Inclusion Criteria:  Individuals between the ages of 18-65 (inclusive) interested in antagonist-based relapse prevention treatment Meets current DSM-5 criteria for current opioid use disorder of at least six months duration supported by urine toxicology positive for opioids OR naloxone challenge if seeking detoxification and XR-NTX induction OR confirmed recent detoxification treatment for opioids. 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. Participants with active opioid use and those who recently completed detoxification and received XR-NTX are eligible for the study. Participants may be enrolled before initial XR-NTX injection or up to 2 weeks following an initial XR-NTX injection given in any outside research or community-based treatment setting (inpatient, outpatient residential). However, participants who had 30 or more opioid-free days prior to consent will not be eligible for study inclusion. Voluntarily seeking treatment for opioid use disorder. Able to give written informed consent to participate in the study and showing a thorough understanding of the difference between agonist and antagonist-based treatment.  Exclusion Criteria:  Methadone maintenance or any use of illicit methadone in the week prior to XR-NTX induction. Maintenance on buprenorphine or frequent buprenorphine use in the week prior to XR-NTX induction (must be using no more than 8 mg of buprenorphine per day and no more than 3 days per week). Active medical illness which might make participation hazardous, such as untreated hypertension, acute hepatitis with AST/ALT> 3 times normal, AIDS (CD4 count under 200 or medically ill), unstable diabetes or unstable heart disease. Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-5 Schizophrenia or any psychotic disorder, severe Major Depressive Disorder, chronic Neurocognitive Disorder, or suicide risk or 1 or more suicide attempts within the past year Pregnancy, lactation, or a plan of becoming pregnant. Women need to have negative blood pregnancy test at screening and agree to practice dual contraceptives. Physiological dependence on alcohol or sedative-hypnotics with impending withdrawal. Other substance use diagnoses are not exclusionary. History of allergic or adverse reaction to buprenorphine, naltrexone, naloxone, clonidine, or clonazepam. History of accidental drug overdose in the prior 6 months defined as an episode of opioid-induced unconsciousness, whether or not medical treatment was sought or received. Painful medical condition that requires ongoing opioid analgesia or anticipated surgery necessitating opioid medications.