Nabilone for Cannabis Dependence: A Pilot Study

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.

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 .