A systematic review of ketamine's anxiolytic potential in rodent behavioral models of anxiety and PTSD.
Alena Lemeshova, Kaya A Patel, Alexander J Bloom, Lindsay Golan, Haney Haidari, Aiman Limbada, Cherish Zhao, Jennifer A. Honeycutt
Pharmacology, biochemistry, and behavior February 2026 DOI: 10.1016/j.pbb.2025.174144 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Rodent models of anxiety and post-traumatic stress disorder |
| Intervention | Ketamine |
| Dose | 10 to 30 mg/kg intraperitoneally |
| Topics | Anxiety Esketamine Ketamine PTSD |
| Key findings | The authors conclude that evidence suggests ketamine at 10 to 30 mg/kg intraperitoneally, with behavioral testing at least 24 hours later, produces anxiolytic effects in rodent deficit models, but that inconsistent methods and inadequate inclusion of female animals limit the clinical translatability of this research. |
Abstract
Ketamine, a nonselective NMDA-receptor antagonist, is an emerging therapeutic for treatment-resistant depression and could also be a promising treatment for anxiety and post-traumatic stress disorders. However, preclinical studies in these areas lack methodological standardization, limiting clinical translatability. This review evaluates ketamine's anxiolytic potential in rodents by examining outcomes among different animal models, dosages, and treatment timing. A PubMed search of studies published up to July 21, 2025, identified 562 articles assessing ketamine's effects on anxiety and PTSD in rodent models. After applying inclusion and exclusion criteria, 35 studies were analyzed. Key methodological variables, model type, dosage, and timing were summarized to assess consistency and effectiveness across studies. Current research on ketamine's anxiolytic potential in rodents is limited by inconsistent methods and inadequate sex inclusion. Evidence suggests that administering 10 to 30 mg/kg intraperitoneally and waiting ≥24 h before behavioral testing procedures produces anxiolytic effects, in deficit models. Future studies should include female subjects and standardized designs to enhance clinical translatability and relevance.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin Adults with PTSD | 2020 | Systematic review | n = 9 |
| The Multivariate Effect of Ketamine on PTSD: Systematic Review and Meta-Analysis Soldiers with combat experience, including wounded or burn soldiers | 2022 | Meta-analysis | n = 503 |
| Effectiveness of Ketamine for the Treatment of Post-Traumatic Stress Disorder - A Systematic Review and Meta-Analysis. Adults with post-traumatic stress disorder | 2024 | Systematic review and meta-analysis | |
| Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD. | 2025 | Systematic review | |
| Ketamine in the effective management of chronic pain, depression, and posttraumatic stress disorder for Veterans: A meta-analysis and systematic review. Military populations (active-duty and Veterans) | 2024 | Meta-analysis and systematic review |