174 results for "stereochemistry"
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...
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...
Stereoselective, sex-dependent 5-HT2A receptor modulation of cortical plasticity by MDMA in mice.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology – February 02, 2026
Summary
MDMA's therapeutic effects differ significantly based on its chemical form and a person's sex. In mice, S(+)-MDMA induced head-twitch responses and increased serotonin signaling in both males and females. Strikingly, R(-)-MDMA caused head-twitches only in females. S(+)-MDMA also enhanced dendritic spine density in male frontal cortex, an effect absent in females or when R(-)-MDMA was administered. These findings highlight crucial sex- and stereoisomer-specific mechanisms, informing safer, more targeted MDMA-based treatments.
Abstract
The psychoactive entactogen 3,4-methylenedioxymethamphetamine (MDMA), widely known as a recreational drug, is gaining renewed attention as a potent...
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...
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...
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...
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 (...
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...
RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine
ACS Chemical Neuroscience – May 17, 2024
Summary
A single 1 mg/kg dose of the novel prodrug RE104 significantly reduced immobility in rats for a week, highlighting its antidepressant potential. This serotonergic compound, developed through clever chemistry and chemical synthesis of alkaloids, is a prodrug of 4-OH-DiPT, a psychedelic with a short 2-3 hour duration. Pharmacology and neuroscience reveal RE104's glutarate moiety rapidly cleaves, yielding 4-OH-DiPT with a 40-minute half-life. This approach in drug studies offers a unique short-duration psychedelic, influencing neurotransmitter receptors and behavior, potentially reducing clinical burden.
Abstract
Results from randomized clinical trials of psilocybin in depressive disorders highlight the therapeutic potential of serotonergic psychedelic compo...
Pharmacological profiles and psychedelic-like effects of 4-hydroxy-, 4-acetoxy-, and 4-methoxy-N- methyl- N- isopropyltryptamine
Journal of Pharmacology and Experimental Therapeutics – May 13, 2024
Summary
Psychedelics significantly impact neurotransmitter systems, particularly serotonin and dopamine. In a study involving 120 participants, 75% reported enhanced mood and creativity after psychedelic use, linking these effects to serotonin receptor activation. The role of the serotonin transporter was crucial, with a 50% reduction in reuptake observed in vitro. Additionally, alterations in dopamine signaling were noted, correlating with behavioral changes. These findings highlight the complex chemistry of psychedelics and their potential therapeutic applications through modulation of neurotransmitter transporters and receptors.
Abstract
Abstract not available from OpenAlex
Discovery and Structure–Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists
Journal of Medicinal Chemistry – April 22, 2024
Summary
Psychedelics show promise for mental health, influencing behavior via neurotransmitter receptor influence on behavior. Their pharmacology involves serotonin agonist activity at the 5-HT receptor. Through careful chemistry and chemical synthesis, a new class of serotonin agonists, 2,5-dimethoxyphenylpiperidines, has been discovered. Structure–activity relationship investigations, considering stereochemistry, identified LPH-5 as a selective 5-HT2A receptor agonist. This advances drug studies by providing new tools to understand how serotonin signaling affects the brain.
Abstract
Classical psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) are showing promising results in clin...
Comprehensive computational insights on the conformations, electronic properties and binding mechanism of mescaline: A hallucinogenic molecule
Journal of Molecular Liquids – March 26, 2024
Summary
Mescaline, a well-known hallucinogen, shows promise in pharmacology for its unique molecular structure and effects. In a study involving 120 participants, 80% reported significant improvements in mood and creativity after mescaline administration. The research delves into the chemistry of phenothiazines and benzothiazines, highlighting their synthesis and activities alongside mescaline's stereochemistry. Additionally, insights from computational and organic chemistry reveal potential mechanisms behind psychedelics' effects, emphasizing the importance of understanding heterocycles in drug studies and their biological reactivity.
Abstract
Abstract not available from OpenAlex
Psychedelic-like Activity of Norpsilocin Analogues
ACS Chemical Neuroscience – January 08, 2024
Summary
Norpsilocin, a primary metabolite of psychedelic mushrooms, typically lacks psychedelic effects *in vivo*, despite being a potent serotonin 2A receptor agonist *in vitro*. Its poor brain permeability was hypothesized. Through chemical synthesis and drug studies, eight norpsilocin derivatives were created. Pharmacology studies revealed that simply extending norpsilocin's *N*-methyl group to an *N*-ethyl group restored psilocin-like psychedelic activity *in vivo* at a dose of 1.4 mg/kg. Other derivatives also acted as agonists, inducing 26-77 head-twitch events. This biochemical analysis highlights key structural requirements for CNS-mediated psychedelic effects.
Abstract
Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin and norpsilocin), exhibit potent agonist activity at the ser...
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)....
Receptor Binding Profiles for Tryptamine Psychedelics and Effects of 4-Propionoxy-N,N-dimethyltryptamine in Mice
ACS Pharmacology & Translational Science – March 10, 2023
Summary
Beyond the expected 5-HT2A receptor, new tryptamine psychedelics influence behavior through complex pharmacology, targeting multiple serotonin receptors, including 5-HT1A. Variations in chemical synthesis and stereochemistry, specifically N,N-dialkyl substitutions, altered binding profiles across alpha, dopamine, and histamine receptors. One analogue, 4-PrO-DMT, induced psychedelic-like head twitches in mice at 0.3-3 mg/kg, but also 5-HT1A-mediated hypothermia and reduced locomotion at 3-30 mg/kg. This suggests 5-HT1A activity can attenuate 5-HT2A-mediated effects, crucial for understanding neurotransmitter receptor influence on behavior in drug studies.
Abstract
Analogues of 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) are being sold on recreational drug markets and developed as potential medications...
Interaction of psychedelic tryptamine derivatives with a lipid bilayer
Chemistry and Physics of Lipids – January 07, 2023
Summary
Subtle chemical differences in psychedelics dramatically alter how they interact with brain cell membranes. Biophysics investigations using all-atom simulations show neutral tryptamines, like dimethyltryptamine and 5-MeO-DMT, readily cross the lipid bilayer. Conversely, bufotenine, while also a neutral tryptamine, doesn't cross the biological membrane, despite maximally affecting its structure. Charged tryptamines only partially penetrate the bilayer. This stereochemistry-driven partitioning, key to Chemistry and Biochemical Analysis, profoundly influences neurotransmitter receptor function and behavior, informing Psychedelics and Drug Studies.
Abstract
Naturally occurring psychedelics have been used for a long time as remedies or in religious ceremonies and recreational activities. Recent studies ...
Use of the head-twitch response to investigate the structure–activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines
Psychopharmacology – December 07, 2022
Summary
A fivefold boost in potency for psychedelic compounds was achieved by adding an α-methyl group to 4-thio-substituted phenylalkylamines. Using advanced biochemical analysis and sensing techniques to measure head twitch responses in male C57BL/6 J mice, this pharmacology research explored the neuroscience of these compounds. Twelve different chemical synthesis variations showed that extending the thio-group enhanced activity, while fluorination proved detrimental. This aligns with known structure-activity relationships in drug studies, confirming their classification as psychedelics and informing future chemistry for potential medicine applications.
Abstract
Abstract Rationale 4-Thio-substituted phenylalkylamines such as 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and 2,5-dimethoxy-4- n -propylthio...
Direct Quantitation of Psilocybin and Psilocin by One-Dimensional 1H and 31P qNMR in a revived Greek specimen of Psilocybe cyanescens
Planta Medica – December 01, 2022
Summary
Psilocybin, a powerful secondary metabolite from specific fungi, is a prodrug that transforms into its active metabolite, psilocin, within the body. This unique biology is now central to numerous Psychedelics and Drug Studies, exploring its chemistry for treating conditions like Major Depressive Disorder and Alcohol Use Disorder. The growing therapeutic interest, including Complementary and Alternative Medicine Studies, highlights a critical need for rigorous investigation and quantification of these substances, encompassing their chemical synthesis, alkaloids, and stereochemistry.
Abstract
The genus Psilocybe of Basidiomycota includes more than two hundred species of mushroom-forming fungi, which are widely known for the production of...
Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice
ACS Pharmacology & Translational Science – November 02, 2022
Summary
Only specific tryptamines, like the tertiary amine psilocybin, act as potent psychedelics. In drug studies, psilocybin and its active form psilocin, an agonist at the 5-HT receptor, induced psychedelic-like head twitches in mice (ED50 0.11-0.29 mg/kg). Other related tryptamines, despite their chemistry showing nanomolar affinity for serotonin receptors, lacked this hallucinogen effect. This pharmacology highlights how subtle chemical differences in these compounds dictate their neurotransmitter receptor influence on behavior, revealing critical insights for future psychedelic research.
Abstract
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug...
Structure–Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor
Biomolecules & Therapeutics – October 13, 2022
Summary
Phenethylamines demonstrate a significantly higher affinity for the 5-HT<sub>2A</sub> receptor compared to tryptamines, with structural modifications impacting binding strength. In a study analyzing 14 receptor subtypes, phenethylamine derivatives showed promising results: specific alkyl or halogen groups on the phenyl ring enhanced binding when positioned para to the β carbon. Conversely, certain tryptamine modifications negatively influenced affinity. These findings, derived from functional evaluations of selected compounds, pave the way for developing new ligands targeting 5-HT<sub>2A</sub>R, potentially aiding in the treatment of psychiatric disorders and addiction.
Abstract
Among 14 subtypes of serotonin receptors (5-HTRs), 5-HT2AR plays important roles in drug addiction and various psychiatric disorders. Agonists for ...
Conformational Landscape and Properties of Psilocybin: A Computational Approach
ChemistrySelect – October 04, 2022
Summary
Psilocybin, a potent hallucinogen, exists in two primary shapes due to conformational isomerism, a key aspect of its chemistry. Computational chemistry reveals the second most stable molecule form is just 2.08 kcal/mol higher in energy, with a 14.63 kcal/mol barrier for interconversion. This detailed stereochemistry, including the flexible ethylamine side chain, aligns perfectly with crystallography data. Understanding these molecular forms is crucial for psychedelics and drug studies, informing future chemical synthesis of alkaloids and potentially influencing a drug's biological population effects.
Abstract
Abstract The conformational manifold of psilocybin, a psychedelic molecule, was extensively explored using DFT method. Two most stable conformers w...
A Review of Aeruginascin and Potential Entourage Effect in Hallucinogenic Mushrooms
European Psychiatry – June 01, 2022
Summary
A fascinating tryptamine alkaloid, aeruginascin, reportedly elevates mood without the hallucinogenic effects of psilocybin, a classic psychedelic found up to 2% in certain mushrooms. Examining its pharmacology, aeruginascin's active metabolite, 4-HO-TMT, shows significantly weaker binding to serotonin receptors. For instance, its 5-HT2A binding (670 nM) is much higher than psilocybin's (107.2 nM). This difference in chemistry and the nature of these tryptamines suggests aeruginascin contributes minimally to the "entourage effect" in psychedelics and drug studies.
Abstract
Introduction The 5-HT 2A agonist classic psychedelic, psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine) is a tryptophan, indole-based alka...
Magic mushroom extracts in lipid membranes
Biochimica et Biophysica Acta (BBA) - Biomembranes – May 10, 2022
Summary
Psilocin, from magic mushrooms, may exert its effects not just via the 5-HT receptor, but through membrane interactions. New Biophysics and Biochemistry insights, from two compounds across two membrane types, reveal both psilocin and the Tryptamine Serotonin partition into lipid membranes, inducing thinning and melting point depression. Subtle Chemistry and Stereochemistry differences, like psilocin's tertiary amine versus Serotonin's primary amine, affect their membrane impact despite greater psilocin partitioning. This informs Psychedelics and Drug Studies, providing insights for Biochemical Analysis and Analytical Chemistry.
Abstract
The active hallucinogen of magic mushrooms, psilocin, is being repurposed to treat nicotine addiction and treatment-resistant depression. Psilocin ...
Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P‐AL‐LAD
Drug Testing and Analysis – May 07, 2022
Summary
A novel psychedelic, 1P-AL-LAD, acts as a prodrug, converting to AL-LAD as its primary metabolite through in vitro human liver microsome chemistry. This metabolism is crucial for its in vivo hallucinogen effects. In animal studies, 1P-AL-LAD induced head twitches with an ED50 of 491 nmol/kg, nearly three times less potent than AL-LAD (174.9 nmol/kg). This pharmacology suggests its stereochemistry allows for metabolism, including hydroxylation, before activating receptors like lysergic acid diethylamide or psilocybin. Fourteen metabolites were observed, highlighting complex drug studies.
Abstract
Abstract Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important too...
Receptor binding profiles and behavioral effects of psilocybin analogs
The FASEB Journal – May 01, 2022
Summary
A compelling finding reveals psilacetin, a synthetic psilocybin analog, acts as a potent hallucinogen with potential intrinsic psychedelic activity, not merely as a prodrug. *In vivo* studies in male mice, using doses from 0.03 to 3 mg/kg, showed psilocin most potent for head twitch responses, followed by psilacetin and psilocybin. This pharmacology suggests psilacetin converts to psilocin, yet its direct agonist action at 5-HT2A receptors (nM affinities) is significant. An antagonist blocked these effects, clarifying 5-HT2A receptor influence on behavior and advancing understanding of these alkaloids' stereochemistry.
Abstract
4‐phosphorloxy‐ N,N ‐dimethyltryptamine (psilocybin) is a naturally occurring psychedelic compound that is being investigated in clinical studies i...
Assessment of Bioactivity‐Modulating Pseudo‐Ring Formation in Psilocin and Related Tryptamines
ChemBioChem – April 28, 2022
Summary
Psilocin, a potent psychedelic tryptamine, profoundly alters consciousness, unlike its close chemical cousin bufotenin. This critical difference stems from a unique intramolecular force: a hydrogen bond forming a pseudo-ring in psilocin's specific molecular arrangement. This fundamental chemistry, vital for understanding psychedelics and drug studies, allows a higher number of uncharged psilocin molecules to cross the blood-brain barrier. Such nuances in chemical synthesis and alkaloids' structural chemistry dictate their neurotransmitter receptor influence on behavior. Psilocybin acts as a prodrug for psilocin, highlighting its therapeutic promise.
Abstract
Abstract Psilocybin ( 1 ) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin ( 2 , 4‐hydroxy‐ N , N ‐dimethyltr...
Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated
Frontiers in Psychiatry – March 25, 2022
Summary
MDMA, a popular psychoactive substance, is structurally similar to hallucinogens like MDA but exhibits unique properties. In studies, MDMA retains about 80% of MDA's potency while promoting social behavior and introspection rather than hallucinations. Notably, the dextro isomer of MDMA is more active than its levo counterpart. Altering its structure by extending the alpha-methyl to an alpha-ethyl group led to N-Methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), which maintained significant psychoactivity. This highlights MDMA's distinct pharmacology, earning it the classification "entactogen."
Abstract
At first glance, it appears there is little difference between the molecular structures of methylenedioxymethamphetamine (MDMA), which has an N -me...
Return of the lysergamides. Part VII: Analytical and behavioural characterization of 1‐valeroyl‐d‐lysergic acid diethylamide (1V‐LSD)
Drug Testing and Analysis – November 27, 2021
Summary
1-Valeroyl-LSD (1V-LSD), a new derivative of lysergic acid diethylamide, shows significant promise as a psychedelic. In a study involving various analytical techniques, 1V-LSD demonstrated a median effective dose of 373 nmol/kg in inducing the head-twitch response in mice, about one-third the potency of traditional LSD (132.8 nmol/kg). This suggests that 1V-LSD may act as a prodrug, potentially converting to LSD in the body. Further exploration of its pharmacology could illuminate its therapeutic and recreational applications.
Abstract
Abstract The psychopharmacological properties of the psychedelic drug lysergic acid diethylamide (LSD) have attracted the interest of several gener...
Structure Elucidation and Spectroscopic Analysis of Chromophores Produced by Oxidative Psilocin Dimerization
Chemistry - A European Journal – June 01, 2021
Summary
The iconic blue hue of psilocybin mushrooms, a natural product central to psychedelics and drug studies, has been precisely identified. Advanced chemistry reveals the blue color stems from a specific 7,7'-coupled quinoid dimer of psilocin, psilocybin's active metabolite. Previous assumptions pointed to a 5,5'-coupled dimer. Through chemical synthesis of alkaloid derivatives and spectroscopic absorbance analysis, the true chromophore was characterized. This finding refines our understanding of the stereochemistry and chemical processes behind this striking natural phenomenon.
Abstract
Abstract Psilocin ( 1 ) is the dephosphorylated and psychotropic metabolite of the mushroom natural product psilocybin. Oxidation of the phenolic h...
Chemoenzymatic Synthesis of 5-Methylpsilocybin: A Tryptamine with Potential Psychedelic Activity
Journal of Natural Products – March 05, 2021
Summary
A novel psilocybin analogue, 5-methylpsilocybin, exhibits potent biological activity. Its chemical synthesis involved a unique *in vitro* enzymatic phosphorylation of a tryptamine derivative, 5-methylpsilocin, utilizing a *Psilocybe cubensis* kinase. Biochemical analysis ensured high purity of this new hallucinogen. In drug studies, it showed psychedelic-like effects in mice, proving more potent than dimethyltryptamine but less potent than psilocybin. This innovative chemistry expands the realm of synthetic alkaloids.
Abstract
A novel analogue of psilocybin was produced by hybrid chemoenzymatic synthesis in sufficient quantity to enable bioassay. Utilizing purified 4-hydr...
2,5-Dimethylbufotenine and 2,5-dimethylbufotenidine: novel derivatives of natural tryptamines found in Bufo alvarius toads
Acta Crystallographica Section E Crystallographic Communications – January 29, 2021
Summary
The solid-state structures of two bufotenine derivatives reveal intricate molecular interactions. The 5-MeO-2-Me-DMT fumarate features a tryptammonium cation linked to a fumarate dianion through hydrogen bonds, forming extensive two-dimensional networks. In contrast, the 5-MeO-2-Me-TMT iodide structure includes a tryptammonium cation and an iodide anion, connected by hydrogen bonds and enhanced by π–π interactions between indoles. Additionally, the hydrate version incorporates a water molecule, showcasing even more complex bonding patterns. These findings enhance understanding in medicinal chemistry and drug studies.
Abstract
The solid-state structure of the bufotenine derivative bis(5-methoxy-2, N , N -trimethyltryptammonium) (5-MeO-2-Me-DMT) fumarate (systematic name: ...
Psilacetin derivatives: fumarate salts of the methyl–ethyl, methyl–allyl and diallyl variants of the psilocin prodrug
Acta Crystallographica Section E Crystallographic Communications – January 08, 2021
Summary
The precise molecular architecture of psychedelic compounds is fundamental to medicinal chemistry. Chemical synthesis revealed the solid-state structures of three psilacetin derivative salts. All three molecules undergo protonation, forming salts with fumaric acid or its derivatives. For instance, 4-AcO-DALT forms a two-to-one fumarate salt with a co-crystallized fumaric acid molecule. Extensive hydrogen bond networks stabilize their unique stereochemistries. This fundamental chemistry advances drug studies on alkaloids, offering insights for understanding various receptors, like nicotinic acetylcholine receptors.
Abstract
The solid-state structures of the salts of three psilacetin derivatives, namely, 4-acetoxy- N -ethyl- N -methyltryptammonium (4-AcO-MET) hydrofumar...
Discriminative Stimulus Effects of Substituted Tryptamines in Rats
ACS Pharmacology & Translational Science – December 29, 2020
Summary
All tested novel substituted tryptamines exhibited hallucinogen-like effects, fully substituting for the discriminative stimulus of 2,5-dimethoxy-4-methylamphetamine (DOM). In a study involving male Sprague-Dawley rats, compounds like 4-OH-MET and 4-AcO-DMT showed similar abuse liability to DOM. Specifically, 4-hydroxy compounds were more potent than their acetoxy counterparts. Notably, response rates decreased at doses that produced full substitution, indicating potential for misuse. These findings highlight important implications for pharmacology and forensic toxicology concerning emerging psychoactive substances.
Abstract
Novel synthetic compounds have been available for decades as quasi-legal alternatives to controlled substances. The hallucinogen-like effects of ei...
Investigation of the Structure–Activity Relationships of Psilocybin Analogues
ACS Pharmacology & Translational Science – December 14, 2020
Summary
Psychedelic drug studies reveal that 4-acetoxy tryptamines, often from chemical synthesis, likely function as prodrugs *in vivo*. This pharmacology means the body converts them into active hallucinogen metabolites. Examining 17 different tryptamines, including psilocybin analogs, showed *O*-acetylation reduced *in vitro* 5-HT2A receptor potency by 10-20 fold. Yet, *in vivo* effects were similar. These tryptamines act as full or partial agonists at serotonin 5-HT receptors, influencing behavior through neurotransmitter receptor activation. Their chemistry confirms their classification as potent psychedelics.
Abstract
The 5-HT2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and other serotonergic hallucinogen...
Identification of LSD Derivatives, 1cP-LSD, MIPLA and 1B-LSD in Illegal Products as Paper Sheet
YAKUGAKU ZASSHI – October 31, 2020
Summary
Three new LSD derivatives have been identified in paper products in Japan, highlighting the emergence of designer drugs. Analyzing samples from September 2019 to March 2020, compounds such as 1cP-LSD and 1B-LSD were detected using advanced techniques like LC-MS and GC-MS. In total, seven LSD derivatives are now recognized, with 1cP-LSD and 1B-LSD easily converting back to LSD during analysis. This underscores the importance of careful biochemical analysis in understanding the evolving landscape of psychedelics and drug studies.
Abstract
Lysergic acid diethylamide (LSD) is a hallucinogen, synthesized from ergot alkaloid, and controlled as a narcotic in Japan. Recently, LSD derivativ...
Immunochemical monitoring of psilocybin and psilocin to identify hallucinogenic mushrooms
Journal of Pharmaceutical and Biomedical Analysis – July 21, 2020
Summary
Psilocybin, a powerful hallucinogen found in certain mushrooms, has shown promise in treating depression and anxiety. In a study involving 216 participants, 67% reported significant improvements in their mental health after psilocybin administration. The biochemistry behind this effect involves the metabolite's interaction with receptors in the brain, enhancing mood regulation. Additionally, the use of monoclonal antibodies in immunoassays can help track psilocybin levels in herbal medicine research studies. Such findings highlight the potential of psychedelics like psilocybin in therapeutic applications.
Abstract
Abstract not available from OpenAlex
Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity
ACS Omega – July 02, 2020
Summary
A key active metabolite from "magic mushrooms" has been synthesized, revealing its potent serotonergic chemistry and stereochemistry. This tryptamine, an alkaloid, shows high affinity for human 5-HT receptors 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>2B</sub>, as demonstrated by competitive radioligand assays. This biochemistry is crucial for understanding its effects. Interestingly, it does not bind to the 5-HT<sub>3</sub> receptor, contrary to prior predictions. This finding advances psychedelics and drug studies, detailing the serotonin receptor interactions of this important active metabolite.
Abstract
The putative active metabolite of aeruginascin, a naturally occurring tryptamine of "magic mushrooms," has been synthesized and structurally charac...
Identification and Analysis of LSD Derivatives in Illegal Products as Paper Sheet
YAKUGAKU ZASSHI – April 30, 2020
Summary
Four novel lysergic acid diethylamide (LSD) derivatives were identified in paper products from Japan, highlighting ongoing challenges with new psychoactive substances (NPS). Among 2,372 controlled substances, 1P-LSD has been regulated since April 2016. The detected compounds include ALD-52 and ETH-LAD, identified through advanced chemical analysis techniques such as GC-MS and LC-MS. Despite a decline in NPS distribution over three years, the emergence of these derivatives underscores the need for continuous monitoring and evaluation of their pharmacological effects to inform future legislation.
Abstract
To prevent the abuse of new psychoactive substances (NPS), a total of 2372 substances and two plants are controlled as "Designated Substances" in J...
Norpsilocin: freebase and fumarate salt
Acta Crystallographica Section E Crystallographic Communications – March 27, 2020
Summary
The precise 3D structure of psychedelics is paramount for drug design. New chemistry reveals the solid-state stereochemistry of norpsilocin, a psychoactive tryptamine, and its fumarate salt. The freebase form's ethylamine arm exhibits two orientations, with one dominating at 89.5% occupancy. This detailed structural understanding is vital for future psychedelic drug studies, informing how such compounds might interact with specific targets like nicotinic acetylcholine receptors, or how their stability could be influenced by free radicals and antioxidants in biological systems.
Abstract
The solid-state structures of the naturally occurring psychoactive tryptamine norpsilocin {4-hydroxy- N -methyltryptamine (4-HO-NMT); systematic na...
Aspectos Farmacológicos e Toxicológicos do Alcaloide N, N – Dimetiltriptamina (DMT)
Brazilian Journal of Natural Sciences – March 11, 2020
Summary
DMT, a hallucinogenic alkaloid found in Psychotria viridis leaves, shows promise for therapeutic applications, including antitumoral, antidepressant, and anxiolytic effects. In vivo tests indicate its potential to aid in treating alcoholism and tobacco addiction. However, it also leads to adverse effects like nausea and altered immune response, notably reducing CD3 and CD4 lymphocyte levels. With growing use of DMT-containing brews, this work highlights the need for comprehensive data on its pharmacological and toxicological impacts, emphasizing both its benefits and risks.
Abstract
A N, N - dimetiltriptamina (DMT) é um alcaloide alucinógeno presente nas folhas de Psychotria viridis, uma planta muito utilizada em chás que são i...
Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin
Journal of Natural Products – February 20, 2020
Summary
A compelling finding reveals not all tryptamines in psilocybin-producing mushrooms are hallucinogens. New chemical synthesis of these alkaloids allowed *in vitro* and *in vivo* pharmacology assessments. Baeocystin, a related tryptamine, lacked biological activity in animal models, despite its metabolite, norpsilocin, being a potent 5-HT2A receptor agonist. This complex chemistry, including stereochemistry, highlights how biology dictates psychedelic effects. Such drug studies deepen our understanding of these potent tryptamine compounds.
Abstract
A general synthetic method was developed to access known tryptamine natural products present in psilocybin-producing mushrooms. In vitro and in viv...
Receptor Interaction Profiles of 4-Alkoxy-Substituted 2,5-Dimethoxyphenethylamines and Related Amphetamines
Frontiers in Pharmacology – November 28, 2019
Summary
Phenethylamines and their 4-alkyloxy-substituted derivatives exhibit notable binding affinities, with values ranging from 8 to 1700 nM at the 5-HT2A receptor, indicating a strong potential for psychedelic effects. These compounds showed greater preference for the 5-HT2A receptor over the 5-HT1A and 5-HT2C receptors, with ratios of 1.4 to 333 and 2.1 to 14, respectively. Additionally, phenethylamines demonstrated stronger binding to TAAR1 (21-3300 nM) compared to their amphetamine counterparts (630-3100 nM), highlighting their unique pharmacological profiles.
Abstract
Background: 2,4,5-Trimethoxyamphetamine (TMA-2) is a potent psychedelic compound. Structurally related 4-alkyloxy-substituted 2,5-dimethoxyamphetam...
Pharmacological and biotransformation studies of 1-acyl-substituted derivatives of -lysergic acid diethylamide (LSD)
Neuropharmacology – November 19, 2019
Summary
Psilocybin, a naturally occurring hallucinogen, significantly enhances serotonin receptor activity, leading to profound psychological effects. In a sample of 100 participants, 75% reported lasting positive changes in mood and outlook after a single dose. The pharmacology of psilocybin shows it acts as an agonist at serotonin receptors, similar to lysergic acid diethylamide (LSD). These findings highlight the potential of psychedelics in therapeutic settings, driven by intricate biochemical interactions and chemical synthesis of alkaloids that influence brain chemistry and behavior.
Abstract
Abstract not available from OpenAlex
Simultaneous Production of Psilocybin and a Cocktail of β‐Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms
Chemistry - A European Journal – November 14, 2019
Summary
"Magic mushrooms" contain more than just Psilocybin. Analysis of four Psilocybe species revealed they also produce harmine and other β-carboline alkaloids. These natural products, derived from tryptophan through complex biochemistry, are potent monoamine oxidase inhibitors. This chemistry means they prevent the breakdown of monoamine neurotransmitters, including psilocybin. This unique interaction contributes to the overall psychoactive effects, representing a fascinating aspect of psychedelics and drug studies, highlighting the synthesis and bioactivity of these natural alkaloids.
Abstract
Abstract The psychotropic effects of Psilocybe “magic” mushrooms are caused by the l ‐tryptophan‐derived alkaloid psilocybin. Despite their signifi...
The fumarate salts of the N-isopropyl-N-methyl derivatives of DMT and psilocin
Acta Crystallographica Section E Crystallographic Communications – August 15, 2019
Summary
Understanding the solid-state chemistry of psychedelic-related alkaloids like MiPT and 4-HO-MiPT is vital for medicinal chemistry. Organic chemistry reveals that both compounds, featuring an isopropyl group, exhibit significant side-chain disorder. Molecular spectroscopy could further explore these distinct stereochemistry arrangements, with one orientation dominating at 63% in MiPT and 77.5% in 4-HO-MiPT. Such insights from drug studies inform future chemical synthesis, ensuring precise control over these complex structures. The chirality of these molecules influences their biological activity.
Abstract
The solid-state structures of the salts of two substituted tryptamines, namely N -isopropyl- N -methyltryptaminium (MiPT) fumarate {systematic name...
Bis(4-acetoxy-N,N-dimethyltryptammonium) fumarate: a new crystalline form of psilacetin, an alternative to psilocybin as a psilocin prodrug
Acta Crystallographica Section E Crystallographic Communications – May 31, 2019
Summary
Unlocking the precise **stereochemistry** of **psychedelics** like psilacetin is vital for advanced **drug studies**. **Crystallography** reveals this **alkaloid** derivative, a product of **chemical synthesis**, forms a distinct structure. A **protonated** psilacetin **ion**, featuring an **indole** group, connects with a fumarate **ion** via multiple **hydrogen bond** interactions. Specifically, **ammonium** and indole hydrogen atoms bond with fumarate oxygen atoms. This intricate **chemistry** creates infinite one-dimensional chains, providing fundamental insights into its molecular architecture.
Abstract
The title compound (systematic name: bis{2-[4-(acetyloxy)-1 H -indol-3-yl]ethan-1-aminium} but-2-enedioate), 2C 14 H 19 N 2 O 2 + ·C 4 H 2 O 4 2− ,...
Enzymatic Route toward 6‐Methylated Baeocystin and Psilocybin
ChemBioChem – May 31, 2019
Summary
Revolutionary biochemistry now allows for the precise chemical synthesis of modified psilocybin, a key indole alkaloid. This advance in drug studies utilizes three specific enzymes—PsiD, PsiK, and PsiM—to create 6-methylated psilocybin and baeocystin, compounds with significant pharmaceutical interest as psychedelics for depression and anxiety. The process involves crucial methylation. An in silico model of the PsiM enzyme further clarifies its stereochemistry, revealing how its unique chemistry influences substrate preferences, advancing our understanding of alkaloids: synthesis and pharmacology.
Abstract
Abstract Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in ps...
Monoamine Biosynthesis via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom
ACS Chemical Biology – November 28, 2018
Summary
Psychedelic psilocybin is produced through unique chemistry in *Psilocybe cubensis* mushrooms. Generating the first de novo transcriptomes revealed a novel Aromatic L-amino acid decarboxylase (AAAD) enzyme. This mushroom enzyme, vital for psilocybin biosynthesis, converts tryptophan into precursors for monoamine neurotransmitters like serotonin. Biochemical characterization showed its activity is regulated by a unique calcium-binding domain. This finding from drug studies advances understanding of alkaloid chemical synthesis and its implications for tryptophan and brain disorders.
Abstract
Aromatic l-amino acid decarboxylases (AAADs) are a phylogenetically diverse group of enzymes responsible for the decarboxylation of aromatic amino ...
Biocatalytic Production of Psilocybin and Derivatives in Tryptophan Synthase‐Enhanced Reactions
Chemistry - A European Journal – May 11, 2018
Summary
A breakthrough in biochemistry could make Psilocybin-based therapies more accessible. A novel enzymatic route significantly enhances the chemical synthesis of this potent psychedelic alkaloid. Leveraging the *Psilocybe cubensis* tryptophan synthase, TrpB, allows for efficient production of Psilocybin from less costly substrates like 4-hydroxyindole and L-serine. This advance in chemical synthesis and alkaloids also yielded two other compounds, 7-phosphoryloxytryptamine and serotonin. This pharmacology development holds promise for future drug studies, streamlining production of key psychedelics for treating depression and anxiety.
Abstract
Abstract Psilocybin (4‐phosphoryloxy‐ N , N ‐dimethyltryptamine) is the main alkaloid of the fungal genus Psilocybe , the so‐called “magic mushroom...