Adolescent cannabis use increases risk for neuropsychiatric disorders, possibly through amygdala dysfunction. Chronic THC treatment in male adolescent nonhuman primates and rats disrupted sleep and increased anxiety-related behavior. THC activated proinflammatory glial cells (astrocytes) exclusively in the adolescent amygdala, upregulating GFAP and complement factor-B, effects absent in adults or other brain regions. THC also reduced synaptic plasticity markers stathmin-1 and NrCAM. Co-administered cannabidiol prevented astrocyte inflammation but did not restore plasticity markers. Astrogliosis correlated with fragmented sleep, attenuated plasticity markers with anxiety. Elevated CB1R expression in the maturing brain was astrocyte-localized in the amygdala, linking THC to unique adolescent amygdala vulnerability.
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.