Sakmar Elcin, Wemm Stephanie, Fogelman Nia, Hermes Gretchen, Sinha Rajita, Milivojevic Verica
The Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, United States.
The Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, United States.
Drug Alcohol Depend. 2025 Jun 20;274:112765. doi: 10.1016/j.drugalcdep.2025.112765.
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.
长期使用可卡因会降低神经活性甾体（NAS）水平，这促使可卡因使用障碍（CUD）患者持续使用可卡因并存在高复发风险。这项初步研究评估了在一项为期8周的试验中，使用两种剂量的NAS前体孕烯醇酮进行长期治疗，以提高内源性NAS水平并影响诱发的渴望及可卡因使用结果，该试验针对患有CUD的男性和女性。
55名寻求治疗的CUD患者被随机分配，接受安慰剂（PLA；n = 18；12名男性/6名女性）、每日300mg孕烯醇酮（PREG；n = 20；15名男性/5名女性）或每日500mg孕烯醇酮（n = 17；12名男性/5名女性）治疗8周。在第2、5和7周采集的血浆用于评估孕烯醇酮水平。在试验约第2周时，一个亚组参与了为期3天的引导性意象暴露试验，暴露于压力、可卡因和中性线索，以评估渴望反应。在治疗期间评估可卡因使用结果。使用线性混合效应模型进行意向性分析。
与PLA组相比，300mg和500mg PREG组的孕烯醇酮水平更高（p值<0.032）。PLA组中，压力（p<0.001）和可卡因线索（p<0.001）诱发的渴望增加，但在PREG组中未增加。与500mg PREG组（p = 0.01）和PLA组（p = 0.047）相比，300mg PREG组使用的可卡因量更低。可卡因使用天数的百分比有非显著下降（p = 0.122）。
这些初步研究结果表明，孕烯醇酮可降低患有CUD的寻求治疗个体对可卡因的渴望，并改善可卡因使用结果，支持进一步评估孕烯醇酮在CUD治疗中的作用。
