Ask the Doctors by Eve Glazier, M.D. and Elizabeth Ko, M.D

Link Between Marijuana Use and Schizophrenia Needs Further Study

Dear Doctor: Could you comment on the marijuana study done in early 2016 at the University of Exeter and University College London? I'm worried about the 14-year-olds with whom I work and their dangers of psychosis. I was hoping we might start a dialogue about the risky business of marijuana.

Dear Reader: One of the big concerns about marijuana use, especially among adolescents and young adults, is the connection to psychotic episodes and lifelong schizophrenia. In people with a family history of schizophrenia, marijuana can increase the risk of such episodes and decrease the age of schizophrenia onset. The study to which you refer sheds some light on that risk.

That study focused on the AKT1 gene, which has been proposed as a possible genetic connection to this response to marijuana. The gene produces the enzyme serine-threonine protein kinase, necessary for many cellular processes throughout the body -- including the transmission of dopamine, which carries signals between brain cells. This function is known as dopamine signaling, and proper signaling is necessary for the brain responses controlling behavior and emotion.

As background, studies in mice have shown that marijuana activates the AKT1 gene in the brain's cerebellum, hippocampus and striatum. Second, schizophrenia has been linked to disturbed and hyperactive dopamine signaling. The concern is that, if AKT1 is stimulated by marijuana -- increasing dopamine transmission in the brain -- then psychosis may occur.

Note, however, that the AKT1 gene differs in people. In schizophrenia, the AKT1 2494732 type is the one most likely to be stimulated by marijuana. People with two copies of this gene type have twice the likelihood of a psychotic episode and other symptoms of schizophrenia.

The study you mention looked at 422 people, ages 16 to 23, who used marijuana at least once a month. Participants were given a pair of psychological tests at two different times: once without the use of marijuana and once with use. One psychological test was designed to detect psychotic symptoms; the other test was designed to detect dissociative and imaginative states, also called schizotypal symptoms, similar to those seen in schizophrenia. The researchers also did genotype testing to identify people with the AKT1 2494732 type.

Of the 422 participants, 197 had one copy of the gene and 91 had two copies. When intoxicated with marijuana, people with one or two copies of the AKT1 2494732 type had moderately greater psychotic symptoms, but other participants were not free of symptoms. Also, interestingly enough, schizotypal symptoms were not associated with this gene type, but were associated with a dependency to marijuana. People who were both dependent on marijuana and who had the AKT1 genotype were more likely to have psychotic symptoms.

Overall, the study does point to a genetic link between psychotic symptoms and marijuana use, but the link is more complicated than the presence of a specific genotype. Because 288 of the 422 participants had at least one copy of the gene, the data should have been more overwhelming. Clearly something else is occurring to push some people toward schizophrenia; we just don't know what.

With more definitive research, individuals could be genetically tested as to their susceptibility to schizophrenia with the use of marijuana. For now, we simply know that a family history of schizophrenia increases the risk among people who use marijuana -- making it risky business indeed.

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