Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilo...
Recent advancements in the study of psilocybin and its active metabolite psilocin have highlighted their unique psychedelic properties and potential therapeutic applications, particularly in the rapid and sustained treatment of depression. However, the potent acute psychedelic effects of psilocybin necessitate a deeper understanding of the neural mechanisms ...
4-Hydroxytryptamines such as psilocin and its prodrug psilocybin are of considerable current interest for innovative antidepressant and other neuropsychiatric treatments. We here present a synthetic route towards 4-hydroxytryptamines displaying a high versatility for SAR exploration at the aliphatic nitrogen. The core concept is to apply HATU-mediated amide ...
Psilocybin is an active alkaloid found in magic mushrooms (Psilocybe cubensis). It is classified as a Class I Psychoactive Substance due to its psychoactive properties. Recent research has suggested that psilocybin holds potential for treating major depressive disorder. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK)...
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 the demand for legitimate pharmaceutical purposes. Here, we report an in vitro approach to biocatalytically produce psilocybin on a solid-phase matrix charged with five co...
Psilocybin, a tryptamine-derived alkaloid, has been granted Breakthrough Therapy designation by the U.S. FDA for treatment-resistant depression, underscoring its clinical importance. Therefore, sustainable and economic production is urgently needed. Manufacturing of psilocybin in Escherichia coli has drawn great attention. However, due to the low expression ...
Background/Objectives: Liver inflammatory diseases are a major global health burden and are often exacerbated by inflammation driven by lipopolysaccharides (LPS) through toll-like receptor 4 signaling. This study evaluates the anti-inflammatory effects of psilocybin and eugenol in an LPS-induced liver inflammation model in C57BL/6J mice. Methods: Mice were t...
As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as pote...
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 ...
Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, p...
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 use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-ad...
Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psiloc...
Neuroinflammation has emerged as a central pathology common to several acute and chronic brain diseases. Recent studies have displayed the anti-inflammatory properties of naturally occurring compounds derived from mushrooms and plants could potentially reduce neuroinflammation and disease progression. In this study, we aimed to investigate the impact of psil...
Psilocybin analogues have been synthesized comprising a non-hydrolysable P-C bond to evaluate the biological activity and the selectivity towards 5-HT2A R, 5-HT2B R and the TNAP receptor.
Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key in...
Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin's general mode of action and (2) AUD-specific alterations of responsivity...
