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Fixed or Self-Titrated Dosages of Sativex on Cannabis Users

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ClinicalTrials.gov Identifier: NCT01748799
Recruitment Status : Completed
First Posted : December 13, 2012
Results First Posted : February 1, 2016
Last Update Posted : February 1, 2016
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Bernard Le Foll, Centre for Addiction and Mental Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Cannabis Dependence
Interventions Drug: Sativex
Drug: Placebo
Enrollment 16

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6 Sequence 7 Sequence 8
Hide Arm/Group Description Self-titrated placebo - Self-titrated Sativex - Fixed dose Sativex - Fixed dose placebo Fixed dose placebo - Fixed dose Sativex - Self-titrated Sativex - Self-titrated placebo Fixed dose placebo - Fixed dose Sativex - Self-titrated placebo - Self-titrated Sativex Fixed dose Sativex - Fixed dose placebo - Self-titrated placebo - Self-titrated Sativex Self-titrated Sativex - Self-titrated placebo - Fixed dose Sativex - Fixed dose placebo Self-titrated Sativex - Self-titrated placebo - Fixed dose placebo - Fixed dose Sativex Self-titrated placebo - Self-titrated Sativex - Fixed dose placebo - Fixed dose Sativex Fixed dose Sativex - Fixed dose placebo - Self-titrated Sativex - Self-titrated placebo
Period Title: Overall Study
Started 6 1 1 2 1 2 2 1
Completed SAU of Fixed Dose Placebo 2 1 1 2 1 1 1 1
Completed Fixed Dose Placebo 2 1 1 2 1 1 1 1
Completed SAU of Fixed Dose Sativex 1 1 1 2 1 1 1 1
Completed Fixed Dose Sativex 1 1 1 2 1 1 1 1
Completed SAU of Self-titrated Placebo 5 1 1 2 1 2 1 1
Completed Self-titrated Placebo 4 1 1 2 1 2 1 1
Completed SAU of Self-titrated Sativex 2 1 1 2 1 2 1 1
Completed Self-titrated Sativex 1 1 1 2 1 1 1 1
Completed 1 1 1 2 1 1 1 1
Not Completed 5 0 0 0 0 1 1 0
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6 Sequence 7 Sequence 8 Total
Hide Arm/Group Description Self-titrated placebo - Self-titrated Sativex - Fixed dose Sativex - Fixed dose placebo Fixed dose placebo - Fixed dose Sativex - Self-titrated Sativex - Self-titrated placebo Fixed dose placebo - Fixed dose Sativex - Self-titrated placebo - Self-titrated Sativex Fixed dose Sativex - Fixed dose placebo - Self-titrated placebo - Self-titrated Sativex Self-titrated Sativex - Self-titrated placebo - Fixed dose Sativex - Fixed dose placebo Self-titrated Sativex - Self-titrated placebo - Fixed dose placebo - Fixed dose Sativex Self-titrated placebo - Self-titrated Sativex - Fixed dose placebo - Fixed dose Sativex Fixed dose Sativex - Fixed dose placebo - Self-titrated Sativex - Self-titrated placebo Total of all reporting groups
Overall Number of Baseline Participants 6 1 1 2 1 2 2 1 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 1 participants 1 participants 2 participants 1 participants 2 participants 2 participants 1 participants 16 participants
35.7  (8.6) 24.0  (0.0) 19.0  (0.0) 46.5  (6.4) 36.0  (0.0) 41.5  (6.4) 43.0  (5.6) 22.0  (0.0) 34.8  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 1 participants 1 participants 2 participants 1 participants 2 participants 2 participants 1 participants 16 participants
Female
2
  33.3%
1
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  50.0%
0
   0.0%
4
  25.0%
Male
4
  66.7%
0
   0.0%
1
 100.0%
2
 100.0%
1
 100.0%
2
 100.0%
1
  50.0%
1
 100.0%
12
  75.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Canada Number Analyzed 6 participants 1 participants 1 participants 2 participants 1 participants 2 participants 2 participants 1 participants 16 participants
6 1 1 2 1 2 2 1 16
1.Primary Outcome
Title Feasibility
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
16 participants were enrolled in the study, 9 participants completed the whole (randomly assigned) experimental sequence
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6 Sequence 7 Sequence 8
Hide Arm/Group Description:
Self-titrated placebo - Self-titrated Sativex - Fixed dose Sativex - Fixed dose placebo
Fixed dose placebo - Fixed dose Sativex - Self-titrated Sativex - Self-titrated placebo
Fixed dose placebo - Fixed dose Sativex - Self-titrated placebo - Self-titrated Sativex
Fixed dose Sativex - Fixed dose placebo - Self-titrated placebo - Self-titrated Sativex
Self-titrated Sativex - Self-titrated placebo - Fixed dose Sativex - Fixed dose placebo
Self-titrated Sativex - Self-titrated placebo - Fixed dose placebo - Fixed dose Sativex
Self-titrated placebo - Self-titrated Sativex - Fixed dose placebo - Fixed dose Sativex
Fixed dose Sativex - Fixed dose placebo - Self-titrated Sativex - Self-titrated placebo
Overall Number of Participants Analyzed 6 1 1 2 1 2 2 1
Measure Type: Number
Unit of Measure: participants
1 1 1 2 1 1 1 1
2.Secondary Outcome
Title Tolerability of Sativex in Persons That Are Cannabis Dependent
Hide Description To assess what number of participants might withdrew due non-tolerability of Sativex
Time Frame 8 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data from 16 participants enrolled in the study was analyzed, none of the participants withdrew due non-tolerability of Sativex
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6 Sequence 7 Sequence 8
Hide Arm/Group Description:
Self-titrated placebo - Self-titrated Sativex - Fixed dose Sativex - Fixed dose placebo
Fixed dose placebo - Fixed dose Sativex - Self-titrated Sativex - Self-titrated placebo
Fixed dose placebo - Fixed dose Sativex - Self-titrated placebo - Self-titrated Sativex
Fixed dose Sativex - Fixed dose placebo - Self-titrated placebo - Self-titrated Sativex
Self-titrated Sativex - Self-titrated placebo - Fixed dose Sativex - Fixed dose placebo
Self-titrated Sativex - Self-titrated placebo - Fixed dose placebo - Fixed dose Sativex
Self-titrated placebo - Self-titrated Sativex - Fixed dose placebo - Fixed dose Sativex
Fixed dose Sativex - Fixed dose placebo - Self-titrated Sativex - Self-titrated placebo
Overall Number of Participants Analyzed 6 1 1 2 1 2 2 1
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 0 0 0
3.Secondary Outcome
Title Cannabis Withdrawal
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Fixed Dose Sativex Smoke as Usual FS Self-titrated Sativex Smoke as Usual StS Fixed Dose Placebo Smoke as Usual FP Self-titrated Placebo Smoke as Usual StP
Hide Arm/Group Description:
Participants were requested to abstain from using cannabis and take a fixed dose of Sativex during this condition (40 sprays per day). Each abstinence condition was followed by a smoke as usual condition (SAU).
Smoke as usual condition corresponding to Fixed Sativex
Participants were requested to abstain from using cannabis and self-titrate dosages of Sativex (up to 40 sprays per day) during this condition. Each abstinence condition was followed by a smoke as usual condition (SAU).
Smoke as usual condition corresponding to Self-titrated Sativex
Participants were requested to abstain from using cannabis and administer a fixed dose of placebo daily (40 sprays per day). Each abstinence condition was followed by a smoke as usual condition (SAU).
Smoke as usual condition corresponding to Fixed Placebo
Participants were requested to abstain from using cannabis and self-titrate dosages of placebo (up to 40 sprays per day) during this condition. Each abstinence condition was followed by a smoke as usual condition (SAU).
Smoke as usual condition corresponding to Self-titrated Placebo
Overall Number of Participants Analyzed 9 9 9 9 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
Cannabis Withdrawal Scale (CWS) 10.3  (12.2) 7.9  (10.0) 9.8  (10.9) 6.6  (5.8) 17.9  (15.9) 8.6  (11.4) 13.7  (14.5) 7.5  (8.3)
Cannabis Withdrawal Checklist (CWC) Total 3.6  (3.5) 2.6  (2.0) 4.0  (4.2) 2.3  (2.2) 7.4  (5.9) 3.7  (3.4) 5.9  (5.5) 3.0  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fixed Dose Sativex, Smoke as Usual FS, Self-titrated Sativex, Smoke as Usual StS, Fixed Dose Placebo, Smoke as Usual FP, Self-titrated Placebo, Smoke as Usual StP
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments The level for statistical significance was p< 0.05.
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fixed Dose Sativex, Smoke as Usual FS, Self-titrated Sativex, Smoke as Usual StS, Fixed Dose Placebo, Smoke as Usual FP, Self-titrated Placebo, Smoke as Usual StP
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments The level for statistical significance was p< 0.05.
Method ANOVA
Comments [Not Specified]
Time Frame 8 weeks
Adverse Event Reporting Description Some adverse events were not study-related (e.g. mild cold, tension headache or hot flashes) and some expected side effects, such as nausea, sleep problems or diarrhea, were noted.
 
Arm/Group Title Fixed Dose Sativex Smoke as Usual FS Self-titrated Sativex Smoke as Usual StS Fixed Dose Placebo Smoke as Usual FP Self-titrated Placebo Smoke as Usual StP
Hide Arm/Group Description Participants were requested to abstain from using cannabis and take a fixed dose of Sativex during this condition (40 sprays per day). Each abstinence condition was followed by a smoke as usual condition (SAU). Smoke as usual condition corresponding to Fixed Sativex Participants were requested to abstain from using cannabis and self-titrate dosages of Sativex (up to 40 sprays per day) during this condition. Each abstinence condition was followed by a smoke as usual condition (SAU). Smoke as usual condition corresponding to Self-titrated Sativex Participants were requested to abstain from using cannabis and take a fixed dose of placebo during this condition (40 sprays per day). Each abstinence condition was followed by a smoke as usual condition (SAU). Smoke as usual condition corresponding to Fixed placebo Participants were requested to abstain from using cannabis and self-titrate dosages of placebo (up to 40 sprays per day) during this condition. Each abstinence condition was followed by a smoke as usual condition (SAU). Smoke as usual condition corresponding to Self-titrated placebo
All-Cause Mortality
Fixed Dose Sativex Smoke as Usual FS Self-titrated Sativex Smoke as Usual StS Fixed Dose Placebo Smoke as Usual FP Self-titrated Placebo Smoke as Usual StP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Fixed Dose Sativex Smoke as Usual FS Self-titrated Sativex Smoke as Usual StS Fixed Dose Placebo Smoke as Usual FP Self-titrated Placebo Smoke as Usual StP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      0/9 (0.00%)      0/9 (0.00%)      0/11 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/13 (0.00%)      0/14 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Fixed Dose Sativex Smoke as Usual FS Self-titrated Sativex Smoke as Usual StS Fixed Dose Placebo Smoke as Usual FP Self-titrated Placebo Smoke as Usual StP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/9 (55.56%)      1/9 (11.11%)      7/9 (77.78%)      3/11 (27.27%)      5/10 (50.00%)      5/10 (50.00%)      9/13 (69.23%)      9/14 (64.29%)    
Blood and lymphatic system disorders                 
hot flashes   1/9 (11.11%)  1 0/9 (0.00%)  0/9 (0.00%)  0 0/11 (0.00%)  1/10 (10.00%)  1 0/10 (0.00%)  1/13 (7.69%)  2 0/14 (0.00%) 
Ear and labyrinth disorders                 
Ringing ears   0/9 (0.00%)  1/9 (11.11%)  1 0/9 (0.00%)  1/11 (9.09%)  2 0/10 (0.00%)  0/10 (0.00%)  0/13 (0.00%)  0/14 (0.00%) 
Eye disorders                 
Dry eyes   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/13 (7.69%)  1 0/14 (0.00%) 
Gastrointestinal disorders                 
Nausea *  0/9 (0.00%)  0 0/9 (0.00%)  3/9 (33.33%)  3 0/11 (0.00%)  1/10 (10.00%)  1 0/10 (0.00%)  0/13 (0.00%)  0 0/14 (0.00%) 
Diarrhea   0/9 (0.00%)  0 0/9 (0.00%)  2/9 (22.22%)  2 0/11 (0.00%)  0/10 (0.00%)  0 0/10 (0.00%)  0/13 (0.00%)  0 4/14 (28.57%)  4
heartburn   0/9 (0.00%)  0 0/9 (0.00%)  0/9 (0.00%)  0 0/11 (0.00%)  0/10 (0.00%)  0 0/10 (0.00%)  2/13 (15.38%)  2 0/14 (0.00%) 
Stomach Pain   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  1 0/10 (0.00%)  0/10 (0.00%)  0/13 (0.00%)  0/14 (0.00%) 
General disorders                 
Headache   1/9 (11.11%)  1 0/9 (0.00%)  0/9 (0.00%)  0 0/11 (0.00%)  1/10 (10.00%)  1 1/10 (10.00%)  1 3/13 (23.08%)  3 1/14 (7.14%)  1
Impaired taste sensation of food   0/9 (0.00%)  0 0/9 (0.00%)  0/9 (0.00%)  0 0/11 (0.00%)  1/10 (10.00%)  1 0/10 (0.00%)  1/13 (7.69%)  1 0/14 (0.00%) 
Vertigo   1/9 (11.11%)  1 0/9 (0.00%)  1/9 (11.11%)  1 1/11 (9.09%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0/13 (0.00%)  0 0/14 (0.00%) 
Feeling drowsy   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/13 (7.69%)  1 1/14 (7.14%)  1
Musculoskeletal and connective tissue disorders                 
Pain in the knee  [1]  0/9 (0.00%)  0 0/9 (0.00%)  1/9 (11.11%)  1 0/11 (0.00%)  0/10 (0.00%)  0 0/10 (0.00%)  1/13 (7.69%)  1 0/14 (0.00%) 
Scapula pain   0/9 (0.00%)  0 0/9 (0.00%)  0/9 (0.00%)  0 0/11 (0.00%)  1/10 (10.00%)  1 0/10 (0.00%)  0/13 (0.00%)  0 0/14 (0.00%) 
Sore foot   0/9 (0.00%)  0 0/9 (0.00%)  1/9 (11.11%)  1 1/11 (9.09%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0/13 (0.00%)  0 0/14 (0.00%) 
Back pain   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  2/10 (20.00%)  2 0/13 (0.00%)  0/14 (0.00%) 
Ankle pain   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/13 (0.00%)  1/14 (7.14%)  1
Psychiatric disorders                 
Insomnia   1/9 (11.11%)  1 0/9 (0.00%)  1/9 (11.11%)  1 0/11 (0.00%)  3/10 (30.00%)  3 0/10 (0.00%)  1/13 (7.69%)  1 1/14 (7.14%)  1
Nightmares   0/9 (0.00%)  0 0/9 (0.00%)  0/9 (0.00%)  0 1/11 (9.09%)  1 1/10 (10.00%)  1 0/10 (0.00%)  0/13 (0.00%)  0 0/14 (0.00%) 
Low motivation   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  1 0/10 (0.00%)  0/10 (0.00%)  0/13 (0.00%)  0/14 (0.00%) 
Anxiety   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  1/11 (9.09%)  1 0/10 (0.00%)  0/10 (0.00%)  0/13 (0.00%)  1/14 (7.14%)  1
Respiratory, thoracic and mediastinal disorders                 
Cold   0/9 (0.00%)  0 0/9 (0.00%)  0/9 (0.00%)  0 0/11 (0.00%)  1/10 (10.00%)  1 3/10 (30.00%)  3 3/13 (23.08%)  3 0/14 (0.00%) 
Sore Throat   1/9 (11.11%)  1 0/9 (0.00%)  0/9 (0.00%)  0 0/11 (0.00%)  0/10 (0.00%)  0 0/10 (0.00%)  1/13 (7.69%)  1 0/14 (0.00%) 
Runny nose   0/9 (0.00%)  0/9 (0.00%)  1/9 (11.11%)  1 0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/13 (0.00%)  0 1/14 (7.14%)  1
Skin and subcutaneous tissue disorders                 
Rash   0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/11 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  2/13 (15.38%)  2 1/14 (7.14%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
from an old injury
The main limitation is the small sample size. Also our study did not include experimental conditions containing THC alone and CBD alone for comparison. The short duration of the experimental condition is also a limitation.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Bernard Le Foll
Organization: Centre for Addiction and Mental Health (CAMH)
Phone: 416.535.8501 ext 34772
Responsible Party: Bernard Le Foll, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01748799     History of Changes
Other Study ID Numbers: 103/2011
243152 ( Other Grant/Funding Number: Canadian Institutes of Health Research )
First Submitted: December 8, 2012
First Posted: December 13, 2012
Results First Submitted: August 14, 2015
Results First Posted: February 1, 2016
Last Update Posted: February 1, 2016