NAB CAN: Nabilone for Cannabis Dependence: A Pilot Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Nabilone nabilone titrated to 2 mg daily |
Drug: Nabilone
nabilone titrated to 1 mg by mouth twice daily
Other Names:
|
| Placebo Comparator: Placebo Placebo |
Drug: Placebo
one placebo capsule by mouth twice daily
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
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 .
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | McLean Hospital | Belmont | Massachusetts | United States | 02478 |
Sponsors and Collaborators
- Mclean Hospital
- National Institute on Drug Abuse (NIDA)
Investigators
- Principal Investigator: Kevin P Hill, MD, MHS, Mclean Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.- 2010-P-000096
- 1K99DA029115-01
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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 |
| Arm/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) |
|---|---|---|---|---|
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily |
| Period Title: Overall Study | ||||
| STARTED | 10 | 8 | 16 | 18 |
| COMPLETED | 6 | 6 | 7 | 10 |
| NOT COMPLETED | 4 | 2 | 9 | 8 |
Baseline Characteristics
| Arm/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | Total of all reporting groups |
| Overall Participants | 10 | 8 | 16 | 18 | 52 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
24.40
(5.17)
|
28.88
(7.53)
|
27.81
(6.81)
|
28.11
(7.26)
|
27.42
(6.79)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
30%
|
3
37.5%
|
11
68.8%
|
11
61.1%
|
28
53.8%
|
| Male |
7
70%
|
5
62.5%
|
5
31.3%
|
7
38.9%
|
24
46.2%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
1
5.6%
|
1
1.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
30%
|
2
25%
|
6
37.5%
|
2
11.1%
|
13
25%
|
| White |
6
60%
|
6
75%
|
9
56.3%
|
15
83.3%
|
36
69.2%
|
| More than one race |
1
10%
|
0
0%
|
1
6.3%
|
0
0%
|
2
3.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Baseline Urine THC/Creatinine Ratio (Ratio) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Ratio] |
491.6
(283.0)
|
458.7
(568.9)
|
633.2
(728.5)
|
371.0
(265.4)
|
489.8
(496.1)
|
| Average Number of Inhales of Marijuana Per Day (Inhales per day) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Inhales per day] |
50.1
(43.8)
|
27.1
(13.2)
|
28.9
(31.8)
|
16.53
(29.13)
|
30.52
(33.65)
|
Outcome Measures
| Title | Change From Baseline in Cannabis Use at 10 Weeks |
|---|---|
| Description | Quantitative cannabis urine screens (THC-COOH:Creatinine ratio) |
| Time Frame | baseline and 10 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) |
|---|---|---|---|---|
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily |
| Measure Participants | 6 | 6 | 8 | 10 |
| Mean (Standard Deviation) [Ratio] |
268.8
(183.0)
|
286.7
(349.7)
|
490.3
(615.0)
|
216.9
(188.5)
|
| Title | Number of Marijuana Inhales Per Day |
|---|---|
| Description | Average # of marijuana inhales per day during baseline compared to after 10 weeks of treatment. |
| Time Frame | Week 10 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) |
|---|---|---|---|---|
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily |
| Measure Participants | 6 | 6 | 8 | 10 |
| Mean (Standard Deviation) [Inhales per day] |
33.8
(31.0)
|
22.6
(30.6)
|
15.8
(35.6)
|
10.6
(14.6)
|
| Title | Change From Baseline Neuropsychological Performance at 4 Weeks |
|---|---|
| Description | performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner |
| Time Frame | baseline and 4 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to funding and the principal investigator's change in institutions, this data was not analyzed and is no longer available to the investigator. |
| Arm/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) |
|---|---|---|---|---|
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Change From Baseline Cannabis Use at 14 Weeks |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) |
|---|---|---|---|---|
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily |
| Measure Participants | 6 | 6 | 8 | 10 |
| Mean (Standard Deviation) [Ratio] |
524.2
(466.2)
|
326.7
(403.7)
|
297.7
(291.8)
|
222
(186.53)
|
| Title | Change From Baseline in Neuropsychological Performance at 10 Weeks |
|---|---|
| Description | performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner |
| Time Frame | baseline and 10 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to funding and the principal investigator's change in institutions, this data was not analyzed and is no longer available to the investigator. |
| Arm/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) |
|---|---|---|---|---|
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily |
| Measure Participants | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | Adverse event data was collected from the time the subject was randomized up until the subject's last visit, this encompasses a total of 14 weeks per subject. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | During every visit (twice a week) a study staff member would ask the subject if they were experiencing any adverse events from the medication or participation in the study. Furthermore, during the weekly medication management session with the study physician, the physician asked and checked for adverse events as well | |||||||
| Arm/Group Title | Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) | ||||
| Arm/Group Description | nabilone titrated to 2 mg daily Nabilone: nabilone titrated to 1 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | nabilone titrated to 4 mg daily Nabilone: nabilone titrated to 2 mg by mouth twice daily | Placebo Placebo: one placebo capsule by mouth twice daily | ||||
All Cause Mortality |
||||||||
| Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/8 (0%) | 0/16 (0%) | 0/18 (0%) | ||||
Serious Adverse Events |
||||||||
| Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/8 (0%) | 0/16 (0%) | 0/18 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Nabilone Titrated 2 mg Daily (Phase 1) | Placebo (Phase 1) | Nabilone Titrated to 4 mg Daily (Phase 2) | Placebo (Phase 2) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/8 (0%) | 0/16 (0%) | 0/18 (0%) | ||||
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Kevin P. Hill, M.D., M.H.S., Principal Investigator |
|---|---|
| Organization | Beth Israel Deaconess Medical Center |
| Phone | 617 667 1597 |
| khill1@bidmc.harvard.edu |
- 2010-P-000096
- 1K99DA029115-01