Pregnenolone reduces provoked craving and cocaine use in men and women with cocaine use disorder: A pilot trial.

Abstract

Chronic cocaine use decreases neuroactive steroid (NAS) levels, contributing to continued cocaine use and high risk of return to use in individuals with cocaine use disorder (CUD). This pilot study assessed chronic treatment with two doses of the NAS precursor pregnenolone to boost endogenous NAS levels and affect provoked craving and cocaine use outcomes in an 8-week trial in men and women with CUD. Fifty-five treatment-seeking individuals with CUD were randomly assigned to receive either placebo (PLA; n = 18; 12M/6F), 300mg PREG/day (n = 20; 15M/5F) or 500mg PREG/day (n = 17; 12M/5F) for 8 weeks. Plasma collected at weeks 2, 5 and 7 was assessed for pregnenolone levels. A subset participated in a 3-day experimental component of guided imagery exposure to stress, cocaine and neutral cues in about week 2 of the trial to assess craving response. Cocaine use outcomes were assessed during the treatment period. Intent-to-treat analyses were conducted using linear mixed effects models. Pregnenolone levels were higher in the 300mg and 500mg PREG groups compared to PLA (p's < 0.032). Stress (p < .001) and cocaine cue (p < .001) induced craving increased in PLA, but not in PREG groups. 300mg PREG used lower cocaine amounts compared to 500mg PREG group (p = 0.01) and PLA (p = .047). A non-significant reduction was observed for % days of cocaine used (p = .122). These pilot findings suggest that PREG reduces cocaine craving and improves cocaine use outcomes in treatment seeking individuals with CUD, supporting further assessment of PREG in the treatment of CUD.