Ketamine-From an Anesthetic to a Psychiatric Drug: Mechanisms of Action, Clinical Applications and Potential Risks.
Ewa Gibuła-Tarłowska, Anna Wiszniewska, Magdalena Turyk, Paulina Szymczyk, Jolanta H Kotlińska, Ewa Kędzierska
Molecules June 30, 2025 DOI: 10.3390/molecules30132824 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Ketamine S-ketamine |
| Topics | Addiction Depression Ketamine Esketamine |
| Keywords | Anesthesia Mental health treatment Pain management Medical innovation |
| Citations | 10 |
| Key findings | Ketamine demonstrates multifaceted therapeutic effects, including analgesia, potential treatment for substance use disorder, and rapid antidepressant action in treatment-resistant depression. |
Abstract
Ketamine, originally developed as an anesthetic, is gaining increasing attention due to its multifaceted pharmacological properties. In addition to its use in anesthesia, ketamine exerts potent analgesic effects via N-methyl-D-aspartate (NMDA) receptor antagonism, modulating pain perception and reducing central sensitization, particularly in chronic and neuropathic pain conditions. Emerging evidence also supports ketamine's potential in the treatment of substance use disorder, where it may disrupt maladaptive reward-related memories and promote neuroplasticity which facilitates behavioral change. Moreover, in recent years, S-ketamine has shown rapid and potent antidepressant effects, especially in treatment-resistant depression (TRD), probably due to increased glutamatergic signaling, synaptic plasticity and the release of neurotrophic factors. This heterogeneous therapeutic profile positions ketamine as a unique agent at the interface of anesthesia, pain management, addiction medicine and psychiatry, warranting further exploration into its mechanism and long-term effectiveness.
Comparable studies
Other narrative reviews on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| Can psychedelic compounds play a part in drug dependence therapy? Patients with substance dependency | 2015 | Review | |
| Therapeutic potential of ketamine for alcohol use disorder. | 2021 | Review | |
| Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing | 2022 | Review | |
| Ketamine, an Old–New Drug: Uses and Abuses | 2023 | Review |
Citations in the library
Cited by 9
- Integrating multi-receptor and neuron–glia mechanisms of ketamine's antidepressant action: a convergence framework for understanding efficacy Frontiers in Molecular Neuroscience October 21, 2026
- Ketamine for substance use disorders: a systematic review and meta-analysis Frontiers in Psychiatry July 17, 2026
- Treating addiction with an addictive drug: the ketamine paradox revisited Frontiers in Psychiatry July 9, 2026
- A novel sequential ketamine and D-cycloserine/lurasidone therapy for bipolar depression with acute suicidal ideation. Expert Opinion on Investigational Drugs May 26, 2026
- Neuroscientific Basis of Ketamine as an Analgesic and Emerging Role in the Management of Depression. Current Pain and Headache Reports April 21, 2026
and 4 more in the library
Cites 50
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 45 more in the library