August 2026
Ketamine
What August 2026's 11 new studies found, synthesized from the papers below. All Ketamine research →
The synthesis
Synthesized from 11 studies in the library · AI-generated, grounded in the abstracts below
Found by searching the library for Ketamine, racemic ketamine, arketamine, R-ketamine, then ranked by relevance.
In August 2026, research on ketamine and esketamine for depression consistently showed rapid, moderate-to-large antidepressant effects, with esketamine associated with lower risks of suicidal ideation and anxiety compared to oral antidepressants but higher risks of cardiac arrest and other adverse outcomes compared to injectable ketamine. Evidence also indicated that ketamine may be more effective in bipolar than unipolar depression, and that concomitant benzodiazepines may reduce its efficacy. However, most studies were observational or small, and long-term safety and efficacy in serious illness remain understudied.
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 |
|---|---|---|---|---|
| Therapeutic potential of classic and non-classic psychedelics in neurodevelopmental disorders: Opportunities and challenges 2026 | review | Mixed | Argues that evidence for psychedelics in neurodevelopmental disorders is limited, mostly from small adult studies of low-dose ketamine, with promising but preliminary findings for cognitive and social improvements. | |
| Clinical correlates of anhedonia non-response to ketamine in treatment-resistant depression. 2026 | retrospective analysis of naturalistic, observational registries | 34 | Mixed | Anhedonia non-response to short-term ketamine was associated with single marital status, fewer lifetime depressive episodes, and lower rates of substance use disorder, with 47.1% of patients being non-responders. |
| Brain iron-sensitive markers (magnetic susceptibility and R2*) predict antidepressant response to ketamine in treatment-resistant depression. 2026 | double-blind, randomized placebo-controlled trial followed by an extended single-arm open-label study | 17 | Supports | Baseline magnetic susceptibility in the right nucleus accumbens and R2* in the left amygdala predicted antidepressant response to repeated intravenous ketamine infusions. |
| Faster and greater antidepressant response to intravenous ketamine in bipolar compared with unipolar treatment-resistant depression: Diagnostic and sex-related findings from a naturalistic study. 2026 | observational study | 97 | Supports | Intravenous ketamine produced faster and greater antidepressant effects in bipolar depression compared with unipolar depression, with differences emerging from week 2 and persisting through three months. |
| Ketamine for Depression in Serious Illness: Evidence, Safety, and Practical Approaches. 2026 | review | Supports | Argues that ketamine and esketamine provide the strongest evidence among rapid-acting antidepressants, with rapid moderate-to-large effects lasting one to two weeks, but rigorous psychiatric trials in serious illness are lacking. | |
| Chronic corticosterone biases conflict-related behavior and abolishes ketamine's anticonflict effect in mice. 2026 | experimental study | Opposes | Chronic corticosterone exposure increased conflict behavior in mice and abolished ketamine's anticonflict effect, suggesting stress disrupts ketamine-responsive mechanisms. | |
| Role of concomitant benzodiazepines, lithium, and lamotrigine in modulating the antidepressant effects of subcutaneous esketamine in patients with treatment-resistant depressive episodes: A retrospective naturalistic study. 2026 | observational cohort | 178 | Mixed | Concomitant benzodiazepine use was associated with higher depressive symptom severity during subcutaneous esketamine treatment, while lamotrigine and lithium showed no significant association with outcomes. |
| Comparative effectiveness and safety of esketamine versus injectable racemic ketamine and oral antidepressants for major depressive disorder: A population-based target trial emulation. 2026 | emulated target trial using observational data | 1089419 | Mixed | Esketamine was associated with higher risks of suicidal ideation, generalized anxiety disorder, insomnia, and cardiac arrest compared with injectable ketamine, but lower risks of suicidal ideation, suicide attempt, and generalized anxiety disorder compared with oral antidepressants, though with a higher risk of cardiac arrest. |
| Esketamine alleviates trigeminal neuralgia and anxiety-like behaviors in mice by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis. 2026 | animal study | Supports | Esketamine dose-dependently alleviated mechanical allodynia and anxiety-like behaviors in a trigeminal neuralgia mouse model by inhibiting hippocampal necroptosis via the RIPK1/RIPK3/MLKL pathway. | |
| Intranasal Ketamine for Existential Distress in Advanced Cancer. 2026 | secondary analysis of a clinical trial | 15 | Supports | Intranasal ketamine was associated with clinically meaningful improvements in existential distress, anxiety, symptom burden, and quality of life in individuals with advanced cancer being treated for depression. |
| Dreaming during anaesthesia: a scoping review. 2026 | scoping review | 87866 | Unclear | Anaesthesia dreaming is common, predominantly positive, pharmacologically specific, and not associated with intraoperative awareness, with ketamine and propofol most consistently associated with recall. |
Argues that evidence for psychedelics in neurodevelopmental disorders is limited, mostly from small adult studies of low-dose ketamine, with promising but preliminary findings for cognitive and social improvements.
review
Anhedonia non-response to short-term ketamine was associated with single marital status, fewer lifetime depressive episodes, and lower rates of substance use disorder, with 47.1% of patients being non-responders.
retrospective analysis of naturalistic, observational registries Sample size: 34
Baseline magnetic susceptibility in the right nucleus accumbens and R2* in the left amygdala predicted antidepressant response to repeated intravenous ketamine infusions.
double-blind, randomized placebo-controlled trial followed by an extended single-arm open-label study Sample size: 17
Intravenous ketamine produced faster and greater antidepressant effects in bipolar depression compared with unipolar depression, with differences emerging from week 2 and persisting through three months.
observational study Sample size: 97
Argues that ketamine and esketamine provide the strongest evidence among rapid-acting antidepressants, with rapid moderate-to-large effects lasting one to two weeks, but rigorous psychiatric trials in serious illness are lacking.
review
Chronic corticosterone exposure increased conflict behavior in mice and abolished ketamine's anticonflict effect, suggesting stress disrupts ketamine-responsive mechanisms.
experimental study
Concomitant benzodiazepine use was associated with higher depressive symptom severity during subcutaneous esketamine treatment, while lamotrigine and lithium showed no significant association with outcomes.
observational cohort Sample size: 178
Esketamine was associated with higher risks of suicidal ideation, generalized anxiety disorder, insomnia, and cardiac arrest compared with injectable ketamine, but lower risks of suicidal ideation, suicide attempt, and generalized anxiety disorder compared with oral antidepressants, though with a higher risk of cardiac arrest.
emulated target trial using observational data Sample size: 1089419
Esketamine dose-dependently alleviated mechanical allodynia and anxiety-like behaviors in a trigeminal neuralgia mouse model by inhibiting hippocampal necroptosis via the RIPK1/RIPK3/MLKL pathway.
animal study
Intranasal ketamine was associated with clinically meaningful improvements in existential distress, anxiety, symptom burden, and quality of life in individuals with advanced cancer being treated for depression.
secondary analysis of a clinical trial Sample size: 15
Anaesthesia dreaming is common, predominantly positive, pharmacologically specific, and not associated with intraoperative awareness, with ketamine and propofol most consistently associated with recall.
scoping review Sample size: 87866
Points of agreement
- Ketamine and esketamine produce rapid antidepressant effects in treatment-resistant depression.
- Ketamine is effective in reducing depressive symptoms in serious illness, including cancer.
- Concomitant benzodiazepines may reduce the antidepressant efficacy of esketamine.
- Ketamine's effects are mediated by glutamatergic and neuroplastic mechanisms.
- Esketamine is associated with higher risks of certain adverse outcomes compared to injectable ketamine.
Conflicts
- Esketamine was associated with higher risks of suicidal ideation and anxiety compared to injectable ketamine, but lower risks compared to oral antidepressants.
- Ketamine was more effective in bipolar than unipolar depression in one study, while another found no significant differences in anhedonia response based on diagnosis.
- Chronic stress abolished ketamine's anticonflict effect in mice, suggesting stress may reduce efficacy, but other studies did not examine this interaction.
Gaps
- Long-term efficacy and safety of ketamine and esketamine beyond short-term treatment.
- Rigorous psychiatric trials in serious illness populations.
- Effects of ketamine on anhedonia and existential distress in larger, more diverse samples.
- Impact of concomitant medications (e.g., benzodiazepines) on ketamine efficacy in prospective studies.
- Mechanistic studies translating animal findings (e.g., necroptosis, stress effects) to humans.
- Comparative effectiveness of different ketamine formulations (IV, oral, intranasal, subcutaneous) and dosing regimens.