Cannabis Dependence, Cannabis Withdrawal
Conditions
Keywords
Cannabis Dependence, Marijuana Dependence, Cannabis Withdrawal, Rimonabant, cannabinoid receptor type 1 (CB1) inverse agonist, Neuropsychology, functional magnetic resonance imaging (fMRI), Endocannabinoids, Cortisol
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.
Interventions
DRUGrimonabant
double blind, placebo controlled, single 90 mg dose
DRUGplacebo
matched placebo
Sponsors
National Institute on Drug Abuse (NIDA)
The Scripps Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rimonabant Participants were cannabis dependent and received a single 90 mg dose of rimonabant at baseline visit. | 21 |
| Placebo Participants were cannabis dependent and received matched placebo. | 19 |
| Control Participants were non-cannabis using controls. | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | Rimonabant | Placebo | Control | Total |
|---|---|---|---|---|
| Age, Continuous | 22.33 years STANDARD_DEVIATION 1.53 | 23.53 years STANDARD_DEVIATION 2.76 | 24.15 years STANDARD_DEVIATION 2.83 | 23.32 years STANDARD_DEVIATION 2.51 |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Male | 15 Participants | 12 Participants | 14 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 23 | 10 / 23 | 4 / 20 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 20 |
Outcome results
Primary
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
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimonabant | 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 | -139.80 milliseconds | Standard Deviation 414.68 |
| Placebo | 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 | 420.24 milliseconds | Standard Deviation 2262.39 |
| Control | 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 | 22.01 milliseconds | Standard Deviation 1438.16 |
Primary
Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Strategy Score at 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.
Time frame: Day 0 and Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimonabant | Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Strategy Score at Day 28 | -2.67 units on a scale | Standard Deviation 4.15 |
| Placebo | Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Strategy Score at Day 28 | -1.37 units on a scale | Standard Deviation 5.16 |
| Control | Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Strategy Score at Day 28 | -1.50 units on a scale | Standard Deviation 3.62 |
Primary
Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Total Errors at 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.
Time frame: Day 0 and Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimonabant | Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Total Errors at Day 28 | -10.62 units on a scale | Standard Deviation 13.46 |
| Placebo | Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Total Errors at Day 28 | -1.95 units on a scale | Standard Deviation 11.43 |
| Control | Change From Day 0 in Performance on the Cambridge Neuropsychological Test Automated Batteries Spatial Working Memory (CANTAB SWM) Total Errors at Day 28 | -2.85 units on a scale | Standard Deviation 9.36 |
Primary
Plasma Cortisol
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimonabant | Plasma Cortisol | 27.36 ug/dL | Standard Deviation 15.03 |
| Placebo | Plasma Cortisol | 19.29 ug/dL | Standard Deviation 7.42 |
| Control | Plasma Cortisol | 22.72 ug/dL | Standard Deviation 15.21 |
Primary
Plasma Norepinephrine
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimonabant | Plasma Norepinephrine | 2.12 ng/mL | Standard Deviation 1.14 |
| Placebo | Plasma Norepinephrine | 2.04 ng/mL | Standard Deviation 1.05 |
| Control | Plasma Norepinephrine | 1.75 ng/mL | Standard Deviation 0.84 |
Primary
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
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimonabant | 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 | 6.62 units on a scale | Standard Deviation 5.59 |
| Placebo | 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 | 6.68 units on a scale | Standard Deviation 7.87 |
| Control | 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 | 1.05 units on a scale | Standard Deviation 2.39 |