Effects of psilocybin on sleep quality and brain microstructure in chronic cluster headache

This was a small mechanistic study of 11 patients with chronic cluster headache (CCH) who received three psilocybin doses (0.14 mg/kg) one week apart. Researchers assessed sleep quality and diffusion MRI measures of brain microstructure before and after treatment and compared baseline findings with 24 healthy controls. The researchers found that a short course of psilocybin improved sleep quality in patients with chronic cluster headache, but the study found no clear evidence of significant brain microstructural changes over the same period. The MRI findings suggest possible biological effects that warrant investigation in larger studies.

Abstract

Background:

Patients with chronic cluster headache (CCH) suffer from poor sleep, which may impact their brain microstructure and parenchymal clearance of waste products. Psilocybin has shown promise for the treatment of CCH and has been linked to increased neuroplasticity with possible influences on brain microstructure.

Aims:

To investigate the effects of psilocybin on sleep, brain water diffusivity, and microstructure in CCH.

Methods:

Eleven CCH patients underwent diffusion-weighted MRI and subjective sleep quality assessment with the Pittsburgh Sleep Quality Index (PSQI) before and 1 week after three psilocybin administrations (0.14 mg/kg) spaced 1 week apart. Measures taken prior to intervention were also compared to 24 healthy controls, and subjective sleep quality was related to brain microstructure and diffusivity across groups.

Results:

We found that sleep was poor in CCH patients, but improved after psilocybin treatment (CCH mean PSQI change (SD) = –2.50 (2.1), pFWER = 0.015). When analyzing brain microstructure and water diffusivity in conjunction, we found differences between CCH patients and controls, which were primarily driven by differences in grey matter. On average, psilocybin intervention in CCH patients was not associated with statistically significant changes in brain microstructure or water diffusivity. However, most patients exhibited lower white matter diffusivity and neurite volume after intervention. Subjective sleep quality showed borderline significant correlations of moderate effect size with brain microstructure and water diffusivity.

Conclusion:

Subjective sleep quality improved in CCH patients after psilocybin and showed some evidence of an association with measures of brain microstructure and water diffusivity.

Brendstrup-Brix K, Ozenne B, Fisher PM, et al. Effects of psilocybin on sleep quality and brain microstructure in chronic cluster headache. Journal of Psychopharmacology. 2026;0(0). Read Paper

For more psychedelic news and research, visit the psychedelic health professional network homepage.