Repurposing Semaglutide for the Treatment of Cocaine Use Disorder

NCT07227948 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: HSC-MS-25-0412R01DA062720-01
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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/).

Conditions

Cocaine Use Disorder

Keywords

semaglutide; GLP-1 agonist; cocaine addiction

Outcome Measures

Primary Outcomes (4)

• Amplitude of the Late Positive Potential (LPP) in microvolts in response to visual stimuli on the Picture Viewing Task.

  EEG will be recorded during a passive picture viewing presentation that will include cocaine-related, neutral, and nondrug-related pleasant and unpleasant images. For each participant, the amplitude of the LPP component will be calculated separately for each picture category and used to evaluate the motivational relevance of the images.LPP amplitude reflects the motivational relevance of visual stimuli, with larger amplitudes indicating greater motivational salience.

  End of Treatment (Week 15)

• Intensity of demand as assessed by the amount of cocaine purchased and consumed as assessed by cocaine purchasing task

  Participants will complete the hypothetical Cocaine Purchasing Task, in which they report the amount of cocaine they would purchase and use at escalating price levels. Demand curve metrics (Intensity, Omax, Pmax, and Elasticity) will be calculated to quantify the relative reinforcing value and motivation to obtain cocaine. Lower demand values indicate reduced motivation for cocaine.

  End of Treatment (Week 15)

• Cocaine craving as assessed by the score on the Cocaine Cravings Questionnaire

  Cocaine craving will be assessed using a 10-item self-report questionnaire. Each item is rated on a 5-point Likert scale from 1 = Strongly Disagree to 5 = Strongly Agree. The total craving score is calculated as the mean of all item responses, with higher scores indicating greater craving intensity.

  End of Treatment (Week 15)

• Proportion of cocaine negative urine drug screens (UDS) during the final two weeks of treatment

  Use of cocaine at the end of treatment

  From Week 13 to Week 14

Secondary Outcomes (1)

• Treatment response as a dichotomous outcome during the last two weeks of treatment

  From Week 13 to Week 14

Study Arms (2)

Semaglutide

EXPERIMENTAL

Drug: Semaglutide; Behavioral: cognitive behavioral therapy (CBT).

Placebo

PLACEBO COMPARATOR

Drug: Placebo; Behavioral: cognitive behavioral therapy (CBT).

Interventions

Semaglutide DRUG

Participants will receive 14 weekly injections administered subcutaneously. Semaglutide will be initiated at a dose of 0.25 mg once weekly. After 4 weeks, the dose will be increased to 0.5 mg once weekly for an additional 4 weeks. Thereafter, the dose will be increased to 1 mg once weekly for 6 weeks

Semaglutide

Placebo DRUG

Sterile saline (0.9%) will serve as the placebo for semaglutide and will be administered subcutaneously once-weekly for 14 weeks. The placebo will be administered in the same blinded manner as semaglutide and will be volume-matched.

Placebo

cognitive behavioral therapy (CBT). BEHAVIORAL

Participants will receive fourteen weekly 1-hour sessions of individual cognitive behavioral therapy (CBT), an evidence-based behavioral therapy platform for evaluating pharmacotherapy for CUD. CBT focuses on (1) identifying situations that precipitate drug use and (2) preventing relapse by teaching cognitive and behavioral skills to reduce risk.

Placebo; Semaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) diagnostic criteria for CUD and report recent cocaine use (verified by at least one positive urine drug screen (UDS) for the cocaine metabolite benzoylecgonine (BE), during intake).
• Have body mass index (BMI) of ≥25 kg/m2
• Agree (if the participant is female and of child-bearing potential) to use effective contraceptive methods, unless the participant's male partner(s) is surgically sterile (underwent vasectomy). Acceptable contraceptives include oral contraceptives, contraceptive sponge, patch, double barrier (diaphragm/spermicidal or condom/spermicidal), intrauterine contraceptive system, etonogestrel implant, medroxyprogesterone acetate contraceptive injection, complete abstinence from sexual intercourse, and/or hormonal vaginal ring. Contraceptive measures sold for emergency use after unprotected sex are not acceptable methods for routine use. Women of child-bearing potential must provide negative urine pregnancy test prior to randomization. Note: A woman is considered fertile (of childbearing potential) following menarche and until becoming postmenopausal unless permanently sterile. Women in the following categories are not considered a woman of childbearing potential: premenarcheal, premenopausal female with one of the following: documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy. Postmenopausal female is defined as no menses for 12 months without an alternative medical cause. Females on HRT and whose menopausal status is in doubt will be required to use one of the nonhormonal highly effective contraception methods if they wish to continue their hormone replacement therapy (HRT) during the trial.
• Have a medical and psychiatric history and a brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the Study Physician and the Principal Investigator.
• Be able to provide the names of at least 2 persons who can consistently locate their whereabouts.

You may not qualify if:

• 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.
• Type 1 or type 2 diabetes mellitus (previously diagnosed or indicated by HbA1C ≥48 mol/mol (6.5%) as measured at screening).
• Severe gastrointestinal disease (i.e., severe gastroparesis).
• History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
• History of severe cardiovascular disease.
• History of retinopathy.
• Systolic blood pressure (SBP) \>180 mmHg and/or diastolic blood pressure (DBP) \>105 mmHg)
• End stage renal disease (ESRD, previously diagnosed or indicated by estimated glomerular filtration rate (eGFR) value of eGFR \< 15 ml/min/1.73 m2 at screening).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times the upper limit of normal range at screening.
• Known or suspected hypersensitivity to semaglutide, excipients, or related products.
• History of seizure or elevated risk of seizure.
• Women who are currently pregnant, or plan to become pregnant, or lactating, or of childbearing potential and are not using medically accepted forms of contraception
• Have any medical illness or condition which in the opinion of the PI and/or the Study Physician would preclude safe and/or successful completion of the study.
• Any foreseeable procedure requiring general anesthesia or deep sedation.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

semaglutide; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Luba Yammine, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luba Yammine, PhD

CONTACT

(713) 486-2737; Luba.Yammine@uth.tmc.edu

Jessica Vincent

CONTACT

(713) 486-2645; Jessica.N.Vincent@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 13, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): January 28, 2029
• Study Completion (Estimated): February 28, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)