SAN DIEGO– High-potency marijuana use appears to be associated with an increased risk of a first psychotic episode, based on a case-control study conducted in Europe.

“Daily users of a strong type of cannabis face a significant increase in the probability of developing a psychotic disorder,” reported Marta Di Forti, MD, PhD, MRC, lead author of a study whose preliminary results were presented at the International Congress on Schizophrenia Research.

Dr. Di Forti spawned a media boomlet in 2015 when she and her colleagues raised the prospect of a possible association between so-called “skunk” marijuana and first psychotic episodes. In their study of subjects in London with first-time psychotic episodes and matched population controls, those who had psychotic episodes were three times (adjusted odds ratio: 2.92; 95% confidence interval, 1.52-3.45; = .001) as likely as controls to have used “skunk” marijuana (Lancet Psychiatry. 2015 Mar;2[3]:233-8).

In the new study, Dr. Di Forti and her colleagues analyzed 1,200 first-incident cases of psychosis that were captured between the years 2010 and 2013 by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions project (EU-GEI). The researchers compared the cases to 1,300 population-based controls in five unidentified European countries and found that daily users of high-potency marijuana had the highest adjusted odds ratio (4.5-8, statistical significance not available) of a psychotic episode (Schizophr Bull. 2017 Mar:43:S30. doi: 10.1093/schbul/sbx021.078). “This effect is significant even after controlling for other drugs of abuse such as stimulants, tobacco and alcohol, and main sociodemographic confounders,” the researchers wrote in their abstract.

“The biology of cannabis-associated psychosis is still unclear,” Dr. Di Forti said in an interview. “Nevertheless, we know that THC (tetrahydrocannabinol) binds with two receptors called CB1 and CB2. They’re part of the endocannabinoid system, which from uterus onward protects our central nervous systems from insults. It activates on demand if the brain goes on hypoxia or we experience a brain injury.”

“CB1 activation leads to changes in the transmission of both GABA and glutamate. Downstream, they affect the dopamine system, which is biologically linked to psychosis.”

Dr. Di Forti dismissed the idea that people at risk for psychosis are drawn to high-potency marijuana. “Using genetic data, we’ve showed that cannabis users – both cases and controls – did not have a higher genetic load for schizophrenia than those who never used (marijuana),” she said (Lancet Psychiatry. 2015 May;2[5]:381-2).

The findings point to the importance of asking patients – and students and children – about more than just whether they have ever used marijuana. History-taking for marijuana use needs to be comparable to that performed for alcohol use, she said. “I always ask my patients for details about their past and present use but also try to understand why they use (marijuana). When possible, once I know how frequently and what type (of marijuana) they use, I can negotiate some harm-reduction strategy.”

The study is funded by the U.K.’s Medical Research Council and a European Union grant. Dr. Di Forti reports no relevant disclosures.

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