Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins

Introduction

Microdosing — the intermittent ingestion of sub‑threshold doses of psychedelics such as lysergic acid diethylamide (LSD), psilocybin or, less commonly, MDMA — has become increasingly popular and is reported by an estimated 17% of a surveyed sample of drug and alcohol users. While single high doses or infrequent administration of serotonergic psychedelics are generally considered physically safe, concern arises because certain medications that are chemically similar to psychedelics (for example, methysergide, pergolide, fenfluramine) have been associated with cardiac fibrosis and valvular heart disease (VHD) after chronic use. The existing microdosing literature is sparse: few double‑blind, placebo‑controlled trials exist, many studies have small samples, and evidence for benefits is mixed, leaving the long‑term cardiovascular safety of repeated low‑dose use uncertain. Rouaud and colleagues set out to examine whether chronic microdosing could plausibly increase the risk of cardiac fibrosis and valvulopathy by comparing the pharmacology and empirical evidence for psychedelics with that for established cardiotoxins. The review focuses on the role of the 5‑HT2B receptor in drug‑induced VHD, compares receptor affinity and functional activity across compounds, and makes recommendations for how future microdosing studies and surveillance could assess and mitigate potential cardiac risks.