SCCAN: Clinical and Neurobiological Effects of Cannabis Dependence in Young Adults

• Sponsor: The Scripps Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00656487
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 66
• Location: 1
• Arms: 3
• Actual Duration (Months): 32.2
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to find out more about cognitive functioning in people who are cannabis dependent, relative to people who do not use cannabis, and how their brains process information after one month of not using cannabis. An additional goal is to characterize the severity of cannabis dependence using precipitated and naturalistic withdrawal with a double blind, placebo controlled, single administration of rimonabant. Research assessments occur bi-weekly throughout this 28 day study.

Condition or Disease	Intervention/Treatment	Phase
Cannabis Dependence; Cannabis Withdrawal	Drug: rimonabant; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Translational Center on the Clinical Neurobiology of Cannabis Addiction
• Actual Study Start Date: Apr 30, 2008
• Actual Primary Completion Date: Dec 28, 2010
• Actual Study Completion Date: Jan 6, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cannabis-dependent rimonabant Cannabis dependent young adults administered rimonabant 90 mg at Day 0 and followed for 28 days post.	Drug: rimonabant; double blind, placebo controlled, single 90 mg dose; Other Names: CB1 receptor antagonist
Placebo Comparator: Cannabis-dependent placebo Cannabis dependent young adults administered matched placebo at Day 0 and followed for 28 days post.	Drug: placebo; matched placebo
No Intervention: Non-cannabis using control Non-cannabis using demographically similar young adults followed for 28 days.

Outcome Measures

Primary Outcome Measures

1. Withdrawal Symptom Severity on the Marijuana Withdrawal Checklist (MWC) at 28 Days Following Single Dose Administration of Rimonabant or Placebo, or Commencement of Monitoring, During the Double-Blind Period [Day 28]

   The MWC is a 28-item instrument that is used to assess the severity of frequently reported cannabis withdrawal symptoms. Each item on the measure is recorded as a severity rating between 0-3 where a zero indicates not present and a three indicates severe. The severity rating of each item was summed to obtain a single marijuana withdrawal severity score ranging between 0- 84. A lower score indicates less severe withdrawal.

2. Plasma Norepinephrine [Day 28]

   Blood samples were obtained and plasma concentrations were determined using validated enzyme-linked immunosorbent assay (ELISA) techniques at 28 days following single dose administration of rimonabant or placebo, or commencement of monitoring, during the double-blind period.

3. Plasma Cortisol [Day 28]

   Blood samples were obtained and plasma concentrations were determined using validated enzyme-linked immunosorbent assay (ELISA) techniques at 28 days following single dose administration of rimonabant or placebo, or commencement of monitoring, during the double-blind period.

4. Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Strategy Score at Day 28 [Day 0 and Day 28]

   The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Strategy Score is an estimate of use of the most efficient strategy to complete the task. Scores range from 8-56; higher scores equate to poor use of the most efficient strategy. Change = (Day 28 Score - Day 0 Score). A more negative result indicates greater improvement.

5. Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Total Errors at Day 28 [Day 0 and Day 28]

   The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Total Errors are a measure of performance and are unbounded. Change = (Day 28 Score - Day 0 Score). A more negative result indicates greater improvement.

6. Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Mean Time To First Response at Day 28 [Day 0 and Day 28]

   The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Mean Time To First Response is a measure of latency and is unbounded. Change = (Day 28 Time - Day 0 Time). A more negative result indicates greater improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Cannabis Dependent Subjects:

Inclusion Criteria:

• males or females 21-30 years of age

• meets Diagnostic and Statistical Manual (DSM-IV) diagnosis of Cannabis Dependence

• willing to be abstinent for 28 days during study

• smokes < 10 cigarettes per day

• drinks < 1 (female) or < 2 (male) per day

Exclusion Criteria:

• active suicide ideation

• meets DSM-IV diagnosis for dependence on other substances other than cannabis

• significant medical disorders

• pregnant women

• meets DSM-IV diagnosis for a major Axis I disorder other than cannabis dependence

• currently taking psychoactive medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Scripps Research Institute	La Jolla	California	United States	92037

Sponsors and Collaborators

• The Scripps Research Institute
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Barbara J Mason, Ph.D., The Scripps Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Barbara J. Mason, PI, The Scripps Research Institute
• ClinicalTrials.gov Identifier: NCT00656487
• Other Study ID Numbers: DA024194; P20DA024194
• First Posted: Apr 11, 2008
• Last Update Posted: Jun 19, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Barbara J. Mason, PI, The Scripps Research Institute: Cannabis Dependence; Marijuana Dependence; Cannabis Withdrawal; Rimonabant; cannabinoid receptor type 1 (CB1) inverse agonist; Neuropsychology; functional magnetic resonance imaging (fMRI); Endocannabinoids; Cortisol
• Additional relevant MeSH terms: Marijuana Abuse; Rimonabant

Study Results

Participant Flow

Arm/Group Title	Rimonabant	Placebo	Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.
Period Title: Overall Study
STARTED	23	23	20
COMPLETED	21	19	20
NOT COMPLETED	2	4	0

Baseline Characteristics

Arm/Group Title	Rimonabant	Placebo	Control	Total
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.	Total of all reporting groups
Overall Participants	21	19	20	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.33 (1.53)	23.53 (2.76)	24.15 (2.83)	23.32 (2.51)
Sex: Female, Male (Count of Participants)
Female	6 28.6%	7 36.8%	6 30%	19 31.7%
Male	15 71.4%	12 63.2%	14 70%	41 68.3%

Outcome Measures

1. Primary Outcome

Title	Withdrawal Symptom Severity on the Marijuana Withdrawal Checklist (MWC) at 28 Days Following Single Dose Administration of Rimonabant or Placebo, or Commencement of Monitoring, During the Double-Blind Period
Description	The MWC is a 28-item instrument that is used to assess the severity of frequently reported cannabis withdrawal symptoms. Each item on the measure is recorded as a severity rating between 0-3 where a zero indicates not present and a three indicates severe. The severity rating of each item was summed to obtain a single marijuana withdrawal severity score ranging between 0- 84. A lower score indicates less severe withdrawal.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

One participant in the control group who completed monitoring during the double-blind portion of the trial did not complete a Marijuana Withdrawal Checklist at Day 28.

Arm/Group Title	Rimonabant	Placebo	Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.
Measure Participants	21	19	19
Mean (Standard Deviation) [units on a scale]	6.62 (5.59)	6.68 (7.87)	1.05 (2.39)

2. Primary Outcome

Title	Plasma Norepinephrine
Description	Blood samples were obtained and plasma concentrations were determined using validated enzyme-linked immunosorbent assay (ELISA) techniques at 28 days following single dose administration of rimonabant or placebo, or commencement of monitoring, during the double-blind period.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Five control participants who completed the double blind / monitoring portion of the trial did not have samples available for analysis at Day 28. Two participants did not have blood drawn; two additional participant sample results were not returned by the laboratory; and one participant did not return a result due to an ELISA kit error.

Arm/Group Title	Rimonabant	Placebo	Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.
Measure Participants	21	19	15
Mean (Standard Deviation) [ng/mL]	2.12 (1.14)	2.04 (1.05)	1.75 (0.84)

3. Primary Outcome

Title	Plasma Cortisol
Description	Blood samples were obtained and plasma concentrations were determined using validated enzyme-linked immunosorbent assay (ELISA) techniques at 28 days following single dose administration of rimonabant or placebo, or commencement of monitoring, during the double-blind period.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Two control participants and one placebo participant who completed the double blind / monitoring portion of the trial did not have samples available for analysis at Day 28. The control participants did not have blood drawn; the placebo participant returned a non-detectable value.

Arm/Group Title	Rimonabant	Placebo	Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.
Measure Participants	21	18	18
Mean (Standard Deviation) [ug/dL]	27.36 (15.03)	19.29 (7.42)	22.72 (15.21)

4. Primary Outcome

Title	Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Strategy Score at Day 28
Description	The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Strategy Score is an estimate of use of the most efficient strategy to complete the task. Scores range from 8-56; higher scores equate to poor use of the most efficient strategy. Change = (Day 28 Score - Day 0 Score). A more negative result indicates greater improvement.
Time Frame	Day 0 and Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rimonabant	Placebo	Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.
Measure Participants	21	19	20
Mean (Standard Deviation) [units on a scale]	-2.67 (4.15)	-1.37 (5.16)	-1.50 (3.62)

5. Primary Outcome

Title	Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Total Errors at Day 28
Description	The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Total Errors are a measure of performance and are unbounded. Change = (Day 28 Score - Day 0 Score). A more negative result indicates greater improvement.
Time Frame	Day 0 and Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rimonabant	Placebo	Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.
Measure Participants	21	19	20
Mean (Standard Deviation) [units on a scale]	-10.62 (13.46)	-1.95 (11.43)	-2.85 (9.36)

6. Primary Outcome

Title	Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Mean Time To First Response at Day 28
Description	The CANTAB SWM task is a validated computer-based testing instrument assessing the memory component of executive function. Mean Time To First Response is a measure of latency and is unbounded. Change = (Day 28 Time - Day 0 Time). A more negative result indicates greater improvement.
Time Frame	Day 0 and Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rimonabant	Placebo	Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.	Participants were cannabis dependent and received matched placebo.	Participants were non-cannabis using controls.
Measure Participants	21	19	20
Mean (Standard Deviation) [milliseconds]	-139.80 (414.68)	420.24 (2262.39)	22.01 (1438.16)

Adverse Events

Time Frame	Adverse event data was collected at all ten study visits, an average duration of 28 days.
Adverse Event Reporting Description	Adverse events, both serious and other, were documented at all ten study visits by the Medical Assistant on the adverse experiences case report form.
Arm/Group Title	Rimonabant		Placebo		Control
Arm/Group Description	Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit.		Participants were cannabis dependent and received matched placebo.		Participants were non-cannabis using controls.
All Cause Mortality
	Rimonabant		Placebo		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Rimonabant		Placebo		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Rimonabant		Placebo		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/23 (43.5%)		10/23 (43.5%)		4/20 (20%)
Gastrointestinal disorders
Dyspepsia	2/23 (8.7%)		0/23 (0%)		0/20 (0%)
Nausea	4/23 (17.4%)		1/23 (4.3%)		0/20 (0%)
General disorders
Fatigue	2/23 (8.7%)		0/23 (0%)		0/20 (0%)
Infections and infestations
Nasopharyngitis	0/23 (0%)		5/23 (21.7%)		2/20 (10%)
Metabolism and nutrition disorders
Decreased appetite	4/23 (17.4%)		0/23 (0%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Back pain	3/23 (13%)		2/23 (8.7%)		0/20 (0%)
Nervous system disorders
Headache	5/23 (21.7%)		3/23 (13%)		2/20 (10%)

Limitations/Caveats

[Not Specified]

More Information

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.