Cannabidiol Pharmacotherapy for Adults With Cannabis Use Disorder

Investigators will conduct a Stage 1 pilot feasibility study at McLean Hospital to begin to
evaluate Epidiolex as a pharmacotherapy for adults with cannabis use disorder. In this
randomized, double-blind, placebo-controlled trial, cannabis-dependent subjects ages 18-65
will receive medical management over a 6-week period, with half receiving Epidiolex treatment
and half receiving placebo. Participants will receive either up to 800 mg Epidiolex or
placebo over a 6-week treatment period. Following treatment completion, participants will
have a follow-up visits at 10 and 14 weeks. Primary outcomes will include self-report of
cannabis smoking and results of quantitative urine drug screens for cannabis. Secondary
outcome measures will include treatment retention, patient satisfaction, cannabis withdrawal,
cannabis craving, depressive symptoms, anxiety symptoms, compliance, and cigarette use.

Inclusion Criteria:

- Age range 18-65 years

- DSM 5 diagnosis of cannabis use disorder, based on the Structured Clinical Interview
for DSM 5 (SCID-5)

- Express a desire to quit cannabis use within the next 30 days

- Have used cannabis on ≥4 days within the past 30 days (i.e., an average of ≥1 day per
week)

- For women of childbearing age, a negative pregnancy test at screening with agreement
to use adequate contraception to prevent pregnancy and monthly pregnancy tests; for
men, contraception will be discussed at the beginning of the study with the study
physician

- 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
abnormal liver function tests) 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 CBD

- Inability to read or write in English

- History of seizures, head trauma or other history of CNS insult that could predispose
the subject to seizures

- Currently taking valproic acid, lamotrigine, or propranolol, medication metabolized by
UGT1A9 or UGT2B7 enzymes (CBD may affect these UGT levels)