Repurposing Semaglutide for the Treatment of Cocaine Use Disorder

What Was Tested

In this phase 2 trial, researchers set out to test Semaglutide.

The purpose of this study is to evaluate semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in combination with cognitive behavioral therapy (CBT) for the treatment of cocaine use disorder (CUD).

This project is part of the NIH Helping to End Addiction Long-term (HEAL) initiative (https://heal.nih.gov/).

It had two arms (groups): Semaglutide (experimental) and Placebo (placebo comparator).

The registry classes the interventions as behavioral and drug.

More on the Plan

The United States is facing a resurgence in cocaine use and cocaine-related mortality.

Importantly, GLP-1 receptors are expressed in brain regions involved in reward processing and hedonic behavior.

The primary objective of this trial is to provide proof-of-concept evidence for the use of a GLP-1RA semaglutide as a treatment for CUD.

The study hypothesizes that semaglutide will modulate three key reward-related target mechanisms underlying cocaine use: (1) motivational relevance of cocaine cues, assessed via event-related potentials (ERPs); (2) cocaine valuation, measured by behavioral economic demand for cocaine; and (3) subjective experience of craving.

Who Took Part

75 planned participants were the target.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Ability to provide informed consent before any study-related activity, willing to comply with all study procedures, and be available for the duration of the study. Have body mass index (BMI) of ≥25 kg/m2. Be able to provide the names of at least 2 persons who can consistently locate their whereabouts.

The full record lists 6 inclusion and 27 exclusion criteria; among the exclusions: personal or first-degree relative(s) history of medullary thyroid carcinoma (mtc) or multiple endocrine neoplasia syndrome type 2 (men 2); history or presence of chronic pancreatitis or recent acute pancreatitis; severe gastrointestinal disease (i.e., severe gastroparesis).

How the Study Was Run

The set-up was randomized, parallel-group and quadruple-blind.

Because people in this Semaglutide study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

The Semaglutide group and the comparison group ran side by side rather than switching.

Neither the participants nor the staff measuring them knew who was on Semaglutide, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2026-01-15 with completion listed for 2029-01-28.

It ran at 1 site in United States.

Its stated primary purpose is treatment.

What Was Measured

Primary outcome: Amplitude of the Late Positive Potential (LPP) in microvolts in response to visual stimuli on the Picture Viewing Task (time frame: End of Treatment (Week 15)). Intensity of demand as assessed by the amount of cocaine purchased and consumed as assessed by cocaine purchasing task (time frame: End of Treatment (Week 15)). Cocaine craving as assessed by the score on the Cocaine Cravings Questionnaire (time frame: End of Treatment (Week 15)).

It also tracked 1 secondary outcome, for example Treatment response as a dichotomous outcome during the last two weeks of treatment.

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of Semaglutide in 75 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Semaglutide compound page, all human trials.