This open-label, case series study (n=6) investigated the efficacy of the non-hallucinogenic LSD-analog BOL-148 (3 doses of 2100µg/70kg) for treating cluster headaches within a clinically diagnosed patient sample. The results show that three single doses of BOL-148 within 10 days can either break a cluster headache cycle or considerably improve the frequency and intensity of attacks, even resulting in changing from a chronic to an episodic form, with remission extending for many months or longer.

Abstract

From the introduction:

“Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic. Its prevalence is 0.1%. Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods. All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain or occipital nerve stimulation. However, serious complications from brain surgery, including death, can occur…”

Authors: Matthias Karst, John H. Halpern, Michael Bernateck & Torsten Passie

Summary

Introduction

Cluster headache is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain. Oxygen and sumatriptan are the treatments of choice for individual attacks, but medication non-responders may need surgical treatment.

A survey of 53 CH patients reported that psilocybin and LSD were better at aborting acute attacks than oxygen and sumatriptan, but were criminalized due to their hallucinogenic properties. We decided to investigate whether a nonhallucinogenic analog of LSD could provide meaningful relief to CH patients.

BOL-148 has been studied in volunteers and patients suffering from vascular headaches, but not in patients with CH. It is non-toxic and non-hallucinogenic, and has only very mild side effects.

Case series

All patients with CH who were seriously affected by the disease were non-responders to verapamil and other prophylactic medications, although not all medication alternatives had been attempted.

All patients signed an informed consent and kept a daily diary of cluster headache symptoms. BOL-148 was administered once every five days for a total of three doses per os and patients were asked to continue completing daily headache diaries for at least one month.

One patient with episodic CH experienced a long-lasting remission period of six months after BOL-148 treatment, and two patients with chronic CH experienced a profound reduction in attack frequency, although patient S4 experienced attack frequency increasing approximately six months after BOL-148 treatment.

No changes to heart rate or blood pressure were observed during BOL-148 treatment. Patients reported mild subjective effects lasting from one to two hours.

Discussion

Three single doses of BOL-148 within 10 days can break a cluster headache cycle or improve the frequency and intensity of attacks, even resulting in changing from a chronic to an episodic form, with remission extending for many months or longer.

Sicuteri et al. used LSD and BOL-148 in the treatment of migraine and other vascular headaches, but no evidence was found that BOL-148 was administered specifically for active CH. A sufferers-driven interest in the clinical effects of LSD and psilocybin for CH developed recently, and BOL-148 also shows long-lasting effects. This suggests that the mechanism of action of BOL-148 is unrelated to those receptor systems thought to be involved with hallucino-genicity.

Methysergide was created to be a completely non-hallucinogenic form of LSD, but it does not generally induce remissions. However, dihydroergotamine is not approved for intravenous or subcutaneous injection in Germany. BOL-148, a new ergot-based medication, seems to exert its effects in a totally different way than methysergide and dihydroergotamine, and seems to be more unlikely to cause fibrotic complications from the limited, non-chronic dosing regimen of BOL-148 we employed.

In this case series, five patients with chronic headache responded to three doses of BOL-148 administered over ten days. Further research with more specific inclusion criteria will allow more specific conclusions to be drawn about BOL-148 as a potential treatment for chronic headache.