Cannabis Dependence
Conditions
Keywords
Cannabis dependence, Sativex
Brief summary
The purpose of this study is to to demonstrate the feasibility and tolerability of the use of Sativex in cannabis dependent individuals and to assess the effects of fixed or self titrated dosages of SATIVEX® (Δ9-tetrahydrocannabinol /cannabidiol combination in a buccal spray) on withdrawal symptoms, craving scores and cannabis consumption during the study period.
Detailed description
This will be a one year pilot/feasibility study, assessing the effects of fixed or self-titrated dosages of SATIVEX® (Δ9-tetrahydrocannabinol /cannabidiol combination in a buccal spray) on withdrawal from cannabis and craving among cannabis dependent subjects. Subjects in this study will undergo an 8-week double-blind, placebo-controlled trial. Subjects will be regular cannabis-users who are not currently seeking treatment for cannabis dependence. Subjects will participate in each of 8 conditions, lasting 5 weekdays each (an ABACADAE study design); four smoke as usual conditions (SAU) and four cannabis abstinence conditions. During each abstinence condition (B, C, D, E conditions), subjects will be allocated to one condition including self-titration of placebo, fixed dose of placebo, self-titration of SATIVEX (up to a max of 40 sprays per day, equal to 108mg THC) or fixed dose of SATIVEX (40 sprays per day). Each medication phase will be followed by a washout period where individuals will be requested to smoke cannabis as usual (A condition). The experimental conditions will be: type of SATIVEX® spray used (active vs placebo), and titration regimen (fixed or self-titrated). This pilot study will allow us to demonstrate the feasibility of our approach and to determine the sample size to use secondarily for a larger study. Our ultimate goal is to determine optimal conditions to use for a subsequent randomized controlled trial assessing the efficacy of SATIVEX® in treatment of Cannabis dependence among treatment-seeking subjects.
Interventions
DRUGSativex
All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.
DRUGPlacebo
All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.
Sponsors
Canadian Institutes of Health Research (CIHR)
Centre for Addiction and Mental Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* age 18-50 * current cannabis dependence * cannabis as primary drug of abuse * frequent cannabis use (i.e., at least 5 days per week) * have experienced at least 2 withdrawal symptoms during previous cessation periods * cannabis use not for medical purposes (i.e., not a government-licensed medical cannabis user) * not seeking treatment for cannabis dependence * willingness to participate in study protocol
Exclusion criteria
* meet criteria for any psychiatric disorder requiring psychiatric intervention * have a history of seizures; c)have known sensitivity to Dronabinol, Cannabidiol, Propylene glycole, Ethanol or peppermint oil (used in Sativex buccal spray * suffer from an unstable medical condition * currently have physical dependence on any other drugs (excluding nicotine) that would require medical detoxification * currently taking psychotropic medication with benefit for any other illness than treatment of insomnia * pregnant or breast-feeding * hold a job that involves operating heavy machinery * currently seeking treatment for cannabis-related problems * family history of psychotic symptoms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility | 12 months | Feasibility will be assessed by analysing how many participants can be recruited/complete the whole (randomly assigned) experimental sequence with a period of one year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of Sativex in Persons That Are Cannabis Dependent | 8 weeks | To assess what number of participants might withdrew due non-tolerability of Sativex |
| Cannabis Withdrawal | 8 weeks | Withdrawal symptoms were assessed using the Cannabis Withdrawal Scale (CWS) (Minimum-Maximum Scores 0-190, high scores represent more withdrawal) and Cannabis Withdrawal Checklist (CWC) (Minimum-Maximum Scores 0-48, high scores represent more withdrawal) by establishing comparisons between Sativex/Placebo and Smoke as usual conditions (4 interventions: Fixed Sativex, Fixed Placebo, Self-titrated Sativex, Self-titrated Placebo and 4 corresponding Smoke as usual conditions). |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Self-titrated placebo - Self-titrated Sativex - Fixed dose Sativex - Fixed dose placebo | 6 |
| Sequence 2 Fixed dose placebo - Fixed dose Sativex - Self-titrated Sativex - Self-titrated placebo | 1 |
| Sequence 3 Fixed dose placebo - Fixed dose Sativex - Self-titrated placebo - Self-titrated Sativex | 1 |
| Sequence 4 Fixed dose Sativex - Fixed dose placebo - Self-titrated placebo - Self-titrated Sativex | 2 |
| Sequence 5 Self-titrated Sativex - Self-titrated placebo - Fixed dose Sativex - Fixed dose placebo | 1 |
| Sequence 6 Self-titrated Sativex - Self-titrated placebo - Fixed dose placebo - Fixed dose Sativex | 2 |
| Sequence 7 Self-titrated placebo - Self-titrated Sativex - Fixed dose placebo - Fixed dose Sativex | 2 |
| Sequence 8 Fixed dose Sativex - Fixed dose placebo - Self-titrated Sativex - Self-titrated placebo | 1 |
| Total | 16 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 | Sequence 5 | Sequence 6 | Sequence 7 | Sequence 8 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.7 years STANDARD_DEVIATION 8.6 | 24.0 years STANDARD_DEVIATION 0 | 19.0 years STANDARD_DEVIATION 0 | 46.5 years STANDARD_DEVIATION 6.4 | 36.0 years STANDARD_DEVIATION 0 | 41.5 years STANDARD_DEVIATION 6.4 | 43.0 years STANDARD_DEVIATION 5.6 | 22.0 years STANDARD_DEVIATION 0 | 34.8 years STANDARD_DEVIATION 10.5 |
| Region of Enrollment Canada | 6 participants | 1 participants | 1 participants | 2 participants | 1 participants | 2 participants | 2 participants | 1 participants | 16 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 9 | 1 / 9 | 7 / 9 | 3 / 11 | 5 / 10 | 5 / 10 | 9 / 13 | 9 / 14 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 13 | 0 / 14 |
Outcome results
Primary
Feasibility
Feasibility will be assessed by analysing how many participants can be recruited/complete the whole (randomly assigned) experimental sequence with a period of one year.
Time frame: 12 months
Population: 16 participants were enrolled in the study, 9 participants completed the whole (randomly assigned) experimental sequence
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence 1 | Feasibility | 1 participants |
| Sequence 2 | Feasibility | 1 participants |
| Sequence 3 | Feasibility | 1 participants |
| Sequence 4 | Feasibility | 2 participants |
| Sequence 5 | Feasibility | 1 participants |
| Sequence 6 | Feasibility | 1 participants |
| Sequence 7 | Feasibility | 1 participants |
| Sequence 8 | Feasibility | 1 participants |
Secondary
Cannabis Withdrawal
Withdrawal symptoms were assessed using the Cannabis Withdrawal Scale (CWS) (Minimum-Maximum Scores 0-190, high scores represent more withdrawal) and Cannabis Withdrawal Checklist (CWC) (Minimum-Maximum Scores 0-48, high scores represent more withdrawal) by establishing comparisons between Sativex/Placebo and Smoke as usual conditions (4 interventions: Fixed Sativex, Fixed Placebo, Self-titrated Sativex, Self-titrated Placebo and 4 corresponding Smoke as usual conditions).
Time frame: 8 weeks
Population: Only 9 of the 16 participants recruited completed the whole experimental sequence (participants were assigned to 1 of 8 different experimental sequences in a randomized order).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 3.6 units on a scale | Standard Deviation 3.5 |
| Sequence 1 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 10.3 units on a scale | Standard Deviation 12.2 |
| Sequence 2 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 2.6 units on a scale | Standard Deviation 2 |
| Sequence 2 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 7.9 units on a scale | Standard Deviation 10 |
| Sequence 3 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 9.8 units on a scale | Standard Deviation 10.9 |
| Sequence 3 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 4.0 units on a scale | Standard Deviation 4.2 |
| Sequence 4 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 2.3 units on a scale | Standard Deviation 2.2 |
| Sequence 4 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 6.6 units on a scale | Standard Deviation 5.8 |
| Sequence 5 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 17.9 units on a scale | Standard Deviation 15.9 |
| Sequence 5 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 7.4 units on a scale | Standard Deviation 5.9 |
| Sequence 6 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 8.6 units on a scale | Standard Deviation 11.4 |
| Sequence 6 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 3.7 units on a scale | Standard Deviation 3.4 |
| Sequence 7 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 13.7 units on a scale | Standard Deviation 14.5 |
| Sequence 7 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 5.9 units on a scale | Standard Deviation 5.5 |
| Sequence 8 | Cannabis Withdrawal | Cannabis Withdrawal Checklist (CWC) Total | 3.0 units on a scale | Standard Deviation 1.6 |
| Sequence 8 | Cannabis Withdrawal | Cannabis Withdrawal Scale (CWS) | 7.5 units on a scale | Standard Deviation 8.3 |
Comparison: Omnibus analysis for Cannabis Withdrawal Scale (CWS) data was a Repeated measures ANOVA (including all the experimental conditions) followed by pair-wise comparisons. The level for statistical significance was p\< 0.05.p-value: <0.01ANOVA
Comparison: Omnibus analysis for Cannabis Withdrawal Checklist (CWC) data was a Repeated measures ANOVA (including all the experimental conditions) followed by pair-wise comparisons. The level for statistical significance was p\< 0.05.p-value: 0.01ANOVA
Secondary
Tolerability of Sativex in Persons That Are Cannabis Dependent
To assess what number of participants might withdrew due non-tolerability of Sativex
Time frame: 8 weeks
Population: Data from 16 participants enrolled in the study was analyzed, none of the participants withdrew due non-tolerability of Sativex
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence 1 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |
| Sequence 2 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |
| Sequence 3 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |
| Sequence 4 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |
| Sequence 5 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |
| Sequence 6 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |
| Sequence 7 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |
| Sequence 8 | Tolerability of Sativex in Persons That Are Cannabis Dependent | 0 participants |