Psilocybin-induced reduction in chronic cluster headache attack frequency correlates with changes in hypothalamic functional connectivity
M. Madsen, Anja Sofie Petersen, Dea Siggaard Stenbæk, Inger Marie Sørensen, Harald Schiønning, Tobias Fjeld, Charlotte H. Nykjær, Sara Marie Ulv Larsen, Maria Zofia Grzywacz, Tobias Mathiesen, Ida L. Klausen, Oliver Overgaard-Hansen, Kristoffer Brendstrup‐brix, Kristían Línnet, Sys Stybe Johansen, Patrick M. Fisher, Rigmor Jensen, Gitte M. Knudsen
medRxiv July 10, 2022 preprint DOI: 10.1101/2022.07.10.22277414 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label clinical trial |
|---|---|
| Population | Patients with chronic cluster headache |
| Intervention | Psilocybin |
| Dose | three low-to-moderate doses |
| Topics | Psilocybin |
| Keywords | Cluster headache Adverse effect Pathophysiology Functional connectivity Functional impairment Clinical trial Anesthesia |
| Citations | 5 |
| Registration | NCT04280055 |
| Key findings | Three low-to-moderate doses of psilocybin reduced attack frequency by an average of 30% and were well-tolerated, with changes in hypothalamic-diencephalic functional connectivity linked to treatment response. |
Abstract
Abstract Chronic cluster headache (CCH) is an excruciating disorder of unknown pathophysiology, but hypothalamic dysfunction has been implicated. CCH is difficult to treat but on a case-basis, the psychedelic compound psilocybin is said to have beneficial effects. In this first-ever clinical trial ( NCT04280055 ), we evaluate in a small open-label study of CCH patients the feasibility and prophylactic effect of three low-to-moderate doses of psilocybin as well as effects on hypothalamic functional connectivity (FC), using functional magnetic resonance imaging. The treatment was well-tolerated and without serious adverse reactions. Attack frequency was on average reduced by 30% from baseline to follow-up (P FWER =0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic-diencephalic FC correlated negatively with relative reduction in attack frequency, implicating this neural pathway in treatment response. Further clinical studies are warranted to confirm the safety and prophylactic efficacy of psilocybin for CCH and hypothalamic involvement in treatment response.
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |
Citations in the library
Cited by 5
- Psilocybin modulation of time-varying functional connectivity is associated with plasma psilocin and subjective effects Neuroimage October 27, 2022
- Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon Cancers April 27, 2024
- Psilocybin and chronic neuropathic pain: a systematic review Regional Anesthesia & Pain Medicine August 5, 2024
- Adapting psychedelic medicine for headache and chronic pain disorders. Expert Review of Neurotherapeutics 2023
- Potential therapeutic effects of psychedelics in small doses: Is there a role for microdosing in psychiatry? International review of neurobiology 2025
Cites 13
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Psychedelics as Medicines: An Emerging New Paradigm Clinical Pharmacology & Therapeutics November 4, 2016
- Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers Biological Psychiatry April 26, 2014
and 8 more in the library