Article 5 of the 1948 Universal Declaration of Human Rights states:

"Obviously, no one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment."

OK, it doesn’t actually start with "obviously," but I like to imagine the commissioners all murmuring to themselves “obviously” when this item was brought up.

I’m not sure what the causal effect of Article 5 (or the 1984 UN Convention Against Torture) has been on reducing torture globally, though the physical integrity rights index (which “captures the extent to which people are free from government torture and political killings”) has increased from 0.48 in 1948 to 0.67 in 2024 (which is good). However, the index reached 0.67 already back in 2001, so at least according to this metric, we haven’t made much progress in the past 25 years. Reducing government torture and killings seems to be low in tractability.

Despite many countries having a physical integrity rights index close to 1.0 (i.e., virtually no government torture or political killings), many of their citizens still experience torture-level pain on a regular basis. I’m talking about cluster headache, the “most painful condition known to mankind” according to Dr. Caroline Ran of the Centre for Cluster Headache, a newly-founded research group at the Karolinska Institutet in Sweden.

Yesterday I had the opportunity to join the first-ever international research symposium on cluster headache organized at the Nobel Forum of the Karolinska Institutet. It was a 1-day gathering of roughly 100 participants interested in advancing our understanding of the origins of and potential treatments for cluster headache. I'd like to share some impressions in this post.

The most compelling evidence for Dr. Ran’s quote above comes from a 2020 survey of cluster headache patients by Burish et al., which asked patients to rate cluster headache pain from 1–10 as well as other very painful conditions they themselves have had. Cluster headache attacks were rated as significantly more painful than other severely painful conditions:

I’ve been actively working on this problem since last summer and following online discussions of patient support groups almost daily since then (e.g. on Reddit and Facebook). After having read hundreds of testimonials and having watched dozens of videos by patients, I now automatically mentally substitute “cluster headache” with “torture”. There really is no other way to describe it. You can read some testimonials yourself in the appendix (warning: disturbing) or watch some of the videos in this playlist (warning: disturbing). In his opening talk, Prof. Peter Goadsby also showed a clip of a woman having an attack in front of her confused 3-year old daughter, which led to audible gasps in the audience.

In a recent post (see also our paper preprint here), I estimated that the ~3 million adults who get cluster headaches worldwide spend roughly 5 million person-days experiencing excruciating pain (at ≥9/10) every year. And the (sparse) epidemiological data we have seems to indicate that the prevalence of cluster headache may be higher in countries in the northern hemisphere. Sadly, even in rich, developed countries, patients struggle to get basic treatment for their pain (such as high-flow oxygen or triptans). Even worse, certain types of psychedelics that are very effective for a large fraction of patients (and likely more effective than the best standard treatments according to a 2018 systematic review by Rusanen et al.) are nearly impossible to get for most patients.

I believe that countries who are not doing everything they can to ensure that cluster headache patients get universal access to all possible treatments are complicit in torture. I think this is one of those instances where future generations will look back with disbelief and horror at our failure to prevent such extreme suffering, similarly to how we judge doctors in the 1800s who knew about anesthetic compounds but refused to use them for surgery for ideological reasons, leading to decades of unimaginable suffering in the operating room.^[1]

My three favorite talks were:

1. Dr. Mario Peres: “GBD and headache disorders”

Dr. Peres is the president-elect of the International Headache Society—so, a big shot. He has significantly contributed to the Global Burden of Disease reports, and in his talk he suggested finally including cluster headache as its own category in the GBD report. He also suggested assigning cluster headache a DALY disability weight of 0.70, which would put it among the most disabling conditions in the world (the condition with the highest weight is “Chronic ischemic stroke severity level 5, with severe heart failure, with severe dementia,” with a weight of 0.79; see full list here).

We’ve argued (e.g. in our paper) that the DALY is ill-suited to capture the severity of extreme suffering. I was lucky to have been one of the two people to be chosen among audience members to ask Dr. Peres a question, and I raised this point (together with the thought experiment I presented in this talk). He was very sympathetic, and agreed that more research is needed. (I was determined to talk to him during the breaks, but he seems to have left the conference shortly after his talk.)

2. Dr. Juan Pablo Lopez: “Psilocybin in research and the clinic”

Dr. Lopez was introduced as a “rising star” in the field of psychedelic research, and while he does not work specifically on cluster headache (he works in psychiatry), he did his homework and looked into the existing evidence on psychedelics for cluster headache, which he admitted being fascinated and impressed by. (Among others, he seems to have read the book Psychedelic Outlaws by Joanna Kempner, which describes in fascinating detail the underground patient community that developed psychedelic treatments for cluster headache years before medical research caught up. Highly recommended!) In his talk, he emphasized the safety of many psychedelic compounds, especially at the low doses that are often enough to eliminate cluster headache pain.

We had a good chat over lunch, during which I also told him about the potential of DMT to abort cluster headache attacks. See for yourself:

(Dr. Schindler at Yale is working on this problem and could use additional funding, so let me know if you have any leads.)

3. Dr. Caroline Ran: “Mental health and headache”

In previous editions of the annual patient conference organized by Clusterbusters, Bob Wold (founder and president of Clusterbusters) has shown pictures of previous attendees who took their lives to escape the pain, asking attendees to support one another, and mentioning that the person to their left or right could be next. Published data on suicidality among cluster headache patients is sparse, so Dr. Ran analyzed patterns of depression, anxiety, social withdrawal, and suicidality in a cohort of Swedish patients. She found that nearly 50% of participants reported suicidal ideation (compared to ~9% in the general population). And remember, this is in one of the countries with the best healthcare in the world.

Sadly, there don’t seem to be any very promising new treatments on the horizon. Some groups (like Dr. Ran’s) are betting on genetic research (cluster headache has a genetic component). Others, on neuropeptides. Prof. Erling Tronvik, who talked about surgical interventions, mentioned that preliminary results injecting onabotulinumtoxinA into the sphenopalatine ganglion were encouraging. However, if I read their study correctly, it’s not as effective as psilocybin or LSD and it has significantly more adverse effects. Honestly, I think I’d rather try a low dose of psilocybin before having this macabre-looking device injected deep into my jaw without anesthesia:

I talked to other attendees primarily about (1) my research on burden quantification / suffering metrics, (2) using DMT as an abortive treatment, and (3) a psychedelic advocacy initiative I’m working on (more details soon). I was pleased with people’s encouraging reactions, especially on the sensitive topic of psychedelic advocacy, though I did hear two people express skepticism: One of them seemed to be ideologically opposed to psychedelics in any context (and was not an expert in cluster headache). The other was a prominent cluster headache researcher who, during a Q&A, expressed concerns about the potential side effects of substances like BOL-148 (a non-hallucinogenic analog of LSD), using a somewhat dismissive tone. However, the BOL-148 paper clearly states that "Only very mild side effects, if any, have been observed, when given in the dose range used in our project." In particular, one patient reported a “flabby feeling” for about 2h. The concerned researcher brought up exactly this side effect, saying that "flabby feeling" sounded kind of concerning. Curiously, the list of pharma-related conflict of interests he disclosed at the beginning of his talk was almost as long as the list of treatments Bob Wold tried over 20 years before finally finding relief in psilocybin:

(Also, both researchers were in their sixties.)

Most attendees were researchers, though I believe there might have been some patients, as well as someone developing a cluster headache tracking app. I couldn’t find anyone else working on advocacy.

The format of the symposium was very traditional for academia, with back-to-back talks in an auditorium and short breaks in between. This made it difficult to talk to people one-on-one (even during the after event, which was a beautiful 4-hour boat trip around Stockholm; everyone remained seated at their dinner table, so I only got to interact with the three other attendees at my table). I’m spoiled by EAGs.

Overall, I found it motivating and inspiring to finally meet others working on cluster headache (outside of QRI). Slowly but surely, the most painful condition known to mankind is getting the attention it deserves.

—

I’m grateful to the EA Infrastructure Fund for providing funding for me to attend.

Appendix: Testimonials of cluster headache patients

Here are a few assorted testimonials I’ve gathered from patients describing cluster headache pain.

From Rossi et al. 2018

“Imagine that a pack of dogs with enormous fangs are tearing you inside your head, tearing off the flesh, crushing everything. Then, a pile of red hot metal passes through your skull, burning the back of your eye and crosses your palate down to your throat. But the most important thing is that, during an attack, the pain moves up to a new dimension. You no longer have a headache, or pain located at a particular site: you are literally plunged into the pain, like in a swimming pool. There is only one thing that remains of you: your agitated lucidity and the pain that invades everything, takes everything. There is nothing but pain. At that point, you would give everything, including your head, your own life, to make it stop.”

“Imagine that someone is stabbing a knife in your eye and turning it for hours. Imagine the worst pain. Imagine a daily torture, gratuitous, incomprehensible. Imagine yourself suffering alone, terribly. Imagine being a prisoner in a straitjacket of suffering... Imagine the desire to finish, with pain, and the desire to finish … with yourself.”

“Imagine how it feels to be subjected to a knife attack on your head, like someone boring a screwdriver into your eye over and over again, sometimes for hours. On a bad day, you suffer up to eight episodes in the space of 24 hours. Not having a normal sleep for days. On a scale of one (no pain) to ten (worst imaginable pain), you rate your pain at eleven and more. Imagine constantly living in fear, not knowing when the next attack will happen, insisting that your wife leave the room when you get an attack because you don’t want her to see you in such pain. Imagine going to bed every night knowing that you will have an attack in less than an hour. If you did, you would understand”

“Imagine the fear, spending the time you are pain-free thinking about it coming back. [..] Feel the anger that gnaws at you when you think that this is your only life, the only one you have, and you have to spend it like this, with no chance of retaliating.”

From clusterheadaches.com

"I've seen him walk down the hallway (holding onto the wall for dear life) with his head cocked to one side and walking like a 100-year old man. I've seen him cry, pull out his hair, and beg me to take him to the emergency room. On one occasion, I was driving to the hospital - in the middle of the night - with 2 daughters in the back seat and he's practically pushing the dash of the car through the windshield because I'm not driving fast enough - and he's crying all the way. I know that he will do ANYTHING - ANYTHING to get rid of this pain. I can't believe that most doctors don't realize this - maybe they'd like to spend a couple of nights at my house and see what he goes through !!! When he's having the series of headaches he won't sleep because he knows that he will wake with another one - what a terrible, scary feeling! Thank God I don't suffer from these headaches - but I feel so helpless when it comes to comforting him. After a while it starts taking its toll on me and our children. I dred for the night to come - since that's when most of his headaches recur and we start all over again!"

"I just gotten over an attack. I've been going 5 weeks non-stop. 4-6 attacks per day. No sleep. No relief. I'm exhausted. I keep telling myself this hell is going to end soon, but I'm beginning to think that it's not. I can't think. I can't eat. I can't leave my house. When I'm not in pain, I'm in dread of it coming back. The attacks are increasing in intensity everyday and I sometimes think that I will go mad. I try everything to ease them a little and nothing seems to be working. I really don't know how much more I can take. I keep telling myself that I am strong enough to deal with it. I've been doing it for a long time now. But then the next one hits, and I become a whimpering little baby with no strength what-so-ever. My only saving grace is being able to write this down and know that you will understand like no one else can. I'll close my eyes now and hope that maybe I will sleep a little before the next one hits. Thanks for being here."

From OPIS 2020

"I hit myself in the head to distract myself from the pain when I have a cluster headache. The pain is indescribable hell, and in desperate moments, I have hit my head against a brick wall."

“Today is one of those days I wonder why I push through…”

“I don’t know how to deal with this day in and day out.. wave after wave of attacks. During some of the attacks I get so desperate to make it stop that I wish I could just not exist.”

“The insane pain just radiates through my brain.”

“No pills work. It’s the worst pain I ever had... If nothing helps I don’t think I can handle this for the rest of my life.”

"On a scale of 1 to 10, the pain is a 50."  (American football player Terrance Knighton)

From support groups on Facebook

"Like an ice pick is stabbed in my eye while a drill is drilling on my head at the same time. Nobody can possibly understand unless they have been through them."

“I've been through three natural childbirths and I say it's worse than that!”

“I tell people I would rather go through the birth of both my kids once a week to avoid cluster headaches."

“Like a broken glass bottle being pushed in my head and a poker coming out of my right eye."

“Like my brain is coming out of my ears and my eye is bleeding acid."

“I describe them as someone drilled a hole into my head and poured a flammable liquid in and set it on fire. With a mouth of rotting teeth. And poking my eye out with a hot poker. All at the same time."

“I never cried during childbirth, but I cry like a baby whenever I experience a cluster attack.”

“I’ve always told myself I’d rather be shot or stabbed when in an attack.”

From MedCrave

“A Cluster Headache is just pure unadulterated crisp pain. Awesome in its crystal clarity, pain far beyond the ultimate severity, pain beyond belief, pain beyond the realm of comprehension!

Just incredibly Violent Pain! Pain in its purest, rawest clinical form. A Cluster is devastatingly brutal in its existence and severely persistent in its relentless assault. Penetrating deep into your soul. Searching for your weakness, many times finding it…

A Cluster completely violates your being and conquers the mind, ripping & tearing through the eye, into your mind, body and soul, demanding your total respect and complete undivided attention, awareness and focus…

A Cluster completely obliterates your thoughts and your whole being. The pain consumes all of you, overtaking all thought, destroying the ability to fight back… Absorbing you and violently dragging you into a deep dark abyss of pure primal all consuming terrifying pain and severe brutal agony. A void hell of existence where only excruciating pain thrives, abounds and exists…

Down there your only defense is raw primal instinct of self preservation and pure thought of survival above all else. A lonely dark excruciatingly painful and terrifying hell, always on the edge of the abyss, always on the edge of one last breath. Pushing us to the utmost limits of endurance and extreme stubborn resistance…

Pain so crisp and untainted and overwhelmingly intense there is nothing to compare it to… It has to be felt to be believed and even then is just unbelievable!… And although you can feel that you are most definitely without a doubt going to die, it doesn’t kill you!! It leaves you embedded as a prisoner to come back and violate you and torture you every day and night, over and over and over again…

And in a sick, cynical cycle, we somehow survive it over and over and over again. A cruel & terrifying ritual beyond any logic, far beyond the realm of imagination, far beyond conceived reality. It is the literal feeling of death without dying… Sometimes lasting for more than 40 years. In my case 41 years…”

1. ^{^}

    More on the history of anesthesia in this talk by Andrés Gómez-Emilsson.