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Clinical treatment of cluster headache with the serotonergic indoleamine psychedelics psilocybin and LSD and with ketamine: A case series

Jonathan A. Leighton, Chieh Grace Lau, Aisha Savdo, L Granata

Cephalalgia Reports May 1, 2025 DOI: 10.1177/25158163251345472 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Case series Case report Peer reviewed
Sample size 9
Population Patients with episodic or chronic cluster headache that did not respond to conventional treatments
Interventions Psilocybin LSD Ketamine
Topics Ketamine LSD Psilocybin Serotonin Esketamine
Keywords Hallucinogen Cluster headache
Citations 2
Key findings Eight of nine patients with treatment-resistant cluster headache responded positively to psilocybin or LSD, with several experiencing extended attack-free periods.

Abstract

Background: Cluster headache is an excruciating condition for which standard treatments are usually insufficient. Evidence has accumulated that serotonergic psychedelic indoleamines including psilocybin and LSD can be effective in preventing attacks.

Methods: In this case series, nine patients with episodic and chronic cluster headache that didn’t respond to conventional treatments were treated at a clinic with psilocybin or LSD, under compassionate use provisions, and in most cases separately with ketamine.

Results: All patients responded positively to at least one of the treatments, and eight of nine responded positively to the treatment with the psychedelic indoleamines, in several cases with extended periods free of attacks.

Conclusion: These clinical data, though of an exploratory nature, add to the existing pool of evidence for the usefulness of these substances for treating cluster headache, and further support the lowering of legal and regulatory barriers to medical access to the psychedelic indoleamines.

Comparable studies

Other case reports and case series on LSD, most cited first.

Study Year Design Participants
Lasting Neuropsychiatric Sequelae of (??)Methylenedioxymethamphetamine (???Ecstasy???) in Recreational Users Persons who ingested large doses of MDMA 1991 Case study n = 2
Further Studies in the Therapeutic Value of Lysergic Acid Diethylamide in Mental Illness Patients with mental illness 1957 Case series
Coma, Hyperthermia, and Bleeding Associated with Massive LSD Overdose a Report of Eight Cases People who self-administered large amounts of pure LSD powder intranasally 1975 Case series n = 8
Using a MDMA- and LSD-Group Therapy Model in Clinical Practice in Switzerland and Highlighting the Treatment of Trauma-Related Disorders Patients with chronic complex post-traumatic stress disorder (c-PTSD), dissociative,... 2022 Case series
Persistent Palinopsia Following Ingestion of Lysergic Acid Diethylamide (LSD) Patients who developed persistent palinopsia after LSD ingestion 1996 Case series n = 3

Citations in the library

Cited by 1

Cites 3

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Ketamine LSD Psilocybin Serotonin Esketamine Psychedelic-assisted therapy