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.
Chronic delta-9-tetrahydrocannabinol (THC) exposure during adolescence alters functional connectivity between the default mode and central executive networks in the adult brain in a dose-dependent manner. In squirrel monkeys given daily low (0.32 mg/kg) or high (3.2 mg/kg) THC injections for six months during adolescence, only the low dose increased connectivity between these networks during the exposure period, an effect that reversed after discontinuation. The high dose and vehicle controls showed no such change. The central executive network appeared to drive this effect. The findings suggest that adolescent THC exposure can produce non-linear, dose-dependent disruptions in large-scale brain networks.