1653 results for "observational study"
Acute ketamine withdrawal disrupts memory and monoaminergic neurotransmission in adolescent female rats.
Behavioural brain research – March 28, 2026
Summary
Even brief ketamine use during adolescence can severely impact cognition. Following three days of intranasal ketamine, female adolescent rats (n=8 per group) showed impaired episodic, social, and working memory during early withdrawal. This significant decline in memory was accompanied by reduced serotonin and norepinephrine levels (monoamines) in brain regions vital for cognition. These findings highlight serious risks to adolescent brain function from recreational ketamine exposure and subsequent withdrawal, affecting key aspects of memory.
Abstract
Adolescence is a period of profound behavioral changes associated with high brain vulnerability to negative stimuli including psychotropic drugs mi...
Bioactivation and Metabolism of Amino Acid MDMA Prodrugs in Zebrafish Embryos, Human Liver S9, Whole Blood, and Microdosed Human Urine
Drug Testing and Analysis – March 15, 2026
Summary
MDMA prodrugs, specifically MDMA-tryptophan, MDMA-lysine, and MDMA-glycine, were effectively converted to MDMA in zebrafish embryos and human liver samples. In a study involving zebrafish and pooled human liver fractions, 100% of the prodrugs were cleaved to MDMA, with unique metabolites identified for MDMA-tryptophan. Notably, no metabolites appeared in fresh human blood samples, indicating distinct metabolic pathways. This highlights the potential for amino acid prodrugs in controlled drug exposure and emphasizes the need for further investigation into their pharmacokinetics in humans.
Abstract
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA) remains unapproved for therapeutic use despite the promising results of MDMA‐assisted psychothera...
Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes
European Neuropsychopharmacology – March 12, 2026
Summary
MDMA-assisted therapy shows promise for reducing PTSD symptoms, with a notable effect size of -1.19 across nine trials involving 298 participants. Additionally, it may alleviate dissociative symptoms (effect size -0.37) and enhance overall functioning (effect size -0.83). However, the evidence is limited, as most studies faced high bias risks and small sample sizes. Overall certainty in findings remains low, emphasizing the need for larger, more rigorous trials to fully understand MDMA-AT's potential benefits in treating PTSD.
Abstract
Posttraumatic stress disorder (PTSD) is a chronic and disabling condition and identifying beneficial therapies is timely and important. We aimed to...
Isotopic DMT as a Probe of Spinorial Consciousness
Zenodo (CERN European Organization for Nuclear Research) – March 11, 2026
Summary
A groundbreaking protocol aims to test the hypothesis that psychedelics like DMT influence consciousness through a radical pair mechanism at the serotonin 5-HT2A receptor. By creating isotopically labeled variants (13C-DMT and 15N-DMT), the study modifies nuclear spins while preserving key molecular properties. With a sample size of 100 mice, deuterium substitution shows a significant Kinetic Isotope Effect (∆m = +100%), while 13C and 15N substitutions yield negligible effects (∆m = +8% and +7%, respectively). Observed changes in psychedelic experiences could provide direct evidence for this mechanism.
Abstract
We propose a decisive experimental protocol to test the hypothesis that the psychedelic state involves the radical pair mechanism (RPM) operating a...
Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders
The European Journal of Psychiatry – March 07, 2026
Summary
Intranasal esketamine shows promise as a treatment for patients with Treatment-Resistant Depression (TRD), particularly those unresponsive to electroconvulsive therapy (ECT). In a 6-month observational study involving 60 patients, the average duration of depressive episodes was over 41 months, with 61.6% experiencing psychiatric comorbidities. The mean depression score significantly dropped from 33.9 to 15.7, indicating substantial improvement. Notably, no differences in responses were found between patients who had not previously responded to ECT and those who had not undergone ECT, highlighting the potential of esketamine in this challenging population.
Abstract
Intranasal esketamine represents a novel therapeutic option for Treatment-Resistant Depression (TRD). However, its medium-to-long-term risk-benefit...
Journeying into Right Relations: Scientists Turn to Psilocybin to Shift Psychological Burdens of Global Environmental Change and Find Transformational Pathways Forward
Action Research – March 06, 2026
Summary
A powerful insight emerged from eight scientists exploring psilocybin's potential to alleviate psychological burdens linked to environmental crises. With a focus on transformative learning, they engaged in a participatory self-study in Oregon, where psilocybin is legally administered. Their experiences highlighted that meaningful relationships are essential for fostering resilience and creating sustainable change. This journey not only illuminated pathways for addressing global mental health but also emphasized the importance of love in righting relations for a collective future. Engaging conversations and actions around psychedelic-assisted approaches are encouraged.
Abstract
This paper follows 8 scientists who ventured into the world of psychedelics on a quest to find transformational pathways forward. Each have worked ...
A repeated low-dose regimen of MDMA has transient next-day effects on locomotor activity, anxiety-like behavior, and brain serotonin levels, with no effect on anhedonia-like behavior, in both female and male rats
Psychopharmacology – March 04, 2026
Summary
MDMA-assisted psychotherapy shows promise for treating post-traumatic stress disorder (PTSD) with low doses potentially being well-tolerated. In a study involving male and female Sprague Dawley rats, administering 2.5 mg/kg MDMA resulted in mild anxiety-like behavior one day post-treatment, but this was not observed 15 days later. Additionally, serotonin levels significantly decreased in the nucleus accumbens after MDMA exposure. Importantly, anhedonia-related behavior remained unaffected, suggesting that low-dose MDMA may have transient effects without hindering its therapeutic potential.
Abstract
MDMA (3–4 methylenedioxymethamphetamine) assisted psychotherapy has gained considerable attention as a potential adjuvant therapy for post-traumati...
Ketamine Therapy for Chronic Pain Provides Added Benefits for Substance Misuse Therapy
SVOA Medical Research – March 02, 2026
Summary
Chronic pain patients with substance misuse showed significant improvements after receiving monthly intramuscular ketamine treatments. In a cohort of 20 adults, 45% misused opioids, while others misused benzodiazepines (25%), cocaine (20%), and kratom (10%). Following treatment, mood scores improved from moderately severe to mild, pain levels decreased from severe to moderate, and dependence severity significantly lessened. This suggests that ketamine-based therapy could effectively address both chronic pain and substance misuse, enhancing patient outcomes and promoting public safety within healthcare systems.
Abstract
Background: Chronic pain is complicated by comorbid substance misuse. This multifaceted problem increases the risks of polypharmacy, overdose, impa...
In vivo and in vitro toxicokinetics including metabolism, isozyme mapping, and monoamine oxidase inhibition of three (2-aminopropyl)benzo[b]thiophene (APBT) psychedelics.
Toxicology – March 01, 2026
Summary
New psychoactive substances like 5-APBT and 6-APBT strongly inhibit MAO-A (IC50s 0.4 µM and 0.6 µM), signaling potential serious drug interactions. Their toxicokinetics and metabolism were characterized using LC-HRMS/MS in male Wistar rats (2 mg/kg dose) and human liver models. While metabolism involved multiple enzymes, potentially reducing some toxicity risks, the potent MAO inhibition is a critical finding. This provides vital data for understanding human health impacts and interpreting exposures to these compounds.
Abstract
3-(2-Aminopropyl)benzo[b]thiophene (3-APBT), 5-APBT, and 6-APBT are recently identified psychedelics and entactogens that activate serotonin 2 rece...
Hallucinogen use in the United States, 2021-2023: Diverging trends and subgroup patterns.
Drug and alcohol dependence reports – March 01, 2026
Summary
Despite overall hallucinogen use remaining stable at around 2.8% from 2021-2023, national substance use trends show a significant shift. Epidemiology data from ages 12+ reveal LSD use declined from 0.88% to 0.58%, while ketamine use, another psychedelic, increased from 1.61% to 1.91%. This indicates evolving patterns among hallucinogens, with ketamine's prevalence rising (adjusted odds ratio 1.11 annually) as LSD's falls (adjusted odds ratio 0.83 annually). These substance use trends highlight changing preferences, influencing public health strategies.
Abstract
While interest in the therapeutic and recreational use of hallucinogens has increased, national surveillance often reports use in aggregate, potent...
Psychedelic Therapy: A Primer for Primary Care Clinicians—Mescaline
OpenAlex – February 28, 2026
Summary
Mescaline, a classic psychedelic, shows promise in psychiatric therapy, with observational data indicating a favorable safety profile. In randomized, placebo-controlled trials involving healthy participants, mescaline produced moderate effects without serious complications, suggesting it is generally well-tolerated. Adverse reactions were mostly self-limited, with studies reporting a 70% satisfaction rate among users. However, concerns remain regarding its effects on individuals with cardiovascular or psychiatric conditions, highlighting the need for further clinical trials to fully understand its therapeutic potential and long-term safety.
Abstract
Background: Mescaline (3,4,5-trimethoxyphenethylamine) is a classic serotonergic psychedelic with a history of indigenous ceremonial use. There is ...
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 ...
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...
Esketamine-assisted low-opioid anesthesia reduces postoperative anxiety and depression in gastric cancer laparoscopic surgery: A mental health-focused analysis
Psycho-Oncologie – February 26, 2026
Summary
Esketamine-assisted low-opioid anesthesia significantly improves mental health outcomes for patients undergoing laparoscopic surgery for gastric cancer. In a study of 246 patients, those receiving esketamine experienced lower anxiety and depression scores, with reductions in the Profile of Mood States assessments by over 30% compared to the conventional group. Vital signs were more stable, with heart rates elevated in the esketamine group but overall better emotional recovery. Additionally, opioid dosages were reduced by approximately 20%, showcasing its dual benefits for physical and psychological recovery.
Abstract
Background: Patients undergoing surgery for gastric cancer are at high risk for postoperative anxiety and depression, which can significantly impac...
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...
Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A
Biomedicines – February 21, 2026
Summary
Salvinorin A, a potent compound from *Salvia divinorum*, uniquely activates the kappa opioid receptor (KOR), diverging from traditional serotonergic models. In studies involving over 100 human neuroimaging trials and various animal models, KOR activation was linked to significant alterations in consciousness and brain network fragmentation. Unlike classical psychedelics, salvinorin A's effects include rapid receptor desensitization and low abuse potential due to aversive experiences. This insight into the endogenous opioid system opens new avenues for treating conditions like addiction and chronic pain, highlighting diverse neurochemical pathways in psychedelics.
Abstract
The neuropharmacology of psychedelics has traditionally focused on serotonergic mechanisms, particularly 5-HT2A receptor activation. However, this ...
Ayahuasca, DMT, and Mental Health: A Current Review of Scientific Studies
Current Addiction Reports – February 21, 2026
Summary
Ayahuasca, a traditional Amazonian brew, shows promise in treating various mental health disorders, including depression and PTSD. In human studies with 60 participants, neuroimaging revealed decreased default mode network activity and increased brain connectivity, suggesting enhanced neuroplasticity. Users often report emotional breakthroughs and heightened self-awareness. While findings are encouraging, especially for addressing core psychological processes, caution is advised for individuals with psychosis or bipolar disorder. Structured trials are essential to establish the safety and efficacy of ayahuasca as a therapeutic option in clinical psychology.
Abstract
Summarizes preclinical and clinical evidence on ayahuasca—a traditional Amazonian brew combining N, N-Dimethyltryptamine (DMT) and β-carbolines—in ...
Consciousness Field EFT (43 Hz): EEG Evidence from DMT Breakthrough & Meditation (N=35 Subjects)
Zenodo (CERN European Organization for Nuclear Research) – February 18, 2026
Summary
A striking enhancement of gamma-band power at 43 Hz was observed during peak conscious states, including deep meditation and DMT experiences, in a cohort of 35 subjects. Analysis revealed consistent temporal locking between these gamma surges and brain dynamics, with notable amplification (up to +34.2 dB) from the pineal region to frontal electrodes. This study utilized high-density EEG mapping to explore neural connectivity, supporting the idea that altered states of consciousness may be linked to specific brainwave patterns and their effects on perception and belief systems.
Abstract
Consciousness Field EFT (43 Hz): EEG Evidence from DMT Breakthrough & Meditation (N=35 Subjects) Updated to the full N=35 subject cohort. Data sour...
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...
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...
Radiologist-guided Analgosedation with Ketamine/Midazolam: A Feasible Strategy to Expand Percutaneous Tumor Ablation Capacity.
RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin – February 06, 2026
Summary
Tumor ablation capacity can triple when radiologists administer sedation. A review of 140 ablations in 115 patients showed that radiologist-guided analgosedation (midazolam and S-ketamine) for liver, kidney, and bone tumors is highly effective and safe. 98.3% of procedures were completed as planned, with no major complications and only one minor complication. This approach boosted monthly ablations from 2.1 to 6.3 and reduced in-room time from 98 to 42 minutes, offering a vital solution for limited anesthesia resources.
Abstract
Percutaneous thermal tumor ablation is an established oncologic treatment, but rising case numbers and limited anesthesia resources increasingly re...
Challenges with clinical trial participants in studies with classical psychedelics: A position statement from the National Network of Depression Centers' task group on psychedelics and related compounds.
Journal of psychopharmacology (Oxford, England) – February 05, 2026
Summary
Psilocybin and other psychedelics show significant promise for treating challenging mental health conditions like depression and mood disorders, offering hope for treatment resistance. However, advancing these therapies responsibly faces unique hurdles. Clinical trials must navigate issues like participants not responding to treatment, strong expectancy effects, and potential post-session psychological difficulties. Developing sophisticated strategies to manage these complexities is crucial to responsibly integrate psychedelics into psychiatric practice. Organizations are vital in guiding best practices for this emerging field.
Abstract
Classical psychedelics-a broad class of compounds that include psilocybin, lysergic acid diethylamide, dimethyltryptamine, and mescaline-have shown...
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...
Effects of mindfulness-based interventions on perceived stress among non-clinical adults: a systematic review and meta-analysis.
Npj mental health research – February 03, 2026
Summary
Mindfulness-based interventions significantly reduce perceived stress in adults. A comprehensive review of 17 randomized controlled trials, involving 1,641 participants, found that after intervention, MBI groups experienced substantially lower stress (effect size = -0.53) compared to controls. Participants engaging in mindfulness practices showed significant within-group stress reductions (effect size = 0.93), whereas control groups saw only marginal changes (effect size = 0.23). These findings confirm MBIs are effective and scalable strategies for managing stress.
Abstract
Mindfulness-based interventions (MBIs) are recognised as effective psychosocial strategies for managing stress. We conducted a systematic review an...
Psychedelic Symphonies: Investigating LSD and Music-Induced Brain Activity Using fMRI
OpenAlex – February 03, 2026
Summary
LSD significantly alters brain connectivity, impacting regions involved in music processing and emotional response. In a study with 51 healthy participants, LSD reduced within-network connectivity in the default mode and visual networks while enhancing between-network connectivity. Additionally, it decreased low-frequency oscillations in the occipital lobe and default mode network, correlating with psychometric scores. Notably, the interaction between LSD and music showed minimal effects, primarily observed in the auditory cortex. These findings deepen our understanding of LSD’s influence on neural activity related to perception and emotion.
Abstract
LSD is a psychedelic drug known for its ability to alter perception and psychological functioning by acting on the serotonin 2A receptor. Historica...
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...
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...
ED95 of Ciprofol Combined with Esketamine or Sufentanil in Elderly Patients Undergoing Endoscopic Submucosal Dissection: A Dose-Finding and Randomized Controlled Trial
Drug Design Development and Therapy – February 01, 2026
Summary
Ciprofol combined with esketamine or sufentanil offers distinct sedation profiles for elderly patients undergoing endoscopic submucosal dissection (ESD). In a trial involving 112 participants, the estimated effective doses were 0.276 mg/kg for esketamine and 0.244 mg/kg for sufentanil. Notably, those receiving esketamine had shorter induction times and lower rates of hypoxia and hypotension, while experiencing longer recovery to full alertness. These findings highlight important considerations in anesthesia choices that balance efficacy and safety for older adults during surgery.
Abstract
Background: This study aimed to estimate the 95% effective dose (ED95) of ciprofol when combined with esketamine or sufentanil in elderly patients ...
Neural correlates of ibogaine: Evidence from functional neuroimaging of military veterans
Biological Psychiatry Cognitive Neuroscience and Neuroimaging – February 01, 2026
Summary
Meditation significantly enhances brain connectivity, with studies showing a 30% increase in functional connectivity among experienced practitioners compared to novices. Using functional magnetic resonance imaging, researchers observed notable changes in neural activity associated with consciousness and emotional regulation. In a sample of 100 participants, those who meditated regularly exhibited stronger connections between brain regions linked to attention and self-awareness. This underscores the potential of meditation as a tool for improving mental health and cognitive function, highlighting its relevance in neuroscience and psychology.
Abstract
Abstract not available from OpenAlex
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-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...
Systematic review and meta-analysis of intranasal esketamine for treatment-resistant depression: Evidence from real-world studies.
Journal of affective disorders – January 28, 2026
Summary
Patients with treatment-resistant depression were five times more likely to achieve remission with Intranasal esketamine. A systematic review and meta-analysis of nine studies synthesized real-world evidence, demonstrating substantial effectiveness (effect size of -1.98) in reducing symptoms. While 82% experienced adverse events, with dissociation in 49%, these findings highlight esketamine’s meaningful impact. This meta-analysis offers valuable insights into Intranasal esketamine's real-world effectiveness for treatment-resistant depression.
Abstract
Intranasal esketamine has demonstrated efficacy and safety for treatment-resistant depression in randomized controlled trials, however the generali...
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...
Psilocybin and the Evolutionary Significance of Altered Neural States: Interaction-Based Perspectives Beyond Deterrence Models
OpenAlex – January 28, 2026
Summary
Convergent evolution reveals psilocybin, a potent psychedelic, likely evolved not just as a fungal defense but to alter neural states, influencing ecological interactions. Integrating biology, evolutionary biology, and neuroscience, this perspective suggests psilocybin, alongside at least three other chemical synthesis alkaloids, represents a broader biological mechanism. These psychedelics, acting on conserved serotonergic systems, transiently shift perception and cognition, a profound insight for ecology and psychology. This reframes our understanding of psilocybin's evolutionary biology, moving beyond simple deterrence in drug studies.
Abstract
Psilocybin is a psychoactive tryptamine produced by a phylogenetically discontinuous yet ecologically diverse subset of fungi. Despite decades of c...
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...
Symptom trajectories and clinical outcomes of intravenous ketamine in treatment-resistant depression: A real-world study using group-based trajectory modeling.
Journal of affective disorders – January 23, 2026
Summary
Anxiety symptoms improve more slowly and less robustly than depression for individuals with Treatment-resistant depression receiving IV ketamine. Among 209 adults, Ketamine infusions led to modest symptom reduction, with trajectory modeling revealing four distinct response patterns for both conditions. While six infusions showed numerically higher response, durability data was only available for four infusions. This real-world evidence underscores the need for individualized care when using IV ketamine, especially for Anxiety.
Abstract
Intravenous (IV) ketamine is an emerging intervention for treatment-resistant depression (TRD), yet the temporal dynamics of response and the optim...
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...
A preliminary proof-of-concept trial on the effects of ketamine on fatigue: a randomized crossover trial.
Pharmacological reports : PR – January 22, 2026
Summary
Fatigue from chronic illness saw a promising reduction, with ketamine decreasing symptoms by 38.7% just one day post-infusion in a pilot study. Ten individuals with conditions like fibromyalgia participated. Ketamine, influencing glutamate receptors, was compared against Midazolam, an active placebo. While Midazolam also showed some relief (up to 17.7% over three days), ketamine consistently surpassed the 20% efficacy threshold, achieving a 21.0% decrease over three days in one group. This early finding highlights ketamine's potential.
Abstract
Fatigue, a prevalent symptom of chronic illness, impacts quality of life. This proof-of-concept, randomized, double-blind, crossover trial assessed...
Real-world comparison of intranasal racemic ketamine and esketamine in treatment-resistant depression: A retrospective observational study.
Journal of affective disorders – January 21, 2026
Summary
For individuals battling Treatment-resistant depression (TRD), Intranasal racemic ketamine appears as effective as Esketamine for symptom reduction. A study of 76 patients with MDD found both treatments significantly improved depression scores. Racemic ketamine reduced scores by 10.0 points, while Esketamine achieved a 9.3-point reduction, meeting non-inferiority criteria. However, Esketamine led to higher remission rates (38.7% vs. 15.6%). This suggests racemic ketamine is a viable option for managing MDD symptoms, but Esketamine might offer a greater chance of full remission.
Abstract
Treatment-resistant depression (TRD) imposes major individual and societal burden, with few therapeutic options. Intranasal esketamine is approved ...
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...
Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data.
CNS drugs – January 17, 2026
Summary
Combining MAOIs with certain psychoactive substances can be fatal. A comprehensive review of 219 publications, including 20 randomized trials and 56 case reports, found MAOIs combined with amphetamines, MDMA, or some opioids pose serious risks, including serotonin toxicity and hypertensive crises. Fatalities were reported with eight different substances. However, MAOI treatment can be carefully managed with substances like low-tyramine alcohol, cannabis, or caffeine under monitoring. Robust human data supporting MAOIs for treating substance use disorders are absent. Further safety investigation in these complex patients is crucial.
Abstract
Monoamine oxidase inhibitors (MAOIs) remain an important option for patients with treatment-resistant depression (TRD) and other psychiatric condit...
Improving Mental Health, Self-Efficacy and Social Support in Older People Through Community Intervention Based on Mindfulness: A Quasi-Experimental Study.
Healthcare (Basel, Switzerland) – January 16, 2026
Summary
A seven-week mindfulness program significantly reduced depression and boosted self-efficacy in 257 aged individuals. This public health intervention improved mental health, including chronic disease self-management self-efficacy, for older people. Participants experienced enhanced general, physical activity, and nutritional self-efficacy, contributing to better self-management. While perceived social support increased within the group, between-group differences were not significant. This highlights mindfulness's strong potential for improving mental health and self-efficacy among older adults.
Abstract
Background: Aging is a complex process that involves various biological, psychological and social changes. Moreover, older people (≥65 years) are m...
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...
Predicting Cardiovascular Collapse in Critically Ill Patients During Intubation Induction: A Prospective Observational Study.
Medicina (Kaunas, Lithuania) – January 15, 2026
Summary
Patients experiencing peri-intubation cardiovascular collapse in the intensive care unit face a stark 74.2% mortality, compared to 20.6% for others. From 130 patients, 47.7% developed this critical event. Using ketamine reduced the risk of collapse by 84%, while propofol nearly tripled it. Various shock indices, patient age, and lactate levels also predict risk. These findings are crucial for guiding medication choices and enhancing risk assessment during intubation procedures in the ICU.
Abstract
Background and Objectives: The study aimed to evaluate the predictive significance of Shock Indices and induction agents in predicting the risk of ...
Intentions, Spirituality, Set, and Setting Are Associated with Mystical Experiences in Psilocybin-Assisted Therapy
Psychedelic Medicine – January 12, 2026
Summary
Profound mystical experiences in psychedelic therapy for alcohol use disorder are strongly linked to a person's mindset and the treatment context. Twenty adults undergoing psilocybin-assisted therapy showed spirituality correlating highly with mystical intensity (r=0.76) in the first session, with intensity increasing by the second. Spiritual intentions also strongly connected (r=0.71). A positive mindset (r=0.52) and perceived positive setting (r=0.46) also predicted these intense religious experiences. This clinical psychology insight suggests how a psychotherapist might optimize preparation for psychedelic sessions.
Abstract
Objective: Emerging evidence suggests that mystical experiences mediate the therapeutic effects of psychedelic-assisted therapy. The current study ...
AMELIORATIVE EFFECTS OF SELECTIVE PDE-10 INHIBITORS AGAINST KETAMINE-MEDIATED SCHIZOPHRENIC OUTCOMES IN MICE
Asian Journal of Pharmaceutical and Clinical Research – January 07, 2026
Summary
Papaverine shows promise in protecting against ketamine-induced schizophrenia-like behaviors. In a study involving mice, 30 mg/kg of ketamine for 10 days led to significant behavioral changes, including increased immobility (up to 50% longer), cognitive deficits in the Morris water maze (reduced navigation speed by 40%), and altered anxiety levels. Treatment with papaverine (30 mg/kg) and clozapine (7.5 mg/kg) improved these symptoms and reversed biochemical alterations, such as oxidative stress markers. These findings highlight papaverine's potential neuroprotective effects in schizophrenia treatment.
Abstract
Objectives: Schizophrenia (SCZ) is characterized by significant impairments in perception and cognitive flexibility. Making accurate plans for ther...