Archives of toxicologyMar 31, 2026

Computer-based toxicity study of tryptamine and related psychedelic compounds

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

All six assessed tryptamines were classified as Cramer Class III, indicating high toxicological concern.

Predicted oral LD values for the tryptamines were in the 100-500 mg/kg range, suggesting moderate to high acute toxicity.
The cardiovascular and gastrointestinal systems were identified as primary targets for toxicity, with predicted effects greater than 90%.
DMT and 5-MeO-DMT exhibited the highest predicted cardiotoxic potential, with hERG inhibition values between 20 and 45 µM.
Psilocybin showed a lower predicted risk for cardiotoxicity, with an IC value around 760 µM.
Most tryptamines were predicted to be non-mutagenic and non-endocrine active, indicated by LogRBA values less than -3.

Simplified

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 (LD), 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 LDvalues 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 < IC < 45 µM), suggesting possible cardiotoxic potential, while psilocybin demonstrated lower risk (IC ≈ 760 µM). Most tryptamines were predicted to be non-mutagenic and non-endocrine active (LogRBA < - 3). 50 50 50 50

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Computer-based toxicity study of tryptamine and related psychedelic compounds

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