PT Mobile Logo

Search form


The Cannabis-Psychosis Link: Page 3 of 3

The Cannabis-Psychosis Link: Page 3 of 3

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. 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 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


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.




1. United Nations Office on Drugs and Crime (UNODC). World Drug Report 2010. Vienna: United Nations; 2010.
2. Koskinen J, Löhönen J, Koponen H, et al. Rate of cannabis use disorders in clinical samples of patients with schizophrenia: a meta-analysis. Schizophr Bull. 2010;36:1115-1130.
3. Iversen LL. The Science of Marijuana. 2nd ed. New York: Oxford University Press; 2008.
4. Ameri A. The effects of cannabinoids on the brain. Prog Neurobiol. 1999;58:315-348.
5. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199-215.
6. Eggan SM, Lewis DA. Immunocytochemical distribution of the cannabinoid CB1 receptor in the primate neocortex: a regional and laminar analysis. Cereb Cortex. 2007;17:175-191.
7. Szabo B, Siemes S, Wallmichrath I. Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. Eur J Neurosci. 2002;15:2057-2061.
8. Murray RM, Morrison PD, Henquet C, Di Forti M. Cannabis, the mind and society: the hash realities. Nat Rev Neurosci. 2007;8:885-895.
9. Morrison PD, Murray RM. From real-world events to psychosis: the emerging neuropharmacology of delusions. Schizophr Bull. 2009;35:668-674.
10. Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370:319-328.
11. McLaren JA, Silins E, Hutchinson D, et al. Assessing evidence for a causal link between cannabis and psychosis: a review of cohort studies. Int J Drug Policy. 2009;21:10-19.
12. Andréasson S, Allebeck P, Engström A, Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet. 1987;2:1483-1486.
13. Arseneault L, Cannon M, Poulton R, et al. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 2002;325:1212-1213.
14. Caspi A, Moffitt TE, Cannon M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005;57:1117-1127.
15. Lachman HM, Papolos DF, Saito T, et al. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996;6:243-250.
16. Bilder RM, Volavka J, Lachman HM, Grace AA. The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology. 2004;29:1943-1961.
17. Fergusson DM, Horwood LJ, Swain-Campbell NR. Cannabis dependence and psychotic symptoms in young people. Psychol Med. 2003;33:15-21.
18. Bowers MB Jr, Mazure CM, Nelson JC, Jatlow PI. Psychotogenic drug use and neuroleptic response. Schizophr Bull. 1990;16:81-85.
19. Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatry. 1994;51:273-279.
20. Rabin RA, Zakzanis KK, George TP. The effects of cannabis use on neurocognition in schizophrenia: a meta-analysis. Schizophr Res. 2011;128:111-116.
21. Zuardi AW, Crippa JA, Hallak JE, et al. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006;39:421-429.
22. Fadda P, Robinson L, Fratta W, et al. Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology. 2004;47:1170-1179.
23. Henquet C, Krabbendam L, Spauwen J, et al. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ. 2005;330:11.
24. Tien AY, Anthony JC. Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences. J Nerv Ment Dis. 1990;178:473-480.
25. van Os J, Bak M, Hanssen M, et al. Cannabis use and psychosis: a longitudinal population-based study. Am J Epidemiol. 2002;156:319-327.

Loading comments...

By clicking Accept, you agree to become a member of the UBM Medica Community.