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2022 October
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 >12 years (R=0.8825; P=0.000029;). 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”.
Authors:
Albert Stuart Reece, Moira Sim, Gary Kenneth Hulse
- 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