Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder.
Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder.
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DOI：
10.3390/biom12111593
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发表时间：
2022-10-29
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
长期使用可卡因会导致应激生物学和神经活性类固醇系统的适应。这些适应与对可卡因的高度渴望和复发风险的增加有关。这项研究测试了前体孕烯醇酮(PREG)增强神经活性类固醇系统是否影响可卡因使用障碍(CUD)患者的应激和线索诱导的可卡因渴求、焦虑和自主神经反应。30名寻求治疗的CUD患者(21名男性，9名女性)被随机分配到安慰剂(PBO)或超生理学PREG剂量，每天300毫克或500毫克，持续8周。在两周的治疗后，参与者被暴露在5分钟的个性化引导图像中，刺激压力、可卡因或中性/放松的暗示，在为期3天的实验中，每天一种条件，在不同的日子，以随机的、平衡的顺序。每天重复评估可卡因渴求、焦虑、心率(HR)、收缩压(SBP)和舒张压(DBP)。与PBO相比，PRG显著增加孕烯醇酮水平。两种剂量的PREG只在500毫克/天组中降低了压力和可卡因线索诱导的渴望，并减少了压力和线索诱导的焦虑。500 mg/d组的应激性心率、SBP和DBP也明显降低。研究结果表明，孕烯醇酮减少了压力和可卡因线索引发的渴望和焦虑，并减少了压力诱导的CUD患者的自主神经唤醒。
Chronic cocaine use leads to adaptations in stress biology and in neuroactive steroid system. These adaptations are associated with high cocaine craving and increased relapse risk. This study tested whether potentiation of the neuroactive steroid system with the precursor pregnenolone (PREG) affects stress- and cue-induced cocaine craving, anxiety and autonomic response in individuals with cocaine use disorder (CUD). Thirty treatment-seeking individuals (21 Male, 9 Female) with CUD were randomized to placebo (PBO) or supraphysiologic PREG doses of 300 mg or 500 mg per day for 8 weeks. After 2 weeks of treatment, participants were exposed to 5-min personalized guided imagery provocation of stress, cocaine, or neutral/relaxing cues in a 3-day experiment, one condition per day on separate days, in a random, counterbalanced order. Repeated assessment of cocaine craving, anxiety, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were assessed on each day. PREG significantly increased pregnenolone levels compared to PBO. Both PREG doses decreased stress- and cocaine cue-induced craving and reduced both stress- and cue-induced anxiety only in the 500 mg/day group. The 500 mg/day PREG group also displayed decreased stress-induced HR, SBP and DBP. Findings indicate that pregnenolone decreases stress- and cocaine cue-provoked craving and anxiety and reduces stress-induced autonomic arousal in individuals with CUD.
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