BACKGROUND Lorcaserin, a high-affinity 5-HT2C receptor agonist approved for treating obesity, decreased self-administration of oxycodone and cue-induced reinstatement of drug-seeking behavior in preclinical studies. The current investigation is the first clinical trial to evaluate the ability of lorcaserin to alter the reinforcing and subjective effects of oxycodone. METHODS In this 7-week inpatient trial, 12 non-treatment-seeking volunteers (11 males) with moderate-to-severe opioid use disorder were detoxified from opioids. In a randomized cross-over fashion, participants were first stabilized on lorcaserin (10 mg BID) or placebo (0 mg BID). Participants underwent a two-week testing period during which the reinforcing and subjective effects of intranasal oxycodone were examined in verbal choice, cue-exposure, and progressive-ratio choice sessions. The two testing weeks were identical with the exception that during the first week, active oxycodone (10 mg) was available during verbal choice (self-administration) sessions, and during the second week placebo oxycodone was available. Subsequently, participants were stabilized on the other medication condition (placebo or lorcaserin) and underwent the same testing procedures again. RESULTS Lorcaserin did not alter oxycodone self-administration. However, lorcaserin had a trend to increase "wanting heroin" when oxycodone was available, and to accentuate oxycodone-induced miosis. CONCLUSION Under the current experimental conditions, lorcaserin at a dose of 10 mg BID did not reliably decrease the abuse liability of oxycodone, even though the study was sufficiently powered (≥80 %) to detect clinically meaningful differences in the main outcome variables between the placebo and active lorcaserin condition. Future research could explore a wider dose range of lorcaserin and oxycodone.

中文翻译：

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氯卡色林对阿片类药物使用障碍参与者羟考酮自我给药和主观反应的影响。

背景技术 氯卡色林是一种被批准用于治疗肥胖症的高亲和力 5-HT2C 受体激动剂，在临床前研究中减少了羟考酮的自我给药和线索诱导的寻药行为恢复。目前的研究是第一个评估氯卡色林改变羟考酮的增强作用和主观作用的能力的临床试验。方法 在这项为期 7 周的住院试验中，12 名患有中度至重度阿片类药物使用障碍的非寻求治疗志愿者（11 名男性）从阿片类药物中脱毒。以随机交叉方式，参与者首先稳定在氯卡色林（10 mg BID）或安慰剂（0 mg BID）上。参与者经历了为期两周的测试期，在此期间检查了鼻内羟考酮在语言选择、​​线索暴露、和渐进比率选择会议。这两个测试周是相同的，除了在第一周期间，在口头选择（自我管理）期间提供活性羟考酮（10 mg），而在第二周期间提供安慰剂羟考酮。随后，参与者在其他药物条件下（安慰剂或氯卡色林）稳定下来，并再次接受相同的测试程序。结果 氯卡色林没有改变羟考酮的自我给药。然而，当羟考酮可用时，氯卡色林有增加“想要海洛因”的趋势，并加重羟考酮诱导的瞳孔缩小。结论 在目前的实验条件下，剂量为 10 mg BID 的氯卡色林不能可靠地降低羟考酮的滥用倾向，即使该研究具有足够的功效 (≥80 %) 来检测安慰剂和活性氯卡色林条件之间主要结果变量的临床意义差异。未来的研究可以探索更宽剂量范围的氯卡色林和羟考酮。