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Editor's Choice

Should we legalise cannabis?

BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4507 (Published 04 July 2019) Cite this as: BMJ 2019;366:l4507

Re: Should we legalise cannabis?

Cannabis Debates and Cannabis Debacles:
Serious Downstream Implications of Cannabis Neurotoxicity and Genotoxicity

The piece by Dr Godlee reminds us on the one hand that weighty decisions are being made on the basis of flawed and incomplete evidence and on the other that much of what we have seen till now in relation to the epidemiology of cannabis has occurred in a low cannabis use environment, a protected situation which is directly due to cannabis’s hitherto illegal status, which bears little resemblance to the high-use high-potency products and consumption patterns which are presently emerging on both sides of the 49th parallel in North America.

Our research group has taken a novel approach which looks for correlates at the population health level of findings which have been made in important and repeated epidemiological studies. As shown below numerous and emphatic confirmations of such laboratory and study findings in relation to cannabis have been found at the population health level. Such repeated confirmations imply careful pause at the national and international policy level.

The 2019 World Drug Report from the United Nations office of Drugs and Crime demonstrates in detail that the presently emerging cannabis epidemic in USA is one of increased intensity of use more than increased numbers of users. The National Survey of Drug Use and Health (NSDUH) shows a rise in lifetime use of cannabis 2006-2017 of 9% compared to an 80% rise in those using cannabis daily or almost daily. When combined with the high potency forms of cannabis and hashish oil presently widely available in North America, this portends a tsunami of serious downstream sequelae. Most published cannabis epidemiology is only marginally relevant to this new high-use high-potency era.

NSDUH quantifies several parameters of mental health including any mental illness, serious mental illness and suicidal thinking against national drug use across both time and space. Close temporospatial association has been demonstrated in unpublished explorations of all three indices with cannabis use and cannabinoid exposure. Such findings confirm at the level of population health the many published studies linking cannabis consumption to numerous measures of serious mental health outcomes including depression, bipolar disorder, anxiety and schizophrenia.

It was recently shown that the autism epidemic in USA is rising exponentially related to the increased use of cannabis whilst the use of most other drugs has fallen (NSDUH) and that the incidence of autism is predicted to be 60% higher in cannabis liberal states than states where cannabis is not legal by 2030 1 2. Such findings imply that the adverse mental health outcomes well described in adults are even more serious in children and confirm epidemiologically the many experimental studies showing interference with brain development by multiple pathways. Such children will likely never have the opportunity to develop normally – as they never were.

Colorado is known as one of the US leaders in cannabis liberalization. It is less well known that an extra 11,753-20,152 major congenital abnormalities occurred din Colorado from 2000-2014 (depending on whether one uses the September 2018 Colorado birth defects data or the October 2018 data), and particularly features 104% rise in spina bifida, 71% rise in microcephalus and 123% rise in atrial septal defect, 45% rise in all cardiovascular defects, 35% rise in major central nervous system defects and 34% rise in chromosomal anomalies including a 25% rise in Down’s syndrome 3. Indeed the emergence of very elevated rates of atrial septal defect in Kentucky, Colorado, Hawaii and many US cannabis-liberal states suggests the emergence of yet another cannabis related congenital defect (CDC data). This in turn suggests our presently described list of over 20 cannabis-associated birth defects is itself incomplete and likely to expand dramatically in coming years.

All seven studies to examine the relationship between cannabis use and gastroschisis have been positive with an odds ratio of about 3.0 4. A recent important CDC study documented impressive racial differences in gastroschisis incidence 5. If one assigns the baseline incidence of gastroschisis in children of African-American teenager mothers (9.0/100,000 live births) to unity, then the incidence of gastroschisis in infants born to non-Hispanic white mothers is twice as common (17.1) and in American Indian / Alaska Natives is three times as common (26.0). These relativities disappeared quickly at older maternal ages consistent with a differential environmental teenage exposure rather than a truly genetic explanation. These changes directly parallel the historical rates of teenage cannabis use in these racial groups as quantified by the Youth Risk Behaviour Survey, the Monitoring the Future Survey and the National Longitudinal Alcohol Survey in USA. A mechanism was recently described whereby interference in late gestational uterine blood flow around the time of birth can cause preeclampsia in the mother and other external sequalae 6.

Cannabis use in parents has been previously linked with childhood leukaemias and sarcomas which are some of the major cancers of childhood 7. Unsurprisingly then one notes a 52% rise in all childhood cancer from 1975-2017 based in CDC Surveillance Epidemiology and End Results (SEER) data. As noted above the use of other drugs has fallen across this time. Cannabis has been shown to be reproductively toxic by many routes including interfering with cell division and mitosis and damaging to many parts of the epigenomic machinery 8 9. Indeed the presence of DNA fragments in the cytoplasm has been shown to be potently stimulating to the innate immune system in a cell autonomous manner which in turn damages the genome. This explains the frequently cited increase in the degree of malignancy of cannabis related cancers, and their occurrence in much younger patients, which were previously not understood. Again the rates of all pediatric cancer in African-Americans is about 60% that occurring in Americans of Caucasian heritage, which again parallels lower rates and lower intensity of cannabis use in African-American communities – a situation which is presently in a state of flux.

Four of four studies examining the relationship between testicular cancer and cannabis use have all been strongly positive with an odds ratio of around 3 7 10. Unsurprisingly there has been a 66% rise in the rate of all-age testicular cancer from 3.8 to 6.3 cases /100,000 (CDC SEER Data).

Dr Godlee’s call to watch carefully the unfolding milieu in North America is timely and salient. However we need to do so with open eyes and carefully and impartially evaluate what we are really seeing judged against the important metrics of earlier eras when cannabis use was less prevalent. Detailed and sophisticated space-time investigations are required. We find it paradoxical – and probably unjustifiable – that at a time when scientific knowledge is so advanced and epidemiological methods are so complex that confusion reigns supreme in this area and the field is overripe with disinformation.

We welcome the call for continued careful surveillance but feel that while so many concerning findings continue to be uncovered studious caution is the only responsible approach. Sophisticated spatial geostatistical investigations are urgently mandated. Public education on cannabis is obviously paramount. Cannabis disinformation is our greatest threat.

References

1. Reece A. S., Hulse G.K. Effect of Cannabis Legalization on US Autism Incidence and Medium Term Projections. Clinical Pediatrics: Open Access 2019;4(2):In Press. doi: DOI: 10.24105/2572-0775.4.154 . [published Online First: May 3rd 2019]
2. Reece A. S., Hulse G.K. Epidemiological Associations of Various Substances and Multiple Cannabinoids with Autism in USA. Clinical Pediatrics: Open Access 2019;4(2):In Press. doi: 10.24105/2572-0775.4.155 [published Online First: May 3rd 2019]
3. Reece A. S., Husle G.K. Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends Clinical Pediatrics 2019;In Press
4. Reece A. S., Hulse G.K. Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends Clinical Pediatrics 2019;In Press
5. Short TD, Stallings EB, Isenburg J, et al. Gastroschisis Trends and Ecologic Link to Opioid Prescription Rates - United States, 2006-2015. MMWR Morb Mortal Wkly Rep 2019;68(2):31-36. doi: 10.15585/mmwr.mm6802a2
6. Robertson SA. Preventing Preeclampsia by Silencing Soluble Flt-1? N Engl J Med 2019;380(11):1080-82. doi: 10.1056/NEJMcibr1817501
7. Reece A.S. Chronic Toxicology of Cannabis. Clinical Toxicology 2009;In Press(Accepted 28/05/09.)
8. Reece AS, Hulse G.K. 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. Epigenetics 2019;In Press
9. Reece AS, Hulse GK. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Mutat Res 2016;789:15-25. doi: 10.1016/j.mrfmmm.2016.05.002
10. Reece A. S., Hulse G.K. Explaining Contemporary Patterns of Cannabis Teratology. Clinical Pediatrics 2019;4(1):1000146. doi: 10.4172/2572-0775.1000146 [published Online First: 20th February 2019]

Competing interests: No competing interests

07 July 2019
Albert S. Reece
Physician
University of Western Australia and Edith Cowan University, Perth, Western Australia
35 Stirling Hwy., Crawley, Western Australia