The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study
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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.
The aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users.
We measured dopamine synthesis capacity (indexed as the influx rate constant K i cer ) via 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users.
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).
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.
KeywordsApathy Cannabis Drugs Dopamine Imaging Motivation PET
Our study was funded by a Medical Research Council (UK) grant to Dr. Howes (grant number: MC-A656-5QD30), a National Institute of Health Research Biomedical Research Council grant to King’s College London and a Medical Research Council (UK) grant to Professor Curran and Dr Morgan. We thank our subjects, the radiographers and staff of GE Imanet for their assistance with PET scans and Professor Federico Turkheimer for statistical and methodological advice.
Conflict of interest
The authors declare no financial conflict of interest. The authors have full control of all primary data, and they agree to allow the journal to review their data if requested.
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