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 ...
Psilocin is a psychedelic indole alkaloid and one of the major human metabolites of its phosphorylated precursor, psilocybin. Psilocin binds to the serotonin receptor, 5-HT2A, and dose-dependently induces hallucinogenic effects stronger than psilocybin. As a result, psilocin has been a drug of interest in the analytical toxicology community for years. In viv...
PsiConnect is a large-scale neuroimaging study designed to investigate context-dependent neural and subjective effects of psilocybin using multimodal neuroimaging. It combines functional, structural, and diffusion-weighted MRI with EEG to examine brain activity in 62 participants before and after a 19 mg dose of psilocybin. The design includes resting-state ...
Serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) show therapeutic promise for psychiatric and neurodegenerative disorders but may be limited by liabilities from serotonin (5-HT)-2A mediated psychoactive effects and potential cardiotoxicity via 5-HT2B activation. To address these limitation...
Background: Psilocybe cubensis mushrooms contain the tryptamines psilocybin and psilocin, which are recognized for their therapeutic potential in mental health [1]. Additionally, due to their psychedelic effects, these mushrooms are also used for religious and recreational purposes. The increasing use of these tryptamines and other psychoactive substances ha...
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a...
BackgroundPsychedelics such as lysergic acid diethylamide (LSD) and psilocybin have shown a beneficial effect on substance use disorder (SUD) symptoms. In this systematic review, we aimed to assess the efficacy and safety of psychoactive tryptamines in patients with an SUD or non-substance-related disorder (i.e., gambling disorder) in order to provide a comp...
Psilocybin is a psychoactive tryptamine produced by a phylogenetically discontinuous yet ecologically diverse subset of fungi. Despite decades of chemical, pharmacological, and ethnobiological research, the evolutionary forces driving the emergence and persistence of this compound remain insufficiently explained. Recent hypotheses proposing that psilocybin e...
Novel psychoactive substances (NPS) remain an ongoing challenge for public health, forensic laboratories, and regulatory agencies, especially when they are chemically related to controlled tryptamines but are marketed as legal alternatives. In the United States, the Federal Analogue Act (FAA) was intended to restrict such substances; however, regulatory loop...
Psychedelics are a group of substances within the heterogeneous class of hallucinogenic drugs. Via binding to the serotonin (5-HT) 2A receptor, psychedelics exert profound alterations in various mental domains, including sensation, cognition, emotions, and self-perception. Psychedelics comprise phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin...
Psychedelic mushrooms of the Psilocybe genus contain the psychoactive tryptamines psilocybin and psilocin, compounds currently under clinical investigation for the treatment of depression and other psychiatric conditions. However, the accurate quantification of these alkaloids in fungal matrices remains analytically challenging. Here, we report an optimized ...
High Resolution Image Download MS PowerPoint Slide Psychedelic mushrooms of the Psilocybe genus contain the psychoactive tryptamines psilocybin and psilocin, compounds currently under clinical investigation for the treatment of depression and other psychiatric conditions. However, the accurate quantification of these alkaloids in fungal matrices remains anal...
Importance: Psilocybin use has surged in the US following decriminalization efforts and promising clinical trial results. Mirroring early cannabis legalization, public access and enthusiasm are outpacing regulatory oversight and scientific understanding, posing potential risks to public health. Objective: To review emerging evidence on the public health impl...
BackgroundOver the past ten years, several psychedelic compounds, including tryptamines like lysergic acid diethylamide/LSD, psilocybin, ayahuasca, and dimethyltryptamine/DMT, have been tested in clinical trials for a range of psychiatric conditions, such as anxiety and depression. While these compounds are relatively available for treatment, ketamine and it...
Novel phenalkylamines and tryptamines such as psilocybin demonstrate promising nontraditional pharmacological profiles for treating psychiatric syndromes. Structural modifications yield functional selectivity at 5-HT receptors, mitigating hallucinogenic risk while preserving therapeutic efficacy. This study integrates receptor and behavioral data to support ...
The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT2A serotonin receptor (5-HT2AR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety,...
ABSTRACT Acyloxymethyl (ACOM) derivatives of tryptamines such as the psychedelic drug psilocin and the anti-migraine drug sumatriptan bear potential as prodrugs. Previous synthetic approaches suffer from insufficient chemoselectivity between the desired functionalization of the phenolic (psilocin) or sulfonamide (sumatriptan) groups versus other reactive gro...
ABSTRACT Three novel 14 C-labelled isotopologues of the psychoactive agents psilocin, psilocybin and 5-methoxy- N, N -dimethyltryptamine (5-MeO-DMT) were synthesised, all labelled at the 2-position of the indole. The syntheses involved incorporating the 3-dimethylaminoethyl substituent common to all three substances onto a 4- or 5-substituted indole intermed...
Mental health disorders and associated economic impact continue to rise domestically and globally. In 2023, to expand treatment options for individuals suffering Treatment Resistant Depression (TRD), the Therapeutic Goods Administration (TGA) of Australia has permitted psychiatrist lead psilocybin-assisted psychotherapy. Psilocybin, a psychedelic tryptamine ...
