Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis
Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis
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DOI：
10.1007/s002130100919
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Kreek, MJ
中科院分区：
文献类型：
--
作者：
O'Malley, SS;Krishnan-Sarin, S;Kreek, MJ
背景：本实验室研究了阿片类拮抗剂纳曲酮降低酒精依赖个体重度饮酒复发风险的机制。方法：18名酒精依赖、非寻求治疗的志愿者随机服用50 mg纳曲酮或安慰剂6天，并在第6天参加酒精自我给药实验。在对渴望和内分泌水平进行基线评估后，首先给受试者提供一种旨在将血液酒精水平提高到0.03 g/dl的启动饮料，然后有机会喝多达8种额外的饮料，或者在2小时内不喝仙人掌饮料获得3美元。每多喝一杯，血液中的酒精含量就会提高0.015克/分升。结果：在基线时，纳曲酮治疗比安慰剂治疗导致皮质醇水平升高，渴望水平降低。虽然对启动剂量的反应没有显著差异，但纳曲酮治疗的受试者喝得更少，喝得更慢，并且在实验的酒精自我给药部分报告了更低的酒精渴望水平。纳曲酮还导致促肾上腺皮质激素和皮质醇水平高于安慰剂治疗，皮质醇水平与酒精渴望程度呈负相关。选择的饮料数量与对酒精的渴望程度呈正相关。在研究的任何时候，纳曲酮组和安慰剂组的恶心评分都很低，没有差异。结论：这些结果证实了纳曲酮降低酒精依赖者的饮酒欲望和饮酒量的假设。据推测，纳曲酮可能通过抑制对酒精的渴望来减少饮酒量，这种效果可能部分与纳曲酮激活下丘脑-垂体-肾上腺皮质轴的能力有关。
Background: This laboratory study investigated the mechanisms by which the opioid antagonist, naltrexone, reduces the risk of relapse to heavy drinking in individuals with alcohol dependence. Methods: Eighteen alcohol-dependent, non-treatment-seeking volunteers were randomized to 50 mg naltrexone or placebo for 6 days and participated in an alcohol self-administration experiment on the sixth day. Following baseline assessments of craving and endocrine levels, subjects were first administered a priming drink designed to raise blood alcohol levels to 0.03 g/dl and then had the opportunity to drink up to eight additional drinks or to receive US $3 for cacti drink not consumed over a 2-h period. Each additional drink was designed to raise blood alcohol levels by 0.015 g/dl. Results: At baseline, naltrexone treatment resulted in higher cortisol levels and lower levels of craving than placebo treatment. Although there were no significant differences in response to the priming dose, naltrexone-treated subjects drank fewer drinks, consumed them more slowly, and reported lower levels of alcohol craving during the alcohol self-administration portion of the experiment. Naltrexone also resulted in higher levels of adrenocorticotropic hormone and cortisol than placebo treatment, and levels of cortisol were negatively correlated with intensity of alcohol craving. The number of drinks chosen was positively correlated with level of alcohol craving. Ratings of nausea were low and did not differ between the naltrexone and placebo groups at any point in the study. Conclusions: These results confirm the hypothesis that naltrexone reduces desire to drink and the amount of alcohol consumed in alcohol-dependent subjects. It is hypothesized that naltrexone may reduce drinking via suppressing craving for alcohol and that this effect may be related in part to naltrexone's ability to activate the hypothalamo-pituitary-adrenocortical axis.