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Stay up to date with the latest research papers, clinical trials, blog posts, and site updates.
This computational study investigates the membrane permeability of 12 selected tryptamines, aiming to elucidate the impact of various structural modifications on their permeation behaviour. Using classical molecular dynamics simulations and umbrella sampling techniques, the study finds that dimethylation of the primary amine group and methoxy substitution at position 5 increase permeability, while positional substitutions on the indole groups and protonation decrease permeability.
This whole-brain simulation reproduces earlier studies where increased entropy was found under the influence of psychedelics. The changes weren't uniform, with larger effects in the optical area. The changes were not well-explained by looking at where the most serotonin (2a) receptors were but mapped closely to the topological (spatial) properties of how the brain is connected.
This in vitro study investigates the receptor binding profiles of NBOMe drugs compared to their 2C drug analogs and LSD. It finds that NBOMe drugs exhibit high affinity for 5-HT2A receptors, suggesting strong hallucinogenic effects similar to LSD, but with potentially more stimulant properties due to interactions with α1 receptors.
This in vitro study examines 2,5-dimethoxy-4-substituted phenethylamines (PEAs) including 2C-I, 2C-B, 2C-D, and 2C-H analogs, focusing on their receptor interactions. It finds these compounds act as 5-HT2A receptor antagonists, differing in potency based on specific substituents. This suggests their psychostimulant effects may not solely derive from 5-HT2A receptor agonism.
This study (2005) conducted phytochemical analysis on 32 Banisteriopsis caapi samples and 36 samples of Psychotria viridis (ayahuasca brews). All B. caapi samples had detectable amounts of harmine, harmaline and tetrahydroharmine, while some samples of P. viridis minimal detectable levels of DMT.
This receptor profiling study (n=41 compounds) maps the pharmacological activity of classical psychedelics across 318 human G-protein-coupled receptors and, for LSD, over 450 human kinases. It finds that psychedelics act potently at nearly all serotonin, dopamine, and adrenergic receptors, with multiple 5-HT2A receptor signalling pathways linked to psychedelic effects in vivo.
This study inspects how LSD binds to the 5-HT2B (serotonin 2B) receptor (not the 2A receptor most commonly studied) to understand what signalling cascades it triggers. The researchers determined the cryo-EM structures of LSD-bound HTR2B in the transducer-free, Gq-protein-coupled, and β-arrestin-1-coupled states. The information from this study can help with the design of novel psychedelics.
This rodent study suggests that activating serotonin 2A receptors is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. The study also suggests that psychedelic tryptamines can induce hallucinogenic and therapeutic effects through activation of the same receptor. It highlights the need for full mechanistic understanding of how these molecules produce therapeutic effects.
This rodent study (2022) shows that the activation of serotonin receptors (5-HT) by mescaline derivatives via 5-HT2CR, alone or in concert with 5-HT2AR, produces comparable hallucinogenic effects to activation via divergent 5-HT2CR- and/or 5-HT2AR signalling pathways. Given that many believe 5-HT2AR activation is the route through which psychedelics exert their effects, these findings show that 5-HT2CR is as important as 5-HT2AR in inducing these effects.
This mouse model study examines the metabolic efficacy of the psychoactive aminoindane derivative MEAI on diet-induced obesity (DIO). MEAI treatment significantly reduced overweight and adiposity, improved glycemic control, decreased hepatic lipid accumulation, increased energy expenditure and fat utilization, and normalized voluntary locomotion without overstimulatory effects, suggesting its potential as a novel therapeutic approach for obesity and related metabolic disorders.
This pre-print multi-laboratory mouse study (n=~200 mice across five sites) demonstrates that psilocybin (2mg/kg) produces robust acute effects in mice including increased anxiety-related behaviours and decreased fear expression. However, it fails to show consistent persistent therapeutic effects 24 hours after administration, suggesting previous claims about psilocybin's lasting benefits may have been overstated.
This paper describes an analogue to ibogaine (tabernanthalog) with similar therapeutic potential that is non-toxic, and non-psychedelic.