# Neural, Cognitive and Abuse-Related Consequences of Chronic THC Exposure during Adolescence in Nonhuman Primates

> **NIH NIH R01** · MCLEAN HOSPITAL · 2022 · $718,402

## Abstract

Cannabis is the most widely self-administered psychoactive substance among adolescents in the U.S., and its
use shows no signs of abatement. Studies in humans suggest that heavy cannabis use during this critical
period of development can alter brain structure and function and impair cognitive and behavioral processes.
However, the extent to which neural changes and neuropsychological deficits produced by cannabis use
during adolescence persist into adulthood remains poorly understood, hampering the assessment of long-term
health risks. Consequently, there continues to be a pressing need for carefully controlled research on the
potential long-term impact of adolescent cannabis exposure on brain development, cognitive competency and
addiction. The present research addresses this need with longitudinal studies in nonhuman primates to
examine the long-term impact of chronic exposure to the cannabinoid Δ9-THC during adolescence. In this
research, groups of adolescent male and female squirrel monkeys will be treated daily with a low active dose
or a high active dose of Δ9-THC or with vehicle. Daily treatment will continue throughout adolescence for 6
months, during which time observational and activity data will be collected to assess behavioral status and the
any tolerance to the effects of drug treatment. Neuroimaging data will be collected before, during, and after
daily treatment to evaluate changes in neural structure or function that may be associated with chronic
exposure to Δ9-THC. After the chronic regimens are discontinued, subjects will remain drug-free for 6 weeks
to allow for the elimination of the lipophilic cannabinoid. Next, using touchscreen-based tasks, subjects will be
studied to determine whether prior exposure to Δ9-THC may have persisting effects on motivation or different
types of cognitive function. First, using a behavioral economic demand analysis, motivation will be assessed
by comparing the reinforcing strength of sweetened condensed milk, a highly palatable reinforcer, in the
different treatment groups. Subsequently, two tasks (stimulus discrimination/reversal and delayed matching to
position) will be used to compare learning, response inhibition, and spatial short-term memory across
treatment groups. Neuroimaging information will be collected prior to and following the above testing. Finally,
the acquisition of Δ9-THC self-administration will be studied to determine whether adolescent exposure to Δ9-
THC may have enhanced its reinforcing effects. Lastly, the study will conclude with a final neuroimaging scan.
Overall, these longitudinal studies will provide information regarding the persistence of neural abnormalities
that may be produced by Δ9-THC exposure during adolescence, their association with cognitive impairments
or changes in sensitivity to abuse-related effects of Δ9-THC, and whether such sequelae and associations can
be related to the chronic dosage Δ9-THC or differ in males and females.

## Key facts

- **NIH application ID:** 10399441
- **Project number:** 5R01DA047575-04
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** JACK BERGMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $718,402
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399441

## Citation

> US National Institutes of Health, RePORTER application 10399441, Neural, Cognitive and Abuse-Related Consequences of Chronic THC Exposure during Adolescence in Nonhuman Primates (5R01DA047575-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399441. Licensed CC0.

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