Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal A Randomized Clinical Trial

被引:175
作者
Allsop, David J. [1 ]
Copeland, Jan [1 ]
Lintzeris, Nicholas [2 ,3 ,4 ]
Dunlop, Adrian J. [5 ,6 ,7 ]
Montebello, Mark [2 ,3 ]
Sadler, Craig [5 ,6 ]
Rivas, Gonzalo R. [2 ,3 ]
Holland, Rohan M. [5 ,6 ]
Muhleisen, Peter [5 ,6 ]
Norberg, Melissa M. [1 ,8 ]
Booth, Jessica [9 ]
McGregor, Iain S. [9 ]
机构
[1] Univ New S Wales, Natl Cannabis Prevent & Informat Ctr, Natl Drug & Alcohol Res Ctr, Fac Med, Sydney, NSW 2031, Australia
[2] South Eastern Sydney Local Hlth Dist New South W, Drug Serv, Sydney, NSW, Australia
[3] South Eastern Sydney Local Hlth Dist New South W, Alcohol Serv, Sydney, NSW, Australia
[4] Univ Sydney, Cent Clin Sch, Fac Med, Sydney, NSW 2006, Australia
[5] New South Wales Minist Hlth, Drug Clin Serv, Newcastle, NSW, Australia
[6] New South Wales Minist Hlth, Alcohol Clin Serv, Newcastle, NSW, Australia
[7] Univ Newcastle, Sch Med & Publ Hlth, Fac Hlth, Newcastle, NSW 2300, Australia
[8] Macquarie Univ, Dept Psychol, Sydney, NSW 2109, Australia
[9] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
ANXIETY SENSITIVITY INDEX; DOUBLE-BLIND; MARIJUANA WITHDRAWAL; OROMUCOSAL SPRAY; MULTIPLE-SCLEROSIS; DIAGNOSTIC CUTOFF; BUPROPION-SR; OPEN-LABEL; FOLLOW-UP; ORAL THC;
D O I
10.1001/jamapsychiatry.2013.3947
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
IMPORTANCE There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. OBJECTIVE To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. DESIGN, SETTING, AND PARTICIPANTS A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. INTERVENTIONS A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Delta 9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. MAIN OUTCOMES AND MEASURES Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. RESULTS Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F-8,F-377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (chi(2)(1) = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F-1,F-6 = 0.22; P = .97). The number (F-1,F-50 = 0.3; P = .59) and severity (F-1,F-50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of nabiximols over placebo for self-reported cannabis use (F-1,F-48 = 0.29; P = .75), cannabis-related problems (F-1,F-49 = 2.33; P = .14), or cannabis dependence (F-1,F-50 < 0.01; P = .89). CONCLUSIONS AND RELEVANCE In a treatment-seeking cohort, nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations.
引用
收藏
页码:281 / 291
页数:11
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