Archives of toxicologyMar 31, 2026

Predicted toxicity of LSD-like psychedelics 1-acetyl-LSD, 1-propionyl-LSD, 1-butyryl-LSD, 1-valeryl-LSD, and 1-cyclopropylmethanoyl-LSD using computer-based methods for clinical and forensic use

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

In silico toxicity models suggest N-1-acyl LSD derivatives may differ in cardiopulmonary, hematologic, and genotoxic risk patterns.

Evidence

This multi-platform in silico toxicology assessment modeled ALD-52, 1P-LSD, 1B-LSD, 1V-LSD, and 1cP-LSD, predicting rat LD50 values of 49-85 mg/kg plus organ-specific, genotoxicity, hERG, irritation, and exposure-route endpoints.

Caveat

The findings are computational predictions with some discordant outputs, including genotoxicity alerts for ALD-52 and 1cP-LSD while OCHEM classified all compounds as non-mutagenic.

Simplified

Lysergamide analogs such as ALD-52, 1P-LSD, 1B-LSD, 1 V-LSD, and 1cP-LSD have emerged as new psychoactive substances (NPS) with hallucinogenic potential, yet their toxicological profiles remain largely unexplored. In this study, a comprehensive in silico assessment was conducted using multiple platforms (e.g., ADMETlab 3.0, Percepta, STopTox, ProTox 3.0, VEGA, TEST 5.1.2) to predict critical toxicological parameters relevant to clinical and forensic toxicology. Acute toxicity was predicted for all compounds, with LDvalues in rats ranging from 49 to 85 mg/kg (Percepta) and oral/inhalation exposure identified as the most concerning routes. Organ-specific toxicity highlighted elevated pulmonary risk for 1 V-LSD (92%) and 1cP-LSD (81%), and highest predicted hematotoxicity for 1P-LSD (76%) and 1B-LSD (75%). Genotoxicity alerts were consistently identified for ALD-52 and 1cP-LSD (up to 90% predicted probability, Percepta), while OCHEM classified all compounds as non-mutagenic. Cardiotoxicity assessment revealed the strongest hERG channel inhibition for 1 V-LSD (IC = 1.4 µM, Percepta), suggesting elevated proarrhythmic potential. Dermal and ocular irritation risks were uniformly low across platforms. The results support that structural modifications at the N-1-acyl position influence toxicity patterns, particularly affecting cardiopulmonary and genotoxic endpoints. These findings underscore the utility of in silico methods for early risk assessment and prioritization of lysergamide-based NPS for further toxicological evaluation. 50 50