title: Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity.
abstract: Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [(11)C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral ("self-reports" for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [(11)C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BPND)] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BPND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857;National Institute on Drug Abuse, Rockville, MD 20857; nvolkow@nida.nih.gov fowler@bnl.gov.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857;
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857;
authors.forename: Frank
authors.initials: F
authors.lastname: Telang
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973; and nvolkow@nida.nih.gov fowler@bnl.gov.
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973; and.
authors.forename: David
authors.initials: D
authors.lastname: Alexoff
authors.affiliation: Department of Radiology, New York University Langone Medical Center, New York, NY 10016.
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857;
authors.forename: Millard
authors.initials: M
authors.lastname: Jayne
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857;
authors.forename: Christopher
authors.initials: C
authors.lastname: Wong
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857;
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
mesh_terms: D000328:Adult; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004644:Emotions; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D008774:Methylphenidate / Q000008:administration & dosage; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000008:administration & dosage; D011859:Radiography; D012720:Severity of Illness Index
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine
keywords: amotivation; brain imaging; cannabinoid 1 receptors; midbrain; nucleus accumbens