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 ΔBPND in 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.
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Funding for this study was provided by grant R01 DA022455-01A1 from the National Institute on Drug Abuse. Dr van de Giessen was supported by a Rubicon grant from the Netherlands Organisation for Scientific Research (825.12.009).
Dr Haney has received partial salary support for investigator-initiated studies from Insys Therapeutics Inc and Lifeloc Technologies and has served as a consultant to Aelis Farma and Health Advances LLC. Dr Kegeles has received research support from Amgen. Dr Slifstein has received research support from Forest Laboratories, Pierre-Fabre, CHDI, and Otsuka and has provided consultation for Amgen. Dr Abi-Dargham has received research support from Takeda and Forest Pharmaceuticals and has served on advisory boards for Roche, Forum, and Otsuka. The remaining authors declare no conflict of interests.
Supplementary Information accompanies the paper on the Molecular Psychiatry website
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van de Giessen, E., Weinstein, J., Cassidy, C. et al. Deficits in striatal dopamine release in cannabis dependence. Mol Psychiatry 22, 68–75 (2017). https://doi.org/10.1038/mp.2016.21
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