This open-label study (n=4) investigated the effects of low-dose oral psilocybin (5-10mg) with psychological support in patients with chronic short-lasting unilateral neuralgiform headache attacks (SUNHA). The study aimed to assess cognitive effects, safety, tolerability, and impact on headache severity and frequency, but was terminated early due to recruitment difficulties.
Abstract of Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks
“Background Short-lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgias that feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best-available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open-label phase Ib ascending dose study, we aimed to assess the effects of low-dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency.
Methods Oral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six-item Headache Impact Test (HIT-6). Subjective dose intensity was assessed via the five-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free-text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes.
Results No significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D-ASC scores 37.8-45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT-6 mean scores 64.3-65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow-up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded “much” (two participants) or “minimal” improvements (one participant) at final follow-up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants’ experience; these insights included re-configured relationships to their headache pain.
Conclusion The study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment.“
Authors: James Rucker, Matt Butler, Sadie Hambleton, Catherine Bird, Mathieu Seynaeve, Sanjay Cheema, Kete Campbell-Coker, Carolina Maggio, Fiona Dunbar, Giorgio Lambru & Manjit Matharu
Summary of Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks
Short-lasting unilateral neuralgiform headache attacks (SUNHA) are a type of trigeminal autonomic cephalalgia, characterised by intense and recurrent paroxysms of pain and autonomic symptoms. SUNHA is a rare condition, with an estimated prevalence of seven per 100,000 people. The disorder is diagnosed based on moderate-to-severe unilateral head pain in the trigeminal nerve distribution, lasting for 1-600 seconds and occurring as single stabs, series of stabs, or in a saw-tooth pattern. These attacks are accompanied by at least one ipsilateral cranial autonomic feature, such as lacrimation, conjunctival injection, or nasal congestion.
The pathophysiology of SUNHA is not fully understood, but it is thought to involve hypothalamic dysfunction and trigeminal neurovascular conflict. The hypothalamus, which plays a role in pain modulation and autonomic function regulation, may be dysfunctional, leading to abnormal activation of the trigeminal autonomic reflex. Additionally, compression or irritation of the trigeminal nerve by nearby cranial vessels may contribute to pain generation and activation of the trigeminal autonomic reflex.
Currently, there are no approved medical treatments specifically for SUNHA. Off-label treatments include anti-neuropathic agents such as lamotrigine, carbamazepine, and duloxetine. Non-medical options further along the treatment pathway include occipital nerve stimulation, microvascular decompression of the trigeminal nerve, and deep brain stimulation of the posterior hypothalamus. However, approximately half of patients remain refractory to medical therapy, highlighting the pressing need for alternative treatments.
Methods
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https://doi.org/10.1111/head.14837
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Cite this paper (APA)
Rucker, J., Butler, M., Hambleton, S., Bird, C., Seynaeve, M., Cheema, S., ... & Matharu, M. Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks: results from an open-label phase Ib ascending dose study. Headache. https://doi.org/10.1111/head.14837
Study details
Compounds studied
Psilocybin
Topics studied
Headache Disorders
Pain
Study characteristics
Original
Open-Label
Participants
4
Humans
Institutes
Institutes associated with this publication
Beckley PsytechBeckley Psytech is working on getting 5-MeO-DMT to market as the first of a variety of psychedelic medicines.
Compound Details
The psychedelics given at which dose and how many times
Psilocybin 5 - 10mg | 3x
Linked Clinical Trial
Phase 1b Study in Patients With Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA)This exploratory open-label phase 1b, ascending dose study is to evaluate the effects of psilocybin on cognition in patients with Chronic Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA)