Alfredo Parra 🔸

• Alfredo Parra 🔸 28 Dec 2025 19:29 UTC

  3 points

  0 ∶ 0

  on: Launch­ing the In­dia An­i­mal Welfare Fund­ing Circle

  Wishing you all the best! :)

• Alfredo Parra 🔸 28 Dec 2025 19:28 UTC

  3 points

  0 ∶ 0

  in reply to: NickLaing’s comment on: The Best Treat­ment for the Most Pain­ful Med­i­cal Con­di­tion Is Illegal

  Thanks for sharing your thoughts! While I’m obviously sad that you’ve updated negatively, this exchange has been very helpful for me to reflect on how to communicate my level of confidence in these treatments, especially given the little data we have from RCTs specifically. The total evidence still looks overall highly compelling to me (I wouldn’t be working on this ~full time otherwise), but I’ll work on improving my communication (and generating more scientific evidence).

  The main thing I’d like to say is that I’m really not committed to psychedelics as an intervention (since you brought up the lobbyist language), and I’m particularly excited and hopeful about non-hallucinogenic analogues (such as BOL-148 and Conjugated Psilocin), as well as about non-pharmaceutical interventions, which we’re also exploring. Ultimately, I just want patients to have universal access to treatments that safely and effectively prevent or abort their attacks. Currently, I sincerely believe those happen to be indoleamines.

  If the effect is really as strong as claimed, you wouldn’t even need 100 patients for an RCT. Perhaps clusterfree could even make this happen faster

  Absolutely agree, and we’re actively thinking about how to do this!

• Alfredo Parra 🔸 20 Dec 2025 13:21 UTC

  3 points

  0 ∶ 0

  on: Where did you donate this year?

  Clusterbusters, because torturous pain belongs to the past (especially if it can be easily prevented).

• Alfredo Parra 🔸 20 Dec 2025 12:49 UTC

  9 points

  1 ∶ 0

  in reply to: Henry Howard🔸’s comment on: The Best Treat­ment for the Most Pain­ful Med­i­cal Con­di­tion Is Illegal

  I understand it seems hard to believe! And yes, I’m motivated to support /​ advocate for RCTs and I’m developing various ideas with some collaborators (not just involving psychedelics). I agree that more data published in peer-reviewed journals is very much needed.

  I still genuinely believe that the funding and legal barriers are very difficult to overcome (plus other barriers). A good resource on this topic is the book Psychedelic Outlaws (describing the history of psychedelic use and research for CH). This deep research by Claude may also provide useful context: Why psychedelic research for cluster headaches has stalled despite decades of patient evidence. It concludes:

  The documented barriers to psychedelic cluster headache research reveal systemic failures across every institution that might otherwise advance treatment. Schedule I classification adds years to research timelines. NIH has invested almost nothing in cluster headache specifically. Pharmaceutical companies see no return in treatments requiring only three doses annually. Academic institutions impose unique scrutiny on psychedelic protocols. Patient recruitment struggles with rarity, episodic presentation, and placebo reluctance.

  The BOL-148 story crystallizes the tragedy: a non-hallucinogenic compound showed unprecedented efficacy in 2010, yet required 13 years to enter Phase 1 trials because it fell between orphan drug and commercial viability. As Bob Wold observed: “You can’t introduce transformative medicine into a broken healthcare system.” The gap between patient discovery in 1998 and the current state of research—with perhaps one dedicated US researcher and trials measured in dozens of participants—represents what Halpern called “a process that has begun 40 years too late.”

• Alfredo Parra 🔸 20 Dec 2025 8:02 UTC

  5 points

  1 ∶ 0

  in reply to: Henry Howard🔸’s comment on: The Best Treat­ment for the Most Pain­ful Med­i­cal Con­di­tion Is Illegal

  Why suspicious? The fact that DMT aborts cluster headaches is a pretty recent discovery. The word is just beginning to spread among sufferers. And there are very few researchers working on this topic, and very little funding generally, and it can be pretty difficult to get all the permissions needed to run trials using psychedelics. (I wouldn’t be surprised if Schindler’s group at Yale was running the DMT survey as a preliminary step to justify running a proper trial. Note that Schindler “is believed to be the only researcher in the United States studying psychedelics in headache disorders.”)

• Alfredo Parra 🔸 18 Dec 2025 14:27 UTC

  10 points

  3 ∶ 0

  in reply to: Henry Howard🔸’s comment on: The Best Treat­ment for the Most Pain­ful Med­i­cal Con­di­tion Is Illegal

  Thanks for your comment!

  It is true that published studies on psychedelics are few and small. Hopefully that will change but, currently, investment into cluster headache is minute relative to its severity and prevalence.

  There are no studies on DMT in particular (though one survey is being carried out at Yale). However, we’ve argued that the little evidence we have on DMT specifically should be taken very seriously (which is what motivates the Yale group).

  In medicine you quickly learn that anectode is extremely unreliable and the average person is positively busting to attribute cause and effect to whatever they just experienced. Every homeopathic remedy/​energy healer/​prayer/​crystal/​snake oil has its die-hards who will give you convincing anectodes of immediate success, so doctors become rightly extremely skeptical about these stories.

  I think this definitely does not apply to DMT for CH. As mentioned in the post I linked above, patients can report going from experiencing the worst possible pain to being completely pain free within seconds of inhaling DMT. The cause and effect could not be any clearer. (There are also other statistical ways to quantify the reliability of anecdotes, see e.g. here.)

  The actual evidence he provides is this review of some case studies and surveys and 4 clinical trials but which have pretty low numbers. The review itself says: “The small number of participants in each study limits reliability and generalizability of the findings. Even with ongoing work, differences in dosing regimens and outcomes among studies will limit the consolidation of findings”

  (And yet it’s worth pointing out that two of the three co-authors of that review, namely Christopher Gottschalk and Emmanuelle Schindler, are among the strongest supporters of psychedelic treatments for CH. Gottschalk is the Director of Headache Medicine at Yale and immediate past president at the Alliance for Headache Disorders Advocacy.)

  Combined with the small risk of psychosis from psilocybin I understand why health systems wouldn’t want to rush into mainstreaming them as treatment.

  How big is the risk of psychosis at low doses, and how does it compare to experiencing literally the worst possible pain, day in and day out?

  I’ve been thinking about /​ working on cluster headaches since summer 2024, not just reading the academic literature but also following support groups online and talking to patients directly. There’s no doubt in my mind that psychedelics help many patients enormously, and at low doses for most patients. I know some patients who decide not to take psychedelics, but we should give those who do want to use them the right to try them without any legal repercussions.

The Best Treat­ment for the Most Pain­ful Med­i­cal Con­di­tion Is Illegal

• Alfredo Parra 🔸 12 Dec 2025 7:46 UTC

  5 points

  0 ∶ 0

  on: Why I donate: seems easy, seems ob­vi­ous, I rarely think about it

  Nice, can relate. Thanks for sharing.

• Alfredo Parra 🔸 1 Dec 2025 8:55 UTC

  4 points

  0 ∶ 0

  in reply to: AlephNull’s comment on: An­nounc­ing ClusterFree: A cluster headache ad­vo­cacy and re­search ini­ti­a­tive (and how you can help)

  Thanks so much for your comment and your support! :) And yes, we definitely want to engage with representatives at all levels, both ourselves as well as in a decentralized manner (e.g., by empowering patients and other volunteers to take action locally). Any efforts are welcome. Get in touch if you’d like to coordinate somehow or if you need any advice. :)

• Alfredo Parra 🔸 26 Nov 2025 15:40 UTC

  10 points

  1 ∶ 0

  in reply to: NickLaing’s comment on: Dona­tion Elec­tion Dis­cus­sion Thread

  Thanks for the shoutout and for the vote! :)

  I’m not convinced that the number of sufferers isas high as claimed. In 13 years as a doctor in Uganda and treating a few thousand patients, I’ve never seen a convincing case of cluster headache here.

  This is indeed quite surprising! The relatively low prevalence and the lack of recognition of the disease /​ misdiagnosis may explain it to some extent, but zero patients in 13 years is still very surprising.

  (Consider that even an average neurologist only ever sees a few dozen CH patients during their entire career. I asked Opus 4.5 and Gemini 3.0 to estimate how many CH patients an average neurologist in the US sees per year, assuming an annual prevalence of 1/​2000 adults, and their responses were 1–2/​year and 1/​year, respectively. They also think that the average neurologist sees 3–5x (5–10x resp.) more CH patients than the average primary care doctor, but the odds of not encountering a single patient in 13 years should still be very, very low. Will look into this!)

  Also, there’s almost no epidemiological data on the prevalence of CH in African countries, so the prevalence error bars are large. (In our paper, we included a sensitivity analysis of the most uncertain variables to add some nuance.)

An­nounc­ing ClusterFree: A cluster headache ad­vo­cacy and re­search ini­ti­a­tive (and how you can help)

• Alfredo Parra 🔸 12 Nov 2025 19:55 UTC

  8 points

  2 ∶ 1

  in reply to: Vasco Grilo🔸’s comment on: Cause prio cruxes in 2026?

  Thanks for your answer! :)

  If so, why not generalise, and conclude you would avert 2^N h of pain of intensity 0.999^N instead of 1 h of pain of intensity 1?

  I think the procedure might not be generalizable, for the following reason. I currently think that a moment of conscious experience corresponds to a specific configuration of the electromagnetic field. As such, it can undergo phase transitions, analogous to how water goes abruptly from liquid to gas at 100°C. Using the 1-dimensional quantity “temperature” can be useful in some contexts but is insufficient in others. Steam is not simply “liquid water but a bit warmer”; steam has very different properties altogether.

  To extend this (very imperfect) analogy, imagine we lived in a world where steam killed people but (liquid) water didn’t (because of properties specific to steam, like being inhalable or something). In this case, the claim “reducing sufficiently many units of lukewarm water would still be better than reducing a unit of steam” would miss the point by the lights of someone who cares about death.

  (Here are some thoughts on phase transitions in certain altered states of consciousness.)

  Do you know how much funding is spent globally per year on preventing human torture?

  I don’t! That’s the sort of question I’d like to see more research on (or discussed more on the Forum if such research already exists), as well as which torture-prevention orgs/​programs are most cost-effective, etc.

• Alfredo Parra 🔸 12 Nov 2025 9:35 UTC

  19 points

  7 ∶ 6

  in reply to: Vasco Grilo🔸’s comment on: Cause prio cruxes in 2026?

  As a panpsychist and suffering abolitionist, I’m one of the most sympathetic people in the world to the cause of reducing suffering even in the smallest beings. And yet, I do not want to see more research on how to increase the welfare of microorganisms on the margin (or at least not with EA resources).

  I probably won’t change your mind about meta ethics, but I strongly disagree with the aggregationist QALY approach to comparing the welfare of humans vs e.g. soil animals (e.g. here). I hope to write more about this at some point, but as an intuition pump, I think there’s a good chance that the problem of reducing soil animal or microorganism suffering is somewhat analogous to the problem of reducing, say, pin pricks in humans. I would not support EA efforts to reduce the number of pin pricks in humans, no matter how vast, given that we also have humans who are actually being tortured right now.

  As much as I care about insects and other small organisms, I’m really sad that the EA community invests far more resources into their well-being than to reducing torture in humans (e.g. there are 120 EA Forum posts on Invertebrate Welfare and only 7 on cluster headache; and there isn’t even an EA Forum tag for “Torture” despite it still being a huge problem globally (Claude estimated 1–2m people tortured per year, ChatGPT estimated 500k–2m)).

  I really appreciate your work, and I think we should absolutely think about these problems. But, on the margin, I’d rather see other work being done.

An­nounc­ing “Com­pu­ta­tional Func­tion­al­ism De­bate” (so­lic­it­ing paid feed­back): Test your in­tu­itions about consciousness

• Alfredo Parra 🔸 3 Nov 2025 9:12 UTC

  4 points

  1 ∶ 0

  on: How Open Phil uses back-of-the-en­velope calcu­la­tions for GHW

  Thanks so much for sharing these resources!!

  Like many experts and institutions in global health, we use “disability-adjusted life years” (DALYs) as a way to measure the burden of a health condition. An intervention that improves health will thereby reduce DALYs.

  It’d be awesome for OP to explore in parallel other cause areas and interventions that the DALY misses, such as less prevalent conditions inflicting very severe suffering. Otherwise, we risk neglecting those who are worst off.

  I make this case in my paper “The Heavy Tail of Extreme Pain Exacerbates Health Inequality: Evidence from Cluster Headache Underinvestment” (forthcoming in “Nature: Humanities & Social Sciences Communications”). My post “How much should we value averting a Day Lived in Extreme Suffering (DLES)?” also touches on some of these themes.

• Alfredo Parra 🔸 3 Nov 2025 9:00 UTC

  5 points

  1 ∶ 0

  on: Emerg­ing ev­i­dence on treat­ing cluster headaches with DMT

  Related video by Andrés Gómez Emilsson (@algekalipso): “The Case for DMT for Cluster Headaches: Practical Tips & Why It Deserves Urgent Scientific Attention”

• Alfredo Parra 🔸 29 Oct 2025 7:24 UTC

  5 points

  4 ∶ 0

  on: Mod­ern­iz­ing the EA Funds website

  I found it insightful to read your criticisms of the old website! And I really like the new website. Congrats on the launch! 🎉

• Alfredo Parra 🔸 21 Oct 2025 10:43 UTC

  2 points

  0 ∶ 0

  in reply to: SiebeRozendal’s comment on: Emerg­ing ev­i­dence on treat­ing cluster headaches with DMT

  This is helpful, thanks! (It would have come in handy for our kidney stone project, where we did something very similar!)

• Alfredo Parra 🔸 21 Oct 2025 8:25 UTC

  2 points

  0 ∶ 0

  in reply to: Alistair Stewart’s comment on: Emerg­ing ev­i­dence on treat­ing cluster headaches with DMT

  Thanks for the encouragement, Alistair! ❤️

• Alfredo Parra 🔸 21 Oct 2025 8:24 UTC

  3 points

  0 ∶ 0

  in reply to: Cameron.K’s comment on: Emerg­ing ev­i­dence on treat­ing cluster headaches with DMT

  Thank you, Cameron! You might be interested in the work of the Psychedelics & Pain Association.