Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines

Kuepper, Rebecca; Morrison, Paul D.; van Os, Jim; Murray, Robin M.; Kenis, Gunter; Henquet, Cécile

doi:10.1016/j.schres.2010.05.031

« Previous Next »Schizophrenia Research
Volume 121, Issue 1 , Pages 107-117, August 2010

Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines

Rebecca Kuepper
- Department of Psychiatry and Psychology, EURON, Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, Maastricht, The Netherlands
Paul D. Morrison
- King’s College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, UK
Jim van Os
- Department of Psychiatry and Psychology, EURON, Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, Maastricht, The Netherlands
- King’s College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, UK
Robin M. Murray
- King’s College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, UK
- NIHR Biomedical Research Centre, Institute of Psychiatry, Kings College, London, United Kingdom
Gunter Kenis
- Department of Psychiatry and Psychology, EURON, Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, Maastricht, The Netherlands
Cécile Henquet
- Department of Psychiatry and Psychology, EURON, Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, Maastricht, The Netherlands
- Mondriaan Zorggroep, Division Addiction Care, South Limburg, The Netherlands
- Corresponding author. Department of Psychiatry and Psychology, EURON, Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, Maastricht, The Netherlands.

Received 14 January 2010; received in revised form 22 March 2010; accepted 16 May 2010. published online 28 June 2010.

Abstract

General population epidemiological studies have consistently found that cannabis use increases the risk of developing psychotic disorders in a dose-dependent manner. While the epidemiological signal between cannabis and psychosis has gained considerable attention, the biological mechanism whereby cannabis increases risk for psychosis remains poorly understood. Animal research suggests that delta-9-tetrahydrocannabinol (THC, the main psychoactive component of cannabis) increases dopamine levels in several regions of the brain, including striatal and prefrontal areas. Since dopamine is hypothesized to represent a crucial common final pathway between brain biology and actual experience of psychosis, a focus on dopamine may initially be productive in the examination of the psychotomimetic effects of cannabis. Therefore, this review examines the evidence concerning the interactions between THC, endocannabinoids and dopamine in the cortical as well as subcortical regions implicated in psychosis, and considers possible mechanisms whereby cannabis-induced dopamine dysregulation may give rise to delusions and hallucinations. It is concluded that further study of the mechanisms underlying the link between cannabis and psychosis may be conducted productively from the perspective of progressive developmental sensitization, resulting from gene–environment interactions.

Keywords: Cannabis, Psychosis, THC, Dopamine, Endocannabinoid system