# 2-Bromo-LSD

2-Bromo-LSD, also known as BOL-148 or as bromolysergide, is a derivative of lysergic acid invented by Albert Hofmann, as part of the original research from which the closely related compound LSD was also derived. It is a non-hallucinogenic serotonin 5-HT$_{2A}$ receptor partial agonist, as well as acting at other targets, with psychoplastogenic and antidepressant-like effects in animals.

## Pharmacology

2-Bromo-LSD was found to be inactive as a psychedelic and so was comparatively little researched for many years, although its similar behaviour in the body made it useful for radiolabelling studies. It was found to bind to many of the same receptors as LSD, but acting as a neutral antagonist rather than an agonist. 2-Bromo-LSD reportedly attenuates the effects of LSD in humans.
In 2023, 2-bromo-LSD was characterised as a non-hallucinogenic serotonin 5-HT$_{2A}$ receptor biased partial agonist and as a serotonin 5-HT$_{2B}$ receptor antagonist. It shows weaker partial agonism of the serotonin 5-HT$_{2A}$ receptor than LSD (E$_{max}$ = 60% vs. 92%, respectively). Unlike LSD, 2-bromo-LSD fails to produce the head-twitch response, a behavioural proxy of psychedelic effects, in animals. In addition, 2-bromo-LSD blocked the head-twitch response of the psychedelic DOI. 2-Bromo-LSD shows weak recruitment of β-arrestin2 and has reduced potential to induce tolerance in the form of serotonin 5-HT$_{2A}$ receptor downregulation. Similarly to LSD, the drug was also found to interact with numerous other serotonin receptors and targets. However, 2-bromo-LSD reportedly shows less off-target activity compared to LSD.
In animals, 2-bromo-LSD shows psychoplastogenic (i.e., neuroplasticity-enhancing) effects and antidepressant-like effects.

## Clinical development

The generally similar behaviour of 2-bromo-LSD to LSD in some respects has shown to be very useful in potential the treatment of cluster headaches. These debilitating attacks have been known for some time to be amenable to treatment with certain hallucinogenic drugs such as LSD and psilocybin, but because of the illegal status of these drugs and the kind of mental changes they induce, research into their medical use has been slow and therapeutic application limited to very specific circumstances under strict supervision. It had been thought that this specific therapeutic action against cluster headaches was limited to hallucinogenic drugs of this type, and would always present a major barrier to their clinical use. However, a serendipitous discovery found that 2-bromo-LSD can also produce this therapeutic effect, despite lacking the other effects of LSD. This has led to a resurgence of interest and research into 2-bromo-LSD and its possible medical uses. Some isolated incidents of hallucinogenic responses with 2-bromo-LSD have been reported, but as with other non-hallucinogenic LSD analogs such as lisuride, this appears to be a rare side effect occurring only in individuals with an as yet unexplained susceptibility to this reaction.
2-Bromo-LSD, under the developmental code name BETR-001 (previously TD-0148A), is under development by BetterLife Pharma for the treatment of cluster headaches and other indications.