July 2026
Ketamine
What July 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, racemic ketamine, arketamine, R-ketamine, then ranked by relevance.
Research on ketamine in July 2026 continued to support its rapid antidepressant and short-term anti-suicidal effects, with evidence of efficacy in treatment-resistant depression and short-term abstinence in substance use disorders, though longer-term durability remains a key unmet need. Mechanistic studies in animals and humans point to synaptic plasticity, mitochondrial, and epigenetic changes, but clinical evidence is limited by small samples, uncontrolled designs, and unresolved questions about durability and long-term safety.
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 |
|---|---|---|---|---|
| Antidepressant-like effects of ketamine involve CX3CL1/CX3CR1 signaling-mediated synaptic plasticity in the mPFC 2026 | animal study | Supports | Ketamine reversed depression-like behaviors and enhanced synaptic plasticity in mice, and blocking CX3CL1/CX3CR1 signaling prevented these effects. | |
| Sustained abstinence in severe ketamine use disorder following ibogaine treatment case report 2026 | case report | 1 | Supports | Ibogaine treatment was associated with immediate cessation of cravings and sustained abstinence from ketamine, cocaine, and alcohol over 17 months, with improvements in depression and quality of life. |
| (Es)ketamine in functional neurological disorder: a systematic review 2026 | systematic review | Mixed | The evidence base for (es)ketamine in functional neurological disorder is insufficient, though some patients reported improvement in functional symptoms across several presentations. | |
| Esketamine's Therapeutic Effect on Anhedonia: A Post-hoc of a Randomized Controlled Trial 2026 | randomized controlled trial, post-hoc analysis | Supports | Esketamine reduced anhedonia symptoms compared to placebo in patients with treatment-resistant depression. | |
| Ketamine-induced analgesia and dissociation show distinct behavioral and neural correlates 2026 | within-subject, placebo-controlled fMRI study | 37 | Supports | Ketamine induced both analgesia and dissociation, which corresponded to distinct neural indices, with pain-related brain activity not covarying with dissociation-related brain connectivity. |
| Intranasal Ketamine Alleviates Depressive-like Behaviors in Chronic Unpredictable Mild Stress Rats in Association with Hypothalamic NADH:Ubiquinone Oxidoreductase Subunit A10. 2026 | animal experimental study | Supports | Intranasal ketamine improved depressive-like behaviors in stressed rats and increased hypothalamic Ndufa10 mRNA and NDUFA10 protein levels, with complex I inhibition attenuating the behavioral improvement. | |
| Beyond Monoamines: Ketamine, Esketamine, and Classic Psychedelics in the Treatment of Depression 2026 | review | Supports | Ketamine and esketamine have the strongest evidence base among rapid-acting antidepressant interventions for treatment-resistant depression, while psilocybin-assisted therapy shows promise but remains investigational. | |
| Ketamine for substance use disorders: a systematic review and meta-analysis 2026 | systematic review and meta-analysis | 798 | Mixed | Ketamine significantly improved short-term abstinence (<1 month) but not longer-term abstinence (1-6 months) in substance use disorder. |
| Clinical guidance on the use of esketamine nasal spray for patients with treatment resistant depression: A European Delphi consensus report. 2026 | modified Delphi panel | 30 | Supports | Expert consensus supported continuing esketamine nasal spray even with modest acute-phase improvement and advocated for dose/frequency maximization, while prolonging maintenance treatment depended on clinical worsening during tapering and relapse risk. |
| Psychedelic Therapies in the Management of Post-Traumatic Stress Disorder 2026 | review | Supports | Psychedelic therapies, particularly MDMA-assisted therapy, represent a potential breakthrough for PTSD by targeting underlying causes, with ketamine offering rapid symptom alleviation for treatment-resistant cases. | |
| Serum brain-derived neurotrophic factor following oral esketamine in treatment-resistant depression: Results from a randomized placebo-controlled trial. 2026 | randomized controlled trial | 54 | No effect | Repeated, low-dose, oral esketamine did not increase serum BDNF relative to placebo, and BDNF changes did not correlate with changes in depression severity. |
| Predictors of responsiveness to ketamine: An updated systematic review of neuroimaging findings. 2026 | systematic review | Supports | The anterior cingulate cortex, amygdala, and their connectivity with other brain regions are potential neuroimaging biomarkers for predicting responsiveness to ketamine in major depressive disorder. | |
| NMDA Receptor Modulation as a Bidirectional Axis: Reframing Ketamine's Antagonism Against Glycine-Site Enhancement, with a Proposed Extension to Sleep-Disrpted 2026 | review | Unclear | The paper proposes treating NMDA receptor modulation as a bidirectional axis, with glycine-site enhancers as the pharmacological inverse of ketamine, representing an underexplored candidate for sleep restoration in NMDA-hypofunction states. | |
| Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response 2026 | review | Unclear | The introduction of ketamine and esketamine has shifted the most important unmet needs in treatment-resistant depression from inducing short-term symptom improvement to managing the post-response trajectory, including durability, relapse prevention, functional recovery, patient selection, and long-term safety. | |
| Erratum to: Calcium/Calmodulin-Dependent Protein Kinase II and Eukaryotic Elongation Factor 2 Kinase Pathways Mediate the Antidepressant Action of Ketamine. 2026 | erratum | Unclear | This is an erratum to a previous article on calcium/calmodulin-dependent protein kinase II and eukaryotic elongation factor 2 kinase pathways mediating the antidepressant action of ketamine. | |
| Interrogating roles for VTA dopamine neurons in locomotion and ultrasonic vocalizations elicited by different classes of rewarding drugs. 2026 | observational study | 26 | Mixed | Ketamine suppressed high-frequency ultrasonic vocalizations and transiently increased locomotion, with distinct effects compared to amphetamine and heroin, and VTA dopamine neuron manipulations similarly suppressed amphetamine- or ketamine-induced locomotion. |
| Longitudinal dream-content shift and void-like dissociative phenomenology around outpatient ketamine infusions in chronic low back pain: a case report. 2026 | case report | 1 | Supports | After ketamine infusions, dream content shifted from recurrent obstruction toward imagery of movement, interpersonal engagement, and everyday role completion. |
| Is the reduction in suicidal ideation and deliberate self-harm during intranasal esketamine treatment independent of antidepressant response? A secondary, longitudinal analysis of a real-world TRD cohort with and without comorbid borderline personality disorder 2026 | secondary analysis of a longitudinal cohort | Supports | The within-person reduction in suicidal ideation over six months remains statistically significant after adjusting for time-varying depressive severity, indicating an anti-suicidal effect partly independent of mood improvement. | |
| Enhancing plasticity to treat depression and other central nervous system diseases using event-driven pharmacology. 2026 | review | Supports | Plastogens, including ketamine and classical psychedelics, operate under an event-driven pharmacology model where transient binding induces long-lasting neuroplastic and metaplastic changes that outlast drug exposure. | |
| S-ketamine, but not R-ketamine, transiently suppresses front-loaded binge-like alcohol self-administration in male rats 2026 | experimental animal study | Supports | S-ketamine, but not R-ketamine, dose-dependently suppressed binge-like alcohol self-administration in male rats, though tolerance developed rapidly with repeated administration. | |
| Brain-targeted epigenetic effects of two emerging psychoplastogens: ketamine & MDMA 2026 | clinical trial | 36 | Supports | Ketamine and MDMA induced peripheral DNA methylation changes that converge on neuroplasticity and neuroimmune pathways. |
| Epigenetic landscapes of classical psychedelics and ketamine: molecular mechanisms of long-lasting neuromodulation 2026 | review | Supports | Classic psychedelics and ketamine may induce lasting therapeutic effects through complex epigenetic reprogramming mechanisms, including DNA methylation, histone modifications, and metabolic pathway interactions, though direct causal evidence remains limited. | |
| Ketamine Metabolites Promote Anxiolysis and Hydrocortisone Stress Buffering in Zebrafish. 2026 | experimental study | Mixed | Hydroxynorketamine isomers produce stereospecific behavioral effects: RANK is anxiolytic under baseline and stress conditions, while SHANK is anxiogenic at baseline but both isomers attenuate hydrocortisone-induced hyperarousal. | |
| Quick protocol for depression with intravenous ketamine. 2026 | review | Supports | Intravenous ketamine is supported by guidelines for treatment-resistant depression but requires careful monitoring due to variable efficacy and side effects. | |
| Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study 2026 | retrospective cohort study | 63 | Supports | Intranasal esketamine and intravenous ketamine both produced large and clinically meaningful reductions in depression severity during induction therapy, with no significant between-group differences. |
Ketamine reversed depression-like behaviors and enhanced synaptic plasticity in mice, and blocking CX3CL1/CX3CR1 signaling prevented these effects.
animal study
Ibogaine treatment was associated with immediate cessation of cravings and sustained abstinence from ketamine, cocaine, and alcohol over 17 months, with improvements in depression and quality of life.
case report Sample size: 1
The evidence base for (es)ketamine in functional neurological disorder is insufficient, though some patients reported improvement in functional symptoms across several presentations.
systematic review
Esketamine reduced anhedonia symptoms compared to placebo in patients with treatment-resistant depression.
randomized controlled trial, post-hoc analysis
Ketamine induced both analgesia and dissociation, which corresponded to distinct neural indices, with pain-related brain activity not covarying with dissociation-related brain connectivity.
within-subject, placebo-controlled fMRI study Sample size: 37
Intranasal ketamine improved depressive-like behaviors in stressed rats and increased hypothalamic Ndufa10 mRNA and NDUFA10 protein levels, with complex I inhibition attenuating the behavioral improvement.
animal experimental study
Ketamine and esketamine have the strongest evidence base among rapid-acting antidepressant interventions for treatment-resistant depression, while psilocybin-assisted therapy shows promise but remains investigational.
review
Ketamine significantly improved short-term abstinence (<1 month) but not longer-term abstinence (1-6 months) in substance use disorder.
systematic review and meta-analysis Sample size: 798
Expert consensus supported continuing esketamine nasal spray even with modest acute-phase improvement and advocated for dose/frequency maximization, while prolonging maintenance treatment depended on clinical worsening during tapering and relapse risk.
modified Delphi panel Sample size: 30
Psychedelic therapies, particularly MDMA-assisted therapy, represent a potential breakthrough for PTSD by targeting underlying causes, with ketamine offering rapid symptom alleviation for treatment-resistant cases.
review
Repeated, low-dose, oral esketamine did not increase serum BDNF relative to placebo, and BDNF changes did not correlate with changes in depression severity.
randomized controlled trial Sample size: 54
The anterior cingulate cortex, amygdala, and their connectivity with other brain regions are potential neuroimaging biomarkers for predicting responsiveness to ketamine in major depressive disorder.
systematic review
The paper proposes treating NMDA receptor modulation as a bidirectional axis, with glycine-site enhancers as the pharmacological inverse of ketamine, representing an underexplored candidate for sleep restoration in NMDA-hypofunction states.
review
The introduction of ketamine and esketamine has shifted the most important unmet needs in treatment-resistant depression from inducing short-term symptom improvement to managing the post-response trajectory, including durability, relapse prevention, functional recovery, patient selection, and long-term safety.
review
This is an erratum to a previous article on calcium/calmodulin-dependent protein kinase II and eukaryotic elongation factor 2 kinase pathways mediating the antidepressant action of ketamine.
erratum
Ketamine suppressed high-frequency ultrasonic vocalizations and transiently increased locomotion, with distinct effects compared to amphetamine and heroin, and VTA dopamine neuron manipulations similarly suppressed amphetamine- or ketamine-induced locomotion.
observational study Sample size: 26
After ketamine infusions, dream content shifted from recurrent obstruction toward imagery of movement, interpersonal engagement, and everyday role completion.
case report Sample size: 1
The within-person reduction in suicidal ideation over six months remains statistically significant after adjusting for time-varying depressive severity, indicating an anti-suicidal effect partly independent of mood improvement.
secondary analysis of a longitudinal cohort
Plastogens, including ketamine and classical psychedelics, operate under an event-driven pharmacology model where transient binding induces long-lasting neuroplastic and metaplastic changes that outlast drug exposure.
review
S-ketamine, but not R-ketamine, dose-dependently suppressed binge-like alcohol self-administration in male rats, though tolerance developed rapidly with repeated administration.
experimental animal study
Ketamine and MDMA induced peripheral DNA methylation changes that converge on neuroplasticity and neuroimmune pathways.
clinical trial Sample size: 36
Classic psychedelics and ketamine may induce lasting therapeutic effects through complex epigenetic reprogramming mechanisms, including DNA methylation, histone modifications, and metabolic pathway interactions, though direct causal evidence remains limited.
review
Hydroxynorketamine isomers produce stereospecific behavioral effects: RANK is anxiolytic under baseline and stress conditions, while SHANK is anxiogenic at baseline but both isomers attenuate hydrocortisone-induced hyperarousal.
experimental study
Intravenous ketamine is supported by guidelines for treatment-resistant depression but requires careful monitoring due to variable efficacy and side effects.
review
Intranasal esketamine and intravenous ketamine both produced large and clinically meaningful reductions in depression severity during induction therapy, with no significant between-group differences.
retrospective cohort study Sample size: 63
Points of agreement
- Ketamine and esketamine show rapid antidepressant effects in treatment-resistant depression, including reductions in anhedonia and suicidal ideation.
- Ketamine's antidepressant mechanisms involve synaptic plasticity, neuroplasticity, and epigenetic changes.
- Ketamine shows short-term efficacy for substance use disorders, particularly for alcohol and polysubstance use.
- Real-world and clinical trial evidence supports the efficacy of both intravenous ketamine and intranasal esketamine for depression.
Conflicts
- One study found ketamine improved short-term but not longer-term abstinence in substance use disorder, while a case report showed sustained abstinence over 17 months following ibogaine treatment.
- A randomized controlled trial found oral esketamine did not increase serum BDNF, while other mechanistic studies suggest neuroplasticity-related changes.
- One study found ketamine-induced analgesia and dissociation have distinct neural correlates, while other research suggests subjective experiences may be necessary for therapeutic benefits.
Gaps
- Durability of ketamine's effects beyond the acute phase remains unclear, with limited long-term follow-up data.
- Most evidence for ketamine in functional neurological disorder and substance use disorders comes from uncontrolled case reports and small studies.
- Long-term safety and abuse liability of repeated ketamine/esketamine treatment are not well established.
- Predictive biomarkers for ketamine response remain elusive, though neuroimaging findings are promising.
- The role of specific molecular pathways (e.g., CX3CL1/CX3CR1, Ndufa10, BDNF) in human ketamine response requires further investigation.