Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey

This survey study (n=496) found that indoleamine hallucinogens such as psilocybin and LSD are reportedly comparable to or superior in efficacy against cluster headaches than conventional treatments. Importantly, infrequent and non-hallucinogenic doses of these substances were reported to suffice for this effect to occur.

Abstract

“Cluster headache is one of the most debilitating pain syndromes. A significant number of patients are refractory to conventional therapies. The Clusterbusters.org medication use survey sought to characterize the effects of both conventional and alternative medications used in cluster headache. Participants were recruited from cluster headache websites and headache clinics. The final analysis included responses from 496 participants. The survey was modeled after previously published surveys and was available online. Most responses were chosen from a list, though others were free-texted. Conventional abortive and preventative medications were identified and their efficacies agreed with those previously published. The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications. Furthermore, infrequent and non-hallucinogenic doses were reported to be efficacious. Findings provide additional evidence that several indoleamine hallucinogens are rated as effective in treating cluster headache. These data reinforce the need for further investigation of the effects of these and related compounds in cluster headache under experimentally controlled settings.”

Authors: Emmanuelle A. D. Schindler, Christopher H. Gottschalk, Marsha J. Weil, Robert E. Shapiro, Douglas A. Wright & Richard Andrew Sewell

Summary

Cluster headache, often rated the most painful of all primary headache disorders, causes significant disability, enormous personal, economic, and psychiatric burden, and is characterized by a unilateral stabbing pain, lasting 15 – 180 minutes, occurring several times daily, usually at strikingly predictable times.

Cluster headache is treated with oxygen inhalation, subcutaneous triptan administration, verapamil, corticosteroids, and other neuromodulators. However, prophylactic medications are not without unwanted effects, and some patients are refractory to medical therapy.

Clusterbusters.org is a website founded by a clusterhead who resolved to share the discovery that the hallucinogenic compound, lysergic acid diethylamide (LSD), treated his cluster headaches. The website’s public message board is openly discussed about LSD and other alternative therapies for cluster headache.

Subjects and Study Design

The survey was created and carried out by Clusterbusters, Inc. and included 41 questions that included demographics, headache characteristics, smoking and drinking habits, and medications. Medication effectiveness was assessed by a four-tier rating scale that included not effective, partially effective, moderately effective, and completely effective. There were 651 responders, 558 of whom completed the survey, and 496 indicated that their diagnosis of cluster headache was verified by a neurologist or headache specialist.

Statistical Analysis

The majority of the data are descriptive. Inferences were calculated using different formulae for single- and dual-population calculations, and efficacy was compared using Fisher’s exact test.

Demographics and Headache Characteristics

Demographic data are shown in Table 1. Cluster headache was more common in earlier decades, and women were diagnosed within one year of their first cluster attack.

Data on cluster headache characteristics are shown in Table 2. Most respondents had fewer than seven attacks daily, and right side-locked attacks were more common in episodics than left side-locked attacks.

Abortive Medications

The most common medications used to abort cluster attacks are illustrated in Figure 1. Triptan injection, high-flow oxygen, triptan pills, intranasal triptan, and psilocybin are the most effective medications, with cafergot/ergotamine and intravenous dihydroergotamine being less effective.

Preventative Medications

The medications most commonly used to prevent cluster attacks along with their relative efficacies are illustrated in Figure 2. Prednisone was significantly more effective than verapamil, psilocybin, LSD, and lysergic acid amide were significantly more effective than methysergide, and DMT was as effective as prednisone and verapamil.

Effects on the Cluster Period, Remission, and Conversion

Many survey responders specified which medications, treatments, or situations shortened or aborted a cluster period. Psilocybin was significantly more commonly identified than all other medications, while LSD was no different from either verapamil or steroid.

Many survey responders felt there was a medication, treatment, or situation that led to remission from chronic cluster headache. Psilocybin was the most commonly identified medication, followed by LSA, verapamil, LSD, steroids, topiramate, vitamin regimen, and lithium.

The most common medications for those who became chronic were verapamil, triptans, lithium, opiates, oxygen, steroids, topiramate, no medication, valproate, cafergot, tricyclic antidepressant, barbiturate, pregabalin, psilocybin, DHE, LSA, and LSD.

Dosing and Regimens

Participants reported that their most effective abortive and preventative medications were between 120 and 1020 mg daily, with 480 mg daily being the most commonly reported dose. The doses of hallucinogens used to abort and prevent attacks were relatively consistent among responders, but the number of seeds consumed varies among plant varieties. The only BOL regimen reported (3.1 mg every five days for three days) corresponds to that used in an earlier case series. Psilocybin, LSD, and LSA were used daily to weekly for abortive purposes, and every few weeks to twice yearly for prevention.

Side-Effects

Though side-effects were not specifically queried, a few participants noted them in the freetext sections. These included rebound headaches, nausea and vomiting, swelling, hypotension, and cardiac arrhythmias, and memory loss, reduced sexual drive, and avascular necrosis of the femur in one respondent.

DISCUSSION

Cluster headache is a neglected condition with only one drug approved by the Food and Drug Administration. The Clusterbusters medication use survey considered both conventional and alternative therapies for cluster headache.

In the current survey, high-flow oxygen and triptan injections were the most commonly used and effective abortive treatments. Psilocybin was tried as an abortive therapy in roughly one-third of responders. In acute treatment of cluster headache, high-flow oxygen, subcutaneous sumatriptan injection, and oral zolmitriptan are effective. Psilocybin is also an effective abortive agent, but LSD and LSA are not included in the list of drug options for abortive medications.

Most people who tried preventive medications for cluster headaches found them effective. Verapamil, prednisone, melatonin, topiramate, and psilocybin were the most commonly used medications, and their efficacy was similar to previous reports. In contrast to conventional medications, psilocybin and LSD provided at least moderate protection from cluster attacks in over 70% of those who tried them. BOL provided at least moderate protection from attacks in 60% of those who tried it.

Participants in the current survey used hallucinogens infrequently for the treatment of cluster headache, compared to other preventive medications that require daily dosing and have many negative side-effects. A single dose of psilocybin or LSD prevented attacks, shortened/aborted a cluster period, or induced remission from chronic cluster headache.

The current survey found that participants used sub-hallucinogenic doses of psilocybin, LSD, and LSA to treat cluster headache, and that the non-hallucinogenic LSD congener, BOL, was on par with psilocybin, LSD, and LSA in preventative efficacy.

This study has several limitations, including bias for those with Internet access, recall bias, lack of diagnostic validity, and the fact that many participants tried multiple drugs, allowing for individual interpretation of efficacy.

CONCLUSION

The Clusterbusters medication use survey supports the efficacy of indoleamine hallucinogens in the treatment of cluster headache. These drugs are historically safe and may provide clinical relief with modest and infrequent use.