Are some people genetically predisposed to psychosis with cannabis use?

People love to chat about whether smoking weed makes you go crazy. Stoners deny it outright and Daily Mail journalists would bet their mother’s life on it. Obviously the answer to this complicated issue comes not from waving a spliff or a tabloid newspaper in the air, but from good old honourable scientific data. One popular factoid that is thrown around is that some of us are genetically predisposed to the psychosis-inducing effects of cannabis and others aren’t. We’re all just rolling the dice over our future mental sanity when we smoke weed because who knows what genes we’re made up of. This attitude, although extreme, originates from a well-received 2005 longitudinal study which found that the combination of adolescent cannabis use and a Val allele in the COMT gene leads to an increased chance of adult psychosis. In fact, they found that adolescent cannabis use did not boost the chances of adult psychosis at all if neither of the COMT alleles were Val. And importantly, cannabis use after the age of 18 also had no relationship with psychosis, regardless of genetics. However, this is most certainly not to say that if you smoke cannabis as a teenager and you have this specific genetic makeup you will end up psychotic; 92% of cannabis users in this study suffered no experience of psychosis. Since 2005, though, this relationship has not been easily replicated. A large 2007 study of both schizophrenic and healthy people found that cannabis use before the age of 18 did predict psychotic experiences but this was not affected by the genetic variation in the COMT gene. Likewise, a 2011 study recently reported that cannabis use at age 14 predicts the presence of psychosis at age 16, but it is not moderated by variation in the COMT gene. Unlike the 2005 study then, these studies found no interactive effect between genes and cannabis use on psychosis. There are problems with these more recent papers though. The 2005 study involved retrospective data collection: people recalled how much cannabis they smoked in their youth, rather than reporting on their use during their youth. And the 2011 study only looked at 16 year olds. Surely two years of cannabis use is not enough to draw strong conclusions about the relationship between genes, cannabis and psychosis. Those 16 year olds have got a good four years of potential weed smoking before they leave teenagedom. So the honourable, scientific data is not providing us with the clear answers we would like. Furthermore, as with all correlational work, there may be many other factors that are influencing the outcome without being recognised. Perhaps it isn’t the interaction between a genetic variation and cannabis use that increases the chance of psychosis, but the interaction between that genetic variation and high stress, which is found concurrently with adolescent cannabis use. It’s just very difficult to tease these variables apart. Admittedly, some elaborate combination of different genes, which may never be discovered, probably underlies part of the complicated association between reefer and madness, but it may well not be this simple variation in the COMT gene.