The straight dopamine theory could be up in smoke

There is now growing evidence that cannabis use causes a small but reliable increase in the chance of developing psychosis. Traditionally, this was explained by the drug increasing dopamine levels in the brain but a new study shortly to be published in NeuroImage suggests that the active ingredient in cannabis doesn’t effect this important neurotransmitter.

Despite some dissenting voices, disruption to the mesolimbic dopamine pathway is widely thought to be the key problem in the development of delusions, hallucinations and the other psychotic symptoms commonly diagnosed as schizophrenia.

This has led to the assumption that the small increased risk of psychosis reliably associated with cannabis use is due to the drug increasing dopamine levels in a deep brain structure called the striatum.

In itself, this is partly based on another assumption – the virtual mantra of recreational drug research that ‘all drugs of abuse increase dopamine levels in the reward system’ of which the striatum is a part.

This new study, led by neuroscientist Paul Stokes, tested dopamine levels by using a type of PET brain scan where participants are injected with a radioactive tracer that binds to free dopamine receptors. Higher dopamine levels will mean that there are less free dopamine receptors and, therefore, lower tracer levels.

Participants were tested twice, once when given placebo and once when given a dose of pure THC – one of the most important active ingredients in cannabis. The dose was designed to be roughly equivalent to the amount you might absorb from a single joint.

The researchers found no difference in dopamine levels between the THC and the sugar pill, even though the participants clearly reported the effects of the drug.

Although they only tested 13 participants, this is the largest study of its kind so far. These type of neurotransmitter tracer studies are know to produce conflicting results at times, so further experiments will be needed to be sure of the result.

But if it is the case that cannabis does not cause a significant increase in dopamine levels, this will mean our ideas about cannabis and psychosis will need a rethink.

It also shakes up the idea common idea that all recreational drugs are pleasurable because they affect the ‘dopamine reward system’.

Link to PubMed entry for the ‘in press’ study.

13 Comments

  1. Posted June 28, 2009 at 11:44 am | Permalink

    “It also shakes up the idea common idea that all recreational drugs are pleasurable because they affect the ‘dopamine reward system’.”
    Right, but actually cannabis has long been known to be rather unique amongst recreational drugs in that animals don’t like it. Animals will self-administer most drugs – notably opiates, cocaine, and amphetamines – also alcohol & nicotine – but not cannabis.
    Or at least you have to work very hard to get them do so. I believe some people have managed it, but it’s hard.
    Animals also don’t like hallucinogens.
    My suspicion is that drugs which humans find “pleasurable” probably do involve dopamine whereas ones which people find “interesting” don’t. And in my experience at least people usually find cannabis interesting (& enhancing to other experiences) rather than pleasuable per se.

  2. Posted June 28, 2009 at 6:53 pm | Permalink

    What is the evidence that cannabis increases the chance of developing psychosis? Can you provide citations?

  3. Posted June 28, 2009 at 11:06 pm | Permalink

    For about 15 years now, the PCP/NMDA model has been an alternative to the straight dopamine theory of schizophrenia (reviewed by Javitt 2008 http://www.ncbi.nlm.nih.gov/pubmed/18497092) – “PCP) and ketamine induce psychotic symptoms and neurocognitive disturbances similar to those of schizophrenia by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors.” This view received more attention with the results from the Phase 2 clinical trial with LY2140023 (a glutamate agonist).
    Neuroskeptic – I thought monkeys *will* self-administer THC, e.g. Justinova et al. (Neuropsychopharmacology 2008).

  4. Richard N
    Posted July 29, 2009 at 7:47 pm | Permalink

    Hey Neuroskeptic–
    I trained dope smelling dogs for the Border Patrol and, well… dogs LOVE pot. You feed them, on average, about 1/4 oz. per day in their food. Yes, they get a tad weird, and yes, they ‘nap’ a lot.
    Do they “like it”… oh, yes. They will tear a car to pieces if they smell any. The hardest part is to keep them from eating the evidence when they find it. Typically we would abstain from feeding any pot for 2 days before they went to the field to work. While dogs can be trained to find drugs without “sampling” them, the ones who have been stoned are a great deal more effective.
    During this training period I also noticed that my two house-cats were very interested in pot and would also eat it, happily. But being cats, it was hard to tell if they liked it. Sure did seem to.

  5. Yezizhang
    Posted June 28, 2010 at 4:11 am | Permalink

    Animals don’t like pot? Just type in cat eating pot in youtube. I grew medical marijuana for a clinic and I had a cat that LOVED to eat the leaves. My stepdad used to grow it in his backyard and his cat would love to nibble on the plants. Where did you hear that animals don’t like cannabis?

  6. Yezizhang
    Posted June 28, 2010 at 4:19 am | Permalink

    CarlLuma-
    http://www.nida.nih.gov/Infofacts/marijuana.html
    http://www.nimh.nih.gov/health/publications/schizophrenia/complete-index.shtml
    http://www.theantidrug.com/drug-information/marijuana-facts/marijuana-mental-health.aspx
    http://www.medpagetoday.com/Psychiatry/Addictions/18722
    And many, many more studies. Just search Google Scholar or any medical journal sites.
    I would know, heavy marijuana use precipitated my schizophrenia.

  7. Yezizhang
    Posted June 28, 2010 at 4:24 am | Permalink

    Neurocritic
    the results from the Phase 2 clinical trial with LY2140023 (a glutamate agonist) were disheartening. Because there was barely any efficacy for LY2140023 they have to do more Phase 2 trials. They were heavily dissapointed with the results

  8. Wag
    Posted August 12, 2010 at 11:43 pm | Permalink

    @Yezizhang the problem with making statements such as this, is that there really are no conclusive studies to support the view that Marijuana causes schizophrenia. Even the most biased government anti-drug campaign funded studies are only reporting a small increased risk for developing schizophrenia. That is well within their margin of error, as they have no way of knowing if the test subjects (which aren’t even human) were already developing schizophrenia before the cannabis was administered.

    In the USA barely 1% of the population at any given time is diagnosed with schizophrenia. According to NIDA (US drug war propaganda think tank), up to 50% of US 12th graders in 1997 had used Marijuana. If there was any actual connection between marijuana and mental disorder, we would have an epidemic on our hands.
    http://drugabuse.gov/ResearchReports/Marijuana/default.html
    At best, modern psychology is guesswork. We throw compounds at the brain and analyze the results. What’s worse, people have wildly variable response to the same compound. Our FDA will approve drugs that have clear risk of death as a side-effect and place a drug such as marijuana on Schedule I (no medicinal value, illegal) that is, at best, tenuously connected to schizophrenia. Even the most biased sources (NIDA, Drug Czar) have not used the “schizophrenia connection” in many years here in the USA. If there was any real science behind the idea, they would use it. In fact, recent studies further discredit it.
    http://www.ncbi.nlm.nih.gov/pubmed/20471224

  9. David
    Posted May 12, 2011 at 1:26 am | Permalink

    Are you trying to prove it’s bad??? Never hurt anyone I know, too late in the evening to get technical on an iPod

  10. Posted July 12, 2011 at 4:46 pm | Permalink

    http://www.ukcia.org/research/keele_study/Assessing-the-impact-of-cannabis.pdf


    A recent systematic review concluded that cannabis use increases risk of psychotic outcomes
    independently of confounding and transient intoxication effects. Furthermore, a model of the
    association between cannabis use and schizophrenia indicated that the incidence and
    prevalence of schizophrenia would increase from 1990 onwards. The model is based on three
    factors: a) increased relative risk of psychotic outcomes for frequent cannabis users compared
    to those who have never used cannabis between 1.8 and 3.1, b) a substantial rise in UK cannabis
    use from the mid-1970s and c) elevated risk of 20 years from first use of cannabis. This paper
    investigates whether this has occurred in the UK by examining trends in the annual prevalence
    and incidence of schizophrenia and psychoses, as measured by diagnosed cases from 1996 to
    2005. Retrospective analysis of the General Practice Research Database (GPRD) was conducted
    for 183 practices in England, Wales, Scotland and Northern Ireland. The study cohort comprised
    almost 600,000 patients each year, representing approximately 2.3% of the UK population aged
    16 to 44. Between 1996 and 2005 the incidence and prevalence of schizophrenia and psychoses
    were either stable or declining. Explanations other than a genuine stability or decline were
    considered, but appeared less plausible. In conclusion, this study did not find any evidence of
    increasing schizophrenia or psychoses in the general population from 1996 to 2005″

    There you go. Cannabis does not cause any extra cases of Schizophrenia when you actually bother to look for them.

    As ever, show me the bodies, then I might see you in court.

  11. Danny T
    Posted January 5, 2012 at 7:49 pm | Permalink

    Im pretty sure cannabis lowers levels of dopamine the same way an anti-psychotic would BUT when the levels are too low for extended periods of time, the brain will increase the natural amount of dopamine created to make up for the lack of, to restore balance to the individuals natural chemical levels.

  12. Patty
    Posted May 13, 2012 at 10:43 pm | Permalink

    The discussion over cannabis is way too abstract. The fact is every strain is different. It’s not like alcohol where the only difference is the amount of alcohol in each type of booze. With cannabis each strain is a completely different drug that can attach to either serotonin, dopamine or acetylcholine. Cannabis for autism is a good idea but not until people learn what the hell they’re talking about should they just abitrarily assume all pot is indicated for autism.

    • Posted February 11, 2013 at 12:46 am | Permalink

      It has been my experience that dopamine antagonists can effect how marijuana is processed. I started taking a dopamine antagonist in 2006. From 2006 thru 2010 marijuana had a profound effect on me, so much that I stayed away from it. The last 3 years however I have not been able to get high no matter how much I smoke or eat.

      I’ve gone through periods in my life where I was a daily marijuana smoker mixed with years of not smoking at all. I’d say over the last 25 years I was a daily smoker for 7 years. I can’t say that marijuana has contributed to my paranoid delusions or not. Personally, I think having used ecstasy 10 times, one time injecting meth and a couple times smoking weed laced with god knows what was far more damaging than all those years of smoking marijuana. I do know that I was drinking myself sick once a week while I was in the Navy. I finally said that enough was enough and started growing/smoking weed everyday. I have never had a problem with alcohol since.

      I miss getting stoned. I really hope that I’ll be able to sometime in the future again, but that is looking like less and less of a possibility. I got off the dopamine antagonist for a couple of months a couple months ago. After two months, I still couldn’t get high. My sex drive was back to normal, I was eating normally again and my head was clear so working was a real pleasure. I did wind up hearing voices and ended up in the hospital again though.

      The only upside I see is that I can eat as much food with marijuana in it as I want. Tasty! No really, I’ve had some really good food with it in it.


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