Marijuana and Madness

The risk depends upon your genes.

Posted May 16, 2018

Given that so many states are now making marijuana available for medical and/or recreational use, the question of whether marijuana causes psychosis is not likely to go away soon.  I am often asked the question “if I smoke marijuana, will I become psychotic?” The answer is “it depends.”   It depends upon the genes of the person who is asking the question.  Having a genetic predisposition to psychosis makes one vulnerable to the consequences of smoking marijuana.  Unfortunately, there are no genetic tests currently available to inform someone with certainty that they are at risk of developing psychosis.  Thus, answering this question remains impossible. One thing is certain, the overwhelming number of people who smoke marijuana will NOT develop psychosis. The problem comes in knowing whether you are going to be one of the unfortunate ones.  

Despite reports from several high-profile observational studies of a dose-dependent association between cannabis use and risk of psychosis, a causal link between cannabis use and psychotic disorders remains controversial.  Why?  Observational results are frequently hindered by the possibility that another risk factor associated with cannabis use might be more closely associated with developing psychosis. Alternatively, people who are affected by the early symptoms of schizophrenia might be turning to marijuana to self-medicate themselves.  Marijuana use by these nascent psychiatric patients might be reducing some of their symptoms long before they become part of their diagnosis. 

A recent study (Molecular Psychiatry 2018, Vol 23, 1287–1292) investigated ten different genetic variants, called single-nucleotide polymorphisms (SNPs), in almost eighty thousand subjects and found an increased risk of schizophrenia if these variants were present in the marijuana users. If you have had your genes analyzed, these are the SNPs that were associated with the greatest risk of developing schizophrenia: rs12518098, rs35053471, rs2033867, rs7107977, rs4471463, rs73067624.  A word of caution when considering your risk—simply having a SNP that places you at risk is not sufficient to actually induce psychosis, should you decide to use marijuana. Reality is much more complicated than one gene = one disease.  

The connection between marijuana use and schizophrenia is also muddied by the fact that cannabis use is strongly associated with tobacco consumption.  Conversely, tobacco use is strongly correlated with marijuana. Indeed, tobacco may act synergistically with marijuana to create the addiction. Making matters worse, tobacco use increases the risk of becoming schizophrenic (we do not read as much about this link in the popular press).  Taken together, current genetic evidence indicates that the association between marijuana and psychosis is significantly influenced by tobacco use. This association essentially undermines any direct genetic link between marijuana use and schizophrenia, i.e. if a person smokes, then it becomes impossible to establish a causal connection between cannabis and psychosis.

Thus, marijuana users who also smoke cigarettes face a challenging dilemma: do they feel genetically lucky?  Today, medical science lacks sufficient data to make a definitive claim regarding whether smoking marijuana induces psychosis.

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