This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by ...
Uncovering the neural basis of psychedelics’ potent effects on brain activity and conscious experience has great potential for understanding their therapeutic effects. Numerous studies using functional magnetic resonance imaging (fMRI) uncovered a strong effect of psychedelics on global properties of fMRI signal, but how they map to underlying neural phenome...
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-admini...
PcncAAAD is a noncanonical fungal aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. Unlike its mammalian and plant counterparts, PcncAAAD is activated by calcium, although the exact activation mechanism remains unclear. Here, we establish an in silico RMSD-based evaluation model throu...
Psychedelic compounds, particularly psilocybin, have demonstrated remarkable therapeutic potential for mental health disorders through mechanisms involving structural neural plasticity. This comprehensive review examines recent breakthrough research revealing how psilocybin triggers activity-dependent rewiring of large-scale cortical networks. Using monosyna...
Psilocybin-assisted interventions have shown rapid reductions in depressive symptoms in controlled clinical settings, raising questions about biological mechanisms supporting durability beyond the acute drug effect. [5,7] Mechanistic accounts increasingly focus on neuroplasticity as a candidate pathway linking transient serotonergic receptor activation to lo...
Emerging evidence suggests that classical psychedelics may offer therapeutic potential for opioid use disorder (OUD) by alleviating key hallmarks such as altered reward processing and dependence. However, the mechanisms behind these effects remain unclear. Our data demonstrate that a single administration of the psychedelic psilocybin (PSI) reduces condition...
Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to the biosynthesis of psilocybin can enhance its production process. In this study, we elucidate the ...
Several fruiting bodies from Mosul forests were collected and were diagnosed using the Polymerase Chain Technique based on ITS region. It was proved they belong to Psilocybe cubensis mushroom, and was registered in the GenBank, NCBI in the serial number OR140556.1. The fruiting body powder was used in order to extract the alkaloid compound “Psilocybe”, which...
ABSTRACT BACKGROUND AND PURPOSE: There is surging interest in the therapeutic potential of psychedelic compounds like psilocybin in the treatment of psychiatric illnesses like major depressive disorder (MDD). Recent studies point to the rapid antidepressant effect of psilocybin; however, the biological mechanisms underlying these differences remain unknown. ...
Cellular aging, driven by oxidative stress, mitochondrial dysfunction, and inflammation, is exacerbated by a high-glucose and high-lipid (HGHL) diet, leading to collagen degradation and skin aging. Psilocybin, a naturally occurring compound, has shown potential in reducing symptoms of aging. This study explores the protective effects of psilocybin on BJ-5ta ...
ABSTRACT Psilocybe is a genus of mushroom-forming fungi with ecological, ethnomycological, and clinical importance due to psilocybin production by most species. We present five genomes that enable deeper discovery and analysis of the psilocybin gene cluster and increase taxonomic resolution within Psilocybe: Psilocybe semilanceata, Psilocybe gandalfiana nom....
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...
BACKGROUND: Although Basidiomycota produce pharmaceutically and ecologically relevant natural products, knowledge of how they coordinate their primary and secondary metabolism is virtually non-existent. Upon transition from vegetative mycelium to carpophore formation, mushrooms of the genus Psilocybe use L-tryptophan to supply the biosynthesis of the psyched...
Abstract Psilocybin, the natural hallucinogen produced by Psilocybe (“magic”) mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolut...
There is a renewed interest in psychedelic drugs as potential therapeutic agents for the treatment of psychiatric disorders. In particular, psilocybin has shown promise for the treatment of refractory depression 1 and major depressive disorder 2, and has also been explored as a treatment for tobacco and alcohol abuse 3, 4. However, despite suggestive evidenc...
Psilocybe mushrooms, otherwise known as “magic” mushrooms, owe their psychedelic effect to psilocin, a serotonin subtype 2A (5-HT2A ) receptor agonist and metabolite of psilocybin, the primary indole alkaloid found in Psilocybe species. Metabolomics is an advanced fingerprinting tool that can be utilized to identify the differences among fungal life stages t...
Introduction: Psilocybin use has been linked to lowered odds of crime-related outcomes across a host of observational studies. No studies have investigated how these associations may differ among those of different races and ethnicities. Methods: Using a nationally-representative sample of 734,061 adults from the National Survey on Drug Use and Health (2002-...
BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hipp...
