The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

Introduction

Cluster headache (CH) is a primary headache disorder marked by strictly unilateral severe orbital or periorbital pain and occurs as either episodic or chronic illness, with a population prevalence around 0.1%. Acute attacks are typically treated with oxygen or subcutaneous sumatriptan, while preventive options include verapamil, lithium, corticosteroids and other neuromodulators; nevertheless, many patients remain refractory and some undergo invasive neurosurgical procedures that carry significant risks. Anecdotal reports and an Internet survey have suggested that classical serotonergic psychedelics (LSD, psilocybin) can both abort attacks and extend remission periods, but their hallucinogenic properties, tight legal control and safety concerns limit clinical research and potential therapeutic use. To explore whether the anti‑cluster effects attributed to LSD and psilocybin depend on their hallucinogenic properties, the investigators examined a structurally related but reportedly non‑hallucinogenic LSD analogue, 2‑bromo‑LSD (BOL‑148). Prior volunteer and vascular‑headache studies had characterised BOL‑148 as non‑toxic and non‑hallucinogenic at doses up to those used historically. This paper reports an open, non‑randomized case series testing whether a short course of orally administered BOL‑148 could reduce attack frequency or intensity or induce remission in patients with refractory CH.