25I-NBOMe

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 of designer drugs. In a slang context, the name of the compound is often shortened to "25I" or is simply called "N-Bomb". 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. 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. although other sources indicate that these figures are incorrect; Erowid tentatively suggests that the threshold dose 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. At this level of potency, it is not possible to accurately measure a single dose of 25I-NBOMe powder without an analytical balance, and attempting to do so may put the user at significant risk of overdose. Effects 25I-NBOMe effects usually last 6–10 hours if taken sublingually, or buccally (between gum and cheek). 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. ==Toxicity and harm potential==

Neurotoxic and cardiotoxic actions Emergency treatment Attributed deaths 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 website Erowid 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." In June 2012, two teens in Grand Forks, North Dakota and East 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. A 21-year-old man from Little 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. 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. and the death of a 17-year-old in Minnesota in January 2014, as well as the death of a 15-year old in Washington in September 2014. 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. 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 and power poles while intoxicated by 25I-NBOMe. A Sydney teenager jumped off a balcony to his death on June 5, 2013, while on 25I-NBOMe. 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. 25I-NBOMe has been linked to a major case on January 20, 2016, in Cork, Ireland, which left six teenagers hospitalized, one of whom later died. At least one of the teenagers suffered a cardiac arrest, according to reports, along with extreme internal bleeding. At least one suicide, and two attempted suicides leading to hospitalisation, have occurred while under the effects of 25I-NBOMe. ==Interactions==

2C drugs like 2C-I are metabolized by the monoamine oxidase (MAO) enzymes, including both MAO-A and MAO-B. As a result, 2C drugs may be potentiated by monoamine oxidase inhibitors (MAOIs), such as phenelzine, tranylcypromine, moclobemide, and selegiline. This has the potential to lead to overdose and serious toxicity. In contrast to 2C drugs, 25I-NBOMe has been found not to be metabolized by MAO-A or MAO-B and instead only by cytochrome P450 enzymes. Other 25-NB drugs besides 25I-NBOMe were not assessed. ==Pharmacology==

Pharmacodynamics 25I-NBOMe acts as a highly potent full agonist for the human 5-HT2A receptor, with a affinity (Ki) of 0.044 nM, making it some 16-fold higher affinity than 2C-I at this receptor. While in-vitro studies showed that N-benzyl derivatives of 2C-I were significantly increased in potency compared to 2C-I, the N-benzyl derivatives of the related compound DOI were inactive. 25B-NBOMe is a low-potency weak partial agonist of the rat and mouse trace amine-associated receptor 1 (TAAR1) but is inactive at the human TAAR1. The affinities and potencies of 25I-NBOMe at the serotonin 5-HT2 receptors have varied in different studies. Its affinities (Ki) have ranged from 0.044 to 0.6nM for the serotonin 5-HT2A receptor, 1.91 to 130nM for the serotonin 5-HT2B receptor, and 1.03 to 4.6nM for the serotonin 5-HT2C receptor. 25I-NBOMe also has weaker interactions with multiple other receptors. Kd values for interaction with the following targets were greater than 500nM: 5-HT1A, D3, H2, 5-HT1D, α1A adrenergic, δ opioid, serotonin uptake transporter, 5-HT5A, 5-HT1B, D2, 5-HT7, D1, 5-HT3, 5-HT1E, D5, muscarinic M1-M5, H3, and the dopamine uptake transporter. Likewise, 25I-NBOMe has been found to increase dopamine levels in the nucleus accumbens in rodents in vivo. 25I-NBOMe has been found to produce neurotoxicity in rodents. A radiolabelled form of 25I-NBOMe can be used for mapping the distribution of 5-HT2A receptors in the brain. It does not appear to be metabolized by the monoamine oxidase (MAO) enzymes MAO-A or MAO-B. ==Chemistry==

Like other 2C-X-NBOMe molecules, 25I-NBOMe is a derivative of the 2C family of phenethylamines described by chemist Alexander Shulgin in his book PiHKAL. Specifically, 25I-NBOMe is an N-benzyl derivative of the phenethylamine molecule 2C-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. The carbon-11 labelled version of 25I-NBOMe, [11C]Cimbi-5, was synthesized and validated as a radiotracer for positron emission tomography (PET) in Copenhagen. Being the first 5-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. ==History==

25I-NBOMe was first described in the scientific literature, in the form of conference abstracts, by Ralf Heim and colleagues at the Free University of Berlin by 2000. Then, in 2003, Heim described 25I-NBOMe in his dissertation. 25I-NBOMe was encountered as a novel recreational drug by 2010, and by 2012, NBOMe drugs like 25I-NBOMe had eclipsed other psychedelics like LSD and psilocybin-containing mushrooms in popularity, at least for a time. 25I-NBOMe became a Schedule I controlled substance in the United States in 2013. ==Society and culture==

Legal status Australia 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. Brazil All drugs in the NBOMe family, including 25I-NBOMe, are illegal. Canada As of October 31, 2016; 25I-NBOMe is a controlled substance (Schedule III) in Canada. China As of October 2015 25I-NBOMe is a controlled substance in China. European Union In September 2014 the European Union implemented a ban of 25I-NBOMe in all its member states. Finland 25I-NBOMe is scheduled in government decree on narcotic substances, preparations and plants as of 2022 and is hence illegal to possess or use. Israel Israel banned 25I-NBOMe in 2013. Russia 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. Serbia 25I-NBOMe was put on the list of prohibited substances in March 2015. Sweden The Riksdag added 25I-NBOMe to Narcotic Drugs Punishments Act under Swedish schedule I ("substances, plant materials and fungi which normally do not have medical use") as of August 1, 2013, published by Medical Products Agency (MPA) in regulation LVFS 2013:15 listed as 25I-NBOMe, and 2-(4-jodo-2,5-dimetoxifenyl)-N-(2-metoxibensyl)etanamin. Taiwan Following the European rule from 2014, 25I-NBOMe was put in class 4 of prohibited substances. United Arab Emirates 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. United Kingdom United States 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. while permanent scheduling was arranged. 25I-NBOMe, 25B-NBOMe and 25C-NBOMe are currently Schedule 1 Substances according to 21 CFR 1308.11(d). ==See also==