Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers
This double-blind placebo-controlled study (n=18) found that psilocybin (5-30mg/70kg) frequently caused mild to moderate delayed and transient headaches in healthy volunteers in a dose-dependent manner.
Authors
- Roland Griffiths
- Matthew Johnson
- Andrew Sewell
Published
Abstract
Background
Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache.
Methods
This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30. mg/70. kg) on headache in 18 healthy participants.
Results
Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration.
Conclusions
Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research.
Research Summary of 'Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers'
Introduction
Classic hallucinogens such as psilocybin produce psychoactive effects largely via 5-HT2A receptor agonism and have a long history of ritual and recreational use. Earlier clinical reports and case series have intermittently noted headache following administration of classic psychedelics, and some small studies and reviews suggested a dose-related occurrence of head pain after psilocybin, but these observations were generally retrospective, inconsistent, or not systematically characterised. At the same time, several tryptamine-based and indole compounds are used in acute and prophylactic headache management, and anecdotal reports and case series have raised the possibility that psilocybin or related compounds might both provoke and, paradoxically, treat certain primary headache syndromes such as cluster headache. Johnson and colleagues designed the present study to prospectively and systematically characterise headache as an adverse event after controlled psilocybin administration. The investigators aimed to examine whether headache incidence, timing, duration and severity were dose-dependent across a broad range of oral psilocybin doses in medically and psychiatrically healthy volunteers, and to explore relationships between headache and other measured drug effects and physiological responses.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Create a free account to open full-text PDFs.
Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Johnson, M. W., Andrew Sewell, R., & Griffiths, R. R. (2012). Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug and Alcohol Dependence, 123(1-3), 132-140. https://doi.org/10.1016/j.drugalcdep.2011.10.029
References (12)
Papers cited by this study that are also in Blossom
Carter, O., Burr, D. C., Pettigrew, J. D. et al. · Journal of Cognitive Neuroscience (2006)
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Psychopharmacology (2011)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Hasler, F., Grimberg, U., Benz, M. A. et al. · Psychopharmacology (2004)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)
Karst, M., Halpern, J. H., Bernateck, M. et al. · Cephalalgia (2010)
Passie, T., Seifert, J., Schneider, U. et al. · Addiction Biology (2002)
Sewell, R. A. · Neurology (2006)
Studerus, E., Kometer, M., Hasler, F. et al. · Journal of Psychopharmacology (2010)
Show all 12 referencesShow fewer
Vollenweider, F. X., Leenders, K. L., Maguire, P. et al. · Neuropsychopharmacology (1997)
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)
Cited By (24)
Papers in Blossom that reference this study
Straumann, I., Holze, F., Becker, A. M. et al. · Neuroscience Applied (2024)
Nicholas, C. R., Horton, D. M., Malicki, J. et al. · Psychedelic Medicine (2023)
Breeksema, J. J., Kuin, B. W., Kamphuis, J. et al. · Journal of Psychopharmacology (2022)
Balaet, M. · Frontiers in Neuroscience (2022)
Sekula, A. D., Downey, L., Puspanathan, P. · Frontiers in Psychology (2022)
Elman, I., Borsook, D., Pustilink, A. · Neuroscience and Biobehavioral Reviews (2022)
Strickland, J. C., Johnson, M. W. · Advances in Pharmacology (2022)
Carhart-Harris, R. L., Giribaldi, B., Watts, R. et al. · New England Journal of Medicine (2021)
Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)
Chi, T., Gold, J. A. · Journal of the Neurological Sciences (2020)
Show all 24 papersShow fewer
Reiff, C. M., Richman, E. E., Nemeroff, C. B. et al. · American Journal of Psychiatry (2020)
Family, N., Maillet, E. L., Williams, L. T. J. et al. · Psychopharmacology (2019)
Anderson, T., Petranker, R., Christopher, A. et al. · Harm Reduction Journal (2019)
Johnson, M. W., Hendricks, P. S., Barrett, F. S. et al. · Pharmacology and Therapeutics (2019)
Schenberg, E. E. · Frontiers in Pharmacology (2018)
Johnson, M. W., Griffiths, R. R., Hendricks, P. S. et al. · Neuropharmacology (2018)
Andersson, M., Persson, M., Kjellgren, A. · Harm Reduction Journal (2017)
Brown, R. T., Nicholas, C. R., Cozzi, N. V. et al. · Clinical Pharmacokinetics (2017)
Garcia-Romeu, A., Kersgaard, B., Addy, P. H. · Experimental and Clinical Psychopharmacology (2016)
Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
Nichols, D. E. · Pharmacological Reviews (2016)
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Litjens, R. P. W., Brunt, T. M., Alderliefste, G. et al. · European Neuropsychopharmacology (2014)
Blough, B. E., Landavazo, A., Decker, A. M. et al. · Psychopharmacology (2014)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.