Psilocybin is increasingly studied as a therapeutic for psychiatric and neurologic conditions, yet comprehensive cardiovascular safety data are limited. Current trials often exclude individuals with blood pressure >140/90 mmHg, criteria established conservatively without robust empirical support. Objective: Characterize the blood pressure and heart rate response to typical therapeutic doses of psilocybin and provide an evidence base for cardiovascular eligibility criteria and monitoring protocols for future clinical trials and emerging therapeutic practice. Methods: We pooled data from 536 psilocybin sessions (oral doses 20-47 mg) among 368 participants across 14 studies at Johns Hopkins University since 1999. Blood pressure and heart rate were measured at baseline and at least hourly up to 360 minutes post-administration. We quantified peak changes, threshold excursions, and excursion duration. Results: Psilocybin produced modest, transient blood pressure elevations. Median peak systolic blood pressure (SBP) was 145 mmHg (IQR 134-156), representing a median increase of 22 mmHg from baseline. Blood pressure peaked at approximately 90 minutes and returned to near-baseline by 300 minutes. SBP exceeded 170 mmHg in 32 sessions (6.0%; median duration 8.5 minutes) and 180 mmHg in 17 sessions (3.2%; median duration 10 minutes). Antihypertensive medication was administered in only 1 session (0.2%). Higher baseline blood pressure was associated with smaller increases, suggesting a ceiling effect rather than exaggerated response. Conclusions: Psilocybin produces modest, transient blood pressure elevations comparable to moderate exercise.

Current exclusion criteria of >140/90 mmHg are not supported by these data. We propose broadening eligibility to <160/100 mmHg while maintaining exclusions for established cardiovascular disease.