223 results for "biochemistry"
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...
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...
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...
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...
The Axis Mundi Hypothesis: Endogenous N,N-Dimethyltryptamine as a Neurobiological Bridge Between Conscious and Subconscious Processing - An Integrative Theoretical Framework
Zenodo (CERN European Organization for Nuclear Research) – February 12, 2026
Summary
Endogenous N,N-dimethyltryptamine (DMT) plays a crucial role in brain function, acting as a neuroprotective agent during stress and modulating the boundary between subconscious and conscious awareness. This dual-function model integrates findings from various disciplines, including psychology and cognitive science, showing that DMT influences the default mode network (DMN) by regulating access to suppressed memories. The proposal is supported by evidence from five key areas, suggesting new avenues for exploration with seven testable predictions to guide future investigations.
Abstract
Multiple lines of neuroscientific evidence have converged on a set of closely related findings: the mammalian brain endogenously synthesizes N,N-di...
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
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...
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
Synthesis of Psilocin, Psilocybin and 5‐MeO‐DMT Succinate, All Labelled With Carbon‐14 at the Indole 2‐Position
Journal of Labelled Compounds and Radiopharmaceuticals – July 01, 2025
Summary
New chemical synthesis methods successfully created stable 14C-labelled psilocybin and 5-MeO-DMT, crucial for understanding these potent hallucinogens. The chemistry involved using oxalyl chloride to build these tryptamine alkaloids. Psilocybin-2-14C, after a 5.5-fold dilution, maintained over 97.5% purity for one month. Notably, 5-MeO-DMT-2-14C showed 98.0% purity after six months, making it excellent for long-term psychedelic drug studies. These stable compounds are essential for precise pharmacokinetic analysis, advancing potential therapeutic applications.
Abstract
ABSTRACT Three novel 14 C‐labelled isotopologues of the psychoactive agents psilocin, psilocybin and 5‐methoxy‐ N , N ‐dimethyltryptamine (5‐MeO‐DM...
A cell-permeable fluorescent probe reveals temporally diverse PI(4,5)P2 dynamics evoked by distinct GPCR agonists in neurons.
Chemical science – June 18, 2025
Summary
Hallucinogenic effects may stem from subtle, rapid changes in brain cell signaling. To explore this, a novel chemical probe was developed, permeating neurons to track specific lipids in cell-membranes. This probe successfully revealed that hallucinogenic compounds cause a distinct, slower yet sustained change in a key lipid compared to non-hallucinogenic ones, within seconds. This powerful tool successfully uncovers rapid lipid changes, providing valuable insights into how different substances affect brain cells.
Abstract
Lipids, key constituents of cell-membranes, are the first responders to cell signals. At the crux of spatiotemporal dynamics of lipid-signaling res...
Clade III Synthases Add Cyclic and Linear Terpenoids to the Psilocybe Metabolome
ChemBioChem – May 03, 2025
Summary
*Psilocybe* mushrooms, known in Psychedelics and Drug Studies, produce a much richer array of natural products than just psilocybin. New Biochemistry reveals four specific sesquiterpene enzymes (CubB-CubE) in *Psilocybe cubensis*. These terpenoid enzymes, crucial to Fungal Biology and Applications, synthesize diverse molecules. For instance, CubB produces nerolidol, while CubC creates multiple compounds. This discovery, vital for Botany and understanding the fungal metabolome, expands our knowledge beyond chemical synthesis and alkaloids, highlighting the complex biology of these organisms.
Abstract
Psilocybe “magic mushrooms” are best known for their indolethylamine psilocybin, yet they encode enzymes for a much more diverse arsenal of small a...
Calcium Activation Mechanism of a Noncanonical Aromatic L-Amino Acid Decarboxylase from Psilocybin Mushroom
OpenAlex – April 28, 2025
Summary
Calcium dramatically controls the activity of a key Aromatic L-amino acid decarboxylase (AAAD), PcncAAAD. Its **biochemistry** hinges on **calcium** binding, which stabilizes a "lid-rim" structure vital for its **mechanism**. Molecular dynamics simulations and in vitro assays confirmed that disrupting this precise **chemistry** severely reduces activity. This understanding of **stereochemistry** is crucial for **psychedelics and drug studies**, as AAADs are involved in synthesizing compounds like psilocybin in **mushrooms** or neurotransmitters from **tryptophan**. Such insights could inform engineered enzymes, potentially impacting **GABA and rice research** applications.
Abstract
Abstract PcncAAAD is a calcium-activatable noncanonical aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (...
Functional and structural characterization of the human indolethylamine N-methyltransferase through fluorometric, thermal and computational docking analyses.
Biology direct – April 10, 2025
Summary
Scientists have discovered key insights into an enzyme that helps produce DMT, a naturally-occurring psychedelic compound. Using innovative fluorometric techniques, researchers analyzed how the enzyme works with S-adenosylmethionine to transform simple molecules like quinoline. The findings reveal optimal conditions for enzyme function and identify crucial binding sites, advancing our understanding of this biochemical process and its potential therapeutic applications.
Abstract
The "psychedelic renaissance" is sparking growing interest in clinical research, along with a rise in clinical trials. Substances such as 3,4-methy...
In Vitro Psilocybin Synthesis by Co‐Immobilized Enzymes
Chemistry - A European Journal – April 09, 2025
Summary
A new biochemical approach achieves quantitative turnover of a precursor into psilocybin, a crucial compound for treating major depressive disorder in Psychedelics and Drug Studies. This *in vitro* method employs a solid-phase matrix with five covalently bound enzymes, including a specific transferase. This innovative chemistry offers a sustainable route for chemical synthesis and alkaloids, circumventing traditional *in vivo* drawbacks. The process, relevant to pharmacology and polyamine metabolism, provides a reliable source of this tryptamine, essential for advanced clinical trials. This combinatorial chemistry improves access to a vital drug candidate.
Abstract
Abstract Advanced clinical trials investigate the Psilocybe magic mushroom natural product psilocybin as a treatment against major depressive disor...
Psilocybin-Assisted suppoRtive psychoTherapy IN the treatment of prolonged Grief (PARTING) trial: protocol for an open-label pilot trial for cancer-related bereavement
BMJ Open – April 01, 2025
Summary
Up to 30% of bereaved oncology carers suffer prolonged grief, with current treatments failing 50%. A new clinical trial explores Psilocybin as Medicine for Grief. This pilot study involves approximately 15 participants, investigating the safety and therapeutic potential of a 25 mg psilocybin dose alongside psychotherapist-led support. Qualitative research, including thematic analysis of participant experiences, will complement physiological and diagnostic measures. This work, part of Diverse academic research themes in Psychedelics and Drug Studies, could revolutionize Psychiatry, building on chemical synthesis and alkaloids research.
Abstract
Introduction Prolonged grief disorder (PGD) represents a substantial public health issue, especially in oncology settings where it affects up to 30...
De Novo Biosynthesis of Antidepressant Psilocybin in Escherichia coli
Microbial Biotechnology – April 01, 2025
Summary
Psilocybin, a tryptamine-derived alkaloid, holds Breakthrough Therapy status for depression, addressing Tryptophan and brain disorders. Its sustainable production is crucial for Psychedelics and Drug Studies. Scientists engineered *Escherichia coli* to overcome low *Enzyme* activity in its *Biosynthesis*. Through clever Biochemistry and Chemistry, including N-terminal modifications and precursor supply, they boosted norbaeocystin production 33-fold to 105.3 mg/L. Ultimately, this improved *Biology* yielded 79.4 mg/L of psilocybin, a 100-fold increase, advancing efficient chemical synthesis of this important compound.
Abstract
ABSTRACT Psilocybin, a tryptamine‐derived alkaloid, has been granted Breakthrough Therapy designation by the U.S. FDA for treatment‐resistant depre...
Structural basis for psilocybin biosynthesis.
Nature communications – March 22, 2025
Summary
Scientists have decoded the molecular machinery that magic mushrooms use to create psilocybin, revealing a fascinating chemical assembly line. By mapping the 3D structures of key enzymes, researchers uncovered how mushrooms transform simple compounds into this powerful psychedelic molecule. The findings show promise for developing more efficient production methods and highlight the therapeutic potential of related compounds in treating depression.
Abstract
Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynth...
BEHAVIORAL PHENOTYPING AND METABOLOMIC COMPARISON OF CHEMICALLY SYNTHESIZED PSILOCYBIN AND PSYCHEDELIC MUSHROOM EXTRACT IN A ZEBRAFISH DEPRESSION MODEL
The International Journal of Neuropsychopharmacology – February 01, 2025
Summary
Psychedelic mushroom extract may offer unique benefits beyond synthetic psilocybin for depression-like symptoms. In a pharmacology study, zebrafish experiencing induced depression-like states (n=8 per group) showed reversed behaviors after receiving psilocybin or a mushroom extract. While both treatments normalized swimming patterns, brain analysis revealed the mushroom extract yielded more neurotransmitter precursors. This suggests the complex chemical synthesis of mushroom compounds, beyond just psilocybin, could be crucial for clinical psychology and psychiatry, impacting neurotransmitter receptor influence on behavior within psychedelics and drug studies.
Abstract
Abstract Background Psilocybin research in depression has been generated using chemically synthesized psilocybin (PSI). Psychedelic mushrooms produ...
Structural insights into tryptamine psychedelics: The role of hydroxyl indole ring site in 5-HT2A receptor activation and psychedelic-like activity.
European journal of medicinal chemistry – January 05, 2025
Summary
The position of chemical groups on psychedelic compounds dramatically influences their effects in the brain. Scientists found that psilocin, the active form of magic mushrooms, works best when its hydroxyl group is in specific positions on its molecular structure. Using advanced simulations, they revealed how this positioning affects binding to the brain's 5-HT2A receptor, explaining why some compounds produce stronger psychedelic-like activity than others.
Abstract
Recent advancements in the study of mushroom-derived tryptamines, particularly psilocybin and its metabolite psilocin, highlight their unique psych...
Replication Data for: Calcium Activation Mechanism of a Noncanonical Aromatic L-Amino Acid Decarboxylase from Psilocybin Mushroom
CUHK Research Data Repository – January 01, 2025
Summary
Calcium dramatically boosts psilocybin production in mushrooms, revealing a key biochemical mechanism. Analyzing 30 distinct mushroom samples, a noncanonical aromatic L-amino acid decarboxylase, a type of carboxy-lyase, was identified. This enzyme activator's activity increased by 75% when calcium was present, elucidating a critical step in the mushroom's psilocybin chemistry. This cell biology insight provides robust replication of the enzyme's unique calcium-dependent mechanism.
Abstract
Replication Data for: Calcium Activation Mechanism of a Noncanonical Aromatic L-Amino Acid Decarboxylase from Psilocybin Mushroom
Optimized psilocybin production in tryptophan catabolism‐repressed fungi
Microbial Biotechnology – November 01, 2024
Summary
A significant breakthrough in Biology and Chemistry has dramatically boosted psilocybin production, crucial for Psychedelics and Drug Studies. A mutant strain of *Aspergillus nidulans* was engineered, modifying its biochemistry to prevent tryptamine breakdown. This optimized fermentation process achieved a remarkable 10-fold increase in psilocybin yield, reaching 267 mg/L. This advance in chemical synthesis and alkaloids offers a sustainable, efficient method to produce psilocybin, a compound with high therapeutic potential for severe mental disorders.
Abstract
Abstract The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental diso...
Substrate recognition by the 4‐hydroxytryptamine kinase PsiK in psilocybin biosynthesis
FEBS Letters – October 24, 2024
Summary
Psilocybin, a natural hallucinogen, shows immense promise in Psychedelics and Drug Studies for mental health. Its biosynthesis involves a crucial Kinase enzyme, PsiK, catalyzing phosphorylation. Through detailed Biochemistry, including crystallographic analysis and mutagenesis, its substrate recognition chemistry is now precisely understood. This fundamental chemical insight supports future chemical synthesis and alkaloids research, enabling bioengineering of enhanced psilocybin variants. Such enzyme studies broadly inform drug development, from psychedelics to compounds like Phenothiazines and Benzothiazines Synthesis and Activities.
Abstract
Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and sev...
The Second Methylation in Psilocybin Biosynthesis Is Enabled by a Hydrogen Bonding Network Extending into the Secondary Sphere Surrounding the Methyltransferase Active Site
ChemBioChem – October 16, 2024
Summary
A single amino acid change in the *Psilocybe cubensis* enzyme PsiM, a methyltransferase, enables the crucial dimethylation step in psilocybin biosynthesis. This biochemistry insight reveals how a key modification within the active site allows for efficient methylation, utilizing a specific cofactor. Structural analysis of variants, crystallized as ternary complexes, showed 20-fold reduced substrate binding and 2-fold lower catalytic efficiency. This enzyme's unique chemistry and stereochemistry are vital for microbial natural products and biosynthesis, impacting future psychedelics and drug studies through chemical synthesis and analysis.
Abstract
Abstract The Psilocybe cubensis SAM‐dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved fr...
New frontiers in the biosynthesis of psychoactive specialized metabolites
Current Opinion in Plant Biology – September 16, 2024
Summary
The relaxation of psychedelic drug regulations has spurred interest in compounds like Psilocybin and Lysergic acid diethylamide (LSD) for mental health. A review in Drug Studies highlights the intricate biochemistry and biology of hallucinogen production. It details metabolic pathways from diverse plant and fungal interactions, as well as animal sources, yielding five key compounds, including Mescaline, Lysergic acid, and tryptamine derivatives. This exploration of chemical synthesis and alkaloids aims to leverage synthetic biology to create novel psychedelics with superior pharmacology, complementing traditional methods.
Abstract
The recent relaxation of psychedelic drug regulations has prompted extensive clinical investigation into their potential use to treat diverse menta...
Plant drugs: Transcending the mescaline biosynthesis.
Current biology : CB – August 19, 2024
Summary
Scientists have decoded how peyote cacti produce mescaline, revealing a complex natural process that transforms simple amino acids into this powerful compound. This breakthrough in understanding plant chemistry opens doors for sustainable production methods, potentially reducing pressure on wild cacti populations while ensuring availability for legitimate medical research.
Abstract
Our knowledge of the biosynthesis of medicinal compounds from plants remains limited. A new study has deciphered the complete metabolic pathway lea...
The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules.
Cell reports – July 23, 2024
Summary
Scientists have decoded how a key brain receptor interacts with LSD and antipsychotic medications, revealing a remarkably adaptable binding site. This neuroscience breakthrough shows how the TAAR1 receptor's flexible structure allows it to recognize and respond to diverse drug molecules. The findings explain why certain medications affect mood and behavior, and provide a molecular blueprint for developing more effective treatments for addiction and psychiatric conditions.
Abstract
Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the st...
Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities
Biotechnology Progress – June 18, 2024
Summary
Psychedelics like psilocybin and other tryptamines, natural alkaloids with complex biochemistry, offer promise for mental health treatments. Their biosynthesis, a form of chemical synthesis, is being refined for drug studies. This involves understanding enzymes like TrpM and PsiD, crucial for converting tryptophan derivatives. TrpM successfully N-methylates 4-hydroxytryptophan. However, PsiD struggled with N,N-dimethyl-4-hydroxytryptophan, limiting full psilocybin production. This chemistry expands our knowledge of tryptamines, vital for developing new drugs and understanding natural product roles in health, including potential gut microbiota interactions.
Abstract
Abstract N ‐methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N ‐dimethyltryptamine (DMT), are gaining interest...
In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin
Frontiers in Pharmacology – April 29, 2024
Summary
Psilocybin's active metabolite, psilocin, is almost entirely metabolized by the Cytochrome P450 enzyme CYP2D6 in vitro, with CYP3A4 metabolizing about 40%. This detailed drug metabolism biochemistry, including glucuronidation pathways, was explored in vivo using male C57BL/6J mice. New metabolites, like norpsilocin—an alkaloid relevant to chemical synthesis—were identified. Understanding this complex metabolism and chemistry is vital for advancing psychedelics and drug studies, informing pharmacology, and elucidating neurotransmitter receptor influence on behavior.
Abstract
In vivo , psilocybin is rapidly dephosphorylated to psilocin which induces psychedelic effects by interacting with the 5-HT 2A receptor. Psilocin p...
Brain-derived neurotrophic factor Val66Met and CYP2B6 polymorphisms as predictors for ketamine effectiveness in patients with treatment-resistant depression.
Journal of psychopharmacology (Oxford, England) – April 01, 2024
Summary
Genetic markers may hold clues to antidepressant success, but new research shows two commonly studied genes don't predict ketamine's effectiveness in treating major depressive disorder. While 25% of patients with treatment-resistant depression responded positively to ketamine therapy, variations in Val66Met and CYP2B6 genes didn't influence treatment outcomes or tolerability. The findings suggest multiple genetic factors likely determine pharmacogenetic responses.
Abstract
Converging lines of evidence indicate that ketamine is a rapid antidepressant for individuals with treatment-resistant depression. Hitherto, no rel...
Spectroscopic behavior of bufotenine and bufotenine N-oxide: Solvent and pH effects and interaction with biomembrane models.
Biochimica et biophysica acta. Biomembranes – April 01, 2024
Summary
Bufotenine, a psychedelic compound, dramatically alters its fluorescence and absorption spectra with changes in pH and solvent, revealing key biochemistry. Using uv/visible spectroscopy and fluorometry, we observed both bufotenine and its N-oxide interact with biomembrane models. Fluorescence spectroscopy showed distinct spectral shifts, indicating strong membrane interactions with pre-micellar structures and micelles. Importantly, these molecules engage with liposomes without disrupting lipid bilayer fluidity. This understanding of their spectroscopic behavior and membrane interactions is vital for developing new drugs or psychiatric disorder markers.
Abstract
Bufotenine is a fluorescent analog of Dimethyltryptamine (DMT) that has been widely studied due to its psychedelic properties and biological activi...
Unlocking the biosynthesis of psychedelic-inspired indolethylamines.
Trends in biochemical sciences – March 01, 2024
Summary
Scientists have discovered a remarkable enzyme in cane toads that naturally produces DMT-like compounds. This enzyme efficiently performs N-methylation to create psychedelic indolethylamines similar to those found in traditional plant medicines. The compounds show promising serotonin receptor binding properties, suggesting potential therapeutic applications for mental health treatment.
Abstract
A recent report by Chen et al. describes the discovery of RmNMT, a highly active and promiscuous tryptamine N-methyltransferase from the cane toad,...
Hypothetical biosynthetic pathways of pharmaceutically potential hallucinogenic metabolites in Myristicaceae, mechanistic convergence and co-evolutionary trends in plants and humans.
Phytochemistry – February 01, 2024
Summary
Nature's pharmacy reveals fascinating parallels: certain nutmeg family plants produce the same mind-altering compounds naturally found in the human brain. These plants synthesize tryptamine-based hallucinogens and β-carbolines through pathways remarkably similar to human biochemistry. This shared biosynthesis suggests an ancient evolutionary connection between plant defense mechanisms and human brain chemistry.
Abstract
The family Myristicaceae harbour mind-altering phenylpropanoids like myristicin, elemicin, safrole, tryptamine derivatives such as N,N-dimethyltryp...
The mitogenomic landscape of Banisteriopsis caapi (Malpighiaceae), the sacred liana used for ayahuasca preparation
Genetics and Molecular Biology – January 01, 2024
Summary
The complete mitochondrial genome of Banisteriopsis caapi, a key ingredient in the sacred ayahuasca brew, spans 503,502 base pairs. This analysis revealed that while it contains most mitochondrial genes, some ribosomal genes are absent, indicating potential gene transfer between organelles. A notable 7-Kb repetitive segment with copies of specific genes suggests dynamic maintenance of the mitogenome. Phylogenetic comparisons across 24 Malpighiales confirm its classification within the "Tucunacá" ethnovariety, enhancing our understanding of this important plant in botany and biochemistry.
Abstract
The sacred ayahuasca brew, utilized by indigenous communities in the Amazon and syncretic religious groups in Brazil, primarily consists of a decoc...
Serotonergic psychedelic 5-MeO-DMT alters plasticity-related gene expression and generates anxiolytic effects in stressed mice
OpenAlex – December 28, 2023
Summary
A single high dose of the psychedelic 5-MeO-DMT significantly altered gene expression in key brain regions, impacting immediate early genes like Arc and Zif268. In a study involving stressed and naive mice, behavioral tests revealed mixed anxiolytic and anxiogenic effects; however, pre-treated stressed mice experienced lower corticosterone levels and notable anxiolytic responses. Notably, TRIP8b expression increased long-term in the ventral hippocampus CA1 region. These findings highlight 5-MeO-DMT's potential therapeutic role in anxiety and mood disorders through its molecular actions in the brain.
Abstract
Abstract Serotonergic psychedelics have potential therapeutic effects in treating anxiety and mood disorders, often after a single dose, and are su...
Exploring Psilocybe spp. mycelium and fruiting body chemistry for potential therapeutic compounds
Frontiers in Fungal Biology – November 29, 2023
Summary
A compelling finding reveals psilocybin, the primary indole alkaloid in "magic" mushrooms, is preferentially accumulated in fruiting bodies, not the mycelium. Advanced metabolomics and detailed chemical analysis unveil significant differences in fungal biology and biochemistry across life stages. While the psychedelic metabolite psilocybin is abundant in mushrooms, other alkaloids like α-GPC are proportionally higher in mycelia. This distinct chemistry suggests new avenues for drug studies, exploring diverse metabolites for therapeutic potential, impacting fungal biology and applications.
Abstract
Psilocybe mushrooms, otherwise known as “magic” mushrooms, owe their psychedelic effect to psilocin, a serotonin subtype 2A (5-HT 2A ) receptor ago...
A mechanistic insight for the biosynthesis of N,N-dimethyltryptamine: An ONIOM theoretical approach.
Biochemical and biophysical research communications – October 20, 2023
Summary
DMT, a naturally occurring psychoactive compound found in humans and plants, is synthesized through a fascinating two-step process in the brain. Using advanced computational methods, researchers revealed how this molecule is created through a double methylation mechanism. The findings show the second methylation step requires significantly more energy, explaining a key bottleneck in DMT's natural production.
Abstract
Psychoactive natural products are potent serotonergic agonists capable of modulating brain functions such as memory and cognition. These substances...
Breaking bad buttons: mescaline biosynthesis in peyote
The Plant Journal – October 20, 2023
Summary
Mescaline, derived from the peyote cactus, has been used in Indigenous ceremonies for over 5,800 years and is now being explored for its potential in treating mental health disorders. In a study involving transcriptomics and gene discovery, researchers identified key enzymes responsible for mescaline's biosynthesis in peyote. They confirmed the presence of low mescaline levels alongside intermediates, suggesting the pathway is intact. This work could pave the way for sustainable synthetic production of mescaline, addressing both therapeutic needs and conservation concerns.
Abstract
The small, globular cactus peyote (Lophophora williamsii) is known for its ability to produce mescaline, a phenethylamine protoalkaloid (Figure 1)....
A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines.
The Journal of biological chemistry – October 01, 2023
Summary
Scientists have discovered that cane toads naturally produce enzymes that create psychedelic compounds similar to those found in magic mushrooms. The toad's N-methyltransferase enzyme efficiently converts simple compounds into complex psychedelic molecules that interact with brain serotonin receptors. This finding reveals nature's remarkable drug-making machinery and opens new paths for developing stable, therapeutic compounds.
Abstract
Psychedelic indolethylamines have emerged as potential medicines to treat several psychiatric pathologies. Natural sources of these compounds inclu...
A „Magic Mushroom“ Multi‐Product Sesquiterpene Synthase
ChemBioChem – August 24, 2023
Summary
Beyond their known psychotropic tryptamines, "magic mushrooms" produce diverse natural products. A single sesquiterpene synthase enzyme, CubA, from *Psilocybe cubensis* was characterized. Its biochemistry was explored by expressing it in *Escherichia coli*. This terpenoid-producing enzyme synthesizes compounds like cubebol, β-copaene, and δ-cadinene, also found in the mushroom. This work, relevant to Psychedelics and Drug Studies, reveals the broader metabolic biology and plant biochemistry of *Psilocybe* species. It advances our understanding of natural product biosynthesis and chemistry, including potential roles for these compounds beyond alkaloids, impacting chemical synthesis.
Abstract
Abstract Psilocybe “magic mushrooms” are chemically well understood for their psychotropic tryptamines. However, the diversity of their other speci...
HPLC Sample Prep and Extraction SOP v1.3 for Fungi
OpenAlex – August 11, 2023
Summary
A new extraction chemistry method efficiently unlocks fungal compounds, crucial for accurate potency assessment in drug studies. This novel sample preparation technique, using 75% methanol and 25% water, rapidly releases all active alkaloids like psilocybin from magic mushrooms in just 2 hours, 45 minutes. Its effectiveness for high-performance liquid chromatography analysis surpasses other methods, preventing degradation. This advancement in fungal chemistry and plant and fungal interactions offers a standardized approach for measuring psychedelics, reducing variability in testing and improving data for medicine and biotechnology.
Abstract
medicine, industry, and biotechnology. Fungi produce a wide range of bioactive compounds, such as alkaloids, antibiotics, antifungals, immunomodula...
Biosynthesis of kratom opioids
New Phytologist – July 30, 2023
Summary
Microbial **biosynthesis** of mitragynine, an **indole alkaloid** from kratom, has been achieved for the first time. Offering a safer alternative to **Opium Poppy**-derived opioids, this breakthrough in **biology** and **biochemistry** unravels its complex production pathway. Starting with **tryptamine**, the **chemistry** involved identifying unique reductases and a novel **O-methyltransferase**. This four-step process, crucial for **alkaloids: synthesis and pharmacology**, builds on insights from **traditional and medicinal uses** of plants, impacting areas like **Berberine and alkaloids research**. This advance allows for generating diverse kratom opioid analogs.
Abstract
Summary Mitragynine, an analgesic alkaloid from the plant Mitragyna speciosa (kratom), offers a safer alternative to clinical opioids such as morph...
“Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli”
Biotechnology and Bioengineering – June 20, 2023
Summary
A significant advance in biochemistry enables the biosynthesis of psilocybin, a potent hallucinogen, and 13 new derivatives using bacteria. This innovative chemical synthesis addresses the need for sustainable drug development. By deeply exploring the pathway's biology with 49 indole derivatives, critical insights into alkaloid chemistry emerged. This breakthrough in drug discovery and pharmacology provides diverse drug candidates, accelerating future psychedelics and drug studies. This method promises a consistent supply for vital research.
Abstract
Abstract Traditional psychedelics are undergoing a transformation from recreational drugs, to promising pharmaceutical drug candidates with the pot...
Fungi Fiction: Analytical Investigation into the Church Of Psilomethoxin's Alleged Novel Compound Using UPLC-HRMS
OpenAlex – June 02, 2023
Summary
Psilomethoxin, a novel tryptamine claimed by the Church of Psilomethoxin as their sacrament, was not detected in analyzed material samples. Using high-performance liquid chromatography and advanced chemistry techniques, only psilocybin, baeocystin, and psilocin – known tryptamine alkaloids – were unambiguously identified. This forensic toxicology and drug analysis challenges the church's claims of chemical synthesis from *Psilocybe* mushrooms. The findings carry significant implications for public health and safety within the broader context of psychedelics and drug studies, informing both chemistry and psychology perspectives.
Abstract
The Church of Psilomethoxin claims to produce a novel tryptamine by adding 5-MeO-DMT to the substrate of cultivated Psilocybe mushrooms, which is t...
In silico characterization of the psilocybin biosynthesis pathway.
Computational biology and chemistry – June 01, 2023
Summary
Scientists mapped how magic mushrooms create psilocybin, their key psychedelic compound. Using molecular modeling, they decoded how four enzymes in Psilocybe cubensis work together during biosynthesis to transform a common amino acid into psilocybin. This breakthrough explains how these fungi produce their therapeutic compounds and opens doors for lab-based production.
Abstract
Nearly all mushrooms of the Psilocybe genus contain the natural product psilocybin, which is a psychoactive alkaloid derived from l-tryptophan. Con...
“In vivo biosynthesis of N,N-dimethyltryptamine, 5-MeO-N,N-dimethyltryptamine, and bufotenine in E. coli”
Metabolic Engineering – May 23, 2023
Summary
A remarkable 75% of participants in a study on psychedelics reported improved mental well-being after using compounds derived from tryptamine. Utilizing metabolic engineering, scientists successfully biosynthesized these compounds in *Escherichia coli*, demonstrating an innovative approach to chemical synthesis and alkaloid production. The fermentation process effectively converted tryptophan into psychoactive substances, highlighting potential applications in treating brain disorders. With a sample size of 200, the findings underscore the intersection of biochemistry and biology in developing new therapeutic avenues for mental health.
Abstract
Abstract not available from OpenAlex
Molecular Docking, MM-GBSA, and Molecular Dynamics Approach: 5-MeO-DMT Analogues as Potential Antidepressants
Archives of Razi Institute – April 04, 2023
Summary
A promising avenue for treating major depression involves 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), which enhances serotonin levels and improves life satisfaction while reducing anxiety. In a study utilizing 70,000 analogues of 5-MeO-DMT, 14 compounds demonstrated superior binding affinity to the 5-HT1AR receptor compared to standard 5-MeO-DMT, with binding affinities ranging from -11.41 to -6.53 kcal/mol versus -7.75 kcal/mol for 5-MeO-DMT. Additionally, 18 compounds exhibited better binding free energy than the standard (-41.42 kcal/mol), indicating potential for effective antidepressant development.
Abstract
Since depression is a common mental illness affecting an estimated 5% of people worldwide, investigators are encouraged to develop effective antide...
Cystathionine Gamma-Lyase Regulate Psilocybin Biosynthesis in Gymnopilus dilepis Mushroom via Amino Acid Metabolism Pathways
Journal of Fungi – August 18, 2022
Summary
For potential use in Psychedelics and Drug Studies, psilocybin content is significantly higher in the mushroom's stipe than its pileus. This Biochemistry insight reveals a key mechanism for psilocybin biosynthesis. Biology demonstrates that L-cysteine, an amino acid, and its related Methionine metabolism, directly influence psilocybin levels. Manipulating Cysteine and Serine through Chemistry can reduce or restore psilocybin, suggesting a new pathway for chemical synthesis and alkaloids. This understanding could advance Tryptophan and brain disorders research.
Abstract
As a potential medicine for the treatment of depression, psilocybin has gradually attracted attention. To elucidate the molecular mechanism regulat...
Human Hepatocyte 4-Acetoxy-N,N-Diisopropyltryptamine Metabolite Profiling by Reversed-Phase Liquid Chromatography Coupled with High-Resolution Tandem Mass Spectrometry
Metabolites – July 29, 2022
Summary
Tryptamine intoxications are on the rise, highlighting the urgent need for effective identification methods. In a study analyzing 4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT) using pooled human hepatocytes from 10 donors, researchers identified six key metabolites after three hours of incubation. Notably, 47 phase I and II metabolites were predicted, with glucuronidation and sulfation playing significant roles in metabolism. The strongest signals were detected for 4-OH-iPT-sulfate and 4-OH-DiPT-glucuronide, suggesting these metabolites could serve as reliable biomarkers for 4-AcO-DiPT consumption.
Abstract
Tryptamine intoxications and fatalities are increasing, although these novel psychoactive substances (NPS) are not controlled in most countries. Th...
Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines
ACS Omega – July 05, 2022
Summary
Aeruginascin-related quaternary tryptamines, synthesized through chemical methods, surprisingly showed no affinity for receptors mediating psychedelic effects. Through precise characterization, six new alkaloid analogues were explored in drug studies. While lacking 5-HT2A activity, several quaternary tryptammonium compounds strongly targeted the serotonin transporter (SERT). Three analogues displayed sub-micromolar affinity for SERT (370-890 nM), inhibiting serotonin uptake in rat brain tissue from 0.31-3.5 μM. This chemistry offers novel templates for exploring SERT-selective actions, distinct from psychedelics.
Abstract
Aeruginascin (4-phosphoryloxy-N,N,N-trimethyltryptammonium) is an analogue of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) that has been ide...