Value Signals Guiding Choices for Cannabis Versus Non-Drug Rewards in Regular Cannabis Users

Background: Despite the critical role of choice processes in substance use disorders, the neurobehavioral mechanisms guiding human decisions about drugs remain poorly understood. We adapted a neuroeconomic framework to characterize the neural encoding of subjective value (SV) for cannabis versus non-drug rewards (snacks) in near-daily cannabis users. We also assessed the impact of cannabis and snack stimuli (‘cues’) on SV encoding. Methods: Twenty-one non-treatment-seeking cannabis users (≥4 days/week; 1 female) participated in an inpatient, crossover experiment with four counterbalanced conditions: 1. neutral cues/cannabis choices; 2. cannabis cues/cannabis choices; 3. neutral cues/snack choices; and 4. snack cues/snack choices. In each condition, participants were exposed to cues before an fMRI scan during which they repeatedly chose between 0-6 cannabis puffs/snacks and a set monetary amount, with randomly-selected choices implemented. The SV signal was operationalized as the neural correlates of the strength of preference for cannabis/snack choices. fMRI data were analyzed for twenty participants. Results: Despite equivalent choice behavior, SV signals for cannabis, but not snacks, were observed in regions known to encode SV for various rewards (ventromedial prefrontal cortex, vmPFC; ventral striatum; dorsal posterior cingulate cortex, dPCC). SV encoding in vmPFC was stronger for cannabis than snacks. In the dPCC, the impact of cues on SV signals was moderated by the reward type. Conclusions: Near-daily cannabis users had expected neural value encoding for cannabis but disrupted non-drug SV encoding, despite equivalent choice behavior. Results provide support for models identifying dysregulated neural valuation of non-drug rewards as a hallmark of problematic substance use.