# A Human Laboratory Study of Exenatide for Reducing the Reinforcing Effects of Cocaine

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2024 · $199,265

## Abstract

PROJECT SUMMARY/ABSTRACT
Cocaine (COC) use disorder (CUD) remains a significant medical, social, and legal public-health concern.
Because behavioral therapies alone have limited efficacy, identification of pharmacotherapy that improves CUD
treatment outcomes is sorely needed. Emerging preclinical evidence supports the potential clinical utility of
stimulating the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) for treating CUD. Preclinical studies show
that administration of a GLP-1R agonist attenuates COC self-administration, as well as COC-induced locomotor
stimulation4, conditioned place preference, and dopamine release in the nucleus accumbens. Significantly,
administering a GLP-1R agonist during abstinence following COC self-administration attenuated the
reinstatement of drug-seeking behavior at doses that did not affect food intake or produce other adverse effects.
Despite promising preclinical findings, and that COC administration significantly reduces serum concentrations
of GLP-1 in humans, there has been only one human laboratory study in which administration of the GLP-1R
agonist, exenatide, did not alter either the self-administration or subjective effects of COC in people with CUD.
Multiple study limitations, including the use of an acute dose of exenatide rather than chronic pre-treatment,
evaluation of only a single dose of COC, as well as the lack of both a placebo COC dose and an alternative to COC
(i.e., a choice) in the free-access self-administration paradigm preclude drawing firm conclusions about the
efficacy of exenatide for CUD. The overall objective of this application is to determine if GLP-1R agonism is a
viable treatment strategy for CUD. This goal will be achieved through the conduct of a rigorous human clinical
pharmacology study in which non-treatment seeking COC users (n=44) will be randomized (1:1) to a
maintenance dose (0 mg (i.e., placebo) or 2 mg subcutaneously once a week) of extended-release (XR) exenatide
for six weeks. The 6-week maintenance period, sufficient to achieve steady-state, will result in more stable
concentrations of clinically effective doses before assessing treatment effects. Before and after the 6-week
maintenance period, we will determine COC (0, 20, 40 mg: IV) self-administration rates. To accurately predict
clinical efficacy, we will use forced-choice procedures in which participants choose to either self-administer COC
or receive money. Our central hypothesis is that XR-exenatide will reduce COC self-administration compared to
placebo. We expect that by (1) using a rigorous human laboratory experimental design, (2) testing treatment
effects after achieving steady-state levels, and (3) employing appropriate endpoints for demonstrating treatment
effectiveness in a laboratory setting, this project will provide definitive data regarding the potential of exenatide
for reducing COC self-administration. The GLP-1R represents a substantial departure from previous treatment
targets for CUD, and...

## Key facts

- **NIH application ID:** 10841703
- **Project number:** 5R21DA057411-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** CHRISTOPHER D VERRICO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $199,265
- **Award type:** 5
- **Project period:** 2023-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841703

## Citation

> US National Institutes of Health, RePORTER application 10841703, A Human Laboratory Study of Exenatide for Reducing the Reinforcing Effects of Cocaine (5R21DA057411-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10841703. Licensed CC0.

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