25I-NBOMe

Systematic (IUPAC) name
2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine
Clinical data
Pregnancy cat.	?
Legal status	Temporary class drug (UK) Unscheduled, prohibited in some states (US)
Routes	Buccal (sublabial), sublingual, insufflated, inhalation, intravenous, intramuscular, rectal
Identifiers
CAS number	919797-19-6  N 1043868-97-8 (hydrochloride)
ATC code	None
PubChem	CID 10251906
ChemSpider	8427392  Y
Chemical data
Formula	C18H22INO3
Mol. mass	427.28 g/mol
SMILES[show] COC1=CC=CC=C1CNCCC2=CC(=C(C=C2OC)I)OC
InChI[show] InChI=1S/C18H22INO3/c1-21-16-7-5-4-6-14(16)12-20-9-8-13-10-18(23-3)15(19)11-17(13)22-2/h4-7,10-11,20H,8-9,12H2,1-3H3  Y Key:ZFUOLNAKPBFDIJ-UHFFFAOYSA-N  Y
N (what is this?)  (verify)

25I-NBOMe (2C-I-NBOMe) is a derivative of the substituted phenethylamine psychedelic 2C-I discovered in 2003 by chemist Ralf Heim at the Free University of Berlin. It is a highly potent serotonin agonist and, due to its psychedelic effects and ambiguous legal status, a designer drug with reports of recreational use beginning in 2010. Reports of deaths and significant injuries have been attributed to the use of 25I-NBOMe, prompting some governments to control its possession, production, and sale.

Discovery[edit source | edit]

25I-NBOMe was discovered in 2003 by Ralf Heim, a chemist at the Free University of Berlin, who published his findings in his PhD dissertation.^[1] The chemical was subsequently investigated by a team at Purdue University led by David Nichols.^[2] The carbon-11 labelled version of this compound ^[11C]Cimbi-5 was synthesized and validated as a radiotracer for positron emission tomography (PET) in Copenhagen.^[3][4] Being the first 5-HT_2A receptor full agonist PET radioligand, ^[11C]Cimbi-5 shows promise as a more functional marker of these receptors, which may be involved in mental disorders such as depression and schizophrenia.^{[citation needed]}

Chemistry and Structure[edit source | edit]

Like other NBOMe chemicals, 25I-NBOMe is a derivative of the 2C family of phenethylamines described by Alexander Shulgin in his book PiHKAL.^[5][6] Specifically, 25I-NBOMe is the N-benzyl derivative of the phenethylamine molecule 2C-I, formed by adding a 2-methoxybenzyl (MeOB) onto the nitrogen (N) of the phenethylamine molecule. This substitution significantly increases the potency of the molecule.^[5]

Synthesis[edit source | edit]

25I-NBOMe is usually synthesised from 2C-I and 2-methoxybenzaldehyde, in a reductive alkylation. It can be done stepwise by first making the imine and then reducing the formed imine with sodium borohydride, or by direct reaction with sodium triacetoxyborohydride.^[1]

Pharmacology[edit source | edit]

25I-NBOMe acts as a highly potent full agonist for the human 5-HT_2A receptor,^[7][9] with a K_i of 0.044 nM, making it some sixteen times the potency of 2C-I itself, and a radiolabelled form of 25I-NBOMe can be used for mapping the distribution of 5-HT_2A receptors in the brain.^[8] In vitro tests showed this compound acted as an agonist but animal studies have not been reported. While the N-benzyl derivatives of 2C-I were significantly increased in potency compared to 2C-I, the N-benzyl derivatives of DOI were inactive.^[10]

Ki values of the following targets were greater than 500 nM: 5-HT_1A, D₃, H₂, 5-HT_1D, α_1A adrenergic, δ opioid, serotonin uptake transporter, 5-HT_5A, 5-HT_1B, D₂, 5-HT₇, D₁, 5-HT₃, 5-HT_1E, D₅, muscarinic M₁-M₅, H₃, and the dopamine uptake transporter.^[8]

Recreational Use[edit source | edit]

25I-NBOMe had no history of recreational use prior to being sold online as a designer drug in 2010; street names of the drug now include "N-Bomb", "Smiles," and "25I". As a recreational drug, 25I-NBOMe is roughly as potent as and similar in effect to LSD; consequently, the drug is sometimes misrepresented on blotter paper as LSD.^[11] Case reports of 25I-NBOMe intoxication, with and without analytical confirmation of the drug in the body, are increasing in the medical literature.^[6] The chemical has emerged as a recreational drug in Europe and the United States^[12] as well as Australia.^[5]

25I-NBOMe is inactive orally, and the most common methods of administration are sublingual, buccal, or nasal. The drug is frequently loaded onto paper "tabs" which are placed under the tongue or in the gums.^[5] There are also reports of intravenous injection of dissolved 25I-NBOMe and smoking the drug in powdered form.^[12][13]

Internet forum reports suggest that the drug debuted in the United States after an amateur American chemist imported from Europe the drug 2C-I, which was unscheduled in the US at the time, before converting it into its more potent NBOMe form and transferring it to blotter paper.^[5] The drug came to media attention in early 2012 after a cluster of seven non-fatal overdoses was reported in and around Richmond, Virginia.^[14][15][16]

25I-NBOMe is frequently sold online through vendors on Silk Road or websites specializing in the sale of designer drugs. Online venders frequently ship wholesale orders from China, a manufacturing hub, for sale in the United States, Europe, and Australia.^[17] Due to its potency, the drug is highly profitable, as small quantities of the drug can comprise large numbers of doses; one kilogram of powdered 25I-NBOMe can generate up to 20 million recreational doses.^[5] Drug dealers often purchase 25I-NBOMe in bulk online and resell individual doses on the street for considerable profit. In Australia, $2 tabs of 25I-NBOMe can be resold for $20-30 each as LSD.^[17] There are, however, methods of differentiating between LSD and adulterants like 25I-NBOMe in the field with and without test kits.^[18]

Dosage[edit source | edit]

25I-NBOMe is extremely potent; a dose is typically less than one milligram (while a dose of the psychedlic phenethylamine 2C-I is approximately 20 milligrams). The UK Advisory Council on the Misuse of Drugs states that a common dose is between 50 and 100µg.^[5] By contrast, Erowid tentatively suggests that the threshold dosage for humans is 50-250µg (though many experience reports posted by consumers suggest this low dosage is merely Erowid's promotion of harm reduction, as the threshold dosage is more likely 500ug+).^[19] At this level of potency, there is significant risk of overdose when consumers fail to take the necessary steps, in order to ensure that they have precisely measured doses.^[5]

Effects[edit source | edit]

25I-NBOMe effects usually last 6-10 hours if taken sublingually or buccally.^[13] When it is insufflated, effects usually last 4–6 hours.^[13] Effects can however last significantly longer depending on dosage; durations longer than 12 hours have been reported.

25I-NBOMe can also be vaporized and inhaled, this may cause significantly quicker effects and shorter duration as is expected from that route of administration. This route of administration is however not recommended, unless when using precise liquid measurement, due to the difficulties of measuring and handling substances active in the microgram range.

Case reports of seven British males who presented to an emergency room following analytically confirmed 25I-NBOMe intoxication suggest the following potential adverse effects: "tachycardia (n = 7), hypertension (4), agitation (6), aggression, visual and auditory hallucinations (6), seizures (3), hyperpyrexia (3), clonus (2), elevated white cell count (2), elevated creatine kinase (7), metabolic acidosis (3), and acute kidney injury (1)."^[12]