The purpose of this study is to examine the role of progesterone (a naturally occurring hormone found in both men and women) on reducing marijuana use. The investigators will see if progesterone effects impulsivity, withdrawal, mood and stress during marijuana cessation.

This double-blind, randomized pilot clinical trial will prescreen an estimated 250 potential subjects, consent and further evaluate approximately 100 potential subjects, and ultimately enroll 70 subjects to ensure 40 subjects will provide a primary marijuana reduction outcome measure at four weeks post quit date. Subjects will be stratified by sex then randomized to one of two treatment groups (n=20 per drug group, 50% female): progesterone (PRO; 200mg 2x/day) or Placebo (PBO). Telephone screening and visit invitation (20 minutes) leads to the consent process and in-person screening including medical-psychiatric evaluation for inclusion/exclusion (two visits, two hours each), then randomization and medication start (7 days), then stable medication (28 days) with medication reduction and final evaluation (7 days).

Inclusion Criteria:

• Males 18-60 years old, females 18-50 years old
• Stable physical and mental health
• Self-report Timeline Follow-Back (TLFB) indicating current marijuana use ≥4 days/week for ≥1 year
• Positive urine THC dipstick test (> 50ng/mL; indicating marijuana use in the past 48-72 hours)
• Motivated to change their marijuana use (>1 on a 10-point Likert-type scale) -Regular or sporadic use of nicotine cigarettes (> 1 cigarettes in the past 30 days) -Self-report of regular menstrual cycles >6 months (female only)
• Willing to use double-barrier contraception if sexually active and not surgically sterilized (female only)
• Ability to comply with study procedures, ability to provide informed consent.

Exclusion Criteria:

• Current breastfeeding (females only),
• Current or planned pregnancy within the next three months (females only)
• DSM-IV diagnoses for psychotic disorders, bipolar disorder, ADHD, major depressive disorder within the last 3 months
• Substance dependence within the last 3 months with the exception of nicotine and marijuana dependence
• Unstable psychotropic medications (<3 months)
• Current use of exogenous hormones, finasteroid (propecia), efavirenz, red clover, ketoconazole and other drugs that are CYP3A4 inhibitors
• Conditions contraindicated to progesterone treatment (including, but not limited to, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, diabetes, history of stroke, allergy to peanuts, hypersensitive to progesterone and liver dysfunction)

5 weeks