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


OBJECTIVE
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 a motivation associated with chronic cannabis use.
Psychiatric Imaging Group, Mansfield Building, Medical Research Council Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 0NN, UK.
Michael A P
MA
Bloomfield
Celia J A
CJ
Morgan
Shitij
S
Kapur
H Valerie
HV
Curran
Oliver D
OD
Howes
D057565:Apathy / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D002188:Cannabis; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology; D004295:Dihydroxyphenylalanine; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals; D057566:Self Report; D055815:Young Adult
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D004295:Dihydroxyphenylalanine; D004298:Dopamine