Effect of oral tryptamines on the gut microbiome of rats—a preliminary study
PeerJ – June 03, 2024
Source: OpenAlex
Summary
Psilocybin, a key compound in Psychedelics and Drug Studies, significantly alters the gut microbiome, suggesting a novel biological pathway for its antidepressant effects. In a pharmacology investigation, male rats given oral psililocybin (0.2 or 2 mg/kg) showed dose- and time-dependent changes in gut bacteria 1 and 3 weeks later. Specifically, Actinobacteria increased, while Proteobacteria decreased, impacting gut microbiota and health. This suggests tryptamines might influence mental health via the microbiome, a new frontier in medicine for conditions linked to tryptophan and brain disorders.
Abstract
Background Psilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota. Methods To address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition. Results We found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in Verrucomicrobia and Actinobacteria , and decreases in Proteobacteria . Conclusion and Implications These preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.