Sunday, May 15, 2011

Cannabis and Psychosis

One of the best things about my blogging gig over at Psychology Today is that I've now attracted the attention of more researchers in the field from all over the world.  I'm a clinician doing my work in a suburb of Boston - I know some pretty cool and important people who make amazing research contributions, but I am certainly not among them.   Most of my musings here at Evolutionary Psychiatry are theoretical - there are NO paleo 2.0 diet trials for any psychiatric condition, after all.  If someone walks into my clinic with bipolar disorder, I can't say "oh, just try a ketogenic diet and a multimineral and you will be fine."  There are no trials and case studies of ketogenic diets in the literature were failures.

That doesn't mean I don't push for elimination of food toxins, put in a little plug for pasture butter, demonstrate and encourage stress reduction techniques, focus on good sleep hygiene (and look for sleep disturbance and medical causes), and I do take people off statins when there is good clinical reason (primarily in folks with dementia, with good results, actually.  Also, a couple of cases of resistant depression.) But I can't go full-blown evolutionary psychiatry with all my patients.  Some aren't interested, and for others the data isn't there.  Which is okay.  EvPsych has reinvigorated my interest in the field and in research, and I feel the preventative potential of a paleo 2.0 diet is amazing - so for subclinical disease, I feel my blog and the diet are likely doing a lot of good, far more good than I could do in the time I have to see patients one by one.   But I don't have any proof of that.  Which is okay.  I'll still keep looking for more evidence and more nutritional links.

But!  Cannabis!  I am honored that my twitter feed (warning - I might tweet about Crossfit, shampoo, and my children) is followed by Dr. Sanjuan in Spain, who sent me a link to this article, which among other articles will be the anchor for this post.

Cannabis.  Evo Med is the province of rebels, and rebels love pot...

Pot might not love you.

Cannabis is the world's most popular recreational drug and its use has accelerated among adolescents in the United States.

There are two circumstances in which I tend to see heavy pot use - young people struggling with psychotic disorders, and older folks with lifetime heavy pot use struggling with cognitive function and anxiety problems.  Such circumstances are weighted to bias my opinion against pot as the happy self-medication of choice.  You are forewarned!

Cannabis use has a high comorbidity with populations with psychotic disorders.  Its continued use is associated with poor outcomes in psychosis and with more frequent and earlier relapses (1).    Use has been associated as a risk factor for emerging psychosis, and a young person with heavy use will have a two-fold risk of developing psychosis (2)(3).  The earlier the age at which cannabis is first consumed, the greater the risk.

So, what might cannabis do that would cause psychosis in vulnerable individuals?  THC will stimulate the cannabinoid receptors type 1 (CB1-R) , which are abundant in the cerebral cortex, particularly the frontal regions. basal ganglia, hippocampus, anterior cingular cortex and cerebellum.   All of these areas can play a role in the neural circuitry of psychosis, and animal studies have implicated cannabis as a causative agent in the psychosis hotspot of the mesolimbic area.

Only a small proportion of cannabis users develop psychosis, suggesting there are genetic forces at play.  The primary effect of endocannabinoid activation is the modulation of neurotransmitter release in the mesolimbic area.  Animal studies also suggest that exogenous cannabinoids like THC affect dopaminergic transmission in the prefrontal cortex and the mesolimbic pathway (the areas affected by schizophrenia).

Let's examine COMT.  This enzyme sits in the synapse and will break down dopamine, norepinephrine, and epinephrine.  There is a common polymorphism of the COMT gene - folks with the valine allele of the COMT gene will have higher COMT function than those with the methionine allele.  Increased COMT activity may result in a combination of reduced dopamine transmission in the prefrontal cortex  and increased dopamine mesolimbic signaling - this combination is higher risk in schizophrenia, which presents with decreased executive functioning and working memory combined with risk of experiencing delusions and hallucinations.

Adolescents carrying the Val allele of the COMT gene are more at risk for schizophrenia in the Caspi research - the Sanjuan research found that those with the Met allele were more at risk.  Other studies of cannabis use suggest that those with psychosis are more likely to use cannabis, and more likely to use the high-potency cannabis called "skunk."

That's all well and good.  Repeated used of a cannabinoid agonist (POT) will produce prolonged and repeated use of the cannabinoid receptor.  This will result in hunger, a bit of paranoia, psychosis, euphoria, cognitive impairment, and pain relief, and withdrawal effects of increased pain and anxiety.

So, does cannabis use increase the risk of schizophrenia use or what?  Well, all the studies are observational, and it is pretty clear that those at risk for psychosis (with prodromal symptoms and high genetic risk) will tend to use more cannabis.   However, the strongest evidence against a causative effect of cannabis is from native populations who regularly use cannabis, and in which there is no increased risk of psychosis.  Your risk will depend upon your genes and experience- but I am not a fan.


  1. I never inhaled...

    Actually the one & only time I ever tried it, I was sick for a couple of weeks. Wasn't my scene. However, cutting shapes on the D-floor until the sun came up was, so my recreational drug use was slightly different :)

    I wonder whether there will be differences in the effects of cannabis on native populations not concurrently consumign neolithic agents vs. those new world types who are? In other words, add in sugar, grains, vegetable oils, alcohol, and so on, and cannabis has an entirely different effect?

  2. I wonder that too. It isn't unreasonable to consider the possibility that poor general health is an enabled for a catalyst to wreak havoc. But do we really want the catalyst in the first place? It depends upon the frequency and potency of use how dumb and dulled the drug makes one. I don't recommend that anyone try cannabis either since while some people are able to keep it to a weekly thing that adds a different flavor to life others decide that there is no such thing as too much. We might tell ourselves that we are strong-willed and rational (and teenagers will say it more frequently with less to back it up) but the drugs are exactly what undermine those faculties in the first place.

    If I want to laugh and be confused I'll read Evolutionary Psychology!

  3. Dr. Deans,

    It comes down to cost/benefit. There's no perfect medication. On a macro level, are the costs of keeping drugs illegal worth the benefits, if so benefits to whom? Then on the micro level, is there a cheaper alternative with less side effects for what THC is good for?

  4. This is really interesting stuff.

    Its interesting that Holland seem to have no increase in psychosis since their decriminalisation, maybe the dutch genes are better! Portugal will be the next test I suppose

    As a point of interest the UK recently gave marketing authorisation to the cannabis based medicine Sativex, I assume as this pretty much cannbis in a spray (its contains the same cannabinoids) it poses exactly the same risks as regular cannabis?

  5. I said this in the vernacular to my kids: Stoners are losers. With many anecdotes of friends from my youth who came to grief. I did not smoke weed myself. I basically scared the hell out of them by pointing to assorted psychotic relatives, to fat relatives and saying "do you want to increase your chances of ending up like them--there's obviously a possible vulnerability...". They don't smoke weed.

    It's also interesting how stimulants used to treat ADHD in kid's with a family history of bipolar often trigger psychosis. Sometimes in VERY young kid's. Have seen this directly. Why medication by pediatricians for childhood mental illness is a bad idea.

  6. Like fruit and wheat, modern cannabis is an entirely unnatural product. The most popular strains are bred for abnormally high THC levels, which produce the couch-locking, classic paranoid "stoner" effects, while cannabidiol content, which counteracts the anxiety-inducing effects of THC, has waned. A recent study looked at the cannabinoid composition of seized plants in California and found that the THC:cannabidiol ratios have dramatically increased:

    Another study used cannabidiol to actually reduce social-speaking anxiety in subjects:

    High-THC strains induce short term memory problems in rats, but strains with balanced THC:cannabidiol ratios do not:

  7. re: cannabidiol and social-speaking anxiety... AKA, the Ricky Williams experiment... :-P

  8. pot and tequila, the key to my success in undergrad and medical school. that must be why i'm not so famous. i do agree that modern pot is just a different animal than that of 20 years ago.

  9. I agree it is certainly a risk benefit analaysis. And of course the data is observational or animal studies - but you arent going to get a randomized trial of this sort of thing in young people at high rosk for psychosis If you have a family history of psychosis the safe bet is to steer far clear. I'm going to do some more lposts on cannabis, so this article is not the end of the story. Erik, that is interesting and I don't doubt it. I would say the clinical population i have seen is not, for the most part, particular about the source. Always, though, this hopeful refrain starts in group - it's not the cocaine (or whatever), they say, it is the adulterants. I'm afraid, I said (when I used to run such groups) one of the toxic things about cocaine is the cocaine.

  10. My son returned from his service in the US Air Force in 2006, flying in out Afghanistan-Iraq, no doubt with some level of PTSD, and the struggles of being a gay serviceman. For the next five years he sunk into a lethargy, probably depression, smoking lots of pot daily. His paternal grandmother had severe schizophrenia, which worried me a lot. But finally, last year, I got him to move in with me for three months. I fed him a primal diet, gave him St. JOhn's Wort 3x daily, along with a good vitamin regimen, and got him into therapy at the VA. He is now , at age 29, a changed young man; back in college doing wonderfully. He had tried anti-depression meds, but didn't like them, and believes even now the pot was better. Your post helped me understand part of my own underlying fears.

  11. Unfortunately most of the psychosis link is correlation related not causation related and there are studies that show one of the main cannabinoids - Cannibidiol is effective in TREATING Schizophrenia - not CAUSING it. Maybe we should look beyond our cognitive biases far enough to see that what we think something is may not be what it is.

    Here is an article in Wikipedia that details some of the characteristics of a cannabinoid that comprises approximately 40% of the content extracted from Cannabis.

    Just for the record - prevailing opinion from the people who study endocannabinoids is that it's more likely individuals susceptible to psychosis self-medicate with cannabis and thus the link between use and psychosis.

    You even point out that there is evidence of it not being related but still lead the reader to the conclusion '.... but it might' when there IS evidence that it is ONLY correlation. Maybe we should talk ACTUAL science instead of scare tactics and FUD.

  12. Sure, write this AFTER I move to Denver, CO - mecca of medical marijuana.

  13. do you know about MAPS? (Multidisciplinary Association for Psychedelic Studies?) they've been running ptsd studies on vets with a lot of success . . .

    "supporting psychedelic and medical marihuana use since 1986"

  14. Psychotic people have an increased use of pretty much every drug including tobacco and alcohol. You could cook up a study just like this for any of them and claim that it is evidence of a causation link.

    Psychosis is serious enough that a person will experience symptoms years before diagnosis, so it doesn't matter whether they start using before diagnosis.

  15. The issue with 'Cannabis and Psychosis' isn't with 'Cannabis.'

    The answer lies in the levels of CBD (Cannabidiol) that are present in the cannabis being used. (Lovely how all these research studies say "Cannabis" like we would say "Trucks"... they're definitely NOT all the same)

    Cannabidiol (CBD) is an extremely powerful anti-psychotic. It's so powerful that it counteracts THC very well.

    Strains of cannabis like "Harlequin" that have more CBD than THC in them (8%CBD vs. 6%THC) are completely impossible to get "High" or "Stoned" with.

    Your patients exhibiting psychosis from cannabis would do the same with Marinol pills... the cannabis they're using has insufficient CBD and will cause Manic Psychosis when enough is taken... just like Marinol pills.

    Prohibition is the main cause of today's "Recreational Cannabis" that's nearly devoid of CBD (Usually 1% or less these days).

    I'm looking forward to the days when people realize the three most important things about cannabis:

    1# It's non-addictive

    #2 It's the most medicinal plant on the face of the planet and safer than any man-made drug.

    #3 The CBD content is what medicinal users are seeking

    Keep it Clean! ;D


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