Cannabis, synthetic cannabinoids, and psychosis risk: What the evidence says


Research suggests marijuana may be a ‘component cause’ of psychosis

Joseph M. Pierre, MD
Co-Chief, Schizophrenia Treatment Unit, VA West Los Angeles Healthcare Center, Health Sciences Associate Clinical Professor, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA

Over the past 50 years, anecdotal reports linking cannabis sativa (marijuana) and psychosis have been steadily accumulating, giving rise to the notion of “cannabis psychosis.” Despite this historic connection, marijuana often is regarded as a “soft drug” with few harmful effects. However, this benign view is now being revised, along with mounting research demonstrating a clear association between cannabis and psychosis.
In this article, I review evidence on marijuana’s impact on the risk of developing psychotic disorders, as well as the potential contributions of “medical” marijuana and other legally available products containing synthetic cannabinoids to psychosis risk.


Cannabis use has a largely deleterious effect on patients with psychotic disorders, and typically is associated with relapse, poor treatment adherence, and worsening psychotic symptoms.1,2 There is, however, evidence that some patients with schizophrenia might benefit from treatment with cannabidiol,3-5 another constituent of marijuana, as well as delta-9-tetrahydrocannabinol (?-9-THC), the principle psychoactive constituent of cannabis.6,7
Three meta-analyses have concluded cannabis use is associated with an increased risk of psychosis

The acute psychotic potential of cannabis has been demonstrated by studies that documented psychotic symptoms (eg, hallucinations, paranoid delusions, derealization) in a dose-dependent manner among healthy volunteers administered ?-9-THC under experimental conditions.8-10 Various cross-sectional epidemiologic studies also have revealed an association between cannabis use and acute or chronic psychosis.11,12
In the absence of definitive evidence from randomized, long-term, placebo-controlled trials, the strongest evidence of a connection between cannabis use and development of a psychotic disorder comes from prospective, longitudinal cohort studies. In the past 15 years, new evidence has emerged from 7 such studies that cumulatively provide strong support for an association between cannabis use as an adolescent or young adult and a greater risk for developing a psychotic disorder such as schizophrenia.13-19 These longitudinal studies surveyed for self-reported cannabis use before psychosis onset and controlled for a variety of potential confounding factors (eg, other drug use and demographic, social, and psychological variables). Three meta-analyses of these and other studies concluded an increased risk of psychosis is associated with cannabis use, with an odds ratio of 1.4 to 2.9 (meaning the risk of developing psychosis with any history of cannabis use is up to 3-fold higher compared with those who did not use cannabis).11,20,21 In addition, this association appears to be dose-related, with increasing amounts of cannabis use linked to greater risk—1 study found an odds ratio of 7 for psychosis among daily cannabis users.16
There are several ways to explain the link between cannabis use and psychosis, and a causal relationship has not yet been firmly established (Table 1).1-7,11-19,21-25 Current evidence supports that cannabis is a “component cause” of chronic psychosis, meaning although neither necessary nor sufficient, cannabis use at a young age increases the likelihood of developing schizophrenia or other psychotic disorders.26 This risk may be greatest for young persons with some psychosis vulnerability (eg, those with attenuated psychotic symptoms).16,18
The overall magnitude of risk appears to be modest, and cannabis use is only 1 of myriad factors that increase the risk of psychosis.27 Furthermore, most cannabis users do not develop psychosis. However, the risk associated with cannabis occurs during a vulnerable time of development and is modifiable. Based on conservative estimates, 8% of emergent schizophrenia cases and 14% of more broadly defined emergent psychosis cases could be prevented if it were possible to eliminate cannabis use among young people.11,26 Therefore, reducing cannabis use among young people vulnerable to psychosis should be a clinical and public health priority

Source: Vol.10 Sept 2011

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