Cannabis Use Disorder
Conditions
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.
Interventions
DRUGNaltrexone 380 MG [Vivitrol]
Three 4ml intramuscular injections of naltrexone 380mg (Vivitrol) administered over 12 weeks (one injection every 4 weeks)
BEHAVIORALMotivational Enhancement Therapy and Cognitive Behavioral Therapy
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
Sponsors
Centre for Addiction and Mental Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dropouts Due to Serious Adverse Events | At end of 12 weeks treatment | 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 |
| Cannabis Abstinence | At end of 12 weeks treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cannabis Withdrawal | During 12 weeks of treatment and up to 3 month follow-up | 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. Each item is scored 0-4 (where 4=severe) and the scale is summed. The outcome variable is the total score (the sum of each individual item score), which can vary from 0 to 64; higher scores indicate a worse outcome (i.e., more number/severity of withdrawal symptoms). |
| Days Cannabis Use | During 12 weeks of treatment and up to 3 month follow-up | Percentage of days of cannabis use. This will be calculated using a self-report timeline follow-back (TLFB) calendar method |
| Urine Cannabis Screens | During 12 weeks of treatment and up to 3 month follow-up | Number of urine samples positive for cannabis use. Urine samples will be collected to perform THC metabolite analysis |
| Cannabis Craving | During 12 weeks of treatment and up to 3 month follow-up | 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. Each subscale is the sum of 3 items from the questionnaire. Each item is rated from 1 (strongly disagree) to 7 (strongly agree). Each subscale can thus vary from 3 to 21, where higher scores represent more craving (worse outcome). |
| Amount Cannabis Use | During 12 weeks of treatment and up to 3 month follow-up | 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 |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vivitrol + MET/CBT 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.
Naltrexone 380 MG \[Vivitrol\]: Three 4ml intramuscular injections of naltrexone 380mg (Vivitrol) administered over 12 weeks (one injection every 4 weeks)
Motivational Enhancement Therapy and Cognitive Behavioral Therapy: 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 | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Vivitrol + MET/CBT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
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.
Time frame: At 3 month follow-up
Population: Only 1 participant was enrolled and this participant withdrew at 6 weeks, so data were not collected for this Outcome Measure.
Primary
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.
Time frame: At end of 12 weeks treatment
Population: Only 1 participant was enrolled and this participant withdrew at 6 weeks, so data were not collected for this Outcome Measure.
Primary
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
Time frame: At end of 12 weeks treatment
Population: Only 1 participant was enrolled, and this participant withdrew prior to completion at 6 weeks; data are reported up to 6 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vivitrol + MET/CBT | Dropouts Due to Serious Adverse Events | 0 Participants |
Primary
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
Time frame: At 3 months follow-up
Population: Only 1 participant was enrolled, and this participant withdrew prior to completion at 6 weeks. Since no participant completed the study and made it to the 3-month follow-up phase, there is no data to report for this outcome.
Secondary
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
Time frame: During 12 weeks of treatment and up to 3 month follow-up
Population: Only 1 participant was enrolled, and this participant withdrew prior to completion at 6 weeks; data are reported up to 6 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vivitrol + MET/CBT | Amount Cannabis Use | Week 2 | 6 g/week of cannabis |
| Vivitrol + MET/CBT | Amount Cannabis Use | Week 3 | 0 g/week of cannabis |
| Vivitrol + MET/CBT | Amount Cannabis Use | Week 4 | 0 g/week of cannabis |
| Vivitrol + MET/CBT | Amount Cannabis Use | Week 1 | 14 g/week of cannabis |
| Vivitrol + MET/CBT | Amount Cannabis Use | Week 5 | 0 g/week of cannabis |
| Vivitrol + MET/CBT | Amount Cannabis Use | Week 6 | 0 g/week of cannabis |
Secondary
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. Each subscale is the sum of 3 items from the questionnaire. Each item is rated from 1 (strongly disagree) to 7 (strongly agree). Each subscale can thus vary from 3 to 21, where higher scores represent more craving (worse outcome).
Time frame: During 12 weeks of treatment and up to 3 month follow-up
Population: Only 1 participant was enrolled, and this participant withdrew prior to completion at 6 weeks; data are reported up to 6 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vivitrol + MET/CBT | Cannabis Craving | Week 1 Compulsivity | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 1 Emotionality | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 1 Expectancy | 5 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 1 Purposefulness | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 2 Compulsivity | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 2 Emotionality | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 2 Expectancy | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 2 Purposefulness | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 3 Compulsivity | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 3 Emotionality | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 3 Expectancy | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 3 Purposefulness | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 4 Compulsivity | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 4 Emotionality | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 4 Expectancy | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 4 Purposefulness | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 5 Compulsivity | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 5 Emotionality | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 5 Expectancy | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 5 Purposefulness | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 6 Compulsivity | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 6 Emotionality | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 6 Expectancy | 3 score on a scale |
| Vivitrol + MET/CBT | Cannabis Craving | Week 6 Purposefulness | 3 score on a scale |
Secondary
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. Each item is scored 0-4 (where 4=severe) and the scale is summed. The outcome variable is the total score (the sum of each individual item score), which can vary from 0 to 64; higher scores indicate a worse outcome (i.e., more number/severity of withdrawal symptoms).
Time frame: During 12 weeks of treatment and up to 3 month follow-up
Population: Only 1 participant was enrolled, and this participant withdrew prior to completion at 6 weeks; data are reported up to 6 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vivitrol + MET/CBT | Cannabis Withdrawal | Week 1 | 4 score on a scale |
| Vivitrol + MET/CBT | Cannabis Withdrawal | Week 2 | 4 score on a scale |
| Vivitrol + MET/CBT | Cannabis Withdrawal | Week 3 | 7 score on a scale |
| Vivitrol + MET/CBT | Cannabis Withdrawal | Week 4 | 13 score on a scale |
| Vivitrol + MET/CBT | Cannabis Withdrawal | Week 5 | 9 score on a scale |
| Vivitrol + MET/CBT | Cannabis Withdrawal | Week 6 | 9 score on a scale |
Secondary
Days Cannabis Use
Percentage of days of cannabis use. This will be calculated using a self-report timeline follow-back (TLFB) calendar method
Time frame: During 12 weeks of treatment and up to 3 month follow-up
Population: Only 1 participant was enrolled, and this participant withdrew prior to completion at 6 weeks; data are reported up to 6 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vivitrol + MET/CBT | Days Cannabis Use | Week 1 | 100 Percentage of days/week |
| Vivitrol + MET/CBT | Days Cannabis Use | Week 2 | 28.6 Percentage of days/week |
| Vivitrol + MET/CBT | Days Cannabis Use | Week 3 | 0 Percentage of days/week |
| Vivitrol + MET/CBT | Days Cannabis Use | Week 4 | 0 Percentage of days/week |
| Vivitrol + MET/CBT | Days Cannabis Use | Week 5 | 0 Percentage of days/week |
| Vivitrol + MET/CBT | Days Cannabis Use | Week 6 | 0 Percentage of days/week |
Secondary
Urine Cannabis Screens
Number of urine samples positive for cannabis use. Urine samples will be collected to perform THC metabolite analysis
Time frame: During 12 weeks of treatment and up to 3 month follow-up
Population: Only 1 participant was enrolled, and this participant withdrew prior to completion at 6 weeks; data are reported up to 6 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vivitrol + MET/CBT | Urine Cannabis Screens | 6 Total number of positive urine samples |