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Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial


Lintzeris, N and Bhardwaj, A and Mills, L and Dunlop, A and Copeland, J and McGregor, I and Bruno, R and Gugusheff, J and Phung, N and Montebello, M and Chan, T and Kirby, A and Hall, M and Jefferies, M and Luksza, J and Shanahan, M and Kevin, R and Allsop, D, Agonist Replacement for Cannabis Dependence (ARCD) study group, Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial, JAMA Internal Medicine, 179, (9) pp. 1242-1253. ISSN 2168-6106 (2019) [Refereed Article]

Copyright Statement

2019 by the American Academy of Ophthalmology

DOI: doi:10.1001/jamainternmed.2019.1993


Importance: There are no effective medications for treating dependence on cannabis.

Objective: To examine the safety and efficacy of nabiximols in the treatment of patients with cannabis dependence.

Design, setting, and participants: This parallel double-blind randomized clinical trial comparing nabiximols with placebo in a 12-week, multisite outpatient study recruited participants from February 3, 2016, to June 14, 2017, at 4 outpatient specialist alcohol and drug treatment services in New South Wales, Australia. Participants had cannabis dependence (as defined by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and were seeking treatment, were nonresponsive to prior treatment attempts, were 18 to 64 years of age, had no other substance use disorder, had no severe medical or psychiatric conditions, were not pregnant, were not mandated by a court to undergo treatment, and provided informed consent. Results for primary efficacy measures and all secondary outcomes were obtained using a modified intention-to-treat data set.

Interventions: Participants received 12-week treatment involving weekly clinical reviews, structured counseling, and flexible medication doses-up to 32 sprays daily (tetrahydrocannabinol, 86.4 mg, and cannabidiol, 80 mg), dispensed weekly.

Main outcomes and measures: Primary outcome was self-reported number of days using illicit cannabis during the 12-week period. Other outcomes included alternate cannabis use parameters (periods of abstinence, withdrawal, cravings, and problems), safety parameters (adverse events and aberrant medication use), health status, other substance use, and treatment retention.

Results: A total of 128 participants (30 women and 98 men; mean [SD] age, 35.0 [10.9] years) were randomized and received at least 1 dose of study medication. Participants had used a mean (SD) of 2.3 (2.1) g of cannabis on a mean (SD) of 25.7 (4.5) days in the past 28 days. Treatment retention was comparable for the 2 groups (placebo, 30 of 67 participants [44.8%]; nabiximols, 30 of 61 participants [49.2%]), and both groups used similar mean (SD) doses (placebo, 18.5 [9.5] sprays daily; nabiximols, 17.6 [9.5] sprays daily, equivalent to a mean [SD] of 47.5 [25.7] mg of tetrahydrocannabinol and 44.0 [23.8] mg of cannabidiol). For the primary end point, the placebo group reported significantly more days using cannabis during the 12 weeks (mean [SD], 53.1 [33.0] days) than the nabiximols group (mean [SD], 35.0 [32.4] days; estimated difference, 18.6 days; 95% CI, 3.5-33.7 days; P = .02). Both groups showed comparable improvements in health status, with no substantial changes in other substance use. Medication was well tolerated with few adverse events.

Conclusions and relevance: This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment.

Item Details

Item Type:Refereed Article
Research Division:Psychology
Research Group:Applied and developmental psychology
Research Field:Applied and developmental psychology not elsewhere classified
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Public health (excl. specific population health) not elsewhere classified
UTAS Author:Bruno, R (Associate Professor Raimondo Bruno)
ID Code:138024
Year Published:2019
Web of Science® Times Cited:45
Deposited By:Psychology
Deposited On:2020-03-20
Last Modified:2020-04-03

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