This double-blind, randomised study (n=65) will investigate if every third-day mini-dosing (25μg) of LSD for three weeks (7x dosing) alleviates chronic cluster headaches (CCH).
Trial DetailsTreatment of cluster headache consists of acute remedies for attacks (mainly 100% O2, sumatriptan), transitional treatment for temporary frequency reduction (subcutaneous steroid injection at the greater occipital nerve (GON block), oral steroids or frovatriptan) and prolonged prophylaxis (e.g. verapamil, lithium, topiramate). Although the latter compounds have shown some efficacy in reducing the attack frequency, the evidence for their effect is weak. Moreover, all are used off-label, may have side effects and safety issues limiting their utility, and efficacy may not persist over time. Invasive, expensive treatments like hypothalamic deep brain stimulation, occipital nerve stimulation and sphenopalatine ganglion stimulation are last resort options. Recently, a monoclonal antibody targeting calcitonin gene related peptide (CGRP) received FDA approval for episodic cluster headache, but was shown to be ineffective in CCH. Thus, there is a considerable unmet need for effective treatments that are better tolerated, safe and affordable, potentially through repeated administration of safe transitional treatments in the long-term control of disease activity. In this study, the investigators will assess the efficacy of interval treatment with LSD in CCH. Formal evidence for the efficacy of LSD in cluster headache is currently lacking. However, several lines of circumstantial evidence provide strong indications that LSD may have potential for cluster headache prophylaxis. The primary objective of this randomized double-blind placebo-controlled trial is to compare the efficacy of LSD 25μg every 3 days for 3 weeks versus placebo in CCH. The investigators aim to show that, at the end of treatment, verum is more efficacious than placebo with comparable tolerability in an ambulatory setting. To explore the sustainability of benefit the investigators will also assess the response at 5 weeks post-treatment (8 weeks postrandomization). If these expectations are realized, LSD might be positioned as a transitional treatment that may outlast currently available options and pave the way for studying repeated transitional treatment as a novel preventive strategy for long-lasting relief with improved tolerability. The hurdle of a listed substance needs to be conquered by many patients and health care professionals, though.
NCT Number NCT05477459
Sponsors & CollaboratorsLeiden University
Leiden University Medical Center is doing several studies into psychedelics. They do this in cooperation with other universities (e.g. Utrecht University) and companies (e.g. COMPASS).