PRevention Of Methamphetamine Use Among Postpartum Women Trial (PROMPT)

Inclusion Criteria:

• Meeting criteria for substance use disorder of methamphetamine in the six monthsprior to conception or during pregnancy

• No active methamphetamine use at time of enrollment or within past 4 weeks prior toenrollment by self-report or urine toxicology.

• If diagnosis of active opioid use disorder (OUD) and no use at time of enrollment orwithin past 4 weeks prior to enrollment by self-report or urine toxicology and onstable dose of medication for OUD (methadone, buprenorphine, naltrexone) for twoweeks prior to enrollment in order to allow for postpartum dose adjustments.

• Intrauterine device or barrier method for contraception during the study period

• End of pregnancy within past 12 weeks

• Residing within 100 miles of study site

• Stable on allowable psychiatric medications including selective serotonin reuptakeinhibitors, serotonin-norepinephrine reuptake inhibitors, and mood stabilizers forfour weeks prior to enrollment

Exclusion Criteria:

• Major medical illness in which progesterone may be contraindicated (significantliver disease, history of thrombophlebitis, stroke, heart disease, suspected orknown malignancy, deep vein thrombosis, pulmonary embolus, clotting or bleedingdisorders)

• Any of the following laboratory abnormalities (within 2 weeks of screening andenrollment)

• Active hepatic dysfunction

• Anemia defined as hemoglobin less than 8 g/dL indicating anemia

• Renal impairment defined as creatinine greater than 2.0 mg/dL

• Hypothyroidism defined as TSH greater than 5 mIU/L

• Abnormal vital signs at baseline visit

• Allergy to micronized progesterone or ingredients in placebo including peanut oil,gelatin or cellulose

• Self-reported progestin-containing oral or depot containing contraceptivesintolerance.

• Do not speak English or Spanish

• Taking potent inhibitors of CY P450 3A4 including clarithromycin, erythromycin,diltiazem, itraconazole, ketoconazole, ritonavir, verapamil and goldenseal.

• Severe depressive symptoms

• Active suicidality

• Current or past history of psychosis, suicidal attempts or psychiatrichospitalizations

• Current or pending incarceration

• Active alcohol use disorder within past six months

• Use of the following concomitant drugs, supplements and over-the-counter medicationsin the two week prior to enrollment: stimulants, barbiturates, benzodiazepines,non-benzodiazepine hypnotics, orexin antagonists, first generation anti-histamine,herbal sedatives, methaqualone and analogues, skeletal muscle relaxants, opioids (other than methadone or buprenorphine), anti-psychotic medications, certainanti-depressants or other medication with significant sedative properties asevaluated by the PI and/or study clinician.

• Progestin containing medications including oral hormonal contraceptive methods