Fixed or Self-Titrated Dosages of Sativex on Cannabis Users

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

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.

Study Overview

• Status: Completed
• Conditions: Cannabis Dependence
• Intervention / Treatment: Drug: Sativex; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2S1
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Bernard Le Foll, Centre for Addiction and Mental Health

Publications and helpful links

Helpful Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: December 8, 2012
• First Submitted That Met QC Criteria: December 11, 2012
• First Posted (ESTIMATE): December 13, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): February 1, 2016
• Last Update Submitted That Met QC Criteria: December 30, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Sativex; Cannabis dependence
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antiemetics; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Anticonvulsants; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Ethanol; Peppermint oil; Dronabinol; Cannabidiol; Nabiximols
• Other Study ID Numbers: 103/2011; 243152 (OTHER_GRANT: Canadian Institutes of Health Research)