Cannabis Directly Linked to Psychosis Relapse

Megan Brooks

September 30, 2016

Continuing to smoke cannabis after a first episode of psychosis (FEP) is causally linked to an increased risk for psychosis relapse, new research shows.

Investigators at King's College London, United Kingdom, note that the study findings indicate that cannabis use is a "risk-modifying factor for relapse, suggesting that discontinuation of cannabis use after the onset of psychosis may help in reducing the risk of relapse."

"Although it has been proposed that a common genetic liability or reverse casation may underlie the association between continued cannabis use and relapse, our results indicate that change in cannabis use represents a robust risk factor for relapse in patients," the researchers, led by Sagnik Bhattacharyya, MD, PhD, write.

The findings were published online September 28 in JAMA Psychiatry.

Modifiable Risk Factors

Cannabis use is associated with poor outcomes for patients with FEP, but the causal nature of this association is uncertain, the investigators note.

For their study, they used a quasiexperimental design to investigate the causal nature of the association between continued cannabis use and risk for psychosis relapse. They employed longitudinal modeling (fixed-effects analysis, cross-lagged path analysis) to determine whether the association between changes in cannabis use and risk for relapse over time stems from shared vulnerability between psychosis and cannabis use, psychosis increasing the risk for cannabis use (reverse causation), or a causal effect of cannabis use on psychosis relapse.

Participants included 90 women and 130 men (average age, 29 years), who were followed for at least 2 years after FEP.

According to the researchers, the relapse rate was highest for individuals who used cannabis continuously after FEP (59.1%), whereas the rate was lowest for those who did not continue cannabis use (28.5%). Among intermittent users, the relapse rate was 36.0%.

In fixed-effects models that controlled for time-variant factors such as other illicit drug use and antipsychotic use as well as genetics and environment, the risk for psychosis relapse was 13% higher during times of cannabis use relative to times in which there was no use (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.03 - 1.24).

There was also a dose-response relationship: a 1-unit change in cannabis use pattern, signifying greater regularity in use over time (from intermittent use to continued use), correlated with an increased likelihood of risk for relapse (OR, 1.10; 95% CI, 1.05 - 1.15).

Cross-lagged analysis confirmed that this association reflected an effect of cannabis use on subsequent risk for relapse rather than an effect of relapse on subsequent cannabis use.

"Although it has been proposed that a common genetic liability or reverse causation may underlie the association between continued cannabis use and relapse, our results indicate that change in cannabis use represents a robust risk factor for relapse in patients with FEP," the investigators write.

"Because cannabis use is a potentially modifiable risk factor that has an adverse influence on the risk of relapse of psychosis and hospitalization in a given individual, with limited efficacy of existing interventions, these results underscore the importance of developing novel intervention strategies and demand urgent attention from clinicians and health care policymakers," they conclude.

A limitation of the study was that cannabis use was self-reported and not objectively measured.

Caveats, Cautionary Notes

Commenting on the study for Medscape Medical News, Rashmi Patel, BMBCh, of King's College London, noted that previous studies have shown that a history of cannabis use is associated with a greater risk of developing a psychotic disorder and worse clinical outcomes.

"However, until now, little was known about the effects of continued cannabis use following the onset of a psychotic disorder," said Dr Patel, who was not involved in the study.

"This novel study," he said, "sheds light on this issue by demonstrating that people who continue to use cannabis regularly following their first episode of psychosis have a greater risk of relapse compared to those who reduce or stop using cannabis. These findings have important implications for clinical practice and highlight a need to develop strategies to reduce the risks of ongoing cannabis use in people with psychotic disorders."

But Marcel Bonn-Miller, PhD, adjunct assistant professor of psychology in psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, said it would be wrong to conclude that "all marijuana is bad and all marijuana causes psychosis.

"There have been a number of studies over a number of years that have shown a link between cannabis and psychosis, and this study adds to that evidence and is important," he said. "But it's also important to consider that cannabis is a heterogeneous drug. It has lots of different components, and I think at this point, most of the evidence suggests that it's the THC [delta-9-tetrahydrocannabinol] content that's driving this association," Dr Bonn-Miller, who was not involved in the study, told Medscape Medical News.

He also made the point that "most of the cannabis that is used on the street or comes from dispensaries have pretty high levels of THC and not a whole lot else in terms of other cannabinoids or pretty low levels of pretty much anything else. That's why I think you are seeing an association [with psychosis]. But there are other cannabinoids, like cannabidiol, or CBD, that's been showing some antipsychotic properties. But these are just very early studies, definitely nothing to the extent of what has been done showing negative consequences."

The study had no commercial funding. One study author has relationships with Janssen, Sunovian, Otsuka, and Lundbeck.

JAMA Psychiatry. Published online September 28, 2016. Full text

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