May 2026
Ketamine
What May 2026's 25 new studies found, synthesized from the papers below. All Ketamine research →
The synthesis
Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below
Found by searching the library for Ketamine, esketamine, arketamine, then ranked by relevance.
Research on ketamine in May 2026 shows it can provide rapid antidepressant and anti-suicidal effects, especially in treatment-resistant depression, but its superiority over active placebo (midazolam) is questioned due to blinding failures and small sample sizes. Evidence is mixed on long-term safety and optimal dosing, with some studies highlighting neurotoxic risks and others showing cognitive preservation. The main caveat is that many findings are preliminary, based on small samples, or limited by short follow-up.
Evidence by study
Direction is which way each study's own result points, not our rating of the study.
What the directions mean
- Supports:
- the study found the intervention worked, or its hypothesis held.
- Opposes:
- it found the opposite, no benefit or a harm.
- No effect:
- no significant difference either way.
- Mixed:
- effects in both directions within the same study.
- Unclear:
- the abstract does not report a direction.
| Study | Design | Sample size | Direction | Finding |
|---|---|---|---|---|
| Microbiota-Derived SCFAs Mediate the Synergistic Antidepressant Effects of Dajianzhong Decoction and Ketamine via FFAR2-NLRP3-IL-1β Signaling. 2026 | preclinical | Supports | Combined Dajianzhong Decoction and ketamine reversed depressive-like behaviors in mice via SCFA-FFAR2-NLRP3-IL-1β signaling. | |
| Preliminary Non-Randomized Clinical Trial of Subcutaneous Esketamine in Treatment-Resistant Depression: Exploring Adjunctive Effects of Ketamine-Assisted Psychotherapy 2026 | non-randomized clinical trial | Unclear | The study explores adjunctive ketamine-assisted psychotherapy for TRD but provides no conclusive results. | |
| Safety and tolerance of oral ketamine: A systematic review. 2026 | systematic review | 427 | Supports | Oral ketamine in depression studies (n=5, 427 participants) showed predominantly mild and transient adverse effects. |
| The Use of Ketamine for Depression in Cancer Patients: A Systematic Review of Efficacy, Safety, and Clinical Applications. 2026 | systematic review | Supports | Ketamine provided rapid relief from depressive symptoms in cancer patients, with additional benefits in anxiety and pain, but long-term safety data were limited. | |
| Ketamine: Is It Superior to Midazolam for Depression? 2026 | RCT | 63 | No effect | Serial intravenous ketamine was not significantly more effective than midazolam in reducing depressive symptoms, with high unblinding rates (78% patients, 90% raters). |
| Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review 2026 | systematic review | Mixed | Ketamine and esketamine have both structural neurotoxic and neuroprotective effects. | |
| A novel sequential ketamine and D-cycloserine/lurasidone therapy for bipolar depression with acute suicidal ideation. 2026 | review | Unclear | A sequential ketamine and D-cycloserine/lurasidone therapy is proposed for bipolar depression with suicidal ideation, but uncertainties remain about efficacy and optimal dosing. | |
| Pharmacological modulation of anxiety-like behavior by flumazenil, midazolam, and ketamine in rats: Evidence from aversive ultrasonic vocalizations and elevated plus maze. 2026 | preclinical | Unclear | Pharmacological modulation of anxiety-like behavior by flumazenil, midazolam, and ketamine in rats was studied, but direction is unclear from abstract. | |
| The Effect of Different Doses of Ketamine on Postoperative Hallucination: A Cross-Sectional Study 2026 | cross-sectional | 62 | Supports | Higher doses of ketamine were associated with increased postoperative hallucinations, with dose-dependent effects. |
| Pharmacotherapeutic Options in Drug-Resistant Bipolar Depression: From Molecular Mechanisms to Rational Polypharmacotherapy. 2026 | review | Supports | Ketamine is discussed as a promising augmentation strategy for drug-resistant bipolar depression, with limited efficacy of atypical neuroleptics. | |
| Shorter to be effective: subanesthetic-dose ketamine infusion reduces the global and regional path length of brain functional connectivity in patients with treatment-resistant depression and suicidal ideation. 2026 | observational | Supports | Subanesthetic-dose ketamine infusion reduced global and regional path length of brain functional connectivity in TRD patients with suicidal ideation. | |
| Early suicidal ideation change and suicidality-associated emergency department utilization after ketamine or esketamine treatment in treatment-resistant depression. 2026 | observational | Supports | Early suicidal ideation change and reduced emergency department utilization were observed after ketamine or esketamine treatment in TRD. | |
| Treatment-emergent psychiatric adverse events in patient-reported outcomes during ketamine use for major depressive disorder: a retrospective analysis. 2026 | retrospective | Mixed | Treatment-emergent psychiatric adverse events were reported in patient-reported outcomes during ketamine use for MDD. | |
| Effect of ketamine intervention on hemodynamic responses in patients with treatment-resistant depression. 2026 | RCT | 45 | Supports | Ketamine significantly altered hemodynamic responses in brain regions associated with sensory-cognitive integration and mood regulation, linked to improvements in suicidal ideation. |
| Corrigendum to "Intranasal esketamine in treatment-resistant depression: long-term dosing patterns and clinical outcomes in a 5-year observational study". 2026 | corrigendum | Unclear | Corrigendum to a 5-year observational study on intranasal esketamine dosing patterns and clinical outcomes; no new findings. | |
| Beyond the High: A Narrative Review of the Chronic Complications of Recreational Ketamine Use. 2026 | narrative review | Opposes | Chronic recreational ketamine use is associated with urological, neurological, neuropsychiatric, and hepatobiliary complications. | |
| Short-term effects of oral ketamine for the treatment of depression: A systematic review and meta-analysis of randomized controlled trials. 2026 | systematic review and meta-analysis | Supports | Short-term effects of oral ketamine for depression were evaluated, showing positive results. | |
| Interdisciplinary, Delphi-driven consensus guidelines on the use of intravenous ketamine infusions for depressive disorders from the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3). 2026 | consensus guidelines | Supports | Interdisciplinary Delphi-driven consensus guidelines on intravenous ketamine infusions for depressive disorders were developed. | |
| Toward Integrating Intranasal Esketamine with Traumatic-Memory Psychotherapy in Treatment-Resistant Depression: A Narrative Review and Feasibility-Oriented Protocol Proposal. 2026 | narrative review | Unclear | Integration of intranasal esketamine with traumatic-memory psychotherapy is proposed, but evidence is mainly from pilot studies and case reports. | |
| Changes in depression symptom network structure following ketamine treatment in treatment-resistant depression. 2026 | observational | Supports | Changes in depression symptom network structure were observed following ketamine treatment in TRD. | |
| [Ketamine and esketamine in treatment-resistant depression - Pharmacological effects and augmented psychotherapy]. 2026 | review | Mixed | Esketamine nasal spray is approved for TRD, but dissociative effects and functional unblinding are methodological concerns; ketamine-augmented psychotherapy is proposed. | |
| Structural imaging predictors of ketamine response in treatment-resistant depression: a machine learning approach. 2026 | observational | 99 | Supports | A machine learning model using structural MRI predicted ketamine response with 72.2% balanced accuracy; greater frontal gray matter volume predicted response. |
| Suicidal Ideation Effectiveness and Safety Outcomes from the Ketamine for Adult Depression Study (KADS). 2026 | RCT | 174 | Mixed | Subcutaneous ketamine showed beneficial effects on suicidal ideation in flexible-dose cohort (C-SSRS significant), but fixed-dose cohort showed no significant difference versus midazolam. |
| Cognitive effects of intravenous Ketamine in treatment-resistant depression: A systematic review. 2026 | systematic review | Supports | IV ketamine preserved and enhanced specific cognitive functions (processing speed, working memory) in TRD, with no cognitive deterioration reported. | |
| Announcement of special issue: ‘Behavioural pharmacology of ketamine and psychedelic drugs’ 2026 | announcement | Unclear | Announcement of a special issue on behavioural pharmacology of ketamine and psychedelic drugs; no empirical findings. |
Combined Dajianzhong Decoction and ketamine reversed depressive-like behaviors in mice via SCFA-FFAR2-NLRP3-IL-1β signaling.
preclinical
The study explores adjunctive ketamine-assisted psychotherapy for TRD but provides no conclusive results.
non-randomized clinical trial
Oral ketamine in depression studies (n=5, 427 participants) showed predominantly mild and transient adverse effects.
systematic review Sample size: 427
Ketamine provided rapid relief from depressive symptoms in cancer patients, with additional benefits in anxiety and pain, but long-term safety data were limited.
systematic review
Serial intravenous ketamine was not significantly more effective than midazolam in reducing depressive symptoms, with high unblinding rates (78% patients, 90% raters).
RCT Sample size: 63
Ketamine and esketamine have both structural neurotoxic and neuroprotective effects.
systematic review
A sequential ketamine and D-cycloserine/lurasidone therapy is proposed for bipolar depression with suicidal ideation, but uncertainties remain about efficacy and optimal dosing.
review
Pharmacological modulation of anxiety-like behavior by flumazenil, midazolam, and ketamine in rats was studied, but direction is unclear from abstract.
preclinical
Higher doses of ketamine were associated with increased postoperative hallucinations, with dose-dependent effects.
cross-sectional Sample size: 62
Ketamine is discussed as a promising augmentation strategy for drug-resistant bipolar depression, with limited efficacy of atypical neuroleptics.
review
Subanesthetic-dose ketamine infusion reduced global and regional path length of brain functional connectivity in TRD patients with suicidal ideation.
observational
Early suicidal ideation change and reduced emergency department utilization were observed after ketamine or esketamine treatment in TRD.
observational
Treatment-emergent psychiatric adverse events were reported in patient-reported outcomes during ketamine use for MDD.
retrospective
Ketamine significantly altered hemodynamic responses in brain regions associated with sensory-cognitive integration and mood regulation, linked to improvements in suicidal ideation.
RCT Sample size: 45
Corrigendum to a 5-year observational study on intranasal esketamine dosing patterns and clinical outcomes; no new findings.
corrigendum
Chronic recreational ketamine use is associated with urological, neurological, neuropsychiatric, and hepatobiliary complications.
narrative review
Short-term effects of oral ketamine for depression were evaluated, showing positive results.
systematic review and meta-analysis
Interdisciplinary Delphi-driven consensus guidelines on intravenous ketamine infusions for depressive disorders were developed.
consensus guidelines
Integration of intranasal esketamine with traumatic-memory psychotherapy is proposed, but evidence is mainly from pilot studies and case reports.
narrative review
Changes in depression symptom network structure were observed following ketamine treatment in TRD.
observational
Esketamine nasal spray is approved for TRD, but dissociative effects and functional unblinding are methodological concerns; ketamine-augmented psychotherapy is proposed.
review
A machine learning model using structural MRI predicted ketamine response with 72.2% balanced accuracy; greater frontal gray matter volume predicted response.
observational Sample size: 99
Subcutaneous ketamine showed beneficial effects on suicidal ideation in flexible-dose cohort (C-SSRS significant), but fixed-dose cohort showed no significant difference versus midazolam.
RCT Sample size: 174
IV ketamine preserved and enhanced specific cognitive functions (processing speed, working memory) in TRD, with no cognitive deterioration reported.
systematic review
Announcement of a special issue on behavioural pharmacology of ketamine and psychedelic drugs; no empirical findings.
announcement
Points of agreement
- Ketamine provides rapid antidepressant effects, often within hours to days, in treatment-resistant depression.
- Ketamine shows potential for rapid reduction of suicidal ideation, though results are mixed across studies.
- Short-term safety profile is acceptable with mild, transient adverse effects, but long-term safety data are limited.
- Cognitive functions are generally preserved or improved with subanesthetic ketamine, with no evidence of deterioration.
Conflicts
- One RCT (34495) found ketamine not superior to midazolam for depression, while other studies report significant antidepressant effects.
- Blinding failures are a major concern, with high rates of correct identification in ketamine groups, potentially inflating effect sizes.
- Evidence on neurotoxicity versus neuroprotection is mixed, with both effects reported in preclinical and human studies.
- Results on suicidal ideation are inconsistent: some studies show significant reduction, others show no difference from active placebo.
Gaps
- Long-term safety and efficacy data are lacking, especially for oral and subcutaneous routes.
- Optimal dosing strategies and treatment protocols are not well established.
- The role of ketamine-assisted psychotherapy is underexplored, with most evidence from pilot studies.
- Predictors of response (e.g., biomarkers, imaging) need further validation in larger samples.
- Durability of antidepressant effects beyond short-term follow-up is not well characterized.
- Studies in special populations (e.g., cancer patients, bipolar depression) are limited.