Nabilone for Cannabis Dependence: A Pilot Study (NAB CAN)

• ClinicalTrials.gov Identifier: NCT01347762
• Recruitment Status: Completed
• First Posted: May 4, 2011
• Results First Posted: June 1, 2018
• Last Update Posted: June 1, 2018
• Sponsor: Mclean Hospital
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Kevin P. Hill, MD, MHS, Mclean Hospital

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
Cannabis Dependence; Marijuana Dependence	Drug: Nabilone; Drug: Placebo	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Nabilone for Cannabis Dependence: A Pilot Study
• Study Start Date: June 2010
• Actual Primary Completion Date: June 9, 2017
• Actual Study Completion Date: June 9, 2017

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 Name: Nabilone (Cesamet), CSA Drug Code 7379, Schedule II, NDC 0037-1221-50
Placebo Comparator: Placebo; Placebo	Drug: Placebo; one placebo capsule by mouth twice daily

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Cannabis Use at 10 Weeks [ Time Frame: baseline and 10 weeks ]
   Quantitative cannabis urine screens (THC-COOH:Creatinine ratio)
2. Number of Marijuana Inhales Per Day [ Time Frame: Week 10 ]
   Average # of marijuana inhales per day during baseline compared to after 10 weeks of treatment.

Secondary Outcome Measures :

1. Change From Baseline Neuropsychological Performance at 4 Weeks [ Time Frame: baseline and 4 weeks ]
   performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner
2. Change From Baseline Cannabis Use at 14 Weeks [ Time Frame: 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)
3. Change From Baseline in Neuropsychological Performance at 10 Weeks [ Time Frame: baseline and 10 weeks ]
   performance on neuropsychological tests administered inside of the fMRI scanner and outside of the fMRI scanner

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

United States, Massachusetts

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)

Documents provided by Kevin P. Hill, MD, MHS, Mclean Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] April 14, 2017

More Information

• Responsible Party: Kevin P. Hill, MD, MHS, Psychiatrist-In-Charge, Mclean Hospital
• ClinicalTrials.gov Identifier: NCT01347762
• Other Study ID Numbers: 2010-P-000096; 1K99DA029115-01 ( U.S. NIH Grant/Contract )
• First Posted: May 4, 2011
• Results First Posted: June 1, 2018
• Last Update Posted: June 1, 2018
• Last Verified: May 2018

Keywords provided by Kevin P. Hill, MD, MHS, Mclean Hospital:

cannabis dependence; marijuana dependence; cannabis use disorders; cannabis withdrawal; nabilone

Additional relevant MeSH terms:

Marijuana Abuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Nabilone; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs