David J Allsop1, Jan Copeland2, Nicholas Lintzeris3, Adrian J Dunlop4, Mark Montebello5, Craig Sadler6, Gonzalo R Rivas5, Rohan M Holland6, Peter Muhleisen6, Melissa M Norberg7, Jessica Booth8, Iain S McGregor8. 1. National Cannabis Prevention and Information Centre, National Drug and Alcohol Research Centre, Faculty of Medicine, University of New South Wales, Sydney, Australia2now with the School of Psychology, University of Sydney, Sydney, Australia. 2. National Cannabis Prevention and Information Centre, National Drug and Alcohol Research Centre, Faculty of Medicine, University of New South Wales, Sydney, Australia. 3. Drug and Alcohol Services, South Eastern Sydney Local Health District New South Wales Ministry of Health, Sydney, Australia4Addiction Medicine, Central Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia. 4. Drug and Alcohol Clinical Services, Hunter New England Local Health District, New South Wales Ministry of Health, Newcastle, Australia6School of Medicine and Public Health, Faculty of Health, University of Newcastle, Newcastle, Australia. 5. Drug and Alcohol Services, South Eastern Sydney Local Health District New South Wales Ministry of Health, Sydney, Australia. 6. Drug and Alcohol Clinical Services, Hunter New England Local Health District, New South Wales Ministry of Health, Newcastle, Australia. 7. National Cannabis Prevention and Information Centre, National Drug and Alcohol Research Centre, Faculty of Medicine, University of New South Wales, Sydney, Australia7Department of Psychology, Macquarie University, Sydney, Australia. 8. School of Psychology, University of Sydney, Sydney, Australia.
Abstract
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 Δ9-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 (F8,377.97 = 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 (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 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 (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 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. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12611000398909.
RCT Entities:
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 Δ9-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 (F8,377.97 = 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. Nabiximolspatients 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 (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 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 (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89). CONCLUSIONS AND RELEVANCE: In a treatment-seeking cohort, nabiximolsattenuated 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. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12611000398909.
Authors: Dustin C Lee; Nicolas J Schlienz; Erica N Peters; Robert H Dworkin; Dennis C Turk; Eric C Strain; Ryan Vandrey Journal: Drug Alcohol Depend Date: 2018-11-15 Impact factor: 4.492
Authors: Margaret Haney; Ziva D Cooper; Gillinder Bedi; Evan Herrmann; Sandra D Comer; Stephanie Collins Reed; Richard W Foltin; Frances R Levin Journal: Addict Biol Date: 2018-04-16 Impact factor: 4.280
Authors: Karim S Ladha; Varuna Manoo; Ali-Faizan Virji; John G Hanlon; Alexander Mclaren-Blades; Akash Goel; Duminda N Wijeysundera; Lakshmi P Kotra; Carlos Ibarra; Marina Englesakis; Hance Clarke Journal: Cannabis Cannabinoid Res Date: 2019-12-06
Authors: David J Allsop; Delwyn J Bartlett; Jennifer Johnston; David Helliwell; Adam Winstock; Iain S McGregor; Nicholas Lintzeris Journal: J Clin Sleep Med Date: 2015-10-15 Impact factor: 4.062