Division on Substance Abuse, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Neuropsychopharmacology. 2013 Jul;38(8):1557-65. doi: 10.1038/npp.2013.54. Epub 2013 Feb 26.
Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Δ(9)-tetrahydrocannabinol (THC; dronabinol), decreases marijuana withdrawal symptoms, yet does not decrease marijuana use in the laboratory or clinic. Dronabinol has poor bioavailability, which may contribute to its poor efficacy. The FDA-approved synthetic analog of THC, nabilone, has higher bioavailability and clearer dose-linearity than dronabinol. This study tested whether nabilone administration would decrease marijuana withdrawal symptoms and a laboratory measure of marijuana relapse relative to placebo. Daily, nontreatment-seeking marijuana smokers (8 men and 3 women), who reported smoking 8.3±3.1 marijuana cigarettes/day completed this within-subject study comprising three, 8-day inpatient phases; each phase tested a different nabilone dose (0, 6, 8 mg/day, administered in counter-balanced order on days 2-8). On the first inpatient day, participants took placebo capsules and smoked active marijuana (5.6% THC) at six timepoints. For the next 3 days, they had the opportunity to self-administer placebo marijuana (0.0% THC; withdrawal), followed by 4 days in which active marijuana was available for self-administration (5.6% THC; relapse). Both nabilone dose conditions decreased marijuana relapse and reversed withdrawal-related irritability and disruptions in sleep and food intake (p<0.05). Nabilone (8 mg/day) modestly worsened psychomotor task performance. Neither dose condition increased ratings of capsule 'liking' or desire to take the capsules relative to placebo. Thus, nabilone maintenance produced a robust attenuation of marijuana withdrawal symptoms and a laboratory measure of relapse even with once per day dosing. These data support testing of nabilone for patients seeking marijuana treatment.
寻求大麻治疗的个体中，很少有人能实现持续的戒除。大麻素受体激动剂 Δ(9)-四氢大麻酚（THC；大麻隆）可减轻大麻戒断症状，但不会减少实验室或临床中的大麻使用。大麻隆的生物利用度较差，这可能导致其疗效不佳。THC 的 FDA 批准的合成类似物纳布隆的生物利用度比大麻隆更高，剂量线性更清晰。本研究测试了纳布隆给药是否会降低大麻戒断症状和实验室测量的大麻复发相对于安慰剂。每天，非治疗性寻求大麻的吸烟者（8 名男性和 3 名女性），报告每天吸烟 8.3±3.1 支大麻烟，完成了这项包括三个 8 天住院阶段的单中心研究；每个阶段测试了不同的纳布隆剂量（0、6、8mg/天，以平衡顺序在第 2-8 天给药）。在第一个住院日，参与者服用安慰剂胶囊并在六个时间点吸食活性大麻（5.6%THC）。接下来的 3 天，他们有机会自行吸食安慰剂大麻（0.0%THC；戒断），然后是 4 天可自行吸食活性大麻（5.6%THC；复发）。纳布隆的两种剂量均降低了大麻复发，并逆转了与戒断相关的易怒和睡眠及食物摄入紊乱（p<0.05）。纳布隆（8mg/天）轻度恶化了精神运动任务表现。两种剂量均未增加相对于安慰剂的胶囊“喜欢”或服用胶囊的意愿评分。因此，即使每天给药一次，纳布隆维持治疗也能显著减轻大麻戒断症状和实验室测量的复发。这些数据支持对寻求大麻治疗的患者进行纳布隆测试。
