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.
Chronic exposure to THC during adolescence in squirrel monkeys produces long-lasting changes in brain functional connectivity and motivation that persist into adulthood. Daily treatment with either a low (0.32 mg/kg) or high dose (3.2 mg/kg) of THC for six months during adolescence led to persistent alterations in connectivity of the medial orbitofrontal cortex, caudate, and ventral striatum. In economic demand tests, THC-treated subjects showed dosage-dependent disruption in reward sensitivity and motivation, unlike vehicle-treated subjects who displayed the expected inverse relationship between reward magnitude and effort. The findings indicate that adolescent THC exposure causes enduring neurocognitive abnormalities in reward processing.