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Cannabis Exposure May Lead to Psychosis

January 12, 2015

By Andrew Penn, RN, MS, NP, CNS, APRN-BC
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The opinions expressed by Psychiatry & Behavioral Health Learning Network bloggers and those providing comments are theirs alone and are not meant to reflect the opinions of the publication.

In a recent blog entry, I wrote about how some of the young people I treat in my practice are using cannabis as a means of avoiding the anxiety-provoking stressors of becoming an adult and how that avoidance is contributing to a delay in maturation.

The good news is that most young people who experiment with cannabis in adolescence will not develop psychosis. But a small percent, especially with genetic loading, can develop psychotic symptoms at a younger age with exposure to cannabis.

In this entry, I want to explore a far more serious question: Does cannabis increase the chances of developing psychosis?

The answer is not a simple one. Cannabis appears to interact with neurodevelopmental processes in a way that in some people can contribute to the genesis of psychotic illnesses such as schizophrenia. However, fortunately for most people, this will not be the case. Global epidemiology studies attribute only a tiny amount of the risk of developing schizophrenia to the use of cannabis. (6) But even if this percentage is small, even as low as 1% of users, the increasing prevalence of cannabis use among young people, coupled with the appearance of relative safety (an image of safety that has been promoted by the cannabis industry, just as the safety of tobacco was once purported by the likes of R.J. Reynolds) and growing societal acceptance of cannabis means that more young people will be exposed to cannabis and this potential attendant harm. Even if this risk is relatively small, the level of disability and suffering associated with schizophrenia behooves us to work towards preventing any cases that we can.

Schizophrenia is a complex illness, likely resultant from disrupted neurotransmission, both on the cellular and network level. It typically emerges in late adolescence and early adulthood, before the age of 25. This is also the time when many people experiment with substance use, and cannabis is the most widely used substance among young people after alcohol and tobacco. In one study, 7.3% of people 12 and older reported using cannabis in the previous month compared with 52.1% who reported alcohol use and 26.7% who reported tobacco use. (1)

We clinicians have all seen the tragedy of young patients who, just as they are getting ready to launch into the world, began to develop the disabling symptoms of schizophrenia. Some of them have also been using cannabis. The question often arises from family members and patients: Did the cannabis cause the illness?

The simple answer in clinical practice is “we will never know,” because of course, there is no ability to have a “control” patient who is not exposed to cannabis to see if the illness would not develop in its absence. Additionally, patients with schizophrenia and their families can better direct their efforts towards helping their loved one heal and manage their illness, rather than feeling regrets about past choices.

However, as clinicians, it is important for us to educate our young patients about the risks of psychosis associated with early, heavy cannabis use. Epidemiologic data indicates that young people who are daily users of cannabis before the age of 15 have a greater risk of developing schizophrenia than their peers who either abstain from cannabis or wait until adulthood to begin using the drug. This risk is further increased by the use of cannabis that is high in THC (9-delta tetrahydrocannabinol), the psychoactive ingredient in cannabis, as many contemporary strains are grown for high levels of this compound. (2) This relationship between psychosis and cannabis use appears to be dose dependent, which further underscores the harm reduction message that while no use is best, any reduction or forestalling of use is better. (3)

Curiously, subjects with prodromal schizophrenia have been found to have elevated endocannabinoid activity. Anandamide, the endogenous ligand for the cannabinoid-1 receptor, has been found to be elevated up to eight times normal in the CSF of patients with emerging schizophrenia. This may represent an attempt by the brain to restore homeostasis to a brain that has become overactive with dopamine. Anandamide may be trying to “put the brakes on” the emerging excessive dopamine activity seen in emergent schizophrenia. Unfortunately, exposing a brain that is already struggling with dopamine homeostasis to the perturbing activity of THC may further worsen the psychotic symptoms. (7)

Why might cannabis use both increase the risk of psychosis? It may be partially explained by genetics. The gene that codes for COMT (catechol-O-methyltransferase) has some regulation of dopamine degradation at the synapse. Schizophrenia is associated with an excess of dopamine activity, particularly at the mesolimbic tract of the brain. (4) Carriers of the Val158Val polymorphism for the COMT gene were more likely to develop psychotic symptoms  at a younger age after exposure to cannabis than peers who carried the Met158Met polymorphism. (5) As genetic testing becomes cheaper, might it make sense to screen young people prior to the age at which drug use is typically initiated for this polymorphism and warn those who are Val/Val carriers that they are at a higher risk for developing a psychotic illness with cannabis exposure?

So what do we tell our young patients? One – by first acknowledging that we have damaged our credibility with a historic message that “all drugs are bad for all people all the time,” young users may be more willing to hear a more nuanced message. Two – there are real risks for young people who use cannabis daily. If they haven’t tried the drug, try to explain the benefits of waiting. Each year that passes before drug initiation lessens the risk of developing psychosis. If they have used the drug, and are unwilling to stop, adopt a position of harm reduction: any reduction of use is better than more use. Discuss changing the relationship with the drug to use less of it and to use it less frequently.


1. Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. Substance Abuse and Mental Health Services Administration.

2. Di Forti M, Sallis H, Allegri, F, et al. Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. Schizophr Bull. 2014;40(6):1509-17.

3. Andreasson S, et al. Lancet. 1987;2(8574):1483-1486. Fergusson DM, et al. Addiction. 2005;100(3):354-366. Henquet C, et al. BMJ. 2005;330(7481):11. Moore TH, et al. Lancet. 2007;370(9584):319-328. Schubart CD, et al. Acta Psychiatr Scand. 2011;123(5):368-375.

4. Stahl, S  (2013) Stahl’s Essential Psychopharmacology. Cambridge Press

5. Estrada G, et al. Acta Psychiatr Scand. 2011;123(6):485-492. Verdejo-Garcia A, et al. Neuropsychopharmacology. 2013;38(8):1598-1606.

6. Degenhardt L, Ferrari A, Calabria B, et al. The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study. PLoS One. 2013;8(10):e76635. doi:10.1371/journal.pone.0076635.

7. Leweke FM. Curr Pharm Des. 2012;18(32):5188-5193. Meltzer HY, et al. Am J Psychiatry. 2004;161(6):975-984. Leweke FM, et al. Transl Psychiatry. 2012;2:e94. Guffrida A, et al. Neuropsychopharmacology. 2004;29(11):2108-2114.

Andrew Penn was trained as an adult nurse practitioner and psychiatric clinical nurse specialist at the University of California, San Francisco. He is board certified as an adult nurse practitioner and psychiatric nurse practitioner by the American Nurses Credentialing Center. Currently, he serves as an Assistant Clinical Professor at the University of California-San Francisco School of Nursing. Mr. Penn is a psychiatric nurse practitioner with Kaiser Permanente in Redwood City, CA, where he provides psychopharmacological treatment for adult patients and specializes in the treatment of affective disorders and PTSD. He is a former board member of the American Psychiatric Nurses Association, California Chapter, and has presented nationally on improving medication adherence, emerging drugs of abuse, treatment-resistant depression, diagnosis and treatment of bipolar disorder, and the art and science of psychopharmacologic practice.

The views expressed on this blog are solely those of the blog post author and do not necessarily reflect the views of Psych Congress Network or other Psych Congress Network authors. Blog entries are not medical advice. 

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