The incidence of opioid use disorders (OUDs) has increased to near-epidemic proportions. While maintenance with long-acting opioids such as methadone or buprenorphine represents an effective treatment strategy, it may be unacceptable to many individuals. As a result, long-acting injectable naltrexone (XR-NTX), an antagonist medication that blocks the effects of opioids for at least 4 weeks, is now indicated for relapse prevention following detoxification. This randomized, controlled trial aims to test the efficacy of a glutamate modulator at facilitating a rapid non-opioid based naltrexone induction.

This study combines a nonopioid detoxification; a naltrexone titration schedule that allows for pushing the dose rapidly while monitoring closely to ensure tolerability; and infusions integrated into the treatment in such a way as to potentially ameliorate spontaneous and precipitated withdrawal. The first part of the treatment trial involves receiving inpatient treatment for up to 5 days. Following week 1, participants will meet with staff twice weekly and receive 12 weeks of mindfulness based relapse prevention and motivational interviewing sessions.

Inclusion Criteria:

1. DSM-5 criteria of current opioid use disorder present for at least six months, supported by a positive urine for opioids or a positive naloxone challenge test
2. Aged 18 to 70 years
3. 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
4. Able to give written informed consent to participate in the study
5. Interested in maintenance treatment with extended-release naltrexone

Exclusion Criteria:

1. Physiologically dependent on alcohol or sedative-hypnotics with impending withdrawal requiring medical management
2. Methadone maintenance treatment or regular use of illicit methadone (>30 mg per week); urine toxicology positive for methadone at admission
3. Buprenorphine maintenance treatment or regular use of buprenorphine (>16 mg per week); urine toxicology positive for buprenorphine at admission
4. Active, or past, psychiatric disorder(s) which might interfere with participation or make participation hazardous, including DSM-V mental disorder due to another medical condition, major depressive disorder, psychotic disorder, or bipolar disorder with psychotic features
5. Significant current suicidal risk or a suicide attempt within the past year
6. On psychotropic or other medications that may interact adversely with study medications, or whose effect might be disrupted by study medications
7. For women of childbearing potential: positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control
8. Unstable physical disorders which might make participation hazardous such as hypertension (>160/90), anemia, active hepatitis or other liver disease (transaminase levels < 2-3 X the upper limit of normal will be considered acceptable), or untreated diabetes. Participants reporting HIV+ status will be asked to provide information about their current treatment, including all medications. Participants who are on the antiretroviral ritonavir (Norvir) will be excluded due to the possibility that the study medications in combination with this medication may increase the risk of drug-induced hepatitis
9. Acute hepatitis with SGOT or SGPT > 3 times the upper end of the laboratory normal range
10. Concurrent participation in another treatment study or another substance abuse program with the exception of a self-help group
11. History of allergy or sensitivity to any study medication
12. Ongoing chronic pain that may require opioid management, or for which surgery is indicated
13. History of inability to tolerate study medications
14. History of a use disorder with the study medications