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. 2018 May 18;18(1):140.
doi: 10.1186/s12888-018-1682-2.

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol

Anjali K Bhardwaj  1   2   3 , David J Allsop  4 , Jan Copeland  5 , Iain S McGregor  4 , Adrian Dunlop  6 , Marian Shanahan  5 , Raimondo Bruno  5   7 , Nghi Phung  8 , Mark Montebello  9 , Craig Sadler  6 , Jessica Gugusheff  10   9 , Melissa Jackson  6 , Jennifer Luksza  8 , Nicholas Lintzeris  10   9 ; Agonist Replacement for Cannabis Dependence (ARCD) study group
Collaborators, Affiliations

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol

Anjali K Bhardwaj et al. BMC Psychiatry. .

Abstract

Background: The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches.

Methods/design: A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures.

Discussion: This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids).

Trial registration: Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

Keywords: Agonist replacement; Cannabis; Cannabis withdrawal; Marijuana; Nabiximols; Study protocol.

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Conflict of interest statement

Ethics approval and consent to participate

Ethics Approval and consent to participate: South Eastern Sydney Local Health District Human Research Ethics Committee. Ref: 14/289 (HREC/14/POWH/701). Hunter New England Local Health District and Western Sydney Local Health District received site-specific ethical approval. All participants signed a Participant Information Consent Form [PICF] before being enrolled in the study. Informed consent involved a 3-step process. 1. Verbal information about the trial was given to potential participant either face-to-face or over the telephone during an initial screen. 2. Participants eligible for a medical screen were asked to sign a ‘consent to participate in a medical screen’ form before seeing the trial medical officer. 3. If participant was deemed eligible by trial medical officer, the medical officer/trial researcher verbally discussed the trial to the participant and invited any queries or concerns to be addressed. The participant was given a copy of the main PICF to take home and review. The PICF was signed by the participant and a witness on day 1 of commencing the trial.

Consent for publication

The participant information consent form includes a section relating to consent for de-identified data to be published. This is however not applicable for this paper.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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Figures

Fig. 1
Fig. 1
Overview of study design
See this image and copyright information in PMC

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