25B-NBOMe, also known as NBOMe-2C-B and Cimbi-36, is a

psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluc ...

of the

25-NB The 25-NB (25''x''-NB''x'') series, or NBOMe series, also known as the ''N''-benzylphenethylamines, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C family. The most commonly encountere ...

(NBOMe) family derived from

2C-B 2C-B, also known as 4-bromo-2,5-dimethoxyphenethylamine or by the slang name Nexus, is a synthetic psychedelic drug of the 2C family, mainly used as a recreational drug. It was first synthesized by Alexander Shulgin in 1974 for use in psychoth ...

. It acts as a potent

full agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agoni ...

for the 5HT_2A

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

. Duration of effects lasts about 3 to 10hours, 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. The carbon-11 labeled version of this compound ( sup>11Cimbi-36) was synthesized and validated as a

radioactive tracer A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to ...

for positron emission tomography (PET) in Copenhagen. As a 5-HT_2A receptor agonist PET radioligand, sup>11Cimbi-36 was hypothesized to provide a more functional marker of these receptors. Also, sup>11Cimbi-36 is investigated as a potential marker of serotonin release and thus could serve as an indicator of serotonin levels

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

. sup>11Cimbi-36 is now undergoing clinical trials as a PET-ligand in humans. 25B-NBOMe was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

by Ralf Heim and colleagues at the

Free University of Berlin The Free University of Berlin (, often abbreviated as FU Berlin or simply FU) is a public university, public research university in Berlin, Germany. It was founded in West Berlin in 1948 with American support during the early Cold War period a ...

by 1999.

Interactions

Toxicity and harm potential

Neurotoxic and cardiotoxic actions

Emergency treatment

Pharmacology

Pharmacodynamics

25B-NBOMe is a selective

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT₂ receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

. It showed roughly the same

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors in one study (K_i = 0.5–1.7nM). However, in another study, it showed 12- to 20-fold selectivity for the serotonin 5-HT_2A receptor (K_i = 0.5nM) over the serotonin 5-HT_2B and 5-HT_2C receptors (K_i = 10 and 6.2nM, respectively). The drug is highly selective for the serotonin 5-HT₂ receptors over a variety of other

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s, as well as over various other

monoamine receptor A monoamine receptor is a receptor for the monoamine neurotransmitters and/or trace amines, endogenous small-molecule signaling molecules with a monoamine structure. The monoamine receptors are almost all G protein-coupled receptors, with the se ...

s and over the

monoamine transporter Monoamine transporters (MATs) are proteins that function as integral Cell membrane, plasma-membrane Neurotransmitter transporter, transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are se ...

s (>200-fold selectivity). However, 25B-NBOMe is a low-

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of ho ...

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

of the rat and mouse

trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is a primarily intracellular amine-activated and G protein-coupled receptor (GPCR) that is p ...

(TAAR1) but is inactive at the human TAAR1. 25B-NBOMe has been found to increase levels of

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, and

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

in the

frontal cortex The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove betw ...

striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...

, and

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...

in rats. Other serotonergic psychedelics like

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

and DOI have also been found to increase glutamate levels in the frontal cortex in rodents, and this effect can be blocked by the serotonin 5-HT_2A receptor antagonist volinanserin (MDL-100,907). 25B-NBOMe shows an inverted U-shaped dose–response curve in terms of

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

elevations in multiple brain areas. This may be due to an inhibitory effect of serotonin 5-HT_2C receptors at higher doses. 25B-NBOMe produces the

head-twitch response The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

, a behavioral proxy of psychedelic effects, in rodents, and this effect shows an inverted U-shaped dose–response curve similarly to its influences on neurotransmitter levels. The head twitches and hallucinogenic effects of 25B-NBOMe may be due to increased cortical glutamate release secondary to serotonin 5-HT_2A receptor activation. The effects of 25B-NBOMe on levels of other neurotransmitters, such as accumbal dopamine concentrations, may also be mediated by activation of serotonin 5-HT_2A receptors and glutamate elevation. It has been suggested that the serotonin elevations with 25B-NBOMe may be involved in its production of

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

in humans. Unlike many other serotonergic psychedelics, 25B-NBOMe has been found to produce reinforcing effects in rodents, including conditioned place preference (CPP) and

self-administration Self-administration is, in its Medicine, medical sense, the process of a subject administering a Pharmacology, pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a Diabetes, diabetic ...

, and hence may have misuse potential. Accordingly, 25B-NBOMe robustly increased

levels in the

in rodents similarly to but a lesser extent than

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

, and its reinforcing effects could be blocked by the

dopamine receptor antagonist A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and have been used in tr ...

s SCH-23390 and

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychos ...

. Serotonin 5-HT_2A receptor activation is known to increase dopamine release in the

mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The v ...

. However, the reinforcing effects of 25B-NBOMe were not blocked by the selective serotonin 5-HT_2A receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.ketanserin Ketanserin, sold under the brand name Sufrexal, is an antihypertensive agent which is used to treat arterial hypertension and vasospasm, vasospastic disorders. It is also used in scientific research as an antiserotonergic medication, agent in th ...

. Similarly to 25B-NBOMe,

25N-NBOMe 25N-NBOMe, also known as 2C-N-NBOMe or NBOMe-2C-N, is a derivative of the hallucinogen 2C-N. The pharmacological properties of 25N-NBOMe have not been described in the scientific literature, but it is believed to act in a similar manner to relate ...

has also shown reinforcing effects in rodents. More research is needed to elucidate how 25B-NBOMe and other NBOMe drugs produce reinforcing effects in animals. 25B-NBOMe has been found to decrease

locomotor activity Locomotor activity is a measure of animal behavior which is employed in scientific research. Hyperlocomotion, also known as locomotor hyperactivity, hyperactivity, or increased locomotor activity, is an effect of certain drugs in animals in whi ...

in rodents.

Chemistry

Analogues and derivatives

Another analogue of 25B-NBOMe is DOB-NBOMe.

History

25B-NBOMe was first described in the

, in the form of conference abstracts, by Ralf Heim and colleagues at the

by 1999.Heim, R., Pertz, H. H., & Elz, S. (1999). Preparation and in vitro pharmacology of novel secondary amine-type 5-HT2A receptor agonists: from submillimolar to subnanomolar activity. Arch. Pharm. Pharm. Med. Chem, 332, 34. https://bitnest.netfirms.com/external/Arch.Pharm.Pharm.Med.Chem/331.S1.34

Society and culture

Legal status

Canada

As of October 31, 2016; 25B-NBOMe is a controlled substance (Schedule III) in Canada.

China

As of October 2015 25B-NBOMe is a controlled substance in China.

Czech Republic

25B-NBOMe is banned in the Czech Republic.

Finland

Scheduled in the "government decree on substances, preparations and plants considered to be narcotic drugs".

Russia

Banned as a narcotic drug since May 5, 2015.

Sweden

In Sweden, the

Riksdag The Riksdag ( , ; also or , ) is the parliament and the parliamentary sovereignty, supreme decision-making body of the Kingdom of Sweden. Since 1971, the Riksdag has been a unicameral parliament with 349 members (), elected proportional rep ...

added 25B-NBOMe to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of August 1, 2013, published by the Medical Products Agency in their regulation LVFS 2013:15 listed as ''25B-NBOMe 2-(4-bromo-2,5-dimetoxifenyl)-N-(2-metoxibensyl)etanamin''.

United Kingdom

United States

In November 2013, the U.S. Drug Enforcement Administration placed 25B-NBOMe (along with

25I-NBOMe 25I-NBOMe, also known as 2C-I-NBOMe, Cimbi-5, and shortened to "25I", is a psychedelic drug of the phenethylamine, 2C, and NBOMe (25-NB) families. Since 2010, it has circulated in the recreational drug scene, often misrepresented as LSD. It is ...

and 25C-NBOMe) in Schedule I of the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

, making it illegal to manufacture, buy, possess, process, or distribute.

Notes

References

External links

25B-NBOMe - Isomer Design
{{Phenethylamines 5-HT2A agonists 25-NB (psychedelics) 2C (psychedelics) Designer drugs Bromobenzene derivatives PET radiotracers 2-Methoxyphenyl compounds TAAR1 agonists