573 results for "metabolite"
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...
Inhibition of cortico-amygdala projections underlies affective bias modification by psilocybin
OpenAlex – March 04, 2026
Summary
Psilocybin, a serotonergic psychedelic, demonstrates rapid and lasting antidepressant effects in patients with major depressive disorder. In a rodent model, psilocin, its active metabolite, was found to significantly modulate negative affective biases by selectively suppressing excitatory inputs to cortico-amygdala projection neurons while enhancing inputs to cortico-cortical targets. Notably, these changes persisted for 24 hours post-infusion. Chemogenetic inhibition of specific neuron types mirrored psilocybin's effects, highlighting the prelimbic cortex's role in altering synaptic transmission and potentially explaining psilocybin's sustained therapeutic benefits.
Abstract
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (...
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...
In vivo and in vitro toxicokinetics including metabolism, isozyme mapping, and monoamine oxidase inhibition of three (2-aminopropyl)benzo[b]thiophene (APBT) psychedelics.
Toxicology – March 01, 2026
Summary
New psychoactive substances like 5-APBT and 6-APBT strongly inhibit MAO-A (IC50s 0.4 µM and 0.6 µM), signaling potential serious drug interactions. Their toxicokinetics and metabolism were characterized using LC-HRMS/MS in male Wistar rats (2 mg/kg dose) and human liver models. While metabolism involved multiple enzymes, potentially reducing some toxicity risks, the potent MAO inhibition is a critical finding. This provides vital data for understanding human health impacts and interpreting exposures to these compounds.
Abstract
3-(2-Aminopropyl)benzo[b]thiophene (3-APBT), 5-APBT, and 6-APBT are recently identified psychedelics and entactogens that activate serotonin 2 rece...
Psilocin glucuronide in whole blood: a stable and useful biomarker of psilocybin intake
Journal of Analytical Toxicology – February 19, 2026
Summary
A new method for detecting psilocybin use shows promise by reliably quantifying its metabolite, psilocin glucuronide (PSG), in human whole blood. The validated LC-MS/MS technique achieved limits of quantification of 2.4 nM for psilocin and PSG, and analyzed 23 forensic samples, identifying PSG in nearly all cases despite low psilocin levels. While psilocin degraded significantly over time—up to 99% after three days at room temperature—PSG remained stable for up to a year at -20 °C, establishing it as a reliable biomarker for psilocybin intake.
Abstract
Detecting psilocybin use is challenging because it rapidly converts to its psychoactive metabolite psilocin, and both compounds are unstable in blo...
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...
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
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...
The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior.
Pharmacological reports : PR – February 01, 2026
Summary
Psilocin, the active compound from psilocybin, creates a more balanced brain response in the Claustrum than the potent synthetic psychedelic 25I-NBOMe. Microdialysis in rats revealed Psilocin (at 100 or 500 µM) significantly elevated noradrenaline and enhanced cholinergic Neurotransmission. In contrast, 25I-NBOMe (500 µM) produced a greater serotonin increase and a more excitatory neurochemical profile. These distinct effects on neurotransmission highlight differing therapeutic and toxicological potentials, with Psilocin engaging circuitry in a more regulated manner.
Abstract
The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, e...
Dissociating pain dimensions in cold allodynia: subanesthetic ketamine reveals heritable affective-motivational traits in mice.
Pain – January 29, 2026
Summary
Emotional pain, not just physical sensation, is selectively targeted by ketamine. In a model of oxaliplatin-induced neuropathy causing cold allodynia, subanesthetic ketamine significantly reduced affective-motivational pain behaviors (like bites and licks) across 6 inbred mouse strains, without affecting somatosensory responses. This parsing of multidimensional pain revealed striking sexual dimorphism: females exhibited higher hydroxynorketamine levels (up to 3300 ng/mL) and distinct ketamine metabolism, impacting analgesic efficacy. Male mice showed higher ketamine plasma levels (up to 6200 ng/mL).
Abstract
Pain perception involves somatosensory-discriminative and affective-motivational components, mediated by separate brain circuits. Traditional mouse...
Psilocybin and the Evolutionary Significance of Altered Neural States: Interaction-Based Perspectives Beyond Deterrence Models
OpenAlex – January 28, 2026
Summary
Convergent evolution reveals psilocybin, a potent psychedelic, likely evolved not just as a fungal defense but to alter neural states, influencing ecological interactions. Integrating biology, evolutionary biology, and neuroscience, this perspective suggests psilocybin, alongside at least three other chemical synthesis alkaloids, represents a broader biological mechanism. These psychedelics, acting on conserved serotonergic systems, transiently shift perception and cognition, a profound insight for ecology and psychology. This reframes our understanding of psilocybin's evolutionary biology, moving beyond simple deterrence in drug studies.
Abstract
Psilocybin is a psychoactive tryptamine produced by a phylogenetically discontinuous yet ecologically diverse subset of fungi. Despite decades of c...
ADME profile of phencyclidine (PCP) analogues: emerging dissociative hallucinogens 3-MeO-PCP (CAS: 72242-03-6) and 4-MeO-PCP (CAS: 2201-35-6)-a multi-in silico approach for comprehensive prediction of absorption, distribution, metabolism and excretion relevant to clinical and forensic toxicology.
Archives of toxicology – January 28, 2026
Summary
New psychoactive substances like 3-MeO-PCP and 4-MeO-PCP, relatives of Phencyclidine, are predicted to readily cross the blood-brain barrier. An in silico analysis revealed their concerning toxicokinetic profiles, showing high gastrointestinal absorption and extensive tissue distribution. Both bind extensively to plasma proteins, around 70-80%. This ADME characterization supports targeted bioanalysis and informs clinical management, highlighting potential drug-drug interactions. This robust computational approach offers a vital tool for understanding these emerging compounds when human data is scarce.
Abstract
A multi-platform in silico workflow was applied to characterize the ADME profile of the methoxy-substituted phencyclidines 3-MeO-PCP and 4-MeO-PCP ...
Psilocin mediates long-term synaptic depression in the prelimbic cortex through 5-HT2A receptor-independent mechanisms
Neuropharmacology – January 21, 2026
Summary
Psilocin, psilocybin's active form, profoundly alters brain chemistry. Neuroscience research reveals it induces long-term synaptic depression in the prefrontal cortex through complex neurotransmission changes. Using electrophysiology in rat prelimbic cortex, this key finding shows excitatory postsynaptic potential reduction is mediated by enhanced GABAergic tone, not directly by typical serotonergic 5-HT2A receptors. Glutamatergic and metabotropic glutamate receptor involvement was also explored. This Biology and Neuropharmacology research, part of Psychedelics and Drug Studies, suggests how psilocin influences behavior via neurotransmitter receptor interactions, impacting prefrontal connectivity.
Abstract
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily...
Rare but relevant: Ibogaine and cardiovascular complications-prolonged QT interval and ventricular arrhythmias.
Addiction (Abingdon, England) – January 20, 2026
Summary
Ibogaine shows significant promise for addiction treatment, effectively reducing craving and withdrawal from opioid and cocaine dependence. However, this psychoactive compound and its metabolite, noribogaine, carry a rare but serious cardiovascular risk. It can cause QT interval prolongation and potentially fatal ventricular arrhythmias, even at therapeutic doses in healthy individuals. Variability in drug metabolism contributes to this danger. Future use demands strict medical supervision, personalized dosing, and rigorous cardiovascular monitoring, with safer ibogaine analogues showing promise.
Abstract
Revived interest in psychedelic-assisted therapies has also renewed focus on ibogaine, a psychoactive alkaloid, for its notable anti-addictive pote...
Generation of enantiospecific monoclonal antibodies against (2R,6R)-hydroxynorketamine.
Bioorganic & medicinal chemistry – January 17, 2026
Summary
A new antibody precisely distinguishes between mirror-image forms of hydroxynorketamine, a key ketamine metabolite. Through advanced bioconjugate chemistry and monoclonal antibody development, an antibody demonstrated strong responsiveness to (2R,6R)-hydroxynorketamine, with no responsiveness to its (2S,6S) counterpart. This antibody showed a sub-nanomolar affinity of 0.4 nM and over 150-fold selectivity compared to ketamine. This breakthrough enables future studies to understand how specific hydroxynorketamine enantiomers contribute to ketamine's rapid antidepressant effects.
Abstract
Antibodies against small psychoactive molecules have been developed for applications ranging from substance detection and overdose protection to me...
Single-dose psilocybin promotes cell-type-specific changes of neurons in the orbitofrontal cortex
Neurotherapeutics – January 01, 2026
Summary
A single dose of the hallucinogen psilocybin, a key compound in Psychedelics and Drug Studies, profoundly alters brain biology. Neuroscience reveals its chemistry induces long-term changes in the orbitofrontal cortex. Specifically, layer 5 pyramidal cells showed reduced glutamate receptor expression and decreased excitatory postsynaptic potential at the synapse, impacting neurotransmission. This contrasts with minimal changes in inhibitory postsynaptic potential. This work illuminates the neurotransmitter receptor influence on behavior, offering insights for Forensic Toxicology and Drug Analysis.
Abstract
Recent clinical breakthroughs hold great promise for the application of psilocybin in the treatments of psychological disorders, such as depression...
Simultaneous quantitative determination of 2-fluoro-2-oxo-phenylcyclohexylethylamine, methylenedioxymethamphetamine and ketamine in postmortem blood using liquid chromatography-tandem mass spectrometry.
Forensic toxicology – January 01, 2026
Summary
Fatal intoxications involving the dissociative anesthetic 2F-2-oxo-PCE have been forensically confirmed in postmortem cases for the first time. Blood concentrations ranged from 664 to 7911 ng/mL. Often found alongside MDMA and Ketamine, this suggests dangerous polydrug use contributed to deaths. A robust LC-MS/MS method was developed to simultaneously quantify 2F-2-oxo-PCE and related compounds. This vital data provides a critical baseline for interpreting emerging substance abuse.
Abstract
The abuse of 2-fluoro-2-oxo-phenylcyclohexylethylamine (2F-2-oxo-PCE), a dissociative anesthetic structurally related to phencyclidine (PCP) and ke...
Distinguishing 4- vs 5-Hydroxy- N , N -Dimethyltryptamine (Psilocin vs Bufotenine) Using Hydrogen–Deuterium Back-Exchange
Journal of the American Society for Mass Spectrometry – December 30, 2025
Summary
A groundbreaking method distinguishes between isomers of hydroxy-N,N-dimethyltryptamine, such as psilocin and bufotenine, by leveraging differences in their acidity (pKa) related to ring positions. Using hydrogen-deuterium exchange (HDX), the study demonstrated that only 4-hydroxy-N,N-dimethyltryptamine significantly exchanged deuterium within hours. This innovative approach, with implications for analytical chemistry and forensic toxicology, relies on high-resolution mass spectrometry to monitor kinetic exchange rates, offering a reliable means to differentiate structural isomers without needing external reference data or specific instrument configurations.
Abstract
Distinguishing metabolite isomers often relies on comparing relative data, such as relative chromatographic retention times and ion mobility arriva...
Evolution and horizontal transfer of the psilocybin biosynthetic gene cluster drive the diversification of magic mushrooms
Mycosphere – December 25, 2025
Summary
Psilocybin's genetic journey is remarkably dynamic. Sequencing 30 mushroom genomes and comparing them to 20,608 others revealed the psilocybin gene cluster likely originated from fungal gene duplication, not horizontal gene transfer from nonfungal sources. Yet, four independent horizontal gene transfer events and three distinct gene family configurations highlight complex evolutionary biology. Transcriptome analysis showed high PsiK gene expression in mycelium, but no psilocybin, suggesting precise genetic regulation within this multicellular organism. This genomics work advances fungal biology and applications, informing psychedelics and drug studies, and broader genetics research into fungal compounds, including those relevant to mushroom poisoning.
Abstract
Psilocybin, the psychoactive compound responsible for the hallucinogenic effects of “magic mushrooms,” is synthesized by a biosynthetic gene cluste...
Data: Evolution and horizontal transfer of the psilocybin biosynthetic gene cluster drive the diversification of magic mushrooms
Zenodo (CERN European Organization for Nuclear Research) – December 24, 2025
Summary
Psilocybin, the compound in "magic mushrooms," is produced by a unique gene cluster. Analyzing 30 mushroom genomes and comparing them to 20,608 others in a broad genomics study, evolutionary biology reveals this gene cluster originated via gene duplication within fungal biology. While vertical inheritance shapes species' genetics, comparative genomics identified four independent horizontal gene transfer events. This genetic innovation, involving specific genes and their transcriptome expression, explains how multicellular organisms like fungi diversified psilocybin production, highlighting its pivotal role in evolution.
Abstract
Psilocybin, the psychoactive compound responsible for the hallucinogenic effects of “magic mushrooms,” is synthesized by a biosynthetic gene cluste...
From fungi to pharmacy: Applied technologies in psilocybin production and its therapeutic applications
Creative Science – December 19, 2025
Summary
Psilocybin, a potent alkaloid, demonstrates rapid, sustained antidepressant efficacy in clinical trials, signaling a renaissance in Psychopharmacology. This naturally occurring compound, central to Psychedelics and Drug Studies, functions as a prodrug. Its active form modulates 5-HT2A receptors, enhancing neuroplasticity—a key mechanism explored in Neuroscience. Advances in chemical synthesis and microbial biosynthesis are revolutionizing its production, moving beyond traditional plant sources. This progress in Pharmacology and Drug discovery positions psilocybin as a transformative agent, bridging biological pathways from fungi to therapeutic applications.
Abstract
Psilocybin, a naturally occurring tryptamine alkaloid found in over 200 species of fungi, has emerged as a focal point in the modern revival of psy...
ATP-binding cassette transporter polymorphisms and the pharmacokinetics of oral esketamine
Pharmacogenomics – December 12, 2025
Summary
Oral esketamine shows promise for treating resistant depression, yet genetic variations may affect its effectiveness. In a study with 18 participants, genotypes ABCB1 3435C > T and ABCG2 421C > A were analyzed alongside plasma levels of esketamine four hours post-administration. Findings revealed no significant differences in esketamine concentrations across genotypes: C/C (3.8 µg/L), C/T (2.7 µg/L), and T/T (1.0 µg/L) for ABCB1; and C/A (1.5 µg/L) versus C/C (2.4 µg/L) for ABCG2. These results indicate that pharmacokinetics may not be influenced by these specific polymorphisms.
Abstract
Oral esketamine is a promising new therapy for treatment-resistant depression. However, concerns exist about interindividual pharmacokinetic variab...
Metabolic patterns of new psychoactive substances: Methyl-ketamine and 2-oxo-PCE in rats using UHPLC-QTOF analysis.
Forensic science international. Synergy – December 01, 2025
Summary
Subtle molecular differences profoundly shape how bodies process compounds. Using advanced UHPLC-QTOF analysis, researchers explored the metabolism in vivo of two psychoactive substances, Methyl-ketamine and 2-oxo-PCE, in rats. They discovered distinct markers of metabolism: even slight structural variations, like steric hindrance in Methyl-ketamine, guided unique breakdown pathways compared to 2-oxo-PCE. This work clarifies how molecular shape dictates metabolic outcomes, offering valuable insights for future predictions.
Abstract
This study investigated the metabolic profiles of two isomeric psychoactive agents, methyl-ketamine [2-(ortho-tolyl)-2-(methylamino)cyclohexanone] ...
Acute Blockade of the Serotonin Transporter With Low Doses of Escitalopram Does Not Alter the Behavioural Responses to Acute Psilocybin
European Journal of Neuroscience – December 01, 2025
Summary
Contrary to prior assumptions, the serotonin transporter (5-HTT) does not directly mediate psilocybin's immediate behavioral effects. Psilocybin (1 mg/kg) readily increased movement and induced head twitches in C57BL/6 mice. However, pre-treatment with the 5-HTT inhibitor escitalopram (2.5–5 mg/kg) did not alter these responses. This suggests that the 5-HTT is not directly involved in psilocybin's acute impact. Earlier findings, where psilocybin had no effect on mice genetically lacking 5-HTT, likely reflect developmental differences or varying serotonin levels, not a direct transporter role.
Abstract
ABSTRACT The psychedelic psilocybin has gained popularity in recent years as a therapy for treatment‐resistant depression and has been reported to ...
Electrochemical Simulation of 25B-NBOMe Phase I Metabolism and Metabolite Profiling by HPLC-QTOF-MS.
Molecules (Basel, Switzerland) – November 18, 2025
Summary
Electrochemical simulation of xenobiotic metabolism offers a rapid way to identify 25B-NBOMe's phase I metabolites, crucial for forensic toxicology. Utilizing on-line electrochemistry-mass spectrometry (HPLC-Q-TOF-MS), this method generated key hydroxylated and N-desalkylated derivatives. One significant phase I metabolite, O-desmethyl-25B-NBOMe, was confirmed through biological samples analysis from individuals severely intoxicated. While phase II metabolites, such as glucuronides, appeared exclusively in biological specimens, this electrochemical approach is a valuable screening tool for assessing novel psychoactive substance risks.
Abstract
This is the first report on the electrochemical simulation of phase I metabolism of 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]etha...
Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study.
Translational psychiatry – November 18, 2025
Summary
A new path is emerging for `treatment-resistant depression`. By using `iPSC-derived neurons` from affected individuals, scientists observed that `(2R,6R)-hydroxynorketamine` and `reelin` positively influenced crucial neuronal proteins and gene activity. Notably, `reelin` also enhanced `mTORC1 signaling`. This innovative model offers a powerful tool for developing novel therapies.
Abstract
Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to mod...
Pharmacodynamic effects and plasma pharmacokinetics of N, N-dimethyltryptamine after intranasal versus subcutaneous administration in male rats.
Psychopharmacology – November 15, 2025
Summary
Intranasal delivery of N,N-Dimethyltryptamine in rats achieved blood levels comparable to human psychoactive doses. Researchers explored this psychedelic compound's pharmacokinetics and effects, comparing intranasal and subcutaneous routes. Using Mass spectrometry, they found intranasal administration led to faster drug uptake and similar effects like flat body posture and hypothermia. This confirms intranasal delivery as a promising, non-invasive method.
Abstract
There is growing interest in the therapeutic utility of psychedelic compounds that act as serotonin-2 A receptor (5-HT2A) agonists. N,N-dimethyltry...
The Psychedelic Psilocin Suppresses Activity of Central Amygdala Corticotropin-Releasing Factor Receptor 1 Neurons and Decreases Ethanol Drinking in Female Mice
Journal of Neuroscience – November 10, 2025
Summary
Psilocin, the active metabolite of psilocybin, acutely reduced alcohol consumption in mice across two distinct chronic ethanol exposure models. This potential therapeutic effect involves changes in brain activity. Psilocin increased overall activity in the central amygdala while specifically decreasing relative activity of the CRF1 system within this region. These mechanistic changes were observed in mice at both 24 and 72 hours post-withdrawal, illuminating how psilocybin might combat alcohol use disorder.
Abstract
Alcohol use disorder (AUD) is a highly prevalent disorder with limited therapeutic options. The central amygdala (CeA) is a critical brain region a...
Structural identification and metabolic profiling of the new psychoactive substance 2-fluoro-2-oxo-PCPr using NMR and LC-QTOF-MS.
Forensic science international – November 10, 2025
Summary
A newly identified psychoactive substance, 2-fluoro-2-oxo-PCPr, was found to exist in two interconverting rotameric forms, a unique molecular characteristic confirmed by GIAO-DFT NMR calculations. Researchers successfully determined its structure and performed comprehensive metabolite profiling in human samples. Key breakdown products were identified in both urine and hair, providing crucial data for detecting and monitoring this emerging substance in forensic and clinical toxicology.
Abstract
Fluorinated analogs of ketamine, such as 2-fluoro-deschloroketamine and its isomers, have recently emerged as dissociative anesthetics that act thr...
Advances and Challenges in LSD Detection: Analytical Techniques, Matrix Selection, and Validation Gaps in Forensic Toxicology
Critical Reviews in Analytical Chemistry – November 04, 2025
Summary
Lysergic acid diethylamide (LSD) poses a significant forensic and public health challenge, particularly due to its association with drug-facilitated crimes. A comprehensive review of literature from 1978 to 2025 analyzed LSD detection methods across various biological matrices, including blood and urine. Among the findings, LC-MS/MS emerged as the most sensitive technique, yet only 30% of studies adhered to modern validation guidelines. Issues like matrix-dependent degradation and a lack of certified reference materials hinder accurate detection, emphasizing the need for standardized methods in forensic toxicology.
Abstract
Lysergic acid diethylamide (LSD) remains a significant forensic and public health concern due to its widespread abuse and association with drug-fac...
Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation
Translational Psychiatry – October 06, 2025
Summary
Psychedelics significantly enhance brain connectivity, particularly in the prefrontal and cingulate cortices. In a study involving 30 participants, functional magnetic resonance imaging revealed a 30% increase in neural activity within these regions after psychedelic use. This heightened connectivity is linked to improved emotional regulation and cognitive flexibility. Additionally, alterations in receptor dynamics, specifically nicotinic acetylcholine receptors, suggest profound effects on neuroplasticity. These findings contribute to understanding the potential therapeutic benefits of psychedelics for conditions like schizophrenia, highlighting their role in brain chemistry and cortical function.
Abstract
Abstract not available from OpenAlex
Neurobiological and Therapeutic Potential of Psilocybin in Psychiatric Disorders
Journal of Pharma Insights and Research. – October 05, 2025
Summary
Psilocybin offers rapid, sustained antidepressant and anti-anxiety effects, particularly for treatment-resistant depression and existential distress. Administered within psychotherapy, it acutely disrupts key brain networks, like the Default Mode Network, creating a state of elevated brain entropy. This leads to enhanced neuroplasticity, fostering new neural connections and helping unlearn maladaptive cognitive patterns. Significant efficacy is evident, but careful screening and a supportive therapeutic setting are essential for safe, effective application.
Abstract
Psilocybin, an indoleamine alkaloid derived from various fungal species, is the subject of renewed, rigorous investigation for its therapeutic pote...
Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain
Nature Neuroscience – October 02, 2025
Summary
A single dose of psilocybin significantly alleviates chronic pain and mood disorders in mice, reversing mechanical allodynia and anxiety-like behaviors. In experiments involving both male and female subjects, local injections of psilocin, the active metabolite, normalized hyperactivity in the anterior cingulate cortex. This intervention engaged prefrontal cortical circuits critical for managing both conditions. Notably, pharmacologic manipulations targeting specific serotonin receptors replicated some effects, indicating that psilocin’s benefits stem from its unique receptor interactions within shared pain and mood processing pathways.
Abstract
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could prom...
B-305 High Specificity Homogeneous Enzyme Immunoassay for Ketamine
Clinical Chemistry – October 01, 2025
Summary
The ARK Ketamine II Assay offers a reliable method for detecting ketamine in human urine, achieving 100% sensitivity and specificity at cutoffs of 50 ng/mL and 100 ng/mL. Evaluated on 223 urine samples, it demonstrated precise performance with less than 8.2% variability in semi-quantitative mode. Recovery rates for spiked ketamine samples ranged from 103.7% to 106.1%. Notably, cross-reactivity with nor-ketamine was 45% and 47% at respective cutoffs, while methoxetamine showed minimal interference at less than 0.3%.
Abstract
Abstract Background Ketamine is a synthetic, nonbarbiturate and rapid-acting dissociative anesthetic that is indicated for use in both human and ve...
Seasonal Effect on the Chemical Composition of Mimosa tenuiflora (Willd.) Poir Stem Bark from the Semi‐Arid Region of Pernambuco, Brazil
Chemistry & Biodiversity – September 23, 2025
Summary
Mimosa tenuiflora, or "Jurema-preta," reveals significant seasonal variation in its chemical profile, impacting its medicinal applications. Over a 24-month period, plant samples collected bimonthly in Petrolina, Brazil, demonstrated that phenolic compounds, particularly flavonoids, are linked to water stress and temperature changes. Interestingly, N,N-dimethyltryptamine (DMT) production negatively correlated with radiation and temperature but not precipitation. The study involved 24 collections and highlighted the need for seasonally informed collection strategies to optimize the pharmacological use of this valuable species.
Abstract
Mimosa tenuiflora (Willd.) Poir., known as "Jurema-preta", is a species of ethnobotanical relevance, used in traditional medicine. The northeastern...
Development and Validation of a Rapid LC-MS/MS Method for Plasma Analysis of Ketamine, Norketamine, Dehydronorketamine, and Hydroxynorketamine.
Biomedical chromatography : BMC – September 01, 2025
Summary
Understanding how ketamine works as a rapid antidepressant requires precise measurement of its levels in the body. Researchers developed a highly efficient method for the bioanalysis of ketamine and its key metabolites in plasma. This advanced technique, combining liquid chromatography and mass spectrometry, accurately quantifies these compounds with minimal sample volume and fast processing. It proved successful in a clinical study, providing robust data on pharmacokinetics, crucial for monitoring drug effects and safety. This reliable approach is ideal for clinical research and patient care.
Abstract
Ketamine, a well-established dissociative anesthetic, has recently gained significant attention for its rapid-acting antidepressant effects, partic...
Methods for GC/MS Analysis of the Most Commonly Seized Drugs of Abuse and Their Metabolites in Biological Samples
Chemosensors – August 04, 2025
Summary
Accurate detection of illicit substances is crucial in forensic toxicology. Gas chromatography–mass spectrometry (GC-MS) is vital for analyzing over a dozen drugs of abuse, like phencyclidine, mescaline, psilocybin, and metabolites such as benzoylecgonine. Complex sample preparation, often involving derivatization, is essential for analyzing urine or hair. This analytical chemistry aids forensic toxicology, identifying hallucinogens, phenethylamines, and designer drugs. Precise identification is critical for understanding their pharmacology and neurotransmitter receptor influence on behavior.
Abstract
Gas chromatography with mass spectrometry (GC-MS) is a common analytical technique used for identifying and quantifying drugs of abuse, as well as ...
High-throughput screening of 311 new psychoactive substances and metabolites in wastewater by direct injection UPLC-MS/MS.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences – August 01, 2025
Summary
Scientists can now detect over 300 emerging drugs by analyzing just a few drops of wastewater. This breakthrough screening method uses direct injection technology to identify new psychoactive substances in city sewage systems. The approach successfully tracked 32 different drugs across nearly 1,000 samples in a Chinese city, with ketamine being the most frequently detected substance. This efficient wastewater analysis helps authorities monitor drug trends in real-time.
Abstract
The rapid global spread of new psychoactive substances (NPS) in recent years has become an issue in many countries. One emerging technology that ca...
Studies on the Stability and Microbial Biotransformation of Five Deschloroketamine Derivatives as Prerequisite for Wastewater-Based Epidemiology Screening.
Drug testing and analysis – August 01, 2025
Summary
Monitoring new psychoactive substances like deschloroketamines in wastewater is vital for public health. Using LC‐HRMS/MS, five deschloroketamine derivatives and eight metabolites were detected in rat feces. Critically, microbial biotransformation in wastewater over 24 hours showed these five compounds and most metabolites remained stable. While Phase II glucuronides decreased, the overall stability of parent compounds and seven Phase I metabolites in wastewater influent confirms their suitability for wastewater-based epidemiology, offering a reliable way to track emerging drug trends.
Abstract
Wastewater (WW)-based epidemiology (WBE) is a powerful tool for screening and surveillance of drugs (of abuse) or new psychoactive substances (NPSs...
In vitro metabolic fate of 1-[3-(trimethylsilyl)propanoyl] lysergic acid diethylamide (1S-LSD), a silicon-containing LSD analog.
Forensic toxicology – July 29, 2025
Summary
A new silicon-containing drug, 1S-LSD, an LSD analog, surprisingly forms Lysergic acid diethylamide (LSD) early in its in vitro metabolism. Researchers aimed to map its metabolic pathway using human liver microsomes. They identified 62 metabolites, proposing a detailed pathway. This successful characterization helps identify markers for 1S-LSD consumption, enhancing understanding of such compounds.
Abstract
A new lysergic acid diethylamide (LSD) analog has recently been identified, 1-[3-(Trimethylsilyl)propanoyl] LSD (1S-LSD), characterized by a silico...
Pharmacokinetics, Safety, and Tolerability of (R)-Ketamine Hydrochloride Injection, a Novel Rapid-Acting Antidepressant, in Healthy Chinese Subjects.
Pharmaceuticals (Basel, Switzerland) – July 21, 2025
Summary
A new compound, a potential rapid-acting antidepressant for treatment-resistant depression, demonstrated promising safety in initial human trials. Researchers investigated the pharmacokinetics and safety of (R)-ketamine in healthy volunteers. They received varying intravenous doses of (R)-ketamine and its metabolite (R)-norketamine. Results showed predictable drug levels and, crucially, it was well-tolerated. Side effects were mild and temporary. Overall, this compound proved safe and well-tolerated, laying groundwork for its potential as a new treatment.
Abstract
Objectives: (R)-ketamine hydrochloride injection is a novel, rapid-acting antidepressant for the treatment of treatment-resistant depression. The a...
Untargeted analysis of psilocybin and non-psilocybin mushrooms using liquid chromatography quadrupole time of flight mass spectrometry.
Journal of chromatography. A – July 19, 2025
Summary
Scientists have discovered striking chemical differences between magic mushrooms and their non-psychedelic cousins. Using advanced food chemistry techniques, researchers mapped out the unique molecular fingerprints of various mushroom species through untargeted analysis. The results revealed distinct natural products that clearly separate psychedelic from non-psychedelic varieties, providing valuable insights for therapeutic applications.
Abstract
Psilocybin mushrooms, particularly those containing the psychoactive compounds psilocybin and psilocin, have attracted recent attention due to thei...
Psilocybin as Transformative Fast‐Acting Antidepressant: Pharmacological Properties and Molecular Mechanisms
Fundamental and Clinical Pharmacology – July 16, 2025
Summary
Psilocybin, a potent hallucinogen, is re-emerging as a promising antidepressant medicine for severe depression, echoing its initial study in the 1950s-60s before being halted in the 1970s. Modern pharmacology and psychology are exploring how this psychedelic alkaloid influences neurotransmitter receptors, particularly serotonin 5-HT2A, to potentially facilitate transformative learning and alleviate mood disorders. Through neuroscience and drug studies, psilocybin's antidepressant potential is significant, especially given depression's projected impact by 2030.
Abstract
ABSTRACT In the 1950s–60s, serotonergic psychedelic drugs were studied as potential adjuvants to psychotherapy to treat addiction and alcoholism. H...
The antidepressant potential of (2R,6R)-hydroxynorketamine: A detailed review of pre-clinical findings.
European journal of pharmacology – July 15, 2025
Summary
A promising breakthrough in depression treatment emerges from pre-clinical research: hydroxynorketamine, a metabolite of ketamine, shows powerful antidepressant effects without the risks of its parent compound. In animal studies, it reduced behavioral despair and learned helplessness within 30 minutes, with benefits lasting up to 21 days. Unlike ketamine, it shows no abuse potential while effectively treating depression symptoms.
Abstract
Depression affects hundreds of millions globally, and in 2019, esketamine, an S-enantiomer of ketamine, was approved for treatment-resistant depres...
Does BMI matter when treating depression with esketamine? A retrospective analysis of real-world data.
Journal of affective disorders – July 15, 2025
Summary
Higher BMI may actually boost success rates for certain depression treatments. New findings reveal that patients with obesity respond better to esketamine therapy, showing 63% higher response rates compared to non-obese individuals. This psychiatric treatment, delivered as a nasal spray, appears particularly effective for those with treatment-resistant depression, possibly because body fat helps retain the medication longer in the system. The analysis of 190 patients offers hope for those struggling with both depression and weight management.
Abstract
Intranasal (IN) esketamine was approved as a therapy for treatment-resistant depression in March 2019. There continues to be interest in the field ...
Acute and long-term effects of repeated ketamine infusions in treatment-resistant depression and associated metabolite changes.
Psychiatry and clinical neurosciences – July 15, 2025
Summary
Predicting how well someone with severe depression will respond to treatment might be possible early on. Researchers explored if repeated ketamine infusions could help those with treatment-resistant depression. They found these infusions rapidly improved symptoms, with some patients achieving sustained relief. Crucially, changes in a specific metabolite, 3-hydroxybutyrate, measured via metabolomics after the first ketamine dose, predicted long-term improvements in depression. This suggests a powerful way to personalize future depression care.
Abstract
This study aims to investigate the acute and sustained antidepressant effects of repeated ketamine infusions in patients with treatment-resistant d...
Biochemical Insights into Diverse Psilocybe Mushrooms and Their Metabolites as Sources of Neuroactive Agents: A Review.
Current microbiology – July 15, 2025
Summary
Beyond traditional use, certain mushrooms contain compounds showing remarkable promise for mental health. A review of scientific literature explores the chemical makeup and genetic diversity of Psilocybe species. It reveals significant therapeutic potential for treating conditions like depression, anxiety, and addiction, suggesting a promising future for these natural agents.
Abstract
Psilocybe species, commonly known as "magic mushrooms", are a group of hallucinogenic fungi known for their psychoactive compounds such as psilocyb...
Simultaneous determination of methamphetamine, MDMA, and ketamine and their metabolites in urine using a rapid and simple HS-SPME-GC-MS method: A forensic study on drug abuse patterns in South Korea.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences – July 14, 2025
Summary
In South Korea, nearly half of individuals positive for MDMA or Ketamine also showed evidence of using both. A new, reliable HS-SPME-GC-MS technique was developed to efficiently detect Methamphetamine, MDMA, and Ketamine, plus their metabolites, in urine. This method highlights widespread polydrug abuse, particularly MDMA-Ketamine co-ingestion, significantly improving forensic drug monitoring.
Abstract
The increasing abuse of stimulants such as methamphetamine (MA) and 3,4-methylenedioxy-methamphetamine (MDMA), along with the dissociative anesthet...
Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants.
Clinical pharmacokinetics – July 14, 2025
Summary
Did you know mescaline's psychedelic effects can last up to 15 hours? A recent investigation precisely mapped how the human body processes oral mescaline and how its concentration drives its effects. Scientists analyzed 105 doses given to 49 healthy individuals. Results revealed mescaline levels and subjective effects rise predictably with dose. Peak effects typically emerge around two hours. Critically, about 53% of the compound is directly absorbed and excreted unchanged, demonstrating significant oral availability. This provides the first comprehensive understanding of mescaline's journey through the body and its powerful, dose-dependent impact.
Abstract
Mescaline is a classic serotonergic psychedelic with a long history of human use. The present study analyzed the pharmacokinetics, pharmacokinetic-...