Impact of Progesterone on Stress Reactivity and Cannabis Use

This is a research study to find out if a hormone called progesterone affects marijuana users' stress response and marijuana use. Progesterone is a naturally occurring sex hormone involved in the menstrual cycle and reproduction, and has been shown to reduce withdrawal symptoms when people stop using substances like cocaine and nicotine. It is not FDA approved for treating cannabis users and is considered an investigational drug in this study.

Study Overview

• Status: Completed
• Conditions: Cannabis Use
• Intervention / Treatment: Drug: Progesterone; Drug: Placebo

Detailed Description

Participants will complete a screening visit to determine study eligibility. Eligible subjects will be scheduled to begin 22 days of study participation. During the first week, participants will be randomly assigned to take either progesterone or placebo (inactive medication) twice a day, and to abstain from marijuana use. During this week, participants will upload videos of themselves taking their medication and performing saliva drug tests. They will collect and store additional saliva samples each morning for hormone testing. They will also participate in "CREMA" sessions (Cue Reactivity Ecologic Momentary Assessment) three times a day. These sessions include looking at stressful and neutral pictures and rating stress and craving. At the end of this week, participants will return to the clinic and participate in a stress task. For the next two weeks, participants will continue to collect saliva samples and participate in CREMA sessions. They will return at the end of the two weeks to return study supplies. Urine samples will be collected at each study visit.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aimee McRae-Clark, PharmD; Phone Number: 843-792-5216; Email: mcraeal@musc.edu
• Study Contact Backup: Name: Lisa Nunn, MS; Phone Number: 843-792-0476; Email: jenkinli@musc.edu

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.

  2. Meet DSM-5 criteria for moderate or severe cannabis use disorder (within the past three months) and report using cannabis at least five times weekly over the past month. While individuals may also meet criteria for mild use disorders of other substances, they must identify cannabis as their primary substance of abuse and must not meet criteria for any other moderate or severe substance use disorder (except tobacco) within the last 60 days.

  3. Age 18-45. 4. For women, regular menses (every 25-35 days). 5. Consent to remain abstinent from alcohol for 12 hours prior to study visits, and all other drugs other than cannabis or nicotine for the duration of the study.

  6. Women of childbearing potential must agree to utilize an effective means of birth control.

  7. Must consent to random assignment.

Exclusion Criteria:

• . Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.

  2. Women who are amennorheic or using progesterone-based contraceptives. 3. Evidence or history of major medical illnesses, including liver diseases, abnormal vaginal bleeding, suspected or known malignancy, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, diabetes, history of stroke or other medical conditions that the investigator deems as contraindicated for the individual to be in the study.

  4. History of or current psychotic disorder or bipolar affective disorder. 5. Current suicidal or homicidal ideation/risk. 6. Known allergy to progesterone or peanuts (vehicle for micronized progesterone).

  7. Unwilling or unable to maintain abstinence from alcohol 12 hours prior to study visits and all other drugs other than cannabis or nicotine for the duration of the study.

  8. Meet DSM-5 criteria for moderate or severe substance use disorder (other than nicotine or cannabis) within the past 60 days.

  9. Unable to comply with study procedures or pose threat to study staff.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Progesterone Males; 35 men will take 400 mg of progesterone a day for 7 days and will complete a stress and marijuana cue reactivity task following the final dose.	Drug: Progesterone; 200 mg of exogenous progesterone twice a day; Other Names: Prometrium
Placebo Comparator: Placebo Males; 35 men will take placebo twice a day for 7 days and will complete a stress and marijuana cue reactivity task following the final dose.	Drug: Placebo; One dose of matched placebo twice a day.
Experimental: Progesterone Female; 35 women will take 200 mg of progesterone twice a day for 7 days and will complete a stress and marijuana cue reactivity task following the final dose.	Drug: Progesterone; 200 mg of exogenous progesterone twice a day; Other Names: Prometrium
Placebo Comparator: Placebo Females; 35 women will take placebo twice a day for 7 days and will complete a stress and marijuana cue reactivity task following the final dose.	Drug: Placebo; One dose of matched placebo twice a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cannabis Craving	Subjects will rate marijuana craving on a 0-7 Likert scale where 0 is Not at All and 7 is extremely.	Immediately post stress/cue task.

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2019
• Primary Completion (Actual): November 9, 2022
• Study Completion (Actual): November 9, 2022

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: November 1, 2018
• First Posted (Actual): November 5, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: Pro00081360; 2U54DA016511-16 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes