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.

Marijuana doesn’t count, does it?” Clinicians are familiar with this common reply when screening for drug use. Cannabis—the most common illicit substance—has managed to exempt itself from the hazardous reputation held by other illicit drugs.¹ As mental health practitioners, it is our duty to educate our patients about the potential harms and consequences of cannabis use. This important task is complicated by the disagreement and uncertainty surrounding the nature of the interaction between cannabis and psychotic disorders.

More than 16 million Americans use cannabis on a regular basis, typically beginning in adolescence. Notably, it is estimated that approximately 4% of the population have a diagnosis of either cannabis abuse or dependence.¹ A history of cannabis misuse is even more common in patients who are schizophrenic than in the general population; 25% of patients with schizophrenia have a comorbid cannabis use disorder. Cannabis use disorders are especially common in younger and first-episode patient samples and in samples with high proportions of males.²

Neurobiology

Marijuana contains more than 400 chemical compounds, including over 60 cannabinoids that contribute to its psychopharmacological effects. The primary psychoactive constituent of cannabis is delta-9-tetrahydrocannabinol (THC). Other plant cannabinoids include delta-8-tetrahydrocannabinol; cannabinol; and cannabidiol (CBD); CBD is the second major psychoactive constituent of cannabis.³ The ratios of these and other cannabinoids vary enormously in preparations of cannabis, and little information exists about the concentration of each of the particular cannabinoids in commonly used cannabis products. Concerns have been expressed regarding the large increase in the potency of cannabis and the surrounding health implications. In the 1960s, the THC content was thought to be in the range of 1% to 3%; today it can reach up to 20%.⁴

The endogenous cannabinoid system consists of 2 types of G-protein-coupled receptors: cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors. CB1 receptors are the most abundant in the brain, while CB2 receptors predominate on immune cells. CB1 receptors are highly concentrated in brain regions implicated in the putative neural circuitry of psychosis and cognitive function. These include the hippocampus, prefrontal cortex, anterior cingulate, basal ganglia, cerebellum, and cortex, with lower levels present in the thalamus, hypothalamus, and amygdala. Activation of CB1 receptors mediates the behavioral and physiological effects of both endogenous and exogenous cannabinoids in the brain.⁴

An important role of the CB1 receptor is to modulate neurotransmitter release in a manner that maintains homeostasis by preventing excessive neuronal activity in the CNS.⁵ CB1 receptors are localized on presynaptic neuron terminals on both inhibitory and excitatory neurons, yet they predominate on γ-aminobutyric acid interneurons.⁶ It is the inhibitory neurons that are thought to mediate most of the effects of cannabinoids. In addition, the action of cannabinoids includes interactions, albeit indirectly, with the dopamine(Drug information on dopamine)rgic system.

THC is a partial agonist at the CB1 receptors, where it has modest affinity and low intrinsic activity. In contrast, CBD shows very little affinity for CB1 receptors. Moreover, the precise molecular mechanism of action of CBD remains unclear. The main endocannabinoids are anandamide and 2-arachidonylglycerol. In contrast to classic neurotransmitters, endocannabinoids can function as retrograde synaptic messengers—they are released from postsynaptic neurons and travel backward across synapses, activating CB1 on presynaptic axons and suppressing neurotransmitter release.

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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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