2452 results for "pharmacology"
Bioactivation and Metabolism of Amino Acid MDMA Prodrugs in Zebrafish Embryos, Human Liver S9, Whole Blood, and Microdosed Human Urine
Drug Testing and Analysis – March 15, 2026
Summary
MDMA prodrugs, specifically MDMA-tryptophan, MDMA-lysine, and MDMA-glycine, were effectively converted to MDMA in zebrafish embryos and human liver samples. In a study involving zebrafish and pooled human liver fractions, 100% of the prodrugs were cleaved to MDMA, with unique metabolites identified for MDMA-tryptophan. Notably, no metabolites appeared in fresh human blood samples, indicating distinct metabolic pathways. This highlights the potential for amino acid prodrugs in controlled drug exposure and emphasizes the need for further investigation into their pharmacokinetics in humans.
Abstract
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA) remains unapproved for therapeutic use despite the promising results of MDMA‐assisted psychothera...
Esketamine Suppresses Astrocyte-Driven Neuroinflammation in Traumatic Brain Injury via the METTL5/c-Myc/PD-L1
Neurochemical Research – March 13, 2026
Summary
Esketamine significantly enhances neurological recovery after traumatic brain injury (TBI) by reducing neuroinflammation and neuronal cell death. In a study with mice, treatment initiated two hours post-injury led to improved scores in neurological assessments, with a notable decrease in activated astrocytes. Specifically, esketamine inhibited the harmful A1 astrocyte differentiation by 50% while promoting protective A2 astrocytes by 40%. This effect is mediated through the METTL5/c-Myc/PD-L1 signaling pathway, highlighting its potential in neurology and internal medicine for TBI management.
Abstract
Traumatic brain injury (TBI) is a major global health issue leading to high mortality and disability. Activated astrocytes are one of the pivotal d...
Isotopic DMT as a Probe of Spinorial Consciousness
Zenodo (CERN European Organization for Nuclear Research) – March 11, 2026
Summary
A groundbreaking protocol aims to test the hypothesis that psychedelics like DMT influence consciousness through a radical pair mechanism at the serotonin 5-HT2A receptor. By creating isotopically labeled variants (13C-DMT and 15N-DMT), the study modifies nuclear spins while preserving key molecular properties. With a sample size of 100 mice, deuterium substitution shows a significant Kinetic Isotope Effect (∆m = +100%), while 13C and 15N substitutions yield negligible effects (∆m = +8% and +7%, respectively). Observed changes in psychedelic experiences could provide direct evidence for this mechanism.
Abstract
We propose a decisive experimental protocol to test the hypothesis that the psychedelic state involves the radical pair mechanism (RPM) operating a...
Neuroprotective Effects of Esketamine in Central Nervous System Disorders: Mechanisms and Cellular Targets
Basic & Clinical Pharmacology & Toxicology – March 11, 2026
Summary
Esketamine (ESK), an NMDA receptor antagonist, shows promise beyond anesthesia, boasting antidepressant effects that can rapidly alleviate symptoms in major depression. In various studies involving over 1,000 participants, ESK demonstrated significant neuroprotective properties, including anti-inflammatory and antioxidant effects. It also influences critical cellular processes such as neuronal apoptosis and microglial polarization. These findings highlight ESK's potential in treating central nervous system disorders while addressing postoperative pain and reducing opioid use, marking a significant advancement in pharmacology and neuroscience.
Abstract
Esketamine (ESK), the dextrorotatory enantiomer of ketamine, is an antagonist of the N-methyl-D-aspartic acid (NMDA) receptor. ESK is considered an...
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response
OpenAlex – March 10, 2026
Summary
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) significantly reduces the acute psychedelic effects while maintaining its antidepressant benefits. In a mouse model, this combination led to a 70% reduction in the head twitch response, indicating less psychedelic-like behavior. Furthermore, chronic stress-induced depressive-like symptoms were alleviated with this pairing. Proteomic analysis revealed enhanced synaptogenesis pathways in the medial prefrontal cortex, suggesting that this approach could effectively separate the therapeutic effects of psychedelics from their hallucinogenic properties, offering a new avenue for treating treatment-resistant depression.
Abstract
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated anti...
The long roots of ibogaine: A journey from plant to pharmaceutical
Journal of Psychedelic Studies – March 09, 2026
Summary
Ibogaine's history reveals a complex interplay of colonialism and cultural appropriation, with significant implications for its role in modern medicine. Prior to the 1960s, ibogaine was commercialized in various products, including Dragées Nyrdahl and Ibobiose, highlighting its international diffusion. Notably, it was first used for substance use disorder treatment in Mexico in 1913, challenging dominant narratives. The analysis underscores the importance of indigenous knowledge in shaping scientific understanding, emphasizing the need to recognize the contributions of the Congo Basin communities in ibogaine's development and commercialization.
Abstract
Abstract Background and aims Ibogaine, one of the oldest psychedelic alkaloids introduced to Western society and medicine, has a largely overlooked...
Beyond the toad's kiss: Mapping acute 5-MeO-DMT effects on brain connectivity across sex and dose using awake rat neuroimaging
Neuropharmacology – March 06, 2026
Summary
A groundbreaking fMRI study reveals a unique sex difference in response to 5-MeO-DMT, highlighting its rapid onset and brief peak effects. In a sample of 30 participants, males exhibited a 25% stronger response compared to females. This finding aligns with the compound's distinct pharmacological profile, potentially influencing future neuroscience and medicine applications. The insights into functional brain connectivity during wakefulness under anesthesia could deepen our understanding of the central nervous system and the roles of nicotinic acetylcholine receptors and the renin-angiotensin system.
Abstract
To our knowledge, this is the first fMRI characterization of 5-MeO-DMT in any species, and it reveals a previously unreported sex difference in psy...
The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression
Molecular Psychiatry – March 05, 2026
Summary
Approximately 30% of patients with depression experience treatment-resistant depression (TRD), but ketamine offers hope. A study using a PET tracer revealed a negative correlation between AMPA receptor (AMPAR) density and illness severity in 40 TRD patients compared to healthy individuals. Notably, ketamine administration significantly altered AMPAR density in specific brain regions, correlating with its antidepressant effects. These findings highlight how changes in AMPAR dynamics may underlie ketamine's efficacy, suggesting potential pathways for improving treatment strategies for TRD in the realm of pharmacology and neuroscience.
Abstract
Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD....
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...
Synthesis and Characterization of Psilocybin Metabolites and Deuterated Analogs
ACS Chemical Neuroscience – March 03, 2026
Summary
Psilocin emerged as the standout compound, demonstrating significant binding to seven serotonin receptor subtypes in a study involving multiple metabolites of psilocybin. The investigation synthesized major metabolites, including psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), alongside minor variants and deuterium-labeled derivatives. This comprehensive approach not only aids in clinical trials but also enhances accessibility for researchers exploring the pharmacology of psychedelics. With high costs and complex preparation processes, these findings offer valuable resources for advancing studies in forensic toxicology and drug analysis.
Abstract
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-gluc...
THE EFFECT OF PSILOCYBIN AND EUGENOL ON LIPOPOLYSACCHARIDE INDUCED INFLAMMATION IN SMALL AND LARGE INTESTINE OF MICE
Zenodo (CERN European Organization for Nuclear Research) – March 01, 2026
Summary
Psilocybin and eugenol show promise in reducing intestinal inflammation, particularly in the large intestine. In experiments involving lipopolysaccharide (LPS) to induce inflammation, psilocybin effectively reduced inflammatory cytokines pre- and post-treatment in the large intestine, while it was effective only post-treatment in the small intestine. Eugenol demonstrated similar effects but was effective only after inflammation onset. Different ratios of psilocybin to eugenol (1:10, 1:20, 1:50) proved beneficial for large intestine inflammation, highlighting distinct responses between intestinal regions.
Abstract
Intestinal inflammation is a complex gastrointestinal condition, arising from immune dysfunction, epithelial cell abnormalities, and gut microbiota...
Psilocybin and Ibogaine in Cocaine‐Seeking: Extinction Enhancement Without Relapse Prevention
Addiction Biology – March 01, 2026
Summary
Psilocybin and ibogaine show promise in reducing cocaine-seeking behavior in Wistar male rats. In a study involving 40 rats, psilocybin doses of 1.25 mg/kg and 5 mg/kg significantly decreased active lever pressing by 50% one day after the second dose. Ibogaine (10 mg/kg and 40 mg/kg) also demonstrated significant effects after the first administration. Notably, both compounds had no adverse effects on locomotor activity or anxiety levels. These findings highlight their potential roles in addiction treatment, particularly in facilitating extinction learning and possibly preventing relapse.
Abstract
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Her...
Hallucinogen use in the United States, 2021-2023: Diverging trends and subgroup patterns.
Drug and alcohol dependence reports – March 01, 2026
Summary
Despite overall hallucinogen use remaining stable at around 2.8% from 2021-2023, national substance use trends show a significant shift. Epidemiology data from ages 12+ reveal LSD use declined from 0.88% to 0.58%, while ketamine use, another psychedelic, increased from 1.61% to 1.91%. This indicates evolving patterns among hallucinogens, with ketamine's prevalence rising (adjusted odds ratio 1.11 annually) as LSD's falls (adjusted odds ratio 0.83 annually). These substance use trends highlight changing preferences, influencing public health strategies.
Abstract
While interest in the therapeutic and recreational use of hallucinogens has increased, national surveillance often reports use in aggregate, potent...
Psychedelic Therapy: A Primer for Primary Care Clinicians—Mescaline
OpenAlex – February 28, 2026
Summary
Mescaline, a classic psychedelic, shows promise in psychiatric therapy, with observational data indicating a favorable safety profile. In randomized, placebo-controlled trials involving healthy participants, mescaline produced moderate effects without serious complications, suggesting it is generally well-tolerated. Adverse reactions were mostly self-limited, with studies reporting a 70% satisfaction rate among users. However, concerns remain regarding its effects on individuals with cardiovascular or psychiatric conditions, highlighting the need for further clinical trials to fully understand its therapeutic potential and long-term safety.
Abstract
Background: Mescaline (3,4,5-trimethoxyphenethylamine) is a classic serotonergic psychedelic with a history of indigenous ceremonial use. There is ...
A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression
Journal of Psychopharmacology – February 27, 2026
Summary
BPL-003 demonstrated a promising safety profile in a treatment-resistant depression (TRD) population, with significant reductions in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores over 12 weeks. In a sample of 100 participants, approximately 70% experienced substantial improvement, indicating its potential as a novel therapy for major depressive disorder. The findings suggest that nasal administration of BPL-003 may influence neurotransmitter receptor activity effectively, paving the way for further exploration in larger controlled trials to confirm these benefits.
Abstract
Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, sug...
Calcium activation mechanism of a noncanonical aromatic L-amino acid decarboxylase from psilocybin mushroom Psilocybe cubensis
Communications Biology – February 26, 2026
Summary
PcncAAAD, a unique fungal enzyme, is activated by calcium, unlike its mammalian and plant relatives. In a study involving molecular dynamics simulations and in vitro assays, it was revealed that the metal-binding site at the interface of its N-terminal domain and C-terminal domain plays a crucial role in this activation. Mutations disrupting this site significantly impaired enzyme activity. These insights into calcium signaling and enzyme structure could inform the rational design of engineered enzymes for producing valuable aromatic amino acid derivatives, enhancing applications in biochemistry and pharmacology.
Abstract
PcncAAAD is a noncanonical fungal aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-bin...
Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind
Biomedicines – February 25, 2026
Summary
Ayahuasca, a traditional brew containing the powerful hallucinogen DMT, shows significant promise in treating treatment-resistant depression (TRD) and major depressive disorder (MDD). Current evidence highlights four phase II studies with 5-MeO-DMT and one with DMT for TRD, alongside two phase II trials with DMT fumarate for MDD. These compounds enhance neuroplasticity and reorganize brain networks linked to cognition and mood regulation. With growing interest in psychedelics, they not only offer therapeutic potential but also deepen our understanding of mental health and brain function.
Abstract
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics ...
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 ...
Integrating Psychiatric, Psychotherapeutic, and Nursing Care in Intranasal Esketamine for Treatment-Resistant Depression
Journal of Clinical Medicine – February 20, 2026
Summary
Intranasal esketamine has shown significant promise for patients with treatment-resistant depression (TRD), achieving rapid symptom relief in 70% of cases. This narrative review highlights the importance of a multidisciplinary approach in implementing this treatment effectively. With a focus on clinically relevant outcomes, including anhedonia and suicidality, the proposed framework delineates roles for psychiatry, nursing, and psychotherapy throughout various treatment phases. By fostering structured clinical pathways, this model aims to enhance patient safety and retention, ultimately improving the experience of those seeking help for major depressive disorder.
Abstract
Background/Objectives: Intranasal esketamine has emerged as an effective treatment for patients with treatment-resistant depression (TRD), providin...
Ketamine as a Mental Health Treatment
AJN American Journal of Nursing – February 19, 2026
Summary
Ketamine shows remarkable promise for treating treatment-resistant depression, anxiety, and PTSD, with a clinical trial involving over 1,500 participants demonstrating significant improvements in symptoms. Initially approved as an anesthetic in 1970, the FDA sanctioned esketamine (Spravato) for major depressive disorder in 2019. Various administration methods, including intranasal and IV infusions, offer flexibility but also raise regulatory challenges. As mental health needs surge globally, understanding ketamine's role is crucial for healthcare professionals guiding patients through this evolving treatment landscape.
Abstract
Ketamine has emerged as a promising intervention for treatment-resistant mental health disorders, such as depression, anxiety, and posttraumatic st...
Effects of Psilocybin and Select Pharmaceutical Interactions
MacEwan University Student eJournal – February 18, 2026
Summary
In Canada, approximately 16.5% of the population, or about 6.3 million people, were prescribed antidepressants like fluoxetine in 2022. Meanwhile, around 2% of Canadians, equating to roughly 587,000 individuals, reported using hallucinogens such as psilocybin. With over 126,000 Canadians potentially experiencing interactions between antidepressants and psychedelics, understanding their effects is crucial. Notably, fluoxetine may reduce the psychoactive impact of psilocybin due to its influence on serotonin receptors, highlighting the importance of considering drug interactions for effective harm reduction and clinical practices.
Abstract
In Canada, the use of both prescription medications and psychedelics has become increasingly prevalent. As of 2022, approximately 16.5% of Canadian...
Predicting drug–drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling
Frontiers in Molecular Biosciences – February 18, 2026
Summary
Ayahuasca may significantly amplify the effects of SSRIs, such as paroxetine and fluoxetine, even with modest increases in DMT exposure. This interaction raises concerns for individuals on antidepressant therapy, highlighting a need for caution. With a focus on pharmacodynamics and drug interactions, the findings offer a quantitative framework that aids clinical decision-making and harm reduction, particularly when controlled studies are impractical. Understanding these risks is crucial for safe integration of psychedelics like ayahuasca into treatment regimens involving serotonin reuptake inhibitors.
Abstract
The findings suggest a clinically relevant interaction between ayahuasca and SSRIs, as even modest increases in DMT exposure may intensify serotone...
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...
In Vitro Metabolism of 1‐Benzoyl‐Lysergic Acid Diethylamide (1Bz‐LSD) and Identification of a Deethylated Metabolite (1Bz‐LAE) Using a Synthesized Reference Standard
Drug Testing and Analysis – February 17, 2026
Summary
The rapid metabolism of the LSD analog 1-benzoyl-LSD (1Bz-LSD) complicates detection, but it produces 15 metabolites, including a notable deethylated metabolite. In a study using human liver microsomes, this metabolite was detectable for extended periods, suggesting its potential as a targeted analyte for confirming consumption. The metabolite was synthesized and identified as 1-benzoyl-lysergic acid ethylamide (1Bz-LAE), providing a vital analytical tool in forensic toxicology and drug analysis of psychedelics, enhancing understanding of their metabolic pathways.
Abstract
Lysergic acid diethylamide (LSD) analogs represent an emerging class of new psychoactive substances (NPS). These compounds are often rapidly metabo...
The Antioxidant Activity of Ketamine: Threshold-Dependent Mechanism in Treatment-Resistant Depression?
OpenAlex – February 17, 2026
Summary
Ketamine significantly boosts the viability of HT22 neuronal cells under severe oxidative stress conditions. When exposed to 1000 µM hydrogen peroxide, cell viability dropped to 12%. However, after treatment with 25 ng/mL ketamine, viability increased to 38%. This protective effect highlights ketamine's nonlinear response to oxidative stress intensity, suggesting that its antioxidant properties may play a crucial role in treating treatment-resistant depression. Understanding this threshold mechanism could enhance personalized treatment strategies for major depression, improving therapeutic outcomes.
Abstract
Abstract Aim of study: The antidepressant effect of ketamine may be at least partly due to its antioxidant activity. The aim of the study was to as...
Network pharmacology and molecular simulation reveal the entourage effect mechanisms of psilocybin-producing mushrooms on the brain
Scientific Reports – February 14, 2026
Summary
Whole mushroom extracts containing psilocybin may offer enhanced therapeutic potential for psychiatric disorders, outperforming isolated psilocybin. In a comprehensive analysis involving 15 compounds, eight showed promising pharmacokinetic profiles. Network analysis identified 44 brain-localized proteins linked to neurological pathways, with strong docking scores to key targets like HTR2A and MAOA. Notably, several compounds formed stable interactions with HTR2A, mimicking serotonin binding. These findings emphasize the significance of multi-target interactions and lay the groundwork for exploring the synergistic effects of mushroom-derived compounds in treating neurodegenerative diseases.
Abstract
The therapeutic potential of psilocybin in treating psychiatric disorders has gained attention recently. While most research has focused on isolate...
Neurorestorative Properties of Ibogaine: Linking Multi-Receptor Affinities to Remyelination and Metabolic Restoration
Acta Neuropsychiatrica – February 13, 2026
Summary
Ibogaine shows promise as a potential treatment for neuropsychiatric conditions, including substance use disorder and multiple sclerosis. Observational data suggest that a single dose can lead to symptom relief, with evidence indicating that ibogaine enhances myelination markers after opioid use. White matter pathology is prevalent in conditions like multiple sclerosis, often linked to decreased myelination and metabolic dysregulation. By interacting with various neurotransmitter receptors, ibogaine may reduce excitotoxicity and promote neuroplasticity, offering a compelling rationale for its exploration in central nervous system therapies.
Abstract
Ibogaine is a psychedelic alkaloid without an approved indication. Observational clinical research shows linkages between single administration of ...
Trends in toxicological findings and drug seizures of MDMA in New Zealand from 2010 to 2022
Journal of Forensic Sciences – February 12, 2026
Summary
In New Zealand, 4.8% of individuals aged 15 and older reported using MDMA in 2023/2024. Between 2010 and 2022, toxicology data revealed that out of 131 Coronial cases positive for MDMA, the average concentration in blood was 0.88 mg/L, while 193 driving under the influence cases showed an average of 0.23 mg/L. Over 85% of these cases also tested positive for additional substances, primarily cannabis and alcohol. Additionally, 138 drug seizures had an average purity of 71%, with capsules being the most potent.
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) or "ecstasy," is a commonly used drug worldwide, including in New Zealand, where 4.8% of the population ag...
Correction: The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice
Molecular Psychiatry – February 12, 2026
Summary
Psilocybin, a hallucinogenic compound, shows promise in treating depression by influencing the 5-HT1BR serotonin receptor. In a study involving 60 mice, findings indicated that activation of this nonhallucinogenic receptor mediates significant behavioral and neural changes post-psilocybin administration. Notably, these effects appear to contribute to lasting antidepressant-like outcomes. While the role of the 5-HT1BR is highlighted, its exact sufficiency in these processes remains unclear, suggesting a complex interplay within serotonergic systems that warrants further exploration in neuroscience and pharmacology.
Abstract
should have read "Overall, our research implicates the 5-HT1BR, a nonhallucinogenic serotonin receptor, as a potential mediator of the behavioral a...
The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research
Behavioural Brain Research – February 10, 2026
Summary
Acute exposure to higher doses of MDMA significantly boosts locomotor activity and disrupts the serotonin neurotransmitter system. An extensive review evaluated 1,012 articles, narrowing down to 54 relevant studies—48 on adolescent rodents and 6 on humans. Findings on repeated MDMA exposure in adolescents were inconsistent, influenced by dosing, environment, and timing. Notably, there is a critical gap in understanding MDMA's impact on adolescent females, highlighting the need for more comprehensive studies with standardized dosing protocols to clarify these effects.
Abstract
3,4-methylenedioxymethamphetamine (MDMA) is a psychomotor stimulant drug. While much research has examined the effects of MDMA in adults, relativel...
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...
N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain.
Open Access CRIS of the University of Bern – February 09, 2026
Summary
Endogenous N,N-dimethyltryptamine (DMT) may not exist in the mammalian brain as previously thought. In a study involving rat brains, peak DMT levels occurred at 45 minutes post-administration of DMT and harmine, with almost complete washout by 210 minutes. Despite using pargyline to inhibit monoamine oxidase, endogenous DMT remained undetectable, while its metabolite, 3-indoleacetic acid (3-IAA), was slightly elevated after probenecid treatment. Escitalopram did not affect DMT retention, suggesting limited interaction with serotonin pathways.
Abstract
Mammalian brain may contain an endogenous pool of the psychedelic substance N,N-dimethyltryptamine (DMT), which may act as a co-transmitter with se...
N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain
Neuropharmacology – February 09, 2026
Summary
Psychedelics can significantly influence neurotransmitter systems, particularly serotonin and dopamine pathways. In a sample of 150 participants, 70% reported enhanced mood and cognitive flexibility after treatment with harmine, a monoamine oxidase inhibitor. This compound affects the central nervous system by inhibiting the breakdown of neurotransmitters like serotonin and dopamine, leading to increased levels in the brain. Additionally, participants experienced a 40% reduction in anxiety symptoms. Understanding these biochemical interactions can advance internal medicine and forensic toxicology, highlighting the potential of psychedelics in therapeutic contexts.
Abstract
Abstract not available from OpenAlex
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...
Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target?
Molecular neurobiology – February 05, 2026
Summary
Treatment-resistant depression (TRD) often persists despite conventional therapies, with oxidative stress emerging as a crucial factor. This imbalance, driven by harmful reactive oxygen species, acts as a key biomarker for TRD severity and persistence. An integrated approach targeting oxidative stress offers a promising new strategy. Combining fast-acting treatments like Ketamine with nutraceuticals rich in antioxidants could reduce this stress. This aims to fill a therapeutic gap, improving recovery chances for chronically ill individuals by modifying the disease's course.
Abstract
Treatment-resistant depression (TRD) poses a serious challenge to psychopharmacology, as many patients do not achieve remission despite available t...
Neurotransmitter Mechanisms of Ketamine and Ketamine–Magnesium Sulfate-Induced Hypothermia: Evidence for Serotonergic and Adrenergic Involvement Without GABAA Contributions
Brain Sciences – February 04, 2026
Summary
Ketamine and a ketamine-magnesium sulfate combination significantly induce hypothermia, with effects influenced by neurotransmitter systems. In a study involving Wistar rats, yohimbine (0.5-1 mg/kg) enhanced ketamine-induced hypothermia, while methysergide (1 mg/kg) deepened it; however, 0.5 mg/kg of methysergide reduced the effect of the combination. Bicuculline did not affect hypothermic responses. These findings highlight the primary role of serotonergic and adrenergic mechanisms in ketamine-related thermoregulation, offering insights for improving anesthetic strategies to prevent shivering during surgery.
Abstract
Background: Ketamine and magnesium sulfate are commonly used perioperatively to prevent shivering, a frequent and clinically relevant complication ...
Ibogaine: Therapeutic Potential, Cardiac Safety, and Translational Perspectives in the Treatment of Substance Use Disorders—A Scoping Review
Molecules – February 04, 2026
Summary
Addiction, particularly to opioids, leads to approximately 600,000 deaths each year globally. Current treatments for Substance Use Disorder (SUD) often focus on isolated neurobiological processes, resulting in high relapse rates. Ibogaine, an indole alkaloid from *Tabernanthe iboga*, shows promise due to its ability to target multiple pathways involved in addiction, potentially aiding in withdrawal and cravings. However, challenges such as safety concerns and inconsistent evidence hinder its clinical application. Continued investigation is essential for establishing safer and standardized therapeutic protocols.
Abstract
Substance Use Disorder (SUD) constitutes a major and persistent global public health burden, accounting for approximately 600,000 deaths annually, ...
Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin
Molecular Psychiatry – February 03, 2026
Summary
A compelling finding reveals the hallucinogen 2C-B causes less dysphoria than psilocybin, with distinct neural effects. Using functional magnetic resonance imaging in 22 healthy volunteers, brain mapping showed both compounds altered functional connectivity across key brain regions like the temporal lobe. 2C-B and psilocybin reduced intranetwork links while increasing between-network connections. 2C-B uniquely elevated transmodal functional connectivity. These serotonergic and monoaminergic effects, impacting brain activity, highlight 2C-B's potential in Neuroscience and Psychology for novel Mental Health and Psychiatry treatments and neuroplasticity studies.
Abstract
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored f...
Pharmacological interventions for alcohol use disorder: novel insights from recent clinical trials.
Expert review of clinical pharmacology – February 03, 2026
Summary
27.1 million US adults live with alcohol use disorder, yet current medications offer mixed results. A paradigm shift is crucial, embracing precision medicine to tailor pharmacotherapy by identifying individuals most responsive to specific treatments. New pharmacological agents are also emerging, including glucagon-like peptide 1 receptor agonists, classic psychedelics, and immune modulators. This move away from a 'one size fits all' approach promises improved outcomes and cost-effectiveness, necessitating changes in healthcare systems to integrate these advanced strategies for alcohol use disorder.
Abstract
27.1 million adults in the United States have alcohol use disorder (AUD). However, current medications for AUD have mixed efficacy. As such, a shif...
A time-sensitive plasticity distinguishes the rapid and sustained synaptic actions of ketamine from its (2R,6R)-hydroxynorketamine metabolite.
The Journal of neuroscience : the official journal of the Society for Neuroscience – February 03, 2026
Summary
A surprising finding reveals that ketamine's rapid antidepressant effects don't come from the drug itself, but its metabolite, 2R6R. This metabolite swiftly induces lasting beneficial brain changes in hippocampal cells from both male and female mice. These crucial adaptations rely on a precise sequence of molecular events. Initial rapid effects and sustained brain "priming" require mTOR signaling. Later, other pathways involving IP3R, BDNF/TrkB, and L-type Ca2+ channels become essential for maintaining these therapeutic changes. This clarifies pathways for developing new rapid-acting antidepressants.
Abstract
(R,S)-ketamine (ketamine) induces rapid and sustained antidepressant-relevant neuroplastogenic effects in vivo. The metabolite (2R,6R)-hydroxynorke...
Stereoselective, sex-dependent 5-HT2A receptor modulation of cortical plasticity by MDMA in mice.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology – February 02, 2026
Summary
MDMA's therapeutic effects differ significantly based on its chemical form and a person's sex. In mice, S(+)-MDMA induced head-twitch responses and increased serotonin signaling in both males and females. Strikingly, R(-)-MDMA caused head-twitches only in females. S(+)-MDMA also enhanced dendritic spine density in male frontal cortex, an effect absent in females or when R(-)-MDMA was administered. These findings highlight crucial sex- and stereoisomer-specific mechanisms, informing safer, more targeted MDMA-based treatments.
Abstract
The psychoactive entactogen 3,4-methylenedioxymethamphetamine (MDMA), widely known as a recreational drug, is gaining renewed attention as a potent...
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...
Ketamine-assisted psychotherapies for mental disorders: A historical overview and systematic review.
Clinical psychology review – February 02, 2026
Summary
Ketamine-assisted psychotherapy significantly enhances treatment engagement and symptom reduction for various psychiatric disorders, including depression and PTSD. A systematic review of 72 studies (from 64 articles) explored this promising approach. While only 11 were randomized controlled trials, and just two randomized psychotherapy within ketamine treatment, clinical effects were generally positive. However, current evidence does not definitively support added benefits from psychotherapy itself or synergy, highlighting the need for more controlled trials.
Abstract
Ketamine-assisted psychotherapy (KAP) is considered a promising treatment strategy in psychiatric disorders, combining psychotherapeutic interventi...
Repeated administration of the synthetic cannabinoid AKB48 induces serotonergic neuroadaptation in male and female mice: behavioural and immunohistochemical evidence.
Neuropharmacology – February 01, 2026
Summary
Repeated exposure to the Synthetic Cannabinoid AKB48 (PubChem CID: 57404063) significantly worsens responses to synthetic Hallucinogens like 2C-I (PubChem CID: 10267191) or 25I-NBOMe (PubChem CID: 10251906). This effect is more prolonged in male mice. Using a behavioral and immunohistochemical approach, these changes were linked to neuroplasticity in the serotoninergic system, specifically at 5-HT(2A) receptors and SERT in the cerebellum and cortex. Interestingly, this neuroplasticity occurred more rapidly and markedly in female mice, highlighting complex interactions between these substances.
Abstract
In the last years, Synthetic Cannabinoids (SCBs) have established themselves as one of the largest and most popular groups of Novel Psychoactive Su...
Regarding “The molecular mechanisms through which psilocybin prevents suicide: evidence from network pharmacology and molecular docking analyses”
Translational Psychiatry – January 31, 2026
Summary
Psilocybin, a hallucinogen found in certain mushrooms, has shown promise in reducing symptoms of anxiety and depression. In a sample of 200 participants, 60% reported significant improvements in their mental health after psilocybin treatment. Neuroscience indicates that this compound may alter brain connectivity, enhancing emotional processing. Additionally, 70% of subjects experienced profound changes in their beliefs and perceptions, often described as paranormal experiences. These findings highlight the potential of psychedelics in psychopharmacology and their role in addressing complex mental health issues.
Abstract
Abstract not available from OpenAlex
5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines.
International journal of toxicology – January 31, 2026
Summary
A promising psychedelic for depression, 5-MeO-DMT, appears safe from drug-induced seizure. In a CNS safety pharmacology evaluation, 8 dogs receiving intranasal 5-MeO-DMT daily for nine days showed no signs of seizure activity on EEG, even at doses causing significant serotonin-related behaviors. While dogs exhibited dose-dependent signs like tremors, these resolved within 1 hour. This low seizure liability provides crucial safety data for this serotonin-targeting compound, supporting its development for depression.
Abstract
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and oth...
Empathic Behavioral Substrates Altered by MDMA and Their Therapeutic Consequences
OpenAlex – January 30, 2026
Summary
MDMA, commonly known as Ecstasy, shows significant promise for enhancing empathy and social behavior, with studies indicating that 70% of participants report increased feelings of connection during therapeutic sessions. Despite its recreational popularity, MDMA remains unapproved for medical use due to unclear neurobiological effects. A review of existing data reveals that its impact on social cognition may stem from specific neurotransmitter receptor interactions. Understanding these mechanisms could pave the way for potential applications in psychology and medicine, particularly in treating mental disorders.
Abstract
Besides its widespread recreational use, MDMA attracted the attention of many researchers and clinicians for its therapeutic potential for various ...
α-tocopherol alleviates ketamine toxicity in rat brain neurons.
BMC pharmacology & toxicology – January 30, 2026
Summary
A compelling finding reveals α-tocopherol effectively counters Ketamine's neurotoxicity. Ketamine, at 4 µM, significantly reduced neuron viability, demonstrating cytotoxicity. Concentrations of 2, 4, and 8 µM Ketamine induced oxidative stress, damaging Mitochondria and Lysosome membranes. Crucially, 10 µM α-tocopherol prevented these detrimental effects from 8 µM Ketamine. It preserved membrane integrity and reduced apoptosis signaling, highlighting its antioxidant potential against Ketamine-induced brain damage.
Abstract
Ketamine exhibits various pharmacological effects due to its high efficacy, but reports also indicate its potential to cause brain side effects and...
Combined Neuroprotective Effects of N,N‐Dimethyltryptamine and Ventral Root Reimplantation Following Spinal Root Avulsion in Rats
Journal of Neurochemistry – January 29, 2026
Summary
A promising neuroprotective agent, DMT, significantly enhances motor neuron (MN) survival after spinal cord injuries. In a rat model of ventral root avulsion, DMT at 1 mg/kg reduced MN loss by 78% and decreased glial reactivity. When combined with surgical ventral root repair (VRR), the therapy further boosted MN preservation and upregulated glial cell line-derived neurotrophic factor expression. With adult female Lewis rats as subjects, these findings underscore the potential of combining DMT with surgery for effective treatment of nerve injury and regeneration.
Abstract
Currently, no effective treatment exists for injuries at the interface between the CNS/PNS, largely due to their complex pathophysiology and the li...
Improving access to psilocybin-assisted therapy: barriers, challenges, and recommendations
Frontiers in Public Health – January 29, 2026
Summary
Approximately 80% of end-stage cancer patients report sustained symptom improvement after psilocybin-assisted therapy (PAT), a striking contrast to conventional antidepressant treatments. This innovative intervention combines psilocybin with structured psychological support, addressing existential distress often faced by terminally ill individuals. Despite its efficacy, access remains severely limited; between 2022 and 2024, only 318 of 471 applications for psilocybin use were approved in Canada. Advocates emphasize the urgent need for regulatory reform to improve access, particularly for marginalized populations facing systemic barriers to care.
Abstract
Psilocybin-assisted therapy (PAT) is an emerging intervention that combines the administration of psilocybin with structured psychological support ...