Using LSD to treat chronic cluster headaches

Efficacy and Safety of Minidosing Lysergic Acid Diethylamide (LSD) for Chronic Cluster Headache: a Randomized Placebo-controlled Study

This study is testing if taking a small dose of LSD every three days can help people with chronic cluster headaches feel better and have fewer headaches.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 65 (estimated)
• Ages: 16 Years to 75 Years
• Sex: All
• Sponsor: Radboud University Medical Center (other)
• Locations: 2 sites (Leiden and 1 other locations)
• Trial ID: NCT05477459 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of administering 25μg of LSD every three days for three weeks to patients suffering from chronic cluster headaches, compared to a placebo. The study includes a four-week baseline observation period followed by a five-week post-treatment observation phase. The primary objective is to evaluate how effective LSD is in reducing headache frequency and severity, while also assessing its safety and potential impact on patients' quality of life. The trial aims to address the significant unmet need for better-tolerated and effective treatments for chronic cluster headaches.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals diagnosed with chronic cluster headaches who experience an average of at least eight headache attacks per week.

Not a fit: Patients who have recently used certain medications or treatments for cluster headaches may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel and effective option for patients suffering from chronic cluster headaches.

How similar studies have performed: While there is limited evidence from previous case reports suggesting LSD may be effective, this approach is relatively novel and has not been extensively tested in controlled trials.

Eligibility 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 (changed setting within 3 months before screening) 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

Where this trial is running

Leiden and 1 other locations

• Leiden University Medical Center (LUMC) — Leiden, Netherlands (RECRUITING)
• Canisius-Wilhelmina Ziekenhuis (CWZ) — Nijmegen, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Kees Kramers, Prof. — Radboud University Medical Center
• Study coordinator: Julia Jansen, MD

Conditions: Chronic Cluster Headache, Chronic cluster headache, Lysergic acid diethylamide