Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence

Phase 2

Completed

Conditions: Cannabis Dependence

Interventions: Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy
Drug: Placebo spray
Drug: Sativex

Registration Number: NCT01747850

Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary: The purpose of this study is assess Sativex as a treatment for Cannabis dependence. Initially a pilot study will be conducted in five subjects seeking treatment for cannabis dependence to ensure that our planned self-titration regimen is appropriate using Sativex. This phase will be open label, with no placebo control. Then, there will be a twelve-week, double-blind, placebo-controlled study in male and female subjects seeking treatment for cannabis dependence (n=40). All participants will receive a combination of pharmacotherapy (Sativex Spray or Placebo Spray) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). The subjects will have to come daily to the centre to assess usage of medication. Following the medication phase, participants will have a follow-up weekly for another four weeks and then monthly until the 6 month follow up visit after the target quit date. The investigators are planning to enroll 45 subjects over the two-year period.

Detailed Description: In the pilot study subjects will be treated with SATIVEX® (THC/cannabidiol combination in a buccal spray) using the same approach as outlined below for the randomized controlled trial. In the twelve-week, double-blind, placebo-controlled study visits will occur weekly during the medication phase of the study. The medication will be self-titrated over three weeks and a target quit date will be set up at Day 21. There will be a total of 12 weeks of drug exposure. Throughout these 12-weeks, all participants will receive a combination of pharmacotherapy (Sativex Spray or Placebo Spray) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT) in accordance with the intervention practices shown to be effective in treatment of cannabis dependence. The intervention will be adapted from the Brief Counselling for Marijuana Dependence manual published by the Substance Abuse and Mental Health Services Administration (SAMHSA). At each study visit, vital signs and self-report ratings will be collected. In addition, the subjects will have to come daily to the centre to assess medication usage and will be asked to provide urine sample (two times weekly) and blood sample weekly. As there may be compliance issues, a contingency management approach will be also implemented.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

Inclusion Criteria

Adult male or female (gender to be analyzed as a covariate)
Understand and willing to comply with study requirements and restrictions
Willing to use appropriate contraceptive method throughout the study
Otherwise healthy as judged by investigator based on medical history, physical exam, vitals, ECG and labs
DSM-IV criteria for current marijuana dependence
Report marijuana as primary drug of abuse
Report using marijuana at least 5 days a week for at least one month
Have marijuana positive urine drug screen
Treatment seeking cannabis smoker
Smoke less than or equal to the equivalent of 4 joints per day (or four grams per day if participants smokes cannabis in other forms)

Exclusion Criteria

Meets DSM-IV criteria for a current axis I disorder including substance use disorder other than cannabis, nicotine or caffeine dependence.
First-degree relative with schizophrenia
History of seizures
History of cardiovascular disease
History of pulmonary disease such as asthma, COPD
Clinically significant pathology in oral cavity and poor oral hygiene
Known sensitivity to dronabinol, cannabidiol, propylene glycole, ethanol or peppermint oil (used in SATIVEX® buccal spray)
Unstable medical conditions
Pregnant or breast-feeding
Currently taking psychotropic medication with benefit for any other illness than treatment of insomnia,
Holding a job that involves driving, operating heavy machines

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo spray	Placebo spray	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy
Pilot Study	Motivational Enhancement/Cognitive Behavioral Therapy	The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label. These subjects will be instructed to use the Sativex Spray according to the induction schedule provided above. These first subjects will allow us to determine if our schedule for dosing is appropriate for the subsequent phase of the study.
Placebo spray	Motivational Enhancement/Cognitive Behavioral Therapy	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy
Sativex	Motivational Enhancement/Cognitive Behavioral Therapy	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). Study subjects will be randomized in blocks of ten to one of the two groups (Sativex vs. placebo) in a double blind manner. There will be a gradual increase of the maximal allowed dose starting at five sprays per day for the first two days and increasing of five sprays per day until reaching the max number of 42 sprays per day at the end of week 2. There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.
Sativex	Sativex	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). Study subjects will be randomized in blocks of ten to one of the two groups (Sativex vs. placebo) in a double blind manner. There will be a gradual increase of the maximal allowed dose starting at five sprays per day for the first two days and increasing of five sprays per day until reaching the max number of 42 sprays per day at the end of week 2. There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.
Pilot Study	Sativex	The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label. These subjects will be instructed to use the Sativex Spray according to the induction schedule provided above. These first subjects will allow us to determine if our schedule for dosing is appropriate for the subsequent phase of the study.

Primary Outcome Measures

Name	Time	Method
Tolerability	six months	Assessment of tolerability will be determined by the number of subjects that withdrawal from the study due to SAEs.

Secondary Outcome Measures

Name	Time	Method
Cannabis Use (in Days)	six months	The percentage of days that participants self-reported use of cannabis over the study duration until 6 month follow-up will be assessed (i.e. smoking diary self-report)
Withdrawal	six months	Effect of Sativex on withdrawal symptom scores will be assessed using the Marijuana Withdrawal Checklist (MWC). Average Total score for the trial (6 months) is reported. Range 0 - 46. Higher scores indicate more severe symptoms associated with marijuana withdrawal.
Cannabis Craving	six months	Effect of Sativex on cannabis craving will be assessed using the Marijuana Craving Questionnaire (MCQ). Average Total score for the trial (6 months) is reported. Participants rate the 12 items using a 7-item Likert scale ranging from strongly disagree to strongly agree, and the total score ranges from 4 to 28 (subscales compulsivity (mean items 2, 7 and 10), emotionality (mean items 4, 6 and 9), expectancy (mean items 5, 11 and 12) and purposefulness (mean items 1, 3 and 8); total score is the sum for the 4 subscales). Higher scores indicate more severe craving for marijuana.
Cannabis Use (Grams)	six months	Amount of cannabis used in grams over the study duration until 6 month follow-up will be assessed