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People who used cannabis every day were at higher risk of developing a first psychotic episode versus people who never used cannabis, in a case-control study conducted in Europe and Brazil.

Compared with non-users, daily cannabis users had more than a three-fold higher odds for incident psychosis (adjusted odds ratio 3.2, 95% CI 2.2-4.1), reported Marta Di Forti, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience at King's College London, and colleagues.

Daily users in cities with relatively widespread availability of high-potency cannabis -- defined as a tetrahydrocannabinol (THC) concentration ≥10% -- saw an even higher chance for psychosis versus non-users (aOR 4.8, 95% CI 2.5-6.3), they stated in .

However, one notable study limitation was the lack of data on cannabidiol (CBD) concentrations in the cannabis used by these patients. Also, cannabis use in general was self-reported, and not validated by measures like blood or urine samples. The cutoff between high and low potency (10% THC ) was rather conservative, the authors noted.

Despite the researchers "assuming causality" many times throughout their study, "does this mean we can now be sure that (daily and high potency) cannabis use causes psychosis? Unfortunately, not all the evidence utilising different methods is consistent about causality," said Suzanne Gage, PhD, of the University of Liverpool in England, in an .

"Di Forti and colleagues' study asks participants about their cannabis use prior to their first episode psychosis diagnosis, but it is possible that subclinical symptoms might have existed prior to cannabis initiation, meaning that associations in the opposite direction cannot be ruled out," she wrote. It is "perfectly possible" the relationship is bidirectional, Gage added, "as using genetic variables as proxies for the exposures of interest in a .

But Gage also conceded that the bulk of evidence to date indicates "that for some individuals there is an increased risk of psychosis resulting from daily use of high potency cannabis," which the current study supports. (Indeed, a longitudinal study reported last year found that psychotic episodes more often followed cannabis initiation than the other way around.)

The current analysis included data on 901 adults (ages 18 to 64) with first-episode psychosis diagnosed with ICD-10 criteria at a mental health service. These patients came from across 11 different sites in Brazil and Europe, including the Netherlands, the U.K., France, Spain, and Italy. They were compared with over 1,200 psychosis-free controls from the same sites.

People with first-episode psychosis tended to be younger, male, an ethnic minority, and less educated than controls. Some 65% of cases reported any lifetime use of cannabis compared with 46% of controls.

Via the Cannabis Experience Questionnaire, participants reported six measures of cannabis use, which included lifetime use, current use, age of first use, lifetime frequency, and weekly money spent on cannabis. Those who spent at least €20 per week (around $23) on cannabis also had higher odds of psychosis (aOR 2.5, 95% CI 1.6-3.8, P<0.0001), as well as those who first used cannabis before they were age 16 years (aOR 1.6, 95% CI 1.1-2.1, P=0.01).

Di Forti and colleagues wanted to determine whether cannabis potency had any relationship with psychosis risk, but they did not have direct data from the cannabis products that participants reported using. The city of residence was used as a proxy instead, based on published reports about the availability of high-potency cannabis by city. Those reports indicated that THC content varied widely: up to 70% in Amsterdam versus less than 10% in Italy, Spain, and France, where weaker herbal types of marijuana were typical.

On the basis of these data, the researchers estimated that if only cannabis with <10% THC was available, about 12% (95% CI 3.0-16.1%) of first-episode psychosis cases from the overall sample could have been prevented. In areas where more potent cannabis is popular, they suggested upwards of 30% (95% CI 15.2-40.0%) of first psychosis cases could have been avoided in London (where the most common product is 14% THC) and over 50% (95% CI 27.4-66.0%) of cases in Amsterdam could have been prevented if only low potency cannabis was an option.

"Given the changing legal status of cannabis across the world, and the associated potential for an increase in use," Gage concluded in her editorial, "the next priority is to identify which individuals are at risk from daily potent cannabis use, and to develop educational strategies and interventions to mitigate this."