Abstract
Rationale
Greater availability of cannabis in the USA has raised concerns about adverse effects of the drug, including possible amotivational states. Lack of motivation may be assessed by examining acute effects of cannabinoids on reward processing.
Objectives
This study examined single doses of delta-9-tetrahydrocannabinol (∆9-THC; 7.5, 15 mg oral) in healthy adults using a version of the monetary incentive delay (MID) task adapted for electroencephalography (EEG; e-MID) in a within-subjects, double blind design.
Methods
Two phases of reward processing were examined: anticipation, which occurs with presentation of cues that indicate upcoming reward, punishment, or neutral conditions, and outcome, which occurs with feedback indicating hits or misses. During anticipation, we measured two event-related potential (ERP) components: the P300, which measures attention and motivation, and the LPP, which measures affective processing. During outcome processing, we measured P300 and LPP, as well as the RewP, which measures outcome evaluation.
Results
We found that ∆9-THC modulated outcome processing, but not reward anticipation. Specifically, both doses of ∆9-THC (7.5 and 15 mg) reduced RewP amplitudes after outcome feedback (hits and misses) relative to placebo. ∆9-THC (15 mg) also reduced P300 and LPP amplitudes following hits compared to misses, relative to both placebo and 7.5 mg ∆9-THC.
Conclusions
These findings suggest that ∆9-THC dampens responses to both reward and loss feedback, which may reflect an “amotivational” state. Future studies are needed to determine generalizability of this effect, such as its pharmacological specificity and its specificity to monetary vs other types of reward.
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Funding
This research was supported by the National Institutes of Health (DA02812). CHM was supported by the National Institutes of Health (T32DA043469). The authors declare no biomedical financial interests or potential conflicts of interest related to this project. HdW is or has been scientific advisor to PharmAla Biotech, Awakn Life Sciences, Gilgamesh Pharmaceuticals, and Schedule I Therapeutics for projects unrelated to this study, and has received research support from the Beckley Foundation for an unrelated project.
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Murray, C.H., Glazer, J.E., Lee, R. et al. Δ9-THC reduces reward-related brain activity in healthy adults. Psychopharmacology 239, 2829–2840 (2022). https://doi.org/10.1007/s00213-022-06164-y
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DOI: https://doi.org/10.1007/s00213-022-06164-y