In-silico toxicity study of tryptamine, psilocin, psilocybin, N,N-dimethyltryptamine, 5'-methoxy-N,N-dimethyltryptamine and O-acetylpsilocin.
Kamil Jurowski, Damian Kobylarz, Maciej Noga
Archives of toxicology March 31, 2026 Peer reviewed DOI: 10.1007/s00204-026-04365-4 via PubMed
Summary
A comprehensive in silico assessment of six serotonergic tryptamines revealed that all compounds are classified as Cramer Class III, indicating high toxicological concern. Predicted oral LD50 values were between 100-500 mg/kg, suggesting moderate to high acute toxicity. The cardiovascular and gastrointestinal systems were identified as primary targets for toxicity. DMT and 5-MeO-DMT showed significant potential for cardiotoxicity, while psilocybin presented a lower risk. Most compounds were predicted to be non-mutagenic and non-endocrine active.
Study at a glance
| Design | computational study |
|---|---|
| Population | six tryptamines of clinical and forensic interest |
| Key finding | All assessed tryptamines were classified as having high toxicological concern, with predicted oral LD50 values indicating moderate to high acute toxicity. |
Abstract
Understanding the toxicity of serotonergic tryptamines is becoming increasingly important from both clinical and forensic perspectives, yet experimental data for these compounds remain extremely limited. Despite their growing medical relevance and widespread non-medical use, there is still no systematic evaluation of their toxicological risks. This study presents the first comprehensive in silico assessment of key toxicological endpoints for six tryptamines of clinical and forensic interest: tryptamine, psilocin, psilocybin (4-PO-DMT),N, N-dimethyltryptamine (DMT), 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT),and O-acetylpsilocin (4-AcO-DMT). A multi-model computational approach was applied using STopTox, admetSAR 3.0, ADMETlab 3.0, ACD/Labs Percepta, Toxtree, ProTox 3.0, OCHEM, TEST, and VEGA QSAR, following OECD principles for QSAR model validation. The study covered acute systemic toxicity (LD50), organ-specific effects, cardiotoxicity (hERG inhibition), genotoxicity (Ames test), irritation potential, and estrogenic activity (ER-α binding). All compounds were classified as Cramer Class III (high toxicological concern). Predicted oral LD50 values were in the 100-500 mg/kg range, indicating moderate to high acute toxicity. Cardiovascular and gastrointestinal systems were consistently identified as primary targets (predicted effect ≥ 90%). DMT and 5-MeO-DMT showed the highest predicted hERG inhibition (20 < IC50 < 45 µM), suggesting possible cardiotoxic potential, while psilocybin demonstrated lower risk (IC50 ≈ 760 µM). Most tryptamines were predicted to be non-mutagenic and non-endocrine active (LogRBA < - 3).