Cannabis Dependence
Conditions
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.
Interventions
BEHAVIORALMotivational Enhancement/Cognitive Behavioral Therapy
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.
DRUGSativex
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).
DRUGPlacebo spray
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).
Sponsors
National Institute on Drug Abuse (NIDA)
Centre for Addiction and Mental Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability | six months | Assessment of tolerability will be determined by the number of subjects that withdrawal from the study due to SAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sativex Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). 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 associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.
Sativex: 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 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). | 20 |
| Placebo Spray Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy
Placebo spray: 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 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%). | 20 |
| Pilot Study The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label. These first subjects will allow us to determine if our schedule for dosing is appropriate for the subsequent phase of the study.
All participants will receive a combination of pharmacotherapy (Sativex) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.
Sativex: 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 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). | 5 |
| Total | 45 |
Baseline characteristics
| Characteristic | Sativex | Placebo Spray | Pilot Study | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 5 Participants | 45 Participants |
| Region of Enrollment Canada | 20 participants | 20 participants | 5 participants | 45 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 3 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 20 | 18 / 20 | 4 / 5 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 5 |
Outcome results
Primary
Tolerability
Assessment of tolerability will be determined by the number of subjects that withdrawal from the study due to SAEs.
Time frame: six months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sativex # of Participants That Withdrew Due SAE | Tolerability | 0 Participants |
| Placebo # of Participants That Withdrew Due SAE | Tolerability | 0 Participants |
| Pilot Study # of Participants That Withdrew Due SAE | Tolerability | 0 Participants |
Secondary
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.
Time frame: six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sativex # of Participants That Withdrew Due SAE | Cannabis Craving | 8.2 Total Craving Scores | Standard Deviation 4.3 |
| Placebo # of Participants That Withdrew Due SAE | Cannabis Craving | 9.6 Total Craving Scores | Standard Deviation 5.7 |
| Pilot Study # of Participants That Withdrew Due SAE | Cannabis Craving | 9.5 Total Craving Scores | Standard Deviation 5.2 |
Secondary
Cannabis Use (Grams)
Amount of cannabis used in grams over the study duration until 6 month follow-up will be assessed
Time frame: six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sativex # of Participants That Withdrew Due SAE | Cannabis Use (Grams) | 2.3 grams of cannabis | Standard Error 0.76 |
| Placebo # of Participants That Withdrew Due SAE | Cannabis Use (Grams) | 3.5 grams of cannabis | Standard Error 1.26 |
| Pilot Study # of Participants That Withdrew Due SAE | Cannabis Use (Grams) | 1.6 grams of cannabis | Standard Error 1.48 |
Secondary
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)
Time frame: six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sativex # of Participants That Withdrew Due SAE | Cannabis Use (in Days) | 42.9 percentage of days | Standard Deviation 7.7 |
| Placebo # of Participants That Withdrew Due SAE | Cannabis Use (in Days) | 47.1 percentage of days | Standard Deviation 12.9 |
| Pilot Study # of Participants That Withdrew Due SAE | Cannabis Use (in Days) | 48.3 percentage of days | Standard Deviation 22.5 |
Secondary
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.
Time frame: six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sativex # of Participants That Withdrew Due SAE | Withdrawal | 5.0 Total Withdrawal score | Standard Deviation 4.7 |
| Placebo # of Participants That Withdrew Due SAE | Withdrawal | 5.1 Total Withdrawal score | Standard Deviation 3.9 |
| Pilot Study # of Participants That Withdrew Due SAE | Withdrawal | 2.7 Total Withdrawal score | Standard Deviation 2.5 |