Vivitrol Treatment for Cannabis Use Disorder

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the safety and effectiveness of 12 weeks treatment with an extended-release injectable form of naltrexone (Vivitrol) combined with a psychological intervention in 10 treatment-seeking adults with Cannabis Use Disorder. The hypotheses are that Vivitrol combined with a psychological intervention will be well tolerated, and will reduce cannabis use, improve abstinence rates, and reduce cannabis withdrawal and craving.

Detailed Description
-----------------
This study will be an open-label trial, with no placebo control. Ten male or female treatment-seeking adults with Cannabis Use Disorder (CUD) will be recruited. All participants will receive 3 x 4ml intramuscular injections of Vivitrol (380mg naltrexone). Injections will be administered once every 4 weeks for 12 weeks. In addition, all participants will receive a weekly psychological intervention (Motivational Enhancement Therapy and Cognitive Behavioral Therapy; MET/CBT) for 12 weeks. The aim of this study is to investigate if the proposed Vivitrol dosing schedule, combined with MET/CBT, is appropriate for subsequent randomized controlled trials in people with CUD. This will be achieved by assessing the safety and effectiveness of 12 weeks open-label treatment with Vivitrol (3 x 4 ml intramuscular injections, 380mg naltrexone) combined with weekly MET/CBT. Safety will be assessed by monitoring adverse events during the 12 week treatment period, and up to 3 months follow-up. Effectiveness will be assessed after 12 weeks of treatment and at 3 month follow-up using: (1) seven-day point prevalence cannabis abstinence, (2) percentage of days of cannabis use, (3) amount of cannabis use, and (4) effects on withdrawal symptom scores, craving scores and number of urine samples screened positive for cannabis use.

Official Title
-----------------
Vivitrol Associated With Behavioural-Relapse Prevention Strategy as Treatment for Cannabis Use Disorder

Conditions
-----------------
Cannabis Use Disorder

Intervention / Treatment
-----------------
* Drug: Naltrexone 380 MG [Vivitrol]
* Behavioral: Motivational Enhancement Therapy and Cognitive Behavioral Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult (18-64) 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 5 criteria for current CUD Report cannabis as primary drug of abuse Have cannabis positive urine drug screen Treatment seeking cannabis smoker Exclusion Criteria: Meets DSM 5 criteria for a current axis I disorder including substance use disorder other than cannabis, nicotine or caffeine dependence. Unstable medical conditions Pregnant or breast-feeding Positive urine drug test for opioids (including methadone, morphine, buprenorphine) or benzodiazepines (unless prescribed) at baseline Any IM gluteal administration 30 days prior to baseline Participation in a clinical trial of a pharmacological agent within 30 days prior to baseline Known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or polylactide-coglycolide Any finding that, in the view of the principal investigator, would compromise the subject's ability to fulfill the protocol visit schedule or visit requirement (e.g. unadjudicated charges and/or pending parole hearings)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vivitrol + MET/CBT<br>All participants will receive three 4ml doses of extended-release naltrexone 380mg (Vivitrol), administered by intramuscular injection. Three injections will be administered to each participant; one injection every 4 weeks for 12 weeks of treatment. In addition, all participants will receive weekly Motivational Enhancement Therapy and Cognitive Behavioral Therapy for 12 weeks. | Drug: Naltrexone 380 MG [Vivitrol]<br>* Three 4ml intramuscular injections of naltrexone 380mg (Vivitrol) administered over 12 weeks (one injection every 4 weeks)<br>* Other names: Vivitrol;Behavioral: Motivational Enhancement Therapy and Cognitive Behavioral Therapy<br>* Weekly Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT), based upon the Brief Counselling for Marijuana Dependence Manual published by the Substance Abuse and Mental Health Services Administration (SAMHSA), for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dropouts due to serious adverse events | Tolerability will be measured by the number of participants that drop out of the study because of serious adverse events. Adverse events will be monitored weekly during the 12 week treatment phase of the study | At end of 12 weeks treatment | 
| Dropouts due to serious adverse events | Tolerability will be measured by the number of participants that drop out of the study because of serious adverse events. After the treatment phase of the study adverse events will be monitored weekly for the first 4 weeks follow-up, and then monthly until the final follow-up at 3 months post-treatment | At 3 months follow-up | 
| Cannabis abstinence | Seven-day point prevalence of cannabis abstinence. Abstinence will be measured using a self-report timeline follow-back (TLFB) calendar method, and will be confirmed by urine drug screens. | At end of 12 weeks treatment | 
| Cannabis abstinence | Seven-day point prevalence of cannabis abstinence. Abstinence will be measured using a self-report timeline follow-back (TLFB) calendar method, and will be confirmed by urine drug screens. | At 3 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days cannabis use | Percentage of days of cannabis use. This will be calculated using a self-report timeline follow-back (TLFB) calendar method | During 12 weeks of treatment and up to 3 month follow-up | 
| Amount cannabis use | Amount of cannabis used (grams per week). The amount of cannabis consumed will be measured using a self-report timeline follow-back (TLFB) calendar method | During 12 weeks of treatment and up to 3 month follow-up | 
| Cannabis withdrawal | Withdrawal symptom scores. Cannabis withdrawal symptoms will be measured using the Marijuana Withdrawal Checklist (MWC). The 16 item MWC indicates severity of withdrawal in the previous 24 hours | During 12 weeks of treatment and up to 3 month follow-up | 
| Cannabis craving | Craving symptom scores. Cannabis craving will be measured using the Marijuana Craving Questionnaire (MCQ). The 12-item MCQ assesses craving along 4 dimensions: compulsivity, emotionality, expectancy and purposefulness | During 12 weeks of treatment and up to 3 month follow-up | 
| Urine cannabis screens | Number of urine samples positive for cannabis use. Urine samples will be collected to perform THC metabolite analysis | During 12 weeks of treatment and up to 3 month follow-up |