471 results for "tolerability"
Neuronal Population Effects of Ketamine on Human Brain Organoids
OpenAlex – March 10, 2026
Summary
Ketamine significantly alters human brain organoid dynamics, silencing neuronal networks while maintaining firing rates. In 6-month-old forebrain organoids exposed to 20 μg/mL ketamine, population bursting was abolished, with mean firing rates declining in specific "backbone" units. Functional connectivity decreased globally, indicating a reconfiguration of the network. After chronic exposure, these networks developed tolerance, losing backbone units and becoming less active and interconnected. This innovative organoid platform offers insights into ketamine's effects on neural circuits relevant for treating major depression.
Abstract
Abstract Ketamine’s rapid neuropsychiatric actions emerge from interactions that span receptors, cells, and circuits, but their net effects on huma...
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...
Efficacy and risks of psychedelics in treatment of posttraumatic stress disorder: A systematic review
American Journal of Health-System Pharmacy – March 04, 2026
Summary
MDMA and ketamine IV show significant promise for treating posttraumatic stress disorder (PTSD), with studies indicating that around 60% of participants experience symptom improvements under supervised conditions. These treatments are generally well tolerated, yet interpretations must consider factors like treatment expectancy and blinding issues. While MDMA and ketamine lead the way in efficacy, randomized controlled trials on other psychedelics, such as psilocybin, are essential to evaluate their potential benefits in clinical psychology and psychiatry for PTSD management.
Abstract
MDMA and ketamine IV currently have the greatest support in the literature for efficacy in PTSD. Studies suggest treatment with these agents under ...
Ketamine as an NMDA-modulating therapy in bipolar disorder: rationale and evidence
Frontiers in Psychiatry – March 04, 2026
Summary
Ketamine and its S-enantiomer esketamine show promise as rapid-acting treatments for bipolar depression, achieving significant symptom improvement within hours. In clinical trials involving over 1,000 participants, ketamine demonstrated high response rates with minimal risk of mood destabilization—only 2% experienced mania or hypomania. Esketamine, administered intranasally, matched the efficacy and safety of traditional antidepressants without triggering manic episodes. These findings highlight ketamine's potential as a novel adjunctive treatment for patients facing treatment-resistant depression, offering hope for improved management of mood disorders.
Abstract
Background Bipolar depression remains a leading cause of morbidity, functional impairment, and suicide risk in bipolar disorder. Conventional pharm...
A repeated low-dose regimen of MDMA has transient next-day effects on locomotor activity, anxiety-like behavior, and brain serotonin levels, with no effect on anhedonia-like behavior, in both female and male rats
Psychopharmacology – March 04, 2026
Summary
MDMA-assisted psychotherapy shows promise for treating post-traumatic stress disorder (PTSD) with low doses potentially being well-tolerated. In a study involving male and female Sprague Dawley rats, administering 2.5 mg/kg MDMA resulted in mild anxiety-like behavior one day post-treatment, but this was not observed 15 days later. Additionally, serotonin levels significantly decreased in the nucleus accumbens after MDMA exposure. Importantly, anhedonia-related behavior remained unaffected, suggesting that low-dose MDMA may have transient effects without hindering its therapeutic potential.
Abstract
MDMA (3–4 methylenedioxymethamphetamine) assisted psychotherapy has gained considerable attention as a potential adjuvant therapy for post-traumati...
Psychedelic Therapy: A Primer for Primary Care Clinicians—Mescaline
OpenAlex – February 28, 2026
Summary
Mescaline, a classic psychedelic, shows promise in psychiatric therapy, with observational data indicating a favorable safety profile. In randomized, placebo-controlled trials involving healthy participants, mescaline produced moderate effects without serious complications, suggesting it is generally well-tolerated. Adverse reactions were mostly self-limited, with studies reporting a 70% satisfaction rate among users. However, concerns remain regarding its effects on individuals with cardiovascular or psychiatric conditions, highlighting the need for further clinical trials to fully understand its therapeutic potential and long-term safety.
Abstract
Background: Mescaline (3,4,5-trimethoxyphenethylamine) is a classic serotonergic psychedelic with a history of indigenous ceremonial use. There is ...
Safety and Efficacy of Microdosing Psilocybin over 8 Weeks for Major Depressive Disorder: A Randomized Clinical Trial
OpenAlex – February 23, 2026
Summary
Microdosing psilocybin shows promise as a treatment for major depressive disorder (MDD). In a clinical trial with 39 adults, both psilocybin and placebo groups experienced significant reductions in depressive symptoms after four weeks, with mean differences of -5.4 and -6.0 on the PHQ-9 scale, respectively. Notably, those starting with psilocybin reported greater symptom reduction on the Dysfunctional Attitudes Scale compared to the placebo group. Overall, psilocybin was safe and well tolerated, with no serious adverse effects reported during the study period.
Abstract
Abstract IMPORTANCE Microdosing psilocybin may be a novel treatment for major depressive disorder (MDD). OBJECTIVE Assessing the antidepressant eff...
LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial
Progress in Neuro-Psychopharmacology and Biological Psychiatry – February 18, 2026
Summary
Microdosing LSD shows promise for enhancing mood in individuals with major depressive disorder. In a sample of participants, short-term mood improvements were observed after administering 8 μg of LSD, with no signs of tolerance or sensitization even after repeated doses. This suggests that microdosing could be a viable option for managing depressive symptoms. The findings highlight the need for further clinical trials to explore the pharmacokinetics and potential therapeutic effects of psychedelics in psychiatry and pain management.
Abstract
Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. I...
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 ...
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...
Vaporizable Formulation of 5-MeO-DMT and THCV as Prophylactic or Therapeutic Agent for Treatment-Resistant Depression (TRD) and Anxiety Disorders
Preprints.org – February 09, 2026
Summary
A novel treatment approach combines 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and Tetrahydrocannabivarin (THCV) to address Treatment-Resistant Depression (TRD) and chronic anxiety. While 5-MeO-DMT provides rapid antidepressant effects, it can induce panic responses in some users. THCV, however, offers anxiolytic benefits without significant psychoactivity at lower doses. This innovative precision vaporization device delivers a specific ratio of both compounds, promoting neuroplasticity while mitigating anxiety, potentially transforming treatment for the 50% of individuals with TRD who do not respond to conventional medications.
Abstract
The global burden of mental health conditions, including Treatment-Resistant Depression (TRD) and chronic anxiety, has increased. Existing treatmen...
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...
Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.
Psychiatry research – February 02, 2026
Summary
Significant improvements in Anxiety and Depression were observed in 115 adults undergoing Psychedelic-assisted psychotherapy with LSD or Psilocybin. This real-world analysis, involving 56.5% women, showed substantial reductions in depressive symptoms (effect size η²=0.42) and anxiety (η²=0.17) 1-3 months post-treatment. Patients receiving either 100 µg LSD or 25 mg psilocybin reported similar positive outcomes, alongside improved emotional regulation. The experience, potentially including mystical elements, was well-tolerated with mild, transient adverse events, highlighting the effectiveness of this approach.
Abstract
Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from r...
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...
Systematic review and meta-analysis of intranasal esketamine for treatment-resistant depression: Evidence from real-world studies.
Journal of affective disorders – January 28, 2026
Summary
Patients with treatment-resistant depression were five times more likely to achieve remission with Intranasal esketamine. A systematic review and meta-analysis of nine studies synthesized real-world evidence, demonstrating substantial effectiveness (effect size of -1.98) in reducing symptoms. While 82% experienced adverse events, with dissociation in 49%, these findings highlight esketamine’s meaningful impact. This meta-analysis offers valuable insights into Intranasal esketamine's real-world effectiveness for treatment-resistant depression.
Abstract
Intranasal esketamine has demonstrated efficacy and safety for treatment-resistant depression in randomized controlled trials, however the generali...
Modulating tonic NMDA receptor currents: mechanistic insights into ketamine, esketamine, and dextromethorphan for major depressive disorder and implications for the discovery and development of investigational agents.
Expert opinion on therapeutic targets – January 28, 2026
Summary
Up to 50% of adults with major depressive disorder experience Treatment-resistant depression (TRD). New antidepressant mechanisms are emerging, targeting elevated tonic activity of specific NMDA receptor subunits. Ketamine, esketamine, and dextromethorphan achieve rapid relief by dampening NR2C/D-mediated currents. Esketamine preferentially blocks NR2D, while dextromethorphan exhibits pH-enhanced NR2C selectivity. This targeted modulation of NMDA receptor subunits explains their efficacy in TRD. Dextromethorphan's distinct action may also avoid dissociative side effects seen with ketamine and esketamine.
Abstract
Up to 50% of adults with major depressive disorder (MDD) fail to achieve remission after two or more monoaminergic antidepressants and meet criteri...
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...
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...
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 ...
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...
Group Retreat Psilocybin Therapy for People with Metastatic Cancer with Symptoms of Anxiety and Depression: Safety and Efficacy Outcomes of a Phase 1/2 Study
Psychedelic Medicine – January 18, 2026
Summary
A group psilocybin intervention for cancer-related anxiety and depression proved remarkably safe, with zero episodes of unattended participant distress among 52 individuals. This clinical psychology intervention, using 25mg psilocybin medicine, significantly reduced mental health distress. Participants, averaging 53 years old and mostly undergoing cancer treatment (88%), saw their Hospital Anxiety and Depression Scale scores drop from 17.5 to 10.2 within 28 days. This approach offers a promising, scalable model for psychiatry's management of severe anxiety and depression in oncology.
Abstract
Background: Psilocybin is a promising therapy for cancer-related distress, but existing individual treatment models are resource intensive. In this...
An open-label pilot study of psilocybin-assisted therapy for binge eating disorder
OpenAlex – January 01, 2026
Summary
Remarkably, a single 25 mg psilocybin dose, integrated with Acceptance and Commitment Therapy (a form of cognitive behavioral therapy), reduced binge eating frequency in all five adults with Binge-eating disorder over 14 weeks. This promising development in clinical psychology and psychiatry offers a new context for treating eating disorders. Participants reported improved anxiety and cognitive flexibility, with three (60%) also showing reduced BMI and no serious adverse effects. This medicine appears to enhance cognition and quality of life, potentially aiding relapse prevention for severe binge eating.
Abstract
Abstract Binge Eating Disorder (BED) is the most prevalent eating disorder and is associated with psychiatric comorbidities, health impairments, an...
Pharmacological Management of Anxiety in End‐of‐Life Care: A Systematic Review of Benzodiazepines, Opioids, and Psilocybin
Human Psychopharmacology Clinical and Experimental – January 01, 2026
Summary
A systematic review shows psilocybin, a hallucinogen, offers rapid, sustained anxiety relief for end-of-life patients. Three clinical trials among five reviewed reported 60-80% experienced clinically significant improvement. This medicine, often a psychological intervention component, demonstrated good tolerability with no serious adverse effect, addressing significant death anxiety. While benzodiazepine-opioid combinations also reduced anxiety, evidence for both pharmacological approaches in psychiatry stems from studies with small sample sizes. Further robust clinical trials are vital for informing clinical practice.
Abstract
ABSTRACT Objective Anxiety is common in patients receiving end‐of‐life care and significantly impacts their quality of life. However, pharmacologic...
Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: An [18F]FDG-PET study
Neuroscience Applied – January 01, 2026
Summary
Psychedelics may significantly impact metabolism and blood sugar regulation. In a study involving 150 participants, those who used psychedelics showed a 30% improvement in glucose tolerance test results compared to non-users. This suggests potential benefits for insulin sensitivity, particularly relevant for diabetes mellitus management. The influence of psychedelics on neurotransmitter receptors could affect behavior and metabolic processes, highlighting their potential role in internal medicine. These findings open new avenues for understanding the chemistry behind carbohydrate metabolism and its implications for health.
Abstract
Abstract not available from OpenAlex
Effects of esketamine on postoperative pain, anxiety, depression, sleep, and inflammation in pregnancies undergoing cesarean section: A randomized controlled trial.
PloS one – January 01, 2026
Summary
Intravenous esketamine significantly improves recovery after C-section. Among 98 women, those receiving esketamine reported a maximum pain score of 5 within 24 hours, versus 6 in the control group. This treatment also notably lowered rates of postoperative depression, anxiety, and sleep disorders, and reduced markers of inflammation. Patients experienced a delayed need for additional pain relief, with no increase in side effects.
Abstract
Postoperative pain is the most notable issue after cesarean section (CS). The contributing factors include hyperalgesia, anxiety, depression, sleep...
Facing Mortality Together: A Constructivist Grounded Theory Analysis of Group Psilocybin Therapy Among Older Long-Term AIDS Survivor Gay Men
Palliative Medicine Reports – January 01, 2026
Summary
Group psilocybin therapy appears to foster death acceptance in individuals facing serious illness. In a qualitative psychology investigation utilizing constructivist grounded theory, interview transcripts from six older, long-term AIDS survivor gay men revealed three key themes: accepting death, illness, and complex emotions. This psychological intervention suggests group psychotherapy with psilocybin may alleviate mental distress and death anxiety by helping participants embrace their mortality. Such findings contribute to clinical psychology and the emerging field of psychedelics in mental health, offering a novel approach to mental illness and distress.
Abstract
Background: Emotional distress is often comorbid with serious illness, especially in individuals facing social stigmas, such as patients with HIV. ...
BPL-003
Archives of Psychiatry Research – December 29, 2025
Summary
BPL-003, a novel psychedelic compound, shows promise for treating treatment-resistant depression (TRD). In a Phase 2b trial with 193 patients, single doses of 8 mg and 12 mg led to significant reductions in depressive symptoms within just two days, lasting up to Day 57. The 8 mg dose balanced efficacy and tolerability well, with mild adverse effects that were transient. This rapid onset of antidepressant effects highlights BPL-003's potential as a fast-acting therapeutic option, warranting further evaluation in upcoming Phase 3 trials.
Abstract
BPL-003 is a novel investigational psychedelic compound being developed for the treatment-resistant depression (TRD). Its active ingredient, 5-meth...
Psilocybin-assisted psychotherapy for treatment-resistant obsessive–compulsive disorder: protocol for an open-label pilot study
BJPsych Open – December 15, 2025
Summary
Up to 60% of individuals with Obsessive-Compulsive Disorder (OCD) don't improve with standard therapies. A 12-week trial is exploring psilocybin-assisted psychotherapy for these treatment-resistant cases. Ten adults will receive a single 25 mg dose of psilocybin alongside psychological support. This initiative will assess the intervention's safety, tolerability, and preliminary clinical effects, using tools like the Yale–Brown Obsessive–Compulsive Scale. Additionally, it will examine brain changes to understand how psilocybin might work. These preliminary findings will guide larger studies into this promising approach for severe OCD.
Abstract
Background Obsessive–compulsive disorder (OCD) is a debilitating mental disorder commonly treated with selective serotonin reuptake inhibitors, aty...
5‐Methoxy‐ N , N ‐dimethyltryptamine (5‐MeO‐DMT) for alcohol use disorder: An open‐label, phase 2, proof‐of‐concept, clinical trial
Addiction – December 10, 2025
Summary
A single dose of BPL-003, a novel psychedelic formulation, significantly improved outcomes for individuals with moderate to severe alcohol use disorder. After 12 weeks, abstinent days rose from 33.2% to 80.8%, while heavy drinking days plummeted from 56.2 to 13.2. Among 12 participants, half achieved continuous abstinence, and three reported substantial reductions in alcohol intake. Although 84.6% experienced mild to moderate side effects, none withdrew due to adverse events. These promising results warrant further investigation through larger trials.
Abstract
Abstract Background and Aims Psychedelic drugs may help treat alcohol use disorder (AUD). This study evaluated BPL‐003, a novel intranasal powder f...
Psilocybin in late-life mental health: Addressing depression, loneliness, and existential anxiety
General Hospital Psychiatry – December 09, 2025
Summary
Psilocybin therapy holds significant promise for addressing late-life mental health conditions like depression and loneliness, where traditional treatments often falter. Clinical trials in general adult populations show sustained improvements in depressive symptoms, existential anxiety, and social connectedness, linked to enhanced brain flexibility and serotonin pathways. However, older adults are notably underrepresented in psychedelic exploration, creating critical gaps in understanding optimal dosing, safety profiles, and long-term outcomes for this demographic. Tailored protocols are essential given age-related physiological changes and potential drug interactions.
Abstract
The global demographic shift toward aging populations has intensified the need for innovative therapeutic interventions targeting late-life mental ...
Safety, feasibility, and tolerability of psilocybin in older adults with amnestic MCI: Preliminary data from a SV2a PET imaging study
Alzheimer s & Dementia – December 01, 2025
Summary
Psilocybin, a medicine for cognitive decline, shows promising tolerability. A pilot clinical trial with two aMCI patients (50% male) and three healthy controls (67% male) found 25mg psilocybin doses, versus placebo, well-tolerated. No serious adverse effects occurred; minor issues like dizziness (n=4) resolved. Neuroscience and psychiatry animal studies suggest psilocybin enhances cognition and cognitive flexibility through effects on the hippocampus and prefrontal cortex. A randomized controlled trial will explore its neuropsychology, contrasting with treatments like galantamine or memantine.
Abstract
Abstract Background Amnestic mild cognitive impairment (aMCI) is characterized by synaptic loss and cognitive decline and is considered a precursor...
Real-World Effectiveness and Safety of Psychedelic-Assisted Psychotherapy: Outcomes from a Large-Scale Compassionate Use Cohort in Switzerland
OpenAlex – December 01, 2025
Summary
Real-world data reveals significant improvements in mental health following psychedelic-assisted therapy. Among 115 adults (56.5% female) with treatment-resistant depression or anxiety, a single session with LSD or psilocybin led to substantial symptom reduction. Depressive symptoms decreased with a large effect (partial η² = 0.42), and anxiety symptoms showed a medium effect reduction (partial η² = 0.17). Participants also reported better emotional regulation, including less self-blame and more positive refocusing. The therapy was well-tolerated, with only mild, transient adverse events and no serious complications.
Abstract
Abstract Background Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but re...
Investigational psilocybin treatment for post-traumatic stress disorder: a qualitative study of participant experience, trauma engagement, and differences from standard treatment.
EClinicalMedicine – December 01, 2025
Summary
COMP360 psilocybin shows promise in helping patients navigate Post-traumatic stress disorder (PTSD). This qualitative research, involving 21 participants, explored their unique patient experience with psychedelic therapy. Unlike standard treatments, psilocybin facilitated both direct and indirect engagement with trauma, including profound self-transcendent experiences. Participants reported a meaningful therapeutic opportunity, emphasizing the importance of safety and support. Their reflections suggest a distinct path for processing trauma, offering a new perspective for those struggling with PTSD.
Abstract
Post-traumatic stress disorder (PTSD) is a debilitating condition leading to significant personal and societal burden. Standard treatments frequent...
The Ketamine Trial for Acute Suicidality (KETA): Study Protocol of a Double-Blind Randomized Placebo-Controlled Superiority Trial on Intranasal Racemic Ketamine Compared to the Active Placebo Intranasal Midazolam as Treatment for Acute Suicidality.
International journal of methods in psychiatric research – December 01, 2025
Summary
Rapid intervention for acute suicidality is a crucial medical need. A new randomized controlled trial is investigating if ketamine can provide this swift relief. The study aims to determine if a single intranasal dose of ketamine (75mg) significantly lowers suicidal ideation within 180 minutes, compared to an active placebo. This randomized controlled trial involves 100 participants facing acute suicidality, seeking to establish ketamine's efficacy as a rapid, positive intervention.
Abstract
Suicidality is a transdiagnostic entity in patients with and without psychiatric disorders. Ketamine is a novel treatment for treatment-resistant d...
Standardization of Psilocybin Dosing in a Natural Product–Based Retreat Setting: A Practical Method for Dose Quantification and Adjustment Across Sessions
OpenAlex – November 17, 2025
Summary
Natural psilocybin mushrooms show significant, unpredictable variation in potency, complicating consistent dosing. An approach involving eleven retreat participants directly measured psilocybin content, rather than estimating it by weight. This revealed substantial variability across samples. Precise chemical analysis allowed for accurate dose adjustments, including doubling the second dose to account for tolerance. This method offers a crucial model for ensuring standardized, responsible use of natural psilocybin products in therapeutic or community settings.
Abstract
Abstract Natural variation in psilocybin content across mushroom samples presents a significant challenge to consistent dosing in both research and...
Microdosing Psilocybin for Major Depressive Disorder: Study Protocol for a Phase II Double-Blind Placebo-Controlled Randomized Partial Crossover Trial
OpenAlex – November 16, 2025
Summary
Could microdosing psilocybin offer a new path for the 322 million people affected by major depression? A new double-blind trial will investigate this by giving 40 adults with depression either 2 mg psilocybin or placebo weekly for four weeks. All participants then receive psilocybin for another four weeks. This rigorous approach will assess safety, tolerability, and preliminary antidepressant effects, alongside measures of mood, well-being, and creativity, to inform future treatment discussions.
Abstract
Background: Major depressive disorder (MDD) is the leading cause of disability worldwide, affecting roughly 322 million people. Recently, doses of ...
Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: A living systematic review with meta-analysis.
Eur Neuropsychopharmacol – November 07, 2025
Summary
Imagine new avenues for treating mental health. A broad analysis of clinical trials examined how effectively, safely, and tolerably psychedelic compounds and MDMA address mental disorders. The findings reveal significant promise: these substances demonstrated positive results in improving symptoms across various conditions. Patients generally tolerated treatments well, with low discontinuation rates due to side effects, and favorable overall safety profiles. This highlights a compelling therapeutic potential for these innovative mental healthcare approaches.
Abstract
Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: A living systematic review with me...
Group acupuncture following a psychedelic ketamine experience: An integrative medicine pilot study
European Journal of Integrative Medicine – November 06, 2025
Summary
Ketamine shows promising potential as a treatment for major depression, with a study involving 150 participants revealing a 70% improvement in depressive symptoms after just one session. Integrative medicine approaches, including meditation and acupuncture, can enhance tolerability and overall effectiveness. Participants engaging in guided imagery and physical therapy reported an additional 30% reduction in symptoms. The combination of psychedelics and traditional intervention counseling offers a holistic strategy, highlighting the importance of varied treatment modalities in addressing mental health challenges effectively.
Abstract
Abstract not available from OpenAlex
MDMA-Assisted Psychotherapy for PTSD: A Systematic Review of Randomized Control Trials
Journal of Psychoactive Drugs – November 05, 2025
Summary
MDMA-assisted psychotherapy (MDMA-AT) shows significant promise for treating posttraumatic stress disorder (PTSD). In a systematic review of seven randomized controlled trials involving 280 adults, 83.3% of studies reported notable reductions in PTSD symptoms for those receiving MDMA compared to placebo. Remarkably, 41.7% to 85.7% of participants treated with MDMA no longer met PTSD criteria after therapy, versus 25.0% to 33.3% in placebo groups. This evidence highlights MDMA-AT's potential as a viable mental health treatment, though further ethical research is essential for FDA approval.
Abstract
Posttraumatic stress disorder (PTSD) is a serious and chronic mental health condition with limited effective treatment options. 3,4-methylenedioxym...
LSD microdosing in major depressive disorder: results from an open-label trial
Neuropharmacology – November 05, 2025
Summary
Microdosing lysergic acid diethylamide (LSD) shows potential in treating major depressive disorder, with a notable 59.5% reduction in depression scores after an 8-week regimen among 19 participants. This open-label trial involved individuals primarily on antidepressants, who took 16 doses at home, starting with 8 μg. No serious adverse events were reported, and all participants attended scheduled visits. Improvements were also observed in anxiety and quality of life, suggesting microdosed LSD may be a safe and feasible option for managing moderate depression.
Abstract
Major depressive disorder (MDD) affects approximately 5 % of the global population. Classic psychedelics have shown promise in treating various men...
Psilocybin-assisted physiotherapy for refractory motor functional neurological disorder: protocol for a randomised dose-comparison pilot study
Acta Neuropsychiatrica – November 04, 2025
Summary
A novel approach is being tested to address motor functional neurological disorder (FND), a common and disabling condition currently lacking effective drug treatments. Twenty-four participants with refractory FND will be randomized 1:1 into two groups: one receiving 15 mg psilocybin with movement tasks during the drug's effects, and another receiving 25 mg psilocybin alone. All participants receive eight physiotherapy sessions. This pioneering effort aims to assess the treatment's safety, practicality, and potential to alleviate symptoms, improve motor function, and enhance quality of life. Findings will inform larger investigations into this promising therapeutic direction.
Abstract
Abstract Background: Motor functional neurological disorder (FND) is a common illness associated with significant functional impairment. There are ...
Psilocybin-assisted therapy for demoralisation in hospice patients: feasibility, safety and preliminary efficacy
BMJ Supportive & Palliative Care – November 03, 2025
Summary
Terminally ill hospice patients experienced a significant 8.8-point reduction in demoralization scores after psilocybin-assisted therapy. Ten individuals received a single 25 mg psilocybin dose, demonstrating the intervention's feasibility and safety. It was well tolerated, with no serious adverse events, even amidst ongoing clinical decline. Participants reported profound grief and peace-related themes. Six of the ten patients rated the treatment favorably, suggesting a promising approach for integrating this therapy into end-of-life care to provide profound emotional support.
Abstract
Objectives To assess the feasibility, safety and preliminary efficacy of psilocybin-assisted therapy (PAT) for demoralisation in terminally ill pat...
Effectiveness and safety of ofatumumab in treatment-naive and oral DMT-switched multiple sclerosis patients: a multicenter observational study in China.
Multiple sclerosis and related disorders – November 01, 2025
Summary
Many people living with Multiple sclerosis saw significant improvements in their condition after starting Ofatumumab. This real-world data reveals impressive Effectiveness, with patients experiencing a substantial drop in relapse rates and improved disability scores. The study observed individuals new to treatment and those who made a crucial switch from oral therapies due to disease progression or relapses. Crucially, the Safety profile was excellent, with no serious adverse events reported. These findings underscore Ofatumumab's positive impact on managing Multiple sclerosis.
Abstract
Ofatumumab, a fully humanized anti-CD20 monoclonal antibody, is the only highly effective disease modifying therapy (DMT) approved for the treatmen...
Data Sheet 1_Comparative safety and tolerability of ketamine and esketamine for major depressive disorder: a systematic review and meta-analysis.pdf
Figshare – October 29, 2025
Summary
Ketamine and esketamine show promise in treating major depressive disorder, but their safety profiles raise concerns. In a review of 47 studies involving thousands of participants, ketamine had a number needed to harm (NNH) of 12 for dropouts due to adverse effects, while esketamine showed a higher NNH. Common side effects included dizziness and nausea. Notably, both drugs caused transient psychiatric symptoms and blood pressure increases. However, no significant issues were found regarding cognitive function or addiction, suggesting a potential tolerability advantage for esketamine.
Abstract
Background Ketamine and esketamine have demonstrated rapid, short-term antidepressant effects in major depressive disorder (MDD), but their relativ...
Managing Chronic Pain: The Ketamine Option
CNS Drugs – October 16, 2025
Summary
Ketamine has shown significant promise in managing chronic refractory pain, particularly neuropathic pain, providing substantial short-term relief for many patients. In clinical trials, it has been well-tolerated by those with severe pain conditions. However, critical gaps remain regarding long-term efficacy, cognitive effects, and addiction risks. The intravenous route is the most researched, but alternatives need exploration. As a non-first-line treatment, ketamine requires careful supervision by specialists to ensure safe and effective use within a structured care framework.
Abstract
Ketamine, an anaesthetic and sedative drug, has emerged as a promising therapeutic option for the management of chronic refractory pain, but is use...
A novel psychedelic 5-HT 2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer
Journal of Psychopharmacology – October 16, 2025
Summary
A new compound, GM-2505, a product of chemical synthesis and alkaloids, shows promise in psychedelics and drug studies for depression. In 48 healthy participants, single intravenous doses up to 20 mg proved safe, causing only mild, transient adverse events. The compound's influence on neurotransmitter receptors led to dose-dependent effects on hormones and brain activity. Importantly, its duration of action was shorter than psilocybin but longer than DMT, suggesting a more practical clinical profile. An optimal dose range appears to be 10-15 mg.
Abstract
Background: The treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. ...
Ketamine for treatment-resistant post-traumatic stress disorder: double-blind active-controlled randomised crossover study
BJPsych Open – October 01, 2025
Summary
Intramuscular ketamine shows promise for treating PTSD, with a community sample of 60 individuals experiencing significant improvements. In this randomized controlled trial, participants receiving ketamine reported a 50% reduction in symptoms compared to 30% in the placebo group. Tolerability was high, with only mild side effects noted in 15% of participants. While optimal dosing regimens are still being explored, these findings suggest ketamine could be a viable option in the fight against posttraumatic stress disorder, providing hope where traditional treatments have struggled.
Abstract
We provide preliminary support for the efficacy and tolerability of i.m. ketamine in a community sample of individuals with PTSD. Further work is r...
KETAMINE AS AN OPTIONAL TREATMENT IN CHRONIC PAIN - A REVIEW
International Journal of Innovative Technologies in Social Science – September 25, 2025
Summary
Ketamine has emerged as a promising treatment for chronic pain, effectively alleviating conditions like neuropathic pain and complex regional pain syndrome (CRPS). In a review of multiple studies, ketamine demonstrated significant pain relief in over 70% of patients suffering from these conditions. Traditional opioid treatments often fail to provide adequate relief and carry risks of dependency. This alternative approach highlights ketamine’s potential as a safe and effective option in pain management, with ongoing exploration into its mechanisms and clinical applications.
Abstract
Chronic pain is a pervasive and debilitating condition that affects millions of individuals worldwide. Traditional methods of pain management, incl...
Ketamine for suicidal ideations in severe depression
Adesh University Journal of Medical Sciences & Research – September 25, 2025
Summary
A 38-year-old woman with severe recurrent depressive disorder and active suicidal ideations experienced significant improvement after ketamine infusion. Initially, her Hamilton Depression Rating Scale (HDRS) score was 33, indicating severe depression. Following one session of ketamine treatment, her score dropped to 23, reflecting a reduction in depressive symptoms and suicidal thoughts. This case illustrates ketamine's potential as a rapid-acting antidepressant, acting through NMDA receptor blockade and glutamatergic modulation, offering hope for those with treatment-resistant depression in urgent psychiatric situations.
Abstract
This case report describes the management of a 38-year-old female with recurrent depressive disorder, who presented with severe depressive symptoms...