Department of Psychiatry, New York State Psychiatric Institute, Columbia University Irving Medical Center, New York, NY, USA.
UCLA Cannabis Research Initiative, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
Addict Biol. 2021 Jul;26(4):e12993. doi: 10.1111/adb.12993. Epub 2021 Jan 3.
There are no FDA-approved treatments for cannabis use disorder (CUD). Preclinical research has shown that the 5HT-2C agonist lorcaserin attenuates cue-induced reinstatement of THC seeking and self-administration. The goal of this placebo-controlled, counterbalanced, within-subject human laboratory study was to examine lorcaserin's effects on cannabis intoxication and self-administration. Lorcaserin (10 mg BID) was administered during one of two 13-day inpatient phases and placebo during the other; each phase was separated by ≥7 days of washout. Inpatient phases comprised (1) standardized cannabis administration (7.0% THC) at no financial cost (intoxication), counterbalanced with (2) the option to self-administer cannabis following either 0 or 3 days of abstinence. Cognitive task performance, food intake, subjective ratings of drug effects, objective/subjective sleep measures, and tobacco cigarette use were also assessed. Fifteen normal-weight, daily cannabis users (4F, 11M) not seeking treatment for CUD completed the study. Lorcaserin significantly reduced cannabis self-administration following 0 and 3 days of cannabis abstinence and also reduced craving for cannabis during abstinence. Lorcaserin produced small but significant increases in positive cannabis ratings and body weight relative to placebo. Lorcaserin also reduced tobacco cigarette smoking on days of cannabis administration relative to placebo. During abstinence, subjective but not objective measures of sleep quality worsened during lorcaserin maintenance. Overall, lorcaserin's ability to decrease drug taking and cannabis craving in nontreatment-seeking cannabis users supports further investigation of 5HT-2C agonists as potential pharmacotherapies for CUD.
目前尚无经美国食品和药物管理局（FDA）批准的大麻使用障碍（CUD）治疗方法。临床前研究表明，5-HT-2C 激动剂lorcaserin 可减轻线索诱导的大麻寻求和自我给药的复吸。本项安慰剂对照、平衡、个体内对照的人体实验室研究旨在研究 lorcaserin 对大麻中毒和自我给药的影响。lorcaserin（每日 2 次，每次 10mg）在两个 13 天住院期的其中一个期间给药，而在另一个期间给药安慰剂；每个阶段之间至少间隔 7 天的洗脱期。住院期包括：（1）在无经济成本的情况下进行标准化大麻给药（THC 含量为 7.0%）（中毒），与（2）在禁欲 0 天或 3 天后自行给药大麻的选项平衡；还评估了认知任务表现、食物摄入量、药物效应的主观评分、客观/主观睡眠测量以及吸烟情况。15 名体重正常、每日吸食大麻的非 CUD 治疗寻求者（4 名女性，11 名男性）完成了该研究。lorcaserin 可显著减少在大麻禁欲 0 天和 3 天后的大麻自我给药，也可减少禁欲期间对大麻的渴望。与安慰剂相比，lorcaserin 使正面的大麻评价和体重略微但显著增加。与安慰剂相比，lorcaserin 还减少了大麻给药日的吸烟量。在禁欲期间，与安慰剂相比，睡眠质量的主观而非客观指标在 lorcaserin 维持期间恶化。总体而言，lorcaserin 能够减少非治疗寻求的大麻使用者的药物使用和大麻渴望，支持进一步研究 5-HT-2C 激动剂作为 CUD 的潜在药物治疗方法。
