Δ9-THC reduces reward-related brain activity in healthy adults

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.

Keywords: Cannabis; EEG; Reward; ∆9-THC.

Fig. 1

Trial progression of the e-MID task. Reward, punishment, or neutral cues were presented in the form of circles encasing “Win $1.50,” squares encasing “Lose $0.75,” or diamonds encasing “$0.00.” Responses to filled circles were made as quickly as possible after a fixation cross was displayed for a randomly jittered time interval between 2000 and 2500 ms. Following another 2000 ms delay, feedback was provided to indicate hits “WIN” or misses “LOSE.” ITI, intertrial interval

Fig. 2

Time course of subjective drug effects. Ratings indicate magnitude of feeling a drug effect (A) and liking a drug effect (B); gray shaded region indicates period of EEG assessments

Fig. 3

RewP components in response to feedback (outcomes) in the e-MID task. A RewP amplitudes as a function of dose (placebo, 7.5, 15 mg Δ9-THC; oral) (repeated-measures ANOVA, p < 0.01, n = 24). B RewP amplitudes as a function of positive (hits) or negative (misses) feedback (repeated-measures ANOVA, p < 0.01, n = 24). C RewP amplitudes as a function of cue condition presented at the start of each trial (reward, punishment, neutral) (repeated-measures ANOVA, p < 0.001, n = 24). Shaded region indicates window of analysis (250–350 ms post-stimulus)

Fig. 4

P300 and LPP components in response to feedback (outcomes) in the e-MID task. A P300 and LPP amplitudes as a function of dose (placebo, 7.5, 15 mg Δ9-THC; oral) (n.s., n = 24). B P300 and LPP amplitudes as a function of positive (hits) or negative (misses) feedback (repeated-measures ANOVA, P300, p < 0.001; LPP n.s., n = 24). C P300 and LPP amplitudes as a function of cue condition presented at the start of each trial (reward, punishment, neutral) (repeated-measures ANOVA; P300, p < 0.01; LPP, p < 0.05, n = 24). D Hits minus misses difference waves for each dose (placebo, 7.5, 15 mg Δ9-THC; oral) (t-tests, P300, 15 mg p < 0.01 vs placebo, 7.5 mg p < 0.05 vs placebo; LPP, 15 mg p < 0.01 vs placebo, 7.5 mg p < 0.05 vs placebo, n = 24). Shaded regions indicate windows of analyses (350–450 ms post-stimulus, P300; 450–800 ms post-stimulus, LPP)