Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence

Study Overview
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Brief Summary
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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
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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.

Official Title
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Sativex Associated With Behavioral-relapse Prevention Strategy as Treatment for Cannabis Dependence

Conditions
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Cannabis Dependence

Intervention / Treatment
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* Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy
* Drug: Sativex
* Drug: Placebo spray


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sativex<br>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. | Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy<br>* All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.<br>Drug: Sativex<br>* Study subjects will gradually increase the maximal allowed dose of Sativex 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 maximal per day at end of week 2 (Day 11). The target quit date will be set at Day 21 (but subjects will be allowed to stop using cannabis before if they are willing and able to). The medication treatment phase will then be continued for an additional 9 weeks (the last week will be a reduction phase with the use of Spray that will be decreased by 50% to avoid abrupt withdrawal). Then exposure to medications will be stopped (so there will be a total of 12 weeks medication treatment exposure).<br>* Other names: delta-9-tetrahydrocannabinol and cannabidiol;|
| Placebo Comparator: Placebo spray<br>Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy | Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy<br>* All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.<br>Drug: Placebo spray<br>* Study subjects will gradually increase the maximal allowed dose of Placebo 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 maximal per day at end of week 2 (Day 11). The target quit date will be set at Day 21 (but subjects will be allowed to stop using cannabis before if they are willing and able to). The Placebo treatment phase will then be continued for an additional 9 weeks (the last week will be a reduction phase with the use of Placebo Spray that will be decreased by 50%). Then exposure to Placebo will be stopped (so there will be a total of 12 weeks Placebo treatment exposure).<br>* Other names: Ethanol,propylene glycol,and peppermint oil with colors;|
| Experimental: Pilot Study<br>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. | Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy<br>* All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.<br>Drug: Sativex<br>* Study subjects will gradually increase the maximal allowed dose of Sativex 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 maximal per day at end of week 2 (Day 11). The target quit date will be set at Day 21 (but subjects will be allowed to stop using cannabis before if they are willing and able to). The medication treatment phase will then be continued for an additional 9 weeks (the last week will be a reduction phase with the use of Spray that will be decreased by 50% to avoid abrupt withdrawal). Then exposure to medications will be stopped (so there will be a total of 12 weeks medication treatment exposure).<br>* Other names: delta-9-tetrahydrocannabinol and cannabidiol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability | Assessment of tolerability will be determined by the number of subjects that withdrawal from the study due to SAEs. | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cannabis Use (in Days) | 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) | six months | 
| Withdrawal | 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. | six months | 
| Cannabis Craving | 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. | six months | 
| Cannabis Use (Grams) | Amount of cannabis used in grams over the study duration until 6 month follow-up will be assessed | six months |