurological development. For these reasons the significant concordance between reports from five longitudinal studies of childhood development relating to impaired indices of concentration, startle, excitability, poor visuospatial processing and executive functioning including ADHD-like and autism-like features are of particular concern.26 Under a legalization paradigm the state effectively condones unlimited all day every day exposure to extremely high concentrations of THC, other cannabinoids and cannabis tars. What is especially concerning about this is that many of the neurotoxic and neurodevelopmental toxicities of cannabis exhibit threshold dose effects above which severe damage becomes commonplace.7 In the context of an increasingly solid consensus relating to the harmful impacts of adult and adolescent cannabis exposure8 the implications of PCE-neurotoxicity have not been carefully considered. It has been shown that nationwide autism rates are undergoing an exponential rise and indeed New Jersey has been shown to have 4.5% of 8-year-old boys who carry an autism spectrum disorder diagnosis.9,10 Our space-time and causal inference studies demonstrate that indeed cannabinoid exposure to THC and cannabigerol amongst other fractions of cannabis, is a principal driver of this nationwide epidemic (manuscript submitted).9,10

A very concerning consensus is now emerging relating to cannabis-induced teratogenesis, embryotoxicity and fetotoxicity. A 2007 Hawaiian study found that 21 birth defects including many cardiovascular defects, Downs syndrome, orofacial clefts, gastroschisis and arm and hand defects were elevated in offspring of women exposed only to cannabis gestationally with odds ratios up to 40-fold and upper confidence intervals to 123-fold.11 A report on Canada found that total congenital defects were three times more common in the northern territories where cannabis is smoked about three times as much.12,13 In October 2018 Colorado Health reported an excess of 20,152 total birth defects beyond their baseline expected 67,620 defects 2000–2013 across the period of cannabis legalization when the use of other drugs was falling, representing an elevation of 29.8% above background rates.14 In a high cannabis use area of Australia 13 defects were found to be elevated compared to Queensland, which for methodological reasons is a conservative estimate.15 Concerningly elevated rates of Downs syndrome in Colorado, Hawaii, Australia and Canada clearly indicate that heritable cannabis genotoxicity can occur at the hundred megabase chromosomal scale.11,12,14,15 A close association of atrial septal defect (secundum type) with rising patterns of cannabis use across space and time in the US was recently reported, suggesting that the list of known teratological associations of prenatal cannabis exposure is as yet incomplete.16 This epidemiological literature is closely concordant with studies in experimental animals.1719 Again an abrupt rise in genotoxicity with increasing cannabinoid exposure has been demonstrated for many cannabinoids and is of particular concern.2023

Links between cannabis and several paediatric cancers including acute lymphoid leukaemia (ALL), acute myeloid leukaemia, rhabdomyosarcoma and neuroblastoma suggest further implications of cannabinoid genotoxicity.2428 Since these tumours together encompass the common tumours of childhood, it is at least possible that cannabis is responsible for the 43% elevation in total childhood cancer across US 1975–2017.29 Indeed Downs syndrome is well known to be associated with a 2,000-fold elevated risk of childhood ALL from 2/100,000 to around 5/100.30,31

This diverse assemblage of highly congruent evidence of severe cannabis-related neurotoxicity and genotoxicity from varied locations can only be described as extremely concerning indeed. In view of its well described epigenetic and chromoanagenetic effects3234 and its clearly transgenerational-multigenerational impacts one can only conclude that if the evidence base is not admitted to the cannabis debate and access to fetotoxic and embryotoxic cannabinoids is not immediately restricted the community will inevitably pay a heinous price in terms of avoidable paediatric neurotoxicity, congenital birth defects, heritable cancerogenesis and multigenerational epigenotoxicity.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721409/ Nov-Dec 2020 in response to ‘Cannabis in Pregnancy and Lactation – A Review’ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723128/

Cannabis Use in Pregnancy –  A Tale of 2 Concerns

In an article in JAMA, Corsi and colleagues present the results of a retrospective cohort study of 661 617 women designed to assess associations between maternal cannabis use during pregnancy and adverse obstetrical and birth outcomes.

In a matched analysis designed to control for confounding, the investigators compared 5639 self-reported cannabis users with 92 873 nonusers and found elevated rates of preterm birth (defined as gestational age <37weeks) among those who reported cannabis use. Specifically, the rates of pre term birth in the matched cohort were 10.2% vs 7.2% (risk difference, 2.98% [95% CI, 63%-3.34%]; relative risk, 1.41 [95%CI, 1.36-1.47]). While similar risks were observed for small-for-gestational-age birth and placental abruption, there appeared to be a small protective association between cannabis use and preeclampsia and gestational diabetes.

In another article in JAMA, Volkow and colleagues report findings on cannabis use among 4400 pregnant women and 133,900 nonpregnant women aged 12 to 44 years who participated in the National Survey on Drug Use and Health from 2002 to 2017. The authors documented an increase in the adjusted prevalence of cannabis use during pregnancy from 3.4%in 2002 to 7.0%in 2017—almost of all which appeared to be explained by nonmedical use.

These studies send a straightforward message: cannabis use in pregnancy is likely unsafe; with an increasing prevalence of use (presumably related to growing social acceptability and legalization in many states), its potential for harm may represent a public health problem.

This message is based on the sound, if imperfect, epidemiology of these  studies and is heightened by a misperception that marijuana is safe, as evidenced by its direct marketing to pregnant women for morning sickness despite accumulating evidence of harm.

However, there is an additional series of equally legitimate concerns, rooted more in history than epidemiology. These historical concerns relate to past and ongoing discourses on alcohol use in pregnancy and to the cocaine “epidemic that wasn’t” of the 1980s.

Both of these histories, although imperfect comparators with the emerging data on cannabis, illustrate points that provide important context to the present studies published in JAMA

First, there are issues involving the epidemiology. Randomized designs are impractical for studying risks and harms, and observational studies are prone to unmeasured confounding.

In this respect, the study by Corsi and colleagues is no different

From any other cohort study; it is, however, further limited by use of registry data, derived primarily from clinical encounters, to assess cannabis exposure.  Although the investigators performed some internal validity checks on their measurement of exposure, clinical data in the field of substance use tend to lack validation (and thus are prone to mis- classification error), particularly when unaccompanied by biological markers .  Compounding this limitation is the inability to glean from the data the timing of cannabis exposure or a dose-response relationship between exposure and out comes, both of which represent fundamental epidemiologic principles to support causality.

There was also no assessment of birth weight, which tends to be measured more accurately than gestational age.  Despite these limitations, the study is consistent with previous studies that have assessed the association between cannabis use in pregnancy and birth outcomes and provides important, population-based data.

Second, the historical context requires consideration. What has been learned from the debates about alcohol and cocaine use in pregnancy? Although it is accepted that heavy alcohol drinking during pregnancy poses an unacceptable risk to the developing foetus, the effect of moderate alcohol consumption continues to be controversial. 

On one side of this argument, those who interpret the data using a strict, by-the-numbers approach conclude that there is only minimal evidence that moderate alcohol consumption poses a demonstrable risk.

On the other side of the argument are those who interpret the data more broadly to conclude that without an empirically proven safe level of exposure, abstinence is the only reasonable advice the medical community can give to pregnant women.

One lesson of the current alcohol debate—which is often couched in terms of women’s ability to enjoy wine with dinner and thus assumes the perception of an issue that predominantly affects the privileged—is that two reasonable perspectives can be applied to the same body of opposing, non literature and reach stigmatizing conclusions.

In other words, the issue is not the data but the values that individuals bring to the data and to whom the data are thought to be most relevant.

Extrapolating this logic to the data Corsi et al present on cannabis, some might choose to focus on the reported 41% increased relative risk of pre -term birth as unacceptably high; others might choose to focus on the 2.98% absolute risk difference to be such that cannabis-related relaxation or improvement in morning sickness may not be worth abstaining from this drug.

The study by Corsi and colleagues could also be interpreted through a slightly different lens. Perhaps it represents part of an emerging story of an in utero substance exposure that is neither highly prevalent nor extremely rare, an outcome that is consequential more on a population than individual level, and an association between exposure and outcome that is moderate in both its magnitude and degree of certainty.

Unlike the “wine with dinner” debate, the dialogue on cannabis use is likely to be relevant to many sectors of society and may end up focusing on young people, especially those of colour, among whom use is markedly increasing. In these respects, a comparison with certain aspects of the history of cocaine use in pregnancy may be instructive. In 1985, the first “scientific” observation of the relationship between in utero cocaine exposure and neonatal outcomes was published. Even by the standards of its day, this study (and many that followed) were fundamentally flawed.  Yet they provided “evidence” for those in the medical community and lay press to publicly exaggerate risks of cocaine in pregnancy and to attribute (both implicitly and explicitly) lifelong disability to a large cohort of primarily minority children, for whom subsequent research demonstrated similar outcomes to unexposed children raised in similar environments.

Perhaps worse, this exaggerated risk amplified judgment and stereotype, leading to the enduring racist social constructs of the “cocaine mother” and “crackbaby” and to criminalization of substance use among pregnant women. Regrettably, the exaggerated dialogue on cocaine did little to shed light on the sequelae of urban poverty and legacy of racism in the United States. It is possible to argue that the comparisons of cannabis vs alcohol and cocaine are not entirely fair. Cocaine in particular is biologically more destructive than cannabis, universally illegal in the United States, and without health benefit.

Furthermore, the dialogue on cocaine was defined by exaggeration; so far, the dialogue on cannabis has largely been defined by a false perception of safety. While these are fair criticisms, some historic lessons of both alcohol and cocaine apply: it is impossible to separate data from the values that individuals bring to those data, no group is immune to the judgment of others, and women and minority groups (particularly pregnant women of colour) tend to bear the greatest burden of many of these judgments.

While an obvious reaction to these new data on in utero cannabis exposure is that more research is necessary, more epidemiology is unlikely to completely resolve the complex issue of potentially safe moderate use or to completely remove the tendency to imbue data interpretation with implicit biases about groups of people.

Perhaps the best reflection that can be offered is a reprise of that offered by Mayes et al in 1992. This commentary acknowledged the potential harms of prenatal cocaine exposure, dispassionately delineated the methodologic problems with the state of the literature at the time, and expressed concern that premature conclusions attributing irremediable damage in children to exposure to a single substance (isolated from the broader social milieu) were, in and of themselves, harmful. This harm, the commentary argued, accrued by way of permanently lowered expectations and by a discourse that focused on judgment and attribution as opposed to prevention and positive intervention.

The current data reported by Corsi et al and Volkow et al should spark genuine concern about the association of cannabis use in pregnancy with pre term birth. However, there should be additional concern about whether such findings may ripple through society and re-create some of the mistakes of the past.

Source:  Cannabis Use in Pregnancy: A Tale of 2 Concerns – PubMed (nih.gov) June 2019

Limited information exists on marijuana use and male reproductive health. A recent study from Duke University evaluated differences in sperm quality resulting from tetrahydrocannabinol (THC) exposure in both rats and humans. Findings suggest that paternal marijuana use, prior to conception, may present epigenetic risks to potential offspring.

Public perceptions pertaining to marijuana have evolved radically over the past 2 decades. While marijuana remains criminalized at the federal level, 33 states and the District of Columbia have legalized marijuana, in some capacity, for either medical or recreational use. According to the most recent National Survey on Drug Use and Health, nearly 26 million Americans, over the age of 12, currently use marijuana. While the gender gap is narrowing, men remain significantly more likely to use marijuana than women (11.7% vs. 7.3%, respectively).

In 2017, approximately 1.9 million men, between the ages of 26 and 29, reported using marijuana in the past month. Given that the average age of first-time fathers in the U.S. is around 30, these findings suggest that a substantial number of “fathers-to-be” are using marijuana at the time of conception. Little is known, however, about the impact of paternal marijuana use on reproductive outcomes.

Epigenetics, which literally translates to “above” or “on top of” genetics, refers to the biological mechanism through which genes are activated and expressed. This process acts like a light switch, turning on or off how cells read certain heritable traits written within an individual’s unique genetic code. Sperm matures continually throughout adulthood, making it particularly vulnerable to potential epigenetic modifications, such as DNA methylation, that may result from marijuana use. This study explores differences in sperm profiles, based on cannabis exposure in both humans and rats, to better understand potential heritable effects.

Key Findings

  • Individuals who used marijuana can have higher and also can have significantly lower sperm concentrations, compared to those who did not, posing potential complications for fertility.

  • THC-exposed sperm was associated with significantly altered DNA, in both rat and human samples.

*Associations were even stronger among individuals with higher levels of THC in their urine, implying a “dose-response relationship” such that chronic marijuana users may be impacted more severely.

  • Authors identified three unique potential genetic pathways modified by THC exposure.

Looking to the Future

Past research suggests that offspring born to rats exposed to THC during adolescence demonstrate significant DNA alterations in their brains, display heightened drug-seeking behavior, and are at increased risk of developing opioid dependency over time, compared to controls. The present study is the first to extend this line of research to men of childbearing age, lending additional evidence for potential intergenerational, heritable consequences, resulting from paternal marijuana use. Just as other environmental triggers, such as air pollution, cigarette smoking, certain pesticides (i.e. DDT), and exposure to radiation are known to affect sperm health, THC may also increase the potential for genetic mutations.

For Clinicians

  • Primary care physicians and healthcare professionals, both inside and outside of substance use disorder treatment landscapes, should take time to educate patients about the impact of THC on sperm so individuals may consider potential implications for fertility and children conceived during periods of active use.

For Researchers

  • This article adds to a growing literature on the potential epigenetic impact of paternal marijuana use prior to conception. Findings must first be replicated in larger samples. Additionally, future longitudinal studies are necessary to explore the extent to which THC induced DNA alterations in sperm are passed down to offspring, as well as their long-term consequences.

For Policymakers

  • Marijuana potency continues to increase rapidly, with THC level increasing 300% over the past 20 years. Within the current political landscape and shift towards increased access to medical and recreational marijuana, policymakers should work closely with scientists to stay informed on the extent to which increased THC levels and evolving public attitudes impact men’s reproductive health.

For General Public

  • The full impact of passing THC-related DNA modifications onto offspring, and whether or not these changes are reversible is still unknown. Evidence of DNA alterations to existing Hippo signaling and Cancer genetic pathways may disrupt growth, enhance the potential for miscarriage, or impede healthy embryo development.

Methods

The authors employed a quantitative genome-scale approach, referred to as reduced representation bisulfite sequencing, to compare DNA methylation alterations in sperm across human and rat samples. A number of factors including, time since last ejaculation, semen volume, pH, morphology, and motility were controlled for across participants. Pyrosequencing, a DNA synthesizing method that relies on light detection, was implemented to identify genes with significant methylation differences. Data were then analyzed to uncover specific genetic pathways potentially impacted by paternal, preconception cannabis use.

Study Limitations

  • A relatively small sample size of human subjects, limiting the generalizability of study findings.

*24 males, age 18-40 years: (12 marijuana users & 12 non-users)

  • The methodological approach may fail to identify epigenetic modifications that affect multiple genes simultaneously.

Source: What you should know about Marijuana and Sperm (addictionpolicy.org) March 2019, updated October 2022

Abstract

Rates of cannabis use among adolescents are high, and are increasing concurrent with changes in the legal status of marijuana and societal attitudes regarding its use. Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of Δ-9-tetrahydrocannabinol (THC) on brain structure. In the current study, we used voxel-based morphometry to compare gray matter volume (GMV) in forty-six 14-year-old human adolescents (males and females) with just one or two instances of cannabis use and carefully matched THC-naive controls. We identified extensive regions in the bilateral medial temporal lobes as well as the bilateral posterior cingulate, lingual gyri, and cerebellum that showed greater GMV in the cannabis users. Analysis of longitudinal data confirmed that GMV differences were unlikely to precede cannabis use. GMV in the temporal regions was associated with contemporaneous performance on the Perceptual Reasoning Index and with future generalized anxiety symptoms in the cannabis users. The distribution of GMV effects mapped onto biomarkers of the endogenous cannabinoid system providing insight into possible mechanisms for these effects.

SIGNIFICANCE STATEMENT Almost 35% of American 10th graders have reported using cannabis and existing research suggests that initiation of cannabis use in adolescence is associated with long-term neurocognitive effects. We understand very little about the earliest effects of cannabis use, however, because most research is conducted in adults with a heavy pattern of lifetime use. This study presents evidence suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence. Converging evidence suggests a role for the endocannabinoid system in these effects. This research is particularly timely as the legal status of cannabis is changing in many jurisdictions and the perceived risk by youth associated with smoking cannabis has declined in recent years.

Discussion

We present evidence of GMV differences in adolescents associated with only one or two instances of cannabis use. Although novel, this work is consistent with reports of a dose–response effect of cannabis on behavioral and brain measures following heavier use (Lorenzetti et al., 2010Silins et al., 2014). We identified significantly greater GMV in adolescents who reported only one or two instances of cannabis use relative to cannabis naive controls in large medial temporal clusters incorporating the amygdala, hippocampus, and striatum, extending into the left prefrontal cortex. Significantly greater GMV was also observed in the lingual gyri, posterior cingulate, and cerebellum. The regions identified in this whole-brain, VBM approach replicated previous findings of differences in volume (Yücel et al., 2008Ashtari et al., 2011Schacht et al., 2012) and shape (Gilman et al., 2014Smith et al., 20142015) associated with cannabis use in ROI studies and with the spatial distribution of the eCB system (Burns et al., 2007). Although cannabis use has been associated with reduced brain volumes, studies typically report on adults with heavy substance use histories (cf. Ashtari et al., 2011). Gilman et al. (2014), however, have reported gray-matter density increases in the amygdala and nucleus accumbens of young adult recreational users and Medina et al. (2007) observed hippocampal enlargement in cannabis using adolescents. Our results are also consistent with the Avon Longitudinal Study of Parents and Children (French et al., 2015), which showed a trend for greater cortical thickness in male adolescents with <5 instances of cannabis use relative to THC-naive controls.

Converging evidence suggests that these effects may be a consequence of cannabis exposure. GMV differences could not be explained by group differences in demographic, personality, psychopathology, or other substance use factors. Examination of THC-naive 14-year-olds who later used cannabis showed no GMV differences, even using a more liberal ROI test, suggesting that the differences do not precede cannabis use and are not because of unidentified factors in those predisposed to use. Finally, the spatial distribution of GMV effects was associated with the eCB system, suggesting cannabis exposure may cause these findings.

The preclinical literature presents a number of possible mechanisms by which low levels of cannabis exposure could result in greater GMV relative to THC-naive controls. Adolescent rats treated with cannabinoid agonist showed altered gliogenesis in regions including the striatum and greater preservation of oligodendroglia relative to control animals (Bortolato et al., 2014). Zebra finches treated with cannabinoid agonist showed greater dendritic spine densities (Gilbert and Soderstrom, 2011); critically, these effects were observed in late-prenatal but not adult animals. Of particular relevance to this study, a single dose of Δ9THC transiently abolished eCB-mediated long-term depression (LTD) in the nucleus accumbens and hippocampus of adolescent mice (Mato et al., 2004). Suspension of LTD may interrupt maturation-related neural pruning and preserve gray matter. Future studies should assess whether these processes operate in human adolescents and whether they produce persisting alterations in GMV.

These findings should be interpreted in light of the study’s limitations. The IMAGEN sample is racially and ethnically homogenous so it remains to be determined whether the findings generalize to youth from more diverse backgrounds. Substance use was assessed using self-report and we do not have standard dose units of cannabis nor information on mode of use or a measure of drug metabolites. Combining images from different sites and imaging platforms remains controversial and is not completely controlled by including site as a covariate. Future studies should replicate the present results using images acquired at the same site on the same scanner or with equal numbers of cases and controls per scanner. We also note that the CNR1 gene expression (Hawrylycz et al., 2012) and CB1 receptor density (D’Souza et al., 2016) maps were generated in independent samples of adults and may not accurately represent the eCB system in our sample of adolescents. Although we report significant spatial associations between GMV effects and both CNR1 gene expression and CB1 receptor density, the effect sizes were small and any suggestion that these associations represent mechanisms for the effects we observe is speculative and requires further investigation.

We adopted a whole-brain, VBM approach to detect effects that were not limited by anatomical boundaries and to allow exploration of spatial relationships between GMV effects and the eCB system. There is evidence, however, that brain perfusion can influence VBM measures of local volume (Franklin et al., 20132015Ge et al., 2017; cf. Hawkins et al., 2018) so future studies should combine VBM with other measures of brain structure to provide confirmatory evidence. In particular, shape analysis has been shown to be sensitive to brain structural differences associated with cannabis use (Gilman et al., 2014Smith et al., 20142015Weiland et al., 2015). Moreover, combining morphometry metrics allows for testing of associations between them, which can identify different relationships between shape deformations and local volume (Gilman et al., 2014) providing evidence of further differences between cannabis users and controls.

One source of variability in the human findings on brain structural correlates of cannabis use may be comorbid substance use (Weiland et al., 2015Gillespie et al., 2018). Given recent evidence of different patterns of functional connectivity in groups using alcohol, nicotine, and cannabis alone and in combination (Vergara et al., 2018), it will be important to account for any possible interaction effects of cannabis with other psychoactive substances. This issue is particularly important considering the ways in which comorbid substance use has been addressed in two recent, widely cited studies. Gilman et al. (2014) covaried for alcohol and nicotine use and found gray-matter density increases and shape deformations associated with cannabis use. Weiland et al. (2015) matched groups on alcohol and nicotine use and reported no morphometric differences associated with cannabis use, concluding that previously reported differences associated with cannabis may instead be attributable to alcohol use. The participants in Weiland et al.’s (2015) study, however, were using alcohol and nicotine at higher levels than those in Gilman et al.’s (2014) study. It is possible that cannabis, alcohol, and nicotine have differential effects on brain morphometry; specifically, recreational cannabis use has been associated with volume increases, whereas alcohol has been associated with volume reductions. In the current study, we matched the groups on alcohol and nicotine use and, within the cannabis using group, neither alcohol nor nicotine use was associated with individual differences in GMV, suggesting that the GMV differences we report are associated with cannabis use.

We note individual differences in GMV effects: although regional GMV was greater at the group level for adolescents with low levels of cannabis exposure, the distributions showed a high degree of overlap such that many cannabis users had GMV equivalent to that of controls. None of the tested demographic, personality, or substance use factors stratified GMV in the cannabis users. We note evidence that an association between cannabis use and cortical thickness was stratified by genetic risk for schizophrenia (French et al., 2015) and that an association between cannabis use and hippocampal shape was stratified by dopamine-relevant genes (Batalla et al., 2018). Some adolescents may be vulnerable to GMV effects at extremely low levels of cannabis use and it will be critical to identify those at risk as these structural brain changes may be associated with individual risk for psychopathology and deleterious effects on mood and cognition.

Of the behavioral variables tested, only sensation seeking and agoraphobia differed between the cannabis users and controls and these factors were not related to GMV differences. In the cannabis using participants, GMV in the medial temporal clusters was associated with PRIQ and psychomotor speed such that greater GMV in these regions was associated with reduced performance. The finding that right medial temporal GMV predicted generalized anxiety symptoms at follow-up for those participants who had used cannabis should be interpreted with caution given the small sample size and that we were not able to identify factors that drove the individual differences in cannabis effects on GMV at baseline. These findings are notable, however, as panic and anxiety symptoms are frequently reported side effects by naive and occasional cannabis users (Hall and Solowij, 1998). We also note fMRI evidence of hypersensitivity of the amygdala to signals of threat in a partly overlapping sample of cannabis using adolescents (Spechler et al., 2015) and a relationship between adolescent cannabis use and future mood complaints (Wittchen et al., 2007), even with comparatively low levels of use (Cheung et al., 2010).

We have revealed greater GMV in adolescents with only one or two instances of cannabis use in regions rich in CB1 receptors and CNR1 gene expression. Critically, we were able to control for a range of demographic and substance use effects, to confirm that these structural brain effects were not associated with comorbid psychopathology, and to demonstrate that these effects were unlikely to precede cannabis use. The pattern of results is characterized by individual differences in GMV effects in the cannabis users; these individual differences were associated with PRIQ and with vulnerability to future symptoms of generalized anxiety. Given the increasing levels of cannabis use among adolescents today, we suggest that studying the effects of recreational use early in life is an area of particular importance that should be addressed in the future by large scale, prospective studies.

Source: Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence | Journal of Neuroscience (jneurosci.org) March 2019

Abstract

Rising Δ9-tetrahydrocannabinol concentrations in modern cannabis invites investigation of the teratological implications of prenatal cannabis exposure. Data from Colorado Responds to Children with Special Needs (CRCSN), National Survey of Drug Use and Health, and Drug Enforcement Agency was analyzed. Seven, 40, and 2 defects were rising, flat, and falling, respectively, and 10/12 summary indices rose. Atrial septal defect, spina bifida, microcephalus, Down’s syndrome, ventricular septal defect, and patent ductus arteriosus rose, and along with central nervous system, cardiovascular, genitourinary, respiratory, chromosomal, and musculoskeletal defects rose 5 to 37 times faster than the birth rate (3.3%) to generate an excess of 11 753 (22%) major anomalies. Cannabis was the only drug whose use grew from 2000 to 2014 while pain relievers, cocaine, alcohol, and tobacco did not. The correlation of cannabis use with major defects in 2014 (2019 dataset) was R = .77, P = .0011. Multiple cannabinoids were linked with summary measures of congenital anomalies and were robust to multivariate adjustment.

Introduction

While the teratogenic activities of cannabis have been investigated since the 1960s, substantially higher levels of Δ9-tetrahydrocannabinol of currently used cannabis suggests that the neonatal epidemiology of former years requires reexamination.
Urgency for epidemiological reassessment achieves particular currency in view of recent US data indicating that 24% of pregnant Californian teenagers test positive for cannabinoids, that 69% of pregnant Coloradan mothers have cannabis recommended to them by cannabis dispensaries, and that 161 000 pregnant women across the United States admitted to cannabis use during their pregnancy.
In such a context, experience from flagship states such as Colorado, which has been a pioneer in US cannabis use and also supports a detailed and public database of congenital defects, is invaluable to ascertain current trends and likely future directions. Cannabis was permitted for medicinal use from November 2000 and was decreed legal in November 2011 with full effect from 2014.
Colorado also has one other considerable advantage that greatly simplifies the statistical analysis of its data, as during the period 2000 to 2014, nationally representative datasets indicate that the use of other drugs was static or falling. In this sense, therefore, the Coloradan context is ideal from a statistical and public health perspective to ascertain current teratological trends while statistically isolating the effect of rising cannabinoid exposure to facilitate the study of prenatal cannabis exposure (PCE).
This study explores the presence of any overall trends in the pattern of Coloradan congenital anomalies data and investigates the extent to which ecologically documented drug use trends explained some of this variance.

Conclusion

An excess of 11 753 to 20 152 birth defects occurred in Colorado from 2000 to 2014, which represents a 6.7- to 9.4-fold excess of growth in defects compared with growth in births. Defects in 6 of 8 major organ systems increased significantly in frequency. While other drug use was falling over this period, cannabis use alone rose. Cannabis and many cannabinoids were shown to be associationally linked with this rise with correlation coefficients up to 0.78, were confirmed on bivariate analysis, and were robust to multivariate adjustment. In the context of multiple mechanistic pathways, causality is strongly implied. Longitudinal case-control series denominated by an objective measures of drug use are indicated.

Source: Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends – Albert Stuart Reece, Gary Kenneth Hulse, 2019 (sagepub.com) July 2019

  • Teenagers who smoke have thicker matter in certain parts of their brains
  • This was found in areas involved with emotions, memory, fear and panic
  • Adolescent brains are typically thinning and being refined during this period
  • Experts said ‘most people would assume one or two joints would have no impact’

Just one or two joints is enough to change the structure of a teenager’s brain, scientists have warned.

And the drug could cause changes affecting how likely they are to suffer from anxiety or panic, according to a study.

Researchers found 14-year-old girls and boys exposed to THC – the psychoactive chemical in cannabis – had a greater volume of grey matter in their brains.    

This means the tissue in certain areas is thicker, and it was found to be in the same areas as the receptors which marijuana affects.

Experts said thickening of brain tissue is the opposite of what usually happens during puberty, when teenagers’ brain matter gets thinner and more refined.

Researchers did scans of teenagers’ brains and discovered those who had been exposed to small amounts of marijuana (top row) had thicker regions of the brain (indicated by more orange and yellow tissue) than those who had never smoked cannabis (bottom row)

Researchers from the University of Vermont scanned the brains of teenagers from England, Ireland, France and Germany to study marijuana’s effects. 

They found differences in the volume of grey matter in the amygdala and the hippocampus.

These sections are involved with emotions, fear, memory development and spatial skills – changes to them suggests smoking cannabis could affect these faculties.    

Scientists said theirs is the first evidence to suggest structural brain changes and cognitive effects of just one or two uses of cannabis in young teenagers.

And it suggests as teenagers brains are still developing, they may be particularly vulnerable to the effects of THC.

THC, full name tetrahydrocannabinol, is the chemical in marijuana which makes people high and is what makes it illegal in the UK. 

‘Consuming just one or two joints seems to change grey matter volumes in young adolescents,’ said study author Professor Dr Hugh Garavan.

‘The implication is that this is potentially a consequence of cannabis use. You’re changing your brain with just one or two joints.

‘Most people would likely assume that one or two joints would have no impact on the brain.’

What changes the increased brain volume directly causes is unclear, but the researchers said it is important to understand cannabis’s effects in detail.

This is especially so in the US, where more states are legalising the drug and a view of it being harmless is spreading, they said.

Professor Garavan said cannabis use appears to produce the opposite effect on brain matter of what usually happens during puberty. 

He said a typical adolescent brain undergoes a ‘pruning’ process in which  it gets thinner, rather than thicker, as it refines its connections. 

‘One possibility is they’ve actually disrupted that pruning process,’ he said. 

Previous studies have focused on heavy marijuana users later in life and compared them against non-users. 

Few have looked at the effects of the first few uses of a drug.

Another of the study’s authors, Catherine Orr, now a lecturer at Swinburne University of Technology in Australia said: ‘Rates of cannabis use among adolescents are high and are increasingly concurrent with changes in the legal status of marijuana and societal attitudes regarding its use.

‘Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of THC on brain structure.’

The study, part of a long-term European project known as IMAGEN, involved 46 teenagers who used recreational marijuana once or twice by the age of 14.

They reported how many joints they had smoked and had brain scans.

It also involved 69 teenagers who used the drug at least 10 times between the ages of 14 and 16, and 69 who had not touched the drug by age 16.

Scientists also assessed them for signs of various mental disorders including ADHD, anxiety, depression and panic disorder.    

Dr Orr said: ‘Of the behavioural variables tested, only sensation seeking and agoraphobia differed between the cannabis users and controls. And these factors were not related to greater grey matter differences.’ 

The researchers said the area of the brain which cannabis interacts with is particularly important for brain development in adolescence, suggesting teenagers could be particularly affected by THC. 

Dr Orr concluded: ‘Almost 35 per cent of American 10th graders have reported using cannabis and existing research suggests that initiation of cannabis use in adolescence is associated with long-term neurocognitive effects.

‘We understand very little about the earliest effects of cannabis use, however, as most research is conducted in adults with a heavy pattern of lifetime use.

‘This study presents evidence suggesting structural brain and cognitive effects of just one or two instances of cannabis use in adolescence.’  

The study was published in The Journal of Neuroscience.

Source: Smoking weed just ONCE could change a teenager’s brain | Daily Mail Online January 2019

Abstract

Background: Normalisation of medicinal and recreational marijuana use has increased the importance of fully understanding effects of marijuana use on individual-and population-level health, including prenatal exposure effects on child development. We undertook a systematic review of the literature to examine the long-term effects of prenatal marijuana exposure on neuropsychological function in children aged 1-11 years.

Methods: Primary research publications were searched from Medline, Embase, PsychInfo, CINAHL EbscoHost, Cochrane Library, Global Health and ERIC (1980-2018). Eligible articles documented neuropsychological outcomes in children 1-11 years who had been prenatally exposed to marijuana. Studies of exposure to multiple prenatal drugs were included if results for marijuana exposure were reported separately from other substances. Data abstraction was independently performed by two reviewers using a standardised protocol.

Results: The eligible articles (n = 21) on data from seven independent longitudinal studies had high quality based on the Newcastle-Ottawa Scale. Some analyses found associations (P < 0.05) between prenatal marijuana exposure and decreased performance on memory, impulse control, problem-solving, quantitative reasoning, verbal development and visual analysis tests; as well as increased performance on attention and global motion perception tests. Limitations included concurrent use of other substances among study participants, potential under-reporting and publication biases, non-generalisable samples and limited published results preventing direct comparison of analyses.

Conclusions: The specific effects of prenatal marijuana exposure remain unclear and warrant further research. The larger number of neuropsychological domains that exhibit decreased versus increased psychological and behavioural functions suggests that exposure to marijuana may be harmful for brain development and function.

Keywords: attention; cannabis; intellect; intrauterine; memory; perception.

Source: Effects of prenatal marijuana exposure on neuropsychological outcomes in children aged 1-11 years: A systematic review – PubMed (nih.gov) November 2018

* Correspondence:

Albert Stuart Reece  

A leading perspectives piece in the New England Journal of Medicine recently observed the salience of assessing drug safety in children and emphasized that effects experienced in childhood can have long lasting impacts as they interfere with maturation and growth of the organism into later life.  Senior researchers from the National Institute of Drug Abuse have frequently drawn attention to the implications of adolescent cannabis exposure.  The effects of gestational exposure are even more far reaching.  These factors are given further urgency by studies showing 25% of Californian teenage mothers in California use cannabis.

Cannabis-related neuroteratology appears to clearly fall on a spectrum of deficits.

With the obvious caveats that many of the longitudinal studies of prenatal cannabis exposure (PCE) have been conducted in very different populations, that it is not easy to control for other sociodemographic factors frequently associated with drug use, and that the concentration of cannabis commonly used in the older studies was much lower, findings which together engender a fair degree of heterogeneity in the published reports, a remarkably consistent thread runs through the PCE literature.  Three major longitudinal studies have followed children exposed prenatally from white middle class Ottawa from the late 1970’s; from predominantly African-American Pittsburgh from 1982; and from the Netherlands from 2001.  Reductions in birth weight of 200-300g, slightly smaller head circumferences (2.8mm), and body length are reported in weekly users with several studies reporting dose-response effects.

In terms of neurobehavioural functioning increased neonatal startle response were seen, with specific cognitive defects in grade school, increased impulsivity, hyperactivity and depression at age 10, poor school achievement, adolescent delinquency, increased violence and aggression amongst girls, increased use of tobacco and cannabis in teens, and in the early 20’s in the longest running study, deficits in short term memory, visuospatial memory and motor impulse control.  These defects have been linked with ADHD and with autism.  Microcephaly was also noted in a large Hawaiian study.  Increased neonatal startle and later cognitive defects are also seen in rodents after PCE.

These findings are clinically significant, and may assume public health significance when one notes that autism is increasing in all USA states where it is measured, paralleling rising rates of cannabis use across the country.

Two reports from C.D.C. indicate an almost doubling of the rate of anencephaly following PCE R.R.=1.9 (95%C.I. 1.1-3.2).  In the context of the foregoing findings this major datum implies that cannabis has the unusual distinction of being a neurotoxin which interferes with brain development to the point of chemically amputating the forebrain.  Hence there is clear evidence of a graded spectrum of deficits following PCE from subtle ASD- and ADHD- like neurobehavioural defects, to smaller heads, to microcephaly and to anencephaly including foetal neurological and neonatal death.

In the context of indicative epidemiology consideration of pathophysiological mechanisms is pertinent to address the Hill principles of causality.

There are numerous compelling mechanisms by which PCE can be related to subsequent teratogenic outcomes.

Importantly the cerebellum, midbrain, diencephalon and forebrain express moderate to high levels of type 1 cannabinoid receptors (CB1R) from early in gestation.

It was recently powerfully demonstrated that opposing gradients of the ligand-receptor guidance pairs slit-Roundabout (robo) and the notch ligand dll control and determine mammalian corticogenesis in diverse organisms including snakes, birds, mice and human organoids by controlling the switch for cortical neurogenesis from directly via radial glia cells to a more indirect and proliferative pathway via intermediate progenitors (Figure 1).   Cannabinoids have been shown to reverse this natural gradient for dll, and acting via a 2AG / CB2R / slit2 / Robo1 / 2AG / CB1R / JNK / ERK pathway to stimulate robo.

Neurexin-neuroligin is a trans-synaptic ligand-receptor pair which directly induces and maintains synapse formation, and has been shown to be inhibited by cannabinoids.

Axon guidance is also controlled by robo-slit and by stathmin-induced tubulin polymerization, which are sensitive to cannabinoids.

White matter disconnection is well documented following adolescent and prenatal cannabis use, and in autism, and oligodendrocytes have CB1R’s and CB2R’s.

Mitochondria possess both CB1R’s and cannabinoid signal transduction machinery and are known to be highly sensitive to cannabinoids and interact with DNA maintenance pathways by several routes.

Cannabinoids have also been shown to alter signaling via the neurotransmitters: glutamate, GABA, opioids, dopamine, serotonin and enkephalin.

Cannabinoids have demonstrated intergenerational epigenetic effects on the medium spiny neurons of the nucleus accumbens and amygdala and also on immune cells which sculpt dendritic networks and prune synapses.

Acting via CB1R, GPR55, and vanilloid type 1 receptors cannabis has been linked with arteritis with likely downstream actions on neurogenic and other stem cell niches.

Endocardial cushions also carry high levels of CB1R’s and the American Academy of Pediatrics has a position statement noting the increased incidence of Ebstein’s syndrome and ventricular septal defect (VSD) after PCE.  Both syncytiotrophoblast and placental arteries carry high concentrations of CB1R’s and abnormalities of uterine blood flow have been documented.

Cannabinoids interfere with tubulin polymerization and mitotic spindle function and thereby act as indirect genotoxins. The implication of cannabis with four inheritable cancers implies malignant teratogenicity and genotoxicity.

Colorado reports dramatic rises of total congenital anomalies, microcephaly, VSD, ASD, Down’s syndrome and chromosomal defects, all of which are relatively straightforward to quantify.

Colorado legislators have also moved to declare a state of crisis related to an autism rate presently growing by 30% 2012-2014.  Similarly in northern California a coincident hotspot of cannabis use, gastroschisis and autism has been reported.  In New Jersey 4.5% of 8 year old boys are autistic.

The above findings comprehend both positive and negative association along with multiple plausible biological pathways linking causality.

As rising rates of community cannabis use augment rising cannabis concentrations and intersect often asymptotic cannabinoid dose-response genotoxicity curves, increased clinical teratogenesis is to be expected.  Of these anomalies the neurobehavioural teratology will likely be the most common, is arguably the most costly and severe, and is also most difficult to quantify.

Are we prepared?

Source:  Paper by Albert Stuart Reese sent to Elinore.Mccance-katz@samhsa.hhs.gov  2018

Source: 2017-Cannabis-Toxic-Trend-Report.pdf (wapc.org) 2017

From a Colorado Springs Gazette Opinion

Last week marked the fifth anniversary of Colorado’s decision to sanction the world’s first anything-goes commercial pot trade.

Five years later, we remain an embarrassing cautionary tale.

Visitors to Colorado remark about a new agricultural smell, the wafting odor of pot as they drive near warehouse grow operations along Denver freeways. Residential neighborhoods throughout Colorado Springs reek of marijuana, as producers fill rental homes with plants.

Five years of retail pot coincide with five years of a homelessness growth rate that ranks among the highest rates in the country. Directors of homeless shelters, and people who live on the streets, tell us homeless substance abusers migrate here for easy access to pot.

Five years of Big Marijuana ushered in a doubling in the number of drivers involved in fatal crashes who tested positive for marijuana, based on research by the pro-legalization Denver Post.

Five years of commercial pot have been five years of more marijuana in schools than teachers and administrators ever feared.

“An investigation by Education News Colorado, Solutions and the I-News Network shows drug violations reported by Colorado’s K-12 schools have increased 45 percent in the past four years, even as the combined number of all other violations has fallen,” explains an expose on escalating pot use in schools by Rocky Mountain PBS in late 2016.

The investigation found an increase in high school drug violations of 71 percent since legalization. School suspensions for drugs increased 45 percent.

The National Survey on Drug Use and Health found Colorado ranks first in the country for marijuana use among teens, scoring well above the national average.

The only good news to celebrate on this anniversary is the dawn of another organization to push back against Big Marijuana’s threat to kids, teens and young adults.

The Marijuana Accountability Coalition formed Nov. 6 in Denver and will establish satellites throughout the state. It resulted from discussions among recovery professionals, parents, physicians and others concerned with the long-term effects of a commercial industry profiteering off of substance abuse.

“It’s one thing to decriminalize marijuana, it’s an entirely different thing to legalize an industry that has commercialized a drug that is devastating our kids and devastating whole communities,” said coalition founder Justin Luke Riley. “Coloradans need to know, other states need to know, that Colorado is suffering from massive normalization and commercialization of this drug which has resulted in Colorado being the number one state for youth drug use in the country. Kids are being expelled at higher rates, and more road deaths tied to pot have resulted since legalization.”

Commercial pot’s five-year anniversary is an odious occasion for those who want safer streets, healthier kids and less suffering associated with substance abuse. Experts say the worst effects of widespread pot use will culminate over decades. If so, we can only imagine the somber nature of Big Marijuana’s 25th birthday.

Source: Five Years Later, Colorado Sees Toll of Pot Legalization (illinoisfamily.org) February 2017

(Reuters Health) – Cannabis use by mothers or fathers during pregnancy, or even only before pregnancy, is associated with an increased risk of psychotic-like episodes in their children, a Dutch study suggests.

Because pot use by mothers and fathers carried similar risk, and a mother’s use before pregnancy had the same effect as use during pregnancy, the study team speculates that parental pot use is likely a marker for genetic and environmental vulnerability to psychotic experiences rather than a cause, and could be useful for screening kids at risk for psychosis later in life.

Babies exposed to cannabis in the womb do have an increased risk of being underweight and unusually small when they’re born and developing cognitive and behavior problems early in life, the researchers note in Schizophrenia Research. Cannabis can also cause hallucinations in adults, particularly with frequent use and at high doses, but less is known about the potential for infants exposed to the drug in the womb to develop psychotic-like symptoms.

For the study, researchers examined data from questionnaires asking 3,692 10-year-olds whether they had symptoms that are similar to what adults might experience with psychosis: hearing voices that nobody else detects, seeing things others don’t see, and having thoughts that others might find strange.

They also examined mothers’ reports on their own marijuana use as well as any use by their partners, and they also looked at lab tests for signs of cannabis in mothers’ urine.

When mothers used marijuana during pregnancy, children were 38 percent more likely to have these psychotic-like symptoms than the children of mothers who abstained from use during pregnancy, the study found. But children of mothers who used pot only before, but not during, pregnancy also had a 39 percent higher risk than the kids of mothers who didn’t use it.

Fathers’ cannabis use during pregnancy, meanwhile, was associated with a 44 percent greater likelihood of psychotic-like experiences in their kids.

“Some children with psychotic experiences are at increased risk to develop psychosis or other psychiatric disorders,” said lead study author Dr. Koen Bolhuis, a researcher at Erasmus Medical Center Rotterdam in the Netherlands.

“Unfortunately very little is known about how to treat psychotic experiences in children, or to prevent them from getting worse,” Bolhuis said by email.

Psychotic-like experiences aren’t disabling or frequent enough to be classified as psychosis, a severe mental health disorder in which patients’ thoughts and emotions are impaired on such a regular basis that they routinely experience delusions and hallucinations that make it impossible to know what’s real and what isn’t.

Psychosis can be caused by schizophrenia, and it can also happen as a result of some other medical conditions and as a side effect of certain prescription medications or illegal drugs.

In the current study, mothers who used cannabis during pregnancy were more likely than other women to smoke and drink during pregnancy, which can both independently influence the risk of emotional and behavioral health problems in children. They were also more likely to have partners who used cannabis while they were pregnant.

The study wasn’t a controlled experiment designed to prove whether or how cannabis exposure might directly cause psychotic experiences in children.

Researchers also lacked data on how much of infants’ cannabis exposure came from parent’s smoking versus ingesting pot.

With inhaled cannabis, it’s difficult to separate the impact of the drug itself from the effect of carbon monoxide also released in the smoke, noted Marcel Bonn-Miller of the University of Pennsylvania Perelman School of Medicine in Philadelphia.

“Carbon monoxide is a known toxicant which causes hypoxia, or oxygen deprivation, which has several well-known and well-studied detrimental effects on pregnancy and offspring development,” Bonn-Miller, who wasn’t involved the study, said by email.

Still, the current study results add to evidence that there’s no safe amount of cannabis exposure for babies in the womb, said Dr. Nathaniel DeNicola of George Washington University in Washington, D.C.

“We have sufficient data and biologic plausibility that marijuana use during pregnancy increases the risk of preterm birth and growth restricted babies,” DeNicola, who wasn’t involved the study, said by email. “The data is mixed on stillbirth, but still cause for concern.”

Source: Pot smoking by parents tied to risk of psychotic episodes in kids | Reuters August 2018

NEARLY 800 babies were born suffering the effects of their mother’s drug addiction in the past three years in Scotland – with experts warning the true toll is likely to be higher.

New figures show 774 babies were recorded as affected by addiction or suffering withdrawal symptoms from drugs between 2014 and 2017.

The drugs pass from mother to foetus through the bloodstream, resulting in babies suffering a range of withdrawal symptoms after birth and developmental delays in childhood.

Consultant neonatologist Dr Helen Mactier, honorary secretary of the British Association of Perinatal Medicine, said there was a “hidden” number of women who took drugs in pregnancy and varying definitions of drug misuse in pregnancy which meant figures were likely to be an underestimate.

She said: “The problem largely in Scotland is opioid withdrawal – heroin and methadone.

“The baby withdraws from these substances and they are very irritable, cross, unhappy children who can be quite difficult to feed until they finally get over the withdrawal.”

Dr Mactier said at birth the babies were usually small, and had small heads and visual problems. She added there is evidence they suffer developmental delays in early childhood.

The figures, revealed in a written parliamentary answer, show an increase of 80% in cases from the three-year period from 2006-9, when 427 babies were born with the condition.

However, it said the data over time should be treated with caution as there has been an improvement in recording drug misuse.

The highest numbers over the past three years were recorded in Grampian, which had 169 cases. Glasgow had 137 cases, while Tayside recorded 90, Lanarkshire 78 and Lothian 72.

Numbers have been dropping since 2011-14, when a peak of 1,073 cases were recorded.

Dr Mactier, who works at Glasgow’s Princess Royal Maternity Hospital, said having to treat babies born addicted to drugs was becoming less common in recent years.

She said: “The numbers are coming down, but we are not sure why. It is partly because women who use drugs intravenously tend to be older, so are becoming too old to have children.”

However, she pointed out one controversial area was stabilising pregnant addicts on heroin substitutes such as methadone.

She added: “That may be good for the mum, to keep her more stable and out of criminality. It is not entirely clear if that is safe for the babies, so we need more research.”

Scottish Conservative health spokesman Miles Briggs, who obtained the figures, said: “It’s a national tragedy that we see such numbers of babies being born requiring drug dependency support – we need to see action to help prevent this harm occurring.”

Martin Crewe, director of Barnardo’s Scotland, said: “We know how important it is for children to get a good start in life. We would like to see no babies born requiring drug dependency support.”

Source: https://www.sundaypost.com/fp/hundreds-of-babies-suffering-because-of-mums-drug-addiction October 2018

The fact that 1 in 6 infants and toddlers admitted to a Colorado hospital with symptoms of bronchiolitis tested positive for marijuana exposure should concern Canadians as they move to legalization on 17 October. The dangers of 2nd-hand, carcinogenic and psychoactive chemically-laden marijuana smoke were ignored by the Trudeau government in its push to legalize pot, Pamela McColl writes.

PAMELA McCOLL’S STATEMENT IN FULL…

What About Us? October 17 2018

No amount of second-hand smoke is safe. Children exposed to second-hand smoke are more likely to develop lung diseases and other health problems.  Second hand-smoke is a cause of sudden infant death syndrome (SIDS). The fact that one in six infants and toddlers admitted to a Colorado hospital with symptoms of bronchiolitis tested positive for marijuana exposure should be of grave to Canadians as they too have moved to legalization.

The dangers of second-hand, carcinogenic and psychoactive chemically-laden marijuana smoke were ignored by the Trudeau government in their push to legalize pot. This government in fact sanctioned the smoking of marijuana in the presence of children.

The government did not commission an in-depth child risk assessment of the draft legalization framework, a study called for by child advocates across the country.

The Alberta Ministry of Children’s Services’ – Child, Youth and Family Enhancement Act Placement Resource Policy on Environmental Safety states; that a foster parent must be aware of, and committed to provide a non-smoking environment by not allowing smoking in the home when a foster child is placed; not allowing smoking in a vehicle when a foster child is present; and not allowing use of smokeless tobacco when a foster child is present. As the Alberta government’s policy contains all-inclusive language of “non-smoking environment,” the same rules have been extend to legalized marijuana. Some children in the province of Alberta have been protected under policy while the majority of Albertan children and other children in Canada should rightly ask: “What About Us?”

The Canadian Charter of Rights and Freedoms secures the safety of children from threats to their health and their life. Section 15 of the Charter prohibits discrimination perpetrated by the governments of Canada. The Equality Rights section states that every individual is equal before and under the law and has the right to the equal protection and equal benefit of the law without discrimination. The provisions that protect children in foster care should extend to every child.

Section 7 of the Charter is a constitutional provision that protects an individual’s personal legal rights from actions of the government of Canada, the right to life, liberty and security of the person. The Cannabis Act fails to protect Canadian children’s right to security of the self. The right to security of the person consists of the rights to privacy of the body and its health and of the right protecting the “psychological integrity” of an individual.  Exposure to marijuana in poorly ventilated spaces exposes the non-user to the impact of a psychotropic high, including the distortion of one’s sense of reality.

Canada is a party to the Rights of the Child Treaty, the most widely ratified piece of human rights law in history.  The treaty establishes the human rights of children to health and to protection under law. Placing marijuana products and plants into children’s homes fails to protect their rights under international treaty obligations.

A petition, before the BC Government Legislative Assembly via the Minister of Municipal Affairs and Housing, seeks to make all multi-unit dwellings in BC smoke-free. Smoke-free housing is needed to protect the non-user’s health. Smoke travels, it escapes and contaminates beyond a single unit. Law consists, primarily, in preserving a person from death and violence and in securing their free enjoyment of their property. The Cannabis Act fails to preserve the rights of non-users of marijuana. It rests with citizens to stand up for their rights and those of children. Be prepared this will be an ugly, costly and lengthy process.

“We think that the true rule of law is, that the person who for his own purposes brings on his land and collects and keeps there anything likely to do mischief if it escapes, must keep it at his peril, and, if he does not do so, is prima facia answerable for all the damage which is the natural consequence of its escape. “ House of Lords Rule. Doctrine of Strict Liability of Dangerous Conditions Rylands versus Fletcher – 1868. Successful argued in Delta, Canada 1983. Individual prevented from smoking in his residence.

Provincial governments can correct the mistakes made by the federal government. Concerned citizens must see that they do.

Pamela McColl – www.cleartheairnow.org

Source: What about the children? | DB Recovery Resources October 2018

Abstract

Objectives To estimate the prevalence of fetal alcohol spectrum disorder (FASD) among young people in youth detention in Australia. Neurodevelopmental impairments due to FASD can predispose young people to engagement with the law. Canadian studies identified FASD in 11%–23% of young people in corrective services, but there are no data for Australia.

Design Multidisciplinary assessment of all young people aged 10–17 years 11 months and sentenced to detention in the only youth detention centre in Western Australia, from May 2015 to December 2016. FASD was diagnosed according to the Australian Guide to the Diagnosis of FASD.

Participants 99 young people completed a full assessment (88% of those consented; 60% of the 166 approached to participate); 93% were male and 74% were Aboriginal.

Findings 88 young people (89%) had at least one domain of severe neurodevelopmental impairment, and 36 were diagnosed with FASD, a prevalence of 36% (95% CI 27% to 46%).

Conclusions This study, in a representative sample of young people in detention in Western Australia, has documented a high prevalence of FASD and severe neurodevelopmental impairment, the majority of which had not been previously identified. These findings highlight the vulnerability of young people, particularly Aboriginal youth, within the justice system and their significant need for improved diagnosis to identify their strengths and difficulties, and to guide and improve their rehabilitation.

Source: https://bmjopen.bmj.com/content/8/2/e019605 February 2018

SCIENTISTS have captured graphic ultrasound images of the damage done to unborn babies as a result of women drinking during pregnancy. Just one glass of wine a week can make babies “jump” in the womb throughout a nine-month pregnancy. Experts believe this abnormal hyperactive behavior is the result of alcohol slowing or retarding the formation of the central nervous system. Doctors have warned for decades that women who consume large amounts of alcohol during pregnancy can affect their child’s mental development.

However, the new research suggests even moderate alcohol consumption makes a baby 3½ times more likely to suffer from abnormal spasms in the womb. The findings, by Peter Hepper, a professor at Belfast University’s fetal behavior research unit, appear to back the view that there is no safe level of alcohol consumption during pregnancy. Hepper’s findings have surprised child neurology experts. Between conception and 18 weeks, babies display a primitive “startle reflex” which causes babies to jump involuntarily in the womb at loud noises and other stimuli. However, once the nervous system is fully formed at 18 weeks, the reflex disappears in healthy babies and is replaced by a calmer “adult” reflex. Hepper found that the babies of mothers who drank — whether one unit a week or four — all continued to display a “startle reflex” throughout their pregnancy. The reflex in the babies of the non-drinking mothers tailed off at 18 weeks.

The professor also found that the babies of women who drank suffered more “startles” during the first 18 weeks. Hepper, who published his findings in the Journal of Physiology and Behaviour, concluded that even moderate consumption of alcohol had a serious effect on the formation of a baby’s central nervous system. He explained: “This indicates that the nerve pathways in the brain have been damaged.” Hepper concluded: “Our study shows that alcohol is having an effect on the baby even at low levels and that is quite disturbing. We don’t think there is a safe limit for alcohol consumption in pregnancy.” Hepper’s study appears to corroborate US research, conducted after birth, which has shown that drinking during pregnancy lowers a child’s IQ and increases hyperactivity. Some doctors believe the babies scanned by Hepper are showing the early signs of fetal alcohol syndrome (FAS) which is thought to cause a range of behavioral and neurological disorders in children.

The Fetal Alcohol Syndrome Trust estimates that between 6,000 to 12,000 babies are affected in the UK each year. Margaret Burrows, a clinical geneticist at Leicester royal infirmary, said: “The startle movement (in the womb) is clearly not normal and would seem to indicate the child has the traits of fidgeting which we see in attention deficit hyperactive disorder (ADHD). “We believe that a proportion of children who have ADHD may have developed it as a result of their mother’s drinking during pregnancy.” The next stage of Hepper’s study will monitor whether the babies go on to suffer mental and behavioral problems. Hepper presented the findings of his study of 40 pregnant women from the Royal Maternity hospital, Belfast, to the Royal Society of Medicine on Wednesday. None of the mothers was asked to drink but 20 admitted that they would continue to drink during their pregnancy. The other 20 drank no alcohol. Researchers questioned the 20 pregnant drinkers and found they consumed between one and four units of alcohol (four glasses of wine) a week. In the first half of the study all the women underwent three ultrasound scans during the first 18 weeks of their pregnancy. In the second half, the women had four more scans at 20, 25, 30 and 35 weeks. The scans lasted up to 45 minutes to try to capture hyperactivity.

Fetal Alcohol Spectrum Disorders (FASD), Fetal Alcohol Syndrome (FAS), Fetal Alcohol Effects (FAE), Partial Fetal Alcohol Syndrome (pFAS), Alcohol Related Neurodevelopmental Disorders (ARND), Static Encephalopathy Alcohol Exposed (SEAE) and Alcohol Related Birth Defects (ARBD) are all names for a spectrum of disorders caused when a pregnant woman consumes alcohol. FASD is 100% preventable. If you are pregnant or plan to become pregnant, don’t drink any beverage alcohol. There is no known safe level. To ignore the facts does not change the facts.

Source: Ultrasound Fetal Response To Alcohol Fetal Alcohol Syndrome – YouTube May 2008

(Denver, CO) – A new state-funded report out of Colorado found that the state continues to hold the top ranking when it comes to past month use of marijuana, more young children are being exposed to highly potent pot products, use of edibles and vaping/dabbing is way up among high school students, and emergency department visits have increased. 

“The data in this report show that Colorado’s marijuana industry is threatening public health,” said Luke Niforatos Senior Policy Advisor to Smart Approaches to Marijuana (SAM) and longtime Colorado resident. “Just last year, the industry was caught recommending pot to pregnant mothers. It’s time to start holding them accountable.”

According to the report, past month use has increased 14% over the last year and adult use in the state of Colorado continues to be significantly higher than the national average. Young adults, aged 18-25 reported the greatest instance of past month use at 29.2%. This is concerning as this age group is still in a crucial period of brain development and heavy use at this age can lead to the development of serious mental health issues. 

Adult Past Month Marijuana Use 

The report notes that “at least 23,009 homes with children in Colorado may not be storing marijuana products safely, which increases the risk of accidental ingestion.” On this front, the report also finds that calls to the poison center for marijuana exposure to young children remains high after it began skyrocketing following legalization. Prior to legalization, there was an average of 5 calls per year related to marijuana exposure in children under the age of nine. After legalization, this number shot up to 27 in 2013, 45 in 2014, 40 in 2016, and now 50 in 2017. Ingestion of marijuana edibles comprised 65% of these reports. Additionally, the report finds that approximately 32,800 homes with children 1-14 years old had possible secondhand marijuana smoke or vapor exposures.

Number of Children Exposed to Marijuana

Of note, this report still fails to accurately depict the real data when it comes to youth use in Colorado. The findings on rates of youth use are based on data collected by the Healthy Kids Colorado Survey which suffers from multiple methodological issues. That fact notwithstanding, according to the flawed HKCS data, past month edible use is up significantly among high school students, rising 22% since 2015. Additionally, the “dabbing” of high potency THC concentrates has increased 43% since 2015 among high schoolers.

“As a Colorado physician, I am incredibly concerned with the findings of this report,” said Dr. Ken Finn, a pain doctor in Colorado Springs. “The harms to public health that are documented here are alarming, especially the rising risk of exposure of pot products to young children whose brains are still in development. Additionally, I find this report to be sorely lacking key data points, such as the fact that marijuana is the most prevalent substance found in Colorado completed teen suicide. The state needs to get serious with the documentation of the real consequences of marijuana legalization.”

“Is this the type of outcome people wanted when they voted to legalize? Tens of thousands of young people in Colorado are now living in homes where they are either actively breathing in marijuana smoke or are at risk of eating highly potent THC gummies, candies, brownies, and ice creams,” said Niforatos. “As public health and safety professionals, we will continue to hold the state accountable for this reckless policy of marijuana commercialization.”

Source:  learnaboutSam.org  Feb.2019

Abstract

Background

Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain.

Methods and findings

This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3–54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34–0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration.

Conclusions

We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

Author summary

Why was this study done?

  • High numbers of people who use (illicit) drugs (PWUD) experience chronic pain, and previous research shows that illicit use of opioids (e.g., heroin use, non-prescribed use of painkillers) is a common pain management strategy in this population.
  • Previous research has suggested that some patients might substitute opioids (i.e., prescription painkillers) with cannabis (i.e., marijuana) to treat pain.
  • Research into cannabis as a potential substitute for illicit opioids among PWUD is needed given the high risk of opioid overdose in this population.
  • We conducted this study to understand if cannabis use is related to illicit opioid use among PWUD who report living with chronic pain in Vancouver, Canada, where cannabis is abundant and the rate of opioid overdose is at an all-time high.

What did the researchers do and find?

  • Using data from 2 large studies of PWUD in Vancouver, Canada, we analyzed information from 1,152 PWUD who were interviewed at least once and reported chronic pain at some point between June 2014 and December 2017.
  • We used statistical modelling to estimate the odds of daily opioid use for (1) daily and (2) occasional users of cannabis relative to non-users of cannabis, holding other factors (e.g., sex, race, age, use of other drugs, pain severity) equal.
  • For participants who reported cannabis use, we also analyzed their responses to a question about why they were using cannabis (e.g., for intoxication, for pain relief)
  • We found that people who used cannabis every day had about 50% lower odds of using illicit opioids every day compared to cannabis non-users. People who reported occasional use of cannabis were not more or less likely than non-users to use illicit opioids on a daily basis. Daily cannabis users were more likely than occasional cannabis users to report a number of therapeutic uses of cannabis including for pain, nausea, and sleep.

What do these findings mean?

  • Although more experimental research (e.g., randomized controlled trial of cannabis coupled with low-dose opioids to treat chronic pain among PWUD) is needed, these findings suggest that some PWUD with pain might be using cannabis as a strategy to alleviate pain and/or reduce opioid use.

Introduction

Opioid-related morbidity and mortality continue to rise across Canada and the United States. In many regions, including Vancouver, Canada—where drug overdoses were declared a public health emergency in 2016—the emergence of synthetic opioids (e.g., fentanyl) in illicit drug markets has sparked an unprecedented surge in death. The overdose crisis is also the culmination of shifting opioid usage trends (i.e., from initiating opioids via heroin to initiating with pharmaceutical opioids) that can be traced back, in part, to the over-prescription of pharmaceutical opioids for chronic non-cancer pain.

Despite this trend of liberal opioid prescribing, certain marginalized populations experiencing high rates of pain, including people who use drugs (PWUD), lack access to adequate pain management through the healthcare system. Under- or untreated pain in this population can promote higher-risk substance use, as patients may seek illicit opioids (i.e., unregulated heroin or counterfeit/diverted pharmaceutical opioids) to manage pain. In Vancouver, this practice poses a particularly high risk of accidental overdose, as estimates show that almost 90% of drugs sold as heroin are contaminated with synthetic opioids, such as fentanyl. Another less-examined pain self-management strategy among PWUD is the use of cannabis. Unlike illicit opioids and illicit stimulants, the cannabis supply (unregulated or regulated) has not been contaminated with fentanyl, and cannabis is not known to pose a direct risk of fatal overdose. As a result, cannabis has been embraced by some, including emerging community-based harm reduction initiatives in Vancouver, as a possible substitute for opioids in the non-medical management of pain and opioid withdrawal. Further, clinical evidence supports the use of cannabis or cannabinoid-based medications for the treatment of certain types of chronic non-cancer pain (e.g., neuropathic pain).

As more jurisdictions across North America introduce legal frameworks for medical or non-medical cannabis use, ecological studies have provided evidence to suggest that states providing access to legal cannabis experience population-level reductions in opioid use, opioid dependence, and fatal overdose. However, these state-level trends do not necessarily represent changes within individuals, highlighting a critical need to conduct individual-level research to better understand whether cannabis use is associated with reduced use of opioids and risk of opioid-related harms, particularly among individuals with pain. Of particular interest is a possible opioid-sparing effect of cannabis, whereby a smaller dose of opioids provides equivalent analgesia to a larger dose when paired with cannabis. Although this effect has been identified in pre-clinical studies, much of the current research in humans is limited to patient reports of reductions in the use of prescription drugs (including opioids) as a result of cannabis use. However, a recent study among patients on long-term prescription opioid therapy produced evidence to counter the narrative that cannabis use leads to meaningful reductions in opioid prescriptions or dose. These divergent findings confirm an ongoing need to understand this complex issue. To date, there is a lack of research from real-world settings exploring the opioid-sparing potential of cannabis among high-risk individuals who may be engaging in frequent illicit opioid use to manage pain. We therefore sought to examine whether frequency of cannabis use was related to frequency of illicit opioid use among PWUD who report living with chronic pain in Vancouver, Canada, the setting of an ongoing opioid overdose crisis.

Methods

Study sample

Data for this study were derived from 2 ongoing open prospective cohort studies of PWUD in Vancouver, Canada. The Vancouver Injection Drug Users Study (VIDUS) consists of HIV-negative people who use injection drugs. The AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS) consists of people living with HIV who use drugs. The current study, nested within these cohorts, was designed as part of a larger doctoral research project (SL) examining cannabis use and access among PWUD in the context of changing cannabis policy and the ongoing opioid overdose crisis. The analysis plan for this study is provided in S1 Text. This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies (S1 Checklist).

Recruitment for the cohort studies has been ongoing since 1996 (VIDUS) and 2005 (ACCESS) through extensive street outreach in various areas across Vancouver’s downtown core, including the Downtown Eastside (DTES), a low-income neighbourhood with an open illicit drug market and widespread marginalization and criminalization. To be eligible for VIDUS, participants must report injecting drugs in the previous 30 days at enrolment. To be eligible for ACCESS, participants must report using an illicit drug (other than or in addition to cannabis, which was a controlled substance under Canadian law until October 17, 2018) in the previous 30 days at enrolment. For both cohorts, HIV serostatus is confirmed through serology. Other eligibility requirements include being aged 18 years or older, residing in the Metro Vancouver Regional District, and providing written informed consent. Aside from HIV-disease-specific assessments, all study instruments and follow-up procedures are harmonized between the 2 studies to facilitate combined data analysis and interpretation.

At study enrolment, participants complete an interviewer-administered baseline questionnaire. Every 6 months thereafter, participants are eligible to complete a follow-up questionnaire. The questionnaires elicit information on socio-demographic characteristics, lifetime (baseline) and past-6-month (baseline, follow-up) patterns of substance use, risk behaviours, healthcare utilization, social and structural exposures, and other health-related factors. Nurses collect blood samples for HIV testing (VIDUS) or HIV clinical monitoring (ACCESS) and hepatitis C virus serology, providing referrals to appropriate healthcare services as needed. Participants are provided a Can$40 honorarium for their participation at each study visit.

Ethics statement

Ethics approval for this study was granted by the University of British Columbia/Providence Health Care Research Ethics Board (VIDUS: H14-01396; ACCESS: H05-50233). Written informed consent was obtained from all study participants.

Measures

To examine the use of illicit opioids and cannabis for possible ad hoc management of pain among PWUD, we restricted the study sample to individuals experiencing major or persistent pain. Beginning in follow-up period 17 (i.e., June 2014), the following question was added to the study questionnaire: “In the last 6 months, have you had any major or persistent pain (other than minor headaches, sprains, etc.)?” We included all observations from participants beginning at the first follow-up interview in which they reported chronic pain. For example, a participant who responded “no” to the pain question at follow-up 17 and “yes” at follow-up 18 would be included beginning at follow-up 18. For the purpose of these analyses, this first follow-up period with a pain report is considered the “baseline” interview.

The outcome of interest was frequent use of illicit opioids, defined as reporting daily (once or more per day) non-medical use of heroin or pharmaceutical opioids (diverted, counterfeit, or not-as-prescribed use) by injection or non-injection (i.e., smoking, snorting, or oral administration) in the previous 6 months. This outcome was captured through 4 different multipart questions based on class of opioid (i.e., heroin and pharmaceutical opioids) and mode of administration (i.e., injection and non-injection). For example, at each 6-month period, injection heroin use was assessed through the question: “In the last 6 months, when you were using, which of the following injecting drugs did you use, and how often did you use them?” Respondents were provided a list of commonly injected drugs, including heroin, and were asked to estimate their average frequency of injection in the past 6 months according to the following classifications: <1/month, 1–3/month, 1/week, 2–3/week, ≥1/day. An identical question for non-injection drugs assessed the frequency of non-injection heroin use. Pharmaceutical opioid injection was assessed through the question “In the past 6 months, have you injected any of the following prescription opioids? If so, how often did you inject them?” Participants were provided a list of pharmaceutical opioids with corresponding pictures for ease of identification. The question was repeated for non-injection use of pharmaceutical opioids, and the frequency categories were identical to those listed above. Using frequency categorizations from these 4 questions, participants who endorsed past-6-month daily injection or non-injection of heroin or pharmaceutical opioids were coded as “1” for the outcome (i.e., daily illicit opioid use) for that follow-up period. The main independent variable was cannabis use, captured through the question “In the last 6 months, have you used marijuana (either medical or non-medical) for any reason (e.g., to treat a medical condition or for a non-medical reason, like getting high)?” Those who responded “yes” were also asked to estimate their average past-6-month frequency of use according to the frequency categories described above. Frequency was further categorized as “daily” (i.e., ≥1/day), “occasional” (i.e., <1/month, 1–3/month, 1/week, 2–3/week), and “none” (no cannabis use; reference category). Sections of the questionnaire used for sample restriction and main variable building are provided in S2 Text.

We also considered several socio-demographic, substance use, and health-related factors with the potential to confound the association between cannabis use and illicit opioid use. Secondary socio-demographic variables included in this analysis were sex (male versus female), race (white versus other), age (in years), employment (yes versus no), incarceration (yes versus no), homelessness (yes versus no), and residence in the DTES neighbourhood (yes versus no). We considered the following substance use patterns: daily crack or cocaine use (yes versus no), daily methamphetamine use (yes versus no), and daily alcohol consumption (yes versus no). Health-related factors that were hypothesized to bias the association between cannabis and opioid use were enrolment in opioid agonist treatment (i.e., methadone or buprenorphine/naloxone; yes versus no), HIV serostatus (HIV-positive versus HIV-negative), prescription for pain (including prescription opioids; yes versus no), and average past-week pain level (mild–moderate, severe, or none). The pain variable was self-reported using a pain scale ranging from 0 (no pain) to 10 (worse possible pain). We used 3 as the cut-point for mild–moderate pain and 7 as the cut-point for moderate–severe pain. Although there is no universal standard for pain categorization, these cut-points are common and have been validated in other pain populations. Due to low cell count for mild pain (scores 1–3), we collapsed this variable with moderate pain (4–6) to create the mild–moderate category. With the exception of sex and race, all variables are time-updated and refer to behaviours and exposures in the 6-month period preceding the interview. All variables except HIV status were derived through self-report. As data for the present study were derived from 2 large cohort studies with broader objectives of monitoring changing health and substance use patterns in the community, the study participants and interviewers were blinded to the objective of this particular study.

Statistical analysis

We explored differences in characteristics at baseline according to daily cannabis use status (versus occasional/none) using chi-squared tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. Then, we estimated bivariable associations between each independent variable and the outcome, daily illicit opioid use, using generalized linear mixed-effects models (GLMMs) with a logit-link function to account for repeated measures within individuals over time. Next, we built a multivariable GLMM to estimate the adjusted association between frequency of cannabis use and illicit opioid use. We used the least absolute shrinkage and selection operator (LASSO) approach to determine which variables to include in the multivariable model. This method uses a tuning parameter to penalize the model based on the absolute value of the magnitude of coefficients (i.e., L1 regularization), shrinking some coefficients down to 0 (i.e., indicating their removal from the multivariable GLMM). Four-fold cross-validation was used to determine the optimal value of the tuning parameter. GLMMs were estimated using complete cases (98.6%–100% of observations for bivariable estimates; 99.0% of observations for multivariable estimates).

In the most recent follow-up period (June 1, 2017, to December 1, 2017), participants who reported any cannabis use in the previous 6-month period were eligible for the follow-up question: “Why did you use it?” Respondents could select multiple options from a list of answers or offer an alternative reason under “Other”. These data were analyzed descriptively, and differences between at least daily and less than daily cannabis users were analyzed using a chi-squared test, or Fisher’s test for small cell counts.

All analyses were performed in RStudio (version 1.1.456; R Foundation for Statistical Computing, Vienna, Austria). All p-values are 2-sided.

Results

Between June 1, 2014, and December 1, 2017, 1,489 participants completed at least 1 study visit and were considered potentially eligible for these analyses. Of them, 13 participants were removed due to missing data on the fixed variable for race (n = 9), no response to the pain question (n = 1), or multiple interviews during a single follow-up period (n = 3). Of the remaining 1,476 participants, 1,152 (78.0%) reported major or persistent pain during at least one 6-month follow-up period and were included in this analysis. We considered all observations from these individuals beginning from the first report of chronic pain, yielding 5,350 study observations, equal to 2,676.5 person-years of observation. There were 424 (36.8%) female participants in the analytic sample, and the median age at the earliest analytic interview was 49.3 years (IQR 42.3–54.9).

Over the study period, a total of 410 (35.6%) respondents reported daily and 557 (48.4%) reported occasional cannabis use throughout at least 1 of the 6-month follow-up periods; 455 (39.5%) reported daily illicit opioid use throughout at least 1 of the 6-month follow-up periods. At baseline (i.e., the first interview in which chronic pain was reported), 583 (50.6%) participants were using cannabis either occasionally (n = 322; 28.0%) or daily (n = 261; 22.7%), and 269 (23.4%) were using illicit opioids daily. At baseline, 693 (60.2%) participants self-reported a lifetime chronic pain diagnosis including bone, mechanical, or compressive pain (n = 347; 50.1%); inflammatory pain (n = 338; 48.8%); neuropathic pain (n = 129; 18.6%); muscle pain (n = 54; 7.8%); headaches/migraines (n = 41; 5.9%); and other pain (n = 53; 7.6%).

Table 1 provides a summary of baseline characteristics of the sample stratified by daily cannabis use status (yes versus no). Daily cannabis use at baseline was significantly more common among men (odds ratio [OR] 1.76, 95% 95% CI 1.30–2.38, p < 0.001) and significantly less common among those who used illicit opioids daily (OR 0.54, 95% CI 0.37–0.77, p < 0.001).

Discussion

In this longitudinal study examining patterns of past-6-month frequency of cannabis and illicit opioid use, we found that the odds of daily illicit opioid use were lower (by about half) among those who reported daily cannabis use compared to those who reported no cannabis use. However, we observed no significant association between occasional cannabis use and daily opioid use, suggesting that there may be an intentional therapeutic element associated with frequent cannabis use. This is supported by cross-sectional data from the sample in which certain reasons for cannabis use were observed to differ according to cannabis use frequency. Specifically, daily users reported more therapeutic motivations for cannabis use (including to address pain, stress, nausea, mental health, or symptoms of HIV or antiretroviral therapy, or to improve sleep) than occasional users, and non-medical motivations—although common among all users—were not more likely to be reported by daily users. Together, our findings suggest that PWUD experiencing pain might be using cannabis as an ad hoc (i.e., improvised, self-directed) strategy to reduce the frequency of opioid use.

A recent study analyzed longitudinal data from a large US national health survey and found that cannabis use increases, rather than decreases, the risk of future non-medical prescription opioid use in the general population, providing important evidence to challenge the hypothesis that increasing access to cannabis facilitates reductions in opioid use. The findings of our study reveal a contrasting relationship between cannabis use and frequency of opioid use, possibly due to inherent differences in the sampled populations and their motivations for using cannabis. Within the current study population, poly-substance use is the norm; HIV and related comorbidities are common; and pain management through prescribed opioids is often denied, increasing the likelihood of non-medical opioid use for a medical condition. Furthermore, our study is largely focused on this relationship in the context of pain (i.e., by examining individuals with self-reported pain and accounting for intensity of pain). Our findings align more closely with those of a recent study conducted among HIV-positive patients living with chronic pain, in which the authors found that patients who reported past-month cannabis use were significantly less likely to be taking prescribed opioids. While this finding could have resulted from prescription denial associated with the use of cannabis (or any illicit drug), we show that daily cannabis users in this setting were slightly more likely to have been prescribed a pain medication at baseline, and adjusting for this factor in a longitudinal multivariable model did not negate the significant negative association of frequent cannabis use with frequent illicit opioid use.

The idea of cannabis as an adjunct to, or substitute for, opioids in the management of chronic pain has recently earned more serious consideration among some clinicians and scientists. A growing number of studies involving patients who use cannabis to manage pain demonstrate reductions in the use of prescription analgesics alongside favourable pain management outcomes. For example, Boehnke et al. found that chronic pain patients reported a 64% mean reduction in the use of prescription opioids after initiating cannabis, alongside a 45% mean increase in self-reported quality of life. Degenhardt et al. found that, in a cohort of Australian patients on prescribed opioids for chronic pain, those using cannabis for pain relief (6% of patients at baseline) reported better analgesia from adjunctive cannabis use (70% average pain reduction) than opioid use alone (50% average reduction). However, more recent high-quality research has presented findings to question this narrative. For example, in the 4-year follow-up analysis of the above Australian cohort of pain patients, no significant temporal associations were observed between cannabis use (occasional or frequent) and a number of outcomes including prescribed opioid dose, pain severity, opioid discontinuation, and pain interference. Thus, several other explanations for our current results, aside from an opioid-sparing effect, are worthy of consideration.

We chose to include individuals with chronic pain regardless of their opioid use status to avoid exclusion of individuals who may have already ceased illicit opioid use at baseline, as these individuals may reflect an important subsample of those already engaged in cannabis substitution. On the other hand, there may be important characteristics, unrelated to pain, among regular cannabis users in this study that predispose them to engage in less frequent or no illicit opioid use at the outset. We attempted to measure and control for these factors, but we cannot rule out the possibility of a spurious connection. For example, individuals in this cohort who are consuming cannabis daily for therapeutic purposes may simply possess greater self-efficacy to manage health problems and control their opioid use. However, it is notable that our finding is in line with a previous study demonstrating that cannabis use correlates with lower frequency of illicit opioid use among a sample of people who inject drugs in California, all of whom used illicit opioids. Our study builds on this work by addressing chronic pain, obtaining detailed information on motivations for cannabis use, and examining longitudinal patterns.

We observed that daily cannabis users endorsed intentional use of cannabis for a range of therapeutic purposes that may influence pain and pain interference. After pain, insomnia (43%) and stress (42%) were the second and third most commonly reported motivations for therapeutic cannabis use among daily cannabis users. The inability to fall asleep and the inability stay asleep are common symptoms of pain-causing conditions, and experiencing these symptoms increases the likelihood of opioid misuse among chronic pain patients. The relationship between sleep deprivation and pain is thought to be bidirectional, suggesting that improved sleep management may improve pain outcomes. Similarly, psychological stress (particularly in developmental years) is a well-established predictor of chronic pain and is also likely to result from chronic pain. Thus, another possible explanation for our finding is that cannabis use substitutes for certain higher-risk substance use practices in addressing these pain-associated issues without necessarily addressing the pain itself.

Notably, our findings are consistent with emerging knowledge of the form and function of the human endocannabinoid and opioid receptor systems. The endogenous cannabinoid system, consisting of receptors (cannabinoid type 1 [CB1] and type 2 [CB2]) and modulators (the endocannabinoids anandamide and 2-arachidonoylglycerol), is involved in key pain processing pathways. The co-localization of endocannabinoid and μ-opioid receptors in brain and spinal regions involved in antinociception, and the modification of one system’s nociceptive response via modulation of the other, has raised the possibility that the phytocannabinoid tetrahydrocannabinol (THC) might interact synergistically with opioids to improve pain management. A recent systematic review and meta-analysis found strong evidence of an opioid-sparing effect for cannabis in animal pain models, but little evidence from 9 studies in humans. However, the authors of the meta-analysis identified several important limitations potentially preventing these studies in humans from detecting an effect, including low sample sizes, single doses, sub-therapeutic opioid doses, and lack of placebo. Since then, Cooper and colleagues have published the results of a double-blind, placebo-controlled, within-subject study among humans in which they found that pain threshold and tolerance were improved significantly when a non-analgesic dose of an opioid was co-administered with a non-analgesic dose of cannabis. Suggestive of a synergistic effect, these findings provide evidence for cannabis’s potential to lower the opioid dose needed to achieve pain relief.

Finally, there is pre-clinical and pilot clinical research to suggest that cannabinoids, particularly cannabidiol (CBD), may play a role in reducing heroin cue-induced anxiety and cravings and symptoms of withdrawal. Although preliminary, this research supports the idea that cannabis may also be used to stabilize individuals undergoing opioid withdrawal, as an adjunct to prescribed opioids to manage opioid use disorder, or as a harm reduction strategy. Although this evidence extends beyond chronic pain patients, it warrants consideration here given the shared history of illicit substance use amongst the study sample. It is not clear what role harm reduction or treatment motivations may have played in the current study since daily and occasional users did not differ significantly in reporting cannabis use as a strategy to reduce or treat other substance use. The phenomenon of using cannabis as a tool to reduce frequency of opioid injection has been highlighted through qualitative work in other settings, but further research is needed to determine whether this pattern is widespread enough to produce an observable effect. Clinical trials that can randomize participants to a cannabis intervention will be critical for establishing the effectiveness of cannabis both for pain management and as an adjunctive therapy for the management of opioid use disorder. Such trials would begin to shed light on whether the current finding could be causal, what the underlying mechanisms might be, and how to optimize cannabis-based interventions in clinical or community settings.

There are several important limitations to this study that should be taken into consideration. First, the cohorts are not random samples of PWUD, limiting the ability to generalize these findings to the entire community or to other settings. The older median age of the sample should especially be taken into consideration when interpreting these findings against those from other settings. Second, as discussed above, we cannot rule out the possibility of residual confounding. Third, aside from HIV serostatus, we relied on self-report for all variables, including substance use patterns. Previous work shows PWUD self-report to be reliable and valid against biochemical verification, and we have no reason to suspect that responses about the outcome would differ by cannabis use status, especially since this study was nested within a much larger cohort study on general substance use and health patterns within the community. Major or persistent pain, which qualified respondents for inclusion in this study, was also self-reported. Our definition for chronic pain is likely to be more sensitive than other assessments of chronic pain (e.g., clinical diagnoses or assessments that capture length of time with pain). Although more than half (60%) of the sample reported ever having been diagnosed with a pain condition, it is possible that some of the included respondents would not have met criteria for a formal chronic pain diagnosis. Finally, we did not collect information on the type of cannabis, mode of administration, cannabinoid content (e.g., percent THC:percent CBD), or dose during the study period. Future research will need to address these gaps to provide a more detailed picture of the instrumental use of cannabis for pain and other health concerns among PWUD.

Conclusions

In conclusion, we found evidence to suggest that frequent use of cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain in Vancouver. The findings of this study have implications for healthcare and harm reduction service providers. In chronic pain patients with complex socio-structural and substance use backgrounds, cannabis may be used as a means of treating health problems or reducing substance-related harm. In the context of the current opioid crisis and the recent rollout of a national regulatory framework for cannabis use in Canada, frequent use of cannabis among PWUD with pain may play an important role in preventing or substituting frequent illicit opioid use. PWUD describe a wide range of motivations for cannabis use, some of which may have stronger implications in the treatment of pain and opioid use disorder. Patient–physician discussions of these motivations may aid in the development of a treatment plan that minimizes the likelihood of high-risk pain management strategies, yet there remains a clear need for further training and guidance specific to medical cannabis use for pain management.

Source: Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis – PubMed (nih.gov) November 2019

This Notice of Liability Memo and attached Affidavit of Harms give formal notification to all addressees that they are morally, if not legally liable in cases of harm caused by making toxic marijuana products legally available, or knowingly withholding accurate information about the multiple risks of hemp/marijuana products to the Canadian consumer.  This memo further gives notice that those elected or appointed as representatives of the people of Canada, by voting affirmatively for Bill C45, do so with the knowledge that they are breaching international treaties, conventions and law.  They do so also with the knowledge that Canadian law enforcement have declared that they are not ready for implementation of marijuana legalization, and as they will not be ready to protect the lives of Canadians, there may arise grounds for a Charter of Rights challenge as all Canadian citizens are afforded a the right to security of self.

Scientific researchers and health organizations raise serious questions about the safety of ingesting even small amounts of cannabinoids. Adverse effects include risk of harm to the cardio-vascular system, respiratory tract, immune system, reproductive and endocrine systems, gastrointestinal system and the liver, hyperemesis, cognition, psychomotor performance, psychiatric effects including depression, anxiety and bipolar disorder, schizophrenia and psychosis, a-motivational syndrome, and addiction.  The scientific literature also warns of teratogenicity (causing birth deformities) and epigenetic damage (affecting genetic development) and clearly establishes the need for further study. The attached affidavit cites statements made by Health Canada that are grounded in scientific evidence that documents many harms caused by smoking or ingesting marijuana.  

Putting innocent citizens in “harm’s way” has been a costly bureaucratic mistake as evidenced by the 2015 Canadian $168 million payout to victims of exposure to the drug thalidomide. Health Canada approved thalidomide in 1961 to treat morning sickness in pregnant women but it caused catastrophic birth defects and death.

It would be instructive to reflect on “big tobacco” and their multi-billion-dollar liability in cases of misinformed sick and dead tobacco cigarette smokers. Litigants won lawsuits for harm done by smoking cigarettes even when it was the user’s own choice to obtain and smoke tobacco. In Minnesota during the 1930’s and up to the 1970’s tobacco cigarettes were given to generally healthy “juvenile delinquents’ incarcerated in a facility run by the state.  One of the juveniles, now an adult, who received the state’s tobacco cigarettes, sued the state for addicting him. He won.

The marijuana industry, in making public, unsubstantiated claims of marijuana safety, is placing itself in the same position, in terms of liability, as the tobacco companies.
In 1954, the tobacco industry published a statement that came to be known during Minnesota’s tobacco trial as the “Frank Statement.” Tobacco companies then formed an industry group for the purposes of deceiving and confusing the public.

In the Frank Statement, tobacco industry spokesmen asserted that experiments linking smoking with lung cancer were “inconclusive,” and that there was no proof that cigarette smoking was one of the causes of lung cancer. They stated, “We believe the products we make are not injurious to health.” Judge Kenneth Fitzpatrick instructed the Minnesota jurors: “Jurors should assume in their deliberations that tobacco companies assumed a “special duty” by publishing the ad (Frank Statement), and that jurors will have to determine whether the industry fulfilled that duty.” The verdict ruled against the tobacco industry.

Effective June 19, 2009, marijuana smoke was added to the California Prop 65 list of chemicals known to cause cancer. The Carcinogen Identification Committee (CIC) of the Office of Environmental Health Hazard Assessment (OEHHA) “determined that marijuana smoke was clearly shown, through scientifically valid testing according to generally accepted principles, to cause cancer.”

Products liability and its application to marijuana businesses is a topic that was not discussed in the Senate committee hearings. Proposition 65, requires the State to publish a list of chemicals known to cause cancer, birth defects or other types of reproductive harm. Proposition 65 requires businesses to provide their customers with notice of these cancerous causing chemicals when present in consumer products and provides for both a public and private right of action.

The similarities between the tactics of “Big Tobacco” and the “Canadian Cannabis Trade Alliance Institute” and individual marijuana producers would seem to demand very close scrutiny. On May 23, a witness testified before the Canadian Senate claimed that marijuana is not carcinogenic. This evidence was not challenged.

The International Narcotics Control Board Report for 2017 reads: “Bill C-45, introduced by the Minister of Justice and Attorney General of Canada on 13 April 2017, would permit the non-medical use of cannabis. If the bill is enacted, adults aged 18 years or older will legally be allowed to possess up to 30 grams of dried cannabis or an equivalent amount in non-dried form. It will also become legal to grow a maximum of four cannabis plants, simultaneously for personal use, buy cannabis from licensed retailers, and produce edible cannabis products. The Board wishes to reiterate that article 4 (c) of the 1961 Convention restricts the use of controlled narcotic drugs to medical and scientific purposes and that legislative measures providing for non-medical use are in contravention of that Convention….

The situation pertaining to cannabis cultivation and trafficking in North America continues to be in flux owing to the widening scope of personal non-medical use schemes in force in certain constituent states of the United States. The decriminalization of cannabis has apparently led organized criminal groups to focus on manufacturing and trafficking other illegal drugs, such as heroin. This could explain why, for example, Canada saw a 32 per cent increase from 2015 to 2016 in criminal incidents involving heroin possession….The Canadian Research Initiative in Substance Misuse issued “Lower-risk cannabis use guidelines” in 2017. The document is a health education and prevention tool that acknowledges that cannabis use carries both immediate and long-term health risks.”

https://www.incb.org/documents/Publications/AnnualReports/AR2017/Annual_Report_chapters/Chapter_3_Americas_2017.pdf

Upon receipt of this Memo and Affidavit, the addressees can no longer say they are ignorant or unaware that promoting and/or distributing marijuana cigarettes for recreational purposes is an endangerment to citizens. Receipt of this Memo and Affidavit removes from the addressees any claim of ignorance as a defense in potential, future litigation.

Pamela McColl www.cleartheairnow.org

pam.mccoll@cleartheairnow.org

 

AFFIDAVIT May 27, 2018

I, Pamela McColl, wish to inform agencies and individuals of known and potential harm done/caused by the use of marijuana (especially marijuana cigarettes) and of the acknowledgement the risk of harm by Health Canada. 

Marijuana is a complex, unstable mixture of over four hundred chemicals that, when smoked, produces over two thousand chemicals.  Among those two thousand chemicals are many pollutants and cancer-causing substances.  Some cannabinoids are psychoactive, all are bioactive, and all may remain in the body’s fatty tissues for long periods of times with unknown consequences. Marijuana smoke contains carcinogenic (cancer-causing) substances such as benzo(a)pyrene, benz(a)anthracene, and benzene in higher concentrations than are present in tobacco smoke.  The mechanism by which benzo(a)pyrene causes cancer in smokers was demonstrated scientifically by Denissenko MF et al. Science 274:430-432, 1996. 

Health Canada Consumer Information on Cannabis reads as follows:  “The courts in Canada have ruled that the federal government must provide reasonable access to a legal source of marijuana for medical purposes.”

“Cannabis is not an approved therapeutic product and the provision of this information should not be interpreted as an endorsement of the use of cannabis for therapeutic purposes, or of marijuana generally, by Health Canada.”

“Serious Warnings and Precautions: Cannabis (marihuana, marijuana) contains hundreds of substances, some of which can affect the proper functioning of the brain and central nervous system.”

“The use of this product involves risks to health, some of which may not be known or fully understood. Studies supporting the safety and efficacy of cannabis for therapeutic purposes are limited and do not meet the standard required by the Food and Drug Regulations for marketed drugs in Canada.”

Health Canada – “When the product should not be used: Cannabis should not be used if you:-are under the age of 25 -are allergic to any cannabinoid or to smoke-have serious liver, kidney, heart or lung disease -have a personal or family history of serious mental disorders such as schizophrenia, psychosis, depression, or bipolar disorder-are pregnant, are planning to get pregnant, or are breast-feeding -are a man who wishes to start a family-have a history of alcohol or drug abuse or substance dependence Talk to your health care practitioner if you have any of these conditions. There may be other conditions where this product should not be used, but which are unknown due to limited scientific information.

Cannabis is not an approved therapeutic product and the provision of this information should not be interpreted as an endorsement of the use of this product, or cannabis generally, by Health Canada.”

Prepared by Health Canada Date of latest version: February 2013, accessed May 2018. https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-use-marijuana/information-medical-practitioners/information-health-care-professionals-cannabis-marihuana-marijuana-cannabinoids.html

A report published by survey company RIWI Corp. (RIWI.com) can be found at: https://riwi.com/case-study/measuringcanadians-awareness-of-marijuanas-health-effects-may-2018

The report measures Canadians’ awareness of marijuana’s health effects as determined by Health Canada and published on Health Canada’s website. RIWI data indicates: 1. More than 40% of those under age 25 are unaware that marijuana impacts safe driving. Further, 21% of respondents are not aware that marijuana can negatively impact one’s ability to drive safely. Health Canada: “Using cannabis can impair your concentration, your ability to make decisions, and your reaction time and coordination. This can affect your motor skills, including your ability to drive.” 2. One in five women aged 25-34 believes marijuana is safe during pregnancy, while trying to get pregnant, or breastfeeding. • RIWI: “For women of prime childbearing age (25-34), roughly one in five believe smoking marijuana is safe during pregnancy, planning to get pregnant, and breastfeeding.” • Health Canada: “Marijuana should not be used if you are pregnant, are planning to get pregnant, or are breastfeeding. … Long-term use may negatively impact the behavioural and cognitive development of children born to mothers who used cannabis during pregnancy.” 3. One in three Canadians do not think that marijuana is addictive. • Health Canada: “Long term use may result in psychological dependence (addiction).” 4. One in three Canadians believe marijuana aids mental health. • Health Canada: “Long term use may increase the risk of triggering or aggravating psychiatric and/or mood disorders (schizophrenia, psychosis, anxiety, depression, bipolar disorder).” 5. One in two males were unaware that marijuana could harm a man’s fertility • “Marijuana should not be used if you are a man who wishes to start a family.”

ClearTheAirNow.org, a coalition of concerned Canadians commissioned the survey.

Affiant is willing to provide further sources of information about the toxicity of marijuana.

Pamela McColl

www.cleartheairnow.org

pam.mccoll@cleartheairnow.org

Source: From email sent to Drug Watch International May 2018

Abstract

Purpose of review 

Recent widespread legalization changes have promoted the availability of marijuana and its increased potency and perceived safety. The limited evidence on reproductive and perinatal outcomes from marijuana exposure is enough to warrant concern and action. The objective of this review is to provide a current and relevant summary of the recent literature surrounding this topic.

Recent findings 

The available published studies on the effect of marijuana exposure on reproductive health and pregnancy outcomes are conflicting. Human studies are often observational or retrospective and confounded by self-report and polysubstance use. However, the current, limited evidence suggests that marijuana use adversely affects male and female reproductive health. Additionally, prenatal marijuana exposure has been reported to be associated with an increased risk of preterm birth and small for gestational age infants.

Summary 

With the increasing prevalence of marijuana use, there is an urgent need for evidence-driven recommendations and guidelines for couples interested in conception, affected by infertility or who are expecting. At this time, no amount of marijuana use during conception or pregnancy is known to be well tolerated and the limited available evidence suggests that the safest choice is to abstain.

Source: Effects of marijuana on reproductive health: preconception a… : Current Opinion in Endocrinology, Diabetes and Obesity (lww.com) December 2021

Opioid pain relievers are most often prescribed following surgery or to treat cancer pain — situations less common to young people.

However, there are situations or ailments for which opioids may be recommended for your child. These include accidental injury, after oral surgery to remove wisdom teeth, sickle cell disease and other pediatric chronic pain conditions.

Should a health care provider recommend or prescribe an opioid for your child, there are important questions to ask, risks to be aware of and safety precautions to take.

What are some common opioid pain relievers?

  • Hydrocodone (Zohydro)
  • Hydrocodone + Acetaminophen (Vicodin)
  • Oxycodone (Oxycontin, Roxicodone)
  • Oxycodone + Acetaminophen (Percocet)
  • Codeine, Tylenol with Codeine
  • Morphine
  • Fentanyl
  • Tramadol

There are also non-opioid pain relievers (gabapentin, for example) with potential for misuse and abuse, but much lower than that of opioids.

Why is the misuse of opioids so dangerous?

Opioid pain relievers are powerful drugs — very similar to heroin in their chemical makeup and habit-forming by their very nature. This is why the U.S. Centers for Disease Control and Prevention (CDC) strongly recommends against the prescribing of opioids for long-term treatment of chronic pain. Even for treatment of short-term pain, opioid pain relievers should only be prescribed and taken sparingly.

The risk of addiction grows when the patient is a teen or young adult because their brains are still developing and biologically predisposed to experimentation. Suppose your teen or young adult is prescribed an opioid. In that case, you or another caregiver should control the medication, dispense it only as prescribed and monitor closely for signs of misuse or growing dependence.

In addition to the danger of dependence, misuse of opioids can cause dramatic increases in blood pressure and heart rate, organ damage, difficulty breathing, seizures and even death.

What questions should you ask if an opioid is recommended?

Is a prescription opioid necessary?

Ask about alternatives. An over-the-counter (OTC) pain reliever like acetaminophen (e.g., Tylenol) in combination with a non-steroidal anti-inflammatory drug (NSAID) might be just as effective. You can ask about exploring treatments like physical therapy, acupuncture, biofeedback or massage for chronic pain.

What is the quantity and duration of the prescription?

How many pills are being prescribed, and over what period of time?  Is it necessary to prescribe this quantity of pills?

What are the risks of misuse?

The prescriber should be able to answer this question for any drug being prescribed.

Should my child be screened to determine their risk of substance use disorder (SUD) before being prescribed this medication?

If not, why not? Common risk factors include co-occurring mental health disorders such as depression or ADHD, as well as a family history of addiction or a recent trauma such as a death in the family or a divorce.

What if an opioid has been prescribed?

Safeguard medication at home

Don’t just leave it in a medicine cabinet where anyone — family or visitors — can access it, and dispose of any unused medication. For proper disposal, look for a local “takeback” event. If none exist, mix the medication with coffee grounds or other unpleasant garbage and throw it out.

Supervise the dispensing of medication

Keep a count of pills to be sure they are being taken as prescribed, and clearly document when the prescription was filled and when a refill will be needed. Be suspicious of any missing medication.

Communicate the risks of misuse

Make sure your child understands the risks associated with prescription pain relievers, and be very clear that their medication, as with any prescription, is not to be shared with others.

Monitor your child’s levels of pain

Communicate regularly with your child about the level of pain they’re feeling, making sure it’s diminishing with time. Stay alert for any signs that your child is growing dependent on the medication.

What are some signs of misuse or dependence?

If your child is asking for pain medication more frequently than prescribed, or they’re insistent on refilling the prescription, this is a cause for concern. Consult the prescriber to help determine whether pain is going beyond its expected range.

Adverse effects of opioids — which could be a sign of misuse — include drowsiness, nausea, constipation, slowed breathing and slurred speech.

Signs of withdrawal — which would occur if your child has become dependent on an opioid and then stopped taking it — include anxiety, irritability, loss of appetite, craving for the drug, runny nose, sweating, vomiting and diarrhea.

If you’re concerned that your child may be dependent, consult the prescriber, who may in turn consult with a pain specialist. They should consider having a substance use counselor complete an assessment that reviews the extent of your child’s drug and alcohol use, their mental and physical health as well as personal, medical and family history.

Source: When Opioid Pain Relievers Are Prescribed For Your Child: What You Should Know – Partnership to End Addiction (drugfree.org)  March 2019

Abstract

The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB1 cannabinoid receptors (CB1Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB1R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB1Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

Source: Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity | Science May 2007

Damage is caused in several different ways.
BRAIN: Messages are passed from cell to cell (neurons) in the brain by chemicals called neurotransmitters which fit by shape into their own receptor sites on specific cells.
The neurotransmitter, anandamide, an endo-cannabinoid (made in body) whose job is to control by suppression the levels of other neurotransmitters is mimicked and so replaced by a cannabinoid (not made in body) in cannabis called THC (Tetrahydrocannabinol). THC is very much stronger and damps down more forcefully the release of other neurotransmitters. Consequently the total activity of the
brain decreases. Chaos ensues.

Neurotransmitters delivering messages to the hippocampus, the area for learning and memory don’t receive enough stimulation to reach it, so signals are lost for ever.
Academic performance plummets and IQs fall by about 8 points. Neurons can be lost permanently. This is brain damage. No child using cannabis even occasionally will achieve their full potential.
Because signalling is slowed down, reaction times increase. Driving becomes hazardous and fatal accidents are rising in legalised USA states. Alcohol plus cannabis in drivers is 16 times more dangerous.
Since THC is fat-soluble, it stays in cells for weeks, constantly ensuring this decrease in brain activity. In the sixties/seventies the THC content was around 1-3%, now in London only ‘skunk’ at 16-20% THC is available. Professor Sir Robin Murray has said that, ‘users will be in a state of low-grade intoxication most of the time’. The Dopamine neurotransmitter has no receptor sites for anandamide and so THC
doesn’t affect it. But the inhibitory Gaba neurotransmitter has. Gaba normally suppresses dopamine but since it is itself suppressed by THC, levels of dopamine quickly increase. Excess dopamine is found in the brains of psychotics, and even schizophrenics if they have a genetic vulnerability. Anyone taking enough THC at one sitting will suffer a psychotic episode which could become permanent. Aggression, violence, even homicides, suicides and murders have resulted from cannabis-induced psychosis. The first research paper linking THC with psychosis was published in 1845. Cannabis-induced schizophrenia costs the country around £2 billion/year. Some of these mentally ill people will spend the rest of their lives in psychiatric units.
THC also depletes the levels of the ‘happiness’ neurotransmitter Serotonin. This can cause depression which may lead to suicide. THC causes dependence. This will affect 1 in 6 using adolescents and 1 in 9 of the general population. Since THC replaces anandamide, there is no need for its production which reduces and eventually stops so the receptor sites are left empty.
Withdrawal then sets in with irritability, sleeplessness, anxiety, depression, even violence until anandamide production resumes. Rehab specialists have told us that adolescent pot addiction is the most challenging to treat.
Cannabis can also act as a gateway drug – it can ‘prime’ the brain for the use of other drugs. Professor David Fergusson (NZ) in longitudinal studies from birth found that ‘The use of cannabis in late adolescence and early adulthood emerged as the strongest risk factor for later involvement in other illicit drug use’.
THC inhibits the vomiting reflex. If a person has drunk too much alcohol, they are often sick and get rid of it. An overdose of alcohol can kill (respiratory muscles stop working) so using cannabis together with alcohol can be fatal.
The signalling of endo-cannabinoids is crucial in brain development. They guide the formation, survival, proliferation, motility and differentiation of new neurons. THC badly interferes with these essential processes. Chaos ensues among the confused brain signals and a cannabis personality develops. Users can’t think logically. They have fixed opinions and answers, can’t find words, can’t take criticism – it’s always someone else’s fault, and can’t plan their day. Families suffer from their violent mood swings – houses get trashed. Anxiety, panic and paranoia may ensue. At the same time users are lonely, miserable and feel misunderstood.

Respiratory System:
Cannabis smoke has many of the same constituents as tobacco smoke but more of its carcinogens – in cancer terms a joint equals 4/5 cigarettes. More tar is deposited in the lungs and airways. Coughing, wheezing, emphysema, bronchitis and cancers have been seen in the lungs.

Heart:
Heart rates rise and stay high for 3-4 hours after a joint. Heart attacks and strokes have been recorded. Some teenagers had strokes and died after bingeing on cannabis.

Hypothalamus:
The hypothalamus is a region of the brain known to regulate appetite. Endocannabinoids in this area send ‘I’m hungry’ messages. When you take THC, that message is boosted. This is called ‘the munchies’. Nabilone, (synthetic THC) can be used to stimulate the appetite in AIDS patients.

DNA and Reproduction:
THC affects the DNA in any new cells being made in the body. It speeds up the programmed cell death (apoptosis) of our defence white blood cells, so our immune system is diminished. There are also fewer sperm. Infertility and impotence have been reported as far back as the 1990s.
An Australian paper published in July 2016 explains this phenomenon. THC can disrupt the actual process of normal cell division mitosis and meiosis (formation of sperm and eggs). In mitosis, the chromosomes replicate and gather together at the centre of the cell. Protein strands (microtubules) are formed from the ends of the cell to pull half of the chromosomes to each end to form the 2 new cells. Unfortunately THC disrupts microtubule formation. Chromosomes can become isolated, rejoin other bits of chromosome and have other abnormalities. Some will actually be shattered into fragments (chromothripsis).
This DNA damage can also cause cancers. Oncogenes (cancer-causing genes) may be activated, and tumour suppressant genes silenced. Chromosome fragments and abnormal chromosomes are frequently seen in cancerous tissues. This would account for other cancers, leukaemia, brain, prostate, cervix, testes and bladder etc, reported in regions of the body not exposed to the smoke. Pregnant users see a 2-4
fold increase in the number of childhood cancers in their offspring. The DNA damage has also been associated with foetal abnormalities – low birth weight, pre-term birth, spontaneous miscarriage, spina bifida, anencephaly (absence of brain parts), gastroschisis (babies born with intestines outside the body) cardiac defects and shorter limbs. All these defects bear in common an arrest of cell growth and cell migration at critical development stages consistent with the inhibition of mitosis noted with cannabis.
DNA damage at meiosis results in fewer sperm as we have seen. Increased errors in meiosis have the potential for transmission to subsequent generations. The zygote (fertilised egg) death rate rises by 50% after the first division. In infants, birth weight is lower and they may be born addicted. Children may have problems with behaviour and cognitive functions as they grow. Childhood cancers are
more common. Intensive care for newborns doubles. The younger they start using cannabis, the more likely they are to remain immature, become addicted, suffer from mental illnesses or progress to other drugs. Average age of first use is 13. Regular cannabis users have worse jobs, less than average money, downward social mobility, relationship problems and antisocial behaviour.

References:
Cannabis Skunk Website www.cannabisskunksense.co.uk Cannabis: A survey of its
harmful effects by Mary Brett is available on DOWNLOADS. It is a 300+ page report
written in 2006 and kept up to date.

Chromothripsis and epigenomics complete causality criteria for cannabis- and
addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity

Book: Adverse Health Consequencies of Cannabis Use. Jan Ramstrom National Institute of Public Health Sweden www.fhi.se

Source: https://www.cannabisskunksense.co.uk/uploads/site-files/ty,Chromothripsis,CarcinogenicityandFetotoxicity,MR-FMMM.pdf March 2020

  • Cannabis is responsible for 91% of drug addiction cases involving teenagers
  • Skunk – high-potency herbal cannabis – causing more people to seek treatment 
  • Backs up research that skunk is having detrimental impact on mental health

Cannabis is responsible for 91 per cent of cases where teenagers end up being treated for drug addiction, shocking new figures reveal.

Supporters of the drug claim it is harmless, but an official report now warns the ‘increased dominance of high-potency herbal cannabis’ – known as skunk – is causing more young people to seek treatment.

The revelation comes amid growing concerns that universities – and even some public schools – are awash with high-strength cannabis and other drugs.

The findings also back up academic research, revealed in The Mail on Sunday over the past three years, that skunk is having a serious detrimental impact on the mental health of the young. At least two studies have shown repeated use triples the risk of psychosis, with sufferers repeatedly experiencing delusional thoughts. Some victims end up taking their own lives.

The latest UK Focal Point on Drugs report, drawn up by bodies including Public Health England, the Scottish Government and the Home Office, found that:

  • Over the past decade, the number of under-18s treated for cannabis abuse in England has jumped 40 per cent – from 9,043 in 2006 to 12,712 in 2017;
  • Treatment for all narcotics has increased by 20 per cent – up from 11,618 to 13,961;
  • The proportion of juvenile drug treatment for cannabis use is up from four in five cases (78 per cent) to nine in ten (91 per cent);
  • There has been a ‘sharp increase’ in cocaine use among 15-year-olds, up 56 per cent from 16,700 in 2014 to 26,200 in 2016.

Last night, Lord Nicholas Monson, whose 21-year-old son Rupert Green killed himself last year after becoming hooked on high-strength cannabis, said: ‘These figures show the extent of the damage that high-potency cannabis wreaks on the young.

‘The big danger for young people – particularly teens – is that their brains can be really messed up by this stuff because they are still developing biologically. If they develop drug-induced psychosis – as Rupert did – the illness can stick for life.’

The large rise in the number of youngsters treated for cannabis abuse comes despite the fact that total usage is falling slightly.

The report concludes: ‘While fewer people are using cannabis, those who are using it are experiencing greater harm.’

Almost all cannabis on Britain’s streets is skunk, which is four times more powerful than types that dominated the market until the early 2000s. It can even trigger hallucinations.

Lord Monson said: ‘We really need Ministers to get a grip and launch a major publicity campaign about the dangers.’ 

Nine in ten teens at drug clinics are being treated for marijuana use  | Daily Mail Online April 2018

We note the report on the rising gastroschisis incidence 3.1 times 1995-2012

The 20-fold variation across California mirrors the ten-fold variation across Canada here the distribution pattern closely mirrors cannabis consumption, and from where cannabis-related adjusted O.R.= 3.54 (95%C.I. 2.22-5.63) has been reported .

Several clues suggest cannabis is likely involved also in California.  Statewide gastroschisis rose 2.84-fold 2005-2012, whilst last month cannabis use in northern California rose 2.56-fold from 8.41% to 21.55% 2006-2008 to 2014-2016 in the National Survey of Drug Use and Health.

Combining the midrange county rates supplied  with published birth, population and NSDUH data it can be shown that the gastroschisis rate in the NSDUH 1R northern 15 counties rose O.R.=2.33 (95%C.I. 1.91-2.83) compared to the rest of the state for the whole period 1995-2012.

Anderson found rurality was a risk factor for cannabis use which fits with the burgeoning cannabis industry.  Timber production was a probable surrogate marker, and the Federal parks are known to accommodate substantial cannabis plantations.

Moreover as various potent herbicides and rodenticides including carbofuran are used in commercial operations and contaminate the water table these also need to be considered as novel indirect toxins.

Gastroschisis follows cannabis use in many places including Australia, Canada, Mexico, North Carolina, and Washington state.  Mechanistically this is consistent with the appearance of cannabinoid type 1 receptors (CB1R) on the omphalovitelline vessels from the ninth week of gestation, and documented occurrence of cannabis arteritis .

The real possibility clearly needs to be considered that the global rise in cannabis use may underlie the dramatic rise in gastroschisis in many locations.  Indeed since heart and brain defects including anencephaly and brain impairments consistent with autistic deficits are also well described in the congenital cannabis exposure literature, together with Downs syndrome, it may be that a wide variety of defects could be related to the budding industry.

The potential link with the autism spectrum including cannabis-dependent, dose-related and rampant neurexin- neurologin-mediated synaptic dehiscence is of particular concern.  The rapidly growing autism epidemic in Colorado is matched by an autism hotspot in the northern cannabis zone of California which has likely become even hotter since that study was conducted.

Careful substance-spatiotemporal analyses of positive and negative correlation are indicated to investigate causal relationships.

The possibility of worldwide multiorgan cannabis-induced CB1R-mediated severe clinical teratology has not been widely canvassed.

Source:  email: stuart.reece@bigpond.com  

Abstract

Endocannabinoids regulate brain development via modulating neural proliferation, migration, and the differentiation of lineage-committed cells. In the fetal nervous system, (endo)cannabinoid-sensing receptors and the enzymatic machinery of endocannabinoid metabolism exhibit a cellular distribution map different from that in the adult, implying distinct functions. Notably, cannabinoid receptors serve as molecular targets for the psychotropic plant-derived cannabis constituent Δ(9)-tetrahydrocannainol, as well as synthetic derivatives (designer drugs). Over 180 million people use cannabis for recreational or medical purposes globally. Recreational cannabis is recognized as a niche drug for adolescents and young adults. This review combines data from human and experimental studies to show that long-term and heavy cannabis use during pregnancy can impair brain maturation and predispose the offspring to neurodevelopmental disorders. By discussing the mechanisms of cannabinoid receptor-mediated signaling events at critical stages of fetal brain development, we organize histopathologic, biochemical, molecular, and behavioral findings into a logical hypothesis predicting neuronal vulnerability to and attenuated adaptation toward environmental challenges (stress, drug exposure, medication) in children affected by in utero cannabinoid exposure. Conversely, we suggest that endocannabinoid signaling can be an appealing druggable target to dampen neuronal activity if pre-existing pathologies associate with circuit hyperexcitability. Yet, we warn that the lack of critical data from longitudinal follow-up studies precludes valid conclusions on possible delayed and adverse side effects. Overall, our conclusion weighs in on the ongoing public debate on cannabis legalization, particularly in medical contexts.

At the Tip of an Iceberg: Prenatal Marijuana and Its Possible Relation to Neuropsychiatric Outcome in the Offspring – PubMed (nih.gov) September 2015

Many marijuana dispensaries recommend marijuana products for treating pregnant women’s morning sickness, even though marijuana use in pregnancy is linked with health problems for newborns, according to a new study from Colorado researchers.

The study surveyed 400 marijuana dispensaries in Colorado, and nearly 70 percent said they would recommend marijuana products for women experiencing nausea in early pregnancy. Most dispensary employees cited their personal opinions when making the recommendation.

“As cannabis legalization becomes more common, women should be cautioned that advice from dispensary employees might not necessarily be informed by medical evidence,” the researchers, from the University of Colorado School of Medicine and the Denver Health and Hospital Authority, wrote in the June issue of the journal Obstetrics & Gynecology. [25 Odd Facts About Marijuana]

Pot during pregnancy

Marijuana use during pregnancy may be harmful for babies: Some studies have found a link between marijuana use in pregnancy and health problems in newborns, including low birth weight, according to the Centers for Disease Control and Prevention (CDC). Research also suggests that marijuana use during pregnancy could have long-term neurological effects: For example, some studies have found that children exposed to marijuana in the womb are at greater risk for attention and behavior problems, compared with babies not exposed to marijuana. The American College of Obstetricians and Gynecologists recommends that pregnant women not use marijuana.

“Babies exposed to marijuana in utero are at increased risk of admission to neonatal intensive care units. There are also concerns about possible long-term effects on the developing brain, impacting cognitive function and decreasing academic ability later in childhood,” study lead author Dr. Torri Metz, a perinatologist at Denver Health, said in a statement.

However, as more and more U.S. states legalize the drug, more pregnant women may use it, the study authors said. Already, 1 in 20 U.S. women reports using pot while pregnant, according to the CDC.

What’s more, pregnant women may not wish to discuss marijuana use with their doctors, out of fear of legal consequences, and so they may instead seek advice from marijuana retailers, the researchers said.

In the new study, the researchers called Colorado marijuana dispensaries and pretended to be eight weeks pregnant.

The researchers told the dispensary employees that they were feeling “really nauseated” and asked if the dispensaries had any products recommended for morning sickness.

Of the 400 marijuana dispensaries contacted, 277 (69 percent) recommended a marijuana product for morning sickness, and of these, 65 percent based their recommendation on personal opinion, while 30 percent did not specify a reason for their recommendation.

More than a third (36 percent) of dispensary employees contacted said that marijuana was safe in pregnancy, while about half (53 percent) said they weren’t sure about the drug’s safety during pregnancy.

The researchers also made note of some quotes from the dispensary employees, which in some cases were strikingly inaccurate. For example, one employee said that “after eight weeks [of pregnancy], everything should be good with consuming, like, alcohol and weed and stuff, but I would wait an extra week.” Another said that marijuana edibles wouldn’t be a risk to the baby, because “they would be going through your digestional [digestive] tract.”

Still, 80 percent of dispensaries did recommend that the caller discuss use of marijuana in pregnancy with their doctor. But only 32 percent of dispensaries made this recommendation without prompting from the researchers (with the question “Should I talk to my doctor about this?”)

The researchers noted that recommendations from cannabis dispensary employees may vary depending on the person who took the call and may not represent the policy of the dispensary or the views of other employees. Still, the “mystery caller” method used by the researchers reflects a “real world” situation and the advice that a woman may receive when calling the dispensary, the investigators said.

The researchers concluded that “public health initiatives should consider collaborating with dispensary owners … about standards for advice provided to pregnant women.”

Source: Most Marijuana Dispensaries Give Inaccurate Advice on Pot in Pregnancy | Live Science May 2018

Smoking during pregnancy has well-documented negative effects on birth weight in infants and is linked to several childhood health problems. Now, researchers at the University at Buffalo Research Institute on Addictions have found that prenatal marijuana use also can have consequences on infants’ weight and can influence behavior problems, especially when combined with tobacco use.

“Nearly 30 percent of women who smoke cigarettes during pregnancy also report using marijuana,” says Rina Das Eiden, PhD, RIA senior research scientist. “That number is likely to increase with many states moving toward marijuana legalization, so it’s imperative we know what effects prenatal marijuana use may have on infants.”

Through a grant from the National Institute on Drug Abuse, Eiden studied nearly 250 infants and their mothers. Of these, 173 of the infants had been exposed to tobacco and/or marijuana during their mothers’ pregnancies. None were exposed to significant amounts of alcohol.

Eiden found that infants who had been exposed to both tobacco and marijuana, especially into the third trimester, were smaller in length, weight and head size, and were more likely to be born earlier, compared to babies who were not exposed to anything. They also were more likely to be smaller in length and weight compared to babies exposed only to tobacco in the third trimester. The results were stronger for boys compared to girls.

“We also found that lower birth weight and size predicted a baby’s behavior in later infancy,” Eiden says. “Babies who were smaller were reported by their mothers to be more irritable, more easily frustrated and had greater difficulty calming themselves when frustrated. Thus, there was an indirect association between co-exposure to tobacco and marijuana and infant behavior via poor growth at delivery.”

Furthermore, women who showed symptoms of anger, hostility and aggression reported more stress in pregnancy and were more likely to continue using tobacco and marijuana throughout pregnancy. Therefore, due to the co-exposure, they were more likely to give birth to infants smaller in size and who were more irritable and easily frustrated. The infants’ irritability and frustration is also linked to mothers who experienced higher levels of stress while pregnant.

“Our results suggest that interventions with women who smoke cigarettes or use marijuana while pregnant should also focus on reducing stress and helping them cope with negative emotions,” Eiden says. “This may help reduce prenatal substance exposure and subsequent behavior problems in infants.”

The study appeared in the March/April issue of Child Development and was authored by Pamela Schuetze, PhD, Department of Psychology, Buffalo State College, with co-authors Eiden; Craig R. Colder, PhD, UB Department of Psychology; Marilyn A. Huestis, PhD, Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia; and Kenneth E. Leonard, PhD, RIA director.

Source: Prenatal marijuana use can affect infant size, behavior, study finds — ScienceDaily May 2018

Study finds combined use of cigarettes and marijuana may increase children’s exposure to second-hand smoke

Cannabis use increased among parents who smoke cigarettes, as well as among non-smoking parents, according to a latest study from researchers at Columbia University’s Mailman School of Public Health and City University of New York. Cannabis use was nearly four times more common among cigarette smokers compared with non-smokers. Until now, little had been known about current trends in the use of cannabis among parents with children in the home, the prevalence of exposure to both tobacco and cannabis, and which populations might be at greatest risk. The findings will be published online in the June issue of Pediatrics.

“While great strides have been made to reduce children’s exposure to second-hand cigarette smoke, those efforts may be undermined by increasing use of cannabis among parents with children living at home,” said Renee Goodwin, PhD, in the Department of Epidemiology at the Mailman School of Public Health, and corresponding author.

Analyzing data from the National Survey on Drug Use and Health from 2002 to 2015, the researchers found past-month cannabis use among parents with children at home increased from 5 percent in 2002 to 7 percent in 2015, whereas cigarette smoking declined from 28 percent to 20 percent. Cannabis use increased from 11 percent in 2002 to over 17 percent in 2015 among cigarette-smoking parents and from slightly over 2 percent to 4 percent among non-cigarette-smoking parents. Cannabis use was nearly 4 times more common among cigarette smokers versus nonsmokers (17 percent vs 4 percent), as was daily cannabis use (5 percent vs 1 percent). The overall percentage of parents who used cigarettes and/or cannabis decreased from 30 percent in 2002 to 24 percent in 2015.

“While use of either cigarettes or cannabis in homes with children has declined, there was an increase in the percent of homes with both. Therefore, the increase in cannabis use may be compromising progress in curbing exposure to secondhand smoke,” noted Goodwin, who is also at the Graduate School of Public Health and Health Policy at CUNY.

Cannabis use was also more prevalent among men who also smoked compared to women (10 percent vs 6 percent) and among younger parents with children in the home (11 percent) compared with those 50 and older (4 percent). The strength of the relationship between current cannabis use and cigarette smoking was significant and similar for all income levels.

“The results of our study support the public health gains in reducing overall child secondhand tobacco smoke but raise other public health concerns about child exposure to secondhand cannabis smoke and especially high risk for combined exposures in certain subpopulations,” observed Goodwin.

Noteworthy, according to Goodwin, is that there remains a lack of information on the location of smoking, whether it occurs in the house or in the proximity of children. Unlike cigarettes, smoking cannabis outdoors and in a range of public areas is illegal in most places. Therefore, there is reason to believe that cannabis use is even more likely to occur in the home than cigarette smoking given their differences in legal status.

“Efforts to decrease secondhand smoke exposure via cigarette smoking cessation may be complicated by increases in cannabis use,” said Goodwin. “Educating parents about secondhand cannabis smoke exposure should be integrated into public health education programs on secondhand smoke exposure.”

The study was funded by the National Institutes of Health and National Institute on Drug Abuse (DA20892).

Co-authors are Melanie Wall, Deborah Hasin, and Samantha Santoscoy, Mailman School of Public Health; Keely Cheslack-Postava, Columbia University College of Physicians and Surgeons; Nina Bakoyiannis, CUNY; and Bradley Collins and Stephen Lepore, Temple University.

Source: Cannabis use up among parents with children in the home: Study finds combined use of cigarettes and marijuana may increase children’s exposure to second-hand smoke — ScienceDaily May 2018

Yasmin L. HurdOlivier J. ManzoniMikhail V. PletnikovFrancis S. LeeSagnik Bhattacharyya and Miriam Melis

Abstract

The recent shift in sociopolitical debates and growing liberalization of cannabis use across the globe has raised concern regarding its impact on vulnerable populations, such as pregnant women and adolescents. Epidemiological studies have long demonstrated a relationship between developmental cannabis exposure and later mental health symptoms. This relationship is especially strong in people with particular genetic polymorphisms, suggesting that cannabis use interacts with genotype to increase mental health risk. Seminal animal research directly linked prenatal and adolescent exposure to delta-9-tetrahydrocannabinol, the major psychoactive component of cannabis, with protracted effects on adult neural systems relevant to psychiatric and substance use disorders. In this article, we discuss some recent advances in understanding the long-term molecular, epigenetic, electrophysiological, and behavioral consequences of prenatal, perinatal, and adolescent exposure to cannabis/delta-9-tetrahydrocannabinol. Insights are provided from both animal and human studies, including in vivo neuroimaging strategies.

Keywords: adolescence; cannabis; cognition; perinatal; psychiatric disorders; reward.

Source: Cannabis and the Developing Brain: Insights into Its Long-Lasting Effects – PubMed (nih.gov) October 2019

Albert Stuart Reece, MBBS(Hons.), FRCS(Ed.), FRCS(Glas.), FRACGP, MD (UNSW) and Gary Kenneth Hulse, BBSc.(Hons.), MBSc., PhD.

Abstract

Background: The epidemiology of cannabinoid-related cancerogenesis has not been studied with cutting edge epidemiological techniques. Building on earlier bivariate papers in this series we aimed to conduct pathfinding studies to address this gap in two tumours of the reproductive tract, prostate and ovarian cancer.

Methods: Age-standardized cancer incidence data for 28 tumour types (including “All (non-skin) Cancer”) was sourced from Centres for Disease Control and National Cancer Institute using SEER*Stat software across US states 2001-2017. Drug exposure was sourced from the nationally representative household survey National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental Health Services Administration 2003-2017 with response rate 74.1%. Federal seizure data provided cannabinoid concentration data. US Census Bureau provided income and ethnicity data. Inverse probability weighted mixed effects, robust and panel regression together with geospatiotemporal regression analyses were conducted in R. E-Values were also calculated.

Results: 19,877 age-standardized cancer rates were returned. Based on these rates and state populations this equated to 51,623,922 cancer cases over an aggregated population 2003-2017 of 124,896,418,350. Inverse probability weighted regressions for prostate and ovarian cancers confirmed causal associations robust to adjustment. Cannabidiol alone was significantly associated with prostate cancer (β-estimate = 1.61, (95%C.I. 0.99, 2.23), P = 3.75 × 10– 7). In a fully adjusted geospatiotemporal model at one spatial and two temporal years lags cannabidiol was significantly independently associated with prostate cancer (β-estimate = 2.08, (1.19, 2.98), P = 5.20 × 10– 6). Cannabidiol alone was positively associated with ovarian cancer incidence in a geospatiotemporal model (β-estimate = 0.36, (0.30, 0.42), P < 2.20 × 10– 16). The cigarette: THC: cannabidiol interaction was significant in a fully adjusted geospatiotemporal model at six years of temporal lag (β-estimate = 1.93, (1.07, 2.78), P = 9.96 × 10– 6). Minimal modelled polynomial E-Values for prostate and ovarian cancer ranged up to 5.59 × 1059 and 1.92 × 10125. Geotemporospatial modelling of these tumours showed that the cannabidiol-carcinogenesis relationship was supra-linear and highly sigmoidal (P = 1.25 × 10– 45 and 12.82 × 10– 52 for linear v. polynomial models).

Conclusion: Cannabinoids including THC and cannabidiol are therefore important community carcinogens additive to the effects of tobacco and greatly exceeding those of alcohol. Reproductive tract carcinogenesis necessarily implies genotoxicity and epigenotoxicity of the germ line with transgenerational potential. Pseudoexponential and causal dose-response power functions are demonstrated.

Keywords: Cannabidiol; Cannabigerol; Cannabinoid; Cannabis; Chromosomal toxicity; Congenital anomalies; Dose-response relationship; Epigenotoxicity; Genotoxicity; Mechanisms; Multigenerational genotoxicity; Oncogenesis; Sigmoidal dose-response; Supra-linear dose response; Transgenerational teratogenicity; Δ9-tetrahydrocannabinol.

Source: Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017: part 3 – spatiotemporal, multivariable and causal inferential pathfinding and exploratory analyses of prostate and ovarian cancers – PubMed (nih.gov) March 2022

Albert Stuart Reece, MBBS(Hons.), FRCS(Ed.), FRCS(Glas.), FRACGP, MD (UNSW) and Gary Kenneth Hulse, BBSc.(Hons.), MBSc., PhD.

Abstract

Background: As the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco.

Methods: SEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) from National Cancer Institute in US states 2001-2017. Drug exposures taken from the National Survey of Drug Use and Health 2003-2017, response rate 74.1%. Federal seizure data provided cannabinoid exposure. US Census Bureau furnished income and ethnicity. Exposure dichotomized as highest v. lowest exposure quintiles. Data processed in R.

Results: Nineteen thousand eight hundred seventy-seven age-standardized cancer rates were returned. Based on these rates and state populations this equated to 51,623,922 cancer cases over an aggregated population 2003-2017 of 124,896,418,350. Fifteen cancers displayed elevated E-Values in the highest compared to the lowest quintiles of cannabidiol exposure, namely (in order): prostate, melanoma, Kaposi sarcoma, ovarian, bladder, colorectal, stomach, Hodgkins, esophagus, Non-Hodgkins lymphoma, All cancer, brain, lung, CLL and breast. Eleven cancers were elevated in the highest THC exposure quintile: melanoma, thyroid, liver, AML, ALL, pancreas, myeloma, CML, breast, oropharynx and stomach. Twelve cancers were elevated in the highest tobacco quintile confirming extant knowledge and study methodology. For cannabidiol RR declined from 1.397 (95%C.I. 1.392, 1.402), AFE declined from 28.40% (28.14, 28.66%), PAR declined from 15.3% (15.1, 15.5%) and minimum E-Values declined from 2.13. For THC RR declined from 2.166 (95%C.I. 2.153, 2.180), AFE declined from 53.8% (53.5, 54.1%); PAR declined from 36.1% (35.9, 36.4%) and minimum E-Values declined from 3.72. For tobacco, THC and cannabidiol based on AFE this implies an excess of 93,860, 91,677 and 48,510 cases; based on PAR data imply an excess of 36,450, 55,780 and 14,819 cases.

Conclusion: Data implicate 23/28 cancers as being linked with THC or cannabidiol exposure with epidemiologically-causal relationships comparable to those for tobacco. AFE-attributable cases for cannabinoids (91,677 and 48,510) compare with PAR-attributable cases for tobacco (36,450). Cannabinoids constitute an important multivalent community carcinogen.

Keywords: Cannabidiol; Cannabigerol; Cannabinoid; Chromosomal toxicity; Congenital anomalies; Dose-response relationship; Epigenotoxicity; Genotoxicity; Mechanisms; Multigenerational genotoxicity; Oncogenesis; Sigmoidal dose-response; Supra-linear dose response; Transgenerational teratogenicity; cannabis; Δ9-tetrahydrocannabinol.

Source: Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017: part 2 – categorical bivariate analysis and attributable fractions – PubMed (nih.gov) March 2022

Albert Stuart Reece, MBBS(Hons.), FRCS(Ed.), FRCS(Glas.), FRACGP, MD (UNSW) and Gary Kenneth Hulse, BBSc.(Hons.), MBSc., PhD. 

Abstract

Background: The genotoxic and cancerogenic impacts of population-wide cannabinoid exposure remains an open but highly salient question. The present report examines these issues from a continuous bivariate perspective with subsequent reports continuing categorical and detailed analyses.

Methods: Age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) was sourced using SEER*Stat software from Centres for Disease Control and National Cancer Institute across US states 2001-2017. It was joined with drug exposure data from the nationally representative National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental Health Services Administration 2003-2017, response rate 74.1%. Cannabinoid data was from Federal seizure data. Income and ethnicity data sourced from the US Census Bureau. Data was processed in R.

Results: Nineteen thousand eight hundred seventy-seven age-standardized cancer rates were returned. Based on these rates and state populations this equated to 51,623,922 cancer cases over an aggregated population 2003-2017 of 124,896,418,350. Regression lines were charted for cancer-substance exposures for cigarettes, alcohol use disorder (AUD), cannabis, THC, cannabidiol, cannabichromene, cannabinol and cannabigerol. In this substance series positive trends were found for 14, 9, 6, 9, 12, 6, 9 and 7 cancers; with largest minimum E-Values (mEV) of 1.76 × 109, 4.67 × 108, 2.74 × 104, 4.72, 2.34 × 1018, 2.74 × 1017, 1.90 × 107, 5.05 × 109; and total sum of exponents of mEV of 34, 32, 13, 0, 103, 58, 25, 31 indicating that cannabidiol followed by cannabichromene are the most strongly implicated in environmental carcinogenesis. Breast cancer was associated with tobacco and all cannabinoids (from mEV = 3.53 × 109); “All Cancer” (non-skin) linked with cannabidiol (mEV = 1.43 × 1011); pediatric AML linked with cannabis (mEV = 19.61); testicular cancer linked with THC (mEV = 1.33). Cancers demonstrating elevated mEV in association with THC were: thyroid, liver, pancreas, AML, breast, oropharynx, CML, testis and kidney. Cancers demonstrating elevated mEV in relation to cannabidiol: prostate, bladder, ovary, all cancers, colorectum, Hodgkins, brain, Non-Hodgkins lymphoma, esophagus, breast and stomach.

Conclusion: Data suggest that cannabinoids including THC and cannabidiol are important community carcinogens exceeding the effects of tobacco or alcohol. Testicular, (prostatic) and ovarian tumours indicate mutagenic corruption of the germline in both sexes; pediatric tumourigenesis confirms transgenerational oncogenesis; quantitative criteria implying causality are fulfilled.

Keywords: Cannabidiol; Cannabigerol; Cannabinoid; Cannabis; Chromosomal toxicity; Congenital anomalies; Dose–response relationship; Epigenotoxicity; Genotoxicity; Mechanisms; Multigenerational genotoxicity; Oncogenesis; Sigmoidal dose–response; Supra-linear dose response; Transgenerational teratogenicity; Δ9-tetrahydrocannabinol.

Source: Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003-2017: part 1 – continuous bivariate analysis – PubMed (nih.gov) March 2022

Albert Stuart Reece, MBBS(Hons), FRCS(Ed), FRCS(Glas), FRACGP, MD(UNSW), and Gary Kenneth Hulse, BBSc(Hons), MBSc, PhD

Objectives:

Cannabis is a known teratogen. Data availability addressing both major congenital anomalies and cannabis use allowed us to explore their geospatial relationships.

Methods:

Data for the years 1998 to 2009 from Canada Health and Statistics Canada was analyzed in R. Maps have been drawn and odds ratios, principal component analysis, correlation matrices, least squares regression and geospatial regression analyses have been conducted using the R packages base, dplyr, epiR, psych, ggplot2, colorplaner and the spml and spreml functions from package splm.

Results:

Mapping showed cannabis use was more common in the Cannabis Use 2018. Total congenital anomalies, all cardiovascular defects, orofacial clefts, Downs syndrome and gastroschisis were all found to be more common in these same regions and rose as a function of cannabis exposure. When Canada was dichotomized into high and low cannabis use zones by Provinces v Territories the Territories had a higher rate of total congenital anomalies 450.026 v 390.413 (O.R.¼1.16 95%C.I. 1.08-1.25, P¼0.000058; attributable fraction in exposed 13.25%, 95%C.I. 7.04–19.04%).

In geospatial analysis in a spreml spatial error model cannabis was significant both alone as a main effect (P<2.0_10_16) and in all its first and second order interactions with both tobacco and opioids from P<2.0_10_16.

Conclusion:

These results show that the northern Territories of Canada share a higher rate of cannabis use together with elevated rates of total congenital anomalies, all cardiovascular defects, Down’s syndrome and gastroschisis. This is the second report of a significant association between cannabis use and both total defects and all cardiovascular anomalies and the fourth published report of a link with Downs syndrome and thereby direct major genotoxicity.

The correlative relationships described in this paper are confounded by many features of social disadvantage in Canada’s northern territories. However, in the context of a similar broad spectrum of defects described both in animals and in epidemiological reports from Hawaii, Colorado, USA and Australia they are cause for particular concern and indicate further research.

Source: Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis – PubMed (nih.gov) September / October 2020

Abstract

Background

Whilst cannabis commercialization is occurring rapidly guided by highly individualistic public narratives, evidence that all congenital anomalies (CA) increase alongside cannabis use in Canada, a link with 21 CA’s in Hawaii, and rising CA’s in Colorado indicate that transgenerational effects can be significant and impact public health. It was therefore important to study Northern New South Wales (NNSW) where cannabis use is high.

Methods

Design: Cohort. 2008–2015. Setting: NNSW and Queensland (QLD), Australia. Participants. Whole populations. Exposures. Tobacco, alcohol, cannabis. Source: National Drug Strategy Household Surveys 2010, 2013. Main Outcomes. CA Rates. NNSW-QLD comparisons. Geospatial and causal regression.

Results

Cardiovascular, respiratory and gastrointestinal anomalies rose with falling tobacco and alcohol but rising cannabis use rates across Queensland. Maternal age NNSW-QLD was not different (2008–2015: 4265/22084 v. 96,473/490514 > 35 years/total, Chi.Sq. = 1.687, P = 0.194). A higher rate of NNSW cannabis-related than cannabis-unrelated defects occurred (prevalence ratio (PR) = 2.13, 95%C.I. 1.80–2.52, P = 3.24 × 10− 19). CA’s rose more potently with rising cannabis than with rising tobacco or alcohol use. Exomphalos and gastroschisis had the highest NNSW:QLD PR (6.29(2.94–13.48) and 5.85(3.54–9.67)) and attributable fraction in the exposed (84.11%(65.95–92.58%) and 82.91%(71.75–89.66%), P = 2.83 × 10− 8 and P = 5.62 × 10− 15). In multivariable geospatial models cannabis was significantly linked with cardiovascular (atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus), genetic (chromosomal defects, Downs syndrome), gastrointestinal (small intestinal atresia), body wall (gastroschisis, diaphragmatic hernia) and other (hypospadias) (AVTPCDSGDH) CA’s. In linear modelling cannabis use was significantly linked with anal stenosis, congenital hydrocephalus and Turner syndrome (ACT) and was significantly linked in borderline significant models (model P < 0.1) with microtia, microphthalmia, and transposition of the great vessels. At robust and mixed effects inverse probability weighted multivariable regression cannabis was related to 18 defects. 16/17 E-Values in spatial models were > 1.25 ranging up to 5.2 × 1013 making uncontrolled confounding unlikely.

Conclusions

These results suggest that population level CA’s react more strongly to small rises in cannabis use than tobacco or alcohol; cardiovascular, chromosomal, body wall and gastrointestinal CA’s rise significantly with small increases in cannabis use; that cannabis is a bivariate correlate of AVTPCDSGDH and ACT anomalies, is robust to adjustment for other substances; and is causal.

Source: Broad Spectrum Epidemiological Contribution of Cannabis, Tobacco and Alcohol to the Teratological Profile of Northern New South Wales: Geospatial and Causal Inference Analysis | Research Square November 2020

Researchers in Australia released the results of a new study examining the consequences of long-term marijuana use that began in adolescence or young adulthood. A total of 1,792 participants were included in the longitudinal study spanning 20 years (from ages 15-35). Investigators found that compared to non-users, both young‐adult and adolescent‐onset regular users were 20 times more likely to have used other illicit drugs, 4 times more likely be heavy drinkers, and 7 times more likely to be daily tobacco smokers. There were also less than half as likely as non-users to be in romantic relationships.

Dr. Sharif Mohr, epidemiologist at Drug Free America Foundation commented, “The results of this study clearly show the negative effects of marijuana use that can follow youth far into adulthood. It also confirms marijuana’s role as a gateway drug. We’ve already learned from Colorado and other states that no matter what safeguards are in place, legal weed will always manage to find its way into the hands of young people, much to their detriment. It’s time for lawmakers to do the right thing and put an end to this disastrous large-scale experiment which only serves to enrich Big Marijuana and other players at the expense of our young people.”

Source:  https://www.dfaf.org/australian-study-demonstrates-consequences-of-youth-marijuana-use/     29th Jan. 2021

Abstract

BACKGROUND Marijuana is the considered the most widely available and used drug across the world. Up to this time, there have been no reports of human death directly caused by acute marijuana toxicity in adults, fetuses, or newborn neonates.

CASE REPORT We report a death of an 11-day-old white female neonate due to acute marijuana toxicity. She died of extensive necrosis and hemorrhage of the liver and adrenals due to maternal use of marijuana.

CONCLUSIONS This case is unique in that other possible causes of death can be eliminated. With growing use of marijuana by pregnant women and increases in newborn drug screening of umbilical cord homogenate, more cases of neonatal death due to acute marijuana toxicity could be discovered.

 

Figure 1. 

Macroscopic examination of both adrenals, showing extensive hemorrhage. The arrows point to areas of severe hemorrhage

Figure 2. 

Macroscopic examination of entire liver, showing petechial hemorrhage. The arrow points to one of the petechiae.

Figure 3. 

Macroscopic examination of thymus, showing focal hemorrhage. The arrow points to the center of one of the focal hemorrhages.

Figure 4. 

Microscopic examination of liver (hematoxylin and eosin, 40×) showing extensive necrosis and hemorrhage. The arrow points to the center of one area of necrosis. The hemorrhage is the background of the photo, consisting of red cells.

Figure 5. 

Microscopic examination of adrenal (hematoxylin and eosin, 40×) showing extensive necrosis and hemorrhage. The arrow points to the center of one area of necrosis and hemorrhage.

Figure 6. 

Microscopic examination of thymus (hematoxylin and eosin, 40×) showing focal hemorrhage without necrosis. The arrow points to the center of one area of focal hemorrhage.
Source: Neonate Death Due to Marijuana Toxicity to the Liver and Adrenals – PubMed (nih.gov) December 2019

CBD IS NOT SAFE AS A MEDICINE UNLESS IT ACQUIRES FDA APPROVAL AFTER RIGOROUS TESTING DEMONSTRATING EFFICACY AND SAFETY.

Cannabidiol (CBD) and Tetrahydrocannabinol (THC) come from the cannabis plant. A pure form of CBD (Epidiolex) is approved by the FDA as a medicine for two rare disorders to be used only under proper medical protocols. Other CBD products sold as medicines, or food or food supplements, that are not approved by the FDA are Black-Market and are illegally trafficked and sold.

In addition, CBD cosmetics must be properly labeled under FDA law and not be adulterated by deleterious substances. Black Market CBD products have not been evaluated by the FDA to determine if they are effective or safe for any medical use, and if safe, what the proper dosage would be. In addition, they are not administered with any federally approved medical protocols as are prescription drugs and there may be no warnings for how they interact with other drugs, or whether they have dangerous side effects.

CBD IS NOT SAFE TO BE PUT INTO FOODS OR FOOD SUPPLEMENTS
Under the federal Food, Drug and Cosmetic Act it’s illegal to introduce THC and CBD into the food supply, or to market them as dietary supplements. It is not safe to do so unless approved by the FDA.

MULTIPLE STUDIES SHOW BLACK MARKET CBD PRODUCT CONTAMINATION
The FDA has tested the chemical contents of many Black-Market CBD products and many were found to not contain the levels of CBD they claimed to contain. Black Market CBD often contains THC and/or contaminants such as pesticides, heavy metals, bacteria, and fungus. Synthetic CBD use has caused adverse reactions, including altered mental status, seizures, confusion, and loss of consciousness.

CBD CAUSES PHYSICAL DISEASE AND SAFETY RISKS
The marijuana industry has touted CBD as a “wonder drug.” * They may claim it is perfectly safe and legal and can be used for all that ails you or makes you uncomfortable physically. People are consuming CBD under the misapprehension that it is safe to do so. It is not. CBD has known health risks based on FDA clinical studies in humans and other clinical reports. The known adverse reactions include:
1. Hepatocellular Injury (liver injury) – inflammation or damage to cells
2. Somnolence and Sedation
3. Suicidal Behavior and Ideation
4. Hypersensitivity Reactions – allergic reactions
5. Negative interaction with anti-epilepsy drugs such as Tegretol, Dilantin, Luminal, Solfoton,
Tedral, Primidone (anti-seizure)
6. Interactions with immunosuppressive drugs used in transplants or chemotherapy and with
warfarin.
7. CBD use can impair kidney function and cause anemia.

We advocate for no use of illegal drugs and no illegal use of legal drugs.

CBD AND PREGNANCY
The FDA strongly advises that during pregnancy and while breastfeeding you should not use CBD or THC. You may put yourself or your baby at serious risk by using these marijuana products. CBD products may also be contaminated with substances that may pose a risk to the fetus or breastfed baby such as pesticides, heavy metals, bacteria, and fungus. Studies in laboratory animals show male reproductive toxicity, including in the male offspring of CBD-treated pregnant females. This includes decrease in testicular size, inhibition of sperm development, and decreased testosterone.

TAKING CBD CAN BE DANGEROUS WHEN DRIVING OR USING MACHINERY
Recent FDA studies show that CBD can cause sleepiness, sedation and that may make operating a motor vehicle or machinery dangerous after consuming CBD products.

DRUG TESTS
CBD may affect drug test results. A truck driver lost his job when he tested positive for THC on a drug test after being told by the manufacturer that a CBD product had no THC.

FDA Reports
To make a report to the FDA about CBD being used as a medicine or as a food or food supplement go to:
https://www.accessdata.fda.gov/scripts/email/oc/buyonline/english.cfm#whattoreport

www.aalm.info POB 158 Carmichael, CA 95609 Phones 916-708-4111, 619-990-7480

March 6, 2020

Source: CBD.POSITION.3.6.2020.pdf (squarespace.com)

Abstract

The recent demonstration that massive scale chromosomal shattering or pulverization can occur abruptly due to errors induced by interference with the microtubule machinery of the mitotic spindle followed by haphazard chromosomal annealing, together with sophisticated insights from epigenetics, provide profound mechanistic insights into some of the most perplexing classical observations of addiction medicine, including cancerogenesis, the younger and aggressive onset of addiction-related carcinogenesis, the heritability of addictive neurocircuitry and cancers, and foetal malformations. Tetrahydrocannabinol (THC) and other addictive agents have been shown to inhibit tubulin polymerization which perturbs the formation and function of the microtubules of the mitotic spindle. This disruption of the mitotic machinery perturbs proper chromosomal segregation during anaphase and causes micronucleus formation which is the primary locus and cause of the chromosomal pulverization of chromothripsis and downstream genotoxic events including oncogene induction and tumour suppressor silencing. Moreover the complementation of multiple positive cannabis-cancer epidemiological studies, and replicated dose-response relationships with established mechanisms fulfils causal criteria. This information is also consistent with data showing acceleration of the aging process by drugs of addiction including alcohol, tobacco, cannabis, stimulants and opioids. THC shows a non-linear sigmoidal dose-response relationship in multiple pertinent in vitro and preclinical genotoxicity assays, and in this respect is similar to the serious major human mutagen thalidomide. Rising community exposure, tissue storage of cannabinoids, and increasingly potent phytocannabinoid sources, suggests that the threshold mutagenic dose for cancerogenesis will increasingly be crossed beyond the developing world, and raise transgenerational transmission of teratogenicity as an increasing concern.

Keywords: Cannabis; Chromothripsis; Dose-response relationship; Epigenetics; Foetal malformations; Heritable; Interdisciplinary; Microtubules; Oncogenesis; Population effects; Threshold dose; Transgenerational; Tubulin.

  • Researchers found smoking infrequently carries a high risk of schizophrenia
  • Cannabis use less than twice a week was as risky as smoking the drug daily 
  • Comes after psychiatric admissions for cannabis use soared in Scotland 

Teens who occasionally use cannabis are just as likely to develop schizophrenia as daily smokers, a study has claimed. Researchers in the Caribbean reviewed more than 590 papers looking at cannabis use in children aged 12 to 18. Smoking the drug at low frequencies came with the same six-fold increased risk of getting the mental disorder as doing it daily, results showed. Rates of schizophrenia in both groups were compared against non-smokers. Experts warned it is vital teenagers avoid using the drug while their brains are still developing. NHS figures show cannabis use in people aged 16 to 24 is rising in England and Wales, with 32.6 percent admitting having used it in 2020, compared to 30.2 per cent in 2016. It comes after data revealed psychiatric hospital admission among cannabis users soared 74 per cent since the drug was effectively decriminalised in Scotland. Scottish police changed its guidance in January 2016 so anyone found possessing cannabis could be issued with a warning rather than face prosecution. The number of prosecutions halved over the period. Last year, a record 1,263 patients in Scotland sought NHS treatment for psychiatric disorders blamed on cannabis, including schizophrenia.

The review, published in Journal of Clinical Psychology, included 591 studies from 2010 and 2020 about cannabis use in adolescents from across the globe. They classified cannabis users into two groups: low frequency users — smoking twice a week or less — and higher frequency users — who smoke daily or nearly every day. Using statistical analysis, they compared the groups’ chances of developing schizophrenia compared to teenagers who never smoked the drug. The chances of getting the mental disorder were six times higher in both groups, the researchers said. They did not specify how long it usually takes to develop the disorder after smoking. It tends to occur in men in their late teens and early 20s, and in the late 20s to early 30s in women — although it can develop at any age for either gender. 

Writing in the article, the researchers said: ‘Both high- and low-frequency marijuana usage were associated with a of schizophrenia. ‘The frequency of use among high- and low-frequency users is similar in both, demonstrating statistically significant increased risk in developing schizophrenia.’

Adam Winstock, the founder of the Global Drugs Survey and honorary professor of clinical medicine at University College London, said the study showed the need for caution around cannabis use at younger ages. He told the Daily Telegraph: ‘If you want to optimise your health and wellbeing and minimise your risk of developing psychotic illnesses, don’t use drugs when you are young. ‘Grow your brain before you expand it.’ 

The researchers were based in the Saint James School of Medicine in Arnos Vale, St Vincent and the Grenadines. The country last month made its first ever shipment of medical cannabis to Germany, sending 110lb (49.8kg) worth of the drug. The Caribbean nation with a population of just over 110,000 people has been developing its local cannabis industry for years. In 2018, Saint Vincent created a state agency to oversee licensing and ensure its medical cannabis is available to local patients. 

It comes after a host of research further bolstered the link between cannabis use and psychological disorders, including schizophrenia. One US study found that cannabis-linked psychosis admissions are 2.5 times higher in areas where the drug has been legalised. 

And official NHS figures show psychiatric hospital admissions for cannabis users rocketed from 1,191 in 2015 to 2016 to 2,067 last year. Professor Jonathan Chick, of Castle Craig Hospital, a private rehabilitation centre in Peeblesshire, said lawmakers have taken their eyes ‘off the ball’ with cannabis legislation. He said the number of young people suffering psychosis and schizophrenia because of cannabis use is a ‘worry’.

NHS figures show cannabis use in people aged 16 to 24 is rising in England and Wales, with 32.6 percent admitting having used it in 2020, compared to 30.2 per cent in 2016.

Graph shows: Drug use in different ages in England and Wales over time

 

Despite numerous studies linking the two, scientists have yet to firm up exactly how the drug may lead to the condition. And other research has suggested the drug itself may not be enough to cause serious mental disorders.

A separate study by Harvard researchers in 2014 of cannabis users with and without a family history of schizophrenia suggested cannabis use alone does not result in the disorder. The risk of developing the disorder was higher in those with a family history, regardless of cannabis use.

Dr Lynn DeLisi, one of the authors of the paper, told the New York Times at the time: ‘My study clearly shows that cannabis does not cause schizophrenia by itself. ‘Rather, a genetic predisposition is necessary. ‘It is highly likely, based on the results of this study and others, that cannabis use during adolescence through to age 25, when the brain is maturing and at its peak of growth in a genetically vulnerable individual, can initiate the onset of schizophrenia.’ 

Source: https://www.dailymail.co.uk/health/article-10467473/Teenagers-smoke-cannabis-six-times-likely-develop-schizophrenia-study-claims.html February 2022

Case for Caution with Cannabis

There exists sufficient empirical data from cellular to epidemiological studies to warrant caution in the use cannabinoids including cannabidiol as recreational and therapeutic agents.

 

Cannabinoids bind to CB1R receptors on neuronal mitochondrial membranes where they can directly disrupt key functions including cellular energy generation, DNA maintenance and repair, memory and learning .

 

Empirical literature associates cannabinoid use with CB1R-mediated vasospastic and vasothrombotic strokes, myocardial infarcts and arrhythmias .  Cannabis has been associated with increased cardiovascular stiffness and vascular aging, a major surrogate for organismal aging.  In the pediatric-congenital context CB1R-mediated cannabis vasculopathy forms a major pathway to teratogenesis including VSD, ASD, endocardial cushion defects, several other cardiovascular anomalies  and, via the omphalo-vitelline arterial CB1R’s  gastroschisis.  Cannabis has been linked with several other malformations including hydrocephaly.  Cannabinoids also induce epigenetic perturbations; and, like thalidomide, interfere with tubulin polymerization and the stability of the mitotic spindle providing further major pathways to genotoxicity.

 

Assuming validity of the above data, increased levels of both adult and neonatal morbidity should accompany increased cannabis use. The “Colorado Responds to Children with Special Needs” program tracked congenital anomalies 2000-2013.  Importantly this data monitors the teratological history of Colorado since 2001 when the state was first advised that intrastate cannabis would not be prosecuted by the Federal Government.

 

Over the period 2000-2013 Colorado almost doubled its already high congenital anomaly rate rising from 4,830 anomalies / 65,429 births (7.4%) to 8,165 / 65,004 (12.6%); the US mean is 3.1%.  Major cardiovascular defects rose 61% (number and rate); microcephaly rose 96% (from 30 to 60 cases peaking at 72 in 2009); and chromosomal anomalies rose 28% (from 175 to 225, peaking at 264 in 2010).  Over the whole period this totals to 87,772 major congenital anomalies from 949,317 live births (9.25%).

 

The use of cannabis in Colorado can be determined from the SAMHSA National Survey on Drug Use and Health.  A close correlation is noted between major congenital anomaly rates and rates of cannabis use in Coloradans.  Although data is not strictly comparable across U.S. registries, the Colorado registry is a passive rather than active case-finding registry and so might be expected to underestimate anomaly rates.  Given the Colorado birth rate remained almost constant over the period 2000-2013, rising only 3.6%, a simple way to quantitate historical trends is to simply project forwards the historical anomaly rate and compare it to the rise in birth numbers.  However rather than remaining relatively stable in line with population births, selected defects have risen several times more than the birth rate.

 

Colorado had an average of 67,808 births over the period 2000-2013 and experienced a total of 87,772 birth defects, 20,152 more than would have been predicted using 2000 rates.  Given the association between cannabis use and birth defects and the plausible biological mechanisms, cannabis may be a major factor contributing to birth congenital morbidity in Colorado. If we accept this and apply the “Colorado effect” to the over 3,945,875 births in USA in 2016 we calculate an excess of 83,762 major congenital anomalies annually nationwide if cannabis use rises in the US to the level that it was in Colorado in 2013.

 

In reality both cannabis use and cannabis concentration is rising across USA following legalization which further implies that the above calculations represent significant underestimations.  This data series terminates in 2013 prior to full legalization in 2014.  Moreover parents of children harbouring severe anomalies may frequently elect for termination, which will again underestimate numbers of abnormal live births.

 

In California 7% of all pregnant mothers were recently shown to test positive for cannabis exposure, including almost 25% of teenage mothers in 2015  so cannabinoids clearly constitute a significant population-wide teratological exposure .  This is particularly relevant to cannabis genotoxicity as many studies show a dramatic up-tick in genotoxic effect in the dose-response curve for both tetrahydrocannabinol and cannabidiol above a certain threshold dose as higher, sedating levels are reached.  Cannabis is usually used amongst humans for its sedative effects.

 

Other examples of high congenital anomaly rates accompanying increased cannabis use include North Carolina, Mexico, Northern Canada, New Zealand and the Nimbin area in Australia.

 

The above data leave open the distinct possibility that the rate of congenital anomalies from significant prenatal paternal or maternal cannabis exposure may become substantial.

 

With over 1,000 trials listed on clincaltrials.gov the chance of a type I experimental error for cannabinoid therapeutics and a falsely positive trial finding is at least 25/1,000 trials at the 5% level.

 

The major anomaly rate is just the “tip of the iceberg” of the often subtle neurobehavioral teratology of Foetal Cannabinoid Syndrome (FCS) following antenatal cannabinoid exposure characterized by attention, learning, behavioral and social deficits which in the longer term impose significant educational, other addiction and welfare costs – and is clearly more common .  Foetal Alcohol Syndrome (FAS) is known to be epigenetically mediated and foetal alcohol is known to act via CB1R’s .  Cannabis has significant and heritable epigenetic imprints in neural, immune and germ cell (sperm) tissues, and epigenomic disruption has been implicated in FCS.  CB1R-mediated disruption by disinhibition of the normal gamma and theta oscillatory rhythms of the forebrain which underpin thinking, learning and sanity have been implicated both in adult psychiatric disease and the neurodevelopmental aspects of FCS .

 

All of this implies that in addition to usually short-term therapy-oriented clinical trials, longer term studies and careful twenty-first century next generation studies will be required to carefully review inter-related genotoxic, teratologic, epigenetic, transcriptomic, metabolomic, epitranscriptomic and long term cardiovascular outcomes which appears to have been largely overlooked in extant studies – effects which would appear rather to have taken Coloradans by surprise.  Congenital registry data also needs to be open and transparent which it presently is not.  We note that cannabidiol is now solidly implicated in genotoxicity.  Governments are duty-bound to carefully weigh and balance the implications of their social policies; lest like Colorado, we too unwittingly create a “Children with Special Needs Program”.

 

Source: Email: sreece@bigpond.net.au

As marijuana use becomes increasingly normalized and liberalized, more and more adolescents are initiated into using the drug with serious implications for the healthcare system and public health.   Confirming what those of us in the prevention community have long known, a systematic review and meta-analysis published in JAMA Psychiatry found that marijuana use in adolescence was associated with increased risk of depression and suicide in young adulthood (18-32 years of age). After pooling data from 11 studies of over 23,300 individuals, researchers found that compared to non-users, adolescents who used marijuana were 40% more likely to suffer from depression, 50% more likely to experience suicidal ideation, and 250% more likely to attempt suicide in young adulthood.

Proponents of legalization often argue that alcohol and tobacco are legal even though they are responsible for far more deaths than marijuana. That is true. However, it is precisely because they are legal and widely accessible that they are so deadly. Do we want to add yet another legal intoxicant that has been linked to a number of negative health and social consequences at the individual and population levels? Two wrongs never make a right. Adolescent use of marijuana increases risk of suicidality by 250%. If the nation’s entire population of approximately 25,000,000 adolescents had access to recreational marijuana in the context of legalization, we could expect to see big increases in future suicides among young adults that are directly attributable to marijuana use. That is far too high a price to pay.

 

Source: https://www.dfaf.org/research/

 

Researchers report 63 percent of breast milk samples from mothers using marijuana contained traces of the drug

With the legalization of marijuana in several states, increased use for both medicinal and recreational purposes has been documented in pregnant and breastfeeding women. Although national organizations like the American Academy of Pediatrics recommend that breastfeeding mothers do not use marijuana, there has been a lack of specific data to support health or neurodevelopmental concerns in infants as a result of exposure to tetrahydrocannabinol (THC) or other components of marijuana via breast milk.

To better understand how much marijuana or constituent compounds actually get into breast milk and how long it remains, researchers at University of California San Diego School of Medicine conducted a study, publishing online August 27 in Pediatrics.

Fifty-four samples from 50 women who used marijuana either daily, weekly or sporadically — with inhalation being the primary method of intake — were examined. Researchers detected THC, the primary psychoactive component of marijuana, in 63 percent of the breast milk samples for up to six days after the mother’s last reported use.

“Pediatricians are often put into a challenging situation when a breastfeeding mother asks about the safety of marijuana use. We don’t have strong, published data to support advising against use of marijuana while breastfeeding, and if women feel they have to choose, we run the risk of them deciding to stop breastfeeding — something we know is hugely beneficial for both mom and baby,” said Christina Chambers, PhD, MPH, principal investigator of the study, professor in the Department of Pediatrics at UC San Diego School of Medicine and director of clinical research at Rady Children’s Hospital-San Diego.

The World Health Organization recommends exclusive breastfeeding for up to six months. Early breastfeeding is associated with a reduced risk of obesity, asthma and sudden infant death syndrome and with improved immune health and performance on intelligence tests. In mothers, breastfeeding has been associated with lower risks for breast and uterine cancer and type 2 diabetes.

Cannabinoids — marijuana’s active compounds, such as THC — like to bind to fat molecules, which are abundant in breast milk. This stickiness has suggested that, in women who use marijuana, these compounds can end up in breast milk, raising concerns about their potential effects on nursing babies.

“We found that the amount of THC that the infant could potentially ingest from breast milk was relatively low, but we still don’t know enough about the drug to say whether or not there is a concern for the infant at any dose, or if there is a safe dosing level,” said Chambers, co-director of the Center for Better Beginnings at UC San Diego. “The ingredients in marijuana products that are available today are thought to be much more potent than products available 20 or 30 years ago.”

The samples of breast milk used for the study were obtained from mothers who joined the Mommy’s Milk Human Milk Research Biorepository at UC San Diego, a program that focuses on looking at the numerous benefits of breast milk at the molecular level. Chambers and her research team collaborated with Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego to measure the levels of marijuana in the samples.

Chambers said the results are a stepping stone for future research. More studies need to be done, not only to determine the long-term impact of marijuana in breast milk for children, but more specifically: “Are there any differences in effects of marijuana in breast milk for a two-month-old versus a 12-month-old, and is it different if the mother smokes versus eats the cannabis? These are critical areas where we need answers as we continue to promote breast milk as the premium in nutrition for infants.

Source: https://www.sciencedaily.com/releases/2018/08/180827080911.htm

 

 

Is addiction a biological disease that is driven by environmental factors or not

Posted Mar 11, 2019

It will come as no surprise to you that childhood trauma, particularly unresolved trauma, can lead to mental health issues and addiction later in life. While less was known about the specific correlation in decades past, today we have a pretty good understanding of just how damaging adverse childhood experiences (ACEs) can be on development and coping.

The first few years of life are full of many important developmental milestones in terms of brain pathways, attachment, coping mechanisms and in generally learning how to relate to others and to stress. Those who experience trauma in their early years often develop survival mechanisms that are less than helpful in adulthood. For some people, such interference early on can even drive them towards addiction.

This is an area of addiction that I like to talk about, because people with an addiction are often judged at face-value by who they are right now, without any compassion or understanding of where they have come from or what has happened to them (for more on this mistake see HERE and HERE). Understanding these underlying issues however, becomes KEY in unlocking the secrets of addiction recovery.

Treat people with respect instead of blaming or shaming them. Listen intently to what they have to say. Integrate the healing traditions of the culture in which they live. Use prescription drugs, if necessary. And integrate adverse childhood experiences science: ACEs.”  – Dr. Daniel Sumrok

What are ACEs?

Adverse Childhood Experiences (ACEs) are traumatic events that occur in childhood.

This may include:

  • Abuse (physical, emotional, sexual) and/ or neglect
  • Exposure to parental domestic violence
  • Household dysfunction e.g. parent with an untreated mental health condition or substance use disorder
  • Parental separation or divorce
  • Loss of parent through death, deportation, incarceration or being removed from the family home by child protection services

Stressful experiences in childhood may also stem from outside the family home, for example: bullying, witnessing violence, racism, being an immigrant, homelessness, living in a war zone and moving house often (such as in the case of military families).

A substantial portion of the people I’ve worked with over the past 11 years have experienced at least one of these ACEs. Most have experienced two or more.

What does research say about ACEs and long-term

Much of the research has stemmed from the original CDC-Kaiser Permanente Adverse Childhood Experiences (ACE) Study, the most prominent investigation to date into childhood abuse and neglect and its impact on adult health and wellbeing. Data was collected between 1995 to 1997 from over 17,000 participants.

The ACE study looks at types of early trauma and the long-term outcomes for these children in later life. Participants were required to answer ten questions about specific forms of childhood trauma and mark whether they had experienced this or not. For each type of trauma, they received a score of 1, the highest being 10. For example, a person who was sexually abused, was exposed to domestic violence and had a parent with a substance use disorder, would have an ACE score of three.

The study found that a person with an ACE score of 4 has nearly double the risk of cancer and heart disease than someone without an adverse childhood experience. What’s more, the likelihood of developing an alcohol use disorder increases 7-fold percent and the likelihood of suicideincreased 12-fold.

People who have had an ACE are two to four times more likely to start using alcohol or drugs at an early age, compared to those without an ACE score. People with an ACE score of 5 or higher are up to ten times more likely to experience addiction compared with people who haven’t experienced childhood trauma.

The research has also revealed that people with higher ACE scores are more likely to experience chronic pain and misuse prescription medication, and are at increased risk of serious health conditions such as:

In the United States, 60% of adults had experienced at least one traumatic event in their childhood and 25% had experienced at least 3 ACEs.

How do we make sense of all the research?

There’s an overwhelming amount of evidence supporting this notion: the majority of people currently experiencing mental health or addiction problems have a history of adverse childhood experiences. That’s not to say that all children who experience trauma will go on to have a substance use disorder, because there are a lot of other factors at play, but it is a nearly-necessary component of a person’s history that requires serious consideration in treatment.

“Ritualized compulsive comfort-seeking (what traditionalists call addiction) is a normal response to the adversity experienced in childhood, just like bleeding is a normal response to being stabbed.” – Dr. Daniel Sumrok, director of the Center for Addiction Sciences at the University of Tennessee Health Science Center’s College of Medicine.

It’s also important to note that the ACE study simply reports on correlations, not causal links. We cannot say that experiencing physical abuse or a messy divorce in childhood will directly lead to a substance use disorder.

What we do know is this: Adverse childhood experiences are bad for your emotional and physical health and wellbeing in adulthood.

We must also consider all the other factors that influence a person’s behavior including socioeconomic factors such as income, education and access to resources.

Now, I don’t want to overwhelm you with all the research that points toward the power of our trauma histories. Your ACE score is not destiny. With help, you can learn healthy coping mechanisms, and how to have healthy relationships. We also need to account for geneticenvironmental and spiritual factors that influence our behavior.

And while the research sheds light on how powerful childhood trauma can be in our life’s trajectory, it also helps inform government, communities and individuals about the importance of compassion. The link between adverse childhood experiences and later health problems is even more of a reason to reduce stigma and shame associated surrounding addiction. Children do not have control over their home environment, so therefore, we cannot expect them to overcome their difficulties as adults without compassion and support.

How can we help people with ACEs overcome addiction?

We need to focus on providing resources to the people at greatest risk and making sure those resources go into programs that reduce or mitigate adversity.

Dr. Daniel Sumrock says we can do these things to help people change addiction by:

  • Address a person’s unresolved childhood trauma through individual and/ or group therapy
  • Treat people with compassion and respect
  • Use harm minimization principles such as providing medication treatments for addiction (such as buprenorphine or methadone)
  • Help people with an addiction find a ‘ritualized compulsive comfort-seeking behavior’ (addiction) that is less harmful to their health.

IGNTD Recovery takes ACEs into account, getting to the “why” of the addiction, not just putting a Band-Aid on the compulsive seeking symptom. Indeed, we believe that focusing on the symptoms is harmful.

So if this is something you’d like to address either for yourself or for someone you know then find out more about my approach to addiction at IGNTD Recovery or in my book The Abstinence Myth.

Read more about the ACE study:

Source:  https://www.psychologytoday.com/ca/blog/all-about-addiction/201903/linked-adverse-childhood-experiences-health-addiction

 

 

 

FDA Approved Epidiolex®, a purified form of CDB, this week.

 

Families whose children suffer seizures from epilepsy have asked legislators in several states to “legalize” cannabidiol (CBD), “medicinal” marijuana, and “whole-plant extracts” so they can use them to reduce their children’s seizures. The marijuana industry has been happy to accommodate, helping parents lobby legislators and, when successful, producing CBD products.

But none of these products is approved by FDA as safe or effective. All make unsubstantiated medical claims. Few contain what their labels claim. Some contain contaminants. Recently, the Centers for Disease Control and Prevention reported that 52 people in Utah were poisoned by an unregulated CBD product, which contained a synthetic cannabinoid. The agency warned regulations are needed to address “this emerging public health threat.”

This week, FDA approved Epidiolex to treat two forms of epilepsy in patients ages 2 and older. Epidiolex is an extract of marijuana called cannabidiol (CBD) that is purified and delivers a reliable, consistent dose. Clinical trials proved it reduces epileptic seizures. Now families have a choice. They no longer need to risk giving their children unregulated products that may harm their already fragile health.
Epidiolex

FDA approved
Proven to be safe
Proven to reduce seizures
A purified extract of marijuana that is 99% CBD, less than 1% THC, marijuana’s psychoactive ingredient
Doctors prescribe.
Patients buy at pharmacies.
Likely to be insured.
Likely moved to a lower Schedule
CBD Products States Have Legalized

Not FDA approved
Not proven to be safe
Not proven to reduce seizures
Unpurified extracts containing up to 20% CBD, THC, other components. Some are contaminated.
Doctors recommend.
Patients buy at dispensaries.
Not insured.
Likely to remain in Schedule 1
Many media outlets are reporting that FDA’s approval of Epidiolex means CBD will be placed in a lower schedule of the federal Controlled Substances Act. But FDA Commissioner Scott Gottlieb clarifies, “This is the approval of one specific CBD medication for a specific use . . . based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.” Just as Marinol, Cesamet, and Syndros, FDA-approved forms of THC, are in lower schedules but THC remains in Schedule I, Epidiolex is likely to be placed in a lower Schedule while CBD likely will remain in Schedule I.

Commissioner Gottlieb says FDA continues to support rigorous scientific research into potential medical treatments using marijuana or its components but is concerned about the proliferation and illegal marketing of unapproved CBD-containing products making unproven medical claims. FDA will continue to act to end such behavior, he says.

Action is certainly needed. Searching for CBD Oil on Amazon brings up 929 results. All unregulated.


 

 

Examples of unregulated CBD products. None has applied to FDA to conduct clinical trials for FDA approval.

 

 

Read the Centers for Disease Control and Prevention’s warning about unregulated CBD products here.
Read the FDA announcement of its approval of Epidiolex here.
Read See FDA CBD warning letters here.
Download The Marijuana Report Issue Paper on CBD here.

Disclosure: The author holds stock in GW Pharmaceuticals, the company that makes Epidiolex®.
 

 

From edibles appealing to children to increased use among parents, youth are on the frontlines as America grapples with loosened marijuana access

 

 

In states where marijuana has been legalized, revenues for edibles have skyrocketed. Edibles are food products that contain THC, the substance in marijuana that produces psychological effects, or Cannabidiol (CBD). As marijuana businesses are profiting from these sales, some states are considering the taxation of marijuana products to fill budget gaps. However, most states have seen far less revenue from the taxation of marijuana products than legalization advocates would lead the public to believe, with California receiving less than half of the tax revenue initially projected.

Today, makers of edibles infuse varying quantities of THC into frequently consumed food products such as gummy bears, chocolate bars, beef jerky, soda, and more. With so much money to be made, even major corporations are entering the edibles marketplace. In 2018 Heineken launched “HiFi Hops” a non-alcoholic beer infused with THC; last month the inventor of Jelly Belly® launched a line of CBD-infused jelly beans which promptly sold out; and on April 20th (a noted holiday among marijuana consumers), a Carl’s Junior restaurant will serve the “CheeseBurger Delight,” featuring a CBD-infused sauce. There has been limited research on the effects of CBD among children and adolescents or whether CBD usage normalizes the use of marijuana in general. Therefore, we must be cautious about what the acceptance of marijuana-infused products will have on our society’s understanding of safe marijuana consumption and regulation.

The rise of edibles mimicking popular children’s candies and other frequently purchased family food products has resulted in a troubling increase in marijuana-related hospital visits for minors and adults alike, with legislatures in Colorado and California enacting laws to restrict marketing of edible products and prevent accidental ingestion by minors. However, even with these new marketing restrictions, emergency room visits for minors caused by inhaling or ingesting marijuana continue to rise. In fact, a recent study in the Annals of Internal Medicine reported that “edible products accounted for 10.7% of marijuana-attributable visits between 2014 and 2016 but represented only 0.32% of total marijuana sales in Colorado (in kilograms of tetrahydrocannabinol) during that period.”

Since legalization, marijuana-related traffic deaths increased 151 percent in Colorado, killing drivers, passengers, pedestrians and bicyclists. Furthermore, 48 percent of pediatric marijuana intoxication cases reported to poison control centers in Colorado were attributed to the ingestion of edibles. This double-whammy of decreased regulation of marijuana and increased marketing of marijuana-laced products is detrimental to public health, substance misuse prevention efforts, and puts our kids and teens at risk. Science has taught us that the age of first use of any addictive substance– whether it be marijuana, alcohol, tobacco or another drug– increases the likelihood of that individual going on to develop a substance use disorder in their lifetime, as does exposure to caregiver substance misuse.

The United States is in the midst of an overdose epidemic that is killing more people in one year than car accidents and gun violence. It is imperative that we learn from our mistakes and the actions that could have been taken to prevent the current epidemic, such as investing in evidence-based prevention education, and implement safeguards to prevent future epidemics.

 

Casey Elliott: **Author’s Note: This piece was originally published by Fox News.

Source:  https://www.addictionpolicy.org/blog/edible-marijuana-kids-at-risk   Apr 20, 2019

 

Pregnant women who smoke cannabis almost double the risk of their baby being born autistic, warns a new study.

In the largest ever study of its kind, researchers found that children whose mothers reported using cannabis during pregnancy were at greater risk of autism.

The incidence of autism was four per 1,000 person-years among children exposed to cannabis in pregnancy, compared to 2.42 among unexposed children.

‘There is evidence that more people are using cannabis during pregnancy,’ said senior study author Professor Mark Walker, of the University of Ottawa in Canada.

‘This is concerning, because we know so little about how cannabis affects pregnant women and their babies.

‘Parents-to-be should inform themselves of the possible risks, and we hope studies like ours can help.’

The researchers reviewed data from every birth in Ontario between 2007 and 2012, before recreational cannabis was legalised in Canada.

Of the half a million women in the study, about 3,000 (0.6 per cent) reported using cannabis during pregnancy.

Importantly, these women reported using only cannabis.

The team had previously found that cannabis use in pregnancy was linked to an increased risk of premature birth.

In that study, they found that women who used cannabis during pregnancy often used other substances including tobacco, alcohol and opioids.

Considering those findings, in the current study the researchers specifically looked at the 2,200 women who reported using only cannabis during pregnancy, and no other substances.

The findings, published in the medical journal Nature Medicine. showed that babies born to this group still had an increased risk of autism compared to those who didn’t use cannabis.

The researchers do not know exactly how much cannabis the women were using, how often, at what time during their pregnancy, or how it was consumed.

But as cannabis becomes more socially acceptable, doctors are concerned that some parents-to-be might think it can be used to treat morning sickness.

Dr Daniel Corsi, an epidemiologist at The Ottawa Hospital, said: ‘In the past, we haven’t had good data on the effect of cannabis on pregnancies.’

He added: ‘This is one of the largest studies on this topic to date.

‘We hope our findings will help women and their health-care providers make informed decisions.’

Autism is fairly common, but still poorly understood.

In the US, about one in every 59 children born will fall somewhere on the autism spectrum.

About one in every 66 children in Canada are autistic and, globally, the rate is approximately one in every 160 children.

Research suggests that there is likely some genetic basis for autism,  which is about four-times more common among boys than girls.

But scientists believe exposures in the womb likely play a role as well.

The effects of cannabis are similarly poorly understood to the origins of autism.

Although doctors caution against it, cannabis use has not been linked to miscarriages in humans (though animal studies have suggested an increased risk) and evidence on the link between weed and low birth-weight is mixed.

Marijuana use during pregnancy has been linked, however, to up to 2.3 times greater risks of stillbirth.

The Ottawa Hospital study did not investigate how exactly marijuana use in pregnancy might lead to autism in a child, but scientists believe that the drug’s interaction with the so-called endocannabinoid system within the nervous system could play a role in the development of the behavioral condition.

 

Source:  https://www.eurekalert.org/pub_releases/2020-08/toh-cui080620.php

 

As a growing number of U.S. states legalize the medicinal and recreational use of marijuana, an increasing number of American women are using cannabis before becoming pregnant and during early pregnancy often to treat morning sickness, anxiety, and lower back pain. Although emerging evidence indicates that this may have long-term consequences for their babies’ brain development, how this occurs remains unclear.

A University of Maryland School of Medicine study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain’s dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence. This may contribute to the increased risk of psychiatric disorders like schizophrenia and other forms of psychosis later in adolescence that previous research has linked to prenatal cannabis use, according to the study published today in journal Nature Neuroscience.

The team of researchers, from UMSOM, the University of Cagliari (Italy) and the Hungarian Academy of Sciences (Hungary), found that exposure to THC in the womb increased susceptibility to THC in offspring on several behavioral tasks that mirrors the effects observed in many psychiatric diseases. These behavioral effects were caused, at least in part, by hyperactivity of dopamine neurons in a brain region called the ventral tegmental area (VTA), which regulates motivated behaviors.

More importantly, the researchers were able to correct these behavioral problems and brain abnormalities by treating experimental animals with pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.

The researchers concluded that as physicians caution pregnant women against alcohol and cocaine intake because of their detrimental effects to the fetus, they should also, based on these new findings, advise them on the potential negative consequences of using cannabis specifically during pregnancy.

Recent data from the Kollins lab (‘Cannabinoid exposure and altered DNA methylation in rat and human sperm’ Epigenetics 2018; 13: 1208–1221) indicated epigenetic effects of cannabis use on sperm in man parallel those in rats and showed substantial shifts in both hypo- and hyper-DNA methylation with the latter predominating. This provides one likely mechanism for the transgenerational transmission of epigenomic instability with sperm as the vector. It therefore contributes important pathophysiological insights into the probable mechanisms underlying the epidemiology of prenatal cannabis exposure potentially explaining diverse features of cannabis-related teratology including effects on the neuraxis, cardiovasculature, immune stimulation, secondary genomic instability and carcinogenesis related to both adult and pediatric cancers.

The potentially inheritable and therefore multigenerational nature of these defects needs to be carefully considered in the light of recent teratological and neurobehavioural trends in diverse jurisdictions such as the USA nationally, Hawaii, Colorado, Canada, France and Australia, particularly relating to mental retardation, age-related morbidity and oncogenesis including inheritable cancerogenesis. Increasing demonstrations that the epigenome can respond directly and in real time and retain memories of environmental exposures of many kinds implies that the genome-epigenome is much more sensitive to environmental toxicants than has been generally realized. Issues of long-term multigenerational inheritance amplify these concerns. Further research particularly on the epigenomic toxicology of many cannabinoids is also required.

Introduction

Physiology and pathobiology of the epigenome and its complex interactions with the genome, metabolome and immunometabolome, and cannabinoid physiopharmacology represents some of the most exciting areas of modern biological research. Type 1 and 2 cannabinoid receptors (CB1R and CB2R) are involved in a host of endogenous processes with potential therapeutic applications in numerous fields as diverse as pain, nausea, temperature regulation and weight control amongst others. Several recent detailed structural descriptions of the CB1R and CB2R complexed with high affinity agonists and antagonists, and pathways for the bulk biological synthesis of cannabinoids open the way to the rational design of high affinity molecules to differentially modulate these key receptors which are involved in a host of endogenous processes with diverse potential therapeutic applications. The use of exogenous cannabinoid compounds that bind to CB1R and CB2R may however also produce unwanted side effects including through modulation of DNA methylation states.

Within each nucleated cell, 2 m of DNA is normally stored coiled around four histones known as a nucleosome. A total of 147 bases of DNA are wrapped twice around two sets of H2A, H2B, H3 and H4 which together form the histone octamer. The bases of DNA itself may have a methyl group (CH3-) attached to them, usually to cytosine-phosphate-guanine (CpG), which when it occurs in the region of the gene promoter, blocks the transcription machinery and prevents the gene from becoming activated. The tails of the four histone proteins protrude from the central globular core and normally bind by electrostatic forces to the coiled DNA. Addition of an acetyl group to these histone tails, particularly on H3 and H4, disrupts the salt bridges opening up the DNA code for active transcription. Histone tails can also be methylated or indeed be modified by many groups (mono-, di- and trimethyl, acetyl, phosphoryl, crotonyl, citrulline, ubiquitin and ADP-ribosyl, etc.) which control gene transcription . DNA is transcribed into RNA some of which is made into the many proteins from which our bodies are made. However, much of the RNA also has purely informatic roles, and short and long non-coding RNA’s (ncRNA) controls DNA availability and transcription, RNA processing and splicing and can form a scaffold upon which layers of DNA regulation can be built. These various mechanisms, DNA methylation, post-translational modification of histone tails, nucleosome positioning, histone replacement, nuclear positioning and ncRNA’s form the basis of epigenetic regulation and appear to undergo an ‘epigenetic conversation’ amongst these different layers.

Chromatin loops are extruded through cohesin rings giving rise to transcription factories (topologically active domains) where different regions of the DNA including proximal promoters and distal enhancers are brought into close proximity to control transcription either on the same chromosome (in cis) or sometimes on nearby chromosomes (in trans). Super-enhancers, enhancer cross-talk, and extensive 3D remodelling of euchromatin looping during development are also described.

Moreover, a variety of studies in animals and several epidemiological studies in humans show that the epigenetic code can form a mechanism for inheritable changes across generations from both father and mother to subsequent generations which do not involve changes in the genetic code itself. Such epigenetic inheritance has been shown clinically for starvation, obesity, bariatric surgery and for tobacco and alcohol consumption. It has also been demonstrated in rodents for alcohol, cocaine and opioids, and in rodents’ immune system, nucleus accumbens and sperm following cannabinoid exposure in the parents.

If DNA is thought of as the cells’ bioinformatic ‘hardware’ then the epigenome can be considered its programming ‘software’. The epigenome controls gene expression and is key to cell differentiation into different tissue fates, different states of cellular differentiation, to cellular reprogramming into induced pluripotential stem cell states, cancer, numerous neuropsychiatric diseases including addiction, immune, metabolic and brain memory, aging, and the response of the cell to changes in its environment by way of gene-environment interactions including the development of so-called ‘epigenetic scars’.

This powerful informatic system has recently been shown to have a host of unforeseen capabilities. It has been shown that histone tails sense oxygen tension rapidly within 1 h with resulting modification of gene expression cassettes. Lysine (K) demethylase 5A (KDM5A) is a Jumanji-C domain containing molecular dioxygenase which is inactivated by hypoxia in a hypoxia-inducible factor-independent manner, controls H3K4me3 and H3K36me3 histone trimethylations and governs the transcriptome expression several hours after brief hypoxia. Similarly, KDM6A is also an oxygen sensitive dioxygenase and histone demethylase which controls H3K27me3. Its blockade by hypoxia interferes with cell differentiation and maintains cells in an undifferentiated state. Since the ten eleven translocase enzymes and are key demethylators of DNA and are dioxygenases also sensitive to profound hypoxia, and since hypoxia exists in most stem cell niches and at the centre of many tumours, such histone- and DNA-centred mechanisms are likely to be important in stem cell, aging, cellular differentiation and cancer biology.

Epigenomic regulation of tumour immunometabolome

Similarly, one of the great paradoxes of cancer biology is the presence within tumours of numerous effector T-cells which are able to expand and eradicate large metastatic tumours effectively, but do not do so within clinical cancers. It was recently shown that this effect is due to the very elevated nucleocytosolic potassium level within tumour lymphocytes which stalls metabolism and runs down acetyl-coenzyme A levels, the main acetyl donor for histone acetylation and induces a form of calorie restriction (like starvation) including autophagy and mitophagy and impairs the normal mTOR (mammalian target of rapamycin)-dependent T-cell receptor-mediated activation response. This program was mediated by reduced levels of H3K9 and H3K27 acetylation. Hence, tumour lymphocyte anergy and stemness were both mediated epigenetically and were shown to be reversible when the immunometabolic defect was corrected either genetically or by substrate supplementation. This work elegantly demonstrates the close relationship between the metabolic state of cells, cell differentiation state and starvation response, the control of cell fate by the epigenetic landscape and disease outcome.

Metabolomic supply of epigenetic substrate

Several studies similarly link the supply of metabolic intermediates required as inputs by the epigenetic machinery to epigenetic state and downstream gene control. Indeed, the well-known supplementation of staple foods by folic acid is believed to act because of the central role played by this vitamin in the methyl cycle and the supply of single carbon units to the methylation machinery for DNA and histones. A moments reflection shows that expression of the DNA of the mitochondria and the DNA of the nucleus need to be tightly coordinated to supply the correct number of subunits for the complex machineries of the mitochondrion including electron transport. This mitonuclear balance acts at several levels including RNA transfer, metabolic substrate (acetyl-coenzyme A, nicotinamide mononucleotide) transfer and the control of the epigenetic regulators PARP (polyadenosineribosyl polymerase) and Sirt1 (a major histone deacetylase).

Cannabinoid signalling impacts mitochondria

As noted above the identification of CB1R and CB2R on the plasma membrane has been a major milestone in cellular cannabinoid physiology. It is less well known that CB1R’s also exist on the mitochondrial outer membrane, and that the inner and outer leaflet of the mitochondria, together with the intermembrane space host the same cannabinoid transduction machinery as the plasmalemma. Neuronal mitochondrial CB1R’s have been implicated in memory and several critical neural processes. Hence, the well-substantiated findings that diverse cannabinoids generally suppress mitochondrial activity (in neurons, lung, liver and sperm), lower the mitochondrial transmembrane potential and interfere with oxidative phosphorylation carry major epigenetic implications not only for mitonuclear balance and trafficking including the mitochondrial stress response, but also for the supply of the requisite metabolic intermediates in terms of acetyl-coenzyme A which is an absolute requirement for histone acetylation and normal gene activation.

Histone serotonylation and dopaminylation

Serotonin, which has long been implicated in mood dysregulation and drug addiction was recently shown to act as a novel post-translational modification of the tail of H3 at lysine 4 via serotonylation where it increases the binding of the transcription machinery and allows correct cell differentiation. It is likely that dopamine will soon be similarly implicated.

Almost accompanying the modern bioinformatic explosion of knowledge related to the sequencing of the human genome has been a parallel increase in knowledge of the complexities and intricacies of epigenomic regulation. Nowhere is this more evident than in cancer. Indeed, it has become apparent that there are numerous forms of cross-talk, interaction and cross-regulation between the genome and the epigenome and the two are in fact highly inter-related. This is of particular relevance to chromosomal integrity and cancerogenic mechanisms. Several mechanisms have been described for such interactions including alterations of DNA methylation, altered cytosine hydroxymethylation, alteration of TERT function which is a key catalytic component of the telomerase enzyme which protects chromosome ends and altered architecture of enhancers and their looping interactions with promoters which control gene expression. Indeed, pharmacological modulation of the bromodomain ‘readers’ of epigenomic information has become a very exciting area within modern cancer therapeutic research , and forms an area into which large pharmaceutical companies are presently investing several billion dollars.

Gamete cannabinoid epigenomics – Murphy et. al

In this powerful context, the masterful epigenetic work from the Kollins laboratory of Murphy and colleagues was situated. These workers studied 12 control men who self-reported no psychoactive drug use in the last 6 months, and 12 subjects who reported more than weekly use of cannabis only, with all results confirmed by urine toxicology and ultra performance liquid chromatography/tandem mass spectrometry and enzyme immunoassay. In parallel two groups of 9-week-old male rats were administered solvent or 2 mg/kg THC by gastric lavage for 12 days prior to sacrifice and the epididymis was harvested. Sperm were assayed by the ‘swim out’ method where sperm swam out into normal saline bath solution. Cannabis exposed men had lower sperm counts, and it was found that there was differential sperm DNA methylation at 6,640 CpG sites including at 3,979 CpG islands in gene promoters where methylation was changed by more than 10% (which is alot). Significant changes were in both the hypomethylation and hypermethylation direction were noted with the changes in the hypomethylation group being more marked across the genome and at gene promoters. Pathways in cancer (including the BRAF, PRCACA, APC2 PIK3R2, LAMA1, LAMB1, AKT1 and FGF genes), hippo pathways (which are also important in cancer and in embryonic body pattern formation), the MAP kinase pathway (also involved in growth and cancer), AMPA, NMDA and kainate glutamate receptor subunits, and the Wnt genes 3A, 5A, 9A, 10A (involved in cancer and in body patterning and morphogensis) were found to be particularly affected. A dose–response effect was demonstrated at 183 CpG sites on 177 genes including the PTG1R gene which encodes the prostacyclin (a powerful vasodilator and antithrombotic agent) receptor which was down-regulated.

Twenty-three genes involved in platelet activation and 21 genes involved in glutamate metabolism were also modulated. LAMB1, whose gene product laminin B has been implicated in progeria and is increasingly implicated in genetic ageing pathways through its role in nuclear positioning of chromatin and the maintenance of heterochromatin (including female X-chromosome inactivation) in an inactive state inside the nuclear membrane, and its role in establishing integrity of the nuclear envelope, was also identified.

Results in the rats closely paralleled those found in humans. Fifty-five genes were found to overlap between altered sperm methylation patterns and a previous study of brain Nuclear Accumbens DNA methylation in prenatally cannaboid exposed rats which showing increased heroin self-administration, a highly statistically significant result. These results support the hypothesis that the transgenerational transmission of defects following pre-conceptual exposure to cannabis found in the immune system and limbic system of the brain including increased tendency for drug use in later life in rodents may be transmitted through alterations in the DNA methylation of the male germ line. More work is clearly needed in this area with exhaustive epigenetic, transcriptomic and genomic characterization of these results with larger sample sizes and in other species.

Cannabis – cancer links

Mechanistically these results have very far-reaching implications indeed and appear to account for much of the epidemiologically documented associations of cannabis use. Cannabis has been associated with cancer of the mouth and throat, lung, bladder, leukaemia, larynx, prostate and cervix and in four out of four studies with testicular teratomas with a relative risk of three in meta-analysis. Cannabis has also been implicated with increased rates of the childhood cancers acute lymphocytic leukaemia, acute myeloid leukaemia, acute myelomonocytic leukaemia, neuroblastoma and rhabdomyosarcoma.

These are believed to be due to inheritable genetic or epigenetic problems from the parents, albeit the mechanism of such transmission was not understood in the pre-epigenomic era. Results of Murphy and colleagues may potentially explain mechanistically much of the epidemiologically documented morbidity that has in the past been associated with cannabis use. As noted, cannabis contains the same tars as tobacco and also several known genotoxic compounds, and is also immunoactive. Such actions imply several mechanisms by which cannabis may be implicated in carcinogenic mechanisms.

That cannabis is associated with heritable paediatric cancers where the parents themselves do not harbour such tumours is suggestive evidence that non-genetic and likely epigenetic mechanisms are involved in the childhood cancers which are observed. Detailed delineation of such putative pathways will require further research.

Cannabis has also been shown to be associated with increased rates of gastroschisis in seven of seven studies to examine this association. This pathology, where the bowels of the neonate protrude through the abdominal wall usually to the right of the umbilicus, is believed to be due to a disruption of blood flow to the forming abdominal wall. If cannabinoid exposure powerfully activates platelets through multiple mechanisms and disrupts major vasodilator systems such as the prostacyclin receptor then such a pathway could well damage the tiny blood vessels of the developing foetus and account for the development of gastroschisis. Cannabis use in adults has been linked with both myocardial infarction and stroke possibly by similar mechanisms. It has been shown elsewhere that cannabis use can also stimulate inflammation and be proinflammatory.

Epigenomics of foetal alcohol syndrome

Indeed, foetal alcohol syndrome disorder (FASD) is said to be mediated in part by the CB1R , to be epigenetically mediated, and to comprise amongst other features small heads, microcephaly, impaired visuospatial coordination and to be commonly associated with ventricular septal defect and atrial septal defect all of which have been described in association with prenatal cannabis exposure. However, the facial features of FASD are not described in the congenital cannabis literature.

Cannabis and congenital anomalies

Indeed, one Hawaiian statewide epidemiological report found elevated rates of 21 congenital defects in prenatally cannabis exposed infants. Whilst this paper is unique in the literature it helps explain much about the presently reported patterns of congenital anomalies across USA in relation to atrial septal defect, Downs’ syndrome, Trisomy 18, ventricular septal defect, limb reduction defects, anotia, gastroschisis and autism, all of which crude rates are more common in states with liberal cannabis policies. Similar morbidity patterns were observed in Canada with crude rates of all congenital defects, gastroschisis, total cardiovascular defects and orofacial clefts more common in areas with higher cannabis use. The Colorado birth defects registry has also reported a three-fold increase in the crude (unadjusted) rate of atrial septal defects 2000–2014 spanning the period of cannabis legalization together with increases of 30% or more over the same period in crude rates of total cardiovascular defects, ventricular septal defects, Down’s syndrome and anencephaly. This is highly significant as atrial septal defect has only been found to be linked with cannabis in the Hawaiian study, suggesting that our list of cannabis-related defects is as yet incomplete. As mentioned above the putative link between atrial septal defect and cannabis use has also been found in the generality of states across the USA. It should also be noted that according to a major nationally representative recurrent survey the use of all other drugs in Colorado fell during this period, making cannabis the most likely pharmacological suspect for the surge in congenital anomalies.

These findings are also consistent with data arising from France, wherein three separate regions which have permitted cannabis to be used as feed for the dairy industry calves are born without legs, and an increase in the rate of phocomelia (no arms) in human infants has similarly been observed. In the French northeast region of Ain which is adjacent to Switzerland, the crude rate of phocomelia is said to be elevated 58 times above background, whilst in nearby Switzerland which has not permitted cannabis to be used as a feed crop no such anomalies are observed.

Neuroteratogenesis and beyond

The above comments in relation to epigenetic modulation of the glutamate system have been shown in recent studies to be related to many neuropsychiatric disorders. However, the recent demonstration at least in insects that glutamate could also act as a key morphogen in body patterning processes and major organ formation may have much wider implications well beyond the neuraxis Cannabis and epigenetic ageing.

The finding of overall DNA hypomethylation by Murphy’s group carries particular significance especially in the context of disordered lamin B metabolism. Chronic inflammation is known to be a major risk factor for carcinogenesis in humans in many organs including the skin, oropharynx, bronchi, lungs, oesophagus, stomach, pancreas, liver, biliary tree, colon, bladder and prostate. Inflammatory conditions are invariably strongly pro-oxidative and damage to DNA is not unusual. Because CpGs in gene promoters are more often largely unmethylated and therefore exposed the guanine in these positions is a common target for oxidative damage. Oxo-guanine is strongly mutagenic. This form of DNA damage recruits the maintenance DNA methyltransferase DNMT1 from the gene body to the gene promoter. There DNMT1 recruits Sirt1, a histone deacetylase which tends to epigenetically silence gene expression, and also EZH2 part of the polycomb repressive complexes 2 and 4 which epigenetically silences gene expression and tends to spread the silencing of chromatin. Hence, one of the end results of this form of oxidative DNA damage is to move the DNA methylation from the gene bodies to the gene promoters, thereby hypermethylating the promoters, the CpG Island Methylator Phenotype (CIMP) and hypomethylating the gene bodies and intergenic regions. By this epigenetic means chronic inflammation and tobacco smoke have been shown to induce widespread epigenomic field change right across tissues such as colon, bronchi or bone marrow. Furthermore, this mechanism moves gene expression from the control of histone modification to DNA methylation which tends to be more fixed and less plastic than histone alterations. Such findings are consistent with a previous demonstration of accelerated ageing in cannabis exposed clinical populations.

Epigenomic control of mobile transposable genetic elements

Reducing the global level of DNA methylation also has the effect of reducing the control of mobile transposable repeat elements in the genome. Forty-two per cent of the human genome has been shown to be comprised of these mobile elements of various varieties. Long Interspersed Repeat Elements (LINE-1) are believed to be retroviral repeat elements which long ago became incorporated in the genome and are able when expressed to induce their own reverse transcription back into the genome via endogenous reverse transcriptases. For this reason, they are also called ‘jumping genes.’ Because they become randomly incorporated into the genome after reverse transcription their activity is very damaging to genetic integrity. Whilst retrotransposon mobility is normally controlled by three mechanisms these defences can be overcome in advanced cellular senescence. The presence of double-stranded DNA (dsDNA) in the cytoplasm is strongly stimulating for the immune system and stimulates a type-1 interferon proinflammatory response, which further exacerbates the cycle and directly drives the Senescence Associated Secretory Phenotype (SASP) of advanced senescence and the ‘inflamm-aging’ which is well described in advanced age. Accelerated ageing in patients exposed clinically to cannabis has previously been described using a well validated metric of arterial stiffness. Whilst neither Murphy nor Watson found evidence following cannabinoid exposure for altered methylation of repeat elements the presence of chronic inflammation in the context of widespread preneoplastic change and documented neoplasia suggest that this newly described ageing mechanism might well merit further investigation.

These changes are likely exacerbated by several classical descriptions that cannabinoids reduce the overall level of histone protein synthesis. Since the overall length of DNA does not change this is likely to further open up the genome to dysregulated transcription. Severe morphological abnormalities of human and rodent sperm have been reported.

Similarly classical descriptions exist of grossly disrupted mitoses, particularly in oocytes, which are said to be seriously deficient in DNA repair machinery. Morishima reported as long ago as 1984, evidence of nuclear blebs and bridges due to deranged meiotic divisions in cannabinoid-exposed rodent oocytes . Similar blebs and bridges have been reported by others. It has since been shown that these nuclear blebs represent areas of weakness of the nuclear membrane which are often disrupted spilling their contents into the cytoplasm. They are also a sign of nuclear ageing.

Cannabinoids and micronuclei

Cannabis has long been known to test positive in the micronuclear assay due to interference with the function of the mitotic spindle. This is a major cause of chromosomal disruption and downstream severe genetic damage in surviving cells, has previously been linked with teratogenesis and carcinogenesis, and which is also potently proinflammatory by releasing dsDNA into the cytoplasm and stimulating cGAS-STING (Cyclic GMP-AMP synthase – STimulator of INterferon Gamma) signalling and downstream innate immune pathways.

Cytoplasmic dsDNA has also been shown to be an important factor driving the lethal process of cancer metastasis.

Cannabis and wnt signalling

The findings of Murphy in relation to Wnt signalling are also of great interest. It has been found by several investigators that prenatal cannabis exposure is related to encephalocoele or anencephaly defects. Non-canonical Wnt signalling has been shown to control the closure of the anterior neuropore providing a mechanistic underpinning for this fascinating finding. Wnt signalling has also been implicated in cancer development in numerous studies and in controlling limb development which have been previously linked with cannabis exposure (as noted above).

Cannabis and autism

It was recently demonstrated that the rising use of cannabis parallels the rising incidence of autism in 50 of 51 US states and territories including Washington D.C., and that cannabis legalization was associated with increased rates of autism in legal states. Several cannabinoids in addition to Δ9-tetrahydrocannabinol (THC) were implicated in such actions including cannabidiol, cannabinol, cannabichromene, cannabigerol and tetrahydrocannabivarin. A rich literature demonstrates the impacts of epigenomics on brain development and its involvement in autistic spectrum disorders. Whether cannabis is acting by epigenetic or other routes including those outlined above remains to be demonstrated. Further research is indicated.

Cannabidiol and other cannabinoids

These findings raise the larger issue of the extent to which the described changes reflect the involvement of THC as compared to other cannabinoids in the more general genotoxicity and epigenotoxicity of both oral (edible) and inhaled (smoked) cannabis. THC, cannabidiol, cannabidivarin, and cannabinol have previously been shown to be genotoxic to chromosomes and associated with micronucleus development. American cannabis has been selectively bred for its THC content and the ratio of THC to cannabidiol (CBD) was noted to have increased from 14:1 to 80:1 1998–2018. However in more recent times, cannabidiol is being widely used across the USA for numerous (nonmedical) recommendations.

Cannabidiol is known to inhibit mitochondrial oxidative phosphorylation including calcium metabolism which is known to have a negative effect on genome maintenance and is believed to secondarily restrict the supply of acetyl and other groups for epigenetic modifications. Cannabidiol is known to act via CB1R’s particularly at higher doses. Cannabidiol acts via PPARγ (Peroxisome Proliferator Activator Receptor) which is a nuclear receptor which is implicated in various physiological and pathological states including adipogenesis, obesity, diabetes, atherogenesis, neurodegenerative disease, fertility and cancer. In a human skin cell culture experiment, cannabidiol was shown to act via CB1R’s as a transcriptional repressor by increasing the level of global DNA methylation by enhancing the expression of the maintenance DNA methylase DNMT1 which in turn suppressed the expression of skin differentiation genes and returned the cells to a less differentiated state. One notes, importantly, that this DNA hypermethylation paralleled exactly the changes reported by Murphy for THC hypermethylation. The de-differentiation reported or implied in both studies is clearly a more proliferative and proto-oncogenic state. Hence, while more research is clearly required to carefully delineate the epigenetic actions of cannabidiol, its activity at CB1R’s, its mitochondrial inhibitory action, its implication of PPARγ and particularly its THC-like induction of epigenetic and cellular de-differentiation, together with its implication in chromosomal fragmentation and micronucleus induction would suggest that caution is prudent whilst the results of further research are awaited.

Other cannabinoid receptors and notch signalling

The above discussion is intended to be indicative and suggestive rather than exhaustive as the cannabinoids’ pharmacological effects are very pleiotropic, partly because CB1R’s, CB2R’s – and six other cannabinoid sensing receptors are widely distributed across most tissues. One notes that the mechanisms described above do not obviously account for very important finding that in both Colorado and Canada increasing rates of cannabis use were associated with higher rates of total congenital cardiovascular disease. One observes that in both cases the cited rise in rates refers to an elevation of crude rates unadjusted for other covariates. This finding is important for several reasons not the least of which is that cardiovascular disease is the commonest class of congenital disorders. It may be that this action is related to the effects of cannabinoids binding high-density endovascular CB1R’s from early in foetal life and interacting with the notch signalling system. Notch is a key morphogen involved in the patterning particularly of the brain, heart, vasculature and haemopoietic systems and also in many cancers. Notch signalling both acts upon the epigenome and is acted upon by the epigenome both in benign (atherosclerotic and haemopoietic) and cancerous (ovarian, biliary, colonic, leukaemic) diseases. Clearly in view of their salience, the interactions between cannabinoids and both notch and Wnt signalling pathways constitute fertile areas for ongoing research.

Conclusion

In short the timely paper by Murphy and colleagues nicely fills the gap between extant studies documenting that pre-conception exposure to cannabis is related to widespread changes in epigenetic regulation of the immune and central nervous systems and confirms that male germ cells are a key vector of this inheritance and has given new gravity to epidemiological data on the downstream teratological manifestations of prenatal cannabinoid exposure. The reasonably close parallels in findings between rats and man confirm the usefulness of this experimental model. Since guinea pigs and white rabbits are known to form the most predictive preclinical models for human teratogenicity studies it would be prudent to investigate how epigenomic results in these species compared to those identified in man and rodents. Finally the considerable and significant clinical teratogenicity of cannabis, including its very substantial neurobehavioural teratogenicity imply that such studies need to be prioritized by the research community and the research resourcing community alike, particularly if the alarming findings of recent European experience in terms of cannabinoids allowed in the food chain is not to be repeated elsewhere. Indeed, the recent passage of the nearly $USD1trillion USA Farm Act which encourages hemp to be widely grown for general use together with the advent in some US cafés of ‘hempburgers’ and ‘cannabis cookies’ would appear to have ushered in just such an era. Hemp oil has recently been marketed in Australian supermarkets completely unsupervised. Meanwhile, the rapidly accumulating and stellar discoveries relating to the pathobiology of the epigenome and its remarkable bioinformatical secrets continue to be of general medical and community importance. In some areas, particularly relating to the epigenotoxicology of the non-THC cannabinoids, further research is clearly indicated, especially in view of the widespread use and relatively innocuous reputation of cannabis derivates including particularly cannabidiol.

Such issues suggest that in the pharmacologically exciting era of the development of novel intelligently designed cannabinoids intended for human therapeutics, considerations of genomic and epigenomic toxicity including mutagenicity, teratogenicity, carcinogenicity, pro-ageing and heritable multigenerational effects warrant special caution and attention prior to the widespread exposure of whole populations either to phytocannabinoids or to their synthetic derivatives. Equally, the possibility of locus-specific epigenetic medication development as modifiers of the epigenetic reading, writing and erasing machinery suggests that very exciting developments are also beginning in this area.

Author Note

While this paper was in review our paper examining the epidemiological pattern and trends of Colorado birth defects of 2000-2014 and entitled “Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends” was accepted by the journal Clinical Pediatrics. It provides further details and confirmation on some of the issues discussed in the present paper. It also contains a detailed ecological investigation of the role of cannabidiol at the epidemiological level which confirms and extends the mechanistic observations and the quantitative remarks relating to the epidemiology of birth defects in Colorado made in the present manuscript. The interested reader may also wish to consult this resource.

Source: https://www.tandfonline.com/doi/full/10.1080/15592294.2019.1633868 July 2019

Why don’t we start with a short quiz of general knowledge of current events and topical issues in the community??

 Questions:

 Brain:

Which American state has 500 students with autism in every graduating year group across the whole state?

Which American state has current legislation afoot to declare autism at epidemic proportions in their state?

Which American state has the fastest growing autism epidemic by recent metrics (at 30% every two years)?

Which smoked illegal drug is now linked with causing strokes???

Which smoked illegal drug is linked with causing most major psychiatric diseases – including schizophrenia, bipolar disorder, depression and anxiety.

Which illicit drug is known to cause failure of achievement of major life goals – forming a long term stable relationship, getting a job, having a career, paying tax???

In which US state have city after city been trashed by out of control mental illness, drug use, homelessness, poverty and law enforcement and social relief services completely overwhelmed?

 Heart:

Which American state is amongst the top four for rates of children born with holes in their heart (known as atrial septal defect)?

In which American state did the rate of holes in the heart (atrial septal defect) increase more than threefold from 299 to 912 cases 2000-2012?

Which smoked illegal drug is now recognized to cause heart attacks?

Which illegal drug is known to stop the heart by causing major cardiac arrythmias?

 Head:

Which two American states share the highest rates of children born without ears or with tiny little ears (like peas – called anotia or microtia)???

 Chromosomes:

Which four American states have the highest rates of Downs syndrome in the nation??

What do all four of these states have in common??

Which American state has the highest rates in the nation for all four major chromosomal abnormalities of birth namely Trisomies 13, 18, 21 (Down’s syndrome) and Turner’s syndrome???

 Limbs:

Which are the two leading states for babies born without arms??

What do these two states have in common??

 Drugs:

Drug use is known to damage babies when they are growing inside their mothers. 

In which leading American state, which was also home to most of the above waves of recent deformed babies, was the rate of all drug use actually falling – all except one drug.  Which state was that?

And which drug was the exception??

 Cancer:

Drug use is well recognized as leading to cancer in many organs.  This is widely recognized for both tobacco and alcohol. 

Which drug has been linked with causing cancer of the testicles in 100% of the studies – four out of four – which have examined this question?

Which is the only illicit drug linked to four inheritable cancers in the children born to infants exposed in utero exposed?

Which drug was examined in detail in a 150 page report by the Californian environmental Protection agency and found to be a proven carcinogen in 2009?

Why are virtually all carcinogens considered teratogens – known to harm developing babies?

 Reproduction:

Which smoked illicit drug causes major genetic damage to both eggs and sperm?

Which smoked illicit drug reduces fertility in both males and females?

Our genes not only carry our DNA sequence, but also the software which programs those genes and turns them on and off – which scientists call the “epigenome”. 

Which smoked illicit drug is known to damage the epigenome?

For how many generations does epigenetic inheritance continue?

Is this period more or less than 100 years???

 

 Answers:

 The above series of questions relate to the recent experience of the US state of Colorado following its progressive legalization of cannabis over the period 2000-2014. 

If you answered “Colorado” to most of the questions about congenital defects you were correct.  The two exceptions were the question about babies born without limbs – the two commonest US states for these defects are Alaska and Oregon; and babies born with tiny ears – which are Alaska and Oregon.

 The leading states for cannabis use according to major recent US surveys are Colorado, Alaska, Oregon, Maine, Vermont and Washington.  Scarily Alaska comes at or near the top of the list for: Down’s syndrome, atrial septal defect (ASD), ventricular septal defect (VSD) a defect called Encephalocoele where babies are born with a big bubble blown out the back of their skull where the neck joins, no arms, no ears and gastroschisis which is where the bowels are hanging out.  Colorado leads or co-leads the charge on the three chromosomal trisomies trisomy 21, 18 and 13 and no ears (anotia).  The four states which lead the pack on Downs syndrome are all cannabis liberal states: Colorado, Alaska, Oregon and Massachusetts.

 Downs syndrome, ASD and VSD are relatively common congenital defects.  Congenital defects as a whole affect around 3% of the community – unless you live in Colorado which up until September 2018 reported a major congenital abnormality rate four times higher than that at 12.6%.  One notes that after that the problem “went away” because the state then changed all of their official congenital anomaly figures for the past 15 years after attention was drawn to these facts internationally.

And one cannot attribute these severe changes in Colorado to the use of other drugs as the national survey showed that the use of most other drugs has actually fallen across this recent period.  So it is obviously a cannabis signal.

 This strong “red flag” warning signal for cannabis also shows up loud and clear in the US nation’s leading mental health survey where cannabis use grew most strongly across the nation in the 18-25 year age group, which was also the age group with by far the worse mental health, which was also declining most rapidly.  This implies that the decline in both the US nation’s minds and their gene pool is occurring in close relationship to cannabis use both across the nation geographically, across time with temporal variability, and also within defined demographic groups.

Cannabis is known to damage the epigenome of the sperm in a way which affects brain heart and immune development and has also been traced in human foetal tissue from live born babies.  This damage is presently believed to be inheritable for four generations or 100 years.  Scientists are very concerned about this serious risk.  In one study over 6,000 sites of DNA methylation were affected and thus reprogrammed, and that is a substantial number compared to our around 25,000 genes.

And most worryingly it was recently reported from Ain in the east of France near the Swiss border that the incidence of babies born without arms is 58 times higher than the normal background.  And the same thing was seen in the cattle in the area.  However this was not seen in nearby Switzerland where it is not permitted to add hemp to the food chain via stock feed.  Cannabis has previously been linked with such defects in a major Hawaiian study of over 300,000 births published in 2007.

Most of the cannabis teratological literature is fairly conservative.  The Centres for Disease Control in Atlanta Georgia have admitted in 2014 that cannabis is linked with four defects – no brain (anencephaly – babies die within an hour or two mostly), bowels having out (|gastroschisis) diaphragmatic hernia and oesophageal atresia with or without tracheooesophageal fistula.  The American Academy of paediatrics has issued a position statement in 2007 saying that both ventricular septal defect (holes in the heart) and Ebsteins anomaly (damaged tricuspid valve) are known to be linked with cannabis use. 

And the three longitudinal studies of babies born after prenatal cannabis exposure presently being conducted in Pittsburgh, Ottawa and Netherlands, all very consistently find persistent and subtle brain damage of executive functioning to be major issues.  This finding in three nations is the most concerning and likely by far the most common of all.

Certainly physicians in both Colorado and in Australia are seeing just this pattern of subtle brain abnormalities in the patients who present to our clinics.  This is therefore the most concerning aspect of the cannabis free for all which is being falsely foisted on the west by a relentless media mantra.  If India has its holy cows, then the theistically allergic media are no less as enamoured with their own devoutly protected “deep green god” – regardless of the painfully obvious fallout.

Most worryingly of all – consider these few final major issues.  Of the two perspective described above – the conservative one espoused by well recognized international authorities – and the more worrying picture of 21 defects reported from the massive epidemiological Hawaiian study – which one is the more correct – especially in an era when as is widely known cannabis, cannabis oils and hashish butane oils are rapidly becoming so much more concentrated than in past eras??  It is said that the most stringent test of any theory is its ability to make predictions about future events.  By this criterion only the 2007 Hawaiian report by Forrester predicted the links in Ain in France with the armless defect, and the patterns of chromosomal abnormalities, atrial septal defect and anotia / microtia across USA.  In this important respect then the Forrester – Menz report is more accurate – and of course much more concerning – than the “standard received wisdom”.  It appears to be acting as a kind of a roadmap – as the tide both of cannabis use and of cannabis concentration – rises all around us.

And most concerning of all is that many papers in the cannabinoid genotoxicity literature show an exponential relationship between cannabis dose exposure and the genotoxic damage which is directly responsible for cancers in patients, their children and foetal abnormalities including mental retardation and brain damage.  That is to say that beyond a certain threshold dose doubling the exposure produces not twice as much genetic damage- but 10-20 times as much. Cannabis use during pregnancy has been linked with the following four cancers which are all believed to be due to genotoxic damage uncurred during in utero exposure: acute lymphatic leukaemia, acute myelomonocytic leukemia, neuroblastoma and rhabdomyosarcoma.

 It is very important to appreciate that these concerns relate not just to Δ9 -tetrahydrocannabinol itself, but, since cannabis contains at least 108 cannabinoids, all of them have been implicated in genotoxic damage through the above mentioned epidemiological studies.  Studies in animals and cells have found that cannabidiol, cannabinol, cannabidivarin and cannabichromene – at least – all have direct genotoxic and / or epigenetic effects which are of great concern.  In many cases this effect is worse than that observed with Δ9 -tetrahydrocannabinol.  They all also damage mitochondrial function which exerts severe indirect genotoxicity partly by limiting energy supply to growing, dividing and metabolically active tissues, and partly by close and multichannel signaling from the mitochondria directly to the nucleus and its architecture and genetic management machinery.

And… despite what one might think from the deafening silence from the popular press, the genotoxicity of cannabinoids is not even controversial!  Serious warnings relating to reproductive health are prominently featured in the formally registered patient information inserts for both cannabidiol “Epidiolex” and the cannabidiol / THC mixture “Sativex”.

All of which paints an horrific and ghoulish picture of the drug-wrecked future.  In the USA it is obvious that the guardians of the culture are radically missing in action.  CDC which is charged with protecting the public health; FDA which are charged with protecting the food and pharmaceutical supply and the USA President all seem be absent from the foray.  One can only wonder why…  Intimidated??  Cultural groupthink??  Personal money at stake?? Careers on the line??

My father always taught me:  “If everybody else was jumping over a cliff, would you jump to??”  Paradoxically indeed in 1958 it was the FDA which protected the USA from the holocaust that became the completely avoidable international thalidomide teratogenesis epidemic, whilst societies in Australia, England and in Europe were duped and succumbed to the commercial marketing campaign and the deliberate subversion of the then known truth.  Cannabis was recently been found to be recommended to 78% of pregnant women in Colorado.  Just as in that era, thalidomide was also used for anxiety, sleeplessness, nausea, unwellness and “dis-ease”.  Today America has obviously succumbed to the siren voice of the modern media darling – the “green holy cow” of the west. 

 One can only wonder if anyone in this country has the courage to see the obvious and call “Enough Already” and insist that our public agencies do their duty and discharge their office with honour.       Dr. Stuart Reece.

Source:  January 2019 edition of Family World News

 

MEDICINAL cannabis is no better than conventional drugs for treating children with severe epilepsy, according to a top Victorian doctor.

After months of treatment, none of the 29 Victorian children accessing $1 million worth of medicinal cannabis product, imported from Canada, has been seizure free.

FIRST COMMERCIAL CANNABIS CROP TO HELP VICTORIAN CHILDREN

UNIVERSITY OF MELBOURNE GETS $500K FROM TURNBULL GOVERNMENT FOR RESEARCH INTO MEDICINAL CANNABIS PLANTS

Paediatric neurologist Professor Ingrid Scheffer told the Sunday Herald Sun medicinal cannabis had been effective in some of the cases by reducing fits among some of the group.

However, the results had been similar to outcomes achieved on other pharmaceutical drugs and it was not the miracle solution families were hoping for

Families hear the news kids who need cannabis to help with chronic illness will gain access. Picture: Jason Edwards

“Initially we all had a sense of hope but that didn’t last but that is the nature of these diseases,” Prof Scheffer said.

For more http://www.heraldsun.com.au/news/victoria/medicinal-cannabis-not-miracle-epilepsy-drug-says-professor-treating-victorian-children/news-story/9107a6249aec2e59a7c0a49f6c8b0b71 October 2017

When people like the headline writer of this HealthDay news article talk about “medical marijuana,” they usually mean everything. The plant’s dried flowers which people smoke. Concentrates that can contain up to 90 percent THC, whose extraordinarily high levels are almost certainly what is sending toddlers and children who accidentally consume them and adults who consume them on purpose to emergency rooms with many needing to be hospitalized. “Edibles” – cookies, candies, and soft drinks infused with marijuana that are now in the food chain. And hundreds more, all sold as “medicines.”

 
The HealthDay author does a good job of covering a new study in Pediatrics, the journal of the American Association of Pediatrics. But notice the study’s title: “Medical Cannabinoids – not Medical Marijuana – in Children and Adolescents: A Systematic Review.”
 
What’s the difference?  
 
The marijuana plant contains about 500 different chemicals. Most have not been studied. Some 100 of those are called cannabinoids, so-called because they are unique to the cannabis plant. Most of these have not been studied either, but that is changing. Some cannabinoids show scientific promise and may become medicines. Two already are.
 
By medicines, we mean they have gone through rigorous preclinical (test tubes and animals) and clinical (humans) research. They have proven to FDA that they are both safe and effective, can be manufactured with a consistent dose, and most importantly are pure. They contain no contaminants unlike most of the products in legal states. A further FDA safeguard is that sometimes approved medicines cause dangerous side effects in the larger population after approval. FDA has a notification system that requires doctors to report any that occur so the medicine can be pulled from the market, if necessary.
 
The most studied cannabinoids are delta-9 THC and cannabidiol (CBD). The former makes people high. The latter doesn’t. The two medicines that FDA has approved are nabilone (trade name Cesamet®) and dronabinol (trade names Marinol® and Syndros®). Cesamet® and Marinol® are pills. Syndros® is an oral liquid. They are used to reduce chemotherapy-related nausea and AIDS wasting in patients who do not respond to standard medications.
 
Two more cannabinoids, nabiximols (trade name Sativex®, approved in other countries but not yet in the US yet) and CBD (trade name Epidiolex® which has completed clinical trials and is applying for FDA approval) are in the pipeline.
 
About half our medicines originated in plants. But when drug makers create a new medicine from them, they use pure chemicals to make a molecule-for-molecule carbon copy of the plant’s component. Nabilone and dronabinol are made that way. Patients know when they take these medicines that they will not contain any contaminants and FDA has approved them.
 
Not so the “medical” marijuana products being produced and sold in states that have legalized the drug for medical use. In fact, the American Epilepsy Society calls such CBD products “artisanal CBD” to differentiate them all from Epidiolex®, which may be available as early as next year to treat children and adolescents suffering intractable seizures.
 
Not one of the marijuana products states allow to be sold as medicines has been approved by FDA.
 
This new study searched several databases for scientific articles about pharmaceutical-grade cannabinoids that are being studied to treat a variety of illnesses in children and adolescents. They found 2,743 citations that might meet their search criteria and reviewed the full texts of 103. From these, they found 21 articles about 22 studies with a total sample of 795 participants: 

  • Five were randomized controlled trials, the gold standard of knowledge development.
  • Five were retrospective chart reviews.
  • Five were case reports.
  • Four were open-label trials.
  • Two were parent surveys.
  • One was a case series. 

The medicines used in these studies were nabilone, dronabinol, Epidiolex®, a formulation of delta-8 THC, and other pharmaceutical-grade preparations, not Charlotte’s Web, Haleigh’s Hope, Cannatol, or any of the hundreds of other artisanal CBD products states allow to be shipped – and Amazon sells – to all 50 states in violation of federal law.
 
The researchers found that in children and adolescents:

  • “Evidence for benefit was strongest for chemotherapy-induced nausea and vomiting (four RCTs), with increasing evidence of benefit for epilepsy [1 RTC using Epidiolex® rather than artisanal products]. At this time, there is insufficient evidence to support use for spasticity, neuropathic pain, posttraumatic stress disorder, and Tourette syndrome.
  • “The methodological quality of studies varied, with the majority of studies lacking control groups, limited by small sample size, and not designed to test for the statistical significance of outcome measures. Studies were heterogeneous [varied] in the cannabinoid composition and dosage and lacked long-term follow-up to identify potential adverse effects.
  • “Additional research is needed to evaluate the potential role of medical cannabinoids in children and adolescents, especially given increasing accessibility from state legalization and potential psychiatric and neurocognitive adverse effects identified from studies of recreational cannabis use.” 

Read HealthDay account of this study here.
Read American Association of Pediatrics study abstract here.
Read what Colorado Children’s Hospital tells families who want artisanal CBD for their children here.

Source: Email from National Families In Action http://www.nationalfamilies.org October 2017

Strongest evidence supports use to reduce seizures, side effects of chemotherapy

A systematic review of published studies on the use of medical cannabis in children and adolescents finds a notable lack of studies and a minimal number of the randomized, controlled trials needed to confirm the effectiveness of a treatment. In their paper published in the journal Pediatrics, Massachusetts General Hospital (MGH) investigators Shane Shucheng Wong, MD, and Timothy Wilens, MD — both of the MGH Department of Psychiatry — report that their review suggests only two pediatric uses of medical cannabis — to relieve chemotherapy-induced nausea and vomiting and to reduce seizures — are supported by existing studies.

“Medical cannabis is now legal in 29 states and the District of Columbia, and in those areas with active programs, children and adolescents can legally access medical cannabis with certification from their doctor and consent from a parent or guardian,” says lead author Wong. “This means that doctors and families need to understand what we know and what we don’t yet know about medical cannabis in order to make the best decision for the health of the individual child.”

Two synthetic cannabinoids — compounds that act on specific receptors in the brain — have been approved for medical use in the U.S., both of which mimic a form of THC (tetrahydrocannabinol), the compound responsible for the “high” of recreational cannabis use. Dronabinol (Marinol) is approved to treat chemotherapy-induced nausea and vomiting in both children and adults, while the pediatric use of nabilone (Cesamet) carries a caution. A third cannabinoid, cannabidiol, is currently in phase 3 trials for treatment of seizures.

The researchers followed established procedures in searching for studies of medical cannabis use listed in major research indexes and selected out those that primarily enrolled participants aged 18 and under and included original data about a clinical use. Only 21 papers reporting on a total of 22 studies met their criteria. The papers were published from 1979 to 2017, 14 within the last five years. Only 5 were randomized controlled trials, the others being case reports, open-label trials, parent surveys or case series. The most common conditions studied were chemotherapy-induced nausea and vomiting (6 studies) and seizures (11 studies).

The trials for chemotherapy side effects — 4 of which were randomized controlled trials — found that medical cannabis was significantly better than anti-nausea drugs standard at the time of study for reducing nausea and vomiting. Similarly the epilepsy studies, including a single randomized trial, found that medical cannabis reduced the frequency of seizures in participants, some with treatment-resistant seizures. Limitations of these studies include lack of a control group for many, small sample size, differences in the medications used and lack of long-term follow-up.

Two studies investigating the use of cannabis for spasticity and three case report on use for neuropathic pain, post-traumatic stress disorder or Tourette syndrome all lacked controls or blinding, conferring a high risk of biased findings. “At this time,” Wong says, “we do not have good evidence that cannabis can be useful in children and adolescents for any conditions other than seizures or chemotherapy-induced nausea and vomiting.”

He and Wilens also note that decisions regarding medical cannabis use need to weigh the likely benefits against the known risks, which — based on the results of studies in recreational cannabis users — are probably even greater for children and adolescents. Their still-developing brains may make them even more vulnerable than adults to cannabis’s negative effects on learning, memory, attention and problem solving. Additional research is needed to better understand the risks and long-term effects of cannabis-based drugs in this population.

When asked how he would advise the parents of a child with a condition that could be alleviated with medical cannabis, Wong states, “I would recommend they have a thorough discussion of the risks and benefits with a physician who has specialized knowledge and experience in the area. For chemotherapy side effects, that could be a pediatric oncologist or palliative care specialist; for seizures, that could be a pediatric neurologist, especially at an academic medical center involved in the ongoing clinical trials of medical cannabis for seizure disorders.”

Source: https://www.sciencedaily.com/releases/2017/10/171023094606.htm October 2017

Waiheke Island lawyer and meth researcher Chloe Barker is thrilled to see Jacinda Ardern, who acted on her findings, become Prime Minister.

For her Master’s thesis, Barker carried out heart-breaking research on the impacts on children of growing up in methamphetamine laboratories in New Zealand.

She found that through contact with contaminated environments, children sometimes had levels of meth in their hair, blood and urine that were higher that that of addicts.

Although the impacts on children are devastating, the laws are “toothless” and often fail to protect them, Barker said.

After her research findings were published in a police magazine in 2012, Jacinda Ardern contacted her and suggested meeting over coffee.

“She was amazingly passionate and obviously really cared about the issue,” Barker said.

A Labour list MP at the time, Ardern arranged for broader publication of Barker’s research, helping to raise awareness of the issue.

Ardern cited Barker’s research in parliament to support law changes to make it a crime for people to manufacture meth when a child is present.

However, the Sentencing (Protection of Children from Criminal Offending) Amendment Bill never made it into law.

Police can prosecute meth manufacturers under general child abuse laws, but the rates of conviction are low, because it is hard to prove children have been intentionally harmed by P [methamphetamine] manufacture, Barker said.

Ardern campaigned for a protocol to be introduced assigning responsibilities to the police and Child, Youth and Family (CYF) when children are found in P labs. New protocols have since been developed.

“I was really impressed that she had a million things on her plate, but she cared enough to be proactive and make practical changes that have assisted the police.

“I’m absolutely stoked about Jacinda becoming the Prime Minister.

“I think she’s going to give a voice to a lot of people who don’t have a voice currently,” Barker said.

Examining police files, Barker found that from 2006 to 2010, 191 children were living in the presence of methamphetamine laboratories that were shut down by police.

In 2002, children were living in 34 percent of the houses where laboratories were discovered.

The dangers of growing up in P laboratories include exposure to toxic chemicals, risks of explosions and fires, and a higher likelihood of having weapons in the house.

Children in meth laboratories also face higher risks of physical, sexual and emotional abuse, she said. 

“Given everybody can clearly see the dangers to children, there should be a specific law that says if you cook meth in the presence of a child, you’re committing a crime,” Barker said.

The 39-year-old has returned to her full time job as a commercial lawyer after completing her Master of Forensic Science degree at the University of Auckland.

Barker said Ardern won’t provide a “magic answer” for all life’s ills, but she is hopeful children might yet get the legal protection from meth exposure that they deserve.

“There is obviously a problem with P on Waiheke and I’m sure there are lots of communities around New Zealand that are exactly the same,” she said. 

Source: https://www.stuff.co.nz/national/politics/98147222/meth-researcher-thrilled-with-new-prime-minister October 2017

Research on children living in homes used as methamphetamine labs confirms police concerns over the risks. Ellen Brook reports.

The worrying trend of young children living in meth labs and being exposed to toxic chemicals has been highlighted in a research project with support from the Police National Clan Lab Response team in Auckland.

Auckland lawyer Chloe Barker, who analysed Police and ESR (Environmental Science and Research) data related to children and clandestine (clan) labs as part of a master’s degree thesis last year, has raised the red flag on the risks for young children. Her conclusions not only back up anecdotal evidence from police officers, but go on to say that existing child abuse laws are inadequate for prosecuting offenders.

Ms Barker’s research, based on Police data from 2006 to 2010, showed that dozens of children, with an average age of six years, were exposed to clan lab activity each year. On average, children were living or present in 25 per cent of New Zealand meth labs, rising to 34 per cent in 2010.

Latest figures show that of the 94 clan labs located in 2012, children were in 27 of them; 45 children were identified and 25 were present at the time police found the labs.

Other findings included:

  1. About a quarter of the labs where children were present were either “A” or “B” grade, ie, “up and bubbling” or ready to use.
  2. Weapons were found in about 36 per cent of the labs in which children were present.
  3. There was a higher proportion of gang affiliation for labs in which children were present than in total meth labs (51% compared with 43%).
  4. Fires and explosions occurred in 16 labs between 2006 and 2010, two of which had children present.
  5. The percentage of labs in which children were living or present and in which one or more referrals were made to Child, Youth and Family increased from about 5 per cent in 2006 to 93 per cent in 2010.

A more detailed audit of police files from 2008-2009 gave an even more disturbing picture of the dangers children were exposed to.

  1. In 21 per cent of labs there was evidence that children were present during the manufacturing process.
  2. In 45 of 53 labs reviewed there was evidence of chemicals within reach of children.
  3. In 36 of 53 labs, chemicals were stored in food or drink containers. In one case, a child’s school drink bottle, complete with a name and school room number, was found to contain highly acidic chemicals.

Source: https://www.policeassn.org.nz/newsroom/publications/featured-articles/meth-kids March 2013 

This week, the Rocky Mountain High Intensity Drug Trafficking Area released its fifth annual report titled The Legalization of Marijuana in Colorado: The Impact, Volume 5. We devote today’s issue of The Marijuana Report newsletter to highlighting a few of many significant findings the report contains.

National Families in Action has remade some of the graphs and charts in the report to emphasize key findings. This one shows how many of Colorado’s students were expelled, referred to law enforcement, or suspended in the 2015-2016 school year. This is the first year the Colorado Department of Education differentiated marijuana violations from all drug violations, and this year’s report will serve as a baseline to determine whether marijuana violations increase, decrease, or stay fundamentally the same.

Read The Legalization of Marijuana in Colorado: The Impact, Volume 5 here. This information appears on page 41 (PDF page 49).
The new report explains that although Colorado created its own Healthy Kids Survey, the combination of a poor response rate and the fact that several major counties with large populations had low or no participation rendered the 2015 survey’s results invalid. For a discussion of this see page 33 (PDF page 41). Volume 5 relies on the National Survey on Drug Use and Health to compare Colorado marijuana use with the national average for ages 12-17, 18-25, and 26 & older over a ten year period (2005-2006 to 2014-2015).

See data for these graphs on the following pages:

  • Ages 12-17, page 36 (PDF page 44)
  • Ages 18-25, page 56 (PDF page 64)
  • Ages 26 & Older, page 60 (PDF page 68)

Read The Legalization of Marijuana in Colorado: The Impact, Volume 5 here.
The report notes that data from the National Highway Traffic Safety Administration, 2006-2011 Fatality Analysis Reporting System (FARS), and 2012-2016 Colorado Department of Transportation show that drivers testing positive for marijuana who were killed in traffic crashes rose from 6 percent of all traffic deaths in 2006 to 20 percent eleven years later. Marijuana-related traffic deaths jumped from 9 percent to 14 percent once the state commercialized marijuana for medical use and from 11 percent to 20 percent after legalizing the drug for recreational use.

Read more about marijuana-related driving in Colorado here starting on page 13 (PDF page 21).
In 2016, more than one-third of Colorado drivers who tested positive for marijuana had marijuana only in their systems. Another 36 percent had marijuana and alcohol. Slightly over one-fifth tested positive for marijuana and other drugs but no alcohol, while 7 percent had marijuana, alcohol, and other drugs on board.

See page 18 (PDF page 26) in The Legalization of Marijuana in Colorado: The Impact, Volume 5 here.
The Marijuana Report is a weekly e-newsletter published by National Families in Action in partnership with SAM (Smart Approaches to Marijuana).

Visit National Families in Action’s website, The Marijuana Report.Org, to learn more about the marijuana story unfolding across the nation.

Our mission is to protect children from addictive drugs
by shining light on the science that underlies their effects.

Addictive drugs harm children, families, and communities.
Legalizing them creates commercial industries that make drugs more available,
increase use, and expand harms.

Science shows that addiction begins in childhood.
It is a pediatric disease that is preventable.

We work to prevent the emergence of commercial
addictive drug industries that will target children.

We support FDA approved medicines.

We support the assessment, treatment, and/or social and educational services
for users and low-level dealers as alternatives to incarceration.

About SAM (Smart Approaches to Marijuana)

SAM is a nonpartisan alliance of lawmakers, scientists and other concerned citizens who want to move beyond simplistic discussions of “incarceration versus legalization” when discussing marijuana use and instead focus on practical changes in marijuana policy that neither demonizes users nor legalizes the drug. SAM supports a treatment, health-first marijuana policy.  SAM has four main goals:

  • To inform public policy with the science of today’s marijuana.
  • To reduce the unintended consequences of current marijuana policies, such as lifelong stigma due to arrest.
  • To prevent the establishment of “Big Marijuana” – and a 21st-Century tobacco industry that would market marijuana to children.
  • To promote research of marijuana’s medical properties and produce, non-smoked, non-psychoactive pharmacy-attainable medications.

Source: Email from National Families in Action http://nationalfamilies.org October 2017 

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

Abstract

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

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

INTRODUCTION

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

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

CASE REPORT

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

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

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

Initial electrocardiogram demonstrating wide-complex tachycardia.

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

Repeat electrocardiogram showing disorganized rhythm, peri-arrest.

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

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

DISCUSSION

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

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

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

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

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

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

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

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

CONCLUSION

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

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

Abstract

BACKGROUND

Cannabis is one of the most abused drugs worldwide, with more than 20 million users in the United States (US). As access to cannabis products increases with expanding US legislation and decriminalization of marijuana, emergency physicians must be adept in recognizing unintentional cannabis toxicity in young children, which can range from altered mental status to encephalopathy and coma.

CASE REPORT

     We report the case of a 13-month-old female presenting with self-limiting altered mental status and lethargy, with a subsequent diagnosis of tetrahydrocannabinol exposure on confirmatory urine gas chromatography-mass spectrometry.

Why Should an Emergency Physician Be Aware of This?

         Considering caretakers rarely report possible cannabis exposure, history-taking must review caretakers’ medicinal and recreational drug exposures to prevent inadvertently missing the diagnosis. In the young child with altered mental status, prompt urine screening for cannabinoid detection can prevent further invasive and costly diagnostic investigations, such as brain imaging and lumbar puncture.

CASE REPORT
               A healthy 13-month-old, 12-kg female presented to the ED with injected conjunctiva and inappropriate staring for 2 h, followed by a half-hour period of somnolence. The mother denied any possible ingestions, fevers, vomiting, seizures, or head trauma. Birth and medical history were unremarkable.
        Growth and development were age appropriate. On presentation, patient was somnolent, but arousable with stimulation. Vital signs were: temperature 36.6C, heart rate of 127 beats/min, respiratory rate of 39 breaths/min, blood pressure of 98/66mmHg, and an SpO2 of 100% on room air. Pupils were equal and dilated to 6mm bilaterally.
Physical examination was otherwise unremarkable. Computed tomography of the head, chest x-ray study, electrocardiogram, complete blood count, comprehensive metabolic panel, and serum toxicology were unremarkable.
       The mother appeared intoxicated, with slurred speech and injected conjunctiva. Maternal cannabinoid intoxication was suspected and urine cannabinoids on the child were sent and returned positive. Upon result disclosure, the mother stated that the child recently consumed hemp seed milk. Urine gas chromatography-mass spectrometry (GC-MS) confirmatory test was positive for d-9- tetrahydrocannabinol (THC). Within 8 h, the child returned to baseline without any medical interventions other than observation. Poison control, social work, and child protection services were all notified and involved.

DISCUSSION
           Cannabis is one of the most abused drugs worldwide. Cannabis formulations, such as marijuana (dried, leaves), hashish (resin), and hashish oil (concentrated resin extract) can be inhaled or ingested. THC is the main psychoactive ingredient that binds to brain cannabinoid receptors, producing dose- and time-dependent stimulant, hallucinogenic, or sedative effects. Effects of inhaled cannabis occur within minutes after ingestion, peak within 15–30 min, and last up to 4 h post ingestion.

INTRODUCTION
          Cannabis is a psychoactive plant composed of more than 500 chemical components called cannabinoids, which exert their psychoactive effect by activating specific receptors in the central nervous system and immune system. Cannabinoids are among the most abused drugs worldwide, with an estimated 22.2 million users in the United States. Since 2017, medical marijuana has been legalized in 31 states, and 9 states have decriminalized recreational marijuana. In such states, emergency department (ED) visits and poison center calls for accidental cannabis intoxication have increased. With these changes, emergency physicians must be adept in recognizing unintentional cannabis toxicity in young children, as intoxication can result in encephalopathy and coma.

     Orally consumed cannabis has delayed effects, with onset ranging from 30 min to 3 h, lasting up to 12 h post ingestion. With the increased bioavailability of cannabis concentrates and the smaller body mass in children, toddler cannabis ingestion results in high serum THC levels, despite a small amount ingested.

     Pediatric cannabis intoxication has variable presentations, ranging from mentation changes to encephalopathy and coma. The most common symptoms are central nervous system depression (i.e., lethargy, coma), confusion, agitation, hypotonia, bilateral reactive mydriasis, and ataxia. Nausea and vomiting have been reported, along with bradycardia, bradypnea, hypotension, and respiratory depression necessitating mechanical ventilation. Other symptoms include tremor, hallucinations, nystagmus, slurred speech, and muscle weakness. With such nonspecific symptomatology, cannabis toxicity can mimic postictal states, encephalitis,or sepsis, which lead to unnecessary diagnostic evaluations.
    Prompt urine screening can prevent further invasive and costly workups, such as brain imaging and lumbar puncture, and may thwart the need for mechanical ventilation or i.v. antibiotics/antivirals for presumed meningoencephalitis. Initial urine screening is typically performed with the highly sensitive enzyme multiplied immunoassay technique, but can have false-positive results, as many drug metabolites can influence the test, including hemp seed products. The confirmatory test, GC-MS, will only test positive for THC, making it highly specific for cannabis ingestion.

       Hemp is derived from a strain of the cannabis sativa plant species that contains a much lower concentration of the psychoactive component, THC, and higher concentrations of cannabidiol. Due to the increased availability in natural grocery stores, hemp products have become increasingly popular as health supplements in children. In order for hemp products to be commercially sold in the United States, strict regulations enforce the THC component to be < 0.3% of the total product weight. Despite these strict regulations on THC content, a recent study byYang et al. demonstrated that hemp products, in fact, have a variable THC component and may contain up to 12 times the legal THC limit. Therefore, prolonged use of hemp seed oil may induce neurologic symptoms of THC.

       A recent case by Chinello et al. described a case of a 2-year-old child who developed neurologic symptoms after taking 2 teaspoons of hemp seed oil per day for 3 weeks. No antidote exists for cannabis toxicity and activated charcoal is not effective. Management is largely supportive and most pediatric patients are observed and return to baseline within 8–12 h. Pediatric cannabis intoxication should be reported to child protection services to identify neglect and at-risk families and enhance child safety.

       Pediatric cannabis ingestions are more frequent due to rising marijuana use in the United States (US). In a comparison of state trends in unintentional pediatric marijuana exposures, as measured by call volume to US poison centers, call rates in states that had passed legislation prior to 2005 were increased by 30%, juxtaposed to non-legal states, where call volume remained unchanged. Despite its increasing availability, reports of unintentional pediatric cannabis ingestion leading to toxicity are uncommon. History taking must review both medicinal and recreational drug exposures to prevent missing the diagnosis. Knowledge of substances that can lead to false positives is imperative. Pertinent to our case, hemp product consumption will not result in a positive cannabinoid urine confirmatory test, as hemp does not contain enough THC to induce toxicity. However, recent data show hemp seed oil products may have substantially more THC than the level acceptable for commercial hemp use, and with prolonged exposure may induce toxicity. Our case involved an acute exposure and is therefore unlikely to cause any related toxicities.

      Lastly, with the growing popularity of edible marijuana products, which typically resemble candy and may be alluring to the exploratory toddler, emergency physicians must be vigilant when considering potential cannabis toxicity.

WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?
As access to cannabis increases, emergency physicians must recognize pediatric unintentional cannabis toxicity. Prompt cannabinoid urine screening can prevent further invasive diagnostic investigations.

Source: https://www.ncbi.nlm.nih.gov/pubmed/30340924 January 2019

 

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  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 , especially among populations at high risk. And alerting clinicians to these co-occurring conditions should trigger questions about prenatal .”

“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.

Provided by: Centre for Addiction and Mental Health

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

Dear David,

I am sending you below a copy of a letter I have sent to the Premiers of Canada – and other members of the worldwide drug prevention community, plus an email to UN HQ in New York.   Since they get so many letters I thought it would be sensible to send you a copy direct as it might take time for you to receive it through UN internal mail.

Dear Premiers,

As members of the worldwide drug prevention community we have been reading with increasing concern and disbelief the way that Canada seems to be bulldozing through legislation that can only damage the citizens of your country – not the least the children.

The Rights of the Child Treaty, under article 33 of the international drug conventions, would be breached if this legislation is allowed to be ratified.

Under the terms of the convention, governments are required to meet children’s basic needs and help them reach their full potential. Since it was adopted by the United Nations in November 1989, 194 countries have signed up to the UNCRC,

United Nations Convention on the Rights of the Child (CRC) is an important international legal instrument that obligates States Parties to protect children and youth from involvement with illicit drugs and the drug trade.

Canada is a signatory to the CRC – which is a legally binding document.  Should your country go ahead with the decision to legalise marijuana – against all the evidence from respected scientists and Health authorities worldwide Canada would be an outcast by those 193 nations who have agreed and signed to Article 33.

We find it astonishing that the wealth of evidence and opinion in Canada and  worldwide,  on the harmfulness of marijuana would seem to have been totally ignored by your parliamentarians.   Indeed new evidence relating to the epidemic of gastrochisis was submitted in good time by our Australian colleague Dr. Stuart Reece and was not allowed to be presented.   Instead you have been persuaded by groups that want marijuana to be ‘the new tobacco’ – headed of course by George Soros, that this will not be harmful to your citizens, that it will bring in tax revenues and that it would destroy the black market. 

However, there was a study done a few weeks ago by the Canadian Centre on Substance Abuse and Addiction finding that just in Canada alone, a much smaller country than the U.S. in population, marijuana-related car crashes cost a billion dollars. That’s just the car crashes, and those were directly related to marijuana. And the report came from a government think tank, not any kind of anti-drug group.

We heard many of these same promises in 2012 when Colorado legalized recreational marijuana. Yet  in the years since, Colorado has seen an increase in marijuana related traffic deaths, poison control calls, and emergency room visits. The marijuana black market has increased in Colorado, not decreased. And, numerous Colorado marijuana regulators have been indicted for corruption.

New reports out of Colorado indicate that legal marijuana  is posing real risks to the safety of young people. As Colorado rethinks marijuana, the rest of the nation should watch carefully this failing experiment.

Healthcare officials representing three hospitals in Pueblo, Colorado, issued a statement on April 27 in support of a ballot measure that would end Marijuana commercialization in the city and county of Pueblo. “We continue to see first-hand the increased patient harm caused by retail marijuana, and we want the Pueblo community to understand that the commercialization of marijuana is a significant public health and safety issue,” said Mike Baxter, president and CEO of Parkview Medical Center.

Among their concerns are  a 51 percent increase in number of children under 18 being treated in Parkview Medical Center emergency rooms.  Furthermore, of newborn babies at St. Mary-Corwin Hospital, drug tested due to suspected prenatal exposure, nearly half tested positive for marijuana.

Having read the above, how can Canadian legislators possibly believe that legalising marijuana would, in any way, be advantageous for their country ?

Yours faithfully,

Peter Stoker,  Director,  National Drug Prevention Alliance  (UK)

Source: A letter forwarded by Peter Stoker to David Dadge, spokesperson for UN Office ON Drugs and Crime (UNODC), originally sent to the Premiers of Canada  September 2017

A three-month-old baby boy died after being left alone overnight while his mother smoked cannabis, a serious case review has found.

Social services dealt repeatedly with the child’s family before his death but closed the case after the woman said she had stopped using drugs.

A police investigation into potential neglect is currently ongoing. The review found the level of support provided to the family was “a proportionate response”.

The baby, who can be identified only as Child E, suffered a cardiac arrest in September 2017 after being found unresponsive with a blanket over his head at a home in Rochdale.

His mother, who also cannot be named, subsequently told police she had been using cannabis on the night before his death and had left the house between 01:00 and 02:00 BST to go to a local garage. The baby had been left lying in his pram for 12 hours without being checked.

Substance misuse

A serious case review by the Rochdale Borough Safeguarding Children Board found the family had interacted with police and health and social care workers repeatedly in the months before his death.

An anonymous referral made to Children’s Social Care also raised concerns about the mother’s substance misuse and the state of the home in which the family were living, the Board found.

The Board’s report said the mother “reported cannabis to be her drug of choice and cocaine less frequently.”

“It is true that many parents’ use of drugs does not present a risk of harm to their children. It is also true that many parents who use drugs have chaotic and unpredictable lifestyles that do impact on their ability to maintain stability and safe parenting of their children,” it said.

Despite this, the case was closed after the mother said she had stopped using drugs.

Risk

“This review therefore begs the question about how well professionals can be reassured that substance misuse that impacts on parenting is ever really resolved or whether some level of risk will always remain,” the report said.

It also found that the mother had been given detailed advice on safe sleeping guidelines for babies on three occasions.

“The learning from this review will be important to all agencies and will result in changes to procedures in line with the recommendations,” said the Board’s independent chair, Jane Booth.

Source: https://www.bbc.co.uk/news/uk-england-manchester-45970026 24th October 2018

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Source: http://poppot.org/child-endangerment  August 2018

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Source and link to full articles:

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

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

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

Link to source and full articles:

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

Health visitors and other professionals should do more to deliver safe sleep messages to high-risk families to reduce sudden unexpected deaths in infancy (SUDI).

Researchers have recommended that children’s professionals help parents who use drugs and alcohol to develop safe sleep practices. University of Warwick study of 27 serious case reviews involving SUDI found that if parents followed UK safe sleep guidance many of those infant deaths could have been avoided.

In 19 of the 27 cases, parental drug or alcohol use was directly involved in the lead up to the infant’s death. In 12 of the 16 cases where parents were sleeping with their infants at the time of death, substance use was a factor.

In light of this, the researchers recommended that children’s professionals help parents who use drugs and alcohol to develop safe sleep practices.

“Health visitors and midwives should be encouraged to ask both parents about their use of alcohol and other substances, and help them develop safe sleep practices, including the avoidance of co-sleeping, which can then be used when parents are affected by substances,” the review concluded.

In three of the cases involving intoxicated parents, the mothers said they ignored the safe sleep advice they had been given because they thought “it couldn’t happen to me”. Long-standing neglect was another key feature in 15 of the cases examined. This finding echoes international research that suggests SUDI now predominately occurs among deprived families.

Dr Joanna Garstang, who led the review, said: “Eleven families’ siblings were reported as dirty, hungry, inadequately dressed or had severe dental caries, and seven families lived in homes described as squalid. “Four mothers lacked basic parenting skills, and one father was convicted for child neglect after leaving his young children home alone.”

Other risk factors identified by the review included parents’ unwillingness to engage with services, which occurred in 18 of the 27 serious case reviews.

“If parents are enabled to develop and understand safe sleep practices, they may be able to keep to these if there are unforeseen circumstances,” said the review paper. “Some families, however, are not willing to engage with services; and if there are concerns about parenting this has to be considered and managed as a safeguarding issue to ensure that vulnerable infants are protected.”

The researchers recommended that additional research into how best to deliver safe sleep messages to high-risk families is needed.

Jenny Ward, director of services at the Lullaby Trust, which promotes advice on preventing SUDI, said: “We welcome this study, which demonstrates the urgent need to ensure safer sleep advice reaches all parents and carers, particularly vulnerable families where extra support is often most needed. While reaching vulnerable parents can be challenging, the study shows that it could ultimately save babies’ lives.”

In 13 of the 27 cases parents had been given safe sleep advice prior to the death of their babies.

Every year there are around 300 to 400 deaths in England and Wales due to SUDI. SUDI is defined as the unexplained death of an infant when that had not been considered a reasonable possibility in the previous 48 hours. SUDI cases are often categorised as sudden infant death syndrome.

The University of Warwick’s review examined serious case reviews into deaths that occurred between 2011 and 2014. The full paper, Qualitative Analysis of Serious Case Reviews into Unexpected Infant Deaths, has been published in the Archives of Disease in Childhood journal.

In 2015 Public Health England recommended that all professionals who work with families are trained in how to prevent SUDI.

Source: https://www.cypnow.co.uk/cyp/news/2005572/health-visitors-must-ask-parents-about-alcohol-to-combat-sudden-infant-deaths 26th July 2018

Sydney Parliament House, 09.07.2018

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

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

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

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

1) Cannabis is addictive, particularly when used by teenagers

2) Cannabis affects brain development

3) Cannabis is a gateway to other harder drug use

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

psychosis, schizophrenia and bipolar disorder

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

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

6) Cannabis impairs driving ability 12

7) Cannabis damages the lungs

8) Cannabis is immunosuppressive

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

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

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

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

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

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

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

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

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

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

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

Cannabis Teratogenesis

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

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

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

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

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

1) Babies

2) Children

3) Adolescents

4) Car drivers

5) Commercial Drivers – Taxis, Buses, Trains,

6) Pilots of Aeroplanes

7) Workers – Manual Tools, Construction, Concentration Jobs

8) Children

9) Adolescents

10) Males of Reproductive age

11) Females of Reproductive age

12) Pregnancy

13) Lactation

14) Workers

15) Older People – Mental Illness

16) Immunosuppressed

17) Asthmatics – 80% Population after severe chest infection

18) People with Personal History of Cancer

19) People with Family History of Cancer

20) People with Personal History of Mental Illness

21) People with Family History of Mental Illness

22) Anyone or any population concerned about ageing effects 34

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

Concluding Remarks

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

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

1) Preclinical studies in

i) Rabbits and

ii) Hamsters

2) Cellular and biological mechanisms, particularly relating to:

i) Brain development

ii) Heart development

iii) Blood vessel development

iv) Genetic development

v) Abnormalities of chromosomal segregation

i. Downs syndrome

ii. Turners syndrome

iii. Trisomy 18

iv. Trisomy 13

vi) Cell division / mitotic poison / micronucleus formation

vii) Epigenetic change

viii) Growth inhibition

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

i) Canada 77,85

ii) USA 86,87

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

i) Ottawa 59-63

ii) Pittsburgh

iii) Netherlands

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

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

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

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

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

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

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

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

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

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Response by Prof. Stuart Reece to FDA

Link to FDA

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

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

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

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/

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

Submitted by Livia Edegger

A new study found that children of smokers are not only more likely to take up smoking themselves, but are also at a higher risk of becoming addicted. The longer children are exposed to their parents’ smoking at home, the more likely they are to become nicotine-dependent themselves. Consistent with previous research, quitting smoking is not only crucial for the parents’ personal health, but also for their children’s well-being. Although the findings seem obvious, they do highlight the critical role parents play in preventing their children’s tobacco use.

Links:

Source:

http://preventionhub.org/prevention-update/parent-child-%E2%80%98vicious-cycle%E2%80%99-family-smoking

20th May 2014

BATON ROUGE — When a classmate died of a drug overdose, Symmes Culbertson bought a black suit for the funeral.

“It didn’t feel right to wear a blue sports jacket,” the 23-year-old political science major said.

What he didn’t count on was how many more funerals of classmates he would attend — six since he began attending Louisiana State University in 2013. “The number of people that I have known by name or in passing that have died from prescription drug overdoses, just in my college years, is well into the teens,” Culbertson said.

These kinds of events have become increasingly common at U.S. colleges, where many students view mixing pills and chasing them with alcohol as a rite of passage, rather than a dangerous and often deadly practice.

“It’s a dirty secret,” said April Rovero, whose son, Joey, a student at Arizona State University, overdosed in 2009 after taking prescription opioids, benzodiazepines and alcohol. (Dr. Lisa Tseng, who prescribed the drugs that led to the deaths of him and two other young men, is now serving a 30-years to life prison sentence for illegally prescribing the medication.)

In the year that followed, she said nine more students from there also died at the hands of drugs.

National addiction expert Dr. Drew Pinsky said one thing that is killing many students is mixing opioids with benzodiazepines, such as Xanax — something he says doctors should never prescribe together because it can be lethal.

Since 1999, drug overdose deaths of those 15 to 24 have quadrupled to 5,376 a year, far surpassing the number of those dying from alcohol-related accidents.

“These are perfectly healthy young people,” said Rovero, who founded the National Coalition Against Prescription Drug Abuse. “Every one of these deaths is avoidable.”

‘A Perfect Storm’

Ken Hale, associate director of the Higher Education Center for Alcohol and Drug Misuse Prevention and Recovery on the Ohio State University campus, said “a perfect storm” has hit college campuses and the nation, starting with “the drug-taking culture in which we live. We use more medication than any other country.”

In 2016, the nation filled more than 4.5 billion prescriptions, including antibiotics, cancer drugs and other drug treatment protocols — an average of more than 14 per person.

But Hale said many of those prescriptions are the powerful and often addictive opioids. Even though the U.S. makes up less than 5 percent of the world’s population, it consumes 80 percent of opioids.

As a result, these drugs are easily available to students through family members or friends, he said.

With these prescription drugs come misperceptions about safety and legality, he said. Of those addicted to heroin, 80 percent started on prescription drugs.

“If I go to a party and someone says, ‘Here’s some heroin,’ flags go up, but if someone hands me a Vicodin (an opioid painkiller), they don’t,” he said.

College campuses have become incubators for the bigger problem, where students “may not hit the wall in college, but they start behaviors that led to the problem we have,” he said.

Hale noted that the No. 1 cause of death of those under 50 is drug overdose and that fact has contributed to the U.S. seeing life expectancy decline for two years in a row for the first time since the 1950s.

Ohio State is one of more than 100 colleges that have recovery centers, where students can live, Hale said. “College dormitories are not a good environment for someone trying to get sober.”

Funeral for a friend

Culbertson grew up in Greenville, a fast-growing small town in South Carolina. “In high school, the most hardcore thing was weed,” he said.

By 2014, pills had begun to seep into college life, no longer just for the weekend parties.

Students took Adderall, the stimulant used to treat Attention Deficit Hyperactivity Disorder, if they needed to study or take a test.

And students who didn’t have classes till the afternoon might visit the bar and get Xanax, sometimes chasing that tranquilizer with alcohol — what can be a deadly combination.

When 2015 came, so did news about a high school classmate, a former cross-country track star who became hooked on opioids after hurting his back and blowing out his ACL.

His sister, Callie, had helped him get sober, letting him live with her for six months.

Callie Culbertson, the older sister of Symmes Culbertson, graduated in December from LSU with a degree in animal science, history and psychology. She knows of eight young people from her hometown of Greenville, South Carolina, who have died of drug overdoses. (Photo: SCOTT CLAUSE/USA TODAY Network)

Afterward, she kept in touch by telephone. One morning she learned on Facebook that he had overdosed — news that stunned her because she had just spoken to him the night before.

She and Culbertson attended the funeral, and she couldn’t believe that so many people attending were high, doing the same drugs that killed her friend.

Since that funeral, she knows of eight people from her hometown who have died of overdoses.

“Everybody knows somebody this has touched,” she said. “The problem is no one is changing.”

‘He only took five’

Culbertson returned to LSU, and the next funeral of someone he knew took place just a few months later.

The environment has become “so accepting of the drugs,” he said. “If you don’t enjoy them, then you’re the a–hole — at least if you speak up about it.”

More funerals followed, and last January, he got a call that a friend of his had just overdosed.

Culbertson had just seen his friend the night before, taking Xanax in a bar. “We were with him at midnight,” he said.

When it was obvious he needed help getting home, friends took him there. He never woke up.

Word came that he had died of fentanyl, a drug up to 50 times stronger than heroin, and that fentanyl may have been mixed with the Xanax pills.

After this death, Culbertson said some slowed down in their drug taking, but no one quit.

Months later, he heard of a classmate back home who had been hooked on opioids before secretly moving to heroin and overdosing.

On Oct. 14, hours after LSU defeated Auburn University in football, Culbertson and his friends met at a bar.

After midnight, a friend informed him that he had just stolen a bottle of liquor from the bar, and that he was going back to his place to celebrate with his girlfriend.

The next morning, a friend called him in tears, letting him know their friend was dead.

“That’s crazy,” Culbertson replied. “He only took five (Xanax) sticks last night.”

As soon as he hung up, he realized the insanity of his own words, nonchalantly saying that his friend had taken five Xanax bars.

“And I thought that was completely normal,” he said. “And that’s what has come to scare me — the culture here is so accepting of it that even me, who doesn’t do any of this stuff, it’s normalized to me. My thinking had gotten as distorted as anybody engaging in the culture.”

He wore the dark suit for his friend’s funeral in New Orleans and returned home to write out an idea for a short film, based on what he had experienced.

The next day, he pitched his idea to his film class. His movie proposal, “Only the Good,” resonated with his fellow students.

“I just wanted to tell the story about my peers that shows everybody thinks they’re having a good time, and while that’s true 90 percent of the time, there’s that 10 percent of the time where you not only do, you die from it, but it devastates the lives of the people that care about you.”

Turning a blind eye

Rovero would like to see learning about medicine safety start in kindergarten, saying schools and colleges need to do a better job of educating students.

“Colleges should be educating students about how addictive and dangerous these drugs can be, especially mixed with other drugs and alcohol, and about the risk factors and signs of addiction and overdose,” she said.

Students should be trained to aid those in trouble, she said. “Parents should work with their administrators to have resident assistants have a naloxone rescue kit on hand in dorm settings, just in case, and everyone with a kit needs to be trained to use it.”

All incoming LSU freshman receive orientation regarding alcohol, drug use and sexual violence prevention. University officials say they continue to work with students to identify and reduce high-risk drinking, providing addiction programs and services, including the Anxiety and Addictive Behaviors Clinic.

Culbertson praised LSU for its all of its efforts, including education, outreach and support groups.

But there is a huge hurdle, he said. “There’s not much a support group can do when people aren’t looking for support. Nobody feels like they have a problem.”

The problem is one of perception, he said. “Students don’t really identify themselves as drug addicts, and everybody else is turning a blind eye.”

Source: https://www.clarionledger.com/story/news/2018/02/05

Haven Dubois, 14, died in accidental drowning on May 20, 2015, coroner says

Family members hold a picture of Haven Dubois, 14, who was found in cardiac arrest in a Regina creek on May 20, 2015. (CBC)

Richelle Dubois, the mother of 14-year-old Haven Dubois, says she is determined to learn more about the circumstances surrounding her son’s death. “I’m not done with this until I’m satisfied that they’ve looked into everything,” Dubois said Wednesday following the release of a coroner’s report that looked into the May 20, 2015 death of Haven. “I need to make sure that they’ve done their job properly.”
According to the report, the Regina boy was found drowned. The report said boys who were with Haven on that day told the coroner that he suffered a bad reaction to marijuana.
The boy’s mother Dubois has expressed concerns the death might have been connected to gangs. Police said foul play had been ruled out. Richelle Dubois said last fall she had waited a long time for the coroner to complete her report on her son Haven’s death. (CBC)
Coroner Maureen Stinnen interviewed a number of boys who were with Dubois, who said he was at school in the morning before getting into a car with friends.
“They apparently smoked some marijuana and they indicated that Haven began ‘freaking out,'” Stinnen’s report said. One of the youths Stinnen interviewed said it was Dubois’s first time smoking drugs. After getting out of the car, Dubois continued suffering ill effects and started walking away from the school, F. W. Johnson Collegiate.

Left alone on a bench

“Witnesses indicate he was ‘spinning in circles’ with his arms crossed at his chest,” the report said. One witness said he sat for a while with Dubois on a bench in a park, but left him alone so he could go get a skateboard and backpack. When the boy returned, Dubois wasn’t at the bench.
A friend said he last saw Dubois walking north by the creek in the area where his mother had discovered the body. Over the noon hour, Dubois was found face down in about a metre of water. Efforts to resuscitate him failed.
Dubois had no history or depression or suicidal tendencies, the coroner said. However, a toxicology report indicated he had the active component of cannabis in his blood.

Reactions to marijuana vary, coroner says

“The effect of marijuana on individuals varies considerably, from minor effects such as general feeling of well-being, to agitation and paranoia,” the report said. “These effects are subject to dose, age and experience of the user. Even in low doses, marijuana can precipitate a panic reaction and irrational behaviour.”
Stinnen said the case was thoroughly investigated by the Regina police and while “questions remain,” there were no indications of foul play. She concluded that Dubois’s death was an accidental drowning with drug use a “significant contributing factor.”

Mother seeks more information

Richelle Dubois said Wednesday she feels she did not get enough information from police about their investigation. “It’s so easy for them to brush it aside. It’s just another dead Indian to them,” Dubois said. “That’s how I feel; that we’re just another Indian family.”
According to a spokesperson from the police, officers met with Dubois three times. Dubois said the findings of the coroner, noting how marijuana can lead some people to panic and act irrationally, provide a possible explanation for her son’s death, but she still has questions.
“l know this isn’t the end of it,” she said. “This little two and a quarter page [report] isn’t the end of it.” Dubois added she has made a formal request to view police reports on the case.

Source: http://www.cbc.ca/news/canada/saskatchewan/marijuana-significant-factor-in-haven-dubois-death-1.3392179

There has been a lot of talk recently about marijuana legalization — increasing tax revenue for states, getting nonviolent offenders out of the prison system, protecting personal liberty, possible health benefits for those with severe illnesses. These are good and important conversations to have, and smart people from across the ideological spectrum are sharing their perspectives.

But one key dimension of the issue has been left out of the discussion until now: the marketing machine that will spring up to support these now-legal businesses, and the detrimental effect this will have on our kids.

Curious how this might work? Look no further than Big Tobacco. In 1999, the year after a massive legal settlement that restricted certain forms of advertising, the major cigarette companies spent a record $8.4 billion on marketing. In 2011, that number reached $8.8 billion, according to the Campaign for Tobacco-Free Kids. To put it into context, the auto industry spent less than half of that on advertising in 2011, and car ads are everywhere.

At the same time, despite advertising bans, these notoriously sneaky tobacco companies continue to find creative ways to target kids. Data from the 2011 National Survey on Drug Use and Health found that the most heavily marketed brands of cigarettes were also the most popular among people under 18.

This is not a coincidence, and gets to the very core of Big Tobacco’s approach: Hook them young, and they have a customer for life. Why do we think the legal marijuana industry will behave differently from Big Tobacco? When the goal is addiction, all bets are off.

In Colorado, where there are new rules governing how legal marijuana is advertised in traditional media, there are still many opportunities to market online and at concerts, festivals and other venues where kids will be present. Joe Camel might be retired, but he’s been replaced by other gimmicks to get kids hooked — like snus and flavored cigarettes. The marijuana industry is following suit by manufacturing THC candies, cookies, lollipops and other edibles that look harmless but aren’t. Making marijuana mainstream will also make it more available, more acceptable and more dangerous to our kids.

Addiction is big business, and with legal marijuana it’s only getting bigger.

Not surprisingly, Big Tobacco is also getting on the marijuana bandwagon. Manufacturers Altria and Brown & Williamson have registered domain names that include the words “marijuana” and “cannabis.” Imagine how much they will spend peddling their new brand of addiction to our kids. We cannot sit by while these companies open a new front in their battle against our children’s health.

Why is this an issue? There is a mistaken assumption that marijuana is harmless. It is not. Marijuana use is linked with mental illness, depression, anxiety and psychosis. It affects parts of the brain responsible for memory, learning, attention and reaction time. Developing brains are especially susceptible to all of the negative effects of marijuana and other drug use. In fact, poison control centers in Colorado and Washington state have seen an increase in the number of calls regarding marijuana poisoning. This isn’t a surprise — with legal marijuana comes a host of unintended consequences.

I’ve spent the past several years after leaving Congress advocating for a health care system that treats the brain like it does any other organ in the body. Effective mental health care, especially when it comes to children, is critically important.

Knowing what we now know about the effects of marijuana on the brain, can we really afford to ignore its consequences in the name of legalization? Our No. 1 priority needs to be protecting our kids from this emerging public health crisis. The rights of pot smokers and the marijuana industry end where our children’s health begins.

I’m not alone in my concerns about this trend toward legalization. Even Colorado Gov. John Hickenlooper has said that marijuana legalization in his state was “reckless” and reaffirmed his opposition to it during his campaign for re-election. He also said he will “regulate the heck” out of it. For that, I applaud his leadership and courage.

Alaska, Oregon and the District of Columbia have legalization ballot measures up for a vote this fall. I hope common sense will prevail, and they choose a better path than making addiction the law of the land.

At the end of the day, legalizing and marketing marijuana is making drug use acceptable and mainstream. Just as Big Tobacco lied to Americans for decades about the deadly consequences of smoking, we can’t let “big marijuana” follow in its footsteps, target our kids and profit from addiction.

Patrick J. Kennedy is a former United States representative from the state of Rhode Island.

Source: http://www.npr.org/2014/10/30/360217001/kennedy-are-we-ready-for-big-tobacco-style-marketing-for-marijuana

 

One in five Canadians between 15 and 24 years of age reports daily or almost daily use of cannabis prior to legalization. They see it as “much safer than alcohol and tobacco” and “not as dangerous as drunk driving.”

Author 1. Paul W Bennett

Research Associate in Education, Saint Mary’s University

Disclosure statement

Paul W Bennett does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

Partners

The Conversation UK receives funding from Hefce, Hefcw, SAGE, SFC, RCUK, The Nuffield Foundation, The Ogden Trust, The Royal Society, The Wellcome Trust, Esmée Fairbairn Foundation and The Alliance for Useful Evidence, as well as sixty five university members.

One of the enduring myths about marijuana is that it is “harmless” and can be safely used by teens.

Many high school teachers would beg to disagree, and consider the legalization of marijuana to be the biggest upcoming challenge in and around schools. And the evidence is on their side.

As an education researcher, I have visited hundreds of schools over four decades, conducting research into both education policy and teen mental health. I’ve come to recognize when policy changes are going awry and bound to have unintended effects. As Canadian provinces scramble to establish their implementation policies before the promised marijuana legalization date of July 2018, I believe three major education policy concerns remain unaddressed.

These are that marijuana use by children and youth is harmful to brain development, that it impacts negatively upon academic success and that legalization is likely to increase the number of teen users.

‘Much safer than alcohol’

Across Canada, province after province has been announcing its marijuana implementation policy, focusing almost exclusively on the control and regulation of the previously illegal substance. This has provoked fierce debates over who will reap most of the excise tax windfall and whether cannabis will be sold in government stores or delegated to heavily regulated private vendors.

All of the provincial pronouncements claim that their policy will be designed to protect “public health and safety” and safeguard “children and youth” from “harmful effects.”

Still, one in five young people between 15 and 24 years of age, according to a recent national study, report daily or almost daily use of cannabis.

They also see marijuana as “much safer than alcohol and tobacco” and “not as dangerous as drunk driving.”

Few either know about or seem concerned over the clear linkage between heavy use and early-onset psychosis.

Early-onset paranoid psychosis

So what does the evidence say? First, heavy marijuana use can, and does, damage brain development in youth aged 13 to 18. A 2015 Canadian Centre on Substance Abuse study confirmed the direct link between cannabis use and loss of concentration and memory, jumbled thinking and early onset paranoid psychosis.

One of the leaders in the medical field, Dr. Phil Tibbo, initiator of Nova Scotia’s Weed Myths campaign targeting teens, has seen the evidence, first hand, of what heavy use can do as director of Nova Scotia’s Early Psychosis Program. His brain research shows that regular marijuana use leads to an increased risk of developing psychosis and schizophrenia and effectively explodes popular and rather blasé notions that marijuana is “harmless” to teens and “recreational use” is simply “fun” and “healthy.”

Damaging to academic performance Second, marijuana negatively impacts neurocognitive performance in teens and users perform more poorly in quantitative subjects requiring precision — like mathematics and senior science.

In 2017, Dutch researchers Olivier Marie and Ulf Zolitz found that the academic performance of Maastricht University students increased substantially when they were no longer legally permitted to buy cannabis. The effects were stronger for women and low performers and academic gains were larger for courses needing numerical or mathematical skills.

Third, legalization of marijuana is likely to increase the number of teen users. Research from Oregon Research Institute conducted in 2017 showed that teenagers who were already using marijuana prior to legalization increased their frequency of use significantly afterwards. Research from New York University, published in 2014, indicated that many high school students normally at low risk for marijuana use (e.g., non-cigarette-smokers, religious students, those with friends who disapprove of use) reported an intention to use marijuana if it were legal. Medical researchers and practitioners have warned us that legalization carries great dangers, particularly for vulnerable and at-risk youth between 15 and 24 years of age.

Age of restriction

Marijuana legalization policy across Canada is a top-down federal initiative driven largely by changing public attitudes and conditioned by the current realities of the widespread use of marijuana, purchased though illicit means.

Setting the age of restriction, guided by the proposed federal policy framework, has turned out to be an exercise in “compromise” rather than one focused on heeding the advice of leading medical experts and the Canadian Medical Association (CMA). In a 2016 submission to the government, the CMA argued that 25 would be the ideal age for legal access to marijuana, as the brain is still developing until then, but that a lower minimum age of 21 should be considered — to discourage children from purchasing marijuana from organized crime groups.

The report argued that: “Marijuana use is linked to several adverse health outcomes, including addiction, cardiovascular and pulmonary effects (e.g., chronic bronchitis), mental illness, and other problems, including cognitive impairment and reduced educational attainment. There seems to be an increased risk of chronic psychosis disorders, including schizophrenia, in persons with a predisposition to such disorders.” In fact, the minimum age for purchasing and possessing marijuana is going to be age 18 in Alberta and Quebec, and 19 in most other provinces. Getting it “out of high schools” was a critical factor in bumping it up to age 19 in most provinces.

Every Canadian province is complying with the federal legislation, but — in our federal system – it’s “customized” for each jurisdiction.

The Canadian Western provinces — Alberta, British Columbia and Saskatchewan —have opted for regulating private retail stores, while Ontario and the Maritime provinces (Nova Scotia, New Brunswick and P.E.I.) are expanding their liquor control commissions to accommodate retail sales of cannabis. High school teachers, as of September 2018, may be battling a spike in marijuana use and greater peer pressure to smoke pot on the mistaken assumption that it is “harmless” at any age.

Clamping down in schools

For high school principals and staff, this will be a real test.

By September 2018, the old line of defence that using marijuana is illegal will have disappeared. Recreational marijuana will be more socially acceptable. The cannabis industry will be openly marketing its products. High school students who drive to school will likely get caught under new laws prohibiting motor vehicle use while impaired by drugs or alcohol. Fewer students are likely to abstain when it is perfectly legal to smoke pot when you reach university, college or the workplace. We have utterly failed, so far, in getting through to the current generation of teens, so a much more robust approach is in order.

“Be firm at the beginning” is the most common sage advice given to beginner teachers. Clamping down on teen marijuana use during and after school hours will require clarity and firm resolve in the year ahead — and the support of engaged and responsible parents.

Legalization of recreational marijuana is bound to complicate matters for Canadian high schools everywhere. Busting the “Weed Myths” should not be left to doctors and health practitioners. Pursuing research-based, evidence-informed policy and practice means getting behind those on the front lines of high school education.

Source: https://theconversation.com/marijuana-at-school-loss-of-concentration-risk-of-psychosis-90374 January 25th 2018

University of Michigan’s annual drug abuse survey – Monitoring the Future University of Michigan’s annual drug abuse survey, Monitoring the Future, were released today showing that the percentage of teens using over-the-counter (OTC) cough medicine containing dextromethorphan (DXM) to get high remains at just 3 percent, the lowest level recorded for teen cough medicine abuse since 2015. When first reported in 2006, teen abuse of these OTC cough medicines was nearly 6 percent, but has declined significantly since then.

Since 2006, the rate of teen OTC cough medicine abuse has decreased by 44% (from 5.4% to 3%).

Over the past decade, the Consumer Healthcare Products Association (CHPA) has worked to help reduce teen DXM abuse by employing three strategies: increasing parent engagement in abuse awareness and prevention; heightening teen perceptions of the risks and social disapproval of medicine abuse; and limiting teen access to DXM through age-18 sales restrictions in states. In 2008, CHPA member companies voluntarily placed a “PARENTS: Learn About Teen Medicine Abuse” icon on the packaging of cough medicines containing DXM. The icon serves as a mini public service announcement for parents, making them aware of cough medicine abuse at the point-of-sale and point-of-use and directing them to StopMedicineAbuse.org – a well-established website and abuse prevention campaign aimed at engaging parents and community leaders about teen abuse of OTC cough medicine.

“Public policy and education are both vitally important to combating teen OTC cough medicine abuse,” said CHPA president and CEO Scott Melville. “This is why CHPA has long supported state efforts to limit teen access to DXM and has worked to increase parental awareness through our Stop Medicine Abuse education campaign, while at the same time, ensuring continued access for millions of families who responsibly use medicines containing DXM.” CHPA also collaborates with the Partnership for Drug-Free Kids to target teens who are most likely to abuse DXM based on their online search activity and to provide them with accurate information about the consequences of abusive behavior. Teens are directed to visit WhatIsDXM.com to learn more.

“The Partnership for Drug-Free Kids welcomes the data from this year’s Monitoring the Future Survey showing no year-to-year increases in high school students’ misuse of over-the-counter cough and cold remedies,” said Partnership president and CEO Fred Muench. “For nearly a decade now, the Partnership and CHPA have collaborated on a digital media prevention effort targeting this behavior – and we have seen steady and significant declines over this period in teens’ misuse of OTC cough medicine to get high. It’s compelling evidence that smart, strategic prevention initiatives can work, and can deliver real benefits to teens and their families.”

Additionally recognizing that retailers play a critical role in abuse prevention, this year CHPA launched a new Pharmacists & Retailers page on the StopMedicineAbuse.org site, where retailers can download or order free materials.

Please visit StopMedicineAbuse.org for more information about teen DXM abuse, the retailer education materials, and other helpful resources for parents and community leaders.

The Consumer Healthcare Products Association (CHPA) is the 136-year-old national trade association representing the leading manufacturers and marketers of over-the-counter (OTC) medicines and dietary supplements. Every dollar spent by consumers on OTC medicines saves the U.S. healthcare system $6-$7, contributing a total of $102 billion in savings each year. CHPA is committed to empowering consumer self-care by preserving and expanding choice and availability of consumer healthcare products. chpa.org

Source: https://www.businesswire.com/news/home/20171214006254/en/New-Results-Annual-Survey

The truth is it can indeed mean trouble, especially for young people.

These days, it’s become fairly squ