Marijuana (Cannabinoids)Schizophrenia

Predicting the risk of psychosis in cannabis users

Cannabis use is associated with an increased risk of psychosis. It’s suggested that genetic variation in the AKT1 gene might influence this adverse effect.

Researchers at Kings College London, in the UK, studied the connection.

First, the details.

  • 489 patients with a first-episode of psychosis were compared to 278 control subjects.
  • The interaction between variation at the AKT1 rs2494732 gene and cannabis use in increasing the risk of psychosis was studied.
    • AKT1 molecule sends signals to the dopamine D2 receptor.
      • Decreased AKT1 function may result in exacerbated responses to stimulation of this receptor.
      • Dysfunction of the dopamine D2 receptor leads to aberrant substance seeking behavior (alcohol, drug, tobacco, and food) and related behaviors (pathological gambling, Tourette’s syndrome, and attention deficit hyperactivity disorder).
    • Lower levels of AKT1 are reported in patients with schizophrenia.
      • There are 3 genetic variations of AKT1: C/C, C/T, and T/T.

And, the results.

  • The rs2494732 locus was not associated with…
    • Increased risk of a psychotic disorder
    • Lifetime cannabis use
    • Frequency of use
  • Carriers of the C/C genotype with a history of cannabis use…
    • Greater than 2-fold increased likelihood of a psychotic disorder vs users who were T/T carriers
    • The interaction between the rs2494732 gene and frequency of use was also significant.
  • Among daily users…
    • C/C carriers had a 7-fold increase in the odds of psychosis compared with T/T carriers.

The bottom line?

A biological test that predicts the risk for developing cannabis psychosis would be valuable. However, Dr. John Krystal, Editor of Biological Psychiatry tells us, “The AKT1 genotype does not rise to the level of a clinically useful test of the risk for cannabis psychosis. It does, however, show that this source of psychosis risk has a genetic underpinning.

The relationship between marijuana, cognition, and psychosis is complex and not well understood. While most studies agree that acute cannabis use is associated with cognitive impairment in the short-term, long-term effects of cannabis are unresolved. For example, in schizophrenia, a recent meta-analysis reported better cognition in cannabis-using patients.

And then there’s this report where recreational use of synthetic cannabis lead to psychosis that lasted for days or months in some cases, according to a study at the American Psychiatric Association Annual Meeting in Hawaii.

For now, users should be consider if they’re feelin’ lucky.

11/17/12 13:24 JR

Hi, I’m JR

John Russo, Jr., PharmD, is president of The MedCom Resource, Inc. Previously, he was senior vice president of medical communications at, a complementary and alternative medicine website.