Progesterone for Cannabis Withdrawal

April 26, 2019 updated by: Medical University of South Carolina

Progesterone for the Treatment of Cannabis Withdrawal

Sex and gender differences in behavioral, biological, and clinical correlates of substance use disorders are myriad, yet there exists a dearth of gender-informed treatment options. Ovarian hormones have been identified as potential mechanisms of these disparities , and recent clinical trials have begun to examine their utility as possible pharmacotherapeutic agents. The ovarian hormone progesterone has shown promise as a treatment for female cocaine and nicotine users, but has not yet been tested for cannabis. Gender differences in cannabis withdrawal, which is associated with relapse, are pronounced and several studies report more severe and impairing withdrawal symptoms in women compared to men. Developing pharmacological interventions for cannabis withdrawal remains an important priority given the significant cognitive, psychiatric, and physical consequences of heavy cannabis use.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Substantial evidence demonstrates sex and gender differences in the behavioral, biological, and clinical correlates of substance use disorders. Men tend to initiate use earlier and have higher lifetime prevalence rates of disorder, but women demonstrate more severe withdrawal, more rapid progression from first use to disorder, and greater likelihood of comorbid psychiatric disorder. A growing literature suggests that the ovarian hormones progesterone and estradiol may play a key role in these differences. Evidence from preclinical and clinical research suggests that estradiol enhances drug sensitivity and related behavior, while progesterone attenuates drug sensitivity and behavior. As such, recent clinical trials investigating exogenous progesterone as a potential pharmacologic intervention have shown attenuated subjective and physiological effects of cocaine and nicotine in drug-dependent women, and improved cognitive performance in female smokers. While progesterone has shown promise as a treatment for women with cocaine and nicotine use disorder, it has not yet been tested for cannabis.

To date, there are no approved pharmacologic interventions for cannabis use disorder (CUD) despite numerous clinical trials. Cannabis withdrawal is one potential target for CUD medication development research as withdrawal increases risk of relapse. Important gender differences in cannabis withdrawal have been identified warranting gender-based investigation. Several studies have found that women experience more severe and impairing withdrawal symptoms, primarily physiological (e.g. stomach aches, headaches, nausea) and mood-related (e.g. irritability, mood swings), compared to men. As a naturally occurring sex hormone, progesterone may effectively address these gender differences. The proposed pilot study investigates the feasibility and efficacy of exogenous progesterone administration for cannabis withdrawal among female cannabis users.

Specific Aim 1: Test the feasibility of exogenous progesterone administration among cannabis users.

Hypothesis 1: Exogenous progesterone administration will induce normative elevations in progesterone comparable to the luteal phase of female menstrual cycle and will be well-tolerated by participants.

Specific Aim 2: Examine the efficacy of exogenous progesterone on cannabis withdrawal.

Hypothesis 2: Compared to placebo, progesterone will attenuate withdrawal symptoms among heavy-cannabis-using women.

Exploratory Aim: Examine the effect of exogenous progesterone on cognitive functioning during cannabis withdrawal.

Exploratory hypothesis: Compared to placebo, progesterone will enhance cognitive functioning among heavy-cannabis-using women.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Early Phase 1

Contacts and Locations

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

Study Locations

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

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

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments and study procedures.
  2. Age 18-45, with regular menses (every 25-35 days).
  3. Report using cannabis at least 5 days per week, for at least the past year.
  4. 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.
  5. Consent to random assignment.

Exclusion Criteria:

  1. Participants who are pregnant, nursing, amennorheic, or using oral contraceptives.
  2. 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 patient to be in the study;
  3. Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and recent/current psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder.
  4. Current suicidal or homicidal risk. Any subject who endorses suicidal ideation will be seen by a licensed clinician in the Addiction Sciences Division who will determine the best course of action to ensure patient safety.
  5. Known allergy to progesterone or peanuts (vehicle for micronized progesterone).
  6. 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.
  7. Meet DSM-5 criteria for moderate to severe substance use disorder (other than nicotine, cannabis, or alcohol) within the past year.

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: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Progesterone
Prometrium 200mg. Take one pill in the evening on day 1 with water. Take one pill twice a day on days 2-4. Take one pill on morning day 5.
Drug: Progesterone
Progesterone capsule
Other Names:
  • Prometrium
PLACEBO_COMPARATOR: Placebo
Placebo. ake one pill in the evening on day 1 with water. Take one pill twice a day on days 2-4. Take one pill on morning day 5.
Drug: Placebo
Placebo capsule. Manufactured to mimic progesterone 200mg capsule.
Other Names:
  • Inactive comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Salivary Progesterone Level
Time Frame: Day 1 and Day 5
Participants took progesterone or placebo for 5 days. Salivary progesterone was measured each day. Change score was calculating by subtracting Day 1 progesterone levels from Day 5 progesterone levels.
Day 1 and Day 5
Change in Cannabis Withdrawal Scale Score.
Time Frame: Day 1 and Day 5
Participants took progesterone or placebo for 5 days. The Cannabis Withdrawal Scale was administered each day. The 19-item scale is used to measure cannabis withdrawal symptoms and negative impact on daily life. The item scores range from 0 - not at all to 10- Extremely. Scores on all items are summed to attain the scale score, so individuals can score between 0-190. Higher scores indicates more severe withdrawal symptoms and greater negative impact. Change score was calculating by subtracting Day 1 CWS scores from Day 5 CWS scores. A positive change score reflects an increase in withdrawal symptoms, while a negative change score reflects a decrease in withdrawal symptoms.
Day 1 and Day 5

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)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Brian J Sherman, PhD, Medical University of South Carolina

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 (ACTUAL)

October 16, 2017

Primary Completion (ACTUAL)

April 4, 2018

Study Completion (ACTUAL)

April 4, 2018

Study Registration Dates

First Submitted

January 10, 2018

First Submitted That Met QC Criteria

February 9, 2018

First Posted (ACTUAL)

February 12, 2018

Study Record Updates

Last Update Posted (ACTUAL)

May 22, 2019

Last Update Submitted That Met QC Criteria

April 26, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 65954
  • 5K24DA038240-03 (NIH)

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

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.

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