Clinical treatment of cluster headache with [...] psilocybin and LSD and with ketamine: A case series, 2025, Leighton et al

[forestglip]

Clinical treatment of cluster headache with the serotonergic indoleamine psychedelics psilocybin and LSD and with ketamine: A case series
Jonathan Leighton, Carmen Lau, Aisha Savdo, Livia Granata

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.

Link | PDF (Cephalalgia Reports) [Open Access]

 

[forestglip]

Figure 1. Timeline of treatments and responses for each patient, aligned at moment of first treatment at pain clinic.

 

[Utsikt]

It’s probably impossible to blind the treatments, but the number of attacks seems to me to be a relatively reliable measurement given the severity they usually have. It’s probably impossible to not notice them, and very clear when they are not there.

I hope future trials incorporate objective measures and long term follow up for e.g. work participation, number of sick days, use of other medications, etc.

Also, is there any reason to believe that there might be a dose response relationship that can be tested here?

 

[forestglip]

It’s probably impossible to blind the treatments

I think I remember some talk about using DXM, another hallucinogen, as a placebo in psychedelic trials for mental health conditions. It's not perfect because the effects are different, so it requires participants who don't have experience with these drugs.

Edit: This paper lists potential options, including Salvinorin A, DXM, and THC:

Addressing blinding in classic psychedelic studies with innovative active placebos (2025, International Journal of Neuropsychopharmacology)