Tezampanel for Opioid Withdrawal Syndrome

Inclusion Criteria: 1. Male, female or non-binary, age 18 to 65 years of age at Screening. 2. Diagnosis of Opioid Use Disorder (OUD) 3. Positive Urine Drug Screen (UDS) for opioid(s) at the Screening and Baseline Visits. 4. Recent active/chronic use of short-acting illicit and/or prescribed opioids and/or long-acting Opioid Use Disorder (OUD) maintenance treatments buprenorphine or methadone at the Screening and Baseline Visits. 5. Already engaged and fully assessed in a longitudinal-outpatient treatment program that provides opioid addiction treatment encompassing the full spectrum of opioid maintenance and abstinence (injectable Vivitrol®) treatments, in which the host clinic is prepared and equipped to continue with: 1. maintenance treatment (methadone or buprenorphine treatment) for study non-completers, or 2. long-acting injectable naltrexone treatment (Vivitrol®), for completers with next dose delivered approximately 30 days after Study Day 6. 6. Post-menopausal/sterile or agree to use chemical or barrier methods of birth control from time of informed consent through 30 days post last treatment. 7. Stable concomitant medications. 8. Stable concomitant medications for depression, post-traumatic stress disorder, psychotic disorders, and bipolar spectrum disorders if one of the following: SSRI, SNRI, bupropion, MAOI, trazodone, Tricyclic, typical and atypical antipsychotics, lithium, antihistamine, alpha-adrenergic agent, nicotine replacement. 9. Stable concomitant medications: propranolol, prazosin, and clonidine if used for psychiatric reasons, and not to control hypertension at the Baseline Visit and unchanged on Study Day 1. 10. Provide informed consent. 11. Understand and follow Lifestyle Considerations per protocol. Exclusion Criteria: 1. Clinically at risk or unstable due to: 1. Active psychosis or mania that is impairing insight, decision-making, perception, or ability to provide informed consent as assessed by the PI or designee during the Screening or Baseline Visits, discussion with the outpatient treatment provider, or at Study Day 1. 2. Active suicidal ideation or intent as assessed by the PI or designee during the Baseline Visit interview or the C-SSRS on Study Day 1. 3. Chronic benzodiazepine use, or at significant risk for, or in a state of benzodiazepine withdrawal at the Screening or Baseline Visits, Study Day 1, or in discussion with the outpatient treatment provider. 4. Alcohol Use Disorder as assessed by the PI or designee with \> 14 drinks / week (average of \> 2 / day) at the Screening or Baseline Visits or Study Day 1 or in discussion with the outpatient treatment provider. 5. Seizure disorder; use of anti-convulsant for bipolar disorder, seizure, or chronic pain (including topiramate, gabapentin, carbamazepine, valproic acid) at the Screening or Baseline Visits or Study Day 1. 6. Cardiac abnormalities including arrythmia, conduction abnormality or baseline QTC prolongation (QTcF \> 450 males; 470 females); pacemaker, history of myocardial infarction at the Baseline Visit. 7. Hypertension, diabetes mellitus, cancer, liver, and/or kidney disease and associated medications at the Screening or Baseline Visits or at Study Day 1. 2. Abnormal safety laboratory results. 3. ALT or AST \> 3xs upper limit of normal at Baseline or Study Day 1. 4. Undiagnosed hypertension defined as: 1. Baseline Visit: BP \> 160 / 100 mmHg or heart rate \> 120 bpm 2. Study Day 1: BP ≥ 180 / 120 mmHg or heart rate ≥ 140 bpm that continues after 10 minutes of rest. 5. Temperature \> 38.1°C at the Baseline Visit. Temperature \> 38.9°C at the Study Day 1. 6. Medications that stimulate the dopamine system pre- or post-synaptically, including L-Dopa, lisdexamfetamine, modafinil, gabapentin, phenobarbital, etc.) at the Screening or Baseline Visits or Study Day 1. 7. Medications for addiction, ADHD, insomnia, or bipolar spectrum disorders involving dopamine system stimulants, benzodiazepines, barbiturates, or mood stabilizers active via GABA or glutamate receptor system (e.g. valproic acid, lamotrigine, carbamazepine, acamprosate, disulfiram) at the Screening or Baseline Visits or Study Day 1. 8. Use of naltrexone or acamprosate (active at opioid or glutamatergic receptors) at the Screening or Baseline Visits or Study Day 1. 9. Significant, active infection (e.g., positive for syphilis, tuberculosis, COVID-19, HBV) at the Baseline Visit. 10. Symptomatic HIV or HCV (detectable viral load) at the Baseline Visit. 11. Pregnancy or breastfeeding at the Screening or Baseline Visits or Study Day 1. 12. Poor venous access at the Baseline Visit or Study Day 1. 13. Participation in a research study involving another investigational drug in the last 3 months at the Screening Visit.