# Cerebellar biobehavioral markers in cannabis users

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2022 · $543,194

## Abstract

Cannabis use represents a significant and increasing public health concern as social acceptance
accompanies legalization of this drug for medicinal and recreational purposes. These factors make
understanding the health consequences of cannabis (CB) urgent and critical. For example, a recent study
found university students age 19-22 had the highest rate of CB use in the last 30 years, with 39% having used in
the last year. The prevailing view is that CB is a significant public health risk factor because (1) use is associated
with increased risk for health and accidents, (2) adolescent use likely disturbs crucial brain maturation
processes; (3) chronic use has been associated with cognitive deficits and (4) people who use CB are at
increased risk for psychotic and mood disorders. However, the assessment of risks associated with cannabis is
currently incomplete and equivocal. The proposed research strongly advocates that understanding the risks
(or lack thereof) depends critically on a neural circuit-informed approach to testing the integrity of brain
systems known to be richly endowed with CB-relevant receptors that are altered in response to CB exposure.
The principal psychoactive ingredient of CB is delta-9-tetrahydrocannabinol (THC), which acts as a ligand for
widely distributed CB1 receptors in the human brain. CB1R density in cerebellum is one of the highest in the
brain. Although measures of cerebellar function could provide sensitive probes for the neurobehavioral effects
of CB use, they have rarely been tested in CB users, nor have they been explicitly linked to behavioral deficits.
Specific Aim 1 will measure resting state functional connectivity (rsFC) between cerebellum sub-regions and
established cortical resting state brain networks (RSNs). Specific Aim 2 will test: a) whether cerebellar fMRI
activation during cerebellar-dependent delay eyeblink conditioning (dEBC) is reduced in CB users; and b)
whether task-based cerebellar activations produce different patterns of RSN connectivity (using the 10 RSNs
from Aim 1) that are differentially sensitive to CB use. Specific Aim 3 will test the sensitivity of a set of
cerebellar-dependent behavioral tasks to CB use. Findings from the proposed research will likely identify the
cerebellar paradigms and measures which are most affected in current CB users. If the strongly founded
predictions are borne out, this set of measures could then be utilized in a wide range of studies, including 1)
longitudinal studies of high risk groups and CB users which would be critical for future research projects, 2)
direct administration of cannabis compounds in humans, 3) studies of comparable measures in animal models
of cannabis use and consequences, 4) genetically informed familial and twin studies and 5) field studies of
cannabis intoxication. Additionally, these protocols could be highly informative in parsing cerebellar circuits
which have been implicated in a broad range of addictive behaviors.

## Key facts

- **NIH application ID:** 10359209
- **Project number:** 5R01DA048012-04
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** WILLIAM P HETRICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $543,194
- **Award type:** 5
- **Project period:** 2019-04-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359209

## Citation

> US National Institutes of Health, RePORTER application 10359209, Cerebellar biobehavioral markers in cannabis users (5R01DA048012-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10359209. Licensed CC0.

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