Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial.

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.

Treatment outcomes for methamphetamine users receiving outpatient counselling from the Stimulant Treatment Program in Australia.

INTRODUCTION AND AIMS: The purpose of this study was to document treatment outcomes for methamphetamine users receiving outpatient counselling from the Stimulant Treatment Program (STP) in Australia. DESIGN AND METHODS: Clients attending the STP for methamphetamine use (n = 105) were assessed on entry to the service and at 3 (n = 86) and 6 months (n = 83) after starting treatment. At each interview methamphetamine use (days of use, severity of dependence), other drug use and health and social functioning (HIV risk behaviour, crime, disability, psychotic symptoms and hostility) were assessed for the past month. RESULTS: Participants received a median of six counselling sessions (interquartile range 1-11) over a period of 89 days (interquartile range 41-148 days). Past month methamphetamine use fell from 79% at treatment entry to 53% at the 3-month follow-up (P < 0.001) and 55% at the 6-month follow-up (P < 0.001). There were statistically significant reductions in psychotic symptoms, hostility and disability associated with poor mental health. There was no change in other drug use, crime or HIV risk behaviour. Reductions in methamphetamine were more common among younger participants, those who had no history of drug treatment and those without concurrent heroin use. DISCUSSION AND CONCLUSIONS: Methamphetamine users entering the STP showed reductions in methamphetamine use and improvements in their mental health after treatment. Improved treatment responses are needed to address polydrug use and other harms within in this population.