Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence

NCT ID: NCT01747850

Last Updated: 2017-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2015-11-30

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.

Conditions

Cannabis Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sativex

Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). Study subjects will be randomized in blocks of ten to one of the two groups (Sativex vs. placebo) in a double blind manner. 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. All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.

Group Type: EXPERIMENTAL

Motivational Enhancement/Cognitive Behavioral Therapy

Intervention Type: BEHAVIORAL

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.

Sativex

Intervention Type: DRUG

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).

Placebo spray

Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy

Group Type: PLACEBO_COMPARATOR

Motivational Enhancement/Cognitive Behavioral Therapy

Intervention Type: BEHAVIORAL

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.

Placebo spray

Intervention Type: DRUG

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).

Pilot Study

The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label. These subjects will be instructed to use the Sativex Spray according to the induction schedule provided above. These first subjects will allow us to determine if our schedule for dosing is appropriate for the subsequent phase of the study.

Group Type: EXPERIMENTAL

Motivational Enhancement/Cognitive Behavioral Therapy

Intervention Type: BEHAVIORAL

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.

Sativex

Intervention Type: DRUG

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).

Interventions

Motivational 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.

Intervention Type: BEHAVIORAL

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 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).

Intervention Type: DRUG

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 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).

Intervention Type: DRUG

Other Intervention Names

delta-9-tetrahydrocannabinol and cannabidiol; Ethanol,propylene glycol,and peppermint oil with colors

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Bernard Le Foll

Head, Translational Addiction Research Laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bernard Le Foll, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Countries

Canada

References

Wang R, Trigo JM, Le Foll B. Effects of sub-chronic nabiximols on biological markers of individuals undergoing a clinical trial for the treatment of cannabis use disorder. Am J Transl Res. 2023 Aug 15;15(8):5228-5238. eCollection 2023.

Reference Type: DERIVED

PMID: 37692969 (View on PubMed)

Related Links

http://www.camh.net/research

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

Other Identifiers

R21DA031906

Identifier Type: NIH

Identifier Source: secondary_id

View Link

144/2011

Identifier Type: -

Identifier Source: org_study_id