Thursday, 5 September 2019

Cannabis Use and Potential Epigenetic Damage to Autism Genes

Today we consider another risk factor that may be contributing to the increase in prevalence of autism and it is about the father, for a change.  In the public's perception cannabis is a safe alternative way to treat all kinds of medical problems, many experts do not agree.

Fathers who use marijuana may be using it for two, suggests a study from Duke Medical Center. Although the study is small, encompassing just 24 men and 15 rats, it highlights a potential transgenerational effect of marijuana exposure—the passing on of sperm in which an autism-associated gene, DLGAP2, has accumulated extra epigenetic marks.
The Duke scientists, led by Susan Murphy, PhD, associate professor of obstetrics and gynecology, identified significant hypomethylation at DLGAP2 in the sperm of men who used marijuana compared to controls. A similar observation was made in the sperm of rats exposed to tetrahydrocannabinol (THC) compared to controls. This hypomethylated state was also detected in the forebrain region of rats born to fathers exposed to THC.
Murphy and colleagues said their findings do not establish a definitive link between cannabis use and autism, but the possible connection warrants further, urgent study, given efforts throughout the country to legalize marijuana for recreational and/or medicinal uses.
This study is the first to demonstrate an association between a man’s cannabis use and changes of a gene in sperm that has been implicated in autism,” she emphasized. “Given marijuana’s increasing prevalence of use in the United States and the increasing numbers of states that have legalized its use, we need more studies to understand how this drug is affecting not only those who smoke it, but their unborn children.
“There’s a perception that marijuana is benign. More studies are needed to determine whether that is true.”
The original paper:-

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.


I do not think anyone should be surprised that the THC in cannabis may leave an epigenetic tag on the DNA of the user and that it is passed down to following generations. We saw a long time ago that the same applies to people who smoke. It is just a question of which genes are most affected.  In the case of smoking it affected how your body deals with oxidative stress and this blocked how drugs for severe asthma (COPD) should work, so making COPD a very big problem for ex-smokers. Stopping smoking does not make the problem go away.

Any kind of prolonged chemical exposure may be a problem, the lead that was used in gasoline/petrol, current use of potent pesticides etc.  The same applies to electrical/magnetic exposure. Best not to live very close to high voltage power lines, or have a mobile phone mast on top of your building.

The concern is that these epigenetic markers are heritable and so accumulate over the generations, a kind of epigenetic pollution.

If great great grandpa worked down a coal mine or in a chemical factory, it may be recorded in your DNA.


  1. It is a strange time to be living in the United States right now where you have a lot of otherwise smart people, many even with advanced degrees, believe the myth that cannabis is not harmful and is actually healthful because it is "natural". You even have a trend now in the United States where women will smoke cannabis to relieve morning sickness which is a public health disaster that will unfold years down the road when it is too late.

    As for my own parents, well those epigenetic marks from cannabis were obviously passed down to me, while alcoholism and obesity on my wife's side of the family (both have strong negative epigenetic consequences for future offspring that last multiple generations) and even though I do not have autism myself, it is frustrating to think that the sins of my parents and my wife's parents, whether it be cannabis use, smoking, alcohol abuse or the myriad of other factors that go into obesity, have contributed to the challenges in my children, and the challenges I have has a parent and even having this conversation with them is impossible due to their scientific ignorance. If I could build a time machine and warn them about the risks to their future progeny, well then I would, though I am not sure it would do any good because the boomer generation has never ever displayed any semblance of responsibility for the future.

    All we can do as parents, for those of us who are not burying are heads in the sand and ignoring the scientific evidence that suggests we need to be more responsible with our bodies if we want our progeny to even have a realistic chance at life, is to try and fix what is broken now in our children or at the very least employ any interventions which ameliorate some of the damage we have not inherited in our DNA, but rather have inherited via epigenetics from the irresponsible lifestyles of our elders in the past.

    Epigenetic science is still quite young, but some of its findings now are quite terrifying with regards to some of the lifestyle trends you find these days that 99% of people are ignorant of and which gets ignored in the media because they are inconvenient truths.

    For example, autism is a recognized public health crisis, yet Fetal Alcohol Spectrum Disorders (FASD) affect more people than autism does and those tragedies are 100% preventable if society was not so cavalier and ignorant with the health of the children of the future.

    Seeing your children possibly being punished for the sins of your own parents, sins you have not engaged in yourself, is a feeling of unfairness that never goes away.

    1. Tyler, I think the siblings of those with severe autism are one of the few groups that would make lifestyle changes to reduce future autism.

      Monty's elder brother ignores healthy eating advice, but listens intently to advice on reducing the chance of having his own child with autism. It is all about priorities and self-interest

  2. Hi Peter and All,

    Coincidentally, the Thinking Autism has just published a review of cannabis-based medical products use in autism and related conditions. It is comprehensive and I think reading both articles can give readers balanced view on the topic, still underresearched and with many gaps of knowledge:

    1. Agnieszka, it is ironic, but some things that cause autism, like valproic acid in a pregnant mother, can also be therapeutic in the child born with autism.

      We have to distinguish between THC and CBD in cannabis products. Unfortunately commercial CBD products are often found to also contain THC.

      If all you want is CBD then I think people should just use PEA, which is guaranteed to have zero THC and provide similar effects.

      I think some people with autism who get relief from cannabis derived products are reacting to the THC. If someone is self-injuring and you give them a joint, I think you would expect them to calm down.

      If a 50 year old woman with MS finds relief from cannabis that would seem fine, but a 25 year old woman with MS who wants kids would be ill-advised to use cannabis.

    2. Cannabinoids and other cann. plant constituents, especially THC, have much wider effects than just 'calming', the article covers all of that.

      It is all a question of balance, of course as you mention yourself. Just one example of many - heavy recreational smokers will tend to have increased rates of osteoporosis, at the same time cannabis/THC/CBD etc are super protective and can reverse osteoporosis in people who hadn't 'overused' it in the past.

      So if you are starting from a neutral zero point wrt cannabis use you are more likely to get all the beneficial effects. It all depends on your starting point.

      The thing to keep in mind wrt autism -- most of the things that are known/suspected to cause autism (monogenetic disorders, prenatal exposure to infection/inflammation/toxins/valproid acid etc -- read the article for full list) all those things will mess up endocannabinoid system in developing fetus.

      So our kids' starting point is not neutral when it comes to cannabinoids. It is in the deep red.

      PEA sounds great on paper but unfortunately not many report benefits. Most who have tried report zero/hardly any effects, where the opposite can be said for various cbd/whole plant variations. PEA will only work on one aspect of ECS metabolism too, not on receptors directly. Some of the benefits of CBD and THC and other cannabinoids come from their interaction with other types of receptors like PPARs and vanilloid rs.
      (maybe for some a combo of PEA and cannabis extracts would be best, who knows...)

    3. We are a little at cross purposes.

      My post is highlighting that young people who are likely to become parents at some point in the future and who use cannabis are taking a risk that autism genes in their DNA pick up epigenetic tags, and may increase the risk their future kids and grandchildren have autism.

      Children who already have severe autism are unlikely to have heirs, so there is no heritable risk. The only question is whether they receive a net benefit from cannabis.

      The issue is more with people using cannabis for “trivial autism” who will have kids and then they further increase the risk those kids will have severe autism.

      A person with schizophrenia is likely to benefit from nicotine. If they have no children the only risk they take with smoking is with the health of their lungs/heart and the benefit is that they are less likely to commit suicide and be happier. So it is all a balance. But for the general population smoking is clearly better avoided.

  3. Just to be clear there is a big difference between drugs based on cannabis compounds with scientific evidence to support their use (e.g. CBD) and cannabis itself, especially since modern cannabis strains are selected for their THC potency which can be 10 times as strong as what boomers smoked in their younger years.

    Ironically, cannabis prohibition prevented the research and study of its effects in humans and animals in the United States and now that its safety is getting a second look, the science is quite grim and quite sad now that Pandoras box has been opened and the political will to close it may never ever materialize again, especially since the public will in many parts of the country to address the consequences of defacto legalization of even harder drugs than cannabus simply does not exist.

    1. "How Medical Marijuana Manages Myasthenia Gravis-Related Muscle Weakness"

  4. "Reversal of epigenetic aging and immunosenescent trends in humans"


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