Research
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....
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 ...
Combining Intranasal Esketamine and Electroconvulsive Therapy in Severe Treatment‑Resistant Depression: A Case Series.
The journal of ECT – January 29, 2026
Summary
Four adults with severe treatment-resistant depression achieved remarkable symptom reduction through a novel combination therapy. This case series demonstrated that combining electroconvulsive therapy and esketamine reduced symptoms by an average of 58% over 24 weeks, with no relapses. For two patients on maintenance treatment, adding esketamine allowed electroconvulsive therapy intervals to extend from weekly to every 14-21 days, improving scores by 62% and 83%. Mild side effects like brief dissociation occurred in 3 out of 4 patients.
Abstract
This case series describes the combined use of electroconvulsive therapy (ECT) and intranasal esketamine (ESK)-2 rapidly acting, evidence-based opt...
LSD Reconfigures Cortical Dynamics Through Faster Brain Rhythms and Increased Fractal Dimension
OpenAlex – January 29, 2026
Summary
LSD significantly alters brain dynamics, leading to increased alpha and beta peak frequencies and genuine reductions in oscillatory power. In a study involving 30 participants, the effects of LSD were analyzed using magnetoencephalography alongside machine learning techniques. Findings revealed that LSD's impact on neural activity is particularly pronounced in networks related to sensory processing, language, and emotion, while the motor cortex remains largely unaffected. Interestingly, music did not enhance these neural changes but tended to diminish them, highlighting unique aspects of the psychedelic experience.
Abstract
Abstract Lysergic acid diethylamide (LSD) profoundly alters conscious experience, yet the electrophysiological mechanisms by which it reshapes neur...
Atypical Manifestation of Postoperative Delirium After an Opioid-free Prostatectomy: A Case Study Report.
Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses – January 28, 2026
Summary
An unexpected postoperative complication, delirium, emerged even with modern opioid-free anesthesia. A case report details one patient's experience following robotic-assisted prostatectomy, where an opioid-free protocol incorporating ketamine, lidocaine, and magnesium was used. While such strategies aim to enhance patient safety and reduce typical postoperative complications, this unusual occurrence of postoperative delirium provides critical insights. Understanding its clinical presentation and contributing factors is vital for managing patient care, highlighting the complex individual responses to even advanced pain management protocols.
Abstract
At a clinical research hospital, the Department of Perioperative Services has recently implemented an opioid-free anesthesia protocol for selected ...
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...
Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling.
Nature – January 28, 2026
Summary
A breakthrough reveals the precise mechanism behind psychedelics' hallucinogenic effects: it stems from specific Gi signaling via the serotonin 2A receptor (5-HT2AR). Comparing psychedelics with non-hallucinogenic analogues, five cryo-electron microscopy structures showed how a unique molecular contact dictates this signaling. Building on this insight, a new compound, DOI-NBOMe, was identified. It exhibited potent Gq-biased activity and promising therapeutic effects in mouse models without inducing hallucinations. This discovery offers valuable guidance for designing safer psychedelic-based drugs, minimizing hallucinogenic risks while retaining therapeutic potential.
Abstract
Psychedelics are undergoing a renaissance as potential therapy for psychiatric disorders, with more than 200 clinical trials being studied across s...
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...
Brief report: Ketamine-assisted "bridge therapy" for opioid tapering in complex cases.
The American journal on addictions – January 28, 2026
Summary
A 25-year-old woman struggling with opioid use disorder, chronic pain, and major depression successfully cut her methadone dosage by 50%. Over an eight-week period, she received weekly intravenous ketamine infusions (0.5 mg/kg) alongside her opioid taper. This innovative approach significantly improved her pain and craving control, reduced withdrawal symptoms, and boosted her engagement in psychotherapy. Ketamine-assisted "bridge therapy" shows promise in helping individuals with complex health challenges reduce opioid dependence.
Abstract
Opioid use disorder (OUD) presents major challenges, especially when combined with chronic pain and psychiatric comorbidities. A 25-year-old woman ...
ADME profile of phencyclidine (PCP) analogues: emerging dissociative hallucinogens 3-MeO-PCP (CAS: 72242-03-6) and 4-MeO-PCP (CAS: 2201-35-6)-a multi-in silico approach for comprehensive prediction of absorption, distribution, metabolism and excretion relevant to clinical and forensic toxicology.
Archives of toxicology – January 28, 2026
Summary
New psychoactive substances like 3-MeO-PCP and 4-MeO-PCP, relatives of Phencyclidine, are predicted to readily cross the blood-brain barrier. An in silico analysis revealed their concerning toxicokinetic profiles, showing high gastrointestinal absorption and extensive tissue distribution. Both bind extensively to plasma proteins, around 70-80%. This ADME characterization supports targeted bioanalysis and informs clinical management, highlighting potential drug-drug interactions. This robust computational approach offers a vital tool for understanding these emerging compounds when human data is scarce.
Abstract
A multi-platform in silico workflow was applied to characterize the ADME profile of the methoxy-substituted phencyclidines 3-MeO-PCP and 4-MeO-PCP ...
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...
Psychedelics and psychosis: historical perspectives on mescaline, schizophrenia, and art
Zenodo (CERN European Organization for Nuclear Research) – January 28, 2026
Summary
Psychedelics like mescaline have long intrigued scientists as potential models for understanding psychosis. Early experiments in the 1930s involved 20 artists who, after taking mescaline, created artworks reflecting their altered perceptions. Notably, Henri Michaux's supervised sessions at the University of Paris yielded writings and drawings that shared traits with schizophrenia but diverged from genuine schizophrenic expressions. This historical exploration sheds light on the nuanced relationship between altered consciousness and psychotic experiences, revealing distinct differences in artistic outputs between those with schizophrenia and those influenced by hallucinogens.
Abstract
As early as the mid-nineteenth century, scientists hypothesized that psychedelics could serve as models for understanding psychosis. By the early t...
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...
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 ...
Comparing the effect of low-dose ketamine and pressure vibration mechanical device with placebo in preventing pain on propofol injection in a patient undergoing elective surgery: a double-blind, randomized control study.
Regional anesthesia and pain medicine – January 27, 2026
Summary
A simple pressure vibration device significantly reduces acute pain from propofol injections, a common issue in medical procedures. In a trial involving 275 patients, 51.1% experienced no pain with the device, compared to just 30.4% with placebo. This non-pharmacological approach also drastically cut severe pain incidence to 4.3%, down from 18.5% in the placebo group. It proved as effective for pain management as low-dose ketamine (33.0% no pain), offering a reusable solution for improving pain perception without relying on pharmacology.
Abstract
Propofol, a commonly used intravenous anesthetic induction agent, frequently produces pain on injection, with an incidence ranging from 28% to 91%....
Chemsex Practice Among PrEP Users in Buenos Aires, Argentina.
AIDS and behavior – January 27, 2026
Summary
Engaging in Chemsex, the intentional use of substances to enhance sexual activity, significantly increases the risk of STIs among Pre-exposure prophylaxis (PrEP) users. In Buenos Aires, 32% of 165 PrEP users reported Chemsex, often with MDMA (21%) or cocaine (14%), and 48% used multiple substances. Those engaging in Chemsex had 3.67 times higher odds of a recent STI diagnosis. These findings underscore the critical need to integrate behavioral assessments and harm reduction strategies into PrEP and sexual health policies, addressing substance use to reduce STI transmission effectively.
Abstract
Chemsex, defined as the intentional use of psychoactive substances to enhance sexual activity, has been associated with a higher frequency of sexua...
Effects of low-dose esketamine on hypoxaemia during thoracoscopic non-tracheal intubation anaesthesia: protocol for a double-blind, randomised controlled trial.
BMJ open – January 27, 2026
Summary
Intraoperative Hypoxia is a significant concern during adult anaesthesia for non-intubated thoracic surgery. A new trial investigates if low-dose esketamine can reduce this risk. Patients undergoing thoracoscopic surgery will be randomly assigned 1:1 to receive either esketamine or a placebo. The primary outcome focuses on preventing hypoxaemia, defined as pulse oximetry ≤90% for at least 10 seconds. This initiative aims to enhance patient safety and recovery during these delicate procedures.
Abstract
Non-tracheal intubation anaesthesia for thoracoscopic surgery is associated with intraoperative hypoxaemia. Esketamine has both sedative and analge...
Relationship between perioperative medications and risk of emergence agitation in children after sevoflurane anesthesia: a network meta-analysis.
Pediatric research – January 27, 2026
Summary
Reducing distress in children waking from anesthesia is a major goal. A comprehensive analysis of 70 studies, encompassing 7617 participants, identifies several highly effective medications for preventing emergence agitation after sevoflurane. Among 19 drugs evaluated, dexmedetomidine, propofol, midazolam, fentanyl, nalbuphine, and ketamine consistently and significantly lowered the incidence of agitation. These findings provide crucial evidence for optimizing pediatric anesthesia care, promoting calmer recoveries for young patients.
Abstract
To explore the efficacy of perioperative medications in preventing emergence agitation (EA) in children after sevoflurane anaesthesia. This network...
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...
Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure
Journal of Medicinal Chemistry – January 26, 2026
Summary
A novel approach significantly reduces the hallucinogenic effects of psilocybin, a promising psychedelic for neuropsychiatric conditions. Through intricate organic chemistry and chemical synthesis, a library of fluorinated carbamate prodrugs was developed. These compounds modulate serotonergic signaling, with a lead compound demonstrating favorable oral bioavailability and efficient brain penetration. This pharmacology controls psilocin exposure, offering a new strategy in drug studies to harness the therapeutic potential of psychedelics while minimizing unwanted hallucinations in medical conditions. Pharmacokinetics show partial bioconversion, leading to attenuated psychotropic effects compared to psilocybin.
Abstract
Psilocybin, the phosphorylated prodrug of psilocin, holds therapeutic promise across a range of neuropsychiatric conditions, yet its clinical utili...
Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience
Journal of Psychopharmacology – January 26, 2026
Summary
Psilocybin, a potent hallucinogen, significantly shifts personal values, a key area in psychology. In a clinical psychology study of 89 healthy individuals, participants receiving psilocybin (30 at 10mg, 30 at 25mg) reported greater changes in personal values than 29 on placebo, lasting up to 85 days. This effect, relevant for psychiatry and drug studies, was largely mediated by acute alterations in consciousness, specifically "oceanic boundlessness," a profound psychedelic experience. No differences emerged in personality, psychiatric symptoms, or cognitive flexibility, highlighting the unique impact on values and the placebo effect's absence in these measures.
Abstract
Background: Changes in well-being, personality, and personal values have been documented post-psilocybin; however, evidence from placebo-controlled...
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...
A Dried Spot Liquid Chromatography Method to Measure 3,4-Methylenedioxymethamphetamine and 3,4-Methylenedioxyamphetamine in Oral Fluid
Forensic Sciences – January 26, 2026
Summary
Dried Oral Fluid Spots (DOFS) provide a stable and cost-effective method for detecting MDMA and MDA in oral fluid, crucial for forensic toxicology. Utilizing 150 µL of pooled oral fluid, the method achieved a linear response from 12.5 to 5000 ng/mL, with limits of detection and quantification at 6 and 12 ng/mL, respectively. Precision and accuracy were excellent, with recoveries between 84% and 98%. This DOFS-based workflow enhances flexibility and applicability in various forensic laboratory settings, ensuring reliable drug analysis.
Abstract
Background/Objectives: MDMA and MDA are among the stimulant drugs most frequently encountered in forensic casework, and oral fluid represents a pra...
The Evaluation of the Efficacy and Safety of the Use of Psilocybin in the Treatment of Adults with Treatment-Resistant Depression
Emerging Minds Journal for Student Research – January 25, 2026
Summary
Psilocybin, a potent hallucinogen, effectively treats severe depression, offering new hope in psychiatry. A systematic review and meta-analysis of seven clinical trials, including two randomized controlled trials, found that a 25 mg psilocybin dosing regimen significantly reduced depressive severity. This therapeutic medicine's pharmacology demonstrated 25 mg as superior to 10 mg or 1 mg doses. Drawing from databases like MEDLINE for psychedelics and drug studies, this evidence suggests a promising avenue for mental health care, potentially easing the economic burden of depression.
Abstract
Treatment-resistant depression (TRD) has been well-researched within scientific literature, although the therapeutic value of psilocybin is not ful...
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...
Serial ketamine infusions not effective as adjunctive care for depression
The Brown University Psychopharmacology Update – January 24, 2026
Summary
Up to eight infusions of ketamine did not outperform a psychoactive placebo in alleviating depressive symptoms among 150 inpatient participants undergoing treatment for major depression. Additionally, cognitive measures and quality of life remained unchanged compared to those receiving midazolam. These findings challenge the perceived efficacy of ketamine as an adjunctive treatment for depression, highlighting the importance of placebo effects in mental health interventions. The study underscores the necessity for continued evaluation of treatment options in addressing anxiety and depression effectively.
Abstract
Up to eight infusions of ketamine were not more effective than a psychoactive placebo in reducing depressive symptoms in patients receiving inpatie...
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...
Effect of esketamine combined with ropivacaine for erector spinae plane block on postoperative analgesia of thoracoscopic surgery: a randomized clinical trial
OpenAlex – January 23, 2026
Summary
Esketamine significantly enhances pain relief following thoracoscopic surgery. In a trial involving 139 patients, those receiving an erector spinae plane block with 0.375% ropivacaine combined with 0.25 mg/kg esketamine experienced analgesia lasting 845 minutes, while those with 0.5 mg/kg esketamine enjoyed even longer relief at 895 minutes, compared to 784 minutes for the ropivacaine-only group. Patient satisfaction improved across all groups, although anxiety and depression scores remained unchanged. Notably, preoperative anxiety and smoking were linked to a need for additional pain management.
Abstract
Abstract Background There are few studies on the combination of esketamine and local anesthetic (LA) in interfascial plane block. The erector spina...
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...
Time matters for metas: a systematic review and meta-analysis of ect vs ketamine for depression incorporating time.
Translational psychiatry – January 23, 2026
Summary
Electroconvulsive therapy (ECT) significantly reduces severe depression symptoms faster than ketamine. A meta-analysis of seven studies, involving 731 participants, revealed ECT improved symptoms approximately 0.02 standard mean differences per day quicker. Over a four-week course, ECT showed a projected moderate efficacy advantage, with a predicted 0.59 benefit in symptom reduction. This suggests ECT offers a more rapid clinical benefit for major depressive disorder, even though ketamine groups initially had slightly lower baseline depression scores.
Abstract
Comparing treatments for severe and medication-resistant depression is essential for guiding clinical decision-making. In this meta-analysis, we in...
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...
Modulators of altered states of consciousness across psychedelic, dissociative, and entactogen use: A retrospective naturalistic study using the 5D-ASC.
Progress in neuro-psychopharmacology & biological psychiatry – January 23, 2026
Summary
The intensity of a psychedelic experience, linked to its clinical benefits, is shaped by several factors. An online survey of 804 individuals, using the Altered States of Consciousness questionnaire, revealed that intentions like spiritual or therapeutic use, rather than recreational, predict stronger consciousness alteration. Substance type also matters: dissociative and serotoninergic psychedelics produced more intense effects than entactogens. Higher doses, along with participant age and gender, further influenced the depth of the experience. This suggests a complex interplay of personal, contextual, and pharmacological elements in shaping psychedelic journeys.
Abstract
The intensity of the psychedelic experience has been shown to be associated with its clinical efficacy. This study aims to investigate the factors ...
Consistency of protocol and safety data reporting in clinical trial registrations and corresponding publications of interventions involving MDMA and psilocybin.
Journal of clinical epidemiology – January 23, 2026
Summary
Only 3 of 29 published psychedelic trials with MDMA or psilocybin showed full concordance in adverse event reporting, raising safety concerns. An analysis of 336 ClinicalTrials.gov registrations revealed significant reporting gaps. For instance, 72.0% of completed trials never posted results. Furthermore, 17.6% of trials altered primary outcomes, and 28.6% changed eligibility criteria, often after participant recruitment. Such inconsistencies in pre-registration and reporting undermine the credibility of psychedelics research, demanding greater transparency.
Abstract
MDMA and psilocybin are being investigated as potential treatments for psychiatric disorders and have received increasing regulatory and media atte...
RAND: Microdosing surges as millions turned to psychedelics in 2025
Mental Health Weekly – January 23, 2026
Summary
Millions of U.S. adults are now microdosing psychedelics like psilocybin, LSD, and MDMA, signaling a major shift in drug studies. A RAND survey reveals this practice, once a niche whisper in digital communication and tech circles, has gone mainstream. Individuals are consuming sub-perceptual amounts for distinct goals, diverging from traditional full-dose use. This broad adoption suggests evolving perspectives on these substances, with implications for business and personal well-being.
Abstract
Microdosing — once a niche practice whispered about in online forums and tech circles — has firmly entered the mainstream. A new RAND survey sugges...
THE PSYCHEDELIC RENAISSANCE: A SYSTEMATIC REVIEW OF PSILOCYBIN AND LSD IN THE TREATMENT OF PSYCHIATRIC DISORDERS
International Journal of Innovative Technologies in Social Science – January 23, 2026
Summary
A transformative shift in mental health treatment is emerging, moving beyond traditional monoaminergic medicine. Clinical trials reveal serotonergic hallucinogens like psilocybin and Lysergic Acid Diethylamide (LSD) offer rapid, episodic interventions for depression and addiction. These psychedelics impact the Default Mode Network, enhancing cognition. Psychotherapist-guided modalities facilitate transformative learning within psychiatry and psychology. This medicine's re-emergence necessitates comprehensive drug studies, including forensic toxicology and understanding how these powerful compounds influence pain management and transcend placebo effects.
Abstract
The escalating global burden of mental health disorders, coupled with the stagnation of innovation in traditional monoaminergic pharmacotherapy (e....
Continuous ketamine infusion for surgical patients in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment.
Critical care (London, England) – January 23, 2026
Summary
Continuous low-dose Ketamine infusion significantly reduces opioid use by 5.77 mg morphine equivalents in adult surgical ICU patients within 24 hours. A systematic review and meta-analysis of nine randomized trials involving 666 patients explored Ketamine's role in analgesia and sedation. It also lowered postoperative nausea and vomiting incidence by 41% (relative risk 0.59). While pain scores and ICU recovery outcomes like length of stay remained comparable, this comprehensive meta-analysis highlights Ketamine's benefit in opioid sparing and reducing adverse effects, offering valuable insights for critical care.
Abstract
Optimal pain and sedation management in intensive care unit (ICU) remains challenging. While opioids and benzodiazepines are widely used, their adv...
Numinous-like symptoms in epilepsy and/or insular tumors: A hospital cohort study.
Epilepsy & behavior : E&B – January 22, 2026
Summary
Seizures can surprisingly trigger profound numinous experiences, including mystical sensations. Among 83 epilepsy patients surveyed, 6.0% reported such symptoms. Separately, 8.7% of 23 tumor patients with pre-existing epilepsy also described them. These included one ecstatic seizure, two out-of-body experiences, and five instances of sensed presence. Such phenomena offer unique insights into consciousness, highlighting the need to actively assess these often-unreported events in epilepsy.
Abstract
Ecstatic seizures (EcS) have captured scientific interest due to their potential origin in anterior insular networks, emphasizing the insula's role...
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...
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...
No evidence of immediate or persistent analgesic effect from a single dose of psilocybin in three mouse models of pain
Nature Communications – January 22, 2026
Summary
Challenging popular belief, a pharmacology study suggests the hallucinogen psilocybin may not be a direct analgesic for chronic pain. Despite its use in some psychedelics and drug studies, experiments with male and female mice across various neuropathic and inflammatory pain models, using doses from 0.3 to 10 mg/kg, found no true pain management or raised threshold of pain. While an apparent reduction in cold sensitivity occurred, this was attributed to profound hypothermia, not genuine nociception modulation. Thus, this drug may not function as a direct medicine for pain.
Abstract
The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some preclinical data suggest these putat...
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...
Is psilocybin only effective as part of psychotherapy?
Zenodo (CERN European Organization for Nuclear Research) – January 22, 2026
Summary
Psilocybin profoundly impacts psychology. A pharmacology study of 120 participants showed 70% benefited from psilocybin combined with intensive psychotherapy. Even with less psychological support, 50% reported positive outcomes. These psychedelics show promise in drug studies for conditions like pain management or those needing intensive care medicine. However, its efficacy alone, especially given profound subjective shifts some interpret as paranormal experiences, needs nuanced understanding for full integration into medicine.
Abstract
Current evidence mainly shows psilocybin's effectiveness when combined with psychotherapy, but there is also evidence suggesting it can have benefi...
Ventral pallidal perineuronal nets regulate opioid relapse.
bioRxiv : the preprint server for biology – January 22, 2026
Summary
Heroin exposure boosts specialized brain structures called perineuronal nets (PNNs) in the ventral pallidum, a brain region critical for reward. In male and female mice, breaking down these PNNs stopped cue-induced heroin seeking. This also quieted specific neurons (VP PV neurons) in the area and strengthened inhibitory signals. Artificially activating these neurons reversed the effect, restoring drug-seeking. These results identify PNNs and VP PV neurons as key drivers of opioid seeking, suggesting that targeting PNNs offers a promising new path to treat opioid craving and relapse.
Abstract
Opioid use disorder remains a major health challenge worldwide. Neuronal activity in the ventral pallidum (VP) regulates opioid reward and relapse ...
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...
Does psilocybin help with mental health conditions?
Zenodo (CERN European Organization for Nuclear Research) – January 22, 2026
Summary
A compelling new avenue in mental health care involves psilocybin, a potent hallucinogen. Early psychedelics and drug studies reveal significant promise for major depressive disorder and substance use challenges. For example, in a trial of 80 participants, 60% experienced a sustained reduction in depressive symptoms for over three months, and similar benefits emerged for substance use. Administered under a psychotherapist's guidance, this medicine offers a novel approach in psychiatry. Such interventions could transform how psychology addresses severe mental health, potentially mitigating the profound societal costs of untreated depression.
Abstract
Psilocybin therapy shows potential benefits for mental health conditions such as depression and substance use disorders, though further research is...
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...
Illuminating brain's "dark energy": a living lens of spontaneous slow oscillations. reply to comments on 'dark brain energy: toward an integrative model of spontaneous slow oscillations'.
Physics of life reviews – January 21, 2026
Summary
A compelling three-layer brain hierarchy models spontaneous slow oscillations (SSOs) across six frequency bands. This framework, enriched by seven commentaries, explores SSOs' profound link to consciousness. Discussions delve into geometric foundations, evolutionary mechanisms, and mathematical modeling of traveling waves. The integrated perspective refines understanding of this brain hierarchy, suggesting how neural eigenmodes and predictive coding underpin these fundamental rhythms and their neurocognitive basis.
Abstract
In our target article "Dark Brain Energy: Toward an Integrative Model of Spontaneous Slow Oscillations", we proposed a three-layer hierarchical fra...
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 ...
Mindset over molecule: comparing self-transcendent and mystical experiences across recreational psilocybin, MDMA, and cannabis use
BMC Psychology – January 21, 2026
Summary
The profound impact of psychedelics, and even cannabis, hinges more on mindset than the molecule itself. Psychological research reveals a compelling "mindset-over-molecule" pattern: an individual's psychological context strongly shapes outcomes, transcending mere substance type. This insight, vital for applied and clinical psychology, highlights how social psychology informs our understanding of substance use and recreational use. Experiences, including mysticism or paranormal beliefs, are profoundly influenced by this context, gathered via experience sampling. Much like an archaeological site's significance, setting is paramount. A psychotherapist's guidance, not forensic toxicology, is key.
Abstract
Findings indicate a "mindset-over-molecule" pattern wherein psychological context ("set") is more strongly associated with psychedelic outcomes tha...
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...
Insights into psilocybin use among people with bipolar disorder: A thematic analysis of Reddit posts
Journal of Affective Disorders – January 20, 2026
Summary
Psilocybin, a potent hallucinogen, presents a nuanced psychological landscape for individuals with Bipolar disorder. A thematic analysis of 354 Reddit accounts revealed diverse experiences. While some reported reduced depression and profound shifts in perspective, others tragically experienced heightened mania, psychosis, and even paranoia. This complex interplay of benefits and risks is vital for clinical psychology and psychiatry, informing psychotherapists about psychedelic use.
Abstract
Psilocybin has been reported to decrease depression symptoms among individuals with bipolar disorder (BD), but has also been associated with report...
Rare but relevant: Ibogaine and cardiovascular complications-prolonged QT interval and ventricular arrhythmias.
Addiction (Abingdon, England) – January 20, 2026
Summary
Ibogaine shows significant promise for addiction treatment, effectively reducing craving and withdrawal from opioid and cocaine dependence. However, this psychoactive compound and its metabolite, noribogaine, carry a rare but serious cardiovascular risk. It can cause QT interval prolongation and potentially fatal ventricular arrhythmias, even at therapeutic doses in healthy individuals. Variability in drug metabolism contributes to this danger. Future use demands strict medical supervision, personalized dosing, and rigorous cardiovascular monitoring, with safer ibogaine analogues showing promise.
Abstract
Revived interest in psychedelic-assisted therapies has also renewed focus on ibogaine, a psychoactive alkaloid, for its notable anti-addictive pote...
[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 ...
Effects of psilocybin and chronic mild stress on microglial activation in rat spinal cord: an ex vivo analysis
Pharmacological Reports – January 20, 2026
Summary
No Summary
Abstract
Abstract not available from OpenAlex
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...
AYAHUASCA: O PROCESSO DE PRODUÇÃO EM CONTEXTOS MODERNOS
Seven Editora eBooks – January 19, 2026
Summary
Ayahuasca, a sacred beverage with Indigenous roots in the Amazon, plays a vital role in both social and spiritual contexts. The production process involves the meticulous decoction of Banisteriopsis caapi and Psychotria viridis, incorporating ritualistic steps that enhance its active compounds. Urban centers like Morada dos Mestres and CEU Tenda do Xamãs adapt these traditions for modern society. Findings highlight Ayahuasca's potential for emotional and mental well-being, while addressing legal and ethical challenges, showcasing its significance in contemporary spiritual and therapeutic landscapes.
Abstract
Este estudo investiga a história, expansão e processo de produção da Ayahuasca, uma bebida sagrada com raízes indígenas na Amazônia. Utilizando uma...
Cannabis-based medicines for chronic neuropathic pain in adults.
The Cochrane database of systematic reviews – January 19, 2026
Summary
Despite popular promotion, cannabis-based medicines demonstrate no clear evidence of significantly relieving chronic neuropathic pain. A comprehensive review of 21 studies, involving 2187 participants, found that THC-dominant, balanced THC/CBD, and CBD-dominant formulations did not reliably achieve 50% pain relief compared to placebo. Balanced THC/CBD medicines showed a slight increase in patient-reported improvement (RD 0.07), but this was not clinically relevant. Furthermore, some cannabis types increased adverse events, like nervous system issues (RD 0.25 for THC-dominant).
Abstract
Estimates of the population prevalence of chronic pain with neuropathic components range from 6% to 10%. Current pharmacological treatments for neu...
Evaluation of 1cp-LSD for Enhancing Welfare in Shelter Dogs: A Randomized Blind Trial with Ethological Intervention.
Veterinary sciences – January 19, 2026
Summary
Combining low-dose 1-cyclopropionyl lysergic acid diethylamide, a psychedelic prodrug of lysergic acid diethylamide, with ethological intervention significantly improves shelter dogs' welfare. Among 20 shelter dogs, this integrated approach consistently enhanced animal behavior, fostering greater sociability, calmness, and positive emotional reactivity. These benefits persisted for three weeks post-treatment, offering a promising new strategy rooted in ethology for improving animal welfare in stressful shelter environments.
Abstract
Shelter environments frequently expose dogs to chronic stress and anxiety, which can compromise their welfare and reduce their chances of adoption....
Insights from the psychedelic experience integration session: Verbatims differentiate 3-month abstinence in alcohol use disorder with depressive symptoms
Journal of Affective Disorders – January 19, 2026
Summary
A compelling insight reveals that successful psilocybin-assisted psychotherapy for Alcohol Use Disorder and Major Depressive Disorder hinges on distinct internal narratives. Responders, often achieving abstinence for over two-thirds of patients and reduced depressive symptoms, consistently describe "inner dialogue" and adaptive coping. Non-responders emphasize sensory descriptions and suppressive coping. This suggests inner dialogue is a crucial therapeutic mechanism, underscoring the vital role of psychotherapist preparation and integration in Clinical Psychology and Psychedelics and Drug Studies, potentially alleviating alcohol craving.
Abstract
Responders were distinguished by narratives of inner dialogue and adaptive coping, while non-responders emphasized sensory and affective descriptio...
ALADIN v.O — Langorian Consciousness Field EFT (43 Hz): EEG Evidence from DMT Breakthrough & Meditation
Zenodo (CERN European Organization for Nuclear Research) – January 18, 2026
Summary
A striking finding reveals that during altered states of consciousness, such as high-dose DMT and deep meditation, a significant enhancement of gamma-band power near 43 Hz occurs alongside a collapse in the multifractal spectrum width, indicating transient dynamical ordering. In a sample of multiple subjects, this coupling was consistently observed, with temporal locking between the two phenomena. Surrogate testing confirmed these effects were not due to random dynamics. Core datasets and analyses are fully reproducible, fostering independent verification and further exploration of consciousness dynamics.
Abstract
This Zenodo record accompanies ALADIN v.O — Langorian Consciousness Field EFT (43 Hz) and provides a fully reproducible EEG-based empirical foundat...