Buprenorphine as Adjunct to Outpatient Induction Onto Vivitrol

Procedure 1: 5-day induction with increasing doses of oral naltrexone. Participants will
receive XR-NTX on day five together with buprenorphine, and will continue receiving
buprenorphine for 4 weeks until they receive 2nd XR-NTX dose.

Procedure 2: 10-day induction with buprenorphine administered daily and increasing daily
doses of oral naltrexone beginning on day 2 . On day 10 participants will receive XR-NTX
dose, and another one 4 weeks later. No buprenorphine will be given beyond day 10.

Procedure 3: 10-day induction with buprenorphine administered daily and increasing daily
doses of oral naltrexone beginning on day 2 . On day 10 participants will receive XR-NTX
dose, and another one 4 weeks later. Buprenorphine will continue for 4 weeks until the 2nd
XR-NTX dose.

All participants will receive weekly therapy with a study psychiatrist. All participants will
receive open-label medication.

Inclusion Criteria:

1. Age 18-60.

2. Meets DSM-5 criteria for current opioid use disorder (moderate-severe) of at least six
months duration, supported by urine toxicology OR COWS score > or =6 OR Naloxone
Challenge.

3. Voluntarily seeking treatment for opioid dependence.

4. In otherwise good health based on complete medical history and physical examination
within normal ranges (AST or ALT < 3 times normal). )

5. Able to give written informed consent.

Exclusion Criteria:

1. Methadone maintenance treatment or regular use of illicit methadone (> 30 mg per
week).

2. Maintenance on, or regular use of buprenorphine or other long-acting narcotic
agonists.

3. Pregnancy, lactation, or failure in a sexually active woman to use adequate
contraceptive methods.

4. Active medical illness which might make participation hazardous, such as untreated
hypertension, acute hepatitis with AST or ALT > 3 times normal, AIDS (CD4 count under
200 currently or medically ill with an opportunistic infection), unstable diabetes.

5. Active psychiatric disorder which might interfere with participation or make
participation hazardous, including DSM-5 Schizophrenia or any psychotic disorder,
severe Major Depressive Disorder, or suicide risk or 1 or more suicide attempts within
the past year.

6. Physiologically dependent on alcohol or sedative- hypnotics with impending withdrawal.
Other substance use diagnoses are not exclusionary.

7. History of allergic or adverse reaction to buprenorphine, naltrexone, naloxone,
clonidine, or clonazepam.

8. Chronic organic mental disorder (e.g. AIDS (CD4 count under 200 currently or medically
ill with an opportunistic infection) dementia).

9. History of accidental drug overdose in the last 3 years as defined as an episode of
opioid-induced unconsciousness or incapacitation, whether or not medical treatment was
sought or received.

10. Painful medical condition that requires ongoing opioid analgesia or anticipated
surgery necessitating opioid medications.