Cluster headaches

Cluster headaches and potential therapies

About cluster headaches

Cluster headaches – sometimes referred to as Horton's cephalalgia or neuralgia, or informally as suicide headaches – have been recognised as one of the most excruciating pains known to medicine. The agony they cause is often compared to having a red hot ice pick driven though one’s eye and into the brain, and sufferers are reported to have suicide rates about 20x the average. The term "headache" is thus a misnomer that dramatically mischaracterises them.

Attacks typically last one hour, but the range is 15 minutes to as long as 3 hours, and they can repeat from once every second day to several times a day, in some cases even as often as 8-10 times a day. Attacks can occur in the middle of the night, and patients go to extremes, including banging their head against the wall, to try to distract themselves from the pain. About 80% of patients have episodic clusters lasting 1-3 months, once or twice a year at the same time of year, during which they have daily recurrences at the frequency mentioned; the other 20% have chronic clusters that can last for many months or years, with little or no pause. Cluster headaches affect about 0.1% of the population, with a prevalence in any one year of 0.05%. This means that approximately 7 million people globally suffer from cluster headaches.


Current medical options

Current preventative and therapeutic treatments, including prescription drugs, high-flow oxygen and electrical stimulation of the vagus nerve, can bring relief. However, no treatment is universally effective. Verapamil, used to prevent attacks, is only moderately effective. Sumatriptan, commonly used to abort attacks and most effective when injected under the skin, doesn't always reduce the pain sufficiently, and as it can have serious cardiovascular side effects, there are limits to how frequently it can be used and by whom, and not every attack can be safely treated. Having an oxygen delivery device constantly handy presents logistical constraints. A recently approved antibody-based drug, Emgality, offers a new means to significantly reduce the frequency of attacks in many patients, though it does not abort them. In addition to the limits to current therapies, cluster headaches are typically misdiagnosed, and it can be several years before a patient is correctly diagnosed and prescribed appropriate treatment.


Potential therapies

It has been observed that several drugs belonging to the tryptamine chemical family – including psilocybin (the psychoactive component of "magic mushrooms"), LSD and DMT (N,N-dimethyltryptamine, the psychoactive component of ayahuasca) – can be remarkably effective in aborting attacks and, at least for the first two (for which there is more extensive data), aborting and preventing cluster episodes, in anywhere from 70% to 95% of patients. The evidence comes from a large number of anecdotes from users, desperate to find effective treatments, and more systematic studies of online fora, surveys and interviews (see reference section below). Inhaled DMT can abort an attack in as little as 3-5 seconds according to reports (1, 2, 3). There are a few clinical studies currently underway with psilocybin and LSD, though apparently none with DMT. Aside from their efficacy, these drugs  might be safer to use than existing treatments because of their inherent properties, because lower doses can be used, and because they might not need to be used as often. Indeed, a Phase I clinical trial on psilocybin has found no adverse effects. Preventative effects on cluster headaches have been reported with just 3 doses (days 1, 5 and 11) rather than a daily dose (Prof. Torsten Passie, personal communication). They also offer the potential to reduce the cost of treatment.

Interestingly, the hallucinogenic properties of these drugs seem not to be strictly required for their therapeutic effect: sub-hallucinogenic doses of psilocybin and LSD have been found to be effective for aborting and preventing cluster headaches in some patients, although others required larger doses. Furthermore, a non-hallucinogenic analogue of LSD, 2-bromo-LSD (BOL-148), appeared to have similar efficacy to LSD in a small-scale clinical trial. (However, as it is patent-protected and expensive to manufacture, it appears to be currently unavailable for use.) With DMT there is anecdotal evidence that sub-hallucinogenic doses (e.g. 3 mg) can abort attacks in some people, while in others, "breakthrough" doses of 20-30 mg may be needed. Another related chemical with highly promising evidence for effectiveness is 5-MeO-DALT. There is evidence that LSA (lysergic acid amide) can also be effective, but it has been reported to have serious side effects.

In addition to their usefulness for cluster headaches, there is evidence that some of the drugs mentioned here can also be very effective in treating migraines, which are also highly debilitating.


The ethical need to relax legal restrictions

The severe legal restrictions on the possession and use of most of these drugs complicate research and development and limit their availability to cluster headache patients. Unsurprisingly, most health services make no mention of the potential of these drugs, despite their apparent effectiveness compared to approved treatments. Increasing numbers of clinical trials on psilocybin, LSD and MDMA for the relief of post-traumatic stress disorder (PTSD) and depression, and the trend towards decriminalisation/legalisation of marijuana, are de-stigmatising the use of mind-altering substances. But such stigmas remain, and are probably a significant reason why more politicians are not yet prepared to take a strong stance to facilitate their therapeutic use.

It is nonetheless an ethical imperative that patients in severe or extreme pain be able to access and try the most effective treatments available. When governments restrict such access, compel patients to break the law or impede the development of such treatments out of excessive caution, their policies are not aligned with their ethical responsibilities. Of course, as is the case with access to opioids, a balanced approach is necessary to prevent abuse, and care must be taken to ensure that a drug does not actually cause more harm than it relieves. However, in the case of cluster headaches, there is currently no such balance, and the restrictions in place allow extreme suffering to persist that could, in fact, be prevented.

OPIS advocates that people suffering from cluster headaches should be able to access the most effective treatments known.

Our approach includes:

  • Raising awareness among physicians worldwide to help reduce time to diagnosis
  • Communicating information on cluster headaches and evidence for effective treatments
  • Supporting efforts to develop promising therapies
  • Advocating for changes in legislation to reduce obstacles to availability


Please contact us if you would like to collaborate or support our efforts in any way, or just let us know if you found any of this information helpful. We are grateful for donations to support our advocacy work.

Important note and disclaimer: The information supplied here does not constitute medical advice. We are not encouraging anyone to contravene the law within their jurisdiction. We strongly encourage anyone contemplating use of any potential therapies mentioned here to make informed decisions and to educate themselves. In particular, inhaling DMT, especially in doses >5 mg, can raise blood pressure and lead to powerful experiences that could be traumatic. It is especially important to be accompanied by someone trusted, and not to wait until the onset of a cluster headache for any trials.


References and resources

General information


Support and advocacy organisations and communities
  • Clusterbusters, a US-based advocacy group that provides resources and promotes the research and development of new therapeutics, and their pages on cluster headaches, on using the Clusterbuster method and other tryptamines, and on coping without the usual prescription drugs
  • Cluster Headache Community, a friendly and supportive Facebook group that also provides a collection of files with information on treatment options
  • r/clusterheads, a reddit community for cluster headache sufferers
  • OUCH - Organisation for the Understanding of Cluster Headache, a helpful UK-based support group that, however, does not openly advocate for the development of the drugs mentioned here


Academic papers, talks and posters


Articles and posts


A small request

We rely on private donations to run our projects and our work towards a more compassionate world. This includes providing information and carrying out advocacy to prevent suffering, including for more pragmatic and compassionate drug policies. We are very grateful for support. If you like you can make one-off or monthly PayPal donations by clicking the donate button below. If you prefer to make a direct bank transfer please see our donate section. Thank you!

Last updated 26 January 2020

Credit: Photo "Hell" by VasenkaPhotography used under CC BY 2.0 license

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