As more and more states consider legalizing marijuana for recreational use, the widely held belief that cannabis is associated with few serious health consequences has been challenged by many medical and substance use professionals. One potential risk that has been discussed is the possibility that cannabis use increases the risk for psychotic symptoms that may be long lasting and develop into schizophrenia. The data, however, have not been completely consistent and often are methodologically flawed, leading proponents of legalization to downplay this possible risk. This debate has even made its way to prominent science journals such as Nature where scholars have presented opposing views (Nature. 2015 Sep 24;525[7570]:S14and Nature. 2015 Nov 19;527[7578]:305).
These divergent opinions can lead to some confusion and hesitancy on the part of pediatricians who may be asked to offer an opinion about the dangers of cannabis use to individual patients and families during this time of public debate. Thus, this column will attempt to offer a brief overview and synthesis of the evidence that cannabis plays a causal role in the progression of psychotic disorders.
Dr. David C. Rettew
A recent review of the subject examined 10 epidemiological studies that have now been performed on the association between cannabis and psychotic disorders. Overall, a nearly 50% increased risk of psychosis was found among cannabis users, compared to nonusers (Biol Psychiatry. 2015 Aug 12. pii: S0006-3223[15]00647-2). This association rises among heavier cannabis users (Lancet. 2007 Jul 28;370[9584]:319-28). Because all of these longitudinal studies were observational in nature, however, proving causation in the face of association has remained challenging. Many of these studies have attempted to control for baseline psychotic symptoms to address the “reverse causation hypothesis,” which posits that early psychotic symptoms leads to cannabis use rather than the other way around. It is also worth pointing out that the inevitable limitations and potential biases of these studies could potentially lead to both overestimation and underestimation of the actual risk.
Putting all of this together, the authors concluded that “there is a strong body of epidemiologic evidence to support the view that regular or heavy cannabis use increases the risk of developing psychotic disorders that persist beyond the direct effects of exogenous cannabinoids.” In making this conclusion, despite the inherent uncertainties of interpreting observational studies, the authors describe a number of lines of evidence that support the likelihood of a causal connection. These include the following:
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The link between cannabis and psychosis is not equal for all age groups, but may be stronger for adolescents.
• The well-known fact that acute intoxication of cannabis can produce transient psychotic symptoms.
• The replicated finding that there is a dose-dependent response between amount of cannabis use and psychosis.
• An increased risk of psychosis among cannabis users who carry specific risk genes (Biol Psychiatry. 2012 Nov 15;72[10]:811-6).
• Increasing evidence that the more potent marijuana that is available now may be associated with additional risk.
• The finding that the link between cannabis and psychosis is not equal for all age groups, but may be stronger for adolescents.
One line of argument against a causal role of cannabis in the development of psychotic disorders is that the rate of schizophrenia has remained relatively flat over the years that cannabis use has increased. Countering that assertion, however, Large and colleagues pointed out that some studies do show increasing rates of schizophrenia (Nature. 2015 Nov 19;527[7578]:305). Further, it is somewhat precarious to conclude that a possible risk factor is not consequential when it moves in a different direction than a multifactorial disorder such as schizophrenia. Lead toxicity, for example, is an accepted risk factor for attention-deficit/hyperactivity disorder (ADHD), yet exposure has been decreasing while rates of ADHD climb.
Overall, the data appear to be strengthening that cannabis does play a causal role in the development of psychosis and psychotic disorders. This risk is combined with data showing links between cannabis use and decreased IQ, academic underachievement, car accidents, and use of other types of drugs (Addiction. 2015 Jan;110[1]:19-35). These dangers need to be articulated in discussions about the wisdom of legalizing cannabis at the state and federal level.
Dr. Rettew is associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He said he has no relevant financial disclosures. Follow him on Twitter @pedipsych. E-mail him at pdnews@frontlinemedcom.com.