Alternative and emerging treatments for cluster headache

A substantial part of the community reports that sub-hallucinogenic doses of psilocybin (the active compound in "magic mushrooms") can abort a cluster period, extend remission and reduce attack frequency. These come mainly from patient surveys and case reports, not large randomised trials.

Promising but limited by study size and design. A Sewell and colleagues survey (2006) found a majority of patients who had used psilocybin reported period termination or remission extension. A small 2022 pilot randomised, double-blind, placebo-controlled trial (Schindler et al., Headache) did not reach statistical significance on its primary outcome but suggested possible reductions in attack frequency.

Ten of the original participants returned at least six months later for a blinded extension of the same trial and received a repeat psilocybin pulse regimen (Schindler, Sewell, Gottschalk et al., Journal of the Neurological Sciences, 2024). In the three weeks after the pulse began, attack frequency fell from 18.4 to 9.8 attacks per week, a statistically significant reduction (p=0.013). Everyone who returned received active psilocybin - there was no placebo group in this extension - so it cannot establish that psilocybin works, only that the earlier signal is worth pursuing in a properly controlled trial.

That caution is reinforced by Schindler's group testing psilocybin against an active placebo for the first time this year, in migraine rather than cluster headache: 18 adults received psilocybin or diphenhydramine (an antihistamine with its own noticeable effects, used to help preserve blinding) across two dosing sessions a week apart. Migraine frequency fell by a similar amount in every arm, including the active-placebo arm, and the difference between psilocybin and diphenhydramine was not statistically significant (Schindler et al., Headache, 2026). It is a reminder that open-label or single-blind pulse studies can overstate a drug effect, and that cluster headache research needs the same active-placebo scrutiny.

Not fully understood, though thought to involve serotonergic modulation of trigeminal pathways and possible circadian resetting.

The PEACE trial (Psilocybin Efficacy and Acceptability on Cluster headache Episodes) is a randomised, placebo-controlled pilot recruiting 40 cluster headache patients in Australia, testing 10mg oral psilocybin once weekly for four weeks against placebo as a preventive. It is led by Dr Faraidoon Haghdoost at The George Institute for Global Health and UNSW Sydney, funded through the Australian Medical Research Future Fund (MRFF), and described by the George Institute as the first newly approved cluster headache trial in Australia in at least two decades. The investigators note that with verapamil ineffective for more than half of patients and few other preventives available, people already self-medicate with psilocybin from unregulated sources; the trial aims to generate safety data and help inform a future prescribing pathway.

Beyond the legal risk and the danger of an unregulated, misidentified or contaminated mushroom supply, a specific and predictable danger in this community is people stopping a preventive such as verapamil in order to attempt a self-directed psilocybin "bust". Stopping a preventive mid-bout - rather than tapering it under clinical oversight once the period has settled - can let attacks rebound in frequency and severity. Psilocybin also has real drug interactions: case reports link classic psychedelics combined with therapeutic-dose lithium to seizures, which is why lithium is an exclusion criterion in major psilocybin clinical trials; caution is also needed with SSRIs, SNRIs and MAO-inhibitor antidepressants. Psilocybin is inappropriate for anyone with a personal or family history of psychosis or bipolar disorder, in whom it can precipitate or worsen serious psychiatric illness. None of this is a substitute for discussing your full medical history and medicines with a doctor.

Otherwise unapproved, psilocybin can only be legally prescribed in New Zealand through a narrow, prescriber-specific pathway: as of September 2026, at least two individually named psychiatrists have Medsafe approval under Regulation 22 of the Misuse of Drugs Regulations 1977, and each may prescribe, supply and administer it only to patients they have personally assessed and diagnosed with treatment-resistant depression, following a defined, Medsafe-reviewed treatment protocol. Outside that approval, psilocybin and psilocin remain an unapproved medicine and a Class A controlled drug under the Misuse of Drugs Act 1975. Possession, supply and use are illegal without specific approval. We do not advise or encourage illegal use. We present this because patients seek this information regardless and deserve accurate, evidence-based facts.

Clusterbusters alternative treatments has detailed patient-led resources on psychedelic therapy. The George Institute's PEACE trial announcement has more on the Australian trial. Provided for education only; some substances discussed are illegal in New Zealand.

Patient reports of LSD use for cluster headache predate the psilocybin literature. Some report that very small (sub-hallucinogenic) doses have aborted cluster periods. The mechanism is broadly similar to psilocybin.

Less developed than for psilocybin, consisting mainly of patient reports.

LSD is a Class A controlled drug, illegal to possess or use in New Zealand under the Misuse of Drugs Act 1975. There is no approved clinical access pathway.

Some report cannabis helps manage anxiety around attacks or gives some relief. There are also reports of cannabis triggering attacks in some patients.

Weak for cannabis as a specific cluster headache treatment.

Medical cannabis products are legal in New Zealand and can be prescribed by a GP or specialist. Products vary widely in THC and CBD content. If interested, discuss it with your doctor, who can apply for Medsafe approval for an appropriate product.

A hand-held device applied to the neck. Non-invasive vagus nerve stimulation (gammaCore) is approved in some countries for acute and preventive cluster headache treatment. It is not funded by PHARMAC and must be purchased privately.

More commonly used for migraine, with less evidence for cluster headache.

An implanted sphenopalatine ganglion (SPG) stimulator was developed for refractory cluster headache. The company that originally held the intellectual property collapsed, and insertions have generally not continued since before COVID. It is not a practical treatment pathway in New Zealand at the time of writing.

Some headache services use neck-based assessment, physiotherapy or manual therapy. These may be relevant for neck-related or cervicogenic headache, or secondary headache disorders that can mimic cluster headache features.

Primary cluster headache is a neurological trigeminal autonomic cephalalgia. We are not aware of good clinical trial evidence that manual therapy treats primary cluster headache itself. Reproducing head pain during a neck assessment does not, on its own, prove the neck is the cause.

This is not a warning against physiotherapy if you also have neck pain. It is a reminder to ask what evidence exists specifically for cluster headache, what the total expected cost is, and whether it is being used alongside, not instead of, evidence-based treatments such as oxygen, subcutaneous sumatriptan, verapamil and specialist care.

Case reports and small series suggest ketamine infusions may give temporary relief for refractory cluster headache. This is not a standard treatment and would only be considered in specialist or hospital settings.

Ketamine is a controlled drug in New Zealand and can only be legally administered in clinical settings by authorised practitioners.

A very low carbohydrate, higher fat diet that aims to produce nutritional ketosis. It is established in some neurological settings such as drug-resistant epilepsy, and has been explored in headache disorders including cluster headache.

Interesting but early. A small prospective observational report described improvement during ketogenic diet in drug-resistant cluster headache. A later open-label, single-arm trial of a modified Atkins ketogenic diet in chronic cluster headache reported reduced attack frequency over 12 weeks, but the study was small and had no blinded placebo control.

Treat it as an emerging, non-drug option with limited evidence, not a proven replacement for oxygen, sumatriptan, verapamil or specialist care. It can be hard to sustain and inappropriate for some people, especially those with diabetes, kidney disease, eating disorder history, pregnancy, lipid disorders or complex medical needs. Discuss it with your GP, neurologist or a registered dietitian.

The anti-inflammatory Vitamin D3 regimen is widely discussed in patient communities. It usually involves vitamin D3 plus cofactors such as magnesium and vitamin K2, with blood testing used to monitor 25(OH)D and safety markers.

Some patients report major benefit. A 2014 survey of 110 cluster headache patients using a self-selected, self-funded regimen (10,000 IU/day vitamin D3 as cholecalciferol, plus omega-3 fish oil, bought over the counter rather than prescribed or publicly funded) found around 80% reported reductions in attack frequency, duration and severity (Batcheller P, Neurology, 2014;82(10 Suppl):P1.256, American Academy of Neurology annual meeting). This was a self-selected, self-funded, self-reported patient survey, not a controlled trial, so it cannot rule out placebo effect or selection bias.

Discuss it with your GP or specialist, especially if you have kidney disease, high calcium, sarcoidosis, take thiazide diuretics, or use other supplements or medicines.

A detailed patient-community resource is at vitamindregimen.com. Disclosure: Craig Stewart hosts that website. Cluster Headache Aotearoa NZ links to it for patient education and does not present it as a substitute for medical advice, diagnosis or treatment.