25I-NBOMe, also known as2C-I-NBOMe,Cimbi-5, and shortened to "25I", is apsychedelicdrug of thephenethylamine,2C, andNBOMe (25-NB) families.[1] Since 2010, it has circulated in therecreational drug scene, often misrepresented asLSD.[6] It is the most well-known member of the 25-NB family and the earliest member to be encountered as a novel recreational drug.[6]
Thecarbon-11 labelled version of 25I-NBOMe, [11C]Cimbi-5, was synthesized and validated as aradiotracer forpositron emission tomography (PET) in Copenhagen.[7][8] Being the first5-HT2A receptor full agonist PET radioligand, [11C]CIMBI-5 shows promise as a more functional marker of these receptors, particularly in their high affinity states.[7]
Street and media nicknames for this drug include "N-Bomb", "Solaris", "Smiles", and "Wizard", although the drug is frequently fraudulently sold as LSD.[1][9][10][11]
Due to its physical effects and risk ofoverdose, there have been multiple deaths attributed to the drug.[1] Its long-termtoxicity is unknown due to lack of existing research.
Although 25I-NBOMe was first described by 2000, it did not emerge as a common recreational drug until 2010, when it was first sold by vendors specializing in the supply ofdesigner drugs.[19] In a slang context, the name of the compound is often shortened to "25I" or is simply called "N-Bomb".[20] According to a 2014 survey, 25I-NBOMe was the most frequently used of the NBOMe series.[21] By 2013, case reports of 25I-NBOMe intoxication, with and without analytic confirmation of the drug in the body, were becoming increasingly common in the medical literature.[22]
25I-NBOMe is widely rumored to be orally inactive; however, apparent overdoses have occurred via oral administration. Common routes of administration includesublingual,buccal, andintranasal.[21] For sublingual and buccal administration, 25I-NBOMe is often applied to sheets ofblotter paper of which small portions (tabs) are held in the mouth to allow absorption through the oral mucosa.[23][24] There are reports of intravenous injection of 25I-NBOMe solution and smoking the drug in powdered form.[25][26]
Due to its potency and much lower cost than so-called classical or traditional psychedelics, 25I-NBOMe blotters are frequently misrepresented as, or mistaken forLSD blotters.[27] Even small quantities of 25I-NBOMe can produce a large number of blotters. Vendors would import 25I-NBOMe in bulk (e.g., 1 kg containers) and resell individual doses for a considerable profit.[24]
25I-NBOMe is potent, being active in sub-milligram doses. A common dose of the hydrochloride salt is 600–1,200 μg. The UK Advisory Council on the Misuse of Drugs states that a common dose is between 50 and 100 μg,[24] although other sources indicate that these figures are incorrect;Erowid tentatively suggests that the threshold dosage for humans is 50–250 μg, with a light dose between 200–600 μg, a common dose at 500–800 μg, and a strong dose at 700–1500 μg.[28]
At this level of potency, it is not possible to accurately measure a single dose of 25I-NBOMe powder without ananalytical balance, and attempting to do so may put the user at significant risk of overdose.[24] There is a high risk of overdose due to the small margin between a high-dose and an over-dose, which is not a risk with the similar drugLSD. One study has shown that 25I-NBOMe blotters have 'hotspots' of the drug and the dosage is not evenly applied over the surface of the paper, which could lead to overdose.[29]
25I-NBOMe effects usually last 6–10 hours if taken sublingually, or buccally (between gum and cheek).[1][26] When it is insufflated (snorted), effects usually last 4–6 hours.[1][26]
25I-NBOMe has similar effects to LSD, though users report more negative effects while under the influence and more risk of harm following use as compared to the classical psychedelics.[21]
25I-NBOMe can be consumed in liquid, powder or paper form and can be snorted, injected, mixed with food, or smoked, but sublingual administration is most common.[30]
NBOMe and NBOHs are regularly sold as LSD in blotter papers,[32][40] which have a bitter taste and different safety profiles.[34][31] Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity.[31] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[36] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[34] While most fatalities are due to the physical effects of the drug, there have also been reports of death due toself-harm and suicide under the influence of the substance.[41][42][34]
Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown.[34] NBOMe compounds are not active orally,[a] and are usually taken sublingually.[44]: 3 When NBOMes are administered sublingually,numbness of the tongue and mouth followed by a metallic chemical taste was observed, and researchers describe this physical side effect as one of the main discriminants between NBOMe compounds and LSD.[45][46][47]
Many of the NBOMe compounds have high potency agonist activity at additional 5-HT receptors and prolonged activation of 5-HT2B can cause cardiac valvulopathy in high doses and chronic use.[32][37] 5-HT2B receptors have been strongly implicated in causing drug-inducedvalvular heart disease.[48][49][50] The high affinity of NBOMe compounds foradrenergic α1 receptor has been reported to contribute to the stimulant-type cardiovascular effects.[37]
In vitro studies, 25C-NBOMe has been shown to exhibitcytotoxicity on neuronal cell linesSH-SY5Y,PC12, and SN471, and the compound was more potent thanmethamphetamine at reducing the visibility of the respective cells; the neurotoxicity of the compound involves activation ofMAPK/ERK cascade and inhibition ofAkt/PKB signaling pathway.[33] 25C-NBOMe, including the other derivative25D-NBOMe, reduced the visibility ofcardiomyocytes H9c2 cells, and both substances downregulated expression level of p21 (CDC24/RAC)-activated kinase 1 (PAK1), an enzyme with documented cardiac protective effects.[33]
Preliminary studies on 25C-NBOMe have shown that the substance is toxic to development, heart health, and brain health inzebrafish, rats, andArtemia salina, a common organism for studying potential drug effects on humans, but more research is needed on the topic, the dosages, and if the toxicology results apply to humans. Researchers of the study also recommended further investigation of the drug's potential in damaging pregnant women and their fetus due to the substance's damaging effects to development.[51][52]
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. The websiteErowid states that 25I-NBOMe is extremely potent and should not be snorted, and that the drug "appears to have led to several deaths in the past year."[27] Several non-fatal overdoses requiring prolonged hospitalization have also been reported.[24][22][25]
As of August 2015, 25I-NBOMe has reportedly led to at least 19 overdose deaths in the United States.[20][53] In June 2012, two teens inGrand Forks, North Dakota andEast Grand Forks, Minnesota fatally overdosed on a substance that was allegedly 25I-NBOMe, resulting in lengthy sentences for two of the parties involved and a Federal indictment against the Texas-based online vendor.[54] A 21-year-old man fromLittle Rock, Arkansas died in October 2012 after taking a liquid drop of the drug nasally at a music festival. He was reported to have consumed caffeinated alcoholic beverages for "several hours" beforehand. It is unclear what other drugs he may have consumed, as autopsies generally do not test for the presence of research chemicals.[55] In January 2013, an 18-year-old in Scottsdale, Arizona, died after consuming 25I-NBOMe sold as LSD; a toxicology screening found no other drugs in the person's system. The drug is the suspected cause of death in another Scottsdale, Arizona, incident in April 2013.[24] It is also cited in the death of a 21-year-old woman in August 2013[56] and the death of a 17-year-old in Minnesota in January 2014,[57] as well as the death of a 15-year old in Washington in September 2014.[58] In October 2015, a 20-year-old UCSB student from Isla Vista, California died of "acute hallucinogenic polysubstance intoxication" with an additional significant cause of death being "sharp force trauma of the upper extremity", according to a statement from Santa Barbara County Sheriff's office; the autopsy determined Sanchez was under the influence of two hallucinogenic drugs at the time of his death: ketamine and 25I-NBOMe. The noted sharp force trauma refers to a deep cut on Sanchez's right forearm, which was caused when he punched and broke a large residential window while suffering hallucinations.[59]
25I-NBOMe has been implicated in multiple deaths in Australia. In March 2012, a man in Australia died from injuries sustained by running into trees andpower poles while intoxicated by 25I-NBOMe.[60] A Sydney teenager jumped off a balcony to his death on June 5, 2013, while on 25I-NBOMe.[61]
In July 2015, 25I-NBOMe was involved in the death of 18-year-old Liam Miller in York, England. Miller was stabbed 32 times by his close friend, Samuel Donley, during a psychotic episode after both had ingested the drug. Donley also attacked a passer-by and inflicted self-injuries before being detained. He pleaded guilty to manslaughter on the grounds of diminished responsibility and was sentenced to six years and eight months in prison. The court described the incident as a "drug-crazed frenzy" and highlighted the extreme psychological effects associated with 25I-NBOMe.[62]
25I-NBOMe has been linked to a major case on January 20, 2016, inCork,Ireland, which left six teenagers hospitalized, one of whom later died. At least one of the teenagers suffered acardiac arrest, according to reports, along with extreme internal bleeding.[63]
At least one suicide, and two attempted suicides leading to hospitalisation, have occurred while under the effects of 25I-NBOMe.[64]
25I-NBOMe acts as a highlypotent fullagonist for thehuman5-HT2Areceptor,[84][72][85] with aaffinity (Ki) of 0.044 nM, making it some 16-fold higher affinity than2C-I at this receptor.[86] 25I-NBOMe induces ahead-twitch response in mice which is blocked completely by a selective 5-HT2A antagonist, suggesting its psychedelic effects are mediated by 5-HT2A. This study suggested that 25I-NBOMe is approximately 14-fold more potent than 2C-Iin-vivo.[86] Whilein-vitro studies showed thatN-benzyl derivatives of 2C-I were significantly increased in potency compared to 2C-I, theN-benzyl derivatives of the related compoundDOI were inactive.[87] 25B-NBOMe is a low-potency weakpartial agonist of the rat and mousetrace amine-associated receptor 1 (TAAR1) but is inactive at the human TAAR1.[82]
The affinities and potencies of 25I-NBOMe at the serotonin 5-HT2 receptors have varied in different studies.[86][88][89][71][90] Its affinities (Ki) have ranged from 0.044 to 0.6nM for the serotonin 5-HT2A receptor, 1.91 to 130nM for the serotonin5-HT2B receptor, and 1.03 to 4.6nM for the serotonin5-HT2C receptor.[86][88][89][71] Conversely, its potencies (EC50Tooltip half-maximal effective concentration) have ranged from 0.76 to 240nM at the serotonin 5-HT2A receptor, 111 to 130nM at the serotonin 5-HT2B receptor, and 2.38 to 88.9nM at the serotonin 5-HT2C receptor.[88][71]
Like other 2C-X-NBOMe molecules, 25I-NBOMe is a derivative of the2C family of phenethylamines described by chemistAlexander Shulgin in his bookPiHKAL.[24][22] Specifically, 25I-NBOMe is anN-benzyl derivative of the phenethylamine molecule2C-I, formed by adding a 2-methoxybenzyl (BnOMe) onto the nitrogen (N) of the phenethylamine backbone. This substitution significantly increases the potency of the molecule.[24]
25I-NBOMe was explicitly scheduled in Queensland drug law in April 2012, and in New South Wales in October 2013, as were some related compounds such as 25B-NBOMe. The Australian federal government has no specific legislation concerning any of the N-benzyl phenethylamines.[95]
Russia was the first country to pass specific regulations on the NBOMe series. All drugs in the NBOMe series, including 25I-NBOMe, became illegal in Russia in October 2011.[100]
The Riksdag added 25I-NBOMe toNarcotic Drugs Punishments Act underSwedish schedule I ("substances, plant materials and fungi which normally do not have medical use") as of August 1, 2013, published byMedical Products Agency (MPA) in regulationLVFS 2013:15 listed as 25I-NBOMe, and 2-(4-jodo-2,5-dimetoxifenyl)-N-(2-metoxibensyl)etanamin.[103]
The UAE has a zero-tolerance policy for recreational use of drugs. Federal Law No. 14 of 1995 criminalises production, import, export, transport, buying, selling, possessing, storing of narcotic and psychotropic substances (Including 25i-NBOMe) unless done so as part of supervised and regulated medical or scientific activities in accordance with the applicable laws. The UAE police has dedicated departments to deal with drugs' issues.[105]
On Nov 15, 2013, the DEA added 25I-NBOMe (and 25C-, and 25B-NBOMe) to Schedule I using their emergency scheduling powers, making those NBOMe compounds "temporarily" in Schedule I for 2 years.[53] In November 2015, the temporary scheduling was extended for an additional year[107] while permanent scheduling was arranged.[108] 25I-NBOMe, 25B-NBOMe and 25C-NBOMe are currently Schedule 1 Substances according to 21 CFR 1308.11(d).[109]
^Thepotency ofN-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50- to 100-fold greater (by weight) than oral route compared to the parent2C-x compounds.[43] Researchers hypothesize the low oral metabolic stability ofN-benzylphenethylamines is likely causing the low bioavailability on the oral route, although the metabolic profile of this compounds remains unpredictable; therefore researchers state that the fatalities linked to these substances may partly be explained by differences in the metabolism between individuals.[43]
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Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as theList of trace amines,TAAR, andTAAR1 pages. See also:Receptor/signaling modulators
