Psilocybin-induced neurocardiogenic syncope: a case report

Psilocybin is among the serotonergic psychedelics closest to potential FDA approval, with growing evidence of therapeutic benefit across psychiatric conditions. As clinical trials expand, systematic characterization of adverse events (AEs) remains essential. While transient hypertensive responses are well documented, hypotensive events such as neurocardiogenic syncope (NCS) are rarely reported.

We describe a healthy 35‑year‑old male enrolled in an open‑label study investigating psilocybin‑evoked changes in brain function during transcranial magnetic stimulation and electroencephalography (TMS‑EEG). Approximately 60 minutes after receiving 25 mg oral psilocybin, and shortly after initiation of an eye‑open resting‑state EEG, he experienced prodromal lightheadedness followed by a brief loss of consciousness and postural tone. Immediate blood pressure was 93/51 mmHg with tachycardia and diaphoresis. Supportive measures, including leg elevation and oral hydration, led to rapid stabilization, and no further cardiovascular abnormalities occurred. The participant reported an emotionally intense experience, and contextual factors - including upright seated posture, restrictive EEG equipment, and anticipatory anxiety surrounding TMS - may have contributed to heightened autonomic arousal and susceptibility to NCS.

This case highlights a rare hypotensive AE during psilocybin administration and underscores the importance of vigilant cardiovascular monitoring, particularly during procedures that may amplify emotional arousal. Given that fewer than one‑quarter of contemporary psychedelic trials report systematic AE assessment, transparent documentation of both hypertensive and hypotensive events is critical for defining psilocybin's safety profile as clinical applications expand.

Open Label Psilocybin Brain Stimulation and Imaging Pilot Study; ClinicalTrials.gov: NCT06835699. Date registered: 02/13/2025. The parent‑study consent form explicitly permits publication of de‑identified participant data, and separate institutional approval for this case report was obtained (IRB00543773).