BOL-148 Bromo-LSD

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noticetext: 'The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series'
excerpt: "Introduction\nCluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital\nor periorbital pain and categorized as either episodic or\nchronic (1,2). Its prevalence is 0.1% (3). Oxygen and\nsumatriptan are the treatments of choice for individual\nattacks, whereas verapamil, lithium, corticosteroids\nand other neuromodulators can suppress attacks\nduring cluster periods (1). All standard medication\ntreatments may be ine!ective. Surgical treatment may\nbe an option for medication non-responders, including\ndeep brain (4) or occipital nerve stimulation (5).\nHowever, serious complications from brain surgery,\nincluding death, can occur (6).\nAn Internet survey of 53 CH patients reported on\nclaims that psilocybin is better at aborting acute attacks\nthan either oxygen or sumatriptan and that LSD and\npsilocybin are both better at triggering and extending\nremission than standard drugs (7). However, due to\nhallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed\nwithin the most restrictive Schedule I of the Controlled\nSubstances Act, which sanctions only limited research\nuse. Although the hallucinogenic properties of LSD\nand psilocybin are undesirable from both regulatory\nand patient safety perspectives, it was unclear to us at\nthe outset whether a non-hallucinogenic analog could\nalso provide meaningful relief to CH patients. To\naddress the question of whether the CH relief associated with these two structurally diverse compounds\nis related to the mechanisms triggering intoxication,\nwe decided to investigate the e\"cacy of a nonhallucinogenic analog of LSD. LSD’s hallucinogenic\ne!ects are completely lost when the double bond in\nthe D ring is saturated and with substitution at R2\n(e.g. by bromination in 2-bromo-LSD) (BOL-148) (8).\nBOL-148 has been studied in volunteers (up to 20 mg\nper os) (9) and in patients su!ering from vascular headaches but not, apparently, in patients with CH (9,10).\nThese past studies concluded that BOL-148 is non-toxic\nand non-hallucinogenic. Only very mild side e!ects, if\nany, have been observed, when given in the dose range\nused in our project (30 mg/kg/body weight) (9). No\nlong-term behavioral or psychological e!ects from\nBOL-148 have been reported from past studies with\nmore than 300 healthy, normal subjects (11), and\n30 mg BOL-148 administered daily over four to five\nweeks failed to alter active psychosis in chronically ill\nschizophrenic women (12).\nCase series\nPatients referred to Hannover Medical School’s Pain\nClinic were identified with CH if they met the respective\ndiagnostic criteria of the International Classification of\nHeadache Disorders (2). All patients, who were seriously a!ected by the disease, were non-responders to\nverapamil (or could not tolerate its side e!ects at higher\ndoses) and to some extent to other prophylactic medications as well, although not all medication alternatives\n(e.g. topiramate or prednisone), or more invasive procedures (e.g. intravenous dihydroergotamine or occipital nerve stimulator implantation), had been attempted.\n1\nHannover Medical School, Germany.\n2\nMcLean Hospital and Harvard Medical School, USA.\nCorresponding author:\nMatthias Karst, Department of Anesthesiology, Pain Clinic,\nCarl-Neuberg-Str. 1, 30625 Hannover, Germany.\nEmail: ed.revonnah-hm|saihttam.tsrak#ed.revonnah-hm|saihttam.tsrak\nCephalalgia OnlineFirst, published on March 26, 2010 as doi:10.1177/0333102410363490All patients signed an informed consent that declared\ntheir agreement to participate in this project on the compassionate use of BOL-148 for CH. It was approved by\nthe local ethics committee in accordance with German\nlaw. Patients kept a standardized daily diary of CH\nsymptoms (see www.clusterbusters.com for a copy)\nstarting at least two weeks prior to BOL-148 administration. BOL-148 was manufactured by THC pharm\nGmbH (Frankfurt am Main, Germany). A purity of\n>99.2% was identified by high-performance liquid chromatography (HPLC) and other analytical tests. BOL-\n148 30 mg/kg/body weight was dissolved in distilled\nwater and then given once every five days for a total of\nthree doses per os. BOL-148 was administered in the\npresence of two of the authors (MK, TP). Alterations\nin consciousness, thought disturbances, and vital signs\n(blood pressure, heart rate) were measured during a\nthree-to-four-hour observational period, as BOL-148 is\ntypically active for two to three hours. Patients were\nasked to continue completing daily headache diaries\nfor at least one month or until they experienced three\ndays of attacks, starting a new cluster series.\nResults are summarized in Table 1 and Figure 1. One\npatient (S2) with episodic CH, who was in an active\nattack period, and four patients with the chronic form\nparticipated. All but one patient (S1) had experienced\nsymptoms for more than 10 years. Patient S2’s cluster\nperiod terminated after BOL-148 with a long-lasting\nremission period of six months (at last follow-up) and\ncontinuing. Patients S3 and S5 reported pronounced\nreduction of attack frequency, including full remission\nfor more than one month, indicating transition from a\nchronic to an episodic form. Cluster attacks resumed\nafter a two-month remission for patient S5. In nine\nmonths since BOL-148 treatment, patient S3 describes\nongoing remission of cluster period, reporting only a few\nsolitary sporadic attacks. Patient S4 reported a profound reduction in attack frequency, although without\none full month of remission and attack frequency\nincreasing approximately six months after BOL-148\ntreatment. In addition, patients S3 and S4 found the\npain intensity of remaining occasional attacks so\nimproved that they no longer administered an acute\nintervention, as they had prior to BOL-148. Although\npatient S1 did not experience pronounced attack reduction similar to the other four patients, he indicated a\ndecrease of attack intensity of about 30% within the\nfirst four months. It is likely relevant that patient S1\ncontinued to drink alcohol (contrary to advice), a\nknown and common trigger for attacks.\nNo changes to heart rate and blood pressure were\nobserved during BOL-148 treatment. Most of the\npatients recorded some kind of ‘‘flabby’’ or ‘‘light\ndrunk’’ feelings. Patient S2 noted a ‘‘funny’’ feeling,\ntense muscles, and sweaty palms. These mild subjective\ne!ects lasted from one to two hours. No visual hallucinations or distortions occurred, nor was there any\nevidence of delusional thinking or overt psychosis."

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