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A double blind, randomised, placebo controlled trial of Sativex® for the management of cannabis withdrawal

image - Sativex Square
Date Commenced:
03/2010
Project Supporters:

National Health & Medical Research Council - Project Grant|APP1006036

Drug Type:
Project Members: 
image - Jcopeland Pb Award 1
Professor Jan Copeland
Honorary Visiting Professor
Dr David Allsop
Conjoint Lecturer
image - 1314151390 Melissa Norberg 005
Dr Melissa Norberg
Honorary Lecturer
Project Main Description: 

Treatment admissions for cannabis use disorders have risen considerably over the last few years, globally and within Australia. There is currently no effective pharmacotherapy for cannabis dependence, and very low abstinence rates reported from psychotherapy alone. A defined cannabis withdrawal syndrome has been identified, and while it is not life threatening, the discomfort it causes is reported to contribute to the high incidence of relapse amongst the cannabis using population. As such cannabis withdrawal may be an important intervention target for dependence on the drug. This study represents the world’s first safety and efficacy trial of a novel agonist medication (Sativex®) for alleviating the symptoms of cannabis withdrawal.

Project Collaborators: External: 

A/Pofessor Nicholas Lintzeris
Drug & Alcohol Services, South East Sydney Local Health Network & Faculty of Medicine, University of Sydney

Professor Iain McGregor
School of Psychology, University of Sydney

A/Professor Adrian Dunlop
Drug and Alcohol Clinical Services, Hunter New England Local Health Network, Belmont Hospital

Dr Mark Montebello
School of Psychiatry, University of New South Wales & The Langton Centre

Dr Craig Sadler
Calvary Mater Hospital & Drug and Alcohol Clinical Services HNEAH & Conjoint Senior Lecturer University of Newcastle

Aims: 
  1. To assess the effectiveness of Sativex® compared to a placebo control for alleviating the number, severity and duration of cannabis withdrawal symptoms, as well as the overall withdrawal score measured using the Cannabis Withdrawal Scale.
  2. To assess the effect of Sativex® on detoxification completion rates and length of stay in treatment compared with placebo.
  3. To compare reports of adverse events during detoxification treatment between the two groups.
Design and Method: 

This study is a phase II, multi-site, double-blind, randomised, placebo-controlled inpatient trial. The trial will involve 50 treatment-seeking, cannabis dependent adults.

Findings: 

Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F9,377.97=2.39, P=0.01),  including effects on withdrawal-related irritability, depression and cannabis cravings.  Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbances, anxiety, loss of appetite, physical symptoms and restlessness. Participants given nabiximols remained in treatment longer during medication (Unadjusted HR: 3.66 [95% CI 1.18-11.37], P=0.02) with the numbers needed to treat to achieve successful retention in treatment of 2.84. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21=0.79, P=0.67) and those receiving nabiximols did not reporting greater intoxication (F1,6=0.22, P=0.97). The number (F1, 50=0.3, P=0.59) and severity (F1,50=2.69, P=0.1) of AEs did not differ between groups. Both groups showed reduced cannabis use at 28-day follow-up, with no advantage of nabiximols over placebo for self-reported use (F1, 50=0.1, P=0.75), cannabis-related problems (F1, 50=2.27, P=0.14), or cannabis dependence (F1, 50=0.006, p=0.9).

Output: 

Papers

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. (2014). Nabiximols as an agonist replacement therapy during cannabis withdrawal: A Randomized Clinical Trial. JAMA Psychiatry, March 2014, 71(3): 281-291. doi:10.1001/jamapsychiatry.2013.3947

 

Presentations

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. Nabiximols as an agonist replacement therapy during cannabis withdrawal: A Randomized Clinical Trial . Talk presented at the New Zealand Drug Foundation International Drug Policy Symposium. Through the maze: Cannabis and Health. Auckland, New Zealand, November 29, 2013.

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. Nabiximols as an agonist replacement therapy during cannabis withdrawal: A Randomized Clinical Trial . Talk presented at the Australasian Professional Society on Alcohol and other Drugs Conference, Brisbane, Australia, November 26, 2013.

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Talk presented to South Eastern Sydney Local Health Network In Service Training Day, Sydney Hospital and Sydney Eye Hospital, NSW, August 6, 2013.

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Talk presented to Hunter New England Local Health Network In Service Training Day, Newcastle Community Health Center, NSW, July 25, 2013.

McGregor, I, Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Talk presented at the International Cannabinoid Research Society (ICRS) Conference, Vancouver, Canada, June 24, 2013.

Copeland, J, Allsop, D. J, Lintzeris, N, Dunlop, A. J, McGregor, I. Cannabinoid replacement therapy (Sativex) for the management of cannabis withdrawal. Talk presented at the 11th World Congress of Biological Psychiatry, Kyoto, Japan, 23 June 2013.

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Talk presented at the College on Problems of Drug Dependence Conference, San Diego, USA, June 18, 2013.

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Talk presented at the Langton Centre In Service training, Sydney Hospital and Sydney Eye Hospital, Sydney, June 10, 2013.

Allsop, D. J. Cannabis withdrawal – measurement and treatment. Talk presented at the UNSW Masters in Public Health course, Sydney, June 8, 2013.

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Talk presented at the University of Wollongong Psychology Colloquium, Wollongong, May 29, 2013.

Lintzeris, N, Allsop, D. J, Copeland, J, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Talk presented at the Medicine in Addiction Conference, Sydney, 15 March, 2013.

 

Posters

Taylor, A. Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. Results of a double-blind, randomized, placebo controlled trial of cannabinoid therapy for the management of cannabis withdrawal. Poster presented at the 1st Australasian Mental Health and Addiction Nursing Conference, Auckland, New Zealand, June 19 2013.

Bruno, R, Allsop, D. J, Copeland, J, McGregor, I, Norberg, M, Dunlop, A, Montebello, M, Sadler, C, Holland, R, Rivas, G, Muhleisen, P, Booth, J, Lintzeris, N. The impact of nabiximols (Sativex®) on cognitive function during treatment for cannabis withdrawal. Poster presented at the College on Problems of Drug Dependence Conference, San Diego, USA, June 18, 2013.

Allsop, D. J, Copeland, J, Lintzeris, N, Dunlop, A. J, Montebello, M, Sadler, C, Rivas, G. R, Holland, R. M, Muhleisen, P, Norberg, M. M, Booth, J, McGregor, I. A randomized controlled trial of nabiximols (Sativex®) as an agonist replacement therapy during cannabis withdrawal. Poster presented at the National Institute on Drug Abuse (NIDA) International Forum, San Diego, USA, June 17, 2013.
 

Benefits: 

The project may pave the way for the development of the first medication of its type used to alleviate cannabis withdrawal symptoms.

Project Research Area: 
Drug Type: 
Project Status: 
Completed
Year Completed: 
2013