Is it biologically plausible that cannabis could cause a psychotic disorder?

Yes. Brain scientists know very little about the underlying biology of psychotic conditions, other than that hundreds of common gene variants are likely involved. Schizophrenia, for instance, is not a uniform disorder but an umbrella term for an array of unexplained problems involving recurrent psychosis, and other common symptoms.

Even so, there is circumstantial evidence for a biological mechanism. Psychotic disorders tend to emerge in late adolescence or early adulthood, during or after a period of rapid brain development. In the teenage years, the brain strips away unneeded or redundant connections between brain cells, in a process called synaptic pruning. This editing is concentrated in the prefrontal cortex, the region behind the forehead where thinking and planning occur — and the region that is perturbed in psychotic conditions.

The region is rich with so-called CB1 receptors, which are involved in the pruning, and are engaged by cannabis use. And alterations to the pruning process may well increase schizophrenia risk, according to recent research at the Broad Institute of M.I.T. and Harvard. In a 2016 analysis, scientists there found that people with the disorder often have a gene variant that appears to accelerate the pruning process.

What does this mean for me?

Experts may debate whether cannabis use can lead to psychotic disorders, but they mostly agree on how to minimize one’s risk.

Psychotic conditions tend to run in families, which suggests there is an inherited genetic vulnerability. Indeed, according to some studies, people prone to or at heightened risk of psychosis seem to experience the effects of cannabis differently than peers without such a history. The users experience a more vivid high, but they also are more likely to experience psychosis-like effects such as paranoia.

The evidence so far indicates that one’s familial risk for psychotic disorders outweighs any added effect of cannabis use. In a 2014 study, a team led by Ashley C. Proal and Dr. Lynn E. DeLisi of Harvard Medical School recruited cannabis users with and without a family history of schizophrenia, as well as non-users with and without such a history. The researchers made sure the cannabis users did not use other drugs in addition, a factor that muddied earlier studies. The result: there was a heightened schizophrenia risk among people with a family history, regardless of cannabis use.

“My study clearly shows that cannabis does not cause schizophrenia by itself,” said Dr. DeLisi. “Rather, a genetic predisposition is necessary. It is highly likely, based on the results of this study and others, that cannabis use during adolescence through to age 25, when the brain is maturing and at its peak of growth in a genetically vulnerable individual, can initiate the onset of schizophrenia.”