The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study

• Published in: Psychopharmacology Vol. 231; no. 11; pp. 2251 - 2259
• Main Authors: Bloomfield, Michael A. P., Morgan, Celia J. A., Kapur, Shitij, Curran, H. Valerie, Howes, Oliver D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2014; Springer Nature B.V
• Subjects: Apathy - drug effects; Apathy - physiology; Biomedical and Life Sciences; Biomedicine; Brain - diagnostic imaging; Brain - physiopathology; Brain Mapping; Cannabis; Cohort Studies; Corpus Striatum - diagnostic imaging; Corpus Striatum - physiopathology; Dihydroxyphenylalanine; Dopamine; Dopamine - metabolism; Drug use; Female; Fluorine Radioisotopes; Humans; Male; Marijuana; Marijuana Abuse - diagnostic imaging; Marijuana Abuse - physiopathology; Medical imaging; Neurosciences; Original Investigation; Pharmacology/Toxicology; Positron-Emission Tomography; Psychiatric Status Rating Scales; Psychiatry; Radiopharmaceuticals; Self Report; Young Adult; Apathy; Drugs; Cannabis; Dopamine; Motivation; Imaging; PET
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-014-3523-4

Rationale Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. apathy. Regular long-term cannabis use has been associated with reduced dopamine synthesis capacity. The mesolimbic dopaminergic system mediates the processing of incentive stimuli by modifying their motivational value, which in turn is modulated by endocannabinoid signalling. Thus, it has been proposed that dopaminergic dysfunction underlies the apathy associated with chronic cannabis use. Objectives The aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users. Methods We measured dopamine synthesis capacity (indexed as the influx rate constant K i cer ) via 3,4-dihydroxy-6-[ 18 F]-fluoro- l -phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users. Results All subjects scored in excess of 34 points on the AES-S (median [interquartile range] 59.5 [7.5]), indicative of significant apathy based on normative data. K i cer was inversely correlated to AES-S score in the whole striatum and its associative functional subdivision (Spearman’s rho = −0.64, p  = 0.015 [whole striatum]; rho = −0.69, p  = 0.006 [associative]) but not in the limbic or sensorimotor striatal subdivisions. There were no significant relationships between AES-S and current cannabis consumption (rho = 0.28, p  = 0.34) or age of first cannabis use (rho = 0.25, p  = 0.40). Conclusions These findings indicate that the reduction in striatal dopamine synthesis capacity associated with chronic cannabis use may underlie reduced reward sensitivity and amotivation associated with chronic cannabis use.