Sex Differences in Neurobehavioral Response to THC

Sex Differences in Neurobehavioral Response to Acute THC in Adults With Cannabis Use Disorder

This study investigates sex differences in reward processing following acute THC administration in adults with cannabis use disorder (CUD). Using multimodal neuroimaging (MRS and fMRI), the study will assess glutamate levels in the nucleus accumbens and striatal BOLD response to monetary reward anticipation. Participants will complete two counterbalanced dosing sessions (oral THC 40 mg vs. placebo).

Study Overview

• Status: Recruiting
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Dronabinol

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Recruiting
      • Medical University of South Carolina
      • Contact: Erin Martin, Ph.D.; Phone Number: 843-876-3528; Email: marterin@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 21-45
• DSM-5 criteria for CUD
• Cannabis use ≥4 days/week
• THC-positive urine
• BMI 18-30
• Regular menstrual cycle (females)
• Willingness to use non-hormonal birth control (females)

Exclusion Criteria:

• Lifetime psychotic or bipolar disorder
• Recent drug use other than cannabis
• Current psychotropic medication
• Treatment-seeking for SUD
• Current psychiatric disorder (except mild alcohol, nicotine, or caffeine use disorder)
• Pregnancy/nursing
• MRI contraindications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Males	Drug: Placebo; Matched placebo capsules; Drug: Dronabinol; Oral dronabinol capsules (40 mg); Other Names: Marinol
Other: Females	Drug: Placebo; Matched placebo capsules; Drug: Dronabinol; Oral dronabinol capsules (40 mg); Other Names: Marinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nucleus accumbens glutamate	Concentrations of nucleus accumbens glutamate measured via proton magnetic resonance spectroscopy	2 hours post-dose
Striatal reward anticipation	Blood oxygen-level-dependent (BOLD) signaling in the striatum (caudate, putamen, nucleus accumbens) measured using functional magnetic resonance imaging (fMRI) during a monetary reward task	3 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Effects Questionnaire (DEQ) - Like Drug Effect	Visual Analog Scale rating of subjective drug liking included in the Drug Effects Questionnaire. Score ranges from 0 (not at all) to 100 (extremely) using a 100mm line anchored with none/extreme designation.	0-7 hours
Drug Effects Questionnaire (DEQ) - Want More	Visual Analog Scale rating of subjective desire for more of the same drug included in the Drug Effects Questionnaire. Score ranges from 0 (not at all) to 100 (extremely) using a 100mm line anchored with none/extreme designation.	0-7 hours
Drug Effects Questionnaire (DEQ) - High	Visual Analog Scale rating of subjective "high" included in the Drug Effects Questionnaire. Score ranges from 0 (not at all) to 100 (extremely) using a 100mm line anchored with none/extreme designation.	0-7 hours
Nucleus accumbens GABA	Concentrations of nucleus accumbens GABA measured via proton magnetic resonance spectroscopy	2 hours post-dose

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Erin Martin, Ph.D., Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 5, 2025
• First Submitted That Met QC Criteria: November 5, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Substance Use
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol
• Other Study ID Numbers: Pro00148223; K12DA031794 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No