2-Bromo-LSD

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

Receptor Ki (nM) Species Ref.
5-HT2A 0.48 Human 8
5-HT2B 8.56 Human 8
5-HT2C 7.14 Human 8
5-HT6 17.1 Human 9
5-HT7 30.0 Human 9
    References
  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