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I think the EA community has shown incredible initiative in tackling major global health issues, making a lot of progress on problems such as malaria (which causes 600,000 deaths/year) and lead poisoning (which causes 1.5M deaths/year), among so many others. These efforts really show our ability to mobilize resources and drive change when we identify pressing problems.
My hope is that we can direct a similar amount of attention to helping the ~3 million people worldwide who have this terrible condition. Even if my quantitative estimates of the burden of pain were off by an order of magnitude, the situation would still be tragic (and, as @algekalipso has pointed out, somewhat analogous to times when anesthesia had already been invented but not adopted, given the promise of low dose psychedelics1). I think it would be an incredible success story for our community if we managed to eliminate (or at least significantly reduce) this source of enormous suffering. If you’d like to contribute in any way—either with time or funding—please get in touch!
1 Coincidentally, when I asked Claude to estimate the lifetime prevalence of undergoing major surgery without general anesthesia before it was invented, its initial guess was surprisingly similar to the lifetime prevalence of cluster headaches—0.2%.
The Malaysia prevalence is based on a small sample size of n = 595 (from the Fishera et al. Meta-analysis) so it would suggest leaving that out
While these are very promising effect sizes, the methods are of low quality (e.g. high risk of bias). I would suggest a properly powered RCT before concluding that psychedelics are really that effective.
If you put all the existing evidence together – which is much more than just those two studies – even with the risks of bias, it really is overwhelming. See, for example, Fig. 2 in our policy paper, based on a paper by Schindler et al. https://www.preventsuffering.org/wp-content/uploads/2020/11/Legalising-Access-to-Psilocybin-for-Cluster-Headaches-Policy-Paper.pdf, and also some of the patient testimonials. The usual standards for determining the effectiveness of new medications are understandably more rigorous than for other kinds of situations, but in the case of cluster headaches, the huge number of patient reports claiming the efficacy of psychedelics (while other substances like cannabis are generally ineffective), including chronic cluster headaches that end after a few doses of psychedelics, essentially excludes the possibility that there is no causal relationship. And the extreme pain means that patients have the right to access them even if there were any doubts. We’re actually preparing a case series for submission, with a Zurich-based neurologist who can legally prescribe psychedelics, on the results obtained with her patients.
Thanks! It’d be great if someone (maybe myself, but ideally someone with more experience in the field) published a summary of the existing literature (more research here). Having spent so many hours reading up on the topic these past few months, I’m optimistic about the efficacy. I think funding and/or running a large scale RCT in particular for N,N-DMT (in a country where it is legal) would be a great use of EA money/time.
There’s a real need for large clinical trials. There have been a few on psilocybin and LSD as preventatives. The big obstacles are recruiting a sufficient number of patients and obtaining funding to study substances that aren’t directly patentable. Demonstrating the efficacy of DMT as an abortive compared to placebo could be done on very few patients and reach high statistical significance. Demonstrating greater efficacy than Sumatriptan—a standard abortive—would be more difficult, as the latter is also fast-acting and effective in the short term. Sumatriptan is widely believed among patients to cause rebound attacks and to lose effectiveness over time, so a proper comparative study would probably need to follow patients over a period of months. I don’t think that DMT would have to be legal (e.g. for personal use) to be studied as a controlled substance—just authorisation would be needed.
To what extent are the legal restrictions on psychedelics also obstacles to running trials with them in major pharmaceutical R&D countries like the US?
There was a small trial that was recently completed at Yale. The administrative hurdles are greater, including DEA approval in the US, but certainly not insurmountable. It might be easier in some other countries with more permissive laws and where psychedelics have already been legally prescribed, like Canada and Switzerland, but approval is still necessary.
I think it’s great that you did this analysis. There’s a strong tendency, including among many health economists and rationalists, to want to use one single metric to cover everything that matters and aggregate all the data to get a single number (utility, wellbeing, suffering...). This makes it much easier to make decisions, since you’re just comparing potential outcomes based on single numbers. The problem is that not everything can be added together in a way that is both meaningful and non-arbitrary, even if you introduce different weightings. In this case, while aggregating different intensities of suffering to get a single number can simplify things, it loses critical information. So focusing on something more narrowly defined and maintaining a degree of granularity in the analysis ensures that the worst suffering isn’t neglected against a background of more widespread but less intense suffering.
Thanks for your work on this! In general I would love to see headache disorders like cluster headaches and migraine receive more funding for research because of their burden.
As someone who has chronic migraine, I can only imagine what experiencing cluster headaches would be like.
This is a great writeup. Thank you!
Thank you for a very interesting read.
It seems like an important crux in your analysis is quantifying the intensity of CH.
I’d like to point out that QALYs as a metric is not mentioned here. In the QALY-paradigm, the utility weights are anchored at 1 = full health and 0 = dead. Importantly, negative utility weights are also theoretically possible. For example, an utility weight of −10.0 would imply that removing one person-year of CH would be equivalent to 11 QALYs (which is equivalent to the absolute prognosis loss for one person with chronic migraine, according to one random report from the Norwegian Medical Products Agency i just dug up). However, current methods for eliciting negative values are imprecise and somewhat arbitrary. I’ve been thinking about whether developing better metrics within the QALY paradigm can be useful, since it is more widely adopted. CHs would be the perfect example case. Curious to hear if you have any thoughts on this.
Thanks so much for your comment!
Actually, someone else brought up this point separately, so I agree there’s more to say here. I’d love to dig deeper into this question and possibly write a paper on the topic (e.g. for this collection). If you have literature to recommend (either by you or otherwise), please send it my way. And also let me know if you’d like to get involved in such a project. :)
Thanks for sharing this Alfredo, I hadn’t really thought about trying to map subjective pain scales to a pain magnitude, but it seems very important to be able to do so! If using an exponential scale, what is your intuitive sense of what ranges of base to use seem reasonable? If you’re modeling magnitude as base^(1-10 pain scale value), the relative importance of extreme pain is pretty sensitive to the base used. I see e is used as the default in the paper, but I assume that’s partly arbitrary. A value more like 2 seems most reasonable to me, but that is a weakly held view. Has any other work tried to look at suffering magnitude across the pain scale?
I wish we could have more confidence in the pain intensity data. I’m not sure how exactly we should compare the 5-point scale in Russell to the 10-point one in Torelli & Manzoni, in the mapping you’ve done in the code to a shared 10-point scale, they suggest very different intensities.
Thank you for your comment, Tim!
Indeed, the choice of e is arbitrary and used for illustration purposes. And the base 6 is simply the choice for which the total burden of CH is larger than that of migraines, so it’s also not derived from first principles. This footnote is relevant:
The paper cited also mentions the possibility of a linear relationship for lower pain intensities and an exponential relationship at higher intensities (a “kinked” distribution), highlighting the fact that there are more possibilities beyond a uniform exponential increase.
I personally don’t have a good intuition for what the base should be but might do more work on this specific question.
I’m also not sure what the optimal mapping of intensities for the Russell vs Torelli & Manzoni scales is, also considering the fact that the two studies had different methodologies. I think there’s no correct answer, so that was my best guess (though I could also imagine “Very slight” being more intense than a 1.5). Do let me know if you have other suggestions! (Or feel free to fork the code and play around with the parameters. :) )
Thanks, that’s helpful! I think that footnote may have an error though. 6^10 is 60 million, implying nearly 8 OOMs from 0 to 10. The 1-10 gap would be closer to 4 OOMs if linear from 0-5 and exponential with base 6 from 0-10 though. 2-8 OOMs seems like a reasonable range to me, it’s comically broad but highlights our uncertainty about pain magnitude. I’ll definitely give Gómez-Emilsson & Percy (2023) a read, and will fork your cose and play around with the numbers as well!
Gee, not sure what happened there—thanks for pointing that out! I’ve edited the footnote.
One possible intervention to reduce suffering from cluster headaches is the ketogenic diet: high fat, medium protein, ultra-low carbohydrate.
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00064/full
https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/1129-2377-16-S1-A99
Originally devised around 100 years ago to reduce epileptic fits, especially in children, there is currently a wave of studies showing that it is beneficial for a wide range of neurological disorders, including schizophrenia, depression, bipolar disorder, Parkinson’s disease and Alzheimers.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9890290/
It is also being hailed as beneficial in combatting cancer, which is due to evidence showing that cancer has metabolic origins as well as genetic and environmental causes.
https://www.sciencedirect.com/science/article/pii/S2667394023000072
Additionally, it can benefit diabetes sufferers:
https://www.mdpi.com/2072-6643/15/3/500
A review study in a related area showed that the ketogenic diet can bring relief for migraine sufferers also:
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1204700/full
Funders should therefore consider supporting studies of the application of this dietary regime to combat cluster headaches, especially since it has a wide spectrum of clinical application and can bring additional health benefits.
Due to familial predisposition towards diabetes (among other reasons), I myself have been following a ketogenic lifestyle for several years now and have personally experienced numerous health benefits.
Thanks for sharing, Deborah! I’ll add these resources to my list of interventions. :)
Executive summary: Cluster headaches cause approximately 5 million person-days of extreme suffering (≥9/10 pain) annually worldwide, and while less prevalent than other conditions, they represent an opportunity to eliminate significant extreme suffering at relatively low cost through existing treatments.
Key points:
Cluster headaches affect ~3 million people globally and are considered among the most painful conditions known to medicine, rated significantly more painful than labor, gunshot wounds, or bone fractures.
Current health metrics like DALYs undervalue extreme suffering, as they don’t account for the vast differences in pain intensity suggested by the heavy-tailed valence hypothesis.
Promising treatments exist, particularly tryptamines (psilocybin, LSD, DMT), which show high efficacy but face legal restrictions limiting access.
The global burden includes ~74,200 person-years in pain annually, with ~46,200 at severe pain (≥7/10) and ~13,600 at extreme pain (≥9/10).
Key interventions include funding research, supporting advocacy organizations like Clusterbusters, enabling legal access to tryptamine treatments, and improving diagnosis/treatment access in developing countries.
This comment was auto-generated by the EA Forum Team. Feel free to point out issues with this summary by replying to the comment, and contact us if you have feedback.