Dronabinol Naltrexone Treatment for Opioid Dependence

The goal of this two-year study is to test the efficacy of dronabinol as an adjunct to
maintenance treatment with naltrexone in opioid-dependent individuals. We are proposing a
randomized, double-blind, placebo controlled, parallel-groups, 8 week study of relapse
prevention in opioid-dependent individuals. Participants will be randomized into one of two
conditions (1) Naltrexone and Placebo (N=20) and (2) Naltrexone and dronabinol 15 mg bid
(N=40). Treatment will be delivered in an outpatient setting except for the initial phase of
inpatient detoxification, lasting 8 days. A long-acting, injectable form of naltrexone 380 mg
(Vivitrol) will be administered once per month (the total of two injections), while
dronabinol or placebo will be taken daily. In addition, patients will receive a psychosocial
intervention that will include elements of motivational interviewing and cognitive-behavioral
relapse prevention therapy. The primary aim is to test the efficacy of dronabinol in
improving tolerability of naltrexone induction and reducing attrition during detoxification
and the first two months of naltrexone treatment. The primary outcome will be the severity of
opiate withdrawal and craving. The secondary outcome will be will be retention in treatment
at study's end.

Inclusion Criteria:

- 1. Adult, aged 18-60.

- 2. Meets Diagnostic and Statistical Manual -IV criteria for current opiate dependence
disorder of at least six months duration, supported by a positive urine for opiates
and a positive naloxone challenge test if the diagnosis is unclear.

- 3. Have a history of marijuana use (more than 30 occasions lifetime)

- 4. Voluntarily seeking treatment for opioid dependence

- 5. In otherwise good health based on complete medical history, physical examination,
vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry,
urinalysis) within normal ranges.

- 6. Able to give informed consent.

Exclusion Criteria:

- 1. Physiologically dependent on alcohol or sedative-hypnotics with impending
withdrawal.

- 2. Patients meeting current criteria for cannabis abuse or dependence, and those who
used cannabis in the week prior to study entry as documented by the positive
toxicology

- 3. Current Diagnostic and Statistical Manual -IV criteria of other substance use
disorders. Exceptions include cannabis abuse or dependence, nicotine dependence,
cocaine abuse or dependence, alcohol abuse or alcohol dependence without physiological
dependence as long as opioid dependence is a primary disorder. Alcohol dependence with
physiological dependence is exclusionary.

- 4. Significant current suicidal risk or 1 or more suicide attempts within the past
year

- 5. History of accidental drug overdose in the last three years defined as an episode
of opioid-induced unconsciousness or incapacitation, whether or not medical treatment
was sought or received.

- 6. Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory
method of birth control

- 7. Active psychiatric disorder which might interfere with participation or make
participation hazardous, including Diagnostic and Statistical Manual -IV organic
mental disorder, psychotic disorder, or bipolar disorder with mania

- 8. History of allergic reaction, adverse reaction, or sensitivity to any study
medication.

- 9. Acute hepatitis with serum glutamic-oxaloacetic transaminase or serum
glutamic-pyruvic transaminase > 3 times the upper end of the laboratory normal range
(chronic hepatitis is acceptable as we have found naltrexone treatment well tolerate
and safe among patients with chronic hepatitis)

- 10. Currently prescribed or regularly taking opiates for chronic pain or medical
illness.

- 11. Current participation in a methadone maintenance treatment program and/or regular
use of illicit methadone (>30 mg per week).

- 12. Current participation in another intensive psychotherapy or substance abuse
treatment program or participation in another treatment study.

- 13. Concurrent treatment with psychotropic medications