Minidosing Lysergic Acid Diethylamide (LSD) for Chronic Cluster Headache

• Status: Not yet recruiting
• Trial end date: 2025-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Randomized double-blind placebo-controlled trial of LSD 25μg every 3 days for 3 weeks versus placebo, followed by a 5-week post-treatment observation of persistence of efficacy, in chronic cluster headache (CCH).

Main research objective

1. To assess the efficacy and utility of a 3-week course of LSD 25μg for the relief of CCH

Additional research objectives

2. To explore the persistence of effect at 8 weeks post-randomization

3. To assess the safety and tolerability of a 3-weeks treatment regimen

4. To assess the cost-effectiveness

5. To model the correlation of pharmacokinetic variables and pharmacodynamics effects

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Canisius-Wilhelmina Hospital
• Collaborators: Leiden University Medical Center; Radboud University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development
• Treatments: Lysergic Acid Diethylamide

Criteria

Inclusion Criteria:

• CCH according to the International Classification of Headache Disorders version 3 (ICHD-3)

• At screening: stable weekly attack frequency in the 4 weeks prior to screening (assessed retrospectively), averaging at least 8 per week and each week within a 40% window around the average

• At randomization: average of at least 8 attacks per week and no absence of attacks on more than two consecutive days during baseline

Exclusion Criteria:

• Use of excluded concomitant treatment at screening (lithium; other prophylactics if not on a stable dose for less than one month; steroids/GON block within 2 months before screening; sphenopalatinum block, neurostimulation (stimulator on) or botulinum toxin within 3 months before screening) and during the double-blind phase

• Use of LSD(-derivatives) (other than investigational drug), psilocybin, ketamine or cannabis within 3 months prior to screening and throughout the study

• Lifetime and/or family history (first degree relatives) of psychotic or bipolar disorder, suicidal intention or attempt

• A score of 6 or more on the 'Ervaringenlijst' (PQ-16) to exclude subclinical susceptibility to psychosis

• Actual abuse of alcohol and/or recreational drugs

• Lifetime history of cardiac valvular disease

• History or evidence of cognitive disorder at screening

• Positive urine drug screen at screening

• Females: Pregnancy, lactation, no acceptable contraceptive use