Psilocybin-induced neurocardiogenic syncope: a case report

Psilocybin is described as one of the serotonergic psychedelics closest to potential FDA approval, with increasing evidence of benefit across psychiatric conditions. At the same time, the authors note that adverse events remain an important part of the safety picture. Most published attention has focused on acute, transient reactions such as headache, nausea, anxiety, dizziness, and elevated blood pressure, whereas hypotensive events are rarely reported. The authors also state that current psychedelic monitoring practices emphasise cardiovascular checks mainly because of concern about hypertension rather than low blood pressure or fainting. Against this background, Atiq and colleagues report a case of neurocardiogenic syncope, a brief fainting episode associated with a blood-pressure drop, in a healthy volunteer who received psilocybin during an open-label brain-stimulation and imaging study. The paper aims to document the event, describe the surrounding physiological and contextual factors, and emphasise the importance of recognising both hypertensive and hypotensive adverse events as psilocybin studies expand. It also seeks to place the episode in the context of other emerging reports of loss of consciousness after psilocybin. This is a single-patient case report embedded in a parent clinical trial, so its purpose is descriptive rather than comparative or hypothesis-testing.

The paper is a case report based on a participant enrolled in the open-label Psilocybin Brain Stimulation and Imaging Pilot Study, which investigated psilocybin’s effects on brain function and cognitive control in healthy volunteers using electroencephalography (EEG) during non-invasive transcranial magnetic stimulation (TMS). The participant was a 35-year-old healthy man with a body mass index of 21.6 and no significant medical or psychiatric comorbidities. The extracted text states that the parent-study consent form allowed publication of de-identified participant data, and that separate institutional approval was obtained for the case report. Before dosing, screening tests including a comprehensive metabolic panel, complete blood count, urinalysis, and baseline electrocardiogram were reportedly normal. The participant’s previous psychedelic exposure included LSD once and psilocybin seven times, without significant adverse events; cannabis use was about monthly, and he took only vitamin D supplementation. He had no clear history of epilepsy or syncope. He received 25 mg oral psilocybin. The session appears to have involved seated EEG recording in preparation for TMS, with cardiovascular monitoring throughout. Subjective drug effects were tracked using a 0-5 Likert scale, and acute subjective effects were also assessed with the brief mystical experience questionnaire (MEQ-4). The report focuses on the timing of symptoms, vital signs around the syncopal event, and recovery over the remainder of the session and subsequent aftercare visits. No formal statistical analysis is described, which is consistent with a single-patient report.

Initial subjective effects were noted about 18 minutes after dosing. By 30 minutes, the participant remained stable despite stronger drug effects. At around 50 minutes, he asked to use the bathroom and was briefly escorted out of the room. Approximately 60 minutes after dosing, shortly after returning and one minute into an eye-open resting-state EEG before the first TMS block, he said he felt as though he was “passing out” and then had a brief loss of consciousness with loss of postural tone. The episode lasted less than a minute. On recovery, he was drowsy and had cold, clammy hands and dry oral mucosa. Immediate supportive measures included leg elevation, verbal reassurance, and oral hydration. Blood pressure immediately after the episode was 93/51 mmHg with heart rate 105 bpm, and capillary refill was adequate. Five minutes later, blood pressure had risen to 108/60 mmHg, and it continued to stabilise over the next 30 minutes. Mydriasis was present. Over the following half-hour, he became progressively more alert and able to follow instructions, and no further cardiovascular abnormalities occurred during the rest of the session. The participant described the experience as challenging and emotionally intense, which was also noted during subsequent aftercare. He wished to continue with TMS-EEG, and apart from two stimulation blocks omitted during the syncopal event, the protocol was completed as planned. The paper also states that the brief mystical experience questionnaire data are shown in a figure, but the extracted text does not provide the numerical scores. The authors interpret the event as neurocardiogenic syncope associated with hypotension during psilocybin administration. They note contextual contributors such as upright seated posture, restrictive EEG equipment, and anticipatory anxiety about TMS.

The authors argue that this case shows a rare hypotensive adverse event during psilocybin administration and expands the safety profile beyond the more commonly discussed hypertensive reactions. They suggest that intense emotional arousal during the onset and peak of psilocybin effects may have contributed to autonomic changes that predisposed the participant to neurocardiogenic syncope. They also emphasise that the setting likely mattered: the participant was seated upright rather than lying supine, wearing EEG equipment, and anticipating TMS, all of which may have increased arousal and reduced tolerance to the episode. Atiq and colleagues state that isolated neurocardiogenic syncope is usually benign and rapidly reversible, but they highlight the practical risk of falls and related injury when loss of consciousness occurs. They compare this case with another recent psilocybin-related loss-of-consciousness event that required emergency department care, noting differences in posture, clinical features, and severity. They also mention preliminary unpublished phase III COMP360 data suggesting that a syncopal episode may have occurred there too, implying that hypotensive events may not be unique to one site or protocol. Recreational reports of loss of consciousness after psilocybin ingestion are also cited as consistent with the possibility that this phenomenon exists outside formal trials. A major limitation the authors discuss is the broader weakness of adverse-event reporting in psychedelic research: they state that fewer than one-quarter of contemporary clinical studies systematically assess adverse events. They therefore call for careful, transparent documentation of both physiological and psychological reactions, particularly as psilocybin and other serotonergic psychedelics such as DMT and 5-MeO-DMT move further into clinical testing. The paper’s implication is that cardiovascular monitoring should include vigilance for hypotension and syncope, not only hypertension.