Cluster headaches are considered one of the most excruciating conditions known to medicine. Centred on one eye and likened to a red-hot poker or ice pick being stabbed into the brain, they tend to be rated close to 10/10 on the pain scale, well above the average for childbirth, kidney stones and migraines. Attacks typically last an hour but range from 15 minutes to ca. 3 hours, and they can recur multiple times a day, often during the night. In the more common episodic form they appear once or twice a year at the same time and can last ca. 1-3 months, while in the 15% of patients with the chronic form, attacks occur every day for months and years without a break. Cluster headaches affect ca. 1-2/1000 people, and the suicide rate has been reported to be 20x the population average. Posts from patients in cluster headache groups express their desperation, describing the pain as unbearable.
There are medical therapies that are effective in aborting and preventing attacks for many patients, but they have side effects limiting their use and have limited efficacy in preventing entire episodes. High-flow oxygen is safe and can abort attacks in most patients, but it is cumbersome, takes time to act and doesn’t stop attacks from occurring. Two EA Forum posts last year from the Qualia Research Institute (post 1 and post 2) have described cluster headache distribution and barriers to access, and approaches to treating them, with a focus on DMT. We initially became interested in DMT because of the anecdotal evidence, reported in the above posts, that it can abort a cluster headache within seconds. DMT clearly deserves further study as potentially the most rapid-acting abortive known. However, it turns out that there is far more extensive evidence that psilocybin mushrooms can prevent and abort entire episodes. Such evidence has been published as survey data and is also widely reported by patients in cluster headache groups. Two ongoing Phase I RCTs are ongoing and should add to the existing evidence for efficacy.
Lack of access to psilocybin mushrooms and widespread information about using them are key barriers to effective treatment for many patients. Following our recent work on access to morphine in lower-income countries (see also here), OPIS has been focusing on the cluster headache cause area for the potential to dramatically improve the lives of many patients. One angle is lobbying governments to decriminalise the use of psilocybin, specifically for cluster headache patients or in the context of a larger harm reduction approach to drug policy, and to explicitly allow its therapeutic use. While changing drug laws is a slow process, there is increasing evidence for the therapeutic use of psilocybin for the treatment of depression and anxiety, and also a growing movement for drug decriminalisation (see for example this Effective Altruism Foundation policy paper and the recent Conservative Drug Policy Reform Group psilocybin campaign).
OPIS has a close collaboration with the Finnish Horton Association (a cluster headache association) and we are preparing a white paper to be presented to the Finnish government on improving the treatment of cluster headaches in Finland, with the intention of leveraging any success in Finland elsewhere. However, we are also preparing a version of the white paper focusing specifically on psilocybin and which we will widely distribute internationally to policymakers and influencers, probably this autumn. We are also planning a short animated documentary to support the release of the white paper.
In addition, we plan to create a guide for patients that provides more detailed information on self-treatment. Much of this information is already available online, including on the website of the organisation Clusterbusters (with whom we are now closely collaborating) and in Facebook groups, but there appears not to be a single compact resource page that provides key information about access and use. The legal status of psilocybin may complicate what and how information can be explicitly provided about access, and yet this is one of the single greatest barriers to giving patients their lives back.
Our initiative is described in a presentation prepared for the recent EAGxVirtual Unconference.
More information and extensive references are on the OPIS cluster headache page.
We are looking for financial support for this initiative. 80000 Hours recently included cluster headaches in its list of research questions. However, we haven’t yet identified an institutional source of EA funding aligned with this kind of project, and we’ve been relying on mainly small private donations until now. Donors can contribute via our donation page or to an ongoing general crowdfunder. Questions, suggestions, insights and specific expertise related to this project – including the legal aspects – are most welcome.
Great news, I'm very excited about this! The amount of QALY left by the wayside due to the effective shut down of psychedelics research makes me cringe every time I think about it.
Will you eventually look into psychedelics for migraine as well? They are probably 1–2 orders of magnitude less painful than cluster headaches but also ~2 orders of magnitude more common. (Which could then also make it more difficult to achieve acceptance in the population/regulatory bodies, I suppose...). And as far as I remember, psilocybin/LSD worked for migraine as well.
Thanks! There is actually an RCT for psilocybin in migraines as well, being conducted by the same Yale researcher, Emmanuelle Schindler - results should even be presented this month, I believe. Migraine patient associations are larger and have more clout, so I expect positive results to get traction and make talk of psilocybin and other controlled substances more mainstream. Until now, migraine organisations and even one major cluster headache association (OUCH) tend to avoid talk of controlled substances.
Cool, thanks for the pointer, I'll have a look for the study and hope that it kickstarts broader change.
Any explicit reason why migraine orgs and OUCH avoid the topic? Perhaps they fear that migraines are already viewed as "just a headache" and association with psychedelics would undermine the struggle for serious acceptance? Conformity signaling? Status quo bias? Low-openness staff? One person I know who is suffering from migraines is just very unenthusiastic about exploring treatment options despite ~10 days/month of substantial suffering, which always boggled my mind.
My guess is that it's indeed mainly the stigma of illegal drugs and not wanting to lose credibility as an organisation by promoting alternative treatments from that category that haven't been approved. Probably not status quo bias as there's enthusiasm about new official treatments. Some cluster headache patients themselves may be reluctant to try illegal drugs, but desperation and the encouragement of other patients in the community reduce the psychological barriers.
So, results of the small-scale migraine study I mentioned above were actually published in June and showed a significant effect of psilocybin on migraines. "Preliminary Analysis of the Sustained Effects of a Single Low Oral Dose of Psilocybin in Migraine Headache", https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.13854 The results were also shown at a cluster headache conference I spoke at over the weekend: a single low dose of psilocybin cut migraine frequency in half. Pretty encouraging!