Cannabis Dependence, Marijuana Dependence
Conditions
Keywords
cannabis dependence, marijuana dependence, cannabis use disorders, cannabis withdrawal, nabilone
Brief summary
Cannabis use disorders are an important public health problem in the United States, but there are no effective medications available to treat these disorders. The investigators intend to test a medication with interesting properties, nabilone, as a treatment for cannabis dependence and to study the relationship of this treatment with the brain using functional MRI brain scans. Nabilone and marijuana have similar effects upon behaviors and the human body, suggesting that nabilone may decrease cannabis withdrawal symptoms while allowing treatment-seeking patients to benefit from behavioral treatments when they are trying to stop using cannabis. The investigators propose to assess the relationship of nabilone, when added to behavioral treatment, on cannabis use patterns in cannabis-dependent patients. The investigators also aim to determine the effects of nabilone on performance on neuropsychological tests and to assess the correlation of neuropsychological performance to brain changes using functional MRI brain scans. The investigators hypothesize that patients receiving nabilone will reduce their use of cannabis more than patients receiving placebo during this 10-week treatment trial.
Detailed description
Cannabis use disorders are an important public health problem in the United States, but no effective pharmacotherapies are available to treat these disorders. The investigators intend to test a novel agonist pharmacotherapy, nabilone, for cannabis dependence and to study the relationship of this treatment with the brain using BOLD fMRI measures. The behavioral and physiological effects of nabilone and Δ9-THC overlap, suggesting that nabilone may ameliorate cannabis withdrawal symptoms while allowing treatment-seeking outpatients to benefit from medical management (MM) sessions when they are trying to stop using cannabis. The investigators propose to assess the relationship of nabilone, when added to MM, on cannabis use patterns in cannabis-dependent patients. The investigators also aim to determine the effects of nabilone on performance on neuropsychological tests and to assess the correlation of neuropsychological performance to brain changes using BOLD fMRI measures. In this pilot study, subjects will receive either nabilone or placebo in addition to medical management (MM) over a 10-week treatment period. Subjects' responses to neuropsychological testing carried out while the subject is receiving fMRI scans at 3 time points: at baseline, 4 weeks, and 10 weeks. Following treatment completion, subjects will have a follow-up visit at 14 weeks. This pilot study will evaluate the feasibility of nabilone treatment for cannabis dependence and will establish effect sizes for a larger trial in which subjects will receive high-dose nabilone, low-dose nabilone, or placebo in addition to MM.
Interventions
DRUGNabilone
nabilone titrated to 1 mg by mouth twice daily
DRUGPlacebo
one placebo capsule by mouth twice daily
Sponsors
National Institute on Drug Abuse (NIDA)
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Age range 18-45 years * DSM-IV diagnosis of cannabis dependence, based on the Structured Clinical Interview for DSM-IV (SCID) * express a desire to quit cannabis use within the next 30 days * have used cannabis on more than4 days within the past 30 days * for women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests * consent for us to communicate with their prescribing clinician * furnish the names of 2 locators, who would assist study staff in locating them during the study period * live close enough to McLean Hospital to attend study visits * plan to stay in the Boston area for the next 3 months * are willing and able to sign informed consent.
Exclusion criteria
* current diagnosis of other drug or alcohol dependence (excluding nicotine) * recent (within 3 months) significant cardiac disease * current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder * current medical condition (including significant laboratory abnormalities, such as liver function tests \>5 times the upper limit of normal range) that could prevent regular study attendance * mental retardation or organic mental disorder * acutely dangerous or suicidal behavior * currently in a residential treatment setting in which substance use is monitored and restricted, since the restricted access to drugs could represent an important confounding variable * pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth control judged by the investigator to be effective * concomitant daily treatment with opioid analgesics, sedative hypnotics, or other known CNS depressants * known hypersensitivity to cannabinoids or sesame oil * disease of the gastrointestinal system, liver, or kidneys that may impede metabolism or excretion of nabilone * inability to read or write in English. The potential hazards of a Schedule II medication like nabilone underscore the importance of English proficiency in this medication trial. * unwilling or unable to participate in MRI scanning (e.g., those having pacemakers, bone plates, screws, etc.; claustrophobia) * a history of seizures, head trauma or other history of CNS insult that could predispose the subject to seizures .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cannabis Use at 10 Weeks | baseline and 10 weeks | Quantitative cannabis urine screens (THC-COOH:Creatinine ratio) |
| Number of Marijuana Inhales Per Day | Week 10 | Average # of marijuana inhales per day during baseline compared to after 10 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Neuropsychological Performance at 4 Weeks | baseline and 4 weeks | performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner |
| Change From Baseline Cannabis Use at 14 Weeks | baseline and 14 weeks | quantitative urine screens - Comparing the THC-COOH to creatinine ratio at baseline and at the end of the study (Week 14) |
| Change From Baseline in Neuropsychological Performance at 10 Weeks | baseline and 10 weeks | performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner |
Countries
United States
Participant flow
Pre-assignment details
14 potential subjects were screened but did not qualify for Phase 1 and 18 for Phase 2. Reasons included: positive urine screen for opiates or cocaine, lost to follow up after screening visit, withdrew from the study due to time constraints before randomization, met criteria for alcohol dependence or did not test positive for THC urine screen
Participants by arm
| Arm | Count |
|---|---|
| Nabilone Titrated 2 mg Daily (Phase 1) nabilone titrated to 2 mg daily
Nabilone: nabilone titrated to 1 mg by mouth twice daily | 10 |
| Placebo (Phase 1) Placebo
Placebo: one placebo capsule by mouth twice daily | 8 |
| Nabilone Titrated to 4 mg Daily (Phase 2) nabilone titrated to 4 mg daily
Nabilone: nabilone titrated to 2 mg by mouth twice daily | 16 |
| Placebo (Phase 2) Placebo
Placebo: one placebo capsule by mouth twice daily | 18 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 6 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 3 | 3 |
Baseline characteristics
| Characteristic | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 24.40 years STANDARD_DEVIATION 5.17 | 28.88 years STANDARD_DEVIATION 7.53 | 27.81 years STANDARD_DEVIATION 6.81 | 28.11 years STANDARD_DEVIATION 7.26 | 27.42 years STANDARD_DEVIATION 6.79 |
| Average Number of Inhales of Marijuana Per Day | 50.1 Inhales per day STANDARD_DEVIATION 43.8 | 27.1 Inhales per day STANDARD_DEVIATION 13.2 | 28.9 Inhales per day STANDARD_DEVIATION 31.8 | 16.53 Inhales per day STANDARD_DEVIATION 29.13 | 30.52 Inhales per day STANDARD_DEVIATION 33.65 |
| Baseline Urine THC/Creatinine Ratio | 491.6 Ratio STANDARD_DEVIATION 283 | 458.7 Ratio STANDARD_DEVIATION 568.9 | 633.2 Ratio STANDARD_DEVIATION 728.5 | 371.0 Ratio STANDARD_DEVIATION 265.4 | 489.8 Ratio STANDARD_DEVIATION 496.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 6 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 9 Participants | 15 Participants | 36 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 11 Participants | 11 Participants | 28 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 5 Participants | 7 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 | 0 / 16 | 0 / 18 |
| other Total, other adverse events | 0 / 10 | 0 / 8 | 0 / 16 | 0 / 18 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 16 | 0 / 18 |
Outcome results
Primary
Change From Baseline in Cannabis Use at 10 Weeks
Quantitative cannabis urine screens (THC-COOH:Creatinine ratio)
Time frame: baseline and 10 weeks
Population: Fewer participants had their THC:creatinine ratios analyzed than were randomized due to a high number of subject drop-out. Any subject who dropped out before completing the 10 weeks of treatment were not analyzed using this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nabilone Titrated 2 mg Daily (Phase 1) | Change From Baseline in Cannabis Use at 10 Weeks | 268.8 Ratio | Standard Deviation 183 |
| Placebo (Phase 1) | Change From Baseline in Cannabis Use at 10 Weeks | 286.7 Ratio | Standard Deviation 349.7 |
| Nabilone Titrated to 4 mg Daily (Phase 2) | Change From Baseline in Cannabis Use at 10 Weeks | 490.3 Ratio | Standard Deviation 615 |
| Placebo (Phase 2) | Change From Baseline in Cannabis Use at 10 Weeks | 216.9 Ratio | Standard Deviation 188.5 |
Primary
Number of Marijuana Inhales Per Day
Average # of marijuana inhales per day during baseline compared to after 10 weeks of treatment.
Time frame: Week 10
Population: Fewer participants had their average number of inhales per day analyzed than were randomized due to a high number of subject drop-out. Any subject who dropped out before completing the 10 weeks of treatment were not analyzed using this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nabilone Titrated 2 mg Daily (Phase 1) | Number of Marijuana Inhales Per Day | 33.8 Inhales per day | Standard Deviation 31 |
| Placebo (Phase 1) | Number of Marijuana Inhales Per Day | 22.6 Inhales per day | Standard Deviation 30.6 |
| Nabilone Titrated to 4 mg Daily (Phase 2) | Number of Marijuana Inhales Per Day | 15.8 Inhales per day | Standard Deviation 35.6 |
| Placebo (Phase 2) | Number of Marijuana Inhales Per Day | 10.6 Inhales per day | Standard Deviation 14.6 |
Secondary
Change From Baseline Cannabis Use at 14 Weeks
quantitative urine screens - Comparing the THC-COOH to creatinine ratio at baseline and at the end of the study (Week 14)
Time frame: baseline and 14 weeks
Population: Fewer participants had their THC:creatinine ratios analyzed than were randomized due to a high number of subject drop-out. Any subject who dropped out before completing the 10 weeks of treatment were not analyzed using this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nabilone Titrated 2 mg Daily (Phase 1) | Change From Baseline Cannabis Use at 14 Weeks | 524.2 Ratio | Standard Deviation 466.2 |
| Placebo (Phase 1) | Change From Baseline Cannabis Use at 14 Weeks | 326.7 Ratio | Standard Deviation 403.7 |
| Nabilone Titrated to 4 mg Daily (Phase 2) | Change From Baseline Cannabis Use at 14 Weeks | 297.7 Ratio | Standard Deviation 291.8 |
| Placebo (Phase 2) | Change From Baseline Cannabis Use at 14 Weeks | 222 Ratio | Standard Deviation 186.53 |
Secondary
Change From Baseline in Neuropsychological Performance at 10 Weeks
performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner
Time frame: baseline and 10 weeks
Population: Due to funding and the principal investigator's change in institutions, this data was not analyzed and is no longer available to the investigator.
Secondary
Change From Baseline Neuropsychological Performance at 4 Weeks
performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner
Time frame: baseline and 4 weeks
Population: Due to funding and the principal investigator's change in institutions, this data was not analyzed and is no longer available to the investigator.