Adolescent THC Exposure Caused Lasting Brain and Motivation Problems in Monkeys

Adolescent monkeys treated daily with THC for 6 months showed persistent alterations in medial orbitofrontal cortex, caudate, and ventral striatum functional connectivity that lasted after discontinuation. THC-treated monkeys also showed dose-dependent disorder in reward sensitivity and motivational deficits in economic demand studies as young adults. In vehicle-treated monkeys, brain connectivity and economic demand were correlated with reward sensitivity, but these relationships were disrupted in THC-treated animals.

Twenty-three female and male squirrel monkeys treated daily during adolescence with vehicle, low-dose THC (0.32 mg/kg), or high-dose THC (3.2 mg/kg) for 6 months. Awake fMRI before, during, and after treatment. Economic demand studies conducted as young adults to assess motivation and reward sensitivity.

Nonhuman primate studies bridge the gap between rodent models and human adolescent cannabis research. The finding that brain changes and motivational deficits persist into adulthood strengthens the case for adolescent vulnerability.

This is among the strongest evidence that adolescent cannabis exposure produces lasting neurocognitive changes, as nonhuman primates share key brain development features with humans and allow controlled experimental designs impossible in human studies.

Squirrel monkeys are not identical to humans in brain development timing or cannabinoid receptor distribution. Pure THC does not reflect typical cannabis products. Daily dosing regimen may not reflect typical adolescent use patterns. Moderate sample size for a primate study.