Metabolism of lysergic acid diethylamide (LSD): an update

Introduction

Hallucinogens are psychoactive substances that produce altered perception, thought, and feeling at low doses without strong psychomotor stimulation. The introduction describes chemical classification (phenethylamines and tryptamines, which include ergolines such as LSD), typical acute somatic and perceptual effects, and rarer longer-term phenomena such as transient flashbacks and Hallucinogen Persisting Perception Disorder (HPPD). Unlike many other abused drugs, these compounds are generally considered to have low physiological toxicity and low dependence potential. Lysergic acid diethylamide (LSD) is presented as the prototypical ergoline, synthesised by Hofmann, highly potent at cortical 5-HT2A receptors, historically used experimentally and recreationally, and subject to renewed therapeutic interest for conditions including addiction, anxiety and depression. Filipe and colleagues state that the pharmacology of LSD remains incompletely characterised and that metabolic knowledge in humans is limited. The review therefore aims to compile and discuss available data on LSD metabolism, its metabolites, and the clinical and forensic relevance of those metabolites, emphasising gaps that warrant further research.