Sir,

The article by Sophie Christie (Telegraph Business 22 June ) could be read as a paean for Cannabis based medications and CBD particularly.

While we have long suspected and said, that CBD in particular may well have clinical uses,  that is with caution.

Evidence for the epigenetic and teratogenic effects of cannabis can easily be found via Google Scholar.

The NHS Wales lists the risk for Gastroschisis (babies with large intestines outside their bodies). Cannabis and Cocaine are both suspect.

There has been a gastroschisis outbreak in South Wales.

CBD is not off the hook, therefore self-medication and mass marketing of it and products containing it, may not be a good idea.

As long ago as 1973 Professor Gabriel Nahas MD, PhD, DSc of Columbia University gave evidence to a Senate Committee  that, in vitro at least, molecules of the cannabinoids CBD and CBN, were, like THC, potent inhibitors of DNA production.

There seems to be a danger of CBD being oversold in the rush to market.

The last Teratogen that was marketed extensively was Thalidomide, we all know how that turned out.

The pharmaceutical regulation system, in a 1^st world nation like the UK, is onerous for very good reason.

We should trust that system , not seek to by-pass it

David Raynes

National Drug Prevention Alliance

Slough.

Source: Email from David to dtletters@telegraph.co.uk June 2018

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 school and 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 necessarily impede brain development both in the cortex and in key subcortical major centres including 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:

1. In socially conservative states cannabis use is falling or flat whilst it is rising in more liberal states;
2. 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;
3. The rate of almost all congenital anomalies in the USA has risen when reasonable estimates for ETOPFA rates are employed;
4. Cannabis exposure is significant for all 62 anomalies combined considered as a group;
5. 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;  
6. If one considers the groups of:

1. 1. Cannabis related disorders (as defined by the Hawaiian investigators);
   2. Chromosomal defects;
   3. Cardiovascular defects;
   4. Derivatives of the endocardial cushions

The population exposure to cannabinoids remains highly significant including consideration of state and year

1. Considering all 62 defects collected by the US National Birth Defects Prevention Network :
   1. In 43 cases (69.3%) the community cannabinoid exposure remains significant on linear regression testing before correction for multiple testing;
   2. When one adjusts for multiple testing 38 defects (61.3%) remain significant – mostly as described by the Hawaiian researchers;
   3. 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.

Email sent in copy to Drug Watch International June 2018 drug-watch-international@googlegroups.com

This is a copy of an article which was submitted to BMJ but was deemed unsuitable for publication

Short Title:
Case for Caution with Cannabis
Albert Stuart Reece 1,2
Moira Sim 2
Gary Kenneth Hulse 1,2
1 – Division of Psychiatry,
University of Western Australia,
Crawley, Western Australia 6009, Australia.
2 – School of Medical and Health Sciences,
Edith Cowan University,
Joondalup, Western Australia, 6027, Australia.

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 ^1-7 where they can directly disrupt key functions ^8-12; including cellular energy generation, DNA maintenance and repair, memory and learning ^{1-7,9,10,13-24}.
Empirical literature associates cannabinoid use with CB1R-mediated vasospastic and vasothrombotic strokes, myocardial infarcts, arrhythmias ^25-98 and arteritis ^{25,77,78,99-106}.

Cannabis has been associated with increased cardiovascular stiffness and vascular aging, a major surrogate for organismal aging ¹⁰⁷. 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 75,108 and, via the omphalo-vitelline arterial CB1R’s ²⁵, gastroschisis ^108-114. Cannabis has been linked with several other malformations including hydrocephaly ¹⁰⁸. Cannabinoids also induce epigenetic perturbations ^115-123; and, like thalidomide ^124-126, interfere with tubulin polymerization ^127-132 and the stability of the mitotic spindle precipitating micronucleus formation ^129,133-142, chromosomal shattering (chromothripsis) ^129,143-157 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” (CRCSN) program tracked congenital anomalies 2000-2013 ¹⁵⁸. 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. In 2012 medical cannabis was legalized and in 2014 cannabis was completely legalized.

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%; Figure 1); 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; Figure 2-7). 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; Figure 8).
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 (left hand column Table 1) have risen several times more than the birth rate (right hand column).
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 159,160. This CRCSN 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 ¹⁶¹. 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 ^{132,136,162-166}. Cannabis is usually used amongst humans for its sedative effects.
Other examples of high congenital anomaly rates accompanying increased cannabis use include North Carolina ^167-169, Mexico ^170-175, Northern Canada ^111,176-178, New Zealand ¹⁷⁹ and the Nimbin area in Australia ^180-183.
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 ^121,184-226. Foetal Alcohol Syndrome (FAS) is known to be epigenetically mediated ^227-252 and foetal alcohol is known to act via CB1R’s ^{187,204,207-209,211,217,253-260}.

Cannabis has significant and heritable epigenetic imprints in neural, immune and germ cell (sperm) tissues ^{20,117,119,120,122,261-263}, and epigenomic disruption has been implicated in FCS ²⁴². 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 ²¹².
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 ^134,264-270.

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” ¹⁵⁸.

These data also directly imply that young adults, as the very group which most consumes cannabis ^{160,161,271-274} is the very group which most requires protection from its reproductive, genotoxic and teratogenic effects.

Yours sincerely,
Assoc. Prof. Dr. Stuart Reece.
University of Western Australia and
Edith Cowan University,
Perth,
Australia.

An original copy of the article with full references and figures is available here

Case for Caution with Cannabis JAMA 5.1 – With Full References

Source: Article from Dr Stuart Reece June 2018

This is an email from Professor Stuart Reece sent to the Drug Watch International mailing list: 

Yes indeed there is certainly more to the Cannabis in Canada story than given in Pam McColl’s Oped.

If one looks at the places where the most cannabis is smoked in Canada it is in those same northern reaches where congenital anomalies are commonest – serious defects amongst children like heart defects and born with bowels hanging out.

That is to say – Canada has shown the world what not to do!!!!

Why is this story not being widely told when the maps are so clear???

Canada’s Trudeau’s claims to be following Colorado….

And indeed he is.  Colorado’s congenital anomaly rate  – and especially congenital heart defect rate rose 70% 2000-2013 – prior to legalization in 2014 – it is almost certainly way north of that now – the only question is how far???.

In 2000 only 7.6% of Colorado children had a major congenital anomaly rate – that is more than twice the national USA average about 3.1%. 

In 2013 12.6% of children had a major congenital anomaly – four times the national average – and 1 in 8 Coloradan children!!!!!!!

And we are continuing down this path… because….???

So both Canada – and Colorado – have taught the world what NOT to do….

So why are we rushing as fast as we can in so many places to repeat their mistakes???

Because the media told us to????

Sorry this story is not making sense at all….

Thanks so much,

Prof. Dr. Stuart Reece,

Australia.

Email sent to Drug Watch International (DWI) drug-watch-international@googlegroups.com June 2018

This is an excerpt from an email sent by Stuart Reece to Senator Eric Abetz as part of a Drug Watch International discussion relating to the proposal for Drug Decriminalization in Northern Territory of Australia, more specifically related to the effects of cannabis exposure to malformation of babies.

Eric you might also be interested that I am working on a study of cannabis as a contributing factor to the pattern of congenital malformations seen in babies world wide with  some of the top people in the world.

I am also doing a detailed dissection of some of the congenital anomaly rates in various conservative and liberal USA states again exploring is cannabis exposure can explain the different patterns seen – as we would very much expect from the observed pattern of congenital anomalies and the basic science of cannabis teratogenesis to this point.

Interestingly perhaps there seem to be about five major routes from cannabis exposure in father or mother to malformation of babies.  They are:

1. Epigenetic changes – disordering of the software programming that the DNA gene sequence carries
2. Disruption of mitosis and cell division by disruption of the mitotic spindle and interference with the tubulin rails along which the chromosomes slide in cell division
3. Disruption of cellular energetics which relates to DNA physiology both indirectly and directly and via modulation of epigenetic pathways
4. Interruption of the blood vessel pathways – foetal vessels carry high density cannabinoid type 1 receptors (CB1R’s).  Since they guide nerve and limb and muscle development, disruption of the blood vessels implies major failures of foetal formation, and disruption of the well documented processes of heart valve and major central vessel formation, since the tissue from which heart valves and great arteries are formed also has high levels CB1R’s
5. Major changes to sperm and egg formation with major damage to the DNA, protamine proteins which package DNA in sperm, sperm epigenome, and the physiology of the reproductive tract in both male and female

The spectre  of another thalidomide disaster is a real concern which has very much not been factored in to the debate so far.

Why we cannot learn from history completely eludes me…..???

Source: Email sent in copy to Drug Watch International. May 2018

This is a copy of an email sent by Stuart Reece to members of the Australian Northern Territory government, particularly addressing Dr Jennifer Buckley.

Dear Dr Buckley,

I am a Professor of Addiction Medicine at Edith Cowan University on Western Australia, and an Associate Professor of Addiction Medicine at the University of Western Australia.  I hold an earned Doctorate of Medicine from the University of New South Wales in addiction to my basic medical degree.

I understand that your committee is considering adopting a harm reduction strategy focussed view of the management of drug addiction in the Northern Territory including the potential legalization and or decriminalization of all drugs in your jurisdiction.

I wish to place before you my carefully considered opinion that such a strategy would be an unmitigated disaster for the people in your care.

The strategies employed by the harm minimization lobby globally make it very plain that their rhetoric is merely the soft front edge of the full legalization approach sponsored by George Soros.  In this country it has been championed by its unparalleled champion Dr Alex Wodak, President of Australia’s Drug Reform Foundation which unashamedly openly and overtly proposes the legalization of all drugs – goodness only knows why…

Why indeed …  when there is overwhelming evidence of the innumerable harms directly attributable to drug addiction itself.

I work with drug addicts all day long.  Most of those I work with in my clinic agree that slackening off of the laws in this area would be an unmitigated disaster – and that is drug addicts in treatment!!!!

One of the very obvious features of drug addicted patients – of all sorts – is the accelerated pattern of disease which they virtually all get.  Disorders of brain, heart, circulation, liver, muscle wasting, psychology, bones, reproductive system and immunity together with cancers, elevated death rates and major anomalies in the babies born to addicted parents – have all been described in virtually every addiction.

It has recently been shown that the maintenance of cellular energy stores is critical to the upkeep and maintenance od NA.  Without good energy stores DNA become fractured and broken, cells age, cancers form and abnormal babies are born and infertility rises.  The community pays the cost – obviously; and individual patients bear the brunt of the illnesses.

It is known moreover that from age 20 the energy inside cells halves every 20 years.  Declining cellular energy stores therefore form one of the key cellular measures of ageing.  Restoring those energy stores is therefore a major project within anti-ageing medicine and a major therapeutic goal for clinical medicine.

IT HAS BEEN KNOWN FOR SEVERAL DECADES THAT ALL THE ADDICTIONS DRAMATICALLY REDUCE CELLULAR ENERGY STORES – AND THEREBY DIRECTLY PHENOCOPY CELLULAR AGING –WHICH OBVIOUSLY EXPLAINS THE POLY-SYNDROMIC MULTISYSTEMIC CLINICAL PRESENTATIONS OF DRUG ADDICTION.

For example data emerging from our still on-going analysis of the rates of deformed babies in Colorado show that most of the cannabis related anomalies are rising, which includes all of the fastest growing anomalies, and that the overall rate of congenital heart defects and total defects has almost doubled 2000-2013; Cannabis was only fully legalized in Colorado in 2014!!!  That is the good news – for it has also been shown that cannabis interferes with the basic processes of brain formation also.  The babies born to drug dependent parents are very obviously very far from normal in most cases – certainly when the addictions are severe – when indeed children are lucky to survive even until birth!  So cannabis is a known teratogen and its widespread use is likely to cost the community very dearly in the years to come.

I have attached for your benefit some submissions I recently made to the FDA and WHO on the subject of cannabis genotoxicity and cannabis teratogenicity.  With your permission I would also like to place this material which explores these themes in much greater depth, in evidence before your committee.

Since I have spent a whole professional lifetime studying these issues I trust it is clear that I could place mush more evidence before you.

I am happy to answer any other questions you might have.

Similar remarks can be made in relation to opioid and amphetamine abuse.

I understand clearly that in parts of the Northern Territory drug use is rife.  I also understand that in parts drug use if forbidden by local community law and alcohol is banned in many places, so-called “dry communities.”  The answer to this is proper education of the community and appropriate constraint of drug use and drug trafficking by law enforcement in line with our international obligations under the Single Convention, the United Nations Convention of the Rights of the Child and many others.  

I would point out that it is my view, and also that of many other well informed experts and individuals, that the very obvious gaping hole in the our drug education for the community is an obvious major breech in our community response to the issues of drug enforcement, which almost alone allows the media-driven misinformation and disinformation of the crazy ideologues with virtually unlimited financial resources to push our society in directions which we would never normally go if the truth was well known and widely disseminated and widely taught and widely practised.  It is the yawning gaping hole in the public education program alone which allows the lies, dissembling and dissimulation of the crazy anarchists to threaten not only the wellbeing of our communities, but indeed the sustainability of western culture into the future.

And I might add their genetic and epigenetic pool for the next hundred years….

That is to say – it is not the threats of the lies of the media barons and dysfunctional popular rock idol darlings – who keep committing suicide – which is the major threat to our culture – but the absence of truth in the public place – which is obviously officially sponsored – which allows these lies to flourish in the first place.  The implication is that a modicum of well-informed public health education would quickly drown out a whole cacophony of media-driven highly-paid lies.  It is therefore our joint responsibility to make sure that the popular narratives of our culture are fact-based and evidence-driven rather than purely ideological and agenda-driven as at present.

Thankyou for considering my material.

I am happy to work further with your committee to assist you in your deliberations.

Yours sincerely,

Prof. Dr. Albert Stuart Reece,

MBBS(Hons.), FRCS(Ed.), FRCS(Glas.), FRACGP, MD(UNSW).

Edith Cowan University, Joondalup,

Source: Copy of email sent to Drug Watch International for distribution by Stuart Reece. May 2018

Attached is a submission from Professor Stuart Reece to the Food and Drug Administration in USA for forwarding to the World Health Organization relating to the re-scheduling of cannabis

FDA Federal Register Submission for WHO Review and Consideration – Colorado Teratogenicity Patterns Illustrated

Email from Stuart Reece April 2018

This is an exchange on Drug Watch International with questions from Roger Morgan and responses from Dr Stuart Reece (in bold italics)

Hi Stuart

In reflecting on the studies referred to by Peggy Mann from 40 or 50 years ago, combined with your recent research, I believe we need to do some more research.  I have the following questions:

1. What is involved evaluating the chromosomes in cells of humans?  Do you take a chunk of flesh, or ???? No.  Would most universities have the capability to do this? No.

If you wanted to do this properly studies would involve the following.  I think they need to be detailed and extensive in view of the now massive populations risks which are presented.  You are actually talking about something which may be devastating – if 12% of Coloradan babies are impact PRIOR to legalization then “Houston, Houston we have a problem…  This is Apollo 13 calling.”

1. Cell culture studies – many cells, neurons, sperm and eggs, gut cells skin cells
2. Several species – white rabbit and hamsters model humans best.
3. Human cell lines – many
4. Human cells – skin cells, cheek cells, transformed white blood cells – lymphoblastoid cells – EBV infected lymphocytes taken from blood samples
5. Human sperm

1. A key change would be to apply next generation sequencing to these cells and tissues so:
   1. DNA
   2. RNA
   3. Proteins
   4. DNA methylation
   5. Histone changes – nuclear proteins looking for
   6. Epigenetic changes
   7. Epitranscriptomic changes
   8. Metabolome changes
   9. The interaction between the metabolome and the epigenome
   10. Profile the immune change including cytokines in detail – these are very important and far reaching and cause aging and germ cell damage – cytokines – TH17 cells etc…
   11. Compare the immune and growth factor changes seen in cannabis exposed patients with old folks and compare the way they reproduce clinical aging.

1. Look at pregnancies prospectively.  Look at the sperm of males – sequence them do genetic and epigenetic studies.  Then study their babies and see if they carry the same abnormalities after birth…  See how the correlate with the various congenital anomalies.

2)  What are the implications if the cannabis consumers only have half of the 46 chromosomes that are normal in humans?  Not true.  Physical and mental abnormalities in offspring …. and future generations?..   Chromosomal anomalies will do this yes – and chromosomal shattering processes which cannabis can induce.  Cannabis changes cell division process causing chromosomal shattering and also epigenetic changes – changes in the signalling along the DNA on how the genes are used and expressed.

3)  Will the chromosome levels return to normal if a person quits consuming cannabis?   Short answer – not studied yet.

Long answer – yes I think there will be a degree of repair.  However I also think it is unlikely ever to return to normal. Especially after heavy use because some of the epigenetic imprinting is permanent – obviously from studies which have been done.

4)  Cannabis is known to cause mutations to sperm and ova which can affect a fetus even before pregnancy.  If they stop using, will everything return to normal?  Same as above. Serious concerns.  Depends on level of exposure.  Depends on time between cannabis and making babies…   I do not mean to imply that one or two joints as a young person and babies ten years later is bad.  Nothing suggests that.  But heavy cannabis use such as we are seeing more and more if – and Deborah Hasin from Mailman School of Public Health  in 2017 said USA has an extra 500,000 of in legal states – that is a big problem for later reproduction.

I think the evidence that young people of reproductive age should not go near cannabis for genotoxic reasons is now very strong indeed, and so too do all of my collaborators including my biostatistical friends.

Consider:

1. 12.6% of Coloradan had major congenital anomalies in 2013 PRIOR to legalization
2. The rate of cannabis use by people over 12 years in Colorado was 14% in 2013
3. The rate of cannabis use by all pregnant women in California in 2015 was 8% on testing
4. The rate of cannabis use by mothers less than 20 years in California was 24% in 2015.

So about as many babies are being born deformed AS ARE BEING EXPOSED TO CANNABIS.

So clearly a very high percentage of cannabis exposed babies are experiencing major congenital anomalies.

This should send shivers down our spine – not only that cannabis use is rolling out but that cannabis use is aimed primarily at young adults the very group who should be keeping well away from it.

We need to define these risks much better at the population level by careful studies.

Sperm would be easy to collect and study and define and then correlate with subsequent foetal outcomes.

Thanks and God bless – and spare us all,

Stuart.

Source: Email to Drug Watch International www.drugwatch.org April 2018

The following is an extract from an email by Stuart Reece to Drug Watch International (DWI)

It seems to me that the main pillars of this argument rest on the following primary evidentiary supports:

1. AGEING (spelt “aging” in the USA)  is often defined as an accumulation of deleterious changes over time.  What is the toxicopathology of cannabis characterized by?? An accumulation of deleterious changes over time – which is obviously the same;
2. The multi-system and panorganismal nature of the cannabis related changes is strong clinical evidence that rather than a process limited just to one organ – such as the brain – what we are actually seeing is indicative of a deeper change across all cells, which likely manifests in certain organ specific ways.  This is the list of organ damage below.
3. A concatenation of age-defining illnesses:

1. The arterial toxicity of cannabis is a very big deal because it is one of the major hallmarks of ageing – most people in industrialized nations die from stroke or heart attack, and arterial ageing is the major surrogate for organismal / biological ageing.  So arterial ageing – far from being a curiosity in the cannabis literature – assumes massive importance in general medical terms
2. The association of cannabis with ten cancers is massive.  Cancer is also an age defining disease.  So one cannot say that cancer is associated with cannabis and so what – this is a very big deal indeed.  Cancer is one of the major age defining diseases
3. Immunopathy.  By stimulating the immune system cannabis increases one of the major ageing pathways.  The pro-inflammatory actions of     cannabis are now well documented.  In ageing medicine this is described as “inflamm-aging.”  It is a major pathway to ageing and age related disease, and is known to be linked with high death rates.  Cannabis is usually described as being immunosuppressive.  But we are learning that the immune system is a very complex place.  It is like a trampoline mat.  If it goes down in one place it will go up in another.  Hence patients with immune compromising disorders like rheumatoid arthritis and systemic lupus get immune complications and autoimmune diseases – including cancer.
4. Negative effect on stem cell division.  Obviously we need our stem cells healthy so that we can stay healthy.  Cannabis advocates cannot have their cake and eat it too.  They propose it as a cancer remedy because it stops cell division.  Well if you accept that argument then you must also accept that its effect on cell division is negative which has a catastrophic implication for general stem cell health in all tissue beds
5. The effects on children.  If children are born with mental compromise, paediatric cancers, and foetal malformations then that is a sign of infantile induction of ageing both by definition – since cancer defines age related disease – and since this is obviously an accumulation of deleterious ages in the paediatric age group.
6. Genotoxicity. The association of cannabis with both cancer, congenital malformations, mental retardation in offspring and congenital cancers becomes strong presumptive evidence for genotoxicity.  This is one of the best described pathways to cellular and organismal ageing.  Congenital cancers (rhabdomyosarcoma, leukaemia and neuroblastoma) are ALWAYS due to genetic defects inherited from parents or earlier generations
7. Epigenotoxicity.  As you are aware it is now a matter of record that cannabis has now well documented epigenetic changes (Szutorisz 2018; Neuroscience Behav Rev 85: 93).  The epigenetic levels is one of the strongest hypothesized levels for ageing.  In truth it interacts strongly with the metabolome (since that supplies its substrates) and the genome (since epigenetics seems to often determine sites of DNA cutting and gene splicing both in normal cells and in cancer).  The epigenetic signature of cannabis has even been traced through sperm (Lombard).  Hence ageing has an epigenetic signature and so too does cannabis.  Whilst the two have NOT been formally compared to my knowledge, in view of the above it seems more than likely that significant overlap will be found. Indeed cannabis induced changes in some major epigenetic enzymes, particularly Sirt2 – likely the best age-documented enzyme ever – were documented by Quinn (2008; Neuropsychopharmacology 33:1113).  Inheritable epigenetic immunotoxicity was also documented by Lombard C (2011; JPET 339:607)

Source: Email from Stuart Reece to Drug Watch International drug-watch-international@googlegroups.com February 2018

The implications of these findings on the propagation of cannabis genotoxicity and epigenotoxicity to the next generation extremely significant.

Prior to this research, the field was aware of the effects in the male but the work in females is more recent.

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HUMAN REPRO AND GENOTOXICITY ARTICLE

There are several principal pathways to inheritable genotoxicity, mutagenicity and teratogenesis 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 atrioventricular 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
Cannabidiol 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:  By Professor Dr. A. S Reece
(Edith Cowan University & University of Western Australia) 2019