Cannabis Use DisorderEarly Phase 1NCT03430050
Progesterone for Cannabis Withdrawal
A Early Phase 1 study testing Progesterone in people with Cannabis Use Disorder and Cannabis Withdrawal, run by Medical University of South Carolina at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Cannabis Use Disorder, Cannabis Withdrawal
- What is being tested?
- Progesterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Oct 2017to 4 Apr 2018
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments and study procedures.
- Age 18-45, with regular menses (every 25-35 days).
- Report using cannabis at least 5 days per week, for at least the past year.
- 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.
- Consent to random assignment.
Who cannot join
- Participants who are pregnant, nursing, amennorheic, or using oral contraceptives.
- 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;
- 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.
- 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.
- Known allergy to progesterone or peanuts (vehicle for micronized progesterone).
- 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.
- Meet DSM-5 criteria for moderate to severe substance use disorder (other than nicotine, cannabis, or alcohol) within the past year.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29403
About this study
Official title: 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.
Read the 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.
- Conditions
- Cannabis Use Disorder, Cannabis Withdrawal
- Being tested
- Progesterone, Placebo
- Keywords
- Progesterone, Ovarian hormones, Gender, Cannabis, Withdrawal, Cognitive functioning
- Medical subject headings
- Coitus, Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProgesteroneDrug
Also called Prometrium
Progesterone capsule
PlaceboDrug
Also called Inactive comparator
Placebo capsule. Manufactured to mimic progesterone 200mg capsule.
| Study group | Role | What they receive |
|---|---|---|
| Progesterone | Active comparator | 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. Receives: Drug: Progesterone |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Salivary Progesterone Level
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.
Measured: Day 1 and Day 5
Change in Cannabis Withdrawal Scale Score.
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.
Measured: Day 1 and Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2018
- Study start16 Oct 2017
- Primary completion4 Apr 2018
- Study completion4 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cannabis Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Brian J Sherman, PhD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03430050
- Sponsor's protocol ID
- 65954
- Other IDs
- 5K24DA038240-03
- Status last verified
- Apr 2019
- First submitted
- 10 Jan 2018
- Last updated
- 22 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Progesterone for the Treatment of Cannabis Withdrawal
- ClinicalTrials.gov ID
- NCT03430050
- Acronym / sponsor ID
- 65954
- Conditions
- Cannabis Use Disorder, Cannabis Withdrawal
- Keywords
- Progesterone, Ovarian hormones, Gender, Cannabis, Withdrawal, Cognitive functioning
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)
- Study start
- 16 Oct 2017 (actual)
- Primary completion
- 4 Apr 2018 (actual)
- Study completion
- 4 Apr 2018 (actual)
- First posted
- 12 Feb 2018 (actual)
- Results
- Posted 22 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Progesterone | Active comparator | Drug: ProgesteronePrometrium 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo. 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments and study procedures.
- Age 18-45, with regular menses (every 25-35 days).
- Report using cannabis at least 5 days per week, for at least the past year.
- 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.
- Consent to random assignment.
Key exclusion criteria (7 listed)
- Participants who are pregnant, nursing, amennorheic, or using oral contraceptives.
- 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;
- 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.
- 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.
- Known allergy to progesterone or peanuts (vehicle for micronized progesterone).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProgesteroneAlso: PrometriumProgesterone capsule | Drug | Progesterone |
| PlaceboAlso: Inactive comparatorPlacebo capsule. Manufactured to mimic progesterone 200mg capsule. | Drug | Placebo |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Cannabis Use Disorder
Recruiting
MATAspire: Mental Health Awareness Tailored App for Substance Prevention and Integrated Resilience Education
Alcohol Use, Cannabis Use
Not yet recruitingEarly Phase 1
Research Investigating Drug Effects-2 (RiDE-2)
Cannabis Use, Substance Use Disorder (SUD)
RecruitingObservational study
Study of an Oral Fluid Testing Approach
Cannabis Use, Cannabis Intoxication
Active, not recruiting
Evaluation of a Brief Computerized and Smart Phone-based Intervention for Stress in Regular Cannabis Users
Cannabis Use Disorder
Not yet recruitingPhase 2
Semaglutide for the Treatment of Cannabis Use Disorder
Cannabis Use Disorder, Cue-reactivity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian J Sherman, PhD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Progesterone in people with Cannabis Use Disorder and Cannabis Withdrawal, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Salivary Progesterone Level (time frame: Day 1 and Day 5). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2019; AzTrials last refreshed its copy on 29 Oct 2026.