Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l-tryptophan involves four strictly sequential modifications. The third of these, ATP-dependent phosphorylation of the intermedia...
Abstract The Psilocybe cubensis SAM-dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiM N247M...
Protonation is the most frequent adduct found in positive electrospray ionization collision-induced mass spectra (CID-MS/MS). In a parallel report Lee, J. J. Chem. Inf. Model. 2024, 10.1021/acs.jcim.4c00760, we developed a quantum chemistry framework to predict mass spectra by collision-induced dissociation molecular dynamics (CIDMD). As different protonatio...
The psychedelic mushroom market has expanded rapidly due to changing regulations and increasing consumer demand. Product diversity now extends beyond traditional capsules and tablets to include gummies, powders, and confectionery items, complicating quality control efforts. To assess the quality and potential adulteration of Amanita musca-ria and Psilocybe c...
The recent relaxation of psychedelic drug regulations has prompted extensive clinical investigation into their potential use to treat diverse mental health conditions including anxiety, depression, post-traumatic stress, and substance-abuse disorders. Most clinical trials have relied on a small number of known molecules found in nature, such as psilocybin, o...
This work utilized fMRI to assess the influence of the psychedelics, Psilocybin, a serotonergic agonist, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on functional connectivity (FC) in non-human primates. We used a seed-based FC analysis, probing regions of interest associated with psychedelic hallucinogens. Our findings highlight the overlapping...
Psilocybin is a psychedelic compound found in some hallucinogenic "magic mushrooms". Psilocin is the active metabolite of Psilocybin, and it is the subject of several studies for the treatment of psychological disorders, such as anxiety, depression, and post-traumatic stress disorder. As such, the pharmacokinetic properties of psilocin should be evaluated to...
Many medicines and treatments for varying levels of ailments were found through natural bioactives before complex separation techniques were available.Ironically, as medicine advances, drastically more people seem to be reverting to a desire for these natural bioactives.Due to this, it is important to discover and research the pharmacology of historically us...
Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A42-year-old man with treatment-resistant major depressive disorder took 1 g of Psilocybe cubensis mushrooms, while presc...
Several fungi belonging to the genus Psilocybe, also called “magic mushrooms”, contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to serotonin (5-HT). In addition to being abused as drugs, they are now also being discussed or used as a treatment option for depression. Here, we hypothesized that psilocybin and psilocin may a...
Serotonergic psychedelics hold promise as a treatment modality for various psychiatric disorders and are currently applied in psychedelic-assisted psychotherapy. We investigated the learning effects of the serotonin receptor agonist psilocybin in a probabilistic cue-reward task with emotional cues in the form of neutral or fearful faces, presented either con...
The title compound, C12 H16 N2 O, is a hydroxy-substituted monoamine alkaloid, and the primary metabolite of the naturally occurring psychedelic compound psilocybin. Crystalline forms of psilocin are known, but their characterization by single-crystal structure analysis is limited. Herein, two anhydrous polymorphic forms (I and II) of psilocin are described....
Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders1-3. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT2A (ref. 4). However, 5-HT1A also plays a part in the beha...
We are in the midst of a polycrisis, with any number of thoughts on how to approach the intersecting global crises of environmental, social, political, and other issues. One line of thinking for re...
