Clinical TrialHeadache Disorders (Cluster & Migraine)LSDPlaceboRecruiting

LSD to Improve Cluster Headache Impact Trial

This double-blind, placebo-controlled trial (n=65) will assess the efficacy and safety of LSD (25μg) every 3 days for 3 weeks versus placebo in treating chronic cluster headaches (CCH).

Target Enrollment
65 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomized, double-blind, parallel-group Phase 2 trial comparing low‑dose LSD tartrate (25 µg per vial) given one dose every 3 days for 3 weeks (7 doses) versus matching placebo in adults with chronic cluster headache.

Design includes a 4‑week baseline observation period, 3‑week treatment period and 5‑week post‑treatment observation to assess acute and sustained effects; primary outcome is reduction in attack frequency at end of treatment.

Secondary objectives include safety, exposure–response exploration and cost‑effectiveness; background rationale arises from limited uncontrolled evidence suggesting low‑dose LSD may reduce attack frequency in refractory chronic cluster headache.

Study Protocol

Preparation

sessions

Dosing

7 sessions

Integration

sessions

Study Arms & Interventions

LSD 25µg

experimental

LSD tartrate equivalent to 25 µg LSD base; one dose every 3 days for 3 weeks (7 doses).

Interventions

  • LSD25 µg
    via Oral• one dose every 3 days• 7 doses total

    25 µg LSD base per vial

Placebo

inactive

Placebo vial matched to verum; one vial every 3 days for 3 weeks (7 doses).

Interventions

  • Placebo
    via Oral• one dose every 3 days• 7 doses total

    Matching placebo vial

Participants

Ages
16 – 75
Sexes
Male & Female

Inclusion 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

  • 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

Study Details

Locations

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

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