The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

Cluster headache is a severe, one-sided headache condition affecting 0.1% of people. Standard treatments like oxygen and sumatriptan can fail, and surgical options carry serious risks. An internet survey of 53 patients suggested that the hallucinogens psilocybin and LSD may abort attacks and extend remission better than standard drugs, but these substances are criminalized. To test whether a non-hallucinogenic LSD analog could also help, researchers investigated 2-bromo-LSD (BOL-148). Past studies found BOL-148 non-toxic and non-hallucinogenic, with only mild side effects at the dose used, and no long-term effects in over 300 healthy subjects or in schizophrenic women given 30mg daily for weeks.

Study at a glance

Abstract

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6). An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a nonhallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies concluded that BOL-148 is non-toxic and non-hallucinogenic. Only very mild side effects, if any, have been observed, when given in the dose range used in our project (30mg/kg/body weight) (9). No long-term behavioral or psychological effects from BOL-148 have been reported from past studies with more than 300 healthy, normal subjects (11), and 30mg BOL-148 administered daily over four to five weeks failed to alter active psychosis in chronically ill schizophrenic women (12).