From the Journals

Cannabis use, potency linked to psychotic disorder risk

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Which comes first – psychosis or cannabis use?

Epidemiologic and experimental studies generally have established a link between heavy cannabis use and psychosis. However, a long-running issue has been that, while cannabis use has increased in some populations, the rates of psychosis have not necessarily done the same. The results of this study go against that, suggesting that differing rates and intensity of cannabis use across Europe appear to correlate with differing rates of psychosis.

This does not necessarily imply causality. For example, genetic studies suggest that individuals predisposed to psychosis also may have a predisposition to use cannabis. Another possibility is that subclinical mental health issues existed in those participants before the start of cannabis use. The challenge, therefore, remains to identify which individuals are most at risk from psychosis related to cannabis use, and to develop strategies aimed at mitigating this risk.

Suzanne H. Gage, PhD, is affiliated with the department of psychological sciences at the University of Liverpool in England. These comments are adapted from an accompanying editorial (Lancet. 2019 Mar 19. doi: 10.1016/ S2215-0366[19]30086-0). No conflicts of interest were declared.



Daily cannabis use, particularly high-potency cannabis, might be a significant contributor to the incidence of psychotic disorder, results of a multicenter, case-control study suggest.


“We provide the first direct evidence that cannabis use has an effect on variation in the incidence of psychotic disorders,” Marta Di Forti, PhD, and her coauthors wrote in the Lancet.

In the study, Dr. Di Forti and her coauthors looked at cannabis use in 901 patients presenting with a first psychotic episode to one of 11 sites across Europe and Brazil, compared with 1,237 population controls from the same locations. They found that daily cannabis users had more than threefold higher odds of psychotic disorder, compared with individuals who had never used cannabis (odds ratio, 3.2; P less than .0001), even after adjusting for sociodemographic factors and use of tobacco, stimulants, ketamine, and hallucinogenics.

Those who reported using high-potency cannabis (delta 9-tetrahydrocannabinol greater than or equal to 10%) – also showed a significant 60% increase in the odds of psychotic disorder, compared with never-users, which decreased slightly to 50% after controlling for daily use.

“The large sample size and the different types of cannabis available across Europe have allowed us to report that the dose-response relationship characterizing the association between cannabis use and psychosis reflects not only the use of high-potency cannabis but also the daily use of types with an amount of THC consistent with more traditional varieties,” wrote Dr. Di Forti, of the Social, Genetic, and Developmental Psychiatry Centre at King’s College London, and her coauthors.

When the authors looked at the population-attributable fractions, they calculated that 12.2% of cases of first-episode psychosis would be avoided if high-potency cannabis were not available.

Individuals who started using cannabis at or before 15 years of age had 60% higher odds of psychotic disorder, compared with never-users (P = .0122), while those who started using high-potency cannabis at that age had more than a doubling of risk (OR, 2.3).

Similarly, those who used high-potency cannabis on a daily basis had nearly fivefold higher odds of psychotic disorder, compared with never-users, while daily users of low-potency had a 2.2-fold increase in risk.

Researchers also examined patterns of cannabis use and psychotic disorder across the 11 sites, which included Amsterdam, London; Cambridge, England; Madrid; Palermo, Italy; Paris; and Ribeirão Preto, Brazil.

They noted that there were significant variations in the incidence of psychotic disorder across the study sites, and that those variations correlated with the prevalence of daily cannabis use.

London and Amsterdam, where daily use was the most common, had the highest adjusted incidence rates of psychotic disorder (45.7 cases per 100,000 person-years in London and 37.9 per 100,000 person-years in Amsterdam). In contrast, the incidence in Bologna, Italy – where daily use was less frequent – was half that of London.

They estimated that 43% of new cases of psychotic disorder in Amsterdam were attributable to daily use of cannabis, and 50.3% were attributable to high-potency cannabis, compared with 1.2% and 2.3% of cases in Puy de Dôme in France.

“Use of high-potency cannabis was a strong predictor of psychotic disorder in Amsterdam, London, and Paris, where high-potency cannabis was widely available, by contrast with sites such as Palermo where this type was not yet available,” the authors wrote. “Our results show that, in areas where daily use and use of high-potency cannabis are more prevalent in the general population, there is an excess of cases of psychotic disorder.”

The authors did point out that the study relied on self-reported cannabis use, rather than biological sampling measures. But previous studies have shown self-reported use to be a reliable measure, they said.

“Education is needed to inform the public about the mental health hazards of regular use of high-potency cannabis, which is becoming increasingly available worldwide,” they wrote.

The study was supported by the Medical Research Council, the European Community’s Seventh Framework Program, the São Paulo Research Foundation, the National Institute for Health Research Biomedical Research Centre, and the Wellcome Trust. Five authors declared personal fees and grants from the pharmaceutical industry. No other conflicts of interest were declared.

SOURCE: Di Forti M et al. Lancet. 2019 Mar 19. doi: 10.1016/S2215-0366(19)30048-3.

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