Six months of daily THC during adolescence produced persistent brain connectivity changes and motivational deficits in squirrel monkeys that lasted into adulthood.
Developmental neuroscientists, adolescent health researchers, and cannabis policy decision-makers.
Adolescent THC exposure produced lasting brain and motivational changes that persisted into adulthood in monkeys
What the researchers found
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.
Why it matters
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.
The numbers in context
23 monkeys (female and male). 6 months daily THC at 0.32 or 3.2 mg/kg. Persistent alterations in mOFC, caudate, and ventral striatum connectivity. Dose-dependent motivational deficits. Brain-behavior correlations present in controls but absent in THC-treated animals.
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
Nonhuman primate controlled experiment with both neuroimaging and behavioral outcomes. Strong internal validity despite moderate sample size.
When this study was published
2025 publication in Neuropsychopharmacology.
The bigger picture
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.
Questions still open
- Would co-administration of CBD mitigate the lasting effects of adolescent THC exposure?
- At what frequency of THC exposure do persistent brain changes begin to appear?
Read the original research
Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 50(3), 576-585
Citation
Kangas, Brian D; Deshpande, Harshawardhan U; Withey, Sarah L; Spealman, Roger D; Bergman, Jack; Kohut, Stephen J. (2025). Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 50(3), 576-585. https://doi.org/10.1038/s41386-024-02024-9
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