Division on Substance Abuse, New York State Psychiatric Institute, NY, USA.
Addict Biol. 2013 Sep;18(5):872-81. doi: 10.1111/j.1369-1600.2011.00427.x. Epub 2012 Jan 19.
Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence.
大麻依赖是一个严重的公共卫生问题，现有的治疗方法显示疗效有限。在实验室和临床研究中，大麻素受体 1 激动剂口服 Δ9-四氢大麻酚（THC；大麻隆）已被证明可减轻大麻戒断症状，但不能减少复发。大麻隆的生物利用度差，可能是导致其未能减少复发的原因。合成的 THC 类似物纳布隆的生物利用度优于大麻隆。因此，我们旨在研究纳布隆在当前吸食大麻者中一系列急性剂量下的行为和生理效应，并将其与大麻隆的效应进行比较。参与者（4 名女性；10 名男性）每周吸食大麻 6.6 天（标准差=0.7），完成了这项门诊、单盲、随机、双盲方案。在七个疗程中，评估了纳布隆（2、4、6、8 mg）、大麻隆（10、20 mg）和安慰剂的时间依赖性主观、认知和心血管效应。与安慰剂相比，纳布隆（4、6、8 mg）和大麻隆（10、20 mg）增加了感觉良好、强烈作用和/或“高”的评分；纳布隆的主观效应峰值出现时间比大麻隆慢。纳布隆（6、8 mg）与安慰剂和大麻隆相比，轻度降低了运动速度。纳布隆后心率呈剂量依赖性增加，纳布隆（2 mg）和大麻隆（10 mg）降低了收缩压。因此，纳布隆产生了持续的、剂量相关的积极情绪增加，认知功能下降很少，且有规律的心血管改变。与大麻隆相比，纳布隆的峰值效应出现时间更长，且效应更具剂量相关性，这表明其生物利用度提高。纳布隆被吸食大麻者良好耐受，支持进一步测试其作为大麻依赖潜在药物的用途。
