Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache

NCT03781128 | Recruiting Phase 2

• 1 other identifier: BASEC 2018-01082
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: After no official research in humans in the last 40 years, research and therapeutic uses of the serotonergic psychedelic lysergic acid diethylamide (LSD) are now re-recognized and include its use in brain research, alcoholism, anxiety associated with terminal illness, and treatment of headache disorders. Specifically, LSD has been reported to abort attacks, to decrease frequency and intensity of attacks, and to induce remission in patients suffering from cluster headache (CH). Objective: To investigate the effects of an oral LSD pulse regimen (3 x 100 µg LSD in three weeks) in patients suffering from CH compared with placebo. Design: Double-blind, randomized, placebo-controlled two-phase cross-over study design. Participants: 30 patients aged ≥ 25 and ≤ 75 years with chronic or episodic CH with predictable periods lasting approximately 2 months and attacks responding to oxygen. Main outcome measures: Changes in frequency and intensity of CH attacks assessed with a standardized headache diary Significance: CH is often rated as the most painful of all primary headaches, which not only causes significant disability, but is also associated with enormous personal, economic, and psychiatric burden. At the moment, there is no specific treatment available for CH, but serotonergic compounds represent an important drug class, especially in the abortive management of cluster attacks. However, there is a need for new treatment approaches, as CH is also often insufficiently managed with available medication. This study will evaluate the potential benefit and safety of a treatment with LSD for patients with CH.

Conditions

Cluster Headache

Keywords

lysergic acid diethylamide (LSD); serotonin; hallucinogen; cluster headache

Outcome Measures

Primary Outcomes (2)

• Change in frequency of the cluster headache attacks

  assessed with a standardized headache diary, within-subjects analysis

  8 weeks before and after pulse regimen

• Change in intensity of the cluster headache attacks

  assessed with a standardized headache diary, within-subjects analysis

  8 weeks before and after pulse regimen

Secondary Outcomes (29)

• Episode abortion

  through study completion, an average of 1 year

• Change in duration of attacks

  8 weeks after pulse regimen

• Time to first attack after completion of pulse regimen

  8 weeks after pulse regimen

• Cumulative time with headache

  8 weeks after pulse regimen

• Change in cluster period duration and interval between cluster periods

  8 weeks after pulse regimen

Study Arms (2)

LSD, Placebo

OTHER

Lysergic acid diethylamide (3 x 100 µg LSD in three weeks, per os) followed by Placebo

Drug: Lysergic Acid Diethylamide; Drug: Placebo

Placebo, LSD

OTHER

Placebo (3 x 1 vial looking like LSD in three weeks, per os) followed by Lysergic acid diethylamide

Drug: Lysergic Acid Diethylamide; Drug: Placebo

Interventions

Lysergic Acid Diethylamide DRUG

100 µg, per os, 3 times within 3 weeks

Also known as: LSD

LSD, Placebo; Placebo, LSD

Placebo DRUG

placebo in an identical-looking vial as LSD, per os, 3 times within 3 weeks

LSD, Placebo; Placebo, LSD

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 25 and ≤ 75 years
• Chronic cluster headache (according to the International Headache Society (IHS) criteria) OR
• Attacks respond to oxygen
• Sufficient understanding of the study procedures and risks associated with the study
• Participants must be willing to adhere to the study procedures and sign the consent form
• Participants are willing to abstain from taking preventive and abortive medication (except from oxygen) long enough before and after the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction
• Participants are willing to refrain from taking any psychiatric medications during the experimental session period. If they are being treated with antidepressants, lithium or are taking anxiolytic medications on a fixed daily regimen, such drugs must be discontinued long enough before the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction.
• Participants must also refrain from the use of any psychoactive drugs and caffeine within 24 hours of each LSD/placebo treatment session. They must agree not to use nicotine for at least 2 hours before and 6 hours after each dose of LSD. They must agree to not ingest alcohol-containing beverages for at least 1 day before each LSD treatment session. Non-routine medications for treating breakthrough pain taken in the 24 hours before the LSD treatment session may result in rescheduling the treatment session to another date, with the decision at the discretion of the investigators after discussion with the participant.
• Participants must be willing not to drive a traffic vehicle or to operate machines within 24 hours after LSD/placebo administration.

You may not qualify if:

• Other forms of headache attacks (migraine, paroxysmal hemicranias, shortlasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating and rhinorrhea (SUNCT) or with cranial autonomic symptoms (SUNA))
• Women who are pregnant, nursing or of child-bearing potential and are not practicing an effective means of birth control (double-barrier method, i.e. pill/intrauterine device and preservative/diaphragm)
• Past or present diagnosis of a primary psychotic disorder. Subjects with a first degree relative with psychotic disorders are also excluded.
• Past or present bipolar disorder (DSM-IV).
• Current substance use disorder (within the last 2 months, DSM-V, except nicotine).
• Somatic disorders including severe cardiovascular disease, untreated hypertension (systolic blood pressure \> 160mmHg without treatment, systolic blood pressure \> 140 mmHg with treatment), severe liver disease (liver enzymes increase by more than 5 times the upper limit of normal) or severely impaired renal function (estimated creatinine clearance \<30 ml/min), or other that in the judgement of the investigators pose too great potential for side effects.
• Weight \< 45kg
• Participation in another clinical trial (currently or within the last 30 days)
• Participants taking higher steroid doses (\>10mg/d) over a longer time period (\>2 weeks), as this would require tapering
• Use of immunomodulatory agents (i.e. azathioprine) in the past 2 weeks
• Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Cluster Headache

Interventions

Lysergic Acid Diethylamide

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Matthias Liechti

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthias Liechti, Prof.

CONTACT

0041 61 328 68 68; matthias.liechti@usb.ch

Yasmin Schmid, Dr. med.

CONTACT

0041 61 328 68 66; yasmin.schmid@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, placebo-controlled two-phase cross-over study design.

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: December 19, 2018
• Study Start: January 2, 2019
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)