Cureus
January 31, 2026
Lukasz Siwek, Marta Nowocien, Barbara Balajewicz et al.
Psilocybin, a psychoactive compound from Psilocybe mushrooms that activates serotonergic receptors, is being investigated as a treatment for depression, a psychiatric disorder with rising global prevalence projected to become the leading cause of disability by 2030. This narrative review presents recent reports on psilocybin-assisted therapy, which, based on promising results showing higher therapeutic efficacy compared to conventional treatments, offers hope for a modern approach with sustained clinical effects and minimal or no adverse effects.
International journal of toxicology
January 31, 2026
Amir Lotfi, Samantha Sparapani, Mylene Pouliot et al.
5-MeO-DMT, a serotonin receptor agonist being developed for major depression, was tested for seizure risk in beagle dogs. Eight dogs received intranasal doses of 0.5, 1.0, and 1.5 mg/kg/day for nine days. Continuous EEG monitoring showed no seizures or epileptiform discharges at any dose, despite dose-dependent behavioral signs of serotonergic stimulation such as head shaking, tremors, and dilated pupils. These signs correlated with peak plasma levels and resolved within an hour. In a canine model sensitive to serotonergic drug-induced seizures, 5-MeO-DMT did not induce seizures, indicating low seizure liability.
Journal of affective disorders
January 30, 2026
Yao-Zu Li, Cai-Qun Zhao, Mu-Yan Zuo et al.
A multimodal therapy combining esketamine with dexmedetomidine patient-controlled sleep (PCSL) was associated with sustained improvements in depressive symptoms and sleep quality over 6 months in 233 patients with treatment-resistant depression. Antidepressant response rates were 62% at 1 month, 59.73% at 3 months, and 58.49% at 6 months. Use of PCSL was linked to response at all time points, while additional esketamine during follow-up was associated with response at 3 months but not statistically significantly at 6 months. Age and disease duration also influenced response. No serious adverse events occurred.
European journal of anaesthesiology
January 29, 2026
Tiantian Chu, Xiaoling Peng, Keliang Wan et al.
2 citations
A single dose of esketamine given intravenously around the time of cesarean section, followed by 24 hours of low-dose esketamine in patient-controlled pain relief, reduced the overall incidence of postpartum depression within three months after childbirth in first-time mothers who were not already depressed. The total rate of postpartum depression was 11.59% in the esketamine group versus 20.89% in the saline control group. The benefit was most evident at 7 days postpartum, with no significant differences at 1, 2, or 3 months individually. Mild side effects like dizziness, hallucination, and dissociation occurred in some women. The treatment appears relatively safe and prevents postpartum depression in the short term.
Translational psychiatry
January 29, 2026
Rafael V Lima Da Cruz, Rêmullo B G de Miranda Costa, Gabriel M De Queiroz et al.
2 citations
A single dose of the psychedelic DMT reversed depression-like behavior and restored cognitive performance in male mice exposed to chronic stress, outperforming chronic fluoxetine across most measures. When given during the stress period, DMT reduced anhedonia but did not rescue cognitive deficits, indicating domain-specific long-lasting effects. All DMT regimens increased the integration of adult-born granule cells and reduced abnormally integrated cells in the brain, suggesting structural circuit repair. The role of the psychedelic experience remains uncertain because isoflurane anesthesia may have confounded results.
The journal of ECT
January 29, 2026
Sergi López-rodríguez, Aida De Arriba-Arnau, José Manuel Menchón et al.
1 citation
Combining electroconvulsive therapy (ECT) with intranasal esketamine (ESK) may offer sustained improvement for adults with severe treatment-resistant depression who had only partial benefit from either treatment alone. In four patients aged 50 to 72, the combination reduced depression scores by an average of 58% over 24 weeks, with no relapses. Two patients who added the complementary treatment to partial monotherapy showed symptom reductions of 50% and 37%. Two others who were already responding to maintenance ECT had further improvements of 62% and 83%, allowing ECT sessions to be spaced from weekly to every two to three weeks. Side effects were mild and temporary, including brief dissociation and post-ictal confusion. These findings suggest the combination is feasible and warrants controlled trials.
Journal of psychiatric research
January 29, 2026
Dandan Luo, Wenjun Dang, Jie Luo et al.
A systematic review of 13 clinical studies suggests that Mindfulness-Based Stress Reduction (MBSR) may help improve anxiety and depression in adults with autism spectrum disorder (ASD) and may relieve psychological stress and improve emotional states in their caregivers. Among adults with ASD (8 studies), MBSR showed potential for reducing emotional symptoms. For ASD caregivers (4 studies), preliminary effects included reduced stress and better emotional well-being. Only one study examined children with ASD, and none covered adolescents. The evidence is limited by small sample sizes and high heterogeneity, so conclusions should be interpreted cautiously.
Brazilian Journal of Health Review
January 28, 2026
Ketamine appears to be an alternative treatment for bipolar depression when first- and second-line medications are not effective, according to a review of six clinical trials published between 2010 and 2021. Bipolar depression is the most common mood state in bipolar disorder, yet few studies have focused on its treatment. The review examined evidence on ketamine used either as an adjuvant or as monotherapy. The results suggest ketamine may be effective, but future studies are needed to confirm this.
Journal of affective disorders
January 28, 2026
Clara De Oliveira Lapa, Thiago Viola, Rodrigo Delfino et al.
3 citations
Intranasal esketamine substantially reduces depressive symptoms and increases remission rates over time in patients with treatment-resistant depression treated in routine clinical practice. A meta-analysis of nine observational studies found a large effect size (Hedges' g = -1.98) and that patients were about five times more likely to achieve remission at three months compared with the induction phase (odds ratio = 5.1). Treatment effectiveness was not influenced by gender or the presence of anxiety, personality, or substance use disorders. Any adverse event occurred in 82% of patients, most commonly dissociation (49%). The findings support esketamine's effectiveness and tolerability in real-world settings, though the observational design and lack of control groups warrant cautious interpretation.
International Journal of Innovative Technologies in Social Science
January 28, 2026
Łukasz Deska, Cezary Kosmecki, Dawid Głaz et al.
Psilocybin-assisted therapy shows rapid, robust, and sustained antidepressant effects for major depressive disorder and treatment-resistant depression, often after one or two sessions. Its safety profile is generally favorable, with transient and mild adverse events. The therapy primarily acts on serotonin 5-HT2A receptors, modulating brain networks and enhancing neuroplasticity. However, high costs, limited accessibility due to the intensive therapeutic model, and regulatory hurdles present significant challenges. Compared with conventional antidepressants and ketamine, psilocybin offers a promising alternative, especially when standard treatments fail, by providing durable symptom reduction through unique neurobiological pathways.
Expert opinion on therapeutic targets
January 28, 2026
Gia Han Le, Roger S. McIntyre
1 citation
Up to half of adults with major depressive disorder who do not respond to two or more standard antidepressants may have treatment-resistant depression (TRD). Low-dose intravenous ketamine, intranasal esketamine, and oral dextromethorphan are the first glutamatergic treatments to work rapidly and robustly for TRD, but their exact mechanisms are unclear. This review integrates evidence that elevated tonic NMDA receptor currents, mainly through NR2C/D subunits, underlie TRD. Ketamine, esketamine, and dextromethorphan selectively dampen these currents to produce rapid and sustained antidepressant effects. Ketamine and esketamine's affinity for NR2A/B subunits likely drives dissociative effects not seen with dextromethorphan. Future drug development should focus on subunit-biased ligands.
Progress in neuro-psychopharmacology & biological psychiatry
January 27, 2026
Rhea Subba, Surendar Ellappan, Sugato Banerjee et al.
Astroglial dysfunction is a fundamental component of the pathophysiology of major depressive disorder. Rodent models of depression consistently show structural astroglial abnormalities, including atrophy in the prefrontal cortex and hippocampus, reduced glial fibrillary acidic protein expression, impaired glutamate homeostasis, decreased neurotrophic factor production, disrupted gap junction communication, diminished lactate release, increased neuroinflammation, and synaptic deficits. Clinical postmortem and serum biomarker studies corroborate astroglial dysfunction in cortical regions of patients with MDD. Standard antidepressants (SSRIs, SNRIs, tricyclics, serotonin modulators) and rapid-acting ones like ketamine and esketamine exert therapeutic effects at least partially by restoring astroglial homeostasis, positioning astroglia as critical mediators of treatment response and a promising target for personalized antidepressant strategies.
Quality in Sport
January 26, 2026
Adam Wolski, Ewa Szplit, Mikołaj Franciszek Patalong et al.
Psychedelic substances, including psilocybin, LSD, MDMA, and ketamine, show promise for treating psychiatric disorders such as major depressive disorder, PTSD, substance use disorders, and anxiety. Psilocybin produces robust antidepressant effects, reduces anxiety, and benefits substance use disorders after limited dosing sessions. MDMA-assisted psychotherapy yields high remission rates in PTSD. LSD shows promising effects for anxiety and substance use disorders. Ketamine provides rapid antidepressant and anti-suicidal effects in depression and potential benefits in addiction and anxiety, though results in PTSD are mixed. Risks require careful screening and clinical oversight, but evidence supports psychedelic-assisted therapies as adjunctive or alternative interventions for selected patients.
Zenodo (CERN European Organization for Nuclear Research)
January 26, 2026
Fernando Mora López, Johynny Solís Solís, Ekaterina Daniela Hernández Baker et al.
Psilocybin, acting as a 5-HT2A receptor agonist, alters brain connectivity in networks involved in self-referential processing and emotional regulation, accompanied by neuroplastic changes such as enhanced synaptogenesis and functional reorganization. Neuroimaging shows reduced amygdala activity and modifications in default mode and executive networks. Clinical evidence indicates substantial reductions in depressive symptoms, with meta-analyses reporting large effect sizes and durable benefits lasting from weeks to a year. Randomized controlled trials show rapid onset and higher remission rates than conventional treatments, even in treatment-resistant depression. Adverse events are mild, transient, and predictable, though methodological limitations like small samples and high heterogeneity call for larger Phase III trials.
Emerging Minds Journal for Student Research
January 25, 2026
Rishika Scott, James Smith
A systematic review and meta-analysis of seven studies (five open-label and two randomized controlled trials) found that a single 25 mg dose of psilocybin per clinical session is effective for treatment-resistant depression. The 25 mg dose significantly reduced depressive severity compared to 10 mg and 1 mg doses, with two-dose studies showing greater benefit than single-dose studies. The evidence suggests psilocybin is a promising therapeutic, though more research is needed due to limitations in the available studies.
The Brown University Psychopharmacology Update
January 24, 2026
A randomized trial found that up to eight infusions of ketamine were not more effective than a psychoactive placebo (midazolam) in reducing depressive symptoms among patients receiving inpatient treatment for depression. Patients receiving ketamine also showed no improvement relative to those receiving midazolam on measures of cognition and quality of life. The results suggest that ketamine does not provide additional benefit over a psychoactive placebo in this inpatient setting.
Neuroscience & Biobehavioral Reviews
January 24, 2026
Omer A. Syed, Benjamin Tsang, Sean M. Nestor et al.
Psilocybin-assisted therapy (PAT) shows a large and significant antidepressant effect in treating major depressive disorder, based on a meta-analysis of seven randomized controlled trials involving 522 participants. Larger effects were associated with bodyweight-adjusted dosing, longer preparation, dosing, and integration sessions, and non-manualized psychotherapy, though subgroup differences were not statistically significant. The review provides preliminary guidance for clinicians designing PAT protocols.
Translational psychiatry
January 23, 2026
Stevan Nikolin, Clara Massaneda-Tuneu, Louise Brettell et al.
1 citation
Electroconvulsive therapy (ECT) leads to a faster reduction in depressive symptoms than ketamine for severe, medication-resistant depression. A meta-analysis of seven studies with 731 participants found that depression scores were slightly lower at baseline in the ketamine group. After adjusting for baseline differences, ECT produced an additional improvement of about 0.02 standardized mean difference per day, amounting to a predicted moderate advantage over ketamine after four weeks. This advantage falls within the range considered clinically meaningful.
Figshare
January 23, 2026
David Eckert, Siegfried Kasper
Treatment-resistant depression is a major clinical challenge, and guidelines recommend different pharmacological augmentations. A systematic review of head-to-head studies comparing lithium, quetiapine, and esketamine found only four trials: three comparing lithium and quetiapine, and one comparing esketamine and quetiapine. All three agents are effective, with a descriptive superiority of esketamine over quetiapine and of quetiapine over lithium. The results argue for re-evaluating treatment algorithms, but because the drugs differ in side effects, contraindications, and pharmacological profiles, embedding them in a comprehensive clinical context is important.
Journal of affective disorders
January 23, 2026
Reinhard Janssen-Aguilar, Jithin Joseph, Huda Al-Shamali et al.
In a retrospective chart review of 209 adults with treatment-resistant depression treated with intravenous ketamine, depressive and anxiety symptoms improved significantly over four or six infusions, but the improvements were modest and highly variable across individuals. Anxiety symptoms improved more slowly and less robustly than depressive symptoms. End-of-treatment response and remission rates were numerically higher after six infusions than after four, but the difference was not statistically significant. Four distinct patterns of symptom change emerged for both depression and anxiety, highlighting the heterogeneity of treatment response. Durability after six infusions could not be assessed because follow-up data were available only for the four-infusion group.
BJPsych open
January 23, 2026
Nawfel Ayad, Karim Abdel Aziz, Samer Makhoul et al.
2 citations
In a small real-world study of 20 adults with treatment-resistant depression who received at least 100 sessions of intranasal esketamine alongside oral antidepressants over an average of 2.5 years, depression and anxiety scores significantly decreased. 85% of patients showed improvement in depressive severity, with 25% achieving remission; 65% improved in anxiety severity, and 20% reached remission. Esketamine was generally well tolerated with mild, transient side effects and no serious adverse events, though 20% of patients developed urinary symptoms suggestive of cystitis, indicating a need for ongoing monitoring. The findings support the long-term effectiveness and acceptable safety profile of esketamine in complex clinical populations.
Indian journal of psychological medicine
January 22, 2026
Zaid Ahmad Wani, Rajnish Raj, Shabir Ahmad Dar et al.
In a retrospective study of 41 patients in India with major depressive disorder, bipolar depression, or suicidal ideation, oral ketamine therapy was associated with significant reductions in both depressive symptoms and suicidal thoughts. Depression severity, measured by the Hamilton Depression Rating Scale, decreased by an average of 8.19 points, and suicidal ideation, measured by the Modified Scale for Suicidal Ideation, decreased by an average of 4.95 points after three sessions. Common side effects included dizziness, nausea, and hypertension; diarrhea was least common. The findings suggest oral ketamine is an effective and well-tolerated rapid-acting option for reducing depressive symptoms and suicidality, suitable for outpatient use in the Indian context.
Zenodo (CERN European Organization for Nuclear Research)
January 22, 2026
Psilocybin therapy may help treat depression and substance use disorders, but more research is needed to establish its long-term safety and effectiveness.
Neuroscience
January 22, 2026
Guilherme Lodetti, Gislaine Zilli Réus, Eduardo Pacheco Rico
Fewer than half of patients with major depressive disorder achieve remission with standard pharmacotherapy, and many cannot tolerate it. This narrative review examines classic psychedelics as an alternative treatment. These substances primarily bind to 5-HT2A receptors, increasing connectivity between sensory and motor brain networks. They generate long-term behavioral responses comparable to traditional antidepressants. Clinical and experimental studies show that classic psychedelics alleviate depressive symptoms. The mood improvement is thought to stem from effects on neuroplasticity, including neurogenesis and related signaling pathways.