Cannabis users seem to be at higher than normal risk to develop psychotic symptoms (see CATR, March 2015, “High Potency Cannabis Increases Risk of First Episode Psychosis”), but so far researchers haven’t solved the chicken-and-egg problem.

Studies Reviewed:
Schoeler T et al. Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: An observational study. Lancet 2016;3(10):947–953.

Schoeler T et al. Association between continued cannabis use and risk of relapse in first episode psychosis: A quasi-experimental investigation within an observational study. JAMA Psychiatry 2016;71(11):1173–1179.

Study Type: Prospective cohort study

Cannabis users seem to be at higher than normal risk to develop psychotic symptoms (see CATR, March 2015, “High Potency Cannabis Increases Risk of First Episode Psychosis”), but so far researchers haven’t solved the chicken-and-egg problem. An association between cannabis use and psychosis might reflect a causal relationship—ie, perhaps smoking too much pot causes people to become psychotic. On the other hand, it’s possible that people who are already psychotic gravitate toward smoking pot, in which case cannabis per se is not such a danger.

This prospective study is a follow-up to the above meta-analysis by Schoeler et al, which found that cannabis use increased relapse rates and length of hospitalization in patients with psychosis. Unlike the meta-analysis, this study attempts to further sort out the association-versus-causation issue.

Methods
Patients experiencing first episode psychosis (FEP) were recruited consecutively from local community early intervention programs for psychosis and from psychiatric inpatient units in South London between 2002 and 2013. 256 subjects completed the study. They were assessed when first hospitalized by ­face-to-face or telephone interview, and again 2 years later. The Cannabis Experience Questionnaire was used to assess marijuana use in the 2 years after hospitalization. Subjects were divided into former users, never users, intermittent users, continuous users of low-potency hash-like cannabis, continuous low-frequency users of “skunk” (high-potency) cannabis, and continuous high-frequency users of skunk cannabis.

Results
Researchers measured the relapse rates of these patients, then did statistical analyses to figure out whether degree of use was correlated with relapse. The definition of relapse was rehospitalization for psychosis. In fact, more cannabis use did predict higher relapse rates. Specifically, relapse rates were 24% for former users, 30% for never users, 40% for intermittent users, 44% for continuous users of hash-like cannabis, 54% for low-frequency users of skunk cannabis, and 58% for high-frequency users of skunk cannabis. The statistical analysis showed that subjects who did not use cannabis after FEP had the best outcome. The high-frequency skunk cannabis users had more relapses, shorter time to relapse, longer hospitalizations, and a need for more intensive community services.

It’s unusual for a study to be reported in two journals almost simultaneously, but that’s what occurred in this case. Another article based on the same patients appeared in JAMA Psychiatry a month later (Schoeler T et al, 2016), and this study reported some of the same findings but added interesting information that touches on the causality issue. They found that for any given patient, there was an increased risk of relapse to psychosis during periods of cannabis use as opposed to periods of nonuse, and that the risk of relapse increased as frequency of cannabis use increased.

CATR’s Take
The Lancet article focuses on both usage pattern and potency, comparing ­different user groups based on how often they used marijuana and how potent a ­formulation they consumed. The JAMA article focuses on the risk of psychotic relapse in individual subjects during periods of marijuana use versus nonuse. A significant limitation in both articles is the use of self-report or chart review to assess cannabis use. Another is that the authors did not consider length of untreated psychosis prior to hospitalization, nor did they have access to doses of antipsychotic medication used to treat the subjects. Additionally, although the number of completers in each article (256 in the Lancet article and 220 in the JAMA article) is respectable, the numbers in each group were relatively small after division into several groups.

Despite these limitations, there is important information here for patients and clinicians. It’s encouraging that former cannabis users had a lower risk of relapse when they did not use after FEP than those who continued their use. The study results also suggest that the association between cannabis and psychosis involves more than simply self-medicating psychotic symptoms. In this study, the authors found that relapse risk changed within subjects based on changes in their individual patterns of use. That weakens the argument that people who are more susceptible to psychosis are also more likely to use cannabis.

Practice Implications
These studies reinforce our efforts to discourage cannabis use in patients at risk for psychosis. Patients who have had a psychotic episode should be counseled to discontinue cannabis use. For patients who are reluctant to stop altogether, it may be helpful if they decrease their frequency of use or switch to a less potent strain, as both frequency of use and potency seem to play a role in psychosis risk.