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 Ron Fletcher | May 15, 2013 6:39 PM EDT

As an experienced mental health nurse I believe that there is prima-facia evidence of a relationship between the over-use of cannabis particularly during developmental years. Cannabis, like most of the older drugs have been used throughout history however their use was strictly controlled through ritual and spiritual beliefs. In our society all the "Shamanic"drugs have become drugs of abuse with no control on amount, frequency of mental preparedness of the user. With this in mind, it is reasonable to argue that there may be a relationship between our societies use of these substances and mental illness.

However, I find it unfortunate that in the conclusion of this article it states " While meta-analyses suggest better cognitive function among cannabis-using patients, this may be a reflection of a higher-functioning subgroup of schizophrenia patients" when experience, and talking with clients, clearly shows that the most commonly used reason clients give for cannabis use is that it reduces psychotic symptoms and allows them to relax despite the stress of their condition. In my opinion this omission turned an apparently informative article into a biased and therefore doubtful source of information.

by Chevies Newman | October 24, 2012 6:29 AM EDT

To Mrs. Eisner,
We can say the the movement into schizophrenia AS A RESULT of Cannibis is low. The article points to an association which is not determined to be causel. Cannibas has been used in the US for years; it has a downside, to be certain, but a flood of psychotic teenagers would have hit the wards years ago if Cannibas was the neurotoxin you seem to assert. Think about it.
It is important to assess actual risk while leaving out the emotion. Perhaps you have had a bad experience with illicit drugs or have lost someone as a result; perhaps you have seen bad psychiatry. The question in point is the Cannibis psychosis link. Correlation does not mean causation; My statement nor anyone else's seem to be pushing Cannibas. It is the link to psychosis that is the question.
You are correct on my haphazard statement about the DEA website having a grid demonstrating individual risk and placing Cannibas below alcohol and tobacco. That was not on the website when I rechecked. Even weaker, I do not remember where I saw the grid. You got me on that one.

by Jose Gros-Aymerich | May 21, 2012 4:14 PM EDT

An old and today hard to retrieve article by F Lalonde (CA), in "Toxicomanies", 1973, vol 6, pags 343-355, and entilted: "La personalite psychedelique -the psychedelic personality-" points that the people that voluntarily engaged in medical experiments involving the intake of LSD differed from street users of it, and also that the personalities of people that may consider attractive taking psychodisleptics are the ones that can have more harm from its use. Not considering the fact of if the things people buy as LSD from drug dealers are really this drug, it's known that mandatorily the drug has to be synthesized from the ergot fungus raw materials, no possibility exists of a 100% synthetic LSD, thus greatly limiting the availability and chances of purity of anything offered as psychodisleptics in the streets, are there differences in the baseline traits of cannabis users versus psychodisleptics users, and in the incidence and outcome of psychosis and other mental disorders connected to the use of this similar, but not identical types of drugs of abuse?. Salut +

by david miller | March 28, 2012 12:58 AM EDT

What these studies completely ignore is the fact that individuals with bipolar and schizophrenia use cannabis to self medicate. The more severe the disorder, the higher the dose of the medication. These studies may be placing the cart before the horse. Cannabis does not necessarily increase psychosis, but those with accelerated brain activity, and high probability of psychosis, are more likely to utilize it.

Thus, those using cannabis regularly are going to be more likely to exhibit psychosis, as they are using it to medicate the symptoms of their disorder. The studies should examine the frequency of bipolar and schizophrenia in long term cannabis users, and examine if the drug use is a CAUSE or a SYMPTOM of the disorders.

Cannabis slows the thought process....racing thoughts are a constant battle for a bipolar/schizophrenic patient....and medicating with the street drug of weed is a staple of many individuals battling the onset of psychosis.

by Tammi Snow | March 14, 2012 2:24 PM EDT

I agree with Drs. Newman & Welkowitz. Cannabis has been used for medicinal purposes for centuries. I know many people who utilize cannabis for medicinal & recreational purposes and are very productive in their professional & private lives. The cannabis & schizophrenia link needs to have more in-depth studies with conclusive evidence. It has been a safe & effective medicinal herb with lower side effects than many of our synthetic medications. Frequently, it is the only thing that allows our chronically ill pateints to have some quality of life.

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