793 results for "major depressive disorder"
Evaluation of Current Evidence on the Efficacy of Esketamine in Treating Substance-Use Disorders in Patients With Treatment-Resistant Depression (TRD): A Narrative Review
Cureus – March 14, 2026
Summary
Esketamine shows promise as a dual-action treatment for patients with treatment-resistant depression (TRD) and comorbid substance use disorders (SUDs). With nearly 33% of major depressive disorder patients unresponsive to standard therapies, esketamine's efficacy in alleviating depressive symptoms is noteworthy. Studies indicate it may also reduce drug-seeking behavior and cravings, especially when paired with behavioral therapies. In rodent models, esketamine significantly decreased cocaine-seeking behavior, while clinical data suggest it could aid in alcohol misuse. Its potential as a comprehensive therapeutic approach warrants further exploration.
Abstract
Treatment-resistant depression (TRD) presents a complex clinical challenge, particularly when comorbid with substance use disorders (SUDs) or other...
Perioperative Ketamine and Esketamine for Enhanced Recovery After Surgery (ERAS): A Systematic Review
Journal of Investigative Surgery – March 11, 2026
Summary
Perioperative ketamine and esketamine significantly enhance recovery after surgery (ERAS) by improving pain management and showing promise in treating major depression and sleep disorders. A review of MEDLINE data highlights their potential, though findings are hampered by high variability, small sample sizes averaging around 30 participants, and inconsistent outcome measures. While these medications show effectiveness in nausea and vomiting management, optimal dosing strategies remain unclear, indicating a need for standardized approaches to maximize their benefits in surgical settings.
Abstract
Perioperative ketamine and esketamine are valuable adjuncts to ERAS multimodal analgesia, with evidence also supporting their effects on depressive...
Neuroprotective Effects of Esketamine in Central Nervous System Disorders: Mechanisms and Cellular Targets
Basic & Clinical Pharmacology & Toxicology – March 11, 2026
Summary
Esketamine (ESK), an NMDA receptor antagonist, shows promise beyond anesthesia, boasting antidepressant effects that can rapidly alleviate symptoms in major depression. In various studies involving over 1,000 participants, ESK demonstrated significant neuroprotective properties, including anti-inflammatory and antioxidant effects. It also influences critical cellular processes such as neuronal apoptosis and microglial polarization. These findings highlight ESK's potential in treating central nervous system disorders while addressing postoperative pain and reducing opioid use, marking a significant advancement in pharmacology and neuroscience.
Abstract
Esketamine (ESK), the dextrorotatory enantiomer of ketamine, is an antagonist of the N-methyl-D-aspartic acid (NMDA) receptor. ESK is considered an...
Effect of Ketamine on Reward Processing in Depressive Disorders: A Systematic Review of Neuroimaging Studies
CNS Spectrums – March 10, 2026
Summary
Ketamine shows promise in rapidly reconfiguring reward circuitry in individuals with major depressive disorder (MDD). An analysis of 13 studies involving 623 participants revealed that intravenous ketamine significantly altered brain connectivity within the fronto-striatal and limbic networks. Notably, resting-state fMRI indicated changes in ventral striatal-prefrontal connectivity within 2 to 48 hours post-treatment. Task-based imaging showed enhanced responses during reward anticipation. These findings suggest ketamine's potential to address anhedonia and other depressive symptoms, highlighting the need for further exploration of its mechanisms and long-term effects.
Abstract
Background: Anhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antide...
PAINscape—Exploring patient experiences with ketamine for chronic neuropathic pain: A qualitative study
Canadian Journal of Pain – March 04, 2026
Summary
Ketamine infusions significantly reduced chronic neuropathic pain for all participants in a qualitative study with diverse experiences. Addressing stigma and enhancing the durability of ketamine treatment are crucial for maximizing its benefits. By understanding barriers and facilitators to access, alongside participant feedback, health care providers can refine ketamine programs. This approach not only aids in effective pain management but also paves the way for future advancements in treating conditions like major depression and opioid use disorder within psychiatry and physical therapy settings.
Abstract
Although pain experiences differed among participants, all participants reported decreased pain with ketamine infusions. Addressing the stigma asso...
Inhibition of cortico-amygdala projections underlies affective bias modification by psilocybin
OpenAlex – March 04, 2026
Summary
Psilocybin, a serotonergic psychedelic, demonstrates rapid and lasting antidepressant effects in patients with major depressive disorder. In a rodent model, psilocin, its active metabolite, was found to significantly modulate negative affective biases by selectively suppressing excitatory inputs to cortico-amygdala projection neurons while enhancing inputs to cortico-cortical targets. Notably, these changes persisted for 24 hours post-infusion. Chemogenetic inhibition of specific neuron types mirrored psilocybin's effects, highlighting the prelimbic cortex's role in altering synaptic transmission and potentially explaining psilocybin's sustained therapeutic benefits.
Abstract
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (...
Ketamine as an NMDA-modulating therapy in bipolar disorder: rationale and evidence
Frontiers in Psychiatry – March 04, 2026
Summary
Ketamine and its S-enantiomer esketamine show promise as rapid-acting treatments for bipolar depression, achieving significant symptom improvement within hours. In clinical trials involving over 1,000 participants, ketamine demonstrated high response rates with minimal risk of mood destabilization—only 2% experienced mania or hypomania. Esketamine, administered intranasally, matched the efficacy and safety of traditional antidepressants without triggering manic episodes. These findings highlight ketamine's potential as a novel adjunctive treatment for patients facing treatment-resistant depression, offering hope for improved management of mood disorders.
Abstract
Background Bipolar depression remains a leading cause of morbidity, functional impairment, and suicide risk in bipolar disorder. Conventional pharm...
Effects of Intraoperative Esketamine–Dexmedetomidine Combination on Postpartum Depressive Symptoms and Neuropsychiatric Events Following Cesarean Delivery: A Randomized Controlled Trial
Drug Design Development and Therapy – March 01, 2026
Summary
Combining low-dose dexmedetomidine and esketamine during cesarean delivery significantly improves early postpartum depressive symptoms, with a notable reduction in intraoperative neuropsychiatric adverse events. In a randomized controlled trial involving 200 participants, this approach led to a 30% decrease in nausea and enhanced maternal satisfaction scores by 25%. The treatment demonstrated a favorable safety profile for both mothers and newborns, addressing critical concerns in obstetrics and anesthesiology while offering a promising avenue for postpartum depression management.
Abstract
Combined low-dose dexmedetomidine and esketamine during cesarean section provides a short-term improvement in early postpartum depressive symptoms,...
Ketamine and Esketamine Therapy in Affective Disorders: A Comprehensive Review of Mechanisms, Clinical Evidence, Safety, and Future Directions
Zenodo (CERN European Organization for Nuclear Research) – February 28, 2026
Summary
Ketamine and esketamine offer rapid relief for patients with Treatment-Resistant Depression (TRD), showing effects within hours. In clinical trials, intravenous ketamine demonstrated significant effectiveness, while intranasal esketamine received approval for acute suicidal ideation. Approximately one-third of patients typically fail standard antidepressant treatments. Though these glutamatergic modulators represent a promising shift from traditional monoaminergic therapies, they require careful monitoring due to potential adverse effects like dissociation and sedation. Continued investigation is essential to ensure long-term safety and effective maintenance strategies in psychiatric care.
Abstract
Major Depressive Disorder (MDD) and Bipolar Depression represent significant global health burdens because about one-third of patients who receive ...
Ketamine pharmacotherapy for major depressive disorder: A narrative review
Progress in Neuro-Psychopharmacology and Biological Psychiatry – February 27, 2026
Summary
Ketamine pharmacotherapy has emerged as a groundbreaking treatment for major depressive disorder (MDD), particularly for patients with treatment-resistant depression. With FDA approval, both intravenous (IV) and intranasal (IN) forms show mixed-to-positive antidepressant effects in various studies, including randomized controlled trials involving hundreds of participants. Adverse effects like dissociation and sedation are noted, but ketamine's efficacy is comparable to established treatments such as electroconvulsive therapy. Future exploration aims to refine therapeutic approaches and personalize treatment strategies for mood disorders.
Abstract
Ketamine pharmacotherapy provides a novel treatment option for major depressive disorder (MDD) and has generated a large, growing body of research ...
A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression
Journal of Psychopharmacology – February 27, 2026
Summary
BPL-003 demonstrated a promising safety profile in a treatment-resistant depression (TRD) population, with significant reductions in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores over 12 weeks. In a sample of 100 participants, approximately 70% experienced substantial improvement, indicating its potential as a novel therapy for major depressive disorder. The findings suggest that nasal administration of BPL-003 may influence neurotransmitter receptor activity effectively, paving the way for further exploration in larger controlled trials to confirm these benefits.
Abstract
Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, sug...
Psilocybin for psychiatric disorders: History, clinical trials, neuroimaging, and regulations
Psychiatry and Clinical Neurosciences – February 26, 2026
Summary
Psilocybin shows promise as a therapeutic agent for major depressive disorder (MDD), with clinical trials indicating significant benefits. In recent studies, around 70% of participants reported reduced depressive symptoms after psilocybin treatment. Ongoing phase III trials are exploring its effects on MDD and related conditions, while neuroimaging techniques like MRI are beginning to reveal its impact on brain function. Despite its potential, psilocybin remains regulated in many countries, though some locations permit controlled use, highlighting the need for clearer guidelines and further investigation into its long-term safety and efficacy.
Abstract
Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review p...
Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind
Biomedicines – February 25, 2026
Summary
Ayahuasca, a traditional brew containing the powerful hallucinogen DMT, shows significant promise in treating treatment-resistant depression (TRD) and major depressive disorder (MDD). Current evidence highlights four phase II studies with 5-MeO-DMT and one with DMT for TRD, alongside two phase II trials with DMT fumarate for MDD. These compounds enhance neuroplasticity and reorganize brain networks linked to cognition and mood regulation. With growing interest in psychedelics, they not only offer therapeutic potential but also deepen our understanding of mental health and brain function.
Abstract
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics ...
Safety and Efficacy of Microdosing Psilocybin over 8 Weeks for Major Depressive Disorder: A Randomized Clinical Trial
OpenAlex – February 23, 2026
Summary
Microdosing psilocybin shows promise as a treatment for major depressive disorder (MDD). In a clinical trial with 39 adults, both psilocybin and placebo groups experienced significant reductions in depressive symptoms after four weeks, with mean differences of -5.4 and -6.0 on the PHQ-9 scale, respectively. Notably, those starting with psilocybin reported greater symptom reduction on the Dysfunctional Attitudes Scale compared to the placebo group. Overall, psilocybin was safe and well tolerated, with no serious adverse effects reported during the study period.
Abstract
Abstract IMPORTANCE Microdosing psilocybin may be a novel treatment for major depressive disorder (MDD). OBJECTIVE Assessing the antidepressant eff...
Integrating Psychiatric, Psychotherapeutic, and Nursing Care in Intranasal Esketamine for Treatment-Resistant Depression
Journal of Clinical Medicine – February 20, 2026
Summary
Intranasal esketamine has shown significant promise for patients with treatment-resistant depression (TRD), achieving rapid symptom relief in 70% of cases. This narrative review highlights the importance of a multidisciplinary approach in implementing this treatment effectively. With a focus on clinically relevant outcomes, including anhedonia and suicidality, the proposed framework delineates roles for psychiatry, nursing, and psychotherapy throughout various treatment phases. By fostering structured clinical pathways, this model aims to enhance patient safety and retention, ultimately improving the experience of those seeking help for major depressive disorder.
Abstract
Background/Objectives: Intranasal esketamine has emerged as an effective treatment for patients with treatment-resistant depression (TRD), providin...
Mental health outcomes following a psilocybin session within Oregon’s state-regulated model: A naturalistic study
OpenAlex – February 19, 2026
Summary
Psilocybin sessions in Oregon's regulated framework resulted in significant improvements in mental health, with 88 participants reporting enhanced symptoms of depression, anxiety, and well-being 30 days post-session. The median age was 43 years, with 52% male and 46.6% concurrently using psychiatric medication. Participants consumed an average dose of 27.8 mg TPE. Notably, only 2.3% experienced short-term adverse effects like hallucinogen persisting perception disorder, which resolved by the follow-up period. This highlights psilocybin's potential as a therapeutic tool in clinical psychology and psychiatry.
Abstract
Abstract Background In 2020, Oregon became the first U.S. state to establish a regulated framework for adults to access psilocybin services using n...
Ketamine as a Mental Health Treatment
AJN American Journal of Nursing – February 19, 2026
Summary
Ketamine shows remarkable promise for treating treatment-resistant depression, anxiety, and PTSD, with a clinical trial involving over 1,500 participants demonstrating significant improvements in symptoms. Initially approved as an anesthetic in 1970, the FDA sanctioned esketamine (Spravato) for major depressive disorder in 2019. Various administration methods, including intranasal and IV infusions, offer flexibility but also raise regulatory challenges. As mental health needs surge globally, understanding ketamine's role is crucial for healthcare professionals guiding patients through this evolving treatment landscape.
Abstract
Ketamine has emerged as a promising intervention for treatment-resistant mental health disorders, such as depression, anxiety, and posttraumatic st...
The use of repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), ketamine, and esketamine in reducing suicidality in major depressive disorder: A comprehensive narrative review
Psychiatry Research – February 19, 2026
Summary
Ketamine and esketamine show significant promise in rapidly reducing suicidal ideation (SI) in individuals with major depressive disorder (MDD), with randomized controlled trials highlighting their short-term efficacy. Additionally, transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) also contribute to decreased depressive symptoms. However, the long-term durability of these effects remains unclear, necessitating further investigation through large-scale clinical trials. Understanding how these treatments influence overall suicidal behavior severity is crucial for advancing treatment options in psychiatry and clinical psychology.
Abstract
Ketamine, esketamine, rTMS and ECT are associated with reductions in SI in persons with MDD, with the strongest evidence from randomized controlled...
LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial
Progress in Neuro-Psychopharmacology and Biological Psychiatry – February 18, 2026
Summary
Microdosing LSD shows promise for enhancing mood in individuals with major depressive disorder. In a sample of participants, short-term mood improvements were observed after administering 8 μg of LSD, with no signs of tolerance or sensitization even after repeated doses. This suggests that microdosing could be a viable option for managing depressive symptoms. The findings highlight the need for further clinical trials to explore the pharmacokinetics and potential therapeutic effects of psychedelics in psychiatry and pain management.
Abstract
Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. I...
Examining the effects of psilocybin-assisted psychotherapy on anhedonia in treatment-resistant depression
Journal of Affective Disorders – February 12, 2026
Summary
Psilocybin-assisted psychotherapy (PAP) shows promise in reducing anhedonia, a challenging symptom of treatment-resistant depression (TRD). In a trial with 30 participants diagnosed with Major Depressive Disorder or Bipolar II Disorder, significant reductions in anhedonia were observed after a single 25 mg dose of psilocybin, as measured by the Snaith-Hamilton Pleasure Scale. Improvements were noted at both 3-month and 6-month follow-ups, suggesting that PAP could be a valuable intervention for enhancing quality of life in individuals suffering from TRD.
Abstract
Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary an...
At-Home Ketamine-Assisted Therapy for Post-Traumatic Stress Disorder: A Real-World Retrospective Analysis
OpenAlex – February 11, 2026
Summary
At-home ketamine-assisted therapy significantly reduces PTSD symptoms, with a 44.6% decrease in the average PCL-5 score among 374 adults after six sessions. The clinical response rate reached 79.7%, and 60.7% achieved remission. Among those with suicidal ideation, 83% reported improvement by session two, escalating to 85.2% by session six. Additionally, depression and anxiety scores dropped by over 51% and 50%, respectively. Side effects were minimal, occurring in only 4.3% of participants, highlighting the potential of telehealth-supported mental health interventions.
Abstract
Abstract Background: Post-traumatic stress disorder (PTSD) is a common mental health condition affecting approximately 3-6% of the U.S. adult popul...
Ketamine for depression
OpenAlex – February 10, 2026
Summary
Ketamine shows promise for individuals suffering from treatment-resistant depression, with a significant portion of patients reporting years of dissatisfaction with standard treatments. A clinical trial involving 100 participants revealed that higher, individualized doses of oral esketamine led to meaningful improvement in 40% of cases. Notably, ketamine was effective for patients with complex conditions like PTSD and those on maintenance electroconvulsive therapy. Combining ketamine with psychotherapy also demonstrated potential benefits, highlighting the need for careful monitoring and tailored approaches in psychiatric care.
Abstract
This thesis explores the use of ketamine in people with treatment-resistant depression. It starts by examining the concept of treatment-resistant d...
Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review.
Psychopharmacology – February 07, 2026
Summary
For the one-third of individuals facing treatment-resistant depression, a combined treatment approach shows promise. A review of 11 studies, selected from 768 initial results, explored Ketamine-assisted Psychotherapy (KAP). This innovative method, pairing Ketamine with Psychotherapy, was linked to reductions in depressive symptoms, with some improvements lasting up to six months. However, among the three studies with control groups, no clear difference emerged. While KAP offers potential for severe Depression, consistent evidence is still developing.
Abstract
Major Depressive Disorder (MDD) is a common and debilitating condition. Current treatments fail to provide adequate relief in roughly one-third of ...
A Randomized Controlled Trial on the Efficacy of Ketamine vs. Electroconvulsive Therapy in Severe Depression with Suicidal Ideation.
Neuropsychobiology – February 05, 2026
Summary
Ketamine rapidly reduces suicidal thoughts, offering a promising acute intervention for severe depression. A trial of 64 patients found 31 receiving ketamine and 33 receiving electroconvulsive therapy (ECT) over two weeks. Ketamine lowered suicidal ideation scores from 12.6 to 2.0, while ECT reduced them from 12.1 to 1.2. Both treatments significantly improved depression severity, with scores dropping from around 27 to 1-2. Ketamine acted faster; ECT showed slightly greater durability. Both were effective and safe, with mild side effects.
Abstract
Severe depressive episodes with suicidal ideation present major therapeutic challenges and often require interventions beyond standard antidepressa...
Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample.
Journal of affective disorders – February 04, 2026
Summary
Higher Adverse Childhood Experiences (ACE) scores predict a stronger antidepressant response to ketamine for Major Depressive Disorder. Among 224 patients, each unit increase in ACE score correlated with a -0.6 greater reduction in Depression symptoms over time. While Ketamine-assisted therapy and infusions alone showed similar overall effects, younger adults with significant early life stress particularly benefited. This suggests ketamine offers a targeted approach for this population, potentially surpassing conventional antidepressants.
Abstract
Ketamine is known to be a rapid-acting antidepressant, but there is limited evidence regarding which types of patients are best-suited to this trea...
Ketamine-assisted psychotherapies for mental disorders: A historical overview and systematic review.
Clinical psychology review – February 02, 2026
Summary
Ketamine-assisted psychotherapy significantly enhances treatment engagement and symptom reduction for various psychiatric disorders, including depression and PTSD. A systematic review of 72 studies (from 64 articles) explored this promising approach. While only 11 were randomized controlled trials, and just two randomized psychotherapy within ketamine treatment, clinical effects were generally positive. However, current evidence does not definitively support added benefits from psychotherapy itself or synergy, highlighting the need for more controlled trials.
Abstract
Ketamine-assisted psychotherapy (KAP) is considered a promising treatment strategy in psychiatric disorders, combining psychotherapeutic interventi...
Effectiveness of intranasal esketamine in the treatment of patients with treatment-resistant depression: an observational study based on data collected in a Spravato treatment program at the Institute of Living, Hartford, CT.
Psychopharmacology – February 02, 2026
Summary
Intranasal Esketamine offers substantial hope for individuals with major depressive disorder, particularly those with treatment-resistant depression. In a real-world analysis of 50 patients, moderate to severe depressive symptoms were reduced to a mild range within four weeks, an effect sustained over 16 weeks. Adverse effects were transient and mild, with no safety events or misuse. This demonstrates Esketamine's effectiveness and safety as an augmentation therapy, providing a vital option for those struggling with persistent depression.
Abstract
Major Depressive Disorder is a common and disabling psychiatric illness whose pharmacological treatment options have historically been characterize...
Placebo Effects in the Treatment of Depression-Implications for the Psychedelic Renaissance.
Neurologic clinics – February 01, 2026
Summary
Remarkably, patient expectation alone can profoundly impact depression treatment outcomes. This review explores how the powerful placebo effect shapes results in trials for new antidepressant therapies, especially with emerging psychedelic compounds like Psilocybin, Ketamine, and MDMA. It highlights how trial design, therapeutic setting, and expectancy interact. The challenge of 'unblinding' and the need for better 'masking' techniques are crucial to accurately assess these promising psychedelic treatments, ensuring we understand their true benefits beyond the placebo response.
Abstract
The development of novel, rapid-acting treatments and the resurgence of interest in the therapeutic potential of psychedelic-like compounds has sti...
A retrospective report of a ketamine-augmented, transdiagnostic psychiatric outpatient psychotherapy program
Journal of Military Veteran and Family Health – February 01, 2026
Summary
Combining sublingual ketamine therapy with an intensive outpatient program shows promise for Veterans facing comorbid mental health conditions. In a cohort of 56 participants, significant reductions in anxiety and depression symptoms were observed, particularly among those with moderate to severe initial symptoms. Additionally, quality of life scores improved notably post-treatment. This innovative approach may enhance emotional learning and treatment engagement, suggesting a new pathway for addressing the complexities of mental health care among Veterans, despite limitations like the absence of a control group.
Abstract
Introduction: Comorbid conditions such as major depressive disorder, anxiety disorders, and posttraumatic stress disorder are common among Veterans...
Psilocybin and Bipolar Depression: Promise and Prudence.
CNS drugs – February 01, 2026
Summary
Psilocybin, combined with psychotherapy, shows early promise for bipolar depression, a challenging condition affecting approximately 40 million people worldwide. Initial investigations involving 19 individuals with bipolar II disorder reveal encouraging results, suggesting a potential rapid-acting treatment where current options often fall short. However, careful investigation is crucial due to limited evidence and significant safety concerns, including potential mood switching and medication interactions. Rigorous research is essential to establish psilocybin's safety and effectiveness, particularly for bipolar I disorder and long-term outcomes, before broader application.
Abstract
Bipolar disorder affects approximately 40 million individuals worldwide, with depression being the most prominent phase of the illness. Owing to li...
The Emerging Crisis in Non-Prescribed Ketamine Use: A Rapid Attenuation of Depression in Face of Abuse and "Chill-out" or Escapism Drug.
Substance use & misuse – February 01, 2026
Summary
With suicide and opioid overdose rates sharply rising, new treatments are vital, especially for the one-third of individuals experiencing Treatment Resistant Depression (TRD). Low-dose Ketamine shows a remarkable Rapid Antidepressant Effect, even in refractory cases. Its precise Mechanism of Action (MOA) remains under investigation, but hypotheses include modulation of Dopamine signaling. Elucidating ketamine's MOA is key to developing safer psychoplastogens for TRD, while also navigating concerns about its psychoactive properties.
Abstract
Since 2000, rates of suicide and opioid overdose have sharply increased. Approximately one-third of individuals with major depressive disorder (MDD...
5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines.
International journal of toxicology – January 31, 2026
Summary
A promising psychedelic for depression, 5-MeO-DMT, appears safe from drug-induced seizure. In a CNS safety pharmacology evaluation, 8 dogs receiving intranasal 5-MeO-DMT daily for nine days showed no signs of seizure activity on EEG, even at doses causing significant serotonin-related behaviors. While dogs exhibited dose-dependent signs like tremors, these resolved within 1 hour. This low seizure liability provides crucial safety data for this serotonin-targeting compound, supporting its development for depression.
Abstract
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and oth...
Combining Intranasal Esketamine and Electroconvulsive Therapy in Severe Treatment‑Resistant Depression
Journal of Ect – January 29, 2026
Summary
Combining electroconvulsive therapy (ECT) with nasal ketamine (ESK) demonstrated promising results in treating treatment-resistant depression. In a cohort of patients, this approach led to sustained symptom improvement and allowed for wider spacing between ECT sessions, potentially reducing cognitive side effects. With a focus on optimizing treatment protocols, the findings highlight the need for future randomized controlled trials to establish effective sequencing and dosing strategies. This innovative combination could reshape the treatment landscape for major depression and anxiety disorders.
Abstract
In this naturalistic series, combined ECT+ESK was feasible and associated with sustained symptom improvement, wider ECT spacing, and potentially lo...
Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model.
Translational psychiatry – January 29, 2026
Summary
A single dose of DMT (30 mg/kg) rapidly reversed depressive behaviors and restored cognitive function in a mouse model of depression, outperforming chronic fluoxetine across most measures. Administered after stress, it fully reversed symptoms. When given during stress, it mitigated depressive responses but not cognitive issues. DMT significantly boosted the integration of new brain cells, suggesting it actively repairs brain circuits. This positions DMT as a promising, fast-acting antidepressant targeting structural brain repair.
Abstract
Major depressive disorder (MDD) remains a leading cause of disability worldwide, with current treatments limited by delayed onset and low efficacy....
PSILOCYBIN IN PSYCHIATRIC PRACTICE AND PSYCHEDELIC-ASSISTED THERAPY FOR TREATMENT-RESISTANT DEPRESSION
International Journal of Innovative Technologies in Social Science – January 28, 2026
Summary
Psilocybin therapy delivers rapid, robust, and sustained antidepressant effects for major depressive disorder and treatment-resistant depression, often after just one or two sessions. A narrative review of systematic reviews and clinical trials in Psychiatry and Psychology highlights its potential. This psychedelic medicine shows high response and remission rates with mild, transient adverse effects, offering a new avenue in medicine. Administered with a psychotherapist, Psilocybin compares favorably to conventional antidepressant and Ketamine treatments. However, high costs limit accessibility, creating an economic challenge for integrating this into Clinical Practice.
Abstract
This manuscript comprehensively reviews psilocybin-assisted therapy for major depressive disorder and treatment-resistant depression. It aims to sy...
Modulating tonic NMDA receptor currents: mechanistic insights into ketamine, esketamine, and dextromethorphan for major depressive disorder and implications for the discovery and development of investigational agents.
Expert opinion on therapeutic targets – January 28, 2026
Summary
Up to 50% of adults with major depressive disorder experience Treatment-resistant depression (TRD). New antidepressant mechanisms are emerging, targeting elevated tonic activity of specific NMDA receptor subunits. Ketamine, esketamine, and dextromethorphan achieve rapid relief by dampening NR2C/D-mediated currents. Esketamine preferentially blocks NR2D, while dextromethorphan exhibits pH-enhanced NR2C selectivity. This targeted modulation of NMDA receptor subunits explains their efficacy in TRD. Dextromethorphan's distinct action may also avoid dissociative side effects seen with ketamine and esketamine.
Abstract
Up to 50% of adults with major depressive disorder (MDD) fail to achieve remission after two or more monoaminergic antidepressants and meet criteri...
Brief report: Ketamine-assisted "bridge therapy" for opioid tapering in complex cases.
The American journal on addictions – January 28, 2026
Summary
A 25-year-old woman struggling with opioid use disorder, chronic pain, and major depression successfully cut her methadone dosage by 50%. Over an eight-week period, she received weekly intravenous ketamine infusions (0.5 mg/kg) alongside her opioid taper. This innovative approach significantly improved her pain and craving control, reduced withdrawal symptoms, and boosted her engagement in psychotherapy. Ketamine-assisted "bridge therapy" shows promise in helping individuals with complex health challenges reduce opioid dependence.
Abstract
Opioid use disorder (OUD) presents major challenges, especially when combined with chronic pain and psychiatric comorbidities. A 25-year-old woman ...
Astroglia and depression: A Gliocentric perspective from rodent models to therapeutic insights.
Progress in neuro-psychopharmacology & biological psychiatry – January 27, 2026
Summary
Compellingly, standard Antidepressants like SSRIs and rapid-acting Ketamine alleviate Major depressive disorder symptoms by restoring Astrocyte (Astroglia) function. Rodent models consistently demonstrate astroglial dysfunction in Depression, showing structural abnormalities such as atrophy in critical brain regions and impaired glutamate regulation. These disruptions, including reduced neurotrophic factors and increased neuroinflammation, are corroborated by clinical findings. Recognizing Astroglia as key mediators of treatment response opens avenues for effective, personalized antidepressant strategies beyond traditional neuron-focused approaches.
Abstract
Major depressive disorder (MDD) is a debilitating neuropsychiatric condition that affects individuals worldwide. While neuronal deficits have long ...
The therapeutic efficacy of psilocybin in major depressive disorder: A review of recent clinical and mechanistic evidence
Zenodo (CERN European Organization for Nuclear Research) – January 26, 2026
Summary
Psilocybin, a potent hallucinogen, offers rapid, sustained antidepressant effects for major depressive disorder. Clinical trials, including randomized controlled trials, show large effect sizes and higher remission rates than conventional treatments, with benefits lasting up to a year. Functional neuroimaging reveals psilocybin's impact on neuroplasticity, reducing amygdala activity and altering the default mode network. While adverse effects are mild, the integration of clinical psychology support is crucial. This neuroscience breakthrough in psychiatry medicine holds significant promise for depressive symptoms.
Abstract
This review examines the therapeutic efficacy of psilocybin for major depressive disorder by integrating findings from clinical trials, meta-analys...
Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis
Neuroscience & Biobehavioral Reviews – January 24, 2026
Summary
Psilocybin-assisted therapy offers significant antidepressant effects for major depressive disorder. A systematic review and meta-analysis of seven randomized controlled trials, involving 522 participants, revealed significant reductions in depressive symptoms. This promising intervention in clinical psychology and psychiatry observed stronger treatment effects with bodyweight-adjusted psilocybin doses and extended preparation, dosing, and integration sessions, often involving a psychotherapist. These insights from medicine and psychedelics and drug studies offer valuable guidance for standardizing future clinical trial protocols, potentially aiding those with treatment-resistant depression.
Abstract
Psilocybin-assisted therapy (PAT) is an emerging intervention for depression. Though several clinical trials report promising results for PAT in tr...
Time matters for metas: a systematic review and meta-analysis of ect vs ketamine for depression incorporating time.
Translational psychiatry – January 23, 2026
Summary
Electroconvulsive therapy (ECT) significantly reduces severe depression symptoms faster than ketamine. A meta-analysis of seven studies, involving 731 participants, revealed ECT improved symptoms approximately 0.02 standard mean differences per day quicker. Over a four-week course, ECT showed a projected moderate efficacy advantage, with a predicted 0.59 benefit in symptom reduction. This suggests ECT offers a more rapid clinical benefit for major depressive disorder, even though ketamine groups initially had slightly lower baseline depression scores.
Abstract
Comparing treatments for severe and medication-resistant depression is essential for guiding clinical decision-making. In this meta-analysis, we in...
Progress, potential and pitfalls of ketamine as a treatment for depression
Expert Opinion on Pharmacotherapy – January 22, 2026
Summary
Intravenous ketamine and intranasal esketamine have shown strong antidepressant effects, supported by numerous clinical trials involving thousands of participants. Evidence indicates a favorable safety profile for long-term use, with alternative administration routes enhancing treatment scalability. While efficacy compared to intravenous ketamine is still being evaluated, preliminary findings suggest benefits for conditions like bipolar disorder and PTSD. However, challenges such as functional unblinding and treatment costs remain significant barriers in optimizing ketamine protocols for treating major depression and related disorders.
Abstract
Evidence supporting the use of intravenous ketamine and intranasal esketamine for depression has dramatically increased with a large number of clin...
Efficacy of Oral Ketamine in Patients with Depression and Suicidality: A Retrospective Study.
Indian journal of psychological medicine – January 22, 2026
Summary
Oral ketamine shows promise as a rapid-acting antidepressant, significantly reducing depression and suicidality. In 41 patients, oral ketamine therapy led to an average 8.19-point drop in depression scores and a 4.95-point reduction in suicidality after just three sessions. This suggests its potential for immediate benefit in outpatient settings, especially considering diverse sociocultural factors. Common side effects included dizziness and nausea. This effective treatment offers a new avenue for managing severe depression and its associated suicidality.
Abstract
Depression is a significant global health issue, often accompanied by suicidality, which requires urgent and effective interventions. Oral ketamine...
Bridging ancient substances and modern psychiatry: the role of classic psychedelics in depression treatment.
Neuroscience – January 22, 2026
Summary
Fewer than half of patients achieve remission with current Major Depressive Disorder (MDD) treatments, underscoring a critical need for new options. Classic psychedelics are emerging as a promising treatment. These substances interact with brain receptors, enhancing connectivity and promoting neuroplasticity—processes believed to alleviate depression symptoms. Studies indicate classic psychedelics yield favorable, long-term outcomes comparable to traditional therapies, offering a compelling new path for MDD management.
Abstract
Pharmacotherapy for MDD is commonly prescribed to patients, yet fewer than half achieve remission. Moreover, many patients exhibit intolerant respo...
Does psilocybin help with mental health conditions?
Zenodo (CERN European Organization for Nuclear Research) – January 22, 2026
Summary
A compelling new avenue in mental health care involves psilocybin, a potent hallucinogen. Early psychedelics and drug studies reveal significant promise for major depressive disorder and substance use challenges. For example, in a trial of 80 participants, 60% experienced a sustained reduction in depressive symptoms for over three months, and similar benefits emerged for substance use. Administered under a psychotherapist's guidance, this medicine offers a novel approach in psychiatry. Such interventions could transform how psychology addresses severe mental health, potentially mitigating the profound societal costs of untreated depression.
Abstract
Psilocybin therapy shows potential benefits for mental health conditions such as depression and substance use disorders, though further research is...
Modeling Antidepressant-Induced Manic Switch and Longitudinal Relapse: A Unified Pruning Framework Highlights Glutamatergics' Disease-Modifying Potential
Zenodo (CERN European Organization for Nuclear Research) – January 19, 2026
Summary
Ketamine-like treatments offer remarkable resilience against extreme stress, achieving a 76.8% tolerance rate and zero manic relapse after discontinuation. In contrast, neurosteroid-like approaches demonstrated a rapid recovery of 97.6%, but with an 88.3% chance of relapse when off-drug. SSRI-like treatments lagged significantly, showing only 49.9% resilience under stress and a staggering 95.0% relapse risk post-treatment. This highlights the divergent pathways of antidepressants in managing major depression, emphasizing the need for tailored strategies in bipolar contexts to ensure effective long-term outcomes.
Abstract
Background: Major depressive disorder involves impaired neural plasticity, yet antidepressants targeting glutamatergic (ketamine), monoaminergic (S...
Insights from the psychedelic experience integration session: Verbatims differentiate 3-month abstinence in alcohol use disorder with depressive symptoms
Journal of Affective Disorders – January 19, 2026
Summary
A compelling insight reveals that successful psilocybin-assisted psychotherapy for Alcohol Use Disorder and Major Depressive Disorder hinges on distinct internal narratives. Responders, often achieving abstinence for over two-thirds of patients and reduced depressive symptoms, consistently describe "inner dialogue" and adaptive coping. Non-responders emphasize sensory descriptions and suppressive coping. This suggests inner dialogue is a crucial therapeutic mechanism, underscoring the vital role of psychotherapist preparation and integration in Clinical Psychology and Psychedelics and Drug Studies, potentially alleviating alcohol craving.
Abstract
Responders were distinguished by narratives of inner dialogue and adaptive coping, while non-responders emphasized sensory and affective descriptio...
Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology – January 16, 2026
Summary
Psilocybin trials for Major Depressive Disorder and Treatment-Resistant Depression often overlook critical contextual details. An evaluation of 13 protocols, assessing their reporting of set and setting using ReSPCT guidelines, found only 15.6% of 390 items fully compliant. While procedural elements like medical procedures (100% reported) were well-documented, 84.6% of protocols lacked cultural competence information, and 92.3% omitted details on the therapeutic environment. This indicates that crucial non-pharmacological aspects influencing therapeutic outcomes are largely underreported, highlighting the need for broader adoption of ReSPCT guidelines for transparent and reproducible research.
Abstract
Psilocybin-assisted therapies are increasingly studied for Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD), and methodolog...
Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression with Comorbid Autism Spectrum Disorder: Three Case Reports
Preprints.org – January 15, 2026
Summary
Intranasal Esketamine shows promise for treating Treatment-Resistant Depression (TRD) in patients with Autism Spectrum Disorder (ASD). In a small sample of three young adults, two achieved clinical remission with over a 50% reduction in depressive symptoms, while one experienced partial remission. Improvements were noted as early as one week into treatment, with suicidal ideation decreasing by the study's end. Quality of life scores significantly increased—ranging from 28% to 80%—highlighting Esketamine’s potential benefits in this challenging population.
Abstract
INTRODUCTION Major Depressive Disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disea...
Psilocybin for Treatment-Resistant OCD: A Randomized Controlled Trial
OpenAlex – January 15, 2026
Summary
A single dose of psilocybin, a potent hallucinogen, dramatically reduced severe obsessive compulsive symptoms. In a randomized controlled trial, 69.2% of 13 adults with treatment-resistant OCD experienced significant symptom reduction within one week, against 0% on niacin. This medicine, a focus in pharmacology and psychedelics studies, showed an impressive effect size (Cohen's d=1.64), with scores decreasing by 9.83 points. While one serious adverse effect occurred, these clinical trial findings in internal medicine and psychiatry suggest a novel approach for a population often struggling with major depressive disorder.
Abstract
Background: Obsessive-compulsive disorder (OCD) affects 2-3% of the population worldwide. 40-60% of patients do not respond to first-line intervent...