Cannabis Use
Conditions
Brief summary
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.
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.
Interventions
DRUGProgesterone
200 mg of exogenous progesterone twice a day
DRUGPlacebo
One dose of matched placebo twice a day.
Sponsors
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cannabis Craving | Immediately post stress/cue task. | Subjects will rate marijuana craving on a 0-7 Likert scale where 0 is Not at All and 7 is extremely. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Progesterone Males 39 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.
Progesterone: 200 mg of exogenous progesterone twice a day | 39 |
| Placebo Males 41 men will take placebo twice a day for 7 days and will complete a stress and marijuana cue reactivity task following the final dose.
Placebo: One dose of matched placebo twice a day. | 41 |
| Progesterone Female 34 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.
Progesterone: 200 mg of exogenous progesterone twice a day | 35 |
| Placebo Females 31 women will take placebo twice a day for 7 days and will complete a stress and marijuana cue reactivity task following the final dose.
Placebo: One dose of matched placebo twice a day. | 31 |
| Total | 146 |
Baseline characteristics
| Characteristic | Progesterone Males | Placebo Males | Progesterone Female | Placebo Females | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 41 Participants | 35 Participants | 31 Participants | 146 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 10 Participants | 8 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 35 Participants | 24 Participants | 23 Participants | 114 Participants |
| Region of Enrollment United States | 39 participants | 41 participants | 35 participants | 31 participants | 146 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 35 Participants | 31 Participants | 66 Participants |
| Sex: Female, Male Male | 39 Participants | 41 Participants | 0 Participants | 0 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 41 | 0 / 35 | 0 / 31 |
| other Total, other adverse events | 26 / 39 | 28 / 41 | 24 / 35 | 23 / 31 |
| serious Total, serious adverse events | 0 / 39 | 0 / 41 | 0 / 35 | 0 / 31 |
Outcome results
Primary
Cannabis Craving
Subjects will rate marijuana craving on a 0-7 Likert scale where 0 is Not at All and 7 is extremely.
Time frame: Immediately post stress/cue task.
Population: Males and females randomly assigned to take progesterone or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Progesterone Males | Cannabis Craving | 3.7 units on a scale | Standard Deviation 2.3 |
| Placebo Males | Cannabis Craving | 3.4 units on a scale | Standard Deviation 2.2 |
| Progesterone Female | Cannabis Craving | 4.3 units on a scale | Standard Deviation 2.6 |
| Placebo Females | Cannabis Craving | 4.5 units on a scale | Standard Deviation 2.1 |