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

IF 3.6 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2025-06-20 DOI:10.1016/j.drugalcdep.2025.112765

Elcin Sakmar, Stephanie Wemm, Nia Fogelman, Gretchen Hermes, Rajita Sinha, Verica Milivojevic

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引用次数: 0

Abstract

Aim

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.

Methods

Fifty-five treatment-seeking individuals with CUD were randomly assigned to receive either placebo (PLA; n = 18; 12 M/6 F), 300 mg PREG/day (n = 20; 15 M/5 F) or 500 mg PREG/day (n = 17; 12 M/5 F) 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.

Results

Pregnenolone levels were higher in the 300 mg and 500 mg 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. 300 mg PREG used lower cocaine amounts compared to 500 mg PREG group (p = 0.01) and PLA (p = .047). A non-significant reduction was observed for % days of cocaine used (p = .122).

Conclusions

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.

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孕烯醇酮可减少男性和女性可卡因使用障碍患者的诱发性渴望和可卡因使用：一项试点试验

慢性可卡因使用会降低神经活性类固醇（NAS）水平，导致可卡因使用障碍（CUD）患者继续使用可卡因，并有较高的再次使用风险。在为期8周的男女CUD患者试验中，本初步研究评估了两剂量NAS前体孕烯醇酮的慢性治疗，以提高内源性NAS水平，影响诱发性渴望和可卡因使用结果。方法55名寻求治疗的CUD患者被随机分配接受安慰剂(PLA；n = 18；12 M/6 F)， 300 mg PREG/天(n = 20；15 M/5 F)或500 mg PREG/天(n = 17；12 M/5 F)，为期8周。在第2、5和7周收集血浆，评估孕烯醇酮水平。一部分人在试验的第二周参加了为期3天的应激、可卡因和中性提示引导意象的实验，以评估渴望反应。在治疗期间评估可卡因使用结果。意向治疗分析使用线性混合效应模型进行。结果300 mg和500 mg PREG组孕烯醇酮水平高于PLA组（p 's < 0.032）。应激（p < .001）和可卡因提示（p < .001）诱导PLA组渴望增加，而PREG组没有。与500 mg PREG组（p = 0.01）和PLA组（p = 0.047）相比，300 mg PREG组使用的可卡因量更低。使用可卡因的天数百分比无显著减少（p = 0.122）。这些初步研究结果表明，在寻求CUD治疗的个体中，PREG减少了可卡因渴望并改善了可卡因使用结果，支持进一步评估PREG在CUD治疗中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug and alcohol dependence 医学-精神病学

CiteScore

7.40

自引率

7.10%

发文量

409

审稿时长

41 days

期刊介绍： Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.