An Early Phase 1 interventional study of Progesterone and Placebo in Cannabis Use Disorder and Cannabis Withdrawal, sponsored by Medical University of South Carolina. Completed at 1 site in United States. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2019-05-22.
Sponsored by Medical University of South Carolina · Early Phase 1, Interventional, and Treatment
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.
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.
188 studies on the registry are indexed under Marijuana Abuse; 26 are open to participants now.
This study's enrollment of 8 is below the median of 51 across 160 interventional studies indexed under Marijuana Abuse.
Browse Marijuana Abuse studies →Medical University of South Carolina is the lead sponsor of 874 studies on the registry; 166 are open to participants now.
Of its 131 completed or terminated interventional studies of FDA-regulated products, 104 (79%) have results posted.
Compared within Marijuana Abuse, the registry's first condition term, which may not be this study's main condition. Counted across the registry records on this site, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Progesterone capsule
Also known as: Prometrium
Placebo capsule. Manufactured to mimic progesterone 200mg capsule.
Also known as: Inactive comparator
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.
Time frame: 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.
Time frame: Day 1 and Day 5
| Milestone | Progesterone | Placebo |
|---|---|---|
| Started | 3 | 5 |
| Completed | 3 | 5 |
| Not completed | 0 | 0 |
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.
| pg/ml | Progesterone | Placebo |
|---|---|---|
| Change in Salivary Progesterone Level | 237.86 ± 24.21 | 97.87 ± 14.67 |
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.
| units on a scale | Progesterone | Placebo |
|---|---|---|
| Change in Cannabis Withdrawal Scale Score. | 29.08 ± 4.15 | 20.41 ± 3.18 |
Collected over 5 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Progesterone | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) |
| Placebo | 0/5 (0%) | 0/5 (0%) | 0/5 (0%) |
| Age, Categorical(Participants) | Progesterone | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 3 | 5 | 8 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Progesterone | Placebo | Total |
|---|---|---|---|
| Female | 3 | 5 | 8 |
| Male | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Progesterone | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 0 | 2 |
| White | 1 | 5 | 6 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Progesterone | Placebo | Total |
|---|---|---|---|
| United States | 3 | 5 | 8 |
PDFs hosted by the registry, ClinicalTrials.gov.
This study is completed, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Progesterone
Medical University of South Carolina →