Michael A P Bloomfield1, Celia J A Morgan2, Alice Egerton1, Shitij Kapur3, H Valerie Curran2, Oliver D Howes4. 1. Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital, Imperial College London; Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom. 2. Clinical Psychopharmacology Unit, Division of Psychology and Language Sciences, University College London. 3. Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom. 4. Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital, Imperial College London; Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom. Electronic address: oliver.howes@csc.mrc.ac.uk.
Abstract
BACKGROUND: Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function. METHODS: We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA). RESULTS: Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19). CONCLUSIONS: These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.
BACKGROUND: Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function. METHODS: We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA). RESULTS: Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19). CONCLUSIONS: These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.
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