New Studies on Cannabis Use Yield Some Answers and More Questions

In the second study, Leon French, PhD, of the Rothman Research Institute, and colleagues explored whether risk for schizophrenia moderated the association between cannabis use and cortical maturation in adolescents, based off of prior research indicating that cannabis use during adolescence may increase the risk for schizophrenia in men.

In total, the researchers collected data, including cannabis use, imaging of the brain, and polygenic risk score for schizophrenia, from 1,577 participants (aged 12-21 years; 57% male) from three study samples. A negative association was found between cannabis use in early adolescence and cortical thickness in male participants with a high polygenic risk score, thought this was not seen in low-risk male participants and low- or high-risk female participants.

In participants from the Canadian Saguenay Youth Study (SYS), cannabis use interacted with risk score in regard to cortical thickness, with higher scores associated with lower cortical thickness in males who used cannabis. Cannabis use interacted with increased risk score in relation to change in decreasing cortical thickness from 14.5 to 18.5 years of age (t137 = −2.36; P = .02) in males from the IMAGEN Study, and high-risk males from the ALSPAC study who used cannabis most frequently showed lower cortical thickness than those who had never used cannabis (difference in cortical thickness, 0.07 [95% CI, 0.01-0.12]; P = .02) or those with light use (difference in cortical thickness, 0.11 [95% CI, 0.03-0.18]; P = .004).

“Our findings suggest that cannabis use might interfere with the maturation of the cerebral cortex in male adolescents at high risk for schizophrenia by virtue of their polygenic risk score,” the authors wrote.

While it seems that the results of the studies should bring more clarity to what remains unknown about cannabis, David Goldman, MD, who wrote an accompanying editorial, was quick to uphold warnings about cannabis use.

“Although siblings discordant for cannabis use were similar in brain structure, it would be wrong to conclude that it is safe to use cannabis or, as could be wrongly inferred from the French et al study, to conclude that it would be safe for people with the right genetic makeup or women, in particular, to use cannabis,” he wrote.

He was hesitant to stand behind the findings of French’s study, saying, “More needs to be learned about the risk score and the genes that could be driving the effects on cortical development. Presuming the validity of the 108 schizophrenia genes, not all would moderate cortical thickness because schizophrenia is not just a disease of cortical thickness. Also, genes not implicated in schizophrenia might alter cortical thickness. If replicated, these genotype-mediated effects of cannabis use are of special concern in young men made vulnerable by genetic background.”

Goldman concluded that it is generally safer not to expose people to psychoactive drugs.

“The burden of cannabis’ effects may fall more heavily on people who, because of genetic makeup or early life exposures, are at greatest risk for brain structural changes, psychosis, or addiction,” he said. “However, in evaluating safety, it is important to dissociate correlation from causation, even in longitudinal studies. People predisposed to use cannabis differ from nonusers, regardless of whether they choose to use the drug.”


  1. Pagliaccio D et al. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.1054. 
  2. French L et al. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.1131. 
  3. Goldman D et al. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.1332.