Across 18,499,626 FDA Adverse Event Reporting System cases from 2000–2024, two psychoactive substances stand out for cardiac danger: ibogaine posted a proportional reporting ratio (PRR) of 142.0 for ventricular arrhythmia alone — roughly six times higher than dofetilide, a drug already carrying a black-box warning for arrhythmia — while kratom's active alkaloid mitragynine showed a PRR of 4.4 for ventricular arrhythmia and 15.9 for QTc prolongation, comparable to methadone's well-established cardiac profile. MDMA showed QTc-prolongation signal (PRR 9.9) but not isolated ventricular arrhythmia. Psilocybin, DMT, mescaline, and THC generated no significant arrhythmia signals.
The timing matters enormously. A recent executive order accelerating psychedelic drug development and FDA review has created regulatory momentum that could outpace safety science. This pharmacovigilance analysis, while far from definitive, injects essential cardiovascular caution into that conversation. Ibogaine is already being explored in clinical trials for opioid addiction, and kratom is sold over-the-counter in many U.S. states with minimal oversight. Critical limitations apply: FAERS data are self-reported, subject to confounding by polypharmacy and unreported comorbidities, and cannot establish causation. Effect sizes from small report counts — ibogaine had only 25 total reports — warrant cautious interpretation. As a preprint not yet peer-reviewed, these findings may change upon formal scrutiny. Still, the ibogaine signal is striking enough that cardiac screening protocols deserve serious consideration before any broader clinical rollout.