A thoroughly referenced wake up call and must-read for anyone who thinks THC consumption is harmless and its legalization and commercialization a good idea. This urgent appeal from an Australian Doctor to the US Surgeon General should shake to the core anyone who still believes that increasing use rates of high-potency, industrially manufactured THC products is acceptable. Where there’s more pot, more people use. At population-level use rates the downstream effects of the accumulation of this chemical in our bodies will likely have significant, lasting and generational implications on public health. Read on below…
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US SURGEON GENERAL * Request for a Telephone Appointment with U.S. Surgeon General Adams Regarding EXTREMELY URGENT IMPLICATIONS OF CANNABIS LEGALIZATION FOR TERATOLOGY AND CONGENITAL MALFORMATIONS IN USA
Dear Surgeon General Adams,
I am an Australian Professor of Addiction Medicine and researcher at the University of Western Australia and Edith Cowan University both in Perth, Western Australia.
I have been becoming increasingly concerned at the implications of cannabis legalization across USA for patterns of congenital anomalies both in USA and across the world.The incidence of many congenital anomalies are rising in many places. This rise is even more marked if therapeutic early termination for anomaly (ETOPFA) are taken into account.
In 2007 the American Academy of Pediatrics issued a position statement which noted that cannabis was a known teratogen for cardiovascular anomalies based on three studies. They cited ASD, VSD and Ebstein’s anomaly in particular as major concerns. This is also important as cardiovascular anomalies form the largest single group of congenital anomalies. As you would be well aware foetal anomalies is the single major cause of death in the first year of life. The aetiological pathway is further strengthened by the fact that the endocardial cushions have high density expression of CB1R’s cannabinoid type 1 receptors from very early in embryonic life. This fits with the significant association of cannabis with defects of structures derived from the endocardial cushions and the associated conoventricular ridges including the cardiac valves and the interatrial and interventricular septa.
Prof. Peter Fried in Ottawa has headed up a comprehensive, careful and detailed longitudinal study of brain damage in children exposed to cannabis in utero. They have been publishing positive findings from this study for forty years showing documented deficits of executive and higher brain function, the need to recruit more brain to perform tested tasks documented on fMRI, in primary school, middle school, high schooland even into young adulthood. It has now been convincingly demonstrated that endocannabinoids send the “off” signal halting synaptic neurotransmission at both stimulatory and inhibitory synapses and hence shutting down the brain’s normal oscillatory processes. Brain oscillations are known to form a key an pivotal function early in brain development guiding the migration and axonal projection of developing neuronal progenitor cells, and also guiding synapse formation. As you would be aware many neural progenitor cells fail to integrate into the neural network and die due to lack of circuit stimulated connectivity. This applies to both stimulatory and inhibitory synapses. Hence synaptic firing is therefore critical for synapse formation and integration and survival of the new nerve cells. Since cannabis and its constituent cannabinoids shut down this firing and resultant neural oscillations they necessarilyimpede brain development both in the cortex and in key subcortical major centresincluding the thalamus and hypothalamus. Hence the demonstration by the Fried group that cannabis users have smaller cortical thickness and hippocampal volumes – the hippocampus first encodes memory – fits well with the known developmental biological mechanisms.
Given that cannabis in Colorado now is commonly at or above 30%, and was historically only 1-2% when most of its epidemiological studies were done; and given also that cannabis oils at up to 99% THC content are also increasingly widely available the conclusion becomes inescapable that the vast majority of children significantly exposed to these concentrations of cannabis in utero will be adversely and permanently affected. Importantly no population measure of this very important damage I easily accessible.
10 studies have linked cannabis exposure to incidence or severity of gastroschisis. This case is strengthened by the high density of CB1R’s on the omphalovitelline artery, and the many studies now which implicate vasoactive drugs in the pathogenesis of this condition. Indeed although the activity of cannabinoids on arterial structure is not widely understood is has been documented in minute detail by no lesser a resource that Nature Reviews of Cardiology. And obviously cannabis arteriopathy underlies the elevated rate of both myocardial infarction and stroke seen in adults with cannabis exposure about which Dr Nora Volkow, Director of NIDA has commented in New England Journal of Medicine.
A spectacular study from Hawaii in 2007 demonstrated that cannabis use was associated with Down’s syndrome incidence at a rate 526% elevated above background.
This is significant for several reasons. Firstly a substantial body of evidence shows that cannabis has been known to test positive in the micronucleus assay since the 1960’s. This is a major test for genotoxicity. The implications of this devastating genetic damage were worked out for the whole world to see by David Pellman’s lab in New York and links cannabis exposure directly with abnormalities of cellular division including the three major clinical trisomies – trisomies 21, 18 and 13 – and Turner’s syndrome, XO.
Furthermore this implies that since cannabis is linked with cardiovascular, neuropsychiatric and chromosomal defects, these being the three major groups of congenital disorders.
If one goes to Colorado as a rather obvious test case indeed one finds a rise there of 70% in both total major congenital anomalies, and also cardiovascular anomalies, especially atrial septal defect and ventricular septal defects, which are the most common, exactly as predicted by the embryology.
Indeed, the particular thoroughness of the way in which all kinds of social and health data is collected and made available in the USA, together with the very considerable spread in attitudes to drug legalization in different states, make USA the perfect teratological laboratory to study the mutagenic and genotoxic effects of cannabinoid exposure. My colleagues in addiction medicine and I at my university, aided by some of the top statisticians in this country have now commenced the enormous task of analyzing the US cannabis exposure data by state from the National Survey on Drug Use and Health, together with cannabis concentration data quoted by Dr Nora Volkow the Director of NIDA in New England Journal of Medicine, together with projections of the applicable therapeutic termination rates taken from the Western Australian Register of Developmental Anomalies are analyzing this data at this time.
Whilst our findings have not been finalized the following remarks can already be made:
In socially conservative states cannabis use is falling or flat whilst it is rising in more liberal states;
When one takes into account the dramatically increased cannabis concentration – to only 15% in 2015 in this series – the population exposure to cannabinoids has risen in all states regardless of social ethos;
The rate of almost all congenital anomalies in the USA has risen when reasonable estimates for ETOPFA rates are employed;
Cannabis exposure is significant for all 62 anomalies combined considered as a group;
Not only are congenital anomalies uniformly rising against time, they are also rising against this metric of community cannabis exposure – defined as the product of the national mean cannabis concentration and the state based cannabis use rates;
If one considers the groups of:
Cannabis related disorders (as defined by the Hawaiian investigators);
Chromosomal defects;
Cardiovascular defects;
Derivatives of the endocardial cushions;
The population exposure to cannabinoids remains highly significant including consideration of state and year
Considering all 62 defects collected by the US National Birth Defects Prevention Network :
In 43 cases (69.3%) the community cannabinoid exposure remains significant on linear regression testing before correction for multiple testing;
When one adjusts for multiple testing 38 defects (61.3%) remain significant – mostly as described by the Hawaiian researchers;
For example the national rate of the effect of cannabis exposure on Ebsteins anomaly is P<0.0001 for the effect of cannabis exposure alone and P<0.0001 for the interaction between cannabis exposure and time (multiple testing corrected results). The beta estimate for this effect is 18%, and the P value is much less than P < 10 -16 .
Please note that none of these metrics quantitate what I regard as the most serious area of all – the neurobehavioural toxicology so carefully documented and chronicled with every imaginable psychological and imaging test at every developmental stage into young adult by the methodical Ottawa investigators referenced above.
I am aware of course of the signal service performed in this area by your predecessor Dr Murthy in relation to his report on “Facing Addiction in America.”
Naturally I am very concerned indeed that the USA, having avoided the horrors of thalidomide directly due to the due diligence of your FDA staff at the time, is sailing directly into an even worse teratological morass related to the legalization of cannabis in your country, which apparently even your President appears to be powerless to avert. It is of the greatest concern to me that the carefully orchestrated US cannabis legalization campaign seems to be operating is such a manner as to at once bypass and simultaneously intimidate the FDA quality control and checks and safety balances processes.
The medical conclusion appears inescapable to me that cannabis use should be avoided by males and females in the reproductive age group especially if involved in pregnancy or even considering pregnancy – because of the long half lives involved and its sluggish release from the body’s fat stores. It is well known that these same young adults is the group most keen to use cannabis products! Indeed it is well documented that cannabis both increases sexual libido and reduces inhibitions; albeit after time and habituation it reduces both sexual desire and performance. This sets up an inescapable and unavoidable reproductive and genotoxic paradox – which also greatly escalates the present discussion beyond the arena of personal civil liberties to the future of our coming generations.
Naturally I am particularly keen to discuss these issues with yourself at your earliest available opportunity.
The teratological aspects of this epidemic seem to have been completely and systematically overlooked in the current discussions.
Please help me assist your wonderful, beautiful, noble and courageous nation at this critical juncture in your history.
And I am sure it will be self-evident to you that anything that happens in USA has enormous ramifications around the world, as you are obviously that world’s leading democratic nation.
Hence USA is not only legislating for America – but for all citizens of the planet – present and future. Because of the epigenetic implications – not discussed above but very well substantiated nonetheless – for the next four generations – this is the next 100 years.
In such a circumstance – truth can be your only meaningful defence. And it must be your final bastion – and the last great hope of civilization.
I am very keen to set up a time which would be suitable to yourself to discuss these issues on the phone.
Oddly it seems to me that few professionals understand these issues thoroughly.
And even more strangely – it seems to me strange that USA, having alone amongst the family of nations done so extremely well with thalidomide, at the present time gives every appearance of acting before she has thought carefully, methodically and deeply about the ramifications of her present actions in this field.
With very best wishes,
Yours sincerely,
Dr. Stuart Reece,
Australia.
Referenced Links:
Ascertaining the Burden of Birth Defects. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/27102641/
Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Counci… – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/17519397/
Ebstein’s anomaly – Wikipedia
https://en.m.wikipedia.org/wiki/Ebstein%27s_anomaly
Ascertaining the Burden of Birth Defects. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/27102641/
Effects of prenatal cigarette and marijuana exposure on drug use among offspring. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/15734278/
Differential effects on facets of attention in adolescents prenatally exposed to cigarettes and marihuana. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/11711244/
Effects of marijuana on visuospatial working memory: an fMRI study in young adults. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/20401748/
The effects of Δ9-tetrahydrocannabinol on the dopamine system. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/27853201/
Δ9-THC Disrupts Gamma (γ)-Band Neural Oscillations in Humans. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/25709097/
Frontiers | Pathophysiological power of improper tonic GABAA conductances in mature and immature models | Frontiers in Neural Circuits
https://www.frontiersin.org/articles/10.3389/fncir.2013.00170/full
Effects of marijuana on visuospatial working memory: an fMRI study in young adults
Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/28905873/
Adverse health effects of marijuana use. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/24897085/
Adverse health effects of marijuana use. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/25162899/
Risk of selected birth defects with prenatal illicit drug use, Hawaii, 1986-2002. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/17162495/
Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable g… – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/27208973/
Chromothripsis from DNA damage in micronuclei. – PubMed – NCBI
https://www.ncbi.nlm.nih.gov/m/pubmed/26017310/
National Survey on Drug Use and Health (NSDUH) | SAMHDA
https://www.datafiles.samhsa.gov/study-series/national-survey-drug-use-and-health-nsduh-nid13517
WA Register of Developmental Anomalies (WARDA)
https://www.kemh.health.wa.gov.au/Our-services/Statewide-Services/WARDA
National Birth Defects Prevention Network
Home | Surgeon General’s Report on Alcohol, Drugs, and Health: FACING ADDICTION IN AMERICA
https://addiction.surgeongeneral.gov/
The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development. – PubMed – NCBI