Innov Clin Neurosci. 2025;22(1–3):11–13.

Dear Editor:

I read with interest Lawrence’s article about a 33-year-old male patient with migraine with aura who self-experimented with psilocybin for his migraine attacks, which occurred at a frequency of 2 to 4 attacks per year.¹ At the onset of a migraine attack, he took 1.2g of dried fruiting body of Psilocybe cubensis mushrooms and assessed the intensity of the headache every hour using the Numerical Rating Scale (NRS). Compared to the three previous migraine attacks, which were treated only with common analgesics (ibuprofen, acetaminophen, naproxen), the mushrooms achieved a significant reduction in headache intensity and vomiting episodes. It was concluded that psilocybin has potential for treating migraine but definitively cannot serve as the basis of therapy.¹ The study is impressive, but some points require discussion. 

One limitation of the study is that the patient took psilocybin in the form of mushrooms. Since these mushrooms contain not only psilocybin but several other alkaloids, it cannot be decided with certainty which of the alkaloids was actually effective and useful in this particular case. It cannot be ruled out that the positive effect was due to the combination of psilocybin with conventional analgesics. It is even possible that the common analgesics alone caused the positive effect. Analgesics can have different effectiveness for different migraine attacks.

A second limitation is that the design of the study does not allow general conclusions to be drawn about the effectiveness of a particular treatment. The effect of a medication can only be reliably assessed through a double-blind, placebo-controlled trial. Isolated case reports might indicate a positive effect, but before an active substance is approved for treatment in the general population, evidence of its effectiveness must be provided on more solid basis. 

A third limitation is that the classification of the index patient’s migraine is not adequate.¹ The patient not only suffered from migraine with aura, but also from complicated migraine, as he occasionally reported sensory disturbances in fingers 1 and 2 on the left side and lips. 

A fourth limitation is that no results from imaging studies were reported.¹ Because migraine headaches can be associated with structural² or functional³ imaging abnormalities, it is imperative to report his magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and functional MRI (fMRI) findings. It is also mandatory to report the electroencephalography (EEG) recordings, as migraine can be associated with EEG abnormalities.⁴ 

A fifth limitation is that family history was not reported. Because migraine can occur within families, it is imperative to know whether first-degree relatives of the index patient also suffered from migraines.

We disagree with the assumption that migraine is exclusively a neurovascular disease.¹ Until the pathophysiology and etiology of migraine are fully understood and elucidated, the neurovascular approach remains a theory. However, there is some evidence that migraine is associated with either primary or secondary abnormalities of the cerebral vasculature, as several studies have shown.⁵ 

There is no description of whether psilocybin also had a psychotropic effect in the index patient. Mushrooms are known to have hallucinogenic effects, which is why they are also called “magic” mushrooms. We should know whether there was evidence of such side effects in the index patient. 

In summary, the interesting study has limitations that put the results and their interpretation into perspective. Clarifying these weaknesses would strengthen the conclusions and could improve the study. Until psilocybin has been tested by a properly designed and powered study, it cannot be recommended as a potential treatment for migraine headaches.

With regards,

Josef Finsterer, MD, PhD

Dr. Finsterer is with Neurology & Neurophysiology Center in Vienna, Austria.

Funding/financial disclosures. The author has no conflicts of interest relevant to the content of this letter. No funding was received for the preparation of this letter.

References 

1. Lawrence DW. Self-administration of psilocybin for the acute treatment of migraine: a case report. Innov Clin Neurosci. 2023;20(7–9):37–39. 
2. Xu WJ, Barisano G, Phung D, et al. Structural MRI in migraine: a review of migraine vascular and structural changes in brain parenchyma. J Cent Nerv Syst Dis. 2023;15:11795735231167868. 
3. Messina R, Gollion C, Christensen RH, et al. Functional MRI in migraine. Curr Opin Neurol. 2022;35(3):328–335. 
4. Kim SJ, Yang K, Kim D. Quantitative electroencephalography as a potential biomarker in migraine. Brain Behav. 2023;13(12):e3282. 
5. Chen Z, Chen X, Liu M, et al. Evaluation of gray matter perfusion in episodic migraine using voxel-wise comparison of 3D pseudo-continuous arterial spin labeling. J Headache Pain. 2018; 23;19(1):36.