The Cannabis-Psychosis Link

By Marie-Josee Lynch, MD, Rachel A. Rabin, MSc, and Tony P. George, MD, FRCPC | January 12, 2012

Dr Lynch is a PGY-3 Resident in Psychiatry at the University of Toronto; Ms Rabin is a PhD student in the Institute of Medical Sciences at the University of Toronto; Dr George is Professor and Chair in Addiction Psychiatry at the University of Toronto, and Clinical Director of the Schizophrenia Program at the Centre for Addiction and Mental Health in Toronto. Dr George reports that in the past 2 years, he has received grant support from Pfizer; has been a speaker for Astra Zeneca, Eli Lilly, and Pfizer; and served as a consultant to Abbott, Novartis, Pfizer, and Sepracor. Dr Lynch and Ms Rabin have no conflicts of interest concerning the subject matter of this article.
Acknowledgments—This article was supported in part by the Canada Foundation for Innovation (#16014), the Chair in Addiction Psychiatry from the University of Toronto, and by grants from the Canadian Institute for Health Research (MOP#245931, to T.P.G.) and the Ontario Mental Health Foundation to Dr George. Ms Rabin is supported by Studentships from the Canadian Institutes of Health Research and an Ontario Graduate Scholarship.

Genetic vulnerability

A subsequent study conducted with the Dunedin cohort investigated whether specific genes increase the risks associated with early cannabis use.¹⁴ The researchers examined the role of the catechol-O-methyltransferase (COMT) gene, whose link with psychosis has been the focus of many studies. The COMT gene encodes the enzyme responsible for the synaptic metabolism of dopamine(Drug information on dopamine). A functional polymorphism of this gene, Val158Met, has been shown to slow the breakdown of dopamine, which potentially increases the risk of psychosis.^15,16 The results of the study showed that the presence of the valine polymorphism was not significant unless coupled with adolescent cannabis use.¹³

Persons with Val/Val or Val/Met genotypes and adolescent cannabis use were at increased risk for schizophreniform disorder (with respective odds ratios of 10.9 and 2.5), while individuals with Met/Met genotypes were not. These findings implicate genetic factors as important contributors to the cannabis-psychosis link, but they are in need of replication.

Impact of cannabis use on the course of schizophrenia

The extent to which cannabis use might alter the clinical course of schizophrenia remains a point of contention within the literature. Intuitively, one may expect cannabis to have a negative impact on the expression and course of schizophrenia. Findings suggest that patients with schizophrenia who use cannabis experience increased psychotic symptoms, are more likely to have relapses, have a greater likelihood of rehospitalization, and experience poorer therapeutic response to antipsychotic medication than patients who are cannabis-naive.^17,18 Furthermore, pre-onset cannabis use may trigger an earlier age of onset of psychosis, which is of critical importance given the negative prognostic features associated with earlieronset.¹⁹ These effects have been reported to be dose-dependent.

It is interesting to note that other studies have been unable to confirm these adverse findings after controlling for potential confounding factors, which include but are not limited to alcohol(Drug information on alcohol) and drug use, premorbid functioning, and family history. Moreover, it has been suggested that patients with comorbid cannabis use constitute a clinically distinct subgroup of schizophrenia patients.

In this respect, cannabis use may trigger the onset of psychosis in vulnerable individuals in whom a psychotic disorder otherwise may not have developed. As a result, these patients have a better prognosis, exhibit fewer negative symptoms, have better social skills, and have an enhanced treatment response compared with nonusers. In addition, a recent meta-analysis demonstrated that patients with lifetime cannabis use disorders have superior cognitive function compared with nonuser counterparts.²⁰

These conflicting findings may be due to the varying levels of THC/CBD found in street cannabis. The fact that these constituents have divergent properties may explain the manifestation of different psychological symptoms among users. In fact, CBD may actually attenuate some of the unwanted psychopharmacological effects of THC, because it may have anxiolytic and antipsychotic properties.²¹ Furthermore, CBD has been shown to have neutral or even procognitive effects.²²

Conclusions

Despite all of the uncertainties surrounding the cannabis-psychosis link, we are left with the task of translating these results into clear recommendations for our patients. The evidence suggests that cannabis is associated with an increased risk of psychosis when it is used frequently. Whether cannabis can trigger a primary psychotic disorder that would not have otherwise occurred is unclear. However, in most individuals who use cannabis, psychosis does not develop, which suggests that the increased risk must be related to other vulnerability factors (genetics, frequency, or age of onset of cannabis misuse).

Cannabis also seems to negatively alter the clinical course of schizophrenia. While meta-analyses suggest better cognitive function among cannabis-using patients, this may be a reflection of a higher-functioning subgroup of schizophrenia patients. Accordingly, cannabis-using patients who achieve abstinence may demonstrate improved symptoms and cognitive performance.

The first step in communicating this information to our patients consists of screening for cannabis use and obtaining a thorough substance use history. Psychoeducation and early interventions for young patients who may be vulnerable to psychosis should be used, and motivational interviewing and cognitive-behavioral therapy should be considered to encourage reduction and cessation of use.

There are no accepted pharmacological treatments for cannabis use disorders, yet several potential agents are under investigation. Future studies that control for both environmental and biological risk factors are needed to more clearly elucidate the mechanisms linking cannabis misuse to psychosis.

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by Francine Eisner | March 08, 2012 9:17 PM EST

I disagree with the previous commentators. It seems that there is a substantial amount of evidence. Furthermore, Dr. Newman should provide a reference for his statement. Just stating, "The DEA says"is unprofessional.
>we must say the risk is low for the movement into schizophrenia as a result of Cannibis [sp].

No, "we must say" nothing of the kind. I'm truly astounded that a medical professional would make such a remark. One can call for additional studies; that would be the appropriate course of action. Psychotropic drugs, whether recreational or prescribed, create risk because they alter brain chemistry. It is clear that this is the case with cannabis; what is not clear is how great the the health risk. Worst of all, those who would use cannabis as a recreational drug use statements employ the comments below as "proof" that they are doing nothing harmful to themselves. Teenagers in particular are still undergoing brain development, and the age group of 15-25 is when schizophrenia is most likely to present. If the DEGREE of risk of cannabis use seems unclear to the two of you, it still should be in the category of "not a good idea."

Francine Eisner, RN

by Lawrence Welkowitz | March 08, 2012 5:11 PM EST

I agree with Dr. Newman's comment that not enough is known to make such definitive statements. The authors call for educating patients about cannabis, but reading their own review makes me think, "educate them by saying what?" With conflicting studies, and little conclusive evidence about harm, I'm not sure what exactly the authors would like clinicians to say.

Just another opinion,

Larry Welkowitz, Ph.D.

by Chevies Newman | February 19, 2012 1:06 AM EST

Interesting conversation, I'm not convinced that telling people that they are at increased risk of schizophrenia by the consumption of Cannibis. According to risk analysis from the DEA, the substance has less risk of health problems than both alcohol and tobacco. Do those who develop schizophrenia have prodromal symptoms relieved by Cannibis at the Gamma benzo receptor? Is there a socioeconomic downward drift allowing these young patients greater access to the drug? Does the rush of dopamine into the Mesolimbic pathway exacerbate a predisposition which pushes some into a diagnosis of severe mental illness that would otherwise not occur.

With widespread use and no conclusive evidence, we must say the risk is low for the movement into schizophrenia as a result of Cannibis. Recurrent bronchitis, underlying depression and self treatment with Cannibis overuse, poor academics among younger starters; these are the best approaches. The scare tactic of a psychotic disorder in a healthy person is so uncommon, even good research must admit weaknesses.

In short, too many confounding variables exist to make a definitive statement. One runs the risk of sounding non credible to the user and making them feel unaccepted as people. I would say treat underlying mood dysfunction, encourage non combustion of plant material via new technology, and use your skills in psychopharmacology to have them use less. It's not Crack or Meth, most can improve use if desired.

Just an opinion,

Chevies Newman, M.D.

Article Comment Pages: 1 2 Previous

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