Division on Substance Use Disorders, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Irving Medical Center, 1051 Riverside Drive, Unit #120, New York, NY, USA.
Division on Substance Use Disorders, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Irving Medical Center, 1051 Riverside Drive, Unit #120, New York, NY, USA.
Drug Alcohol Depend. 2020 Mar 1;208:107859. doi: 10.1016/j.drugalcdep.2020.107859. Epub 2020 Jan 17.
Lorcaserin, a high-affinity 5-HT 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.
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.
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.
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.
盐酸氯卡色林是一种高亲和力 5-羟色胺受体激动剂，已被批准用于治疗肥胖症，它可以减少临床前研究中阿片类药物的自我给药和线索诱导的觅药行为的复吸。目前的研究是第一个评估盐酸氯卡色林改变阿片类药物的强化和主观效应的临床试验。
在这项为期 7 周的住院试验中，12 名非治疗性寻求者（11 名男性）患有中度至重度阿片类药物使用障碍，接受了阿片类药物的脱毒治疗。参与者以随机交叉的方式首先稳定在盐酸氯卡色林（10mg BID）或安慰剂（0mg BID）上。在为期两周的测试期内，参与者接受了鼻内羟考酮的强化和主观效应的测试，包括口头选择、线索暴露和逐步比例选择。这两周的测试完全相同，唯一的区别是在第一周，口头选择（自我给药）期间可获得活性羟考酮（10mg），而在第二周可获得安慰剂羟考酮。随后，参与者在另一种药物条件（安慰剂或盐酸氯卡色林）下稳定，并再次进行相同的测试程序。
盐酸氯卡色林并没有改变羟考酮的自我给药。然而，当羟考酮可用时，盐酸氯卡色林有增加“渴望海洛因”的趋势，并加重羟考酮引起的瞳孔缩小。
在当前的实验条件下，盐酸氯卡色林剂量为 10mg BID 并不能可靠地降低羟考酮的滥用倾向，尽管该研究有足够的效力（≥80%）来检测安慰剂和活性盐酸氯卡色林条件之间主要结局变量的临床有意义差异。未来的研究可以探索更广泛的盐酸氯卡色林和羟考酮剂量范围。
