Δ 9 -Tetrahydrocannabinol-induced enhancement of reward responsivity via mesocorticolimbic modulation in squirrel monkeys.
bioRxiv : the preprint server for biology January 24, 2026 Kwang-Hyun Hur, Lisa D Nickerson, Jack Bergman et al.
THC, the psychoactive compound in cannabis, selectively amplifies behavioral and brain responses to cues that predict rewards, without affecting responses to neutral cues or baseline reward consumption. In squirrel monkeys, a low dose of THC (3 μg/kg) increased conditioned approach behavior toward a visual stimulus associated with food delivery. Functional MRI showed that THC enhanced activity in reward-related brain regions—anterior cingulate cortex, striatum, hippocampus, and substantia nigra-ventral tegmental area (SN-VTA)—while leaving visual and motor cortices unaffected. Resting-state connectivity analyses revealed that THC strengthened communication within mesocorticolimbic networks, with the SN-VTA acting as a central hub. These findings indicate that THC boosts incentive salience and motivational drive toward reward-associated stimuli through selective modulation of this circuitry.