A Novel Therapeutic Approach to Improving Quality of Life and Performance in Athletes and Other Patients with Cluster Headache
DOI:
https://doi.org/10.12775/QS.2026.67.74296Keywords
CH, cluster headache, headache, psilocybin, classic psychedelics, athletesAbstract
Background: Cluster headache is a severely disabling headache disorder. Despite the availability of acute and preventive therapies, treatment efficacy remains incomplete, leaving many athletes and other patients with insufficient symptom control leading to decreased quality of life and performance. Increasing interest has emerged in psychedelic compounds, particularly psilocybin, as potential therapeutic agents.
Aim: This narrative review aimed to evaluate the current evidence regarding psilocybin in the treatment of cluster headache.
Material and Methods: A literature search was conducted in the MEDLINE database to identify publications describing psilocybin use in cluster headache. Eight relevant publications were identified.
Results: Clinical evidence remains limited but suggests potential therapeutic benefit. A randomized placebo-controlled trial demonstrated numerically higher response rates with psilocybin compared to placebo, although statistical significance was not achieved. An open-label study reported a mean reduction in attack frequency and identified changes in hypothalamic–diencephalic functional connectivity associated with clinical improvement. Observational studies consistently reported high patient-perceived efficacy for both abortive and preventive use, often exceeding satisfaction reported with conventional therapies. However, interpretation is limited by methodological constraints. Available data suggest a generally favorable safety profile, though psychological adverse effects may occur and long-term safety remains uncertain.
Conclusions: Current evidence indicates a signal of therapeutic potential for psilocybin in cluster headache, particularly in preventive treatment, but remains insufficient for definitive clinical conclusions. Well-designed randomized controlled trials with standardized protocols are urgently needed to clarify efficacy, safety, and optimal therapeutic frameworks.
References
[1] Lund NLT, Petersen AS, Fronczek R, Tfelt-Hansen J, Belin AC, Meisingset T, Tronvik E, Steinberg A, Gaul C, Jensen RH. Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments-a consensus article. J Headache Pain. 2023 Sep 4;24(1):121. https://doi.org/10.1186/s10194-023-01660-8
[2] Diener HC, May A. Drug Treatment of Cluster Headache. Drugs. 2022 Jan;82(1):33-42. https://doi.org/10.1007/s40265-021-01658-z
[3] Schindler EAD. Psychedelics in the Treatment of Headache and Chronic Pain Disorders. Curr Top Behav Neurosci. 2022;56:261-285. https://doi.org/10.1007/7854_2022_365
[4] Aurora SK. Etiology and pathogenesis of cluster headache. Curr Pain Headache Rep. 2002 Feb;6(1):71-5. https://doi.org/10.1007/s11916-002-0027-4
[5] Raskin NH. Serotonin receptors and headache. N Engl J Med. 1991 Aug 1;325(5):353-4. https://doi.org/10.1056/NEJM199108013250509
[6] Garfinkel, D. Headache in Athletes, The Physician and Sportsmedicine 1983 Jan;11:1, 67-76. https://doi.org/10.1080/00913847.1983.11708435
[7] Guidry, A. Crutchfield, K. Athletes with neurologic disease. Handbook of Clinical Neurology, Vol. 158 (3rd series) Sports Neurology. 2018;158:445-462. https://doi.org/10.1016/B978-0-444-63954-7.00041-0
[8] Thal, K. Mayes, C. Headache in the Athlete. Neurol Clin. 2026 Aug;44 (3): 365-379 . https://doi.org/10.1016/j.ncl.2026.03.003
[9] Burns, KN. Langford, TD. Tierney, R. McDevitt, J. Premorbid Primary Headache and Vestibular and Oculomotor Baseline Assessments in Collegiate Athletes. Clin J Sport Med. 2022 Sep 1;32(5). https://doi.org/10.1097/jsm.0000000000001002
[10] Lowe, H. Toyang, N. Steele, B. Valentine, H. Grant, J. Ali, A. Ngwa, W. Gordon, L. The Therapeutic Potential of Psilocybin. Molecules 2021, 26, 2948. https://doi.org/10.3390/molecules26102948
[11] Strand NH, Whitney M, Johnson B, Dunn T, Attanti S, Maloney J, Misra L, Gomez D, Viswanath O, Emami E, Leathem J. Pain and Perception: Exploring Psychedelics as Novel Therapeutic Agents in Chronic Pain Management. Curr Pain Headache Rep. 2025 Jan 7;29(1):15. https://doi.org/10.1007/s11916-024-01353-0
[12] Dworkin RH, Anderson BT, Andrews N, Edwards RR, Grob CS, Ross S, Satterthwaite TD, Strain EC. If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics. J Pain. 2022 Oct;23(10):1666-1679. https://doi.org/10.1016/j.jpain.2022.05.003
[13] Schindler EAD. The Potential of Psychedelics for the Treatment of Episodic Migraine. Curr Pain Headache Rep. 2023 Sep;27(9):489-495. https://doi.org/10.1007/s11916-023-01145-y
[14] Schindler EAD, Sewell RA, Gottschalk CH, et al. Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double-blind, placebo-controlled trial. Headache. 2022;00: 1-12. https://doi.org/10.1111/head.14420
[15] Madsen MK, Petersen AS, Stenbaek DS, Sørensen IM, Schiønning H, Fjeld T, Nykjaer CH, Larsen SMU, Grzywacz M, Mathiesen T, Klausen IL, Overgaard-Hansen O, Brendstrup-Brix K, Linnet K, Johansen SS, Fisher PM, Jensen RH, Knudsen GM. CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity. Headache. 2024 Jan;64(1):55-67. https://doi.org/10.1111/head.14656
[16] Sewell RA, Halpern JH, Pope HG Jr. Response of cluster headache to psilocybin and LSD. Neurology. 2006 Jun 27;66(12):1920-2. https://doi.org/10.1212/01.wnl.0000219761.05466.43
[17] Emmanuelle A. D. Schindler M.D., Ph.D., Christopher H. Gottschalk M.D., Marsha J. Weil, Robert E. Shapiro M.D., Douglas A. Wright D.C. & Richard Andrew Sewell M.D. (2015): Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey, Journal of Psychoactive Drugs, https://doi.org/10.1080/02791072.2015.1107664
[18] Smedfors, G.; Jennysdotter Olofsgård, F.; Steinberg, A.; Waldenlind, E.; Ran, C.; Belin, A.C. Use of Prescribed and Non-Prescribed Treatments for Cluster Headache in a Swedish Cohort. Brain Sci. 2024, 14, 348. https://doi.org/10.3390/brainsci14040348
[19] Di Lorenzo C, Coppola G, Di Lorenzo G, Bracaglia M, Rossi P, Pierelli F. The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey. Cephalalgia. 2016 Feb;36(2):194-8. https://doi.org/10.1177/0333102415583145
[20] de Coo IF, Naber WC, Wilbrink LA, Haan J, Ferrari MD, Fronczek R. Increased use of illicit drugs in a Dutch cluster headache population. Cephalalgia. 2019 Apr;39(5):626-634. https://doi.org/10.1177/0333102418804160
[21] Andersson M, Persson M, Kjellgren A. Psychoactive substances as a last resort-a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduct J. 2017 Sep 5;14(1):60. https://doi.org/10.1186/s12954-017-0186-6
[22] Soslau G. Cardiovascular serotonergic system: Evolution, receptors, transporter, and function. J Exp Zool A Ecol Integr Physiol. 2022 Feb;337(2):115-127. https://doi.org/10.1002/jez.2554
[23] Bjurenfalk Z, Cosmo A, Simonsson O, Ran C. Lifetime classic psychedelic use and headaches: A cross-sectional study. J Psychopharmacol. 2025 Sep;39(9):968-975. https://doi.org/10.1177/02698811251324372
[24] Johnson MW, Sewell RA, Griffiths RR. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug Alcohol Depend. 2012 Jun 1;123(1-3):132-40. https://doi.org/10.1016/j.drugalcdep.2011.10.029
[25] Rusanen SS, De S, Schindler EAD, Artto VA, Storvik M. Self-Reported Efficacy of Treatments in Cluster Headache: a Systematic Review of Survey Studies. Curr Pain Headache Rep. 2022 Aug;26(8):623-637. https://doi.org/10.1007/s11916-022-01063-5
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Michał Lewczuk, Natalia Trędota, Zuzanna Czyżewicz, Kinga Dworak, Dominika Posid, Karol Dańda, Aleksandra Chludek, Barbara Chobot, Marta Wachowska, Julia Chmielowiec
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 22
Number of citations: 0
