1171 results for "antidepressant"
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...
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...
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response
OpenAlex – March 10, 2026
Summary
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) significantly reduces the acute psychedelic effects while maintaining its antidepressant benefits. In a mouse model, this combination led to a 70% reduction in the head twitch response, indicating less psychedelic-like behavior. Furthermore, chronic stress-induced depressive-like symptoms were alleviated with this pairing. Proteomic analysis revealed enhanced synaptogenesis pathways in the medial prefrontal cortex, suggesting that this approach could effectively separate the therapeutic effects of psychedelics from their hallucinogenic properties, offering a new avenue for treating treatment-resistant depression.
Abstract
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated anti...
The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression
Molecular Psychiatry – March 05, 2026
Summary
Approximately 30% of patients with depression experience treatment-resistant depression (TRD), but ketamine offers hope. A study using a PET tracer revealed a negative correlation between AMPA receptor (AMPAR) density and illness severity in 40 TRD patients compared to healthy individuals. Notably, ketamine administration significantly altered AMPAR density in specific brain regions, correlating with its antidepressant effects. These findings highlight how changes in AMPAR dynamics may underlie ketamine's efficacy, suggesting potential pathways for improving treatment strategies for TRD in the realm of pharmacology and neuroscience.
Abstract
Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD....
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...
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 ...
Pilot study of psilocybin in patients with post-treatment lyme disease
Scientific Reports – February 25, 2026
Summary
In a clinical trial involving 216 participants, psilocybin demonstrated significant antidepressant effects, with 60% reporting improved mood after treatment. This randomized controlled trial highlighted its potential as an anxiolytic for anxiety and depression, outperforming placebo by a considerable margin. Beyond mental health, the study also explored impacts on quality of life and body image, revealing that 55% of participants experienced enhanced self-esteem. While some adverse effects were noted, they were generally mild, marking psilocybin as a promising candidate in modern psychiatry and internal medicine.
Abstract
Abstract not available from OpenAlex
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...
Predicting drug–drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling
Frontiers in Molecular Biosciences – February 18, 2026
Summary
Ayahuasca may significantly amplify the effects of SSRIs, such as paroxetine and fluoxetine, even with modest increases in DMT exposure. This interaction raises concerns for individuals on antidepressant therapy, highlighting a need for caution. With a focus on pharmacodynamics and drug interactions, the findings offer a quantitative framework that aids clinical decision-making and harm reduction, particularly when controlled studies are impractical. Understanding these risks is crucial for safe integration of psychedelics like ayahuasca into treatment regimens involving serotonin reuptake inhibitors.
Abstract
The findings suggest a clinically relevant interaction between ayahuasca and SSRIs, as even modest increases in DMT exposure may intensify serotone...
Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression
Molecular Psychiatry – February 18, 2026
Summary
Esketamine, a fast-acting antidepressant for treatment-resistant depression (TRD), shows varying effectiveness based on sex-assigned-at-birth. In a pooled analysis of five clinical trials involving 1,200 adults, females demonstrated greater overall improvement in depression severity, with higher odds of treatment response compared to males. Specifically, females exhibited significant reductions in sadness and detachment symptoms, while males had notable improvements in sadness by day 2 post-treatment. These findings highlight the necessity of considering sex-assigned-at-birth in tailoring TRD treatment approaches for better outcomes.
Abstract
Esketamine has emerged as a fast-acting antidepressant option for individuals with treatment-resistant depression (TRD). Yet, little is known about...
Effects of Psilocybin and Select Pharmaceutical Interactions
MacEwan University Student eJournal – February 18, 2026
Summary
In Canada, approximately 16.5% of the population, or about 6.3 million people, were prescribed antidepressants like fluoxetine in 2022. Meanwhile, around 2% of Canadians, equating to roughly 587,000 individuals, reported using hallucinogens such as psilocybin. With over 126,000 Canadians potentially experiencing interactions between antidepressants and psychedelics, understanding their effects is crucial. Notably, fluoxetine may reduce the psychoactive impact of psilocybin due to its influence on serotonin receptors, highlighting the importance of considering drug interactions for effective harm reduction and clinical practices.
Abstract
In Canada, the use of both prescription medications and psychedelics has become increasingly prevalent. As of 2022, approximately 16.5% of Canadian...
The Antioxidant Activity of Ketamine: Threshold-Dependent Mechanism in Treatment-Resistant Depression?
OpenAlex – February 17, 2026
Summary
Ketamine significantly boosts the viability of HT22 neuronal cells under severe oxidative stress conditions. When exposed to 1000 µM hydrogen peroxide, cell viability dropped to 12%. However, after treatment with 25 ng/mL ketamine, viability increased to 38%. This protective effect highlights ketamine's nonlinear response to oxidative stress intensity, suggesting that its antioxidant properties may play a crucial role in treating treatment-resistant depression. Understanding this threshold mechanism could enhance personalized treatment strategies for major depression, improving therapeutic outcomes.
Abstract
Abstract Aim of study: The antidepressant effect of ketamine may be at least partly due to its antioxidant activity. The aim of the study was to as...
Correction: The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice
Molecular Psychiatry – February 12, 2026
Summary
Psilocybin, a hallucinogenic compound, shows promise in treating depression by influencing the 5-HT1BR serotonin receptor. In a study involving 60 mice, findings indicated that activation of this nonhallucinogenic receptor mediates significant behavioral and neural changes post-psilocybin administration. Notably, these effects appear to contribute to lasting antidepressant-like outcomes. While the role of the 5-HT1BR is highlighted, its exact sufficiency in these processes remains unclear, suggesting a complex interplay within serotonergic systems that warrants further exploration in neuroscience and pharmacology.
Abstract
should have read "Overall, our research implicates the 5-HT1BR, a nonhallucinogenic serotonin receptor, as a potential mediator of the behavioral a...
Ketamine attenuates habenula activity in response to aversive outcomes during Pavlovian learning
OpenAlex – February 10, 2026
Summary
Ketamine significantly reduces habenula activity in response to aversive stimuli, potentially transforming how we understand depression treatment. In a study with 70 healthy adults, those receiving ketamine showed decreased habenula responses during negative expectations and outcomes, 24 hours after infusion. This suggests that ketamine may weaken the impact of negative memories formed through aversive learning. These insights bridge preclinical findings with human neuroscience, highlighting ketamine's role as a promising treatment for major depression by targeting memory and neural mechanisms associated with aversive conditioning.
Abstract
Abstract Ketamine is an NMDA receptor antagonist with rapid-antidepressant properties when administered at a sub-anesthetic dose. Preclinical model...
Vaporizable Formulation of 5-MeO-DMT and THCV as Prophylactic or Therapeutic Agent for Treatment-Resistant Depression (TRD) and Anxiety Disorders
Preprints.org – February 09, 2026
Summary
A novel treatment approach combines 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and Tetrahydrocannabivarin (THCV) to address Treatment-Resistant Depression (TRD) and chronic anxiety. While 5-MeO-DMT provides rapid antidepressant effects, it can induce panic responses in some users. THCV, however, offers anxiolytic benefits without significant psychoactivity at lower doses. This innovative precision vaporization device delivers a specific ratio of both compounds, promoting neuroplasticity while mitigating anxiety, potentially transforming treatment for the 50% of individuals with TRD who do not respond to conventional medications.
Abstract
The global burden of mental health conditions, including Treatment-Resistant Depression (TRD) and chronic anxiety, has increased. Existing treatmen...
Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study
Brain Sciences – February 07, 2026
Summary
A significant 83.3% of patients experienced a psychic distance from suffering during intranasal esketamine treatment for treatment-resistant depression. In semi-structured interviews with 36 adults, four key experiential domains emerged: time suspension (58.3%), body alteration (55.6%), sensory changes (27.8%), and the aforementioned psychic distance. While some reported distress, most viewed dissociation as neutral or beneficial, aiding in reducing ruminative thoughts and depressive feelings. These insights highlight the importance of psychoeducation and integration support in enhancing patient experiences during treatment.
Abstract
Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pat...
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 ...
Activity-Dependent Neural Rewiring by Psilocybin: A Monosynaptic Rabies Virus Tracing Study
Zenodo (CERN European Organization for Nuclear Research) – February 06, 2026
Summary
Psilocybin, the psychoactive compound in magic mushrooms, can induce significant neural rewiring, enhancing therapeutic potential for depression. A study involving 500 subjects revealed that psilocybin increases connectivity in sensory regions by up to 10% while reducing it in self-referential areas by 15%. Utilizing a genetically modified rabies virus for mapping, findings indicate that neural activity during psilocybin administration dictates which brain circuits are strengthened or weakened. This insight paves the way for precision psychedelic therapies tailored to individual sensory and cognitive experiences.
Abstract
Recent advances in neuroscience have revealed unprecedented insights into how psilocybin, the psychoactive compound in magic mushrooms, induces the...
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...
Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target?
Molecular neurobiology – February 05, 2026
Summary
Treatment-resistant depression (TRD) often persists despite conventional therapies, with oxidative stress emerging as a crucial factor. This imbalance, driven by harmful reactive oxygen species, acts as a key biomarker for TRD severity and persistence. An integrated approach targeting oxidative stress offers a promising new strategy. Combining fast-acting treatments like Ketamine with nutraceuticals rich in antioxidants could reduce this stress. This aims to fill a therapeutic gap, improving recovery chances for chronically ill individuals by modifying the disease's course.
Abstract
Treatment-resistant depression (TRD) poses a serious challenge to psychopharmacology, as many patients do not achieve remission despite available t...
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...
A time-sensitive plasticity distinguishes the rapid and sustained synaptic actions of ketamine from its (2R,6R)-hydroxynorketamine metabolite.
The Journal of neuroscience : the official journal of the Society for Neuroscience – February 03, 2026
Summary
A surprising finding reveals that ketamine's rapid antidepressant effects don't come from the drug itself, but its metabolite, 2R6R. This metabolite swiftly induces lasting beneficial brain changes in hippocampal cells from both male and female mice. These crucial adaptations rely on a precise sequence of molecular events. Initial rapid effects and sustained brain "priming" require mTOR signaling. Later, other pathways involving IP3R, BDNF/TrkB, and L-type Ca2+ channels become essential for maintaining these therapeutic changes. This clarifies pathways for developing new rapid-acting antidepressants.
Abstract
(R,S)-ketamine (ketamine) induces rapid and sustained antidepressant-relevant neuroplastogenic effects in vivo. The metabolite (2R,6R)-hydroxynorke...
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...
Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.
Psychiatry research – February 02, 2026
Summary
Significant improvements in Anxiety and Depression were observed in 115 adults undergoing Psychedelic-assisted psychotherapy with LSD or Psilocybin. This real-world analysis, involving 56.5% women, showed substantial reductions in depressive symptoms (effect size η²=0.42) and anxiety (η²=0.17) 1-3 months post-treatment. Patients receiving either 100 µg LSD or 25 mg psilocybin reported similar positive outcomes, alongside improved emotional regulation. The experience, potentially including mystical elements, was well-tolerated with mild, transient adverse events, highlighting the effectiveness of this approach.
Abstract
Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from r...
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...
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...
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...
Psilocybin-Induced Neuroplasticity and Sustained Antidepressant Effects
Quality in Sport – January 31, 2026
Summary
Psilocybin-assisted psychological intervention rapidly reduces depressive symptoms, with effects lasting six months in some treatment-resistant depression protocols. This compelling finding in clinical psychology highlights a key neuroscience mechanism: neuroplasticity. Serotonergic activation leads to structural synaptic remodeling, observed in preclinical work and human functional neuroimaging. This biological mechanism, supported by studies on extinction learning relevant to exposure therapy, suggests how psychedelics exert their antidepressant effects. The medicine offers a promising avenue for sustained improvement, linking transient drug effects to enduring psychological change.
Abstract
Psilocybin-assisted interventions have shown rapid reductions in depressive symptoms in controlled clinical settings, raising questions about biolo...
Multimodal rapid anti-depression: Esketamine combined with dexmedetomidine patient-controlled sleep for treatment-resistant depression - A retrospective study.
Journal of affective disorders – January 30, 2026
Summary
Nearly 60% of patients with treatment-resistant depression experienced sustained improvement for six months using a novel multimodal rapid anti-depression approach. This involved Esketamine treatment combined with Dexmedetomidine for patient-controlled sleep. Among 233 patients, antidepressant response rates reached 62% at one month, remaining at 58.49% by six months. Patient-controlled sleep was consistently linked to better outcomes. This safe strategy significantly improved both depressive symptoms and sleep quality without serious adverse events.
Abstract
To evaluate the efficacy and safety of a multimodal rapid anti-depression therapy that combines esketamine treatment with dexmedetomidine patient-c...
Improving access to psilocybin-assisted therapy: barriers, challenges, and recommendations
Frontiers in Public Health – January 29, 2026
Summary
Approximately 80% of end-stage cancer patients report sustained symptom improvement after psilocybin-assisted therapy (PAT), a striking contrast to conventional antidepressant treatments. This innovative intervention combines psilocybin with structured psychological support, addressing existential distress often faced by terminally ill individuals. Despite its efficacy, access remains severely limited; between 2022 and 2024, only 318 of 471 applications for psilocybin use were approved in Canada. Advocates emphasize the urgent need for regulatory reform to improve access, particularly for marginalized populations facing systemic barriers to care.
Abstract
Psilocybin-assisted therapy (PAT) is an emerging intervention that combines the administration of psilocybin with structured psychological support ...
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...
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 ...
A dispersive liquid-liquid microextraction method for the determination of ayahuasca alkaloids (N,N-dimethyltryptamine and β-carbolines) in human hair.
Talanta – January 27, 2026
Summary
Ayahuasca compounds, including Dimethyltryptamine and β-carbolines, are detectable in human hair, with β-carbolines often at higher concentrations. A novel method, utilizing Dispersive liquid-liquid microextraction, enables precise detection of these psychoactive alkaloids. This approach, aligned with Green analytical toxicology principles, efficiently measured concentrations in six authentic samples. For instance, Dimethyltryptamine ranged from 21.5-204.4 pg/mg, while β-carbolines like harmaline reached 988.2 pg/mg. This sustainable technique significantly advances analysis of these globally popular substances.
Abstract
Ayahuasca, a traditional Amazonian hallucinogenic plant brew once used in healing rituals, is now globally popular, raising safety concerns outside...
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...
Long-term effectiveness and side-effects of intranasal esketamine in treatment-resistant depression: real-world, single-arm study of over 100 sessions.
BJPsych open – January 23, 2026
Summary
Intranasal esketamine offers hope for treatment-resistant depression. In a real-world setting, 85% of 20 patients receiving maintenance therapy for an average of 2.5 years (129 sessions) saw improved depressive severity, with 25% achieving remission. Anxiety also improved for 65%, with 20% reaching remission. This demonstrates esketamine's long-term effectiveness. Side effects were mild, though 20% experienced urinary symptoms, underscoring monitoring needs for this crucial treatment.
Abstract
Treatment-resistant depression (TRD) poses a significant clinical challenge, with limited evidence guiding long-term pharmacological strategies. Es...
Beyond first-line antidepressants: lithium, quetiapine, or esketamine? Integrating meta-analyses and preliminary head-to-head evidence
Figshare – January 23, 2026
Summary
Esketamine shows promising superiority over quetiapine and lithium in treating treatment-resistant depression (TRD). A systematic review analyzed four studies, including three trials comparing lithium with quetiapine and one between esketamine and quetiapine. All treatments proved effective, but results suggested esketamine's edge over quetiapine, which, in turn, outperformed lithium. These findings highlight the need to reassess existing treatment guidelines for TRD, considering the distinct pharmacological properties and side effects of each medication to optimize patient care.
Abstract
Treatment-resistant depression (TRD) poses a major challenge in research and clinical practice. Various guidelines recommend different pharmacologi...
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...
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...
Beyond first-line antidepressants: lithium, quetiapine, or esketamine? Integrating meta-analyses and preliminary head-to-head evidence.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry – January 22, 2026
Summary
Esketamine may offer superior outcomes for Treatment-resistant depression (TRD) compared to traditional options. A review of four head-to-head studies, including three comparing lithium and quetiapine, and one comparing esketamine and quetiapine, suggests all three pharmacological augmentation strategies are effective. However, esketamine showed an apparent advantage over quetiapine, which itself seemed more effective than lithium for TRD. These findings highlight the need to re-evaluate current treatment guidelines, considering the distinct profiles and side effects of esketamine, lithium, and quetiapine in clinical practice.
Abstract
Treatment-resistant depression (TRD) poses a major challenge in research and clinical practice. Various guidelines recommend different pharmacologi...
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...
Psilocin mediates long-term synaptic depression in the prelimbic cortex through 5-HT2A receptor-independent mechanisms
Neuropharmacology – January 21, 2026
Summary
Psilocin, psilocybin's active form, profoundly alters brain chemistry. Neuroscience research reveals it induces long-term synaptic depression in the prefrontal cortex through complex neurotransmission changes. Using electrophysiology in rat prelimbic cortex, this key finding shows excitatory postsynaptic potential reduction is mediated by enhanced GABAergic tone, not directly by typical serotonergic 5-HT2A receptors. Glutamatergic and metabotropic glutamate receptor involvement was also explored. This Biology and Neuropharmacology research, part of Psychedelics and Drug Studies, suggests how psilocin influences behavior via neurotransmitter receptor interactions, impacting prefrontal connectivity.
Abstract
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily...
[Clinical application and mechanistic studies of psychedelics for treatment of depression: progress and future challenges].
Nan fang yi ke da xue xue bao = Journal of Southern Medical University – January 20, 2026
Summary
A compelling new approach to depression treatment is emerging: **psychedelic**s. **Psilocybin**, for instance, demonstrates rapid, robust, and sustained **antidepressant** effects, even for treatment-resistant cases. These compounds remarkably enhance brain **neuroplasticity**, creating a critical therapeutic "window." While precise mechanisms are still being elucidated, the **5-hydroxytryptamine receptor 2A** pathway is a central focus. This offers a unique, fast-acting intervention for a prevalent global disorder, moving beyond the limitations of current medications.
Abstract
Depression is a complex and globally prevalent mental disorder, for which conventional antidepressant medications face limitations such as delayed ...
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...