Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers
Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers
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DOI：
10.1038/npp.2015.108
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发表时间：
2015-10-01
影响因子：
7.6
通讯作者：
Cooper, Ziva D.
中科院分区：
文献类型：
--
作者：
Haney, Margaret;Ramesh, Divya;Cooper, Ziva D.
鉴于大麻在美国的使用正在增加，治疗大麻使用障碍的药物治疗方案是必要的。阿片类拮抗剂调节大麻素的作用，并可能提供一种减少大麻使用的潜在方法。在这项双盲、安慰剂对照的人体实验室研究中，我们评估了纳曲酮维持对活性和非活性大麻的强化、主观、精神运动和心血管影响的影响。不寻求治疗的每日吸食大麻的人被随机分为纳曲酮(50 mg：18名男性和5名女性)或安慰剂(0 mg；26名男性和2名女性)胶囊，为期16天。在药物维持之前、期间和之后，参与者在4-6周内完成了10次实验室会议，评估大麻的行为和心血管影响。用药依从性通过观察胶囊给药、血浆纳曲酮和尿核黄素来验证。与安慰剂相比，纳曲酮的维持显著减少了有效的大麻自我给药及其积极的主观效果(良好效果)。与纳曲酮组相比，安慰剂组的参与者自我注射活性大麻的几率是后者的7.6倍(95%可信区间：1.1-51.8)。这种强化和积极的主观影响的减弱也影响了大麻在自然生态中的使用。纳曲酮有内在的影响：友好度、食物摄入量和收缩压的评分降低，胃部不适和头痛的自发报告增加，但两组之间的辍学率相似。综上所述，我们首次表明，纳曲酮的维持降低了不寻求治疗的每日大麻吸烟者的大麻自我给药和良好效果的评级。有必要对有减少大麻使用动机的患者进行临床研究，以评估纳曲酮治疗大麻使用障碍的疗效。
Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n= 18 M and 5 F) or placebo (0 mg; n = 26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.