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.

Cannabinoids produce an increase in the dopamine(Drug information on dopamine)rgic activity in the mesolimbic reward pathway, which plays a pivotal role in mediating the reinforcing effects of most drugs of abuse. The increased dopaminergic drive elicited by the cannabinoids could underlie the abusive property of the drug and increases in positive psychotic symptoms induced by THC.⁷ Recurrent cannabis use produces prolonged and excessive stimulation of the CB1 receptor, and this is thought to disrupt endocannabinoid system function.⁸ Several lines of evidence exist to suggest a role for cannabinoids and their receptors in the pathophysiology of schizophrenia. It has also been proposed that this CB1 receptor overstimulation may be a contributing factor in triggering THC-induced psychosis.⁹

The cannabis-psychosis link

Many studies have explored the link between cannabis and psychosis (Table). In a systematic review, Moore and colleagues¹⁰ surveyed the literature on this topic. They looked at population-based longitudinal studies as well as nested case-control studies that assessed the impact of cannabis use on the later development of psychosis. The “psychosis” outcomes required the diagnosis of a primary psychotic disorder or affective psychosis, or the occurrence of delusions, hallucinations, or thought disorder during the study period. Results from 7 cohort studies showed a 40% increased risk of psychosis in cannabis users compared with nonusers. The data also revealed a dose-response effect—the risk of psychotic symptoms was increased approximately 50% to 200% in those who used cannabis frequently compared with nonusers.

What is already known about the link between cannabis use and psychosis?

■ There is strong evidence to support the hypothesis that cannabis consumption is a risk factor for the development of psychotic symptoms and schizophrenia.

What new information does this article provide?

■ This article emphasizes the negative effects of cannabis use in young populations and in those who may confer a genetic risk. We further believe that even in the face of enhanced cognitive function among cannabis-using patients with established schizophrenia, this cannabis use worsens the clinical course and overall prognosis of the disorder.

What are the implications for psychiatric practice?

■ While scientists attempt to clarify the relationship between cannabis and psychosis, it is important that we take the link between cannabis and psychosis seriously by definitively assessing patients for cannabis use. Clinicians should be educating their clients about the potential dangers of using cannabis and the potential benefits of quitting.

Critics of this hypothesis believe that cohort studies have inherent limitations that prevent any clear conclusions from being drawn. McLaren and colleagues¹¹ evaluated the methodological strength of the existing cohort studies. The definition of psychosis was a recurrent limitation in the studies. Many studies used psychotic symptoms, not diagnoses, as their outcome, which may not be of clinical significance. Moore and colleagues¹⁰ also noted this limitation and attempted to correct for it by separately analyzing the 2 studies that required the diagnosis of a primary psychotic disorder. Interestingly, they found an odds ratio of 2.6 for the development of psychotic disorders in those who had ever used cannabis compared with nonusers. Important confounding factors, such as noncannabis drug use, a family history of psychosis, and unmeasured vulnerability to psychosis, were not adequately controlled in these studies.¹¹

Age at onset of psychosis and cannabis use

Certain risk factors have been reported to interact with cannabis use to increase vulnerability to developing psychosis. One suspected important variable is the age at which cannabis use is started. The age effect was first noted in a Swedish conscript cohort study that demonstrated that cannabis use by age 18 led to a 6-fold increase in the risk of schizophrenia later in life.¹² It is unclear, however, whether the psychotic symptoms predated the cannabis use.

To clarify this issue, the Dunedin Multidisciplinary Health and Development Study conducted a prospective longitudinal study of adolescent cannabis use, taking into account psychotic symptoms that occurred before cannabis use.¹³ The data were compiled from a birth cohort that consisted of 1037 individuals born in Dunedin, New Zealand. Information about psychotic symptoms was obtained at age 11, and drug use was assessed by self-reports at ages 15 and 18 and by a standardized interview schedule at age 26. Two psychosis-related outcomes were measured—the presence of symptoms of schizophrenia and the diagnosis of schizophreniform disorder.

The results showed that those who had used cannabis by ages 15 and 18 had more schizophrenia symptoms than controls, a finding that remained significant after controlling for the presence of psychotic symptoms at age 11. However, the increased likelihood of schizophreniform disorder at age 26 was no longer significant after controlling for psychotic symptoms at age 11. Taken together, this suggests that early cannabis use confers higher risk of psychosis.

These findings may be explained as follows: Adolescence represents a sensitive period of neurodevelopment, with the brain more vulnerable to the effects of cannabis. Alternatively, the heightened risk may simply be a consequence of greater cumulative cannabis use, since these subjects began using it at a younger age. These theories are not mutually exclusive, and the latter explanation is consistent with the previously mentioned dose-response relationship observed in many studies.

Pages: 1 2 3

Previous Next

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.

Article Comment Pages: 1 2 Next

More like this

The Cannabis-Psychosis Link

Cannabis and Psychosis: What’s Behind the Link

The Cannabis-Psychosis Link

Medical Marijuana: Regulations Surrounding Its Use

The Cannabis-Psychosis Link

What is already known about the link between cannabis use and psychosis? ■ There is strong evidence to support the hypothesis that cannabis consumption is a risk factor for the development of psychotic symptoms and schizophrenia.

Join the Conversation

What is already known about the link between cannabis use and psychosis?

■ There is strong evidence to support the hypothesis that cannabis consumption is a risk factor for the development of psychotic symptoms and schizophrenia.