Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence

• Sponsor: Centre for Addiction and Mental Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01747850
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 45
• Location: 1
• Arms: 3
• Duration (Months): 32
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cannabis Dependence	Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy; Drug: Sativex; Drug: Placebo spray	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Sativex Associated With Behavioral-relapse Prevention Strategy as Treatment for Cannabis Dependence
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Behavioral: 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.; Drug: 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).; Other Names: delta-9-tetrahydrocannabinol and cannabidiol
Placebo Comparator: Placebo spray Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy	Behavioral: 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.; 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).; Other Names: Ethanol,propylene glycol,and peppermint oil with colors
Experimental: 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.	Behavioral: 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.; Drug: 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).; Other Names: delta-9-tetrahydrocannabinol and cannabidiol

Outcome Measures

Primary Outcome Measures

1. Tolerability [six months]

   Assessment of tolerability will be determined by the number of subjects that withdrawal from the study due to SAEs.

Secondary Outcome Measures

1. Cannabis Use (in Days) [six months]

   The percentage of days that participants self-reported use of cannabis over the study duration until 6 month follow-up will be assessed (i.e. smoking diary self-report)

2. Withdrawal [six months]

   Effect of Sativex on withdrawal symptom scores will be assessed using the Marijuana Withdrawal Checklist (MWC). Average Total score for the trial (6 months) is reported. Range 0 - 46. Higher scores indicate more severe symptoms associated with marijuana withdrawal.

3. Cannabis Craving [six months]

   Effect of Sativex on cannabis craving will be assessed using the Marijuana Craving Questionnaire (MCQ). Average Total score for the trial (6 months) is reported. Participants rate the 12 items using a 7-item Likert scale ranging from strongly disagree to strongly agree, and the total score ranges from 4 to 28 (subscales compulsivity (mean items 2, 7 and 10), emotionality (mean items 4, 6 and 9), expectancy (mean items 5, 11 and 12) and purposefulness (mean items 1, 3 and 8); total score is the sum for the 4 subscales). Higher scores indicate more severe craving for marijuana.

4. Cannabis Use (Grams) [six months]

   Amount of cannabis used in grams over the study duration until 6 month follow-up will be assessed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre for Addiction and Mental Health	Toronto	Ontario	Canada	M5S 2S1

Sponsors and Collaborators

• Centre for Addiction and Mental Health
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Bernard Le Foll, MD, PhD, Centre for Addiction and Mental Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• 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

Publications

None provided.

• Responsible Party: Bernard Le Foll, Head, Translational Addiction Research Laboratory, Centre for Addiction and Mental Health
• ClinicalTrials.gov Identifier: NCT01747850
• Other Study ID Numbers: 144/2011; R21DA031906
• First Posted: Dec 12, 2012
• Last Update Posted: Oct 2, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Marijuana Abuse; Ethanol; Nabiximols; Dronabinol; Cannabidiol; Peppermint oil

Study Results

Participant Flow

Arm/Group Title	Pilot Study	Sativex	Placebo Spray
Arm/Group Description	The first five subjects will be treatment-seekers that will be treated open-label. These first subjects will allow us to determine if our schedule for dosing is appropriate for the subsequent phase of the study. Motivational Enhancement/Cognitive Behavioral Therapy: All participants will receive a combination of pharmacotherapy (Sativex) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy. 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 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).	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 (the last week will be a reduction phase with the use of Spray that will be decreased by 50% to avoid abrupt withdrawal). All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy 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 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).
Period Title: Overall Study
STARTED	5	20	20
COMPLETED	4	13	14
NOT COMPLETED	1	7	6

Baseline Characteristics

Arm/Group Title	Sativex	Placebo Spray	Pilot Study	Total
Arm/Group Description	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). 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 associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy. 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 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).	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy 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 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%).	The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label. These first subjects will allow us to determine if our schedule for dosing is appropriate for the subsequent phase of the study. All participants will receive a combination of pharmacotherapy (Sativex) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy. 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 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).	Total of all reporting groups
Overall Participants	20	20	5	45
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	5 100%	45 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 25%	6 30%	2 40%	13 28.9%
Male	15 75%	14 70%	3 60%	32 71.1%
Region of Enrollment (participants) [Number]
Canada	20 100%	20 100%	5 100%	45 100%

Outcome Measures

1. Primary Outcome

Title	Tolerability
Description	Assessment of tolerability will be determined by the number of subjects that withdrawal from the study due to SAEs.
Time Frame	six months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sativex # of Participants That Withdrew Due SAE	Placebo # of Participants That Withdrew Due SAE	Pilot Study # of Participants That Withdrew Due SAE
Arm/Group Description	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy	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. 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. 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
Measure Participants	20	20	5
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Cannabis Use (in Days)
Description	The percentage of days that participants self-reported use of cannabis over the study duration until 6 month follow-up will be assessed (i.e. smoking diary self-report)
Time Frame	six months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sativex % Days Use of Cannabis	Placebo % Days Use of Cannabis	Pilot % Days Use of Cannabis
Arm/Group Description	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy	The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label.
Measure Participants	20	20	5
Mean (Standard Deviation) [percentage of days]	42.9 (7.7)	47.1 (12.9)	48.3 (22.5)

3. Secondary Outcome

Title	Withdrawal
Description	Effect of Sativex on withdrawal symptom scores will be assessed using the Marijuana Withdrawal Checklist (MWC). Average Total score for the trial (6 months) is reported. Range 0 - 46. Higher scores indicate more severe symptoms associated with marijuana withdrawal.
Time Frame	six months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sativex Withdrawal	Placebo Withdrawal	Pilot Withdrawal
Arm/Group Description	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy	The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label.
Measure Participants	20	20	5
Mean (Standard Deviation) [Total Withdrawal score]	5.0 (4.7)	5.1 (3.9)	2.7 (2.5)

4. Secondary Outcome

Title	Cannabis Craving
Description	Effect of Sativex on cannabis craving will be assessed using the Marijuana Craving Questionnaire (MCQ). Average Total score for the trial (6 months) is reported. Participants rate the 12 items using a 7-item Likert scale ranging from strongly disagree to strongly agree, and the total score ranges from 4 to 28 (subscales compulsivity (mean items 2, 7 and 10), emotionality (mean items 4, 6 and 9), expectancy (mean items 5, 11 and 12) and purposefulness (mean items 1, 3 and 8); total score is the sum for the 4 subscales). Higher scores indicate more severe craving for marijuana.
Time Frame	six months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sativex Craving	Placebo Craving	Pilot Craving
Arm/Group Description	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy	The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label.
Measure Participants	20	20	5
Mean (Standard Deviation) [Total Craving Scores]	8.2 (4.3)	9.6 (5.7)	9.5 (5.2)

5. Secondary Outcome

Title	Cannabis Use (Grams)
Description	Amount of cannabis used in grams over the study duration until 6 month follow-up will be assessed
Time Frame	six months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sativex Cannabis Use (g)	Placebo Cannabis Use (g)	Pilot Cannabis Use (g)
Arm/Group Description	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.	Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy	The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label.
Measure Participants	20	20	5
Mean (Standard Error) [grams of cannabis]	2.3 (0.76)	3.5 (1.26)	1.6 (1.48)

Adverse Events

Time Frame	1 year, 10 months
Adverse Event Reporting Description	ADVERSE EVENT COLLECTION BY QUESTIONNAIRE DURING STUDY VISITS (SAFTEE)
Arm/Group Title	Sativex		Placebo Spray		Pilot Study
Arm/Group Description	Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). 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 ) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.		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). There will be a total of 12 weeks Placebo treatment exposure. Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy		The first five subjects will be treatment-seekers that will be treated open-label. 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). There will be a total of 12 weeks medication treatment exposure). Motivational Enhancement/Cognitive Behavioral Therapy: All participants will receive a combination of pharmacotherapy (Sativex) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.
All Cause Mortality
	Sativex		Placebo Spray		Pilot Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Sativex		Placebo Spray		Pilot Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Sativex		Placebo Spray		Pilot Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/20 (80%)		18/20 (90%)		4/5 (80%)
Cardiac disorders
Cardiovascular	0/20 (0%)		2/20 (10%)		0/5 (0%)
Light Headedness	0/20 (0%)		0/20 (0%)		1/5 (20%)
Gastrointestinal disorders
Oro Mucal	2/20 (10%)		2/20 (10%)		2/5 (40%)
Diarrhea	2/20 (10%)		4/20 (20%)		1/5 (20%)
Nausea	2/20 (10%)		6/20 (30%)		2/5 (40%)
Constipation	0/20 (0%)		2/20 (10%)		1/5 (20%)
Indigestion	0/20 (0%)		0/20 (0%)		1/5 (20%)
General disorders
Nightmare	0/20 (0%)		2/20 (10%)		1/5 (20%)
Decreased appetite	2/20 (10%)		2/20 (10%)		1/5 (20%)
Ringing in ears	2/20 (10%)		0/20 (0%)		1/5 (20%)
Tiredness	0/20 (0%)		0/20 (0%)		2/5 (40%)
Musculoskeletal and connective tissue disorders
Pain	0/20 (0%)		2/20 (10%)		2/5 (40%)
Nervous system disorders
Insomnia	11/20 (55%)		8/20 (40%)		3/5 (60%)
excessive sweating	0/20 (0%)		2/20 (10%)		1/5 (20%)
Psychiatric disorders
Mood Disturbance	2/20 (10%)		0/20 (0%)		1/5 (20%)
Decrease in Libido	0/20 (0%)		3/20 (15%)		0/5 (0%)
Walking up in the middle of night	0/20 (0%)		0/20 (0%)		1/5 (20%)
Renal and urinary disorders
Urinary Problems	2/20 (10%)		0/20 (0%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Cold/Influenza	4/20 (20%)		6/20 (30%)		3/5 (60%)
Skin and subcutaneous tissue disorders
Skin rashes	0/20 (0%)		0/20 (0%)		1/5 (20%)
Vascular disorders
Headache	4/20 (20%)		10/20 (50%)		3/5 (60%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.