title: Deficits in striatal dopamine release in cannabis dependence.
abstract: Most drugs of abuse lead to a general blunting of dopamine release in the chronic phase of dependence, which contributes to poor outcome. To test whether cannabis dependence is associated with a similar dopaminergic deficit, we examined striatal and extrastriatal dopamine release in severely cannabis-dependent participants (CD), free of any comorbid conditions, including nicotine use. Eleven CD and 12 healthy controls (HC) completed two positron emission tomography scans with [11C]-(+)-PHNO, before and after oral administration of d-amphetamine. CD stayed inpatient for 5-7 days prior to the scans to standardize abstinence. Magnetic resonance spectroscopy (MRS) measures of glutamate in the striatum and hippocampus were obtained in the same subjects. Percent change in [11C]-(+)-PHNO-binding potential (ΔBPND) was compared between groups and correlations with MRS glutamate, subclinical psychopathological and neurocognitive parameters were examined. CD had significantly lower ΔBPNDin the striatum (P=0.002, effect size (ES)=1.48), including the associative striatum (P=0.003, ES=1.39), sensorimotor striatum (P=0.003, ES=1.41) and the pallidus (P=0.012, ES=1.16). Lower dopamine release in the associative striatum correlated with inattention and negative symptoms in CD, and with poorer working memory and probabilistic category learning performance in both CD and HC. No relationships to MRS glutamate and amphetamine-induced subclinical positive symptoms were detected. In conclusion, this study provides evidence that severe cannabis dependence-without the confounds of any comorbidity-is associated with a deficit in striatal dopamine release. This deficit extends to other extrastriatal areas and predicts subclinical psychopathology.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.|Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van de Giessen
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Weinstein
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Cassidy
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Haney
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ghazzaoui
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ojeil
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Kegeles
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.|Department of Psychiatry, Stony Brook University School of Medicine, New York, NY, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Vadhan
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Slifstein
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Abi-Dargham
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002188:Cannabis / Q000009:adverse effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D002189:Marijuana Abuse / Q000378:metabolism / Q000503:physiopathology*; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D063388:Endocannabinoids; D000661:Amphetamine; D003913:Dextroamphetamine; D004298:Dopamine