Ketamine and Hydroxynorketamine as Novel Pharmacotherapies for the Treatment of Opioid Use Disorders.
Anna Onisiforou, Andria Michael, Markos Apostolakis, Elmar Mammadov, Angeliki Mitka, Maria A Kalatta, Morfeas Koumas, Andrea Georgiou, Andreas Chatzittofis, Georgia Panayiotou, Polymnia Georgiou, Carlos A Zarate, Panos Zanos
Biological psychiatry March 15, 2025 DOI: 10.1016/j.biopsych.2024.09.008 via PubMed
Summary
Opioid use disorder (OUD) has reached epidemic levels, and current medications, while lifesaving, fail to address negative affect and cognitive impairment, leading to high relapse rates even years after drug cessation. Ketamine, an anesthetic and rapid-acting antidepressant, shows promise for treating OUD, including managing acute withdrawal symptoms, negative affect during protracted abstinence, and preventing return to opioid use. This review examines preclinical and clinical research on ketamine and its metabolites as novel therapeutic strategies. Evidence demonstrates that ketamine and its metabolites can modulate pathophysiological processes in OUD, suggesting a promising role in treatment and relapse prevention.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction Ketamine |
| Keywords | Hydroxynorketamine Opioid crisis Opioid use disorders Relapse Addiction treatment |
| Citations | 14 |
| Key finding | Ketamine and its metabolites can effectively modulate pathophysiological processes in opioid use disorder, suggesting a promising therapeutic role in treatment and prevention of return to opioid use during abstinence. |
Abstract
Opioid use disorder (OUD) has reached epidemic proportions, with many countries facing high levels of opioid use and related fatalities. Although currently prescribed medications for OUD are considered lifesaving, they inadequately address negative affect and cognitive impairment, resulting in high relapse rates to nonmedical opioid use even years after drug cessation (protracted abstinence). Evidence supports the notion that ketamine, an anesthetic and rapid-acting antidepressant drug, holds promise as a candidate for OUD treatment, including the management of acute withdrawal somatic symptoms, negative affect during protracted opioid abstinence, and prevention of retaking nonmedical opioids. In this review, we comprehensively discuss preclinical and clinical research that has evaluated ketamine and its metabolites as potential novel therapeutic strategies for treating OUD. Furthermore, we examine evidence that supports the relevance of the molecular targets of ketamine and its metabolites in relation to their potential effects and therapeutic outcomes in OUD. Overall, existing evidence demonstrates that ketamine and its metabolites can effectively modulate pathophysiological processes affected in OUD, suggesting a promising therapeutic role in the treatment of OUD and the prevention of return to opioid use during abstinence.