2-Bromo-LSD

Last updated
2-Bromo-LSD
2-bromo-LSD structure.svg
Clinical data
Other names2-Bromolysergic acid diethylamide; 2-Bromo-LSD; 2-Br-LSD; BOL-148; BOL148; Bromolysergide; BETR-001; TD-0148A; NYPRG-101
Legal status
Legal status
  • Not scheduled (United States, Canada, Germany, EU precursors) [1] [2]
Identifiers
  • (6aR,9R)-5-bromo-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C20H24BrN3O
Molar mass 402.336 g·mol−1
3D model (JSmol)
  • CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3=C(NC4=CC=CC(=C34)C2=C1)Br)C
  • InChI=1S/C20H24BrN3O/c1-4-24(5-2)20(25)12-9-14-13-7-6-8-16-18(13)15(19(21)22-16)10-17(14)23(3)11-12/h6-9,12,17,22H,4-5,10-11H2,1-3H3/t12-,17-/m1/s1 Yes check.svgY
  • Key:VKRAXSZEDRWLAG-SJKOYZFVSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

2-Bromo-LSD, also known as BOL-148, 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. [3]

2-Bromo-LSD was found to be inactive as a psychedelic and so was comparatively little researched for many years, although its similar behavior 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. [4] [5] 2-Bromo-LSD reportedly attenuates the effects of LSD in humans. [6] [7]

However its generally similar behavior to LSD in some respects has shown to be very useful in one specific area, the treatment of cluster headaches. [8] 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 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.

In 2023, 2-bromo-LSD was characterized as a non-hallucinogenic serotonin 5-HT2A receptor biased partial agonist and as a serotonin 5-HT2B receptor antagonist. [9] Similarly to LSD, it was also found to interact with numerous other serotonin receptors and targets. [9]

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. [10] [11]

Related Research Articles

<span class="mw-page-title-main">LSD</span> Hallucinogenic drug

Lysergic acid diethylamide, commonly known as LSD, is a potent psychedelic drug that intensifies thoughts, emotions, and sensory perception. Often referred to as acid or lucy, LSD can cause mystical, spiritual, or religious experiences. At higher doses, it primarily induces visual and auditory hallucinations. While LSD does not cause physical addiction, it can lead to adverse psychological reactions, such as anxiety, paranoia, and delusions. Additionally, it may trigger "flashbacks," also known as hallucinogen persisting perception disorder, where individuals experience persistent visual distortions after use.

<span class="mw-page-title-main">Psychedelic drug</span> Hallucinogenic class of psychoactive drug

Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states and a perceived "expansion of consciousness". Also referred to as classic hallucinogens or serotonergic hallucinogens, the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA, respectively.

<span class="mw-page-title-main">Ergine</span> Chemical compound

Ergine, also known as d-lysergic acid amide (LSA) and d-lysergamide, is an ergoline alkaloid that occurs in various species of vines of the Convolvulaceae and some species of fungi. The psychedelic properties in the seeds of ololiuhqui, Hawaiian baby woodrose and morning glories have been linked to ergine and/or isoergine, its epimer, as it is an alkaloid present in the seeds.

<span class="mw-page-title-main">Ergotamine</span> Chemical compound in the ergot family of alkaloids

Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor. It is used for acute migraines, sometimes with caffeine as the combination ergotamine/caffeine.

<span class="mw-page-title-main">5-Hydroxytryptophan</span> Chemical compound

5-Hydroxytryptophan (5-HTP), used medically as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.

<span class="mw-page-title-main">Psilocin</span> Chemical compound

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).

<span class="mw-page-title-main">Lysergamides</span> Class of chemical compounds

Amides of lysergic acid are collectively known as lysergamides, and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors. Lysergamides contain an embedded tryptamine structure, and as a result can produce similar, often psychedelic, effects to those of the true tryptamines.

<span class="mw-page-title-main">Ergometrine</span> Lysergamide

Ergometrine, also known as ergonovine and sold under the brand names Ergotrate, Ergostat, and Syntometrine among others, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used either by mouth, by injection into a muscle, or injection into a vein. It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection. Effects last between 45 and 180 minutes.

<span class="mw-page-title-main">Methylergometrine</span> Chemical compound

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.

<span class="mw-page-title-main">Methysergide</span> Chemical compound

Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the market in the United States and Canada due to adverse effects. It is taken by mouth.

<span class="mw-page-title-main">Lisuride</span> Chemical compound

Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.

5-HT<sub>2A</sub> receptor Subtype of serotonin receptor

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

<span class="mw-page-title-main">Lysergic acid 2,4-dimethylazetidide</span> Chemical compound

Lysergic acid 2,4-dimethylazetidide (LA-SS-Az, LSZ) is an analog of LSD developed by the team led by David E. Nichols at Purdue University. It was developed as a rigid analog of LSD with the diethylamide group constrained into an azetidine ring in order to map the binding site at the 5-HT2A receptor. There are three possible stereoisomers around the azetidine ring, with the (S,S)-(+) isomer being the most active, slightly more potent than LSD itself in drug discrimination tests using trained rats.

<span class="mw-page-title-main">25B-NBOMe</span> Chemical compound

25B-NBOMe is a derivative of the phenethylamine psychedelic 2C-B, discovered in 2004 by Ralf Heim at the Free University of Berlin. It acts as a potent full agonist for the 5HT2A receptor. Duration of effects lasts about 3–10 hours, although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses. Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.

<span class="mw-page-title-main">Substituted tryptamine</span> Class of indoles

Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.

<span class="mw-page-title-main">25CN-NBOH</span> Chemical compound

25CN-NBOH is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B. A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.

<span class="mw-page-title-main">1-Methylpsilocin</span> Chemical compound

1-Methylpsilocin (developmental code names CMY, CMY-16) is a tryptamine derivative developed by Sandoz which acts as a selective agonist of the serotonin 5-HT2C receptor (IC50Tooltip half-maximal inhibitory concentration of 12 nM, vs. 633 nM at 5-HT2A), and an inverse agonist at 5-HT2B (Ki of 38 nM). While 1-methylpsilocin does have higher affinity for 5-HT2C than 5-HT2A, it does produce a head-twitch response in mice that is dependent on 5-HT2A, so it is not entirely free of effects on 5-HT2Ain vivo. In contrast to psilocin, 1-methylpsilocin did not activate 5-HT1A receptors in mice.

<span class="mw-page-title-main">Pirenperone</span> Chemical compound

Pirenperone (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name; developmental code names R-47456, R-50656) is a serotonin receptor antagonist described as an antipsychotic and tranquilizer which was never marketed. It is a relatively selective antagonist of the serotonin 5-HT2 receptors and has been used in scientific research to study the serotonin system. In the 1980s, the drug was found to block the effects of the lysergic acid diethylamide (LSD) in animals, and along with ketanserin, led to the elucidation of the 5-HT2A receptor as the biological mediator of the effects of serotonergic psychedelics.

<span class="mw-page-title-main">Norpsilocin</span> Chemical compound

Norpsilocin, also known as 4-hydroxy-N-methyltryptamine (4-HO-NMT), is a tryptamine alkaloid recently discovered in 2017 in the psychedelic mushroom Psilocybe cubensis. It is hypothesized to be a dephosphorylated metabolite of baeocystin.

References

  1. "BOL-148 hydrochloride". THC Pharm GmbH. Archived from the original on 2012-12-17. Retrieved 2019-04-23.
  2. "BetterLife Confirms Non-Controlled Status of 2-bromo-LSD with Health Canada - Psilocybin Alpha". Psychedelic Alpha. 19 January 2021.
  3. Troxler F, Hofmann A (1957). "Substitutionen am Ringsystem der Lysergsäure. III. Halogenierung. 45. Mitteilung über Mutterkornalkaloide". Helvetica Chimica Acta. 40 (7): 2160–2170. doi:10.1002/hlca.19570400716.
  4. Ginzel KH, Mayer-Gross W (July 1956). "Prevention of psychological effects of d-lysergic acid diethylamide (LSD 25) by its 2-brom derivative (BOL 148)". Nature. 178 (4526): 210. Bibcode:1956Natur.178..210G. doi: 10.1038/178210a0 . PMID   13348662. S2CID   4169373.
  5. Isbell H, Miner EJ, Logan CR (November 1959). "Cross tolerance between D-2-brom-lysergic acid diethylamide (BOL-148) and the D-diethylamide of lysergic acid (LSD-25)". Psychopharmacologia. 1 (2): 109–116. doi:10.1007/bf00409110. PMID   14405871. S2CID   1915318.
  6. Mehta MA, Tricklebank MD (2019). "Serotonin and the psychedelics". The Serotonin System. pp. 193–202. doi:10.1016/B978-0-12-813323-1.00011-6. ISBN   9780128133231. S2CID   196510587.
  7. Tfelt-Hansen P (April 2011). "Is BOL-148 hallucinogenic?". Cephalalgia. 31 (5): 634, author reply 635-634, author reply 636. doi:10.1177/0333102410392069. PMID   21163816. S2CID   12412491.
  8. Karst M, Halpern JH, Bernateck M, Passie T (September 2010). "The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: an open, non-randomized case series". Cephalalgia. 30 (9): 1140–1144. doi:10.1177/0333102410363490. PMID   20713566. S2CID   33199115.
  9. 1 2 Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, Calkins MM, Bautista-Carro MA, Arsenault E, Telfer A, Taghavi-Abkuh FF, Malcolm NJ, El Sayegh F, Abizaid A, Schmid Y, Morton K, Halberstadt AL, Aguilar-Valles A, McCorvy JD (March 2023). "A non-hallucinogenic LSD analog with therapeutic potential for mood disorders". Cell Rep. 42 (3): 112203. doi:10.1016/j.celrep.2023.112203. PMC   10112881 . PMID   36884348.
  10. "BETR 001". AdisInsight. 29 August 2024. Retrieved 24 October 2024.
  11. "Delving into the Latest Updates on Bromolysergide with Synapse". Synapse. 14 October 2024. Retrieved 24 October 2024.

Further reading