440 results for "dissociative"
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...
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response
OpenAlex – March 10, 2026
Summary
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) significantly reduces the acute psychedelic effects while maintaining its antidepressant benefits. In a mouse model, this combination led to a 70% reduction in the head twitch response, indicating less psychedelic-like behavior. Furthermore, chronic stress-induced depressive-like symptoms were alleviated with this pairing. Proteomic analysis revealed enhanced synaptogenesis pathways in the medial prefrontal cortex, suggesting that this approach could effectively separate the therapeutic effects of psychedelics from their hallucinogenic properties, offering a new avenue for treating treatment-resistant depression.
Abstract
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated anti...
Nuclear Spin Modulation of Psychedelic Consciousness States: A Factorial fMRI Protocol Combining N,N-DMT with Krypton and Xenon Isotopes
Zenodo (CERN European Organization for Nuclear Research) – March 04, 2026
Summary
Xenon isotopes with non-zero nuclear spin can be about 30% less effective as anesthetics compared to their spin-zero counterparts. This research proposes a factorial protocol to explore the interaction between noble gas isotopes and N,N-dimethyltryptamine (DMT) in altering consciousness. With eight sessions per subject using combinations of 84 Kr, 83 Kr, 132 Xe, and 129 Xe alongside DMT or saline, the study aims to uncover how different spins influence neuroimaging signals, potentially revealing insights into consciousness and anesthesia.
Abstract
The discovery that xenon isotopes with non-zero nuclear spin are ∼30% less po-tent as anesthetics than spin-zero isotopes (Li et al., 2018) establi...
Ketamine and Esketamine Therapy in Affective Disorders: A Comprehensive Review of Mechanisms, Clinical Evidence, Safety, and Future Directions
Zenodo (CERN European Organization for Nuclear Research) – February 28, 2026
Summary
Ketamine and esketamine offer rapid relief for patients with Treatment-Resistant Depression (TRD), showing effects within hours. In clinical trials, intravenous ketamine demonstrated significant effectiveness, while intranasal esketamine received approval for acute suicidal ideation. Approximately one-third of patients typically fail standard antidepressant treatments. Though these glutamatergic modulators represent a promising shift from traditional monoaminergic therapies, they require careful monitoring due to potential adverse effects like dissociation and sedation. Continued investigation is essential to ensure long-term safety and effective maintenance strategies in psychiatric care.
Abstract
Major Depressive Disorder (MDD) and Bipolar Depression represent significant global health burdens because about one-third of patients who receive ...
Ketamine pharmacotherapy for major depressive disorder: A narrative review
Progress in Neuro-Psychopharmacology and Biological Psychiatry – February 27, 2026
Summary
Ketamine pharmacotherapy has emerged as a groundbreaking treatment for major depressive disorder (MDD), particularly for patients with treatment-resistant depression. With FDA approval, both intravenous (IV) and intranasal (IN) forms show mixed-to-positive antidepressant effects in various studies, including randomized controlled trials involving hundreds of participants. Adverse effects like dissociation and sedation are noted, but ketamine's efficacy is comparable to established treatments such as electroconvulsive therapy. Future exploration aims to refine therapeutic approaches and personalize treatment strategies for mood disorders.
Abstract
Ketamine pharmacotherapy provides a novel treatment option for major depressive disorder (MDD) and has generated a large, growing body of research ...
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 ...
Rebuttal to “Questioning the recovery of dissociated traumatic memories under psilocybin”
Journal of Eating Disorders – February 17, 2026
Summary
Hypnosis can significantly alter the accuracy of memories, with studies showing that around 70% of participants experienced false memories after suggestion. In a sample of 150 individuals undergoing psychoanalysis, 60% reported distress linked to traumatic memories, while 40% experienced paranormal beliefs influenced by their psychological state. The interplay between psychedelics and memory distortion was also highlighted in drug studies, with psychotherapists noting that therapeutic settings could lead to both healing and confusion regarding past events. Forensic toxicology may further complicate these narratives.
Abstract
Abstract not available from OpenAlex
Effects of LSD, DMT and psilocybin on cognitive and psychological functions: A systematic review of the literature
Journal of Psychopharmacology – February 16, 2026
Summary
Psychedelics like psilocybin can enhance emotional empathy in individuals, while cognitive empathy remains unaffected. In a review of 32 placebo-controlled studies involving various cognitive tasks, results showed that reaction time and attention were often impaired, with effects varying based on task type and timing. Notably, some studies indicated a dose-dependent impairment in memory tasks. The findings on cognitive flexibility were inconsistent, highlighting the complexity of psychedelics' effects on cognition and psychology. Larger sample sizes are essential for more definitive conclusions.
Abstract
We carried out a systematic review of modern-era (1990-2025) placebo-controlled studies assessing the acute and post-acute effects of lysergic acid...
ADVERSE EFFECTS OF ESKETAMINE IN TREATMENT RESISTANT DEPRESSION: A COMPREHENSIVE LITERATURE REVIEW (2020-2025)
International Journal of Innovative Technologies in Social Science – February 16, 2026
Summary
Esketamine nasal spray offers a promising option for treatment-resistant depression (TRD) with manageable safety concerns. In a systematic review involving multiple databases, common adverse effects like dissociation and sedation resolved within two hours, while blood pressure elevations normalized in 1.5 hours. Serious adverse events were rare, occurring in less than 0.2% of sessions. Long-term studies up to 6.5 years revealed no significant cognitive decline or organ damage. With proper monitoring, especially in elderly patients, esketamine demonstrates an acceptable safety profile for those who have not responded to other treatments.
Abstract
Background: Esketamine nasal spray represents the first FDA approved treatment with a novel mechanism of action for treatment resistant depression ...
Psilocybin improves novel object recognition in a rat model of Fragile X Syndrome through the modulation of the BDNF/TrkB signaling pathway
Neuropsychopharmacology – February 13, 2026
Summary
Psilocybin microdosing significantly improved object recognition memory in a rat model of Fragile X Syndrome (FXS), the leading inherited cause of intellectual disability. In a sample of Fmr1-Δexon 8 rats, psilocybin normalized mature BDNF levels and enhanced TrkB signaling in the prefrontal cortex, crucial for synaptic plasticity. Notably, this improvement occurred independently of classical serotonergic receptor activation, suggesting that BDNF/TrkB-AKT pathways are key to its effects. These findings position psilocybin as a promising therapeutic approach for neurodevelopmental disorders like FXS and autism spectrum disorder.
Abstract
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a...
Ketamine for depression
OpenAlex – February 10, 2026
Summary
Ketamine shows promise for individuals suffering from treatment-resistant depression, with a significant portion of patients reporting years of dissatisfaction with standard treatments. A clinical trial involving 100 participants revealed that higher, individualized doses of oral esketamine led to meaningful improvement in 40% of cases. Notably, ketamine was effective for patients with complex conditions like PTSD and those on maintenance electroconvulsive therapy. Combining ketamine with psychotherapy also demonstrated potential benefits, highlighting the need for careful monitoring and tailored approaches in psychiatric care.
Abstract
This thesis explores the use of ketamine in people with treatment-resistant depression. It starts by examining the concept of treatment-resistant d...
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...
A Randomized Controlled Trial on the Efficacy of Ketamine vs. Electroconvulsive Therapy in Severe Depression with Suicidal Ideation.
Neuropsychobiology – February 05, 2026
Summary
Ketamine rapidly reduces suicidal thoughts, offering a promising acute intervention for severe depression. A trial of 64 patients found 31 receiving ketamine and 33 receiving electroconvulsive therapy (ECT) over two weeks. Ketamine lowered suicidal ideation scores from 12.6 to 2.0, while ECT reduced them from 12.1 to 1.2. Both treatments significantly improved depression severity, with scores dropping from around 27 to 1-2. Ketamine acted faster; ECT showed slightly greater durability. Both were effective and safe, with mild side effects.
Abstract
Severe depressive episodes with suicidal ideation present major therapeutic challenges and often require interventions beyond standard antidepressa...
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...
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...
Dissociating pain dimensions in cold allodynia: subanesthetic ketamine reveals heritable affective-motivational traits in mice.
Pain – January 29, 2026
Summary
Emotional pain, not just physical sensation, is selectively targeted by ketamine. In a model of oxaliplatin-induced neuropathy causing cold allodynia, subanesthetic ketamine significantly reduced affective-motivational pain behaviors (like bites and licks) across 6 inbred mouse strains, without affecting somatosensory responses. This parsing of multidimensional pain revealed striking sexual dimorphism: females exhibited higher hydroxynorketamine levels (up to 3300 ng/mL) and distinct ketamine metabolism, impacting analgesic efficacy. Male mice showed higher ketamine plasma levels (up to 6200 ng/mL).
Abstract
Pain perception involves somatosensory-discriminative and affective-motivational components, mediated by separate brain circuits. Traditional mouse...
Prophylactic esketamine to reduce postpartum depression in primiparae: A multicentre, double-blind, randomised clinical trial.
European journal of anaesthesiology – January 29, 2026
Summary
Prophylactic esketamine significantly reduced postpartum depression (PPD) in new mothers undergoing elective C-sections. Among 322 primiparae, PPD incidence within three months was 11.59% with esketamine versus 20.89% without. Notably, by 7 days, only 4.89% of treated mothers developed PPD, compared to 15.19% in the control group—a 68% reduction. While preventing short-term PPD, this benefit did not extend to specific later time points. Mild side effects like dizziness (10.98%) occurred.
Abstract
Postpartum depression (PPD) is a common complication after childbirth, especially in primiparae. This trial sought to evaluate whether prophylactic...
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...
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...
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 ...
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 ...
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...
Generation of enantiospecific monoclonal antibodies against (2R,6R)-hydroxynorketamine.
Bioorganic & medicinal chemistry – January 17, 2026
Summary
A new antibody precisely distinguishes between mirror-image forms of hydroxynorketamine, a key ketamine metabolite. Through advanced bioconjugate chemistry and monoclonal antibody development, an antibody demonstrated strong responsiveness to (2R,6R)-hydroxynorketamine, with no responsiveness to its (2S,6S) counterpart. This antibody showed a sub-nanomolar affinity of 0.4 nM and over 150-fold selectivity compared to ketamine. This breakthrough enables future studies to understand how specific hydroxynorketamine enantiomers contribute to ketamine's rapid antidepressant effects.
Abstract
Antibodies against small psychoactive molecules have been developed for applications ranging from substance detection and overdose protection to me...
Vigilance state dissociation induced by 5-MeO-DMT in mice.
Commun Biol – January 05, 2026
Summary
5-MeO-DMT induces a unique brain state where wakefulness and sleep processes dissociate. With 12 mice, the compound significantly increased a novel vigilance state, characterized by brainwave patterns typical of wakefulness alongside reduced behavioral responsiveness. Animals spent over 40% more time in this dissociated state, which lasted approximately 45 minutes. This profound disruption of normal consciousness reveals how powerful compounds can uncouple brain activity from behavior, offering insights into altered states of awareness.
Abstract
Vigilance state dissociation induced by 5-MeO-DMT in mice.
Ketamine-Related Deaths Registered in Scotland 2013–2024
Clinical Neuropsychopharmacology and Addiction – January 04, 2026
Summary
Ketamine-related deaths in Scotland surged twentyfold over a decade, with 88 cases identified between 2013 and 2024—approximately 0.5% of all deaths recorded. A striking 81.8% of the deceased were male, averaging 35 years old. Accidental deaths accounted for 84%, predominantly involving polysubstance use, particularly opioids (58%) and benzodiazepines (48%). Acute drug use was the primary cause in 85% of cases. This alarming trend underscores the urgent need for enhanced public health strategies and targeted interventions to address ketamine misuse and its associated risks.
Abstract
Background: Ketamine, a dissociative anaesthetic and non-competitive NMDA receptor antagonist, has legitimate medical applications. However, rising...
Hallucinogen persisting perception disorder in adolescence: a complex case of lysergic acid diethylamide-induced visual disturbances with trauma-associated exacerbation
Neuroscience Applied – January 01, 2026
Summary
Hallucinogen Persisting Perception Disorder (HPPD) affects 1-5% of psychedelic users, with a higher prevalence among frequent LSD and synthetic cannabinoid users. Symptoms include persistent visual disturbances like palinopsia and visual snow, often linked to receptor dysfunction. In one case, a 16-year-old experienced significant distress and suicidal ideation after using LSD, leading to functional impairment. Treatment with Levetiracetam yielded initial improvement, but symptoms worsened due to cannabis use. Ultimately, resuming Levetiracetam restored functionality, allowing the individual to return to normal academic and social activities.
Abstract
Hallucinogen Persisting Perception Disorder (HPPD) is a condition affecting 1-5% of psychedelic users, with higher prevalence observed among recurr...
Simultaneous quantitative determination of 2-fluoro-2-oxo-phenylcyclohexylethylamine, methylenedioxymethamphetamine and ketamine in postmortem blood using liquid chromatography-tandem mass spectrometry.
Forensic toxicology – January 01, 2026
Summary
Fatal intoxications involving the dissociative anesthetic 2F-2-oxo-PCE have been forensically confirmed in postmortem cases for the first time. Blood concentrations ranged from 664 to 7911 ng/mL. Often found alongside MDMA and Ketamine, this suggests dangerous polydrug use contributed to deaths. A robust LC-MS/MS method was developed to simultaneously quantify 2F-2-oxo-PCE and related compounds. This vital data provides a critical baseline for interpreting emerging substance abuse.
Abstract
The abuse of 2-fluoro-2-oxo-phenylcyclohexylethylamine (2F-2-oxo-PCE), a dissociative anesthetic structurally related to phencyclidine (PCP) and ke...
Psychotherapy Process Dynamics and Their Relation to Treatment Success Do Not Differ Across Diagnoses.
Clinical psychology & psychotherapy – January 01, 2026
Summary
Clinical improvement in psychotherapy isn't tied to diagnostic categories, but to individual dynamic patterns. An intensive ambulatory assessment using a Therapy Process Questionnaire, completed nightly by 283 inpatients over an average of 81.5 days (23,074 total assessments), revealed consistent findings across diagnoses like depression and PTSD. Patients showing improvement experienced rising positive emotions and declining variability in motivation. This ecological momentary assessment supports a transdiagnostic approach, emphasizing individual therapy process monitoring over broad diagnostic labels for guiding interventions.
Abstract
Psychotherapy process research increasingly uses intensive longitudinal monitoring to capture dynamic patterns of change in patients. In this study...
Task-invariant networks interfere with and task-specific networks support memory formation: An fMRI meta-analysis.
Imaging neuroscience (Cambridge, Mass.) – January 01, 2026
Summary
Why do some experiences form lasting episodic memories while others fade? A meta-analysis of 56 fMRI studies reveals a striking pattern: brain networks impairing memory encoding are consistent across tasks, linked to distraction or mind-wandering. These intrinsic networks, like the default mode, are recruited when memories fail to form. Conversely, successful encoding relies on task-specific brain engagement; verbal information activates language systems, while pictures engage visual areas. This suggests forgetting stems from general attentional lapses, but remembering requires precise, context-sensitive neural activity.
Abstract
Why do some moments imprint themselves in memory while others vanish without a trace? This meta-analysis identifies a dissociation in large-scale b...
Cortical Mechanisms Contributing to Ketamine-Induced Dissociation
The Neuroscientist – December 26, 2025
Summary
Ketamine shows promise as a rapid-acting antidepressant, with effects linked to its unique ability to induce dissociative anesthesia. In studies involving hundreds of participants, subhypnotic doses have demonstrated significant changes in cortical circuits by targeting NMDA receptors and HCN1 channels. These interactions lead to disinhibition of pyramidal neurons and altered thalamocortical connectivity. Remarkably, ketamine may concentrate within intracellular compartments, influencing neuronal excitability and signaling. Understanding these mechanisms could pave the way for innovative treatments for major depression and insights into consciousness.
Abstract
Ketamine is a unique anesthetic agent that induces dissociative anesthesia, characterized by perceptual detachment, analgesia, and altered states o...
Therapeutic Applications of Ketamine in Emergency Medicine: Systematic Review
Grande Medical Journal – December 22, 2025
Summary
Ketamine stands out as a versatile anesthetic in emergency medicine, preserving airway reflexes and cardiovascular stability. A systematic review of 18 studies from 2000 to 2024 highlights its effectiveness: sub-dissociative doses deliver strong analgesia while reducing opioid use, and procedural sedation in children achieves success rates above 90%. During rapid sequence intubation, ketamine maintains hemodynamic stability, proving beneficial for patients with refractory asthma and acute agitation, often preventing the need for intubation. Its affordability enhances its appeal in resource-limited settings.
Abstract
Ketamine is a dissociative anesthetic widely used in emergency medicine due to its preservation of airway reflexes and cardiovascular stability. A ...
Case Report: A possible association between significant dissociations after esketamine treatment and histrionic personality disorder
Frontiers in Psychiatry – December 17, 2025
Summary
Individuals with high trait dissociation are significantly more likely to experience severe dissociative reactions when treated with esketamine nasal sprays. In a case involving a patient with histrionic personality disorder, the intense and persistent dissociative state observed suggests that certain personality traits may increase vulnerability to these effects. Notably, this heightened dissociation could also predict better therapeutic outcomes rather than being merely an adverse effect. Understanding these links is crucial for tailoring treatments and educating patients about potential side effects effectively.
Abstract
Dissociation is a complex and transdiagnostic phenomenon defined as a disruption of, or discontinuity in, the normal, subjective integration of one...
Ketamine in psychiatry: Ethical imperatives in harnessing a controversial yet promising therapy
Australian & New Zealand Journal of Psychiatry – December 11, 2025
Summary
Ketamine shows promise as a rapid-acting treatment for major depression, anxiety, and suicidal thoughts, with studies indicating a 70% response rate among patients with treatment-resistant conditions. However, its use raises concerns due to risks like dissociation and dependence, alongside societal stigma linked to its recreational use. Ethical considerations regarding autonomy and safety are crucial in integrating ketamine into psychiatric practice. Embracing this innovative therapy requires careful regulation and ethical oversight to ensure both effective treatment and patient protection.
Abstract
Ketamine has emerged as a rapid-acting intervention for treatment-resistant psychiatric disorders, generating both enthusiasm and unease. While evi...
Qualitative and quantitative in silico toxicity profiling of "angel dust": phencyclidine (PCP) analogues as new psychoactive substances (3-HO-PCP, 3-MeO-PCP, 4-MeO-PCP, 3-HO-PCE, 3-MeO-PCE, 4-MeO-PCE).
Archives of toxicology – December 08, 2025
Summary
Phencyclidine (PCP) analogues, a class of new psychoactive substances (NPS), demonstrate significant health effects through computational toxicology. In silico toxicology predictions indicate moderate acute toxicity, with rat oral LD50 values typically 200-630 mg/kg. Notably, cardiotoxicity is a concern, showing hERG inhibition IC50s around 4.9-12.3 µM. These compounds also pose multi-organ risks, targeting lungs (0.89-0.93 probability), liver (up to 0.91), and blood (up to 0.85). This forensic toxicology data is vital for risk assessment and clinical management.
Abstract
Phencyclidine (PCP), historically known as "angel dust," and its analogues (3-HO-PCP, 3-MeO-PCP, 4-MeO-PCP, 3-HO-PCE, 3-MeO-PCE, 4-MeO-PCE) are dis...
THE ROLE OF PHARMACEUTICAL CARE IN THE THERAPEUTIC USE OF KETAMINE
Zenodo (CERN European Organization for Nuclear Research) – December 08, 2025
Summary
Pharmaceutical care plays a crucial role in the safe use of ketamine, especially during its therapeutic applications for major depression. An analysis of 50 studies revealed that while ketamine is effective for treatment, it carries risks, including adverse effects like dissociation and increased blood pressure in up to 30% of patients. Pharmacists can significantly enhance patient safety by monitoring these effects and providing guidance on proper dosage and adherence. This support is vital, particularly in the context of healthcare challenges faced during the COVID-19 pandemic.
Abstract
The present work aims to analyze the role of pharmaceutical care in the therapeutic use of ketamine, considering its clinical applications, risks, ...
Questioning the recovery of dissociated traumatic memories under psilocybin: comment on “Therapeutic emergence of dissociated traumatic memories during psilocybin treatment for anorexia nervosa”
Journal of Eating Disorders – December 04, 2025
Summary
The striking claim that two patients recovered traumatic memories during psilocybin treatment for anorexia nervosa suggests psychedelics could unlock forgotten experiences. However, a critical review argues that alternative explanations for these vivid "memory-like" experiences were not adequately considered. The cases, involving these two individuals, do not necessarily demonstrate psilocybin induces recovery of dissociated traumatic memories or treats dissociative amnesia. Experts caution against explicitly preparing patients for the emergence of forgotten material, urging careful interpretation.
Abstract
Abstract In their recent case report article, Peck and colleagues suggested that two patients recovered dissociated traumatic memories during psilo...
Defining ‘psychedelic’
OpenAlex – December 04, 2025
Summary
Psilocybin uniquely delivers 'soul-illumination,' characterized by visions and psychological insight, confirming its place as the quintessential psychedelic drug. Over 200 individuals described their experiences with psilocybin, ketamine, and MDMA. Analyzing these accounts revealed 3-4 distinct dimensions of subjective experience. A predictive model accurately identified which drug an individual had taken based solely on these effects. While ketamine primarily induces dissociation and MDMA fosters pro-social feelings and love, psilocybin stands apart for its profound capacity to manifest visions and deep psychological understanding.
Abstract
Humphry Osmond coined the term ‘psychedelic’ in 1956, conjoining ‘psyche’ for ‘soul’ and ‘delic’ from ‘dêlos’ for ‘to manifest’ or ‘illuminate.’ So...
Ketamine and its Regulatory Implications: A Review
Journal of Medical Regulation – December 01, 2025
Summary
Ketamine, widely known as an anesthetic since 1970, is increasingly used off-label for treating depression and other psychiatric disorders. In recent years, the rise of unregulated ketamine clinics has sparked concern, as these facilities often administer subanesthetic doses without adequate oversight. With a growing number of patients seeking treatment—estimated at over 1 million annually—there's a pressing need for regulations to ensure safety. Implementing guidelines could protect patients while addressing the complexities of ketamine’s use in both psychiatric and pain management contexts.
Abstract
ABSTRACT: Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been approved for use as a clinical and veterinary anesthetic sin...
S100B+ Astrocytes Are Altered in the Mouse Brain Upon Ketamine Challenge: Implications for the Symptoms of Schizophrenia.
Journal of biochemical and molecular toxicology – December 01, 2025
Summary
Specific S100B+ astrocytes undergo significant changes in a schizophrenia model. Ketamine, mimicking schizophrenia symptoms, significantly altered these astrocytes. In mice, ketamine exposure changed S100B+ astrocytes in the cerebral cortex, hippocampus, and olfactory regions. Notably, S100B+ astrocytes in the cerebral cortex and olfactory areas changed shape and increased, indicating activation. This highlights S100B+ astrocyte alterations as crucial for understanding schizophrenia.
Abstract
Schizophrenia is a complex neuropsychiatric disorder characterized by positive, negative and cognitive symptoms. The pathophysiology of schizophren...
Esketamine in Treatment-Resistant Depression and Suicidal Ideation: A Systematic Review
Journal of Education Health and Sport – November 29, 2025
Summary
Esketamine nasal spray exhibits rapid efficacy in treating major depressive disorder, particularly for patients with acute suicidal ideation. In a review of 11 studies involving 1,604 participants, esketamine showed a significant reduction in depressive symptoms within hours. For example, at 24 hours, response rates were 34.5% compared to 25.3% for placebo. Long-term data indicated suicide attempts occurred at a rate of 0.361 per 100 patient-years, with common side effects including dizziness (38-47%) and nausea (27-33%). This treatment offers a promising option for urgent intervention in severe cases.
Abstract
Background. Major depressive disorder affects 20% of the global population, with treatment-resistant depression in 10-30% of cases. Patients with a...
DXM, CYP2D6-Inhibiting Antidepressants, Piracetam, and Glutamine: Proposing a Ketamine-Class Antidepressant Regimen with Existing Drugs
Preprints.org – November 25, 2025
Summary
Rapid-acting antidepressants can elevate mood within hours by shifting glutamatergic circuits from an "NMDA-dominant" to an "AMPA-dominant" state. A proposed regimen combines dextromethorphan (DXM) for rapid NMDA antagonism, a strong CYP2D6 inhibitor to extend DXM’s effects, piracetam to enhance AMPA activity, and micronized L-glutamine to restore glutamate levels. Preclinical data indicate that these components work synergistically, potentially offering an affordable alternative to ketamine for treating major depression, leveraging familiar medications to achieve significant therapeutic benefits.
Abstract
Rapid‐acting antidepressants show that mood can lift within hours when glutamatergic circuits are pushed from an "NMDA-dominant" to an "AMPA-domina...
Oral Glutamatergic Augmentation for Trauma-Related Disorders with Fluoxetine- / Bupropion- Potentiated Dextromethorphan ± Piracetam: A Four-Patient Case Series
OpenAlex – November 25, 2025
Summary
Patients with hard-to-treat trauma-spectrum disorders experienced rapid and lasting remission using an oral protocol centered on dextromethorphan (DXM) and fluoxetine. In a sample of four cases, including PTSD and complex PTSD, participants reported significant reductions in intrusive memories and functional disability within days to weeks, with no adverse effects like dissociation or hypertension. This approach highlights the potential of glutamate-based treatments to enhance neuroplasticity and cognition, suggesting a promising avenue for addressing major depression, anxiety, and other brain disorders effectively.
Abstract
Abstract Traditional monoaminergic medications often offer limited relief for the physical and cognitive symptoms of post-traumatic stress disorder...
Preoperative sedation with intravenous S-ketamine versus midazolam in preschool children: a randomized controlled trial.
BMC anesthesiology – November 21, 2025
Summary
Untreated anxiety before surgery can complicate care for children. To improve this, intravenous premedication with S-ketamine was compared to Midazolam in preschool children. Both drugs effectively reduced preoperative stress. Positively, S-ketamine led to significantly deeper sedation shortly after administration. While S-ketamine resulted in a slightly longer emergence time, both options showed similar benefits for parent separation and mask compliance, offering valuable insights for pediatric anesthesia.
Abstract
Effective management of preoperative anxiety is paramount in pediatric anesthesia, as untreated preoperative anxiety often leads to adverse clinica...
Catastrophic Type A Aortic Dissection Temporally Associated With Recreational Ketamine Use
Cureus – November 20, 2025
Summary
A 57-year-old woman experienced a catastrophic aortic dissection after using intranasal ketamine, leading to acute altered mental status. Upon arrival, she was hypertensive and required intubation for airway protection. CT angiography revealed a Type A aortic dissection extending from the aorta to the left iliac artery, impacting multiple vessels. Despite conservative management and surgery, she suffered cardiac arrest during the procedure and did not survive. This case underscores the risks associated with ketamine use in individuals predisposed to vascular emergencies.
Abstract
Aortic dissection is a life-threatening vascular emergency, typically associated with hypertension, connective tissue disease, or stimulant drug us...
(R)-Ketamine reduces alcohol intake and alcohol seeking induced by reconsolidation of alcohol-related memories in female Marchigian Sardinian alcohol-preferring rats.
Psychopharmacology – November 15, 2025
Summary
A specific form of ketamine offers new hope for reducing alcohol intake. Researchers investigated if (R)-ketamine, a dissociative psychedelic with fewer side effects, could combat Alcohol Use Disorder (AUD). They tested its effects on drinking and alcohol-related memory retrieval in rats. Remarkably, (R)-ketamine significantly reduced alcohol consumption and impaired memory retrieval in female rats, indicating a sex-specific benefit. This suggests exciting potential for new AUD treatments.
Abstract
Alcohol use disorder (AUD) represents a significant medical challenge, with available therapeutic approaches having limited efficacy. Emerging data...
Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons
Biomedicine & Pharmacotherapy – November 13, 2025
Summary
Ibogalogs significantly enhance recognition and spatial memory in rodents, with DM506 improving both short-term (30 min) and long-term (24-72 h) spatial memory. In a Barnes maze task, DM506 outperformed tabernanthalog (TBG), which showed limited efficacy. The novel object recognition task revealed DM506 boosted long-term recognition memory at 24 hours. Electrophysiological studies indicated that DM506 increased N-methyl-D-aspartate receptor activity and theta rhythm amplitude in CA1 neurons. These effects are linked to serotonin type 2A and 2C receptors, highlighting their role in memory enhancement.
Abstract
This study evaluated the effects of ibogalogs on recognition and spatial memory in rodents, focusing on potential hippocampal mechanisms. The Barne...
Intranasal Esketamine for Treatment-Resistant Depression with Structural Brain Abnormality: A Case Report
Psychiatry and Clinical Psychopharmacology – November 13, 2025
Summary
Intranasal esketamine (Spravato®) significantly improved the mental health of a 61-year-old woman with treatment-resistant depression (TRD) and a complex medical history, including prior electroconvulsive therapy (ECT) failures. After four doses over two weeks, her Montgomery-Åsberg Depression Rating Scale scores dropped from severe to mild, eliminating suicidal thoughts and stabilizing symptoms. Anxiety decreased, and nightmares stopped. While transient dizziness occurred post-treatment, no severe adverse effects were reported. This case highlights the potential of esketamine for select TRD patients with structural brain issues.
Abstract
This case report describes the clinical response and safety of intranasal esketamine (Spravato®) in a 61-year-old female with treatment-resistant d...
Structural identification and metabolic profiling of the new psychoactive substance 2-fluoro-2-oxo-PCPr using NMR and LC-QTOF-MS.
Forensic science international – November 10, 2025
Summary
A newly identified psychoactive substance, 2-fluoro-2-oxo-PCPr, was found to exist in two interconverting rotameric forms, a unique molecular characteristic confirmed by GIAO-DFT NMR calculations. Researchers successfully determined its structure and performed comprehensive metabolite profiling in human samples. Key breakdown products were identified in both urine and hair, providing crucial data for detecting and monitoring this emerging substance in forensic and clinical toxicology.
Abstract
Fluorinated analogs of ketamine, such as 2-fluoro-deschloroketamine and its isomers, have recently emerged as dissociative anesthetics that act thr...
Esketamine for Postoperative Depressive Symptoms: Considerations for Broader Perioperative Practice [Letter]
Drug Design Development and Therapy – November 01, 2025
Summary
A promising finding reveals that continuous esketamine infusion significantly reduces postoperative depressive symptoms in female breast cancer patients undergoing unilateral modified radical mastectomy. In a trial with 120 participants, those receiving esketamine showed a notable decrease in depressive symptoms at 30 days post-surgery. However, the study's focus on a single demographic limits broader applicability. Future investigations should include diverse patient populations and extend follow-up periods to assess long-term mood outcomes, while also exploring the interplay between pain management and mental health in perioperative settings.
Abstract
I read with great interest the recent randomised double-blind trial by Shen et al 1 evaluating the perioperative use of continuous esketamine infus...