Endocannabinoids in Reward

September 8, 2026 updated by: Erin Martin, Medical University of South Carolina

The Contribution of the Endocannabinoid System to Sex Differences in THC-associated Reward

This study will examine sex differences in the effects of cannabis in people that regularly use it. Men and women that use cannabis at least 4 days a week will participate in a study involving 3 in-person visits. The first visit will be used to determine eligibility for the study. The other two visits will last 7 hours each and take place at least two days apart. Visits include administration of either THC, the chemical responsible for many of the psychoactive effects of cannabis, or a placebo; completion of questionnaires; and a 1-hour brain scan. One visit will also include a blood draw for genetic testing.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

78

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29403
        • Medical University of South Carolina
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Able and willing to provide informed consent
  2. Age 21-45
  3. Meet DSM-5 criteria for CUD
  4. Report cannabis use ≥4 days/week on average in the last 30 days at screening
  5. Provide a THC-positive urine sample at screening
  6. BMI between 18-30 kg/m2
  7. Regular menstrual cycle (females only)
  8. Willing to use non-hormonal birth control for the duration of study participation (females only)

Exclusion Criteria:

  1. Meet DSM-5 criteria for any lifetime psychotic or bipolar disorder
  2. Urinalysis results indicative of recent drug use other than cannabis
  3. Current use of any psychotropic medication or over-the-counter supplements deemed by the investigator to have the potential to interfere with study outcomes
  4. Current treatment-seeking for CUD or other SUDs
  5. Meet DSM-5 criteria for any current psychiatric disorder other than nicotine or caffeine use disorder, mild alcohol use disorder, CUD, or ADHD
  6. Females who are pregnant, nursing, or planning to become pregnant
  7. MRI contraindications (e.g., metallic implants, claustrophobia)
  8. Significant history of nausea associated with the use of cannabis and/or THC
  9. History of cardiac or seizure disorders
  10. Allergy to sesame oil

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: 2 hours post-dose
Concentrations of nucleus accumbens glutamate measured via proton magnetic resonance spectroscopy
2 hours post-dose
Drug Effects Questionnaire (DEQ) - Like Drug Effect
Time Frame: 0-7 hours post-dose
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 post-dose
Sex differences in genetics
Time Frame: Day 1
Blood-based DNA sample will be tested for genetic variants of interest involved in the endocannabinoid system
Day 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dorsal striatal glutamate
Time Frame: 2 hours post-dose
Concentrations of dorsal striatal glutamate measured via proton magnetic resonance spectroscopy
2 hours post-dose
Drug Effects Questionnaire (DEQ) - Want More
Time Frame: 0-7 hours post-dose
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 post-dose
Drug Effects Questionnaire (DEQ) - High
Time Frame: 0-7 hours post-dose
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 post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of South Carolina

Collaborators

National Institute on Drug Abuse (NIDA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 15, 2026

Primary Completion (Estimated)

July 31, 2031

Study Completion (Estimated)

July 31, 2031

Study Registration Dates

First Submitted

September 3, 2026

First Submitted That Met QC Criteria

September 8, 2026

First Posted (Actual)

September 11, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 8, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00150333

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe