Hormones and Reduction in Co-users of Marijuana and Nicotine

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)