bromolysergide, 2-bromolysergic acid diethylamide, BOL-148, 2-bromo-N,N-diethyllysergimide

The Chemistry of 2-Bromo-LSD

2-Bromo-LSD was first synthesized by Franz Troxler and Albert Hofmann in 1957.1 Just like the more well-known compound synthesized by Hofmann, LSD, the synthesis of 2-Bromo-LSD was not an accident. The 1957 paper details their synthesis of various 2-halogenated derivatives of lysergic acid and dihydrolysergic acid.

The Pharmacology of 2-Bromo-LSD

At the time of their 1957 synthesis paper, Hofmann and Troxler were looking for LSD derivatives that could be made into anti-inflammatory and anti-migraine drugs. One characteristic of such compounds would be their ability to block serotonin receptors. In his book LSD – My Problem Child, Hofmann says that he and Troxler “…searched systematically for LSD derivatives without hallucinogenic effects, but with the highest possible activity as serotonin blockers.” 2

2-Bromo-LSD is a serotonin 5-HT2A receptor antagonist.3 The compound blocks the effects of LSD,4 but has no psychological effects on its own.5 A 1959 human study reported that some tolerance does develop to 2-Bromo-LSD, and prolonged administration does not cause a significant resistance to the effects of LSD.6

The data from receptor binding studies shows that 2-Bromo-LSD has high affinity for serotonin receptors (see table below).

The Applications and Potential of 2-Bromo-LSD

2-Bromo-LSD has not received much research attention. A 2010 open randomized study case series by Karst et al. found 2-Bromo-LSD was effective in improving the frequency and intensity of attacks of cluster headaches.7

Receptor Binding Affinity Data

ReceptorKi (nM)SpeciesNoteRef.
  1. Troxler F, Hofmann A. Substitutionen am Ringsystem der Lysergsäure. III. Halogenierung. 45. Mitteilung über Mutterkornalkaloide. Helvetica Chimica Acta. 1957;40(7):2160-2170. doi:10.1002/hlca.19570400716
  2. Hofmann A. LSD - My Problem Child. McGraw-Hill Book Company; 1980.
  3. Nichols DE. Structure–activity relationships of serotonin 5-HT2A agonists. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 2012;1(5):559-579. doi:10.1002/wmts.42
  4. Ginzel KH, Mayer-Gross W. Prevention of Psychological Effects of d -Lysergic Acid Diethylamide (LSD 25) by its 2-Brom Derivative (BOL 148). Nature. 1956;178(4526):210-210. doi:10.1038/178210a0
  5. Cerletti A, Rothlin E. Role of 5-Hydroxytryptamine in Mental Diseases and its Antagonism to Lysergic Acid Derivatives. Nature. 1955;176(4486):785-786. doi:10.1038/176785a0
  6. Balestrieri A, Fontanari D. Acquired and Crossed Tolerance to Mescaline, LSD-25, and BOL-148. AMA Arch Gen Psychiatry. 1959;1(3):279-282. doi:10.1001/archpsyc.1959.03590030063008
  7. Karst M, Halpern JH, Bernateck M, Passie T. The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series. Cephalalgia. 2010;30(9):1140-1144. doi:10.1177/0333102410363490
  8. Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL. Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences. J Pharmacol Exp Ther. 1996;276(2):720-727. Accessed May 11, 2020. http://jpet.aspetjournals.org/content/276/2/720
  9. Bard J, Zgombick J, Adham N, Vaysse P, Branchek T, Weinshank R. Cloning of a Novel Human Serotonin Receptor (5-HT7) Positively Linked to Adenylate Cyclase. J Biol Chem. 1993;268(31):23422-23426. https://www.jbc.org/content/268/31/23422.full.pdf