title: Cannabis Abusers Show Hypofrontality and Blunted Brain Responses to a Stimulant Challenge in Females but not in Males.
abstract: The extent to which cannabis is deleterious to the human brain is not well understood. Here, we test whether cannabis abusers (CA) have impaired frontal function and reactivity to dopaminergic signaling, which are fundamental to relapse in addiction. We measured brain glucose metabolism using PET and [(18)F]FDG both at baseline (placebo) and after challenge with methylphenidate (MP), a dopamine-enhancing drug, in 24 active CA (50% female) and 24 controls (HC; 50% female). Results show that (i) CA had lower baseline glucose metabolism than HC in frontal cortex including anterior cingulate, which was associated with negative emotionality. (ii) MP increased whole-brain glucose metabolism in HC but not in CA; and group by challenge effects were most profound in putamen, caudate, midbrain, thalamus, and cerebellum. In CA, MP-induced metabolic increases in putamen correlated negatively with addiction severity. (iii) There were significant gender effects, such that both the group differences at baseline in frontal metabolism and the attenuated regional brain metabolic responses to MP were observed in female CA but not in male CA. As for other drug addictions, reduced baseline frontal metabolism is likely to contribute to relapse in CA. The attenuated responses to MP in midbrain and striatum are consistent with decreased brain reactivity to dopamine stimulation and might contribute to addictive behaviors in CA. The gender differences suggest that females are more sensitive than males to the adverse effects of cannabis in brain.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Corinde E
authors.initials: CE
authors.lastname: Wiers
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Shokri-Kojori
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Christopher T
authors.identifier: 0000-0001-5560-3835
authors.initials: CT
authors.lastname: Wong
authors.affiliation: Division of Translational Imaging, Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Şükrü B
authors.initials: ŞB
authors.lastname: Demiral
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.|National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D002189:Marijuana Abuse / Q000000981:diagnostic imaging / Q000473:pathology*; D008774:Methylphenidate / Q000494:pharmacology; D008875:Middle Aged; D010555:Personality Inventory; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D012727:Sex Characteristics; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D019788:Fluorodeoxyglucose F18; D008774:Methylphenidate