A5029982811- Psychedelics and Drug Studies
- Chemical synthesis and alkaloids
- Radioactive element chemistry and processing
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Neurotransmitter Receptor Influence on Behavior
- Alkaloids: synthesis and pharmacology
- Forensic Toxicology and Drug Analysis
- Crystal Structures and Properties
- Vanadium and Halogenation Chemistry
- Receptor Mechanisms and Signaling
- Geochemistry and Geologic Mapping
- Geological and Geochemical Analysis
- Neuropeptides and Animal Physiology
- Hydrocarbon exploration and reservoir analysis
- Catalysis and Oxidation Reactions
- Traditional and Medicinal Uses of Annonaceae
- Crystallography and molecular interactions
- Biochemical Analysis and Sensing Techniques
- Synthesis of Indole Derivatives
- Cannabis and Cannabinoid Research
- Inflammatory mediators and NSAID effects
- Analytical Chemistry and Chromatography
- Radioactive contamination and transfer
- Tryptophan and brain disorders
Usona Institute
2019-2025
University of Kentucky
2021
University of Kansas
2016-2018
University of New Orleans
2012
Louisiana State University Health Sciences Center New Orleans
2009
United States Geological Survey
1953-1959
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical activate both 5-HT2A-Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 recruitment efficacy predicts potential, assessed using head-twitch...
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present psilocybin-containing mushrooms, including secondary 4-phosphoryloxy-N-methyltryptamine (baeocystin) and quaternary ammonium...
Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin norpsilocin), exhibit potent agonist activity at the serotonin 2A receptor (5-HT2A) in vitro but differ their 5-HT2A-mediated effects vivo. In particular, produces centrally mediated psychedelic vivo, whereas norpsilocin, differing only by loss an N-methyl group, is devoid psychedelic-like effects. These observations suggest that secondary methylamine group norpsilocin impacts its central nervous system...
A general synthetic method was developed to access known tryptamine natural products present in psilocybin-producing mushrooms. In vitro and vivo experiments were then conducted inform speculations on the psychoactive properties, or lack thereof, of products. animal models, psychedelic activity by baeocystin alone not evident using mouse head twitch response assay, despite its putative dephosphorylated metabolite, norpsilocin, possessing potent agonist at 5-HT2A receptor.
purpose. To investigate the biosynthesis of resolvins E1 and D1 (RvE1 RvD1) in choroid-retinal endothelial cells (CRECs) leukocytes under inflammatory conditions to define mechanisms anti-inflammatory actions RvE1 RvD1 CRECs leukocytes, crucial posterior ocular inflammation. methods. RvE1, RvD1, markers their were determined by lipidomic analysis. After or cocultures treated with stimuli, signaling molecules quantified Western blot analysis, ELISA, protein array. Transmigration...
Advanced clinical trials investigate the Psilocybe magic mushroom natural product psilocybin as a treatment against major depressive disorder. Currently, synthetic material is used to meet demand for legitimate pharmaceutical purposes. Here, we report an in vitro approach biocatalytically produce on solid‐phase matrix charged with five covalently bound biosynthetic enzymes. These enzymes include three enzymes: IasA*, engineered l‐tryptophan decarboxylase/aromatic aldehyde synthase,...
Opioids are widely used to treat millions suffering from pain, but their analgesic utility is limited due associated side effects. Herein we report the development and evaluation of a chemical probe exhibiting analgesia reduced opioid-induced This compound, kurkinorin (5), potent selective μ-opioid receptor (MOR) agonist (EC50 = 1.2 nM, >8000 μ/κ selectivity). 5 biased activator MOR-induced G-protein signaling over β-arrestin-2 recruitment. Metadynamics simulations 5's binding MOR crystal...
Abstract Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment‐resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes met by synthetic chemistry. We replaced problematic phosphorylation step during synthesis with mushroom kinase PsiK. This enzyme was biochemically characterized used to produce one gram from psilocin within 20 minutes. also describe pilot‐scale...
Abstract Psilocybin ( 1 ) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin 2 , 4‐hydroxy‐ N ‐dimethyltryptamine), potent that exerts remarkable alteration of human consciousness. In contrast, positional isomer bufotenin 7 5‐hydroxy‐ ‐dimethyltryptamine) differs significantly its reported pharmacology. A series experiments was designed explore chemical differences between specifically test hypothesis C‐4 hydroxy group influences observed physical...
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical activate both 5-HT2A-Gq/11 and β-arrestin2 signaling, making their respective roles unclear. To elucidate this, we developed a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 efficacy predicts potential, assessed using head-twitch response (HTR)...
Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these as therapeutics necessitates preclinical assays can accurately screen psychedelics related analogs. We posit a promising approach may be to measure drug action on markers of neural plasticity native brain tissues. therefore developed pipeline for classification light sheet fluorescence microscopy immediate early gene...
Previous structure-activity studies on the neoclerodane diterpenoid salvinorin A have demonstrated importance of acetoxy functionality A-ring in its activity as a κ-opioid receptor agonist. Few focused understanding role conformation these interactions. Herein we describe synthesis and evaluation both flexible conformationally restricted compounds derived from A. One such compound, spirobutyrolactone 14, was synthesized single step B had similar potency selectivity to (EC50 = 0.6 ± 0.2 nM at...
Abstract Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression anxiety is currently being investigated advanced clinical trials. Here, we report biocatalytic route to synthesize 6‐methylated from 4‐hydroxy‐6‐methyl‐ l ‐tryptophan, which was decarboxylated phosphorylated by the cubensis biosynthesis enzymes PsiD PsiK. N‐Methylation catalyzed PsiM. We further...
A second-generation kilogram-scale synthesis of the psychedelic tryptamine psilocybin has been developed. The was designed to address several challenges first encountered with scale-up previously described literature procedures, which were not optimized for providing consistent yield and purity products, atom economy, or being run in pilot plant-scale reactors. These addressed circumvented design route, featured an cGMP large-scale Speeter-Anthony intermediate psilocin improved in-process...
To support clinical use, a multigram-scale process has been developed to provide 5-MeO-DMT, psychedelic natural product found in the parotid gland secretions of toad, Incilius alvarius. Several synthetic routes were initially explored, and selected featured an optimized Fischer indole reaction 5-MeO-DMT freebase high-yield, from which 1:1 succinate salt was produced 136 g crystalline active pharmaceutical ingredient (API) with 99.86% peak area by high-performance liquid chromatography (HPLC)...
Described herein is an improved synthesis of 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate (psilocybin). The protocol outlines: multigram quantities psilocybin, identification critical in-process parameters, and isolation psilocybin without the use chromatography, TLC, or aqueous workup. furnishes in five steps 23% overall yield from inexpensive acetoxyindole starting material. With specific focus on process control impurity fate removal, procedure amenable to providing...