Acute Cardiovascular Effects of Psilocybin: A Pooled Analysis of 14 Studies with Safety Recommendations

Background 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. ### Competing Interest Statement SMN has consulted for Resilient Pharmaceuticals and MMS Holdings. BW owns Axial Therapeutic Research, a company investigating the safety and effectiveness of alternative treatments for military veteran health. DBY has personally received a consulting fee from Soneira and speaking fees from Integrative Psychiatry Institute. AGR has served as a board member/advisor to Psyence Biomedical. BSB holds stock options for CB Therapeutics and has previously held stock in AtaiBeckley Inc and GH Research in the past three years. In the past three years he has served or currently serves as an advisor for AbbVie, CB Therapeutics, GH Research, Livanova, Janssen Pharmaceuticals (Johnson & Johnson), and MindMed (Definium Therapeutics). He also receives monetary compensation for editorial work from DynaMed Plus (EBSCO Industries, Inc) and speaker's fees from Toronto-Dominion Bank. FSB has consulted for MindState Design Labs LLC, Wavepaths Ltd, and Gilgamesh Pharmaceuticals Inc. ### Funding Statement The Center for Psychedelic and Consciousness Research is supported by Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation. SMN, DBY, and BW have received funding from the Gracias Family Foundation. SMN and BW have received funding from Reason for Hope and Fifth Generation. BSB receives research support from Abbott Laboratories, Compass Pathways, Definium Therapeutics, and Reunion Neuroscience. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Johns Hopkins Medicine IRB approved this analysis (IRB00548489) via expedited review. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified data from this pooled analysis are available from the corresponding author upon reasonable request, subject to a data use agreement and institutional review board approval at the requesting institution. Data from individual studies remain subject to the data sharing policies of the original study protocols.