Progesterone for the reduction of cocaine use in post-partum women with a cocaine use disorder: a randomised, double-blind, placebo-controlled, pilot study

Abstract

Background Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD). Methods A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized to placeboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites. Findings Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ2 =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events. Interpretation These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through. Funding US National Institute on Drug Abuse; Veterans Administration

Progesterone and Postpartum Smoking Relapse: A Pilot Double-Blind Placebo-Controlled Randomized Trial

“…Clinic visit attendance (>80%) was comparable to previous clinical trials including postpartum studies. [44][45][46] Study retention (87%) was also comparable to previous cessation studies for addiction. 44,[47][48][49][50] Number of pills taken (69%) or adherence rate to study medication was moderate compared to previous pharmacological clinical trials.…”

“…[44][45][46] Study retention (87%) was also comparable to previous cessation studies for addiction. 44,[47][48][49][50] Number of pills taken (69%) or adherence rate to study medication was moderate compared to previous pharmacological clinical trials. 45,46,51 Of note, 33% of the progesterone group at week 2 had low progesterone blood levels suggesting missing pills.…”

“…Exogenous progesterone effect on postpartum depressive symptoms seemed minimal and consistent with other studies. 36,44 However, our study sample was not depressed. In fact, our study sample reported less depressive symptoms than in the general population of women (18.5%) 59 and during the postpartum period (7%-13%).…”

Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone

“…Another clinical aspect arises regarding GHB-induced progesterone release: GHB is used for the treatment of alcohol withdrawal and as an anti-craving agent (Keating, 2014), while some studies also point to anti-craving and relapse preventing effects of progesterone in nicotine (Lynch and Sofuoglu, 2010) and cocaine addiction (Yonkers et al, 2014). Therefore, increased progesterone release might contribute to the therapeutic effect of GHB in alcohol withdrawal and abstinence maintenance.…”

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

“…One clinical trial met review criteria examining the efficacy of progesterone for treating cocaine dependence (Yonkers et al, 2014). In that study, postpartum women with cocaine use disorder were randomized to receive placebo or 100 mg oral micronized progesterone twice daily for 12 weeks.…”