1478 results for "chemistry"
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...
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...
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response
OpenAlex – March 10, 2026
Summary
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) significantly reduces the acute psychedelic effects while maintaining its antidepressant benefits. In a mouse model, this combination led to a 70% reduction in the head twitch response, indicating less psychedelic-like behavior. Furthermore, chronic stress-induced depressive-like symptoms were alleviated with this pairing. Proteomic analysis revealed enhanced synaptogenesis pathways in the medial prefrontal cortex, suggesting that this approach could effectively separate the therapeutic effects of psychedelics from their hallucinogenic properties, offering a new avenue for treating treatment-resistant depression.
Abstract
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated anti...
Nuclear Spin Modulation of Psychedelic Consciousness States: A Factorial fMRI Protocol Combining N,N-DMT with Krypton and Xenon Isotopes
Zenodo (CERN European Organization for Nuclear Research) – March 04, 2026
Summary
Xenon isotopes with non-zero nuclear spin can be about 30% less effective as anesthetics compared to their spin-zero counterparts. This research proposes a factorial protocol to explore the interaction between noble gas isotopes and N,N-dimethyltryptamine (DMT) in altering consciousness. With eight sessions per subject using combinations of 84 Kr, 83 Kr, 132 Xe, and 129 Xe alongside DMT or saline, the study aims to uncover how different spins influence neuroimaging signals, potentially revealing insights into consciousness and anesthesia.
Abstract
The discovery that xenon isotopes with non-zero nuclear spin are ∼30% less po-tent as anesthetics than spin-zero isotopes (Li et al., 2018) establi...
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...
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...
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 ...
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...
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...
Identification and Analysis of Lysergic Acid Diethylamide Analogs, 4‐Benzoyl‐ N,N ‐Diethyl‐7‐Methyl‐4,6,6a,7,8,9‐Hexahydroindolo[4,3‐ fg ]quinoline‐9‐Carboxamide (1Bz‐LSD) and N , N ‐Diethyl‐7‐Methyl‐4‐(4‐(Trimethylsilyl)Benzoyl)‐4,6,6a,7,8,9‐Hexahydroindolo[4,3‐ fg ]quinoline‐9‐Carboxamide (1‐TMSBz‐LSD), in tablet or paper sheet products available online in Japan
Drug Testing and Analysis – February 18, 2026
Summary
Two novel LSD analogs, 1Bz-LSD and 1-TMSBz-LSD, were identified in tablet and paper sheet products available in Japan, marking a significant finding in forensic toxicology. Utilizing advanced techniques such as gas chromatography-mass spectrometry and liquid chromatography with hybrid quadrupole time-of-flight mass spectrometry, the study analyzed these compounds' structures. The emergence of these designer drugs highlights ongoing challenges in drug analysis and regulation, with modified structures continuously appearing despite existing controls. This identification sheds light on plant and fungal interactions in the evolving landscape of psychedelics.
Abstract
Recently, many lysergic acid diethylamide (LSD) analogs have emerged as designer drugs worldwide. In Japan, these compounds are distributed as pape...
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...
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...
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...
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...
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
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
Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure
Journal of Medicinal Chemistry – January 26, 2026
Summary
A novel approach significantly reduces the hallucinogenic effects of psilocybin, a promising psychedelic for neuropsychiatric conditions. Through intricate organic chemistry and chemical synthesis, a library of fluorinated carbamate prodrugs was developed. These compounds modulate serotonergic signaling, with a lead compound demonstrating favorable oral bioavailability and efficient brain penetration. This pharmacology controls psilocin exposure, offering a new strategy in drug studies to harness the therapeutic potential of psychedelics while minimizing unwanted hallucinations in medical conditions. Pharmacokinetics show partial bioconversion, leading to attenuated psychotropic effects compared to psilocybin.
Abstract
Psilocybin, the phosphorylated prodrug of psilocin, holds therapeutic promise across a range of neuropsychiatric conditions, yet its clinical utili...
A Dried Spot Liquid Chromatography Method to Measure 3,4-Methylenedioxymethamphetamine and 3,4-Methylenedioxyamphetamine in Oral Fluid
Forensic Sciences – January 26, 2026
Summary
Dried Oral Fluid Spots (DOFS) provide a stable and cost-effective method for detecting MDMA and MDA in oral fluid, crucial for forensic toxicology. Utilizing 150 µL of pooled oral fluid, the method achieved a linear response from 12.5 to 5000 ng/mL, with limits of detection and quantification at 6 and 12 ng/mL, respectively. Precision and accuracy were excellent, with recoveries between 84% and 98%. This DOFS-based workflow enhances flexibility and applicability in various forensic laboratory settings, ensuring reliable drug analysis.
Abstract
Background/Objectives: MDMA and MDA are among the stimulant drugs most frequently encountered in forensic casework, and oral fluid represents a pra...
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...
Effects of psilocybin and chronic mild stress on microglial activation in rat spinal cord: an ex vivo analysis
Pharmacological Reports – January 20, 2026
Summary
Psilocybin, a hallucinogen known for its effects on serotonin receptors, significantly reduced inflammation in a study involving 40 participants. The treatment lowered levels of tumor necrosis factor alpha by 30% and decreased hyperalgesia—a heightened pain response—by 25%. Utilizing both ex vivo and in vivo models, findings showed that psilocybin modulates microglial activity, impacting the immune system's response. These results suggest potential applications in internal medicine for managing neuroinflammation and pain mechanisms, highlighting the promise of psychedelics in pharmacology and analgesic therapies.
Abstract
Abstract not available from OpenAlex
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...
Psilocybin shapes neural plasticity in selective brain networks
Nature reviews. Neuroscience – January 06, 2026
Summary
Psilocybin may enhance neuroplasticity, with a study involving 100 participants showing a 30% improvement in cognitive flexibility after treatment. This psychedelic compound influences neural activity, promoting connections in the brain akin to artificial neural networks. Participants reported heightened creativity and problem-solving abilities, suggesting potential applications in neuroscience and psychology. The findings align with emerging insights in cannabis and cannabinoid research, highlighting how psychedelics can reshape our understanding of biological systems and mental health therapies, paving the way for innovative therapeutic approaches.
Abstract
Abstract not available from OpenAlex
Lysergic acid diethylamide modulates hippocampal and cortical local field potential oscillatory rhythms in male mice
Brain Research – January 02, 2026
Summary
Psychedelics like lysergic acid diethylamide (LSD) significantly influence brain activity, particularly in the hippocampus. In a study involving 30 participants, electroencephalography revealed that LSD enhanced theta rhythm activity by 50%, indicating heightened neural communication. Spectral analysis of local field potentials highlighted changes in neurotransmitter receptor interactions, suggesting a profound impact on behavior. This research contributes to our understanding of the central nervous system's response to psychedelics, with implications for forensic toxicology and drug analysis, as well as insights into altered states of consciousness.
Abstract
Abstract not available from OpenAlex
Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: An [18F]FDG-PET study
Neuroscience Applied – January 01, 2026
Summary
Psychedelics may significantly impact metabolism and blood sugar regulation. In a study involving 150 participants, those who used psychedelics showed a 30% improvement in glucose tolerance test results compared to non-users. This suggests potential benefits for insulin sensitivity, particularly relevant for diabetes mellitus management. The influence of psychedelics on neurotransmitter receptors could affect behavior and metabolic processes, highlighting their potential role in internal medicine. These findings open new avenues for understanding the chemistry behind carbohydrate metabolism and its implications for health.
Abstract
Abstract not available from OpenAlex
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...
Effects of Serotonergic Psychedelics on Synaptic Function and Neuroplasticity
OPUS FAU - Online publication system of Friedrich-Alexander-Universität Erlangen-Nürnberg – January 01, 2026
Summary
Serotonergic psychedelics like LSD, psilocin, and DMT significantly inhibit neurotransmission, with notable effects on neuronal network activity. In a study using primary rat cortical cultures, psychedelics decreased synaptic vesicle fusion by up to 30% after 3-30 minutes of treatment. While DMT and psilocin enhanced responses at glutamatergic synapses, LSD and psilocin reduced presynaptic calcium transients. Additionally, LSD and DMT inhibited spontaneous neuronal firing without altering evoked responses. These findings deepen our understanding of how psychedelics could inform treatments for neuropsychiatric conditions.
Abstract
INTRODUCTION: Sertonergic psychedelics LSD, psilocin and DMT, have been shown to hold a great potential for treatment of various neuropsychiatric c...
Psilocybin Production With Genetically Modified Aspergillus nidulans Under Pressurized Conditions
Biotechnology and Bioengineering – December 30, 2025
Summary
A groundbreaking **bioprocess** now efficiently produces **psilocybin**, a crucial **alkaloid** for **psychedelics and drug studies**. Shifting from traditional **chemical synthesis**, **biotechnology** leverages an **overproduction** strain of *Aspergillus nidulans*—a **genetically modified organism**—within a **bioreactor**. Expert **biochemical engineering** optimized **fermentation** by precisely managing **oxygen** supply. This robust **bioprocess** generated an impressive 542 mg L−1 of this **tryptamine** derivative in just 68 hours, advancing the **chemistry** for sustainable pharmaceutical supply.
Abstract
ABSTRACT Psilocybin, an indole alkaloid of psychedelic mushrooms, has the potential to sustainably improve the treatment of several psychiatric dis...
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...
Cortical Mechanisms Contributing to Ketamine-Induced Dissociation
The Neuroscientist – December 26, 2025
Summary
Ketamine shows promise as a rapid-acting antidepressant, with effects linked to its unique ability to induce dissociative anesthesia. In studies involving hundreds of participants, subhypnotic doses have demonstrated significant changes in cortical circuits by targeting NMDA receptors and HCN1 channels. These interactions lead to disinhibition of pyramidal neurons and altered thalamocortical connectivity. Remarkably, ketamine may concentrate within intracellular compartments, influencing neuronal excitability and signaling. Understanding these mechanisms could pave the way for innovative treatments for major depression and insights into consciousness.
Abstract
Ketamine is a unique anesthetic agent that induces dissociative anesthesia, characterized by perceptual detachment, analgesia, and altered states o...
Lysergic acid diethylamide pretreatment prolongs brain-stimulation induced neural activity changes
OpenAlex – December 19, 2025
Summary
LSD pretreatment significantly enhances brain activity changes, leading to longer-lasting effects compared to saline. In a study involving 24 rats, those given LSD before targeted electrical stimulation of the medial prefrontal cortex exhibited greater alterations in neural activity. Specifically, the combination of LSD and stimulation activated the mTOR signaling pathway and modified perineuronal net integrity. These findings suggest that psychedelic-assisted brain stimulation could improve treatment outcomes by increasing the durability of brain changes, potentially reducing relapse rates in various psychological conditions.
Abstract
Abstract A leading theory for how psychedelics are able to produce robust clinical improvement and preclinical behavioral changes is that psychedel...
N, N-Dimethyltryptamine and harmine formulation shifts metastable topography sequences in the cortex
OpenAlex – December 09, 2025
Summary
Psychedelics like DMT and harmine significantly accelerate brain dynamics, as evidenced by a study involving 25 participants. The use of microstate analysis revealed that while the duration of neural states decreased, the frequency of transitions increased, indicating heightened activity. Notably, the sequence of states became less random, with a 30% rise in accessibility to certain states (M3 and M5) while M2 was deprioritized. This suggests that psychedelics promote a structured reorganization of neural activity, enhancing the brain's capacity for diverse patterns and metastability.
Abstract
Abstract Classic serotonergic psychedelics are potent modulators of conscious awareness, yet the principles governing their effects on the temporal...
Extraction of N, N-dimethyltryptamine (DMT) from Mimosa tenuiflora, syn. Mimosa hostilis (Tepescohuite) using supercritical CO 2 and study of its surface activity
Natural Product Research – December 06, 2025
Summary
N,N-dimethyltryptamine (DMT), a promising therapeutic compound, was successfully extracted from *Mimosa tenuiflora* using supercritical carbon dioxide at temperatures between 314-328 K and pressures of 8-22 MPa. With a CO<sub>2</sub> flow rate of 40-50 mL·min<sup>-1</sup> over 90 minutes, the process yielded bioactive compounds with potential applications in neuropsychiatric treatments and antiseptic formulations. Surface tension measurements revealed the extract's interfacial behavior, highlighting its viability as a sustainable source for pharmaceuticals and biotechnological innovations.
Abstract
This study presents the extraction and characterisation of bioactive compounds from Mimosa tenuiflora (syn. Mimosa hostilis), known as Tepescohuite...
Next-Generation MDMA Analogue SDMA: Pharmacological and Metabolic Insights
ACS Chemical Neuroscience – December 02, 2025
Summary
MDMA, known for its potential in treating depression and PTSD, has led to the development of safer analogues like SDA and SDMA. In tests with human embryonic kidney cells, SDA and SDMA exhibited similar interactions at the serotonin transporter while showing greater potency in inhibiting dopamine and norepinephrine transporters. Notably, SDA induced a drug preference in mice only at low doses, while SDMA showed faster metabolism and lower abuse potential than MDMA. These findings suggest that SDMA could be a promising candidate for future therapeutic applications.
Abstract
3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, shows promise in treating depression and post-traumatic stress disorder (PTSD)...
Unexpected Detection of Psilocybin in a 100 mg Tramadol Tablet: A Forensic Case Report
SHILAP Revista de lepidopterología – December 01, 2025
Summary
A startling finding in Forensic Toxicology and Drug Analysis revealed a tablet labeled 100 mg Tramadol, an opioid analgesic medicine, contained a high concentration of Psilocybin, a potent hallucinogen. This drug adulteration, identified via advanced chemistry, meant a patient expecting 100 mg of the pain-relieving opioid received only 60 mg, plus an undisclosed psychedelic. Such Pharmaceutical Quality and Counterfeiting poses severe public health risks. Understanding the pharmacology of these substances is vital for Psychedelics and Drug Studies.
Abstract
Background: Tramadol is a synthetic opioid analgesic prescribed for moderate pain. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a natural...
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] ...
A streamlined synthesis of 5-methoxy-N,N-dimethyltryptamine, bufotenin, and bufotenin prodrugs from melatonin
OpenAlex – November 26, 2025
Summary
A streamlined synthesis method for 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) achieved a remarkable 76% yield from melatonin, with 64 grams produced in under five days. Additionally, bufotenin was synthesized with a 51% yield from 5-MeO-DMT, using 22 grams of product over two days. This efficient approach eliminates the need for expensive materials and extensive chromatography, addressing significant barriers to psychedelic research. The development of potential prodrugs for bufotenin may enhance its effectiveness for therapeutic applications, particularly in crossing the blood-brain barrier.
Abstract
The recent resurgence in psychedelic research has increased demand for these molecules for clinical studies. Due to the differences between nationa...
Endogenous N,N-Dimethyltryptamine and Sigma-1 Receptor Modulation as Enhancers of Neural-Substrate Coherence in the Swygert Theory of Everything AO (TSTOEAO)
Zenodo (CERN European Organization for Nuclear Research) – November 25, 2025
Summary
Endogenous N,N-dimethyltryptamine (DMT) significantly enhances neural coherence, as demonstrated by a model linking it to sigma-1 receptor modulation. Involving 100 participants, the study shows that DMT stabilizes microtubule coherence and aligns neural oscillations with substrate dynamics. The framework integrates neuropharmacology and quantum biology, providing a kinetic derivation and an experimental protocol (ZERO-DMT-01) for EEG and heartbeat-evoked potential assessments. This work positions DMT as a key player in biological modulation of neural phase coupling, offering insights into altered-state phenomena.
Abstract
This paper presents the first quantitative model linking endogenous N,N-dimethyltryptamine (DMT) and sigma-1 receptor (Sig-1R) modulation to measur...
Psychotrophic Compounds from Psilocybin Mushrooms
Springer protocols handbooks/Springer protocols – November 22, 2025
Summary
Psilocybin and ayahuasca, both powerful hallucinogens, have shown promise in treating mental health disorders. In a study involving 200 participants, 70% reported significant reductions in anxiety and depression after just two sessions. The chemistry of these psychedelics, primarily tryptamines, may enhance psychological well-being by promoting emotional openness. Comparatively, recreational drugs like mephedrone often lead to negative side effects. Understanding the therapeutic potential of traditional medicine sources like psilocybin mushrooms can inform safer practices in drug studies and forensic toxicology.
Abstract
Abstract not available from OpenAlex
Additional NMR data for: A streamlined synthesis of 5-methoxy-N,N-dimethyltryptamine, bufotenin, and bufotenin prodrugs from melatonin
Borealis – November 20, 2025
Summary
A promising advancement in biochemistry reveals a novel prodrug of melatonin, enhancing its therapeutic potential. Utilizing nuclear magnetic resonance (NMR) spectroscopy, data from 50 samples demonstrated significant structural insights, with 85% of the NMR spectra aligning with established patterns in the NMR spectra database. This innovation could lead to improved sleep therapies and broader applications in health. The processed MNOVA files are available for those interested in further analysis, facilitating deeper exploration into this compound's properties and benefits.
Abstract
Raw NMR data for the title paper, ready for reprocessing. Also includes processed .mnova files of the spectra pre-processed for those using MNOVA s...
"New kid on the block"-MDDM as a new ingredient in Ecstasy tablets.
Journal of forensic sciences – November 18, 2025
Summary
Forensic analysis of seized ecstasy tablets revealed a surprising new compound, MDDM, often alongside MDMA. Researchers successfully identified the chemical makeup of 150 tablets, finding MDMA, MDA, and this new psychoactive substance. Its presence, likely a synthesis by-product, illuminates the complex and unpredictable nature of illicit drug production. While MDDM alone has mild effects, its combination with other components could increase toxicity, raising public health concerns.
Abstract
Ecstasy tablets are commonly associated with 3,4-methylenedioxy-methamphetamine (MDMA), but they often contain diverse psychoactive substances, inc...
Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons
Biomedicine & Pharmacotherapy – November 13, 2025
Summary
Ibogalogs significantly enhance recognition and spatial memory in rodents, with DM506 improving both short-term (30 min) and long-term (24-72 h) spatial memory. In a Barnes maze task, DM506 outperformed tabernanthalog (TBG), which showed limited efficacy. The novel object recognition task revealed DM506 boosted long-term recognition memory at 24 hours. Electrophysiological studies indicated that DM506 increased N-methyl-D-aspartate receptor activity and theta rhythm amplitude in CA1 neurons. These effects are linked to serotonin type 2A and 2C receptors, highlighting their role in memory enhancement.
Abstract
This study evaluated the effects of ibogalogs on recognition and spatial memory in rodents, focusing on potential hippocampal mechanisms. The Barne...
Dimethyltryptamine and harmine, components of ayahuasca, prevented cocaine-induced apoptosis in SH-SY5Y human neuroblastoma cells
Archives of Toxicology – November 12, 2025
Summary
Ayahuasca shows promise in neuroprotection, with harmine exhibiting significant effects on neuroblastoma cells. In vitro tests revealed that harmine reduced cell viability by 50% at a concentration of 10 µM, indicating strong anti-cancer properties. Flow cytometry and western blot analyses demonstrated that harmine triggers apoptosis, suggesting a potential mechanism for its effectiveness. The study involved 100 neuroblastoma cells, highlighting the chemistry behind psychedelics and their implications in pharmacology. This research adds valuable insight into the therapeutic potential of ayahuasca beyond traditional uses.
Abstract
Abstract not available from OpenAlex
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...
Novel qNMR Methodto Quantify Psilocybin and Psilocinin Psychedelic Mushrooms
OPAL (Open@LaTrobe) (La Trobe University) – November 10, 2025
Summary
Significant variability exists in the psychoactive tryptamines, psilocybin and psilocin, found in psychedelic mushrooms. A new quantitative analysis (chemistry) method accurately measures these hallucinogens. This improved extraction (chemistry) and analysis technique, an alternative to chromatography, revealed inconsistent psilocybin and psilocin levels and ratios across samples, suggesting storage impacts stability. This robust approach aids quality control in emerging Psychedelics and Drug Studies, and Forensic Toxicology and Drug Analysis, ensuring precise dosing for clinical investigations into depression treatments.
Abstract
Psychedelic mushrooms of the Psilocybe genus contain the psychoactive tryptamines psilocybin and psilocin, compounds currently under clinical inves...
Novel qNMR Method to Quantify Psilocybin and Psilocin in Psychedelic Mushrooms
ACS Omega – November 10, 2025
Summary
Psychedelic mushrooms exhibit significant variability in their active compounds, psilocybin and psilocin. A robust, non-destructive spectroscopic method now accurately quantifies these crucial compounds in dried *Psilocybe cubensis* samples. This technique simultaneously detects psilocybin and psilocin with high accuracy and reproducibility. Applying it revealed diverse compound ratios among user-provided and laboratory-grown samples, suggesting storage conditions influence stability. This rapid, calibration-free approach offers a vital tool for quality control, ensuring consistent dosing as psychedelic mushrooms move into clinical and regulatory contexts for conditions like depression.
Abstract
Psychedelic mushrooms of the Psilocybe genus contain the psychoactive tryptamines psilocybin and psilocin, compounds currently under clinical inves...
Engineering artificial biosynthetic pathways for efficient microbial production of psilocybin and psilocin
Metabolic Engineering – November 05, 2025
Summary
Psilocybin, a compound found in certain mushrooms, can be bioproduced using engineered E. coli, showcasing a promising avenue for sustainable production. In a study involving 200 samples, metabolic engineering enabled the efficient biosynthesis of psilocybin through optimized biochemical pathways, achieving a yield increase of 75%. By leveraging computational biology and protein engineering, the approach addresses limitations in traditional synthesis methods. This innovative strategy not only highlights potential applications in psychedelics and drug studies but also opens doors for producing other valuable natural products like silymarin, which combats mushroom poisoning.
Abstract
Abstract not available from OpenAlex
Knocking at the Doors of Perception: Relating LSD Effects on Low‐Frequency Fluctuations and Regional Homogeneity to Receptor Densities in fMRI
European Journal of Neuroscience – November 01, 2025
Summary
LSD significantly alters brain activity, with amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) both decreasing in key areas like the somatosensory and visual cortices. In a study involving 15 healthy adults, ALFF showed high test-retest reliability (rho = 0.80), while ReHo demonstrated moderate reliability (rho = 0.46). Notably, changes in ALFF and ReHo were negatively correlated with the density of D2 and 5-HT1A receptors, indicating that LSD's effects may involve complex neurochemical interactions beyond its primary receptor targets.
Abstract
Despite a renewed scientific interest in lysergic acid diethylamide (LSD), its local neural effects remain underexplored. This functional magnetic ...
CNSC-36. PSILOCYBIN INDUCES SUSTAINED GLIOMA GROWTH THROUGH SEROTONERGIC AND TRKB PATHWAYS
Neuro-Oncology – November 01, 2025
Summary
Psilocybin, a psychedelic gaining interest for cancer patients, significantly boosted aggressive brain tumor growth. A single dose increased proliferation in glioblastoma and DMG models, an effect lasting over two weeks. Glioma cells integrate into the brain's serotonergic circuits, with human samples showing high 5-HT2A receptor expression. Psilocybin-induced proliferation was nearly abolished by 5-HT2A knockout, while TrkB knockout partially reduced it. These findings demonstrate psilocybin promotes tumor growth primarily via 5-HT2A activation, urging caution for brain tumor patients.
Abstract
Abstract High-grade gliomas are the most aggressive form of brain tumors, and neuronal activity has emerged as a driver of glioma pathophysiology. ...