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February 16, 2011

Marijuana (Cannabis) use and Mental Illness

Is marijuana usage associated with an increased incidence or earlier onset of mental illness?  This controversy has received fairly heavy exposure in the media lately.  With the spread of “legal” medical marijuana and increased availability through medical marijuana dispensaries, this issue is becoming more relevant.  Several recent studies examine this issue.

A large meta-analysis published in the Archives of General Psychiatry provided evidence for a relationship between cannabis use and earlier onset of psychotic illness.  They conclude that marijuana usage plays a causal role in the development of psychosis in some patients (1).

Research from Barcelona, Spain suggests that age at first cannabis use is related to age of emergence of psychiatric symptoms, especially related to the schizophrenic spectrum (2).

New synthetic cannabinoids are becoming increasingly prevalent.  An article in the journal Drug and Alcohol Dependency found that these synthetic substances can precipitate psychosis and should be avoided in persons with risk factors for psychosis (3).

An interesting editorial from the United Kingdom discusses marijuana usage and psychosis:

Numerous studies have shown that patients with psychosis are more likely to use illicit drugs than the general population, with cannabis being the most popular. There exists overwhelming evidence that cannabis use can contribute to the onset of schizophrenia and poor outcome in patients with established psychosis. Therefore, understanding why patients use cannabis and whether they are motivated to change their habits is important. The evidence is that patients with psychosis use cannabis for the same reasons the general population does, to ‘get high’, relax and have fun. There is little support for the ‘self-medication’ hypothesis, while the literature points more towards an ‘alleviation of dysphoria’ model. There is a lack of research reporting on whether psychotic patients are ready to change their use of cannabis, which has obvious implications for identifying which treatment strategies are likely to be effective (4).

Researchers in Norway found that excessive use of cannabis was associated with earlier onset of Bipolar Disorder, in contrast to alcohol usage, which was associated with later onset of Bipolar Disorder.  They surmised that early onset of Bipolar Disorder may increase the risk of cannabis use and that use of cannabis may trigger the onset of bipolar symptoms in vulnerable individuals (5).

Overall, it appears that usage of marijuana is common among patients with mental illness, especially among the schizophrenic spectrum.  While there is increased usage in persons with psychosis and mood disorders, marijuana also is associated with earlier onset of psychotic illness and bipolar disorder.

1. Arch Gen Psychiatry. 2011 Feb 7. [Epub ahead of print]
Cannabis Use and Earlier Onset of Psychosis: A Systematic Meta-analysis.
Large M, Sharma S, Compton MT, Slade T, Nielssen O.
Prince of Wales Hospital (Drs Large and Sharma), and School of Psychiatry (Drs Large and Sharma), Clinical Research Unit for Anxiety and Depression, School of Psychiatry (Dr Nielssen), and National Drug and Alcohol Research Centre (Dr Slade), University of New South Wales, Sydney, Australia; and Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia (Dr Compton). Dr Compton is now with the Department of Psychiatry and Behavioral Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC. CONTEXT: A number of studies have found that the use of cannabis and other psychoactive substances is associated with an earlier onset of psychotic illness. OBJECTIVE: To establish the extent to which use of cannabis, alcohol, and other psychoactive substances affects the age at onset of psychosis by meta-analysis. DATA SOURCES: Peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non-substance-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science. STUDY SELECTION: Studies in English comparing the age at onset of psychosis in cohorts of patients who use substances with age at onset of psychosis in non-substance-using patients. The searches yielded 443 articles, from which 83 studies met the inclusion criteria. DATA EXTRACTION: Information on study design, study population, and effect size were extracted independently by 2 of us. DATA SYNTHESIS: Meta-analysis found that the age at onset of psychosis for cannabis users was 2.70 years younger (standardized mean difference = -0.414) than for nonusers; for those with broadly defined substance use, the age at onset of psychosis was 2.00 years younger (standardized mean difference = -0.315) than for nonusers. Alcohol use was not associated with a significantly earlier age at onset of psychosis. Differences in the proportion of cannabis users in the substance-using group made a significant contribution to the heterogeneity in the effect sizes between studies, confirming an association between cannabis use and earlier mean age at onset of psychotic illness. CONCLUSIONS: The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.
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2. Acta Psychiatr Scand. 2011 Jan 14. doi: 10.1111/j.1600-0447.2010.01665.x.
Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism.
Estrada G, Fatjó-Vilas M, Muñoz MJ, Pulido G, Miñano MJ, Toledo E, Illa JM, Martín M, Miralles ML, Miret S, Campanera S, Bernabeu C, Navarro ME, Fañanás L.
Anthropology Unit, Department of Animal Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain; Biomedicine Institute of the University of Barcelona (IBUB), Centre for Biomedical Research Network on Mental Health (CIBERSAM), Spain Adolescents Unit, Medical Complex in Mental Health Benito Menni, Sant Boi de Llobregat, Barcelona, Spain Child and Adolescent Mental Health Service, Parc Taulí Health Corporation, Sabadell, Spain Mental Health Centre of Lleida, Mental Health and Addictions Service, Santa Maria Hospital, Lleida, Spain.
Abstract
Estrada G, Fatjó-Vilas M, Muñoz MJ, Pulido G, Miñano MJ, Toledo E, Illa JM, Martín M, Miralles ML, Miret S, Campanera S, Bernabeu C, Navarro ME, Fañanás L. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Objective:  To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene. Method:  Cannabis use profiles and COMT Val158Met genotypes were obtained from 80 inpatients with schizophrenia-spectrum disorders and 77 inpatients with other non-psychotic disorders. Results:  First, age at first cannabis use correlates with age at onset in both schizophrenia-spectrum and other psychiatric disorder groups: those who started using cannabis earlier had an earlier age at onset of psychiatric disorders. Second, the distribution of the Val158Met genotypes was not different either between diagnosis groups or between cannabis users and non-users. Third, an interaction between Val158Met genotypes and cannabis use was observed specifically on age at emergence of psychotic disorders, with Val/Val genotype carriers showing an earlier age at onset than Met carriers. Conclusion:  Our results suggest the importance of brain maturation timing in which exposure to cannabis occurs. The COMT Val158Met genotype seems to modulate the association between cannabis and age at onset of psychotic disorders. These results are consistent with previous studies.
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3. Drug Alcohol Depend. 2011 Feb 10.
Synthetic cannabinoid JWH-018 and psychosis: An explorative study.

Every-Palmer S.

Te Korowai-Whāriki, A Capital and Coast District Health Board Service, Ratonga Rua O Porirua, Regional Forensic Service, Raiha Street, P O Box 50-233 Porirua, New Zealand.

BACKGROUND: Aroma, Spice, K2 and Dream are examples of a class of new and increasingly popular recreational drugs. Ostensibly branded “herbal incense”, they have been intentionally adulterated with synthetic cannabinoids such as JWH-018 in order to confer on them cannabimimetic psychoactive properties while circumventing drug legislation. JWH-018 is a potent cannabinoid receptor agonist. Little is known about its pharmacology and toxicology in humans. This is the first research considering the effects of JWH-018 on a psychiatric population and exploring the relationship between JWH-018 and psychotic symptoms. METHOD: This paper presents the results of semi-structured interviews regarding the use and effects of JWH-018 in 15 patients with serious mental illness in a New Zealand forensic and rehabilitative service.  RESULTS: All 15 subjects were familiar with a locally available JWH-018 containing product called “Aroma” and 86% reported having used it. They credited the product’s potent psychoactivity, legality, ready availability and non-detection in drug testing as reasons for its popularity, with most reporting it had replaced cannabis as their drug of choice. Most patients had assumed the product was “natural” and “safe”. Anxiety and psychotic symptoms were common after use, with 69% of users experiencing or exhibiting symptoms consistent with psychotic relapse after smoking JWH-018. Although psychological side effects were common, no one reported becoming physically unwell after using JWH-018. Three subjects described developing some tolerance to the product, but no one reported withdrawal symptoms.  CONCLUSION: It seems likely that JWH-018 can precipitate psychosis in vulnerable individuals. People with risk factors for psychosis should be counseled against using synthetic cannabinoids.

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4. Int J Dev Neurosci. 2010 Dec 21. [Epub ahead of print]

Why do patients with psychosis use cannabis and are they ready to change their use?

Kolliakou A, Joseph C, Ismail K, Atakan Z, Murray RM.

Department of Psychosis Studies, Institute of Psychiatry, King’s College London, United Kingdom.

Numerous studies have shown that patients with psychosis are more likely to use illicit drugs than the general population, with cannabis being the most popular. There exists overwhelming evidence that cannabis use can contribute to the onset of schizophrenia and poor outcome in patients with established psychosis. Therefore, understanding why patients use cannabis and whether they are motivated to change their habits is important. The evidence is that patients with psychosis use cannabis for the same reasons the general population does, to ‘get high’, relax and have fun. There is little support for the ‘self-medication’ hypothesis, while the literature points more towards an ‘alleviation of dysphoria’ model. There is a lack of research reporting on whether psychotic patients are ready to change their use of cannabis, which has obvious implications for identifying which treatment strategies are likely to be effective.

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5. Eur Arch Psychiatry Clin Neurosci. 2011 Jan 26. [Epub ahead of print]

Excessive cannabis use is associated with earlier age at onset in bipolar disorder.

Lagerberg TV, Sundet K, Aminoff SR, Berg AO, Ringen PA, Andreassen OA, Melle I.

Psychosis Research Unit, Department of Research and Development, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway, t.v.lagerberg@medisin.uio.no.

The aim of the study was to investigate which factors are associated with age at onset in bipolar disorder with a specific focus on excessive alcohol and cannabis use, and the sequence of the onsets of excessive substance use and bipolar disorder. We investigated a naturalistic sample of 151 patients with bipolar I and II disorder receiving psychiatric treatment. Whether the presence of excessive substance use prior to bipolar disorder onset or the type of substance used (alcohol or cannabis) was associated with differences in age at onset was investigated using hierarchical and multiple linear regression analyses, adjusting for potential confounders. Patients with excessive alcohol use had a significantly later onset compared with patients with excessive cannabis use. Excessive general substance use prior to bipolar disorder onset was associated with a later onset. However, excessive cannabis use was associated with an earlier onset whether it preceded or followed bipolar disorder onset, also after adjusting for possible confounders. Excessive use of alcohol or other substances was not independently associated with age at onset in multivariate analyses. Alcohol use was associated with a later onset compared with cannabis use, suggesting different relationships to the onset of bipolar disorder. Lifetime use of cannabis predicted an earlier onset, independent of the sequence of onsets. This indicates that an early onset may increase the risk of cannabis use and that cannabis use may trigger bipolar disorder in vulnerable individuals.

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