Fixed or Self-Titrated Dosages of Sativex on Cannabis Users

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Fixed or Self-Titrated Dosages of Sativex on Cannabis Users

Conditions
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Cannabis Dependence

Intervention / Treatment
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* Drug: Sativex
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sequence 1<br>Self-titrated placebo - Self-titrated Sativex - Fixed dose Sativex - Fixed dose placebo | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|
| Other: Sequence 2<br>Fixed dose placebo - Fixed dose Sativex - Self-titrated Sativex - Self-titrated placebo | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|
| Other: Sequence 3<br>Fixed dose placebo - Fixed dose Sativex - Self-titrated placebo - Self-titrated Sativex | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|
| Other: Sequence 4<br>Fixed dose Sativex - Fixed dose placebo - Self-titrated placebo - Self-titrated Sativex | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|
| Other: Sequence 5<br>Self-titrated Sativex - Self-titrated placebo - Fixed dose Sativex - Fixed dose placebo | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|
| Other: Sequence 6<br>Self-titrated Sativex - Self-titrated placebo - Fixed dose placebo - Fixed dose Sativex | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|
| Other: Sequence 7<br>Self-titrated placebo - Self-titrated Sativex - Fixed dose placebo - Fixed dose Sativex | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|
| Other: Sequence 8<br>Fixed dose Sativex - Fixed dose placebo - Self-titrated Sativex - Self-titrated placebo | Drug: Sativex<br>* All participants received the same interventions (Fixed or Self-Titrated Sativex), just in different sequences.<br>* Other names: Delta-9-tetrahydrocannabinol and cannabidiol;Drug: Placebo<br>* All participants received the same interventions (Fixed or Self-Titrated Placebo), just in different sequences.<br>* Other names: Ethanol, propylene glycol and peppermint oil with colors;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of Sativex in Persons That Are Cannabis Dependent | To assess what number of participants might withdrew due non-tolerability of Sativex | 8 weeks | 
| 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). | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabis dependence, Sativex