# 25C-NBOMe

25C-NBOMe (NBOMe-2C-C, 2C-C-NBOMe, Cimbi-82) is a psychedelic drug and derivative of the psychedelic phenethylamine 2C-C. 25C-NBOMe appeared on online vendor sites in 2010 but was not reported in the literature until 2011. It acts as a potent agonist of the 5-HT$_{2A}$ receptor, and has been studied in its $^{11}$C radiolabelled form as a potential ligand for mapping the distribution of 5-HT$_{2A}$ receptors in the brain, using positron emission tomography (PET). Multiple deaths have occurred from usage of 25C-NBOMe due to the ease of accidental overdose. The long-term toxic effects of the drug have not been researched.

## History

25C-NBOMe is derived from the psychedelic phenethylamine 2C-C by substitution on the amine with a 2-methoxybenzyl group. 25C-NBOMe is a clumpy white powder with a notably bitter and metallic taste. 25C-NBOMe has been found on blotter mimics sold as LSD.

## Dosage

25C-NBOMe is extremely potent and the effects of the drug increase greatly within a small window of dosage adjustment. Overdose may occur at as little as double an average dose. With inaccurate dosing of street blotter paper, when mistaken for LSD, or when taken as a powder or liquid, this has resulted in multiple accidental deaths.
One study has shown that 25C-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. Sublingually, the threshold for the onset of hallucinogenic effects reportedly is about 100–250 μg, with mild effects at 250–450, strong effects at 450–800, and very strong effects over 800 μg.
NBOMe-substituted compounds have a diminished absorption rate passing through mucous membranes, but generally remain inactive when taken orally. Buccal, sublingual or insufflated routes of administration are all viable options. Absorption rate buccally and sublingually can be increased when complexed with HPBCD complexing sugar, however the most efficient is nasal administration, which shortens the duration while increasing intensity, but has been attributed to several overdoses and deaths.

## Toxicity and harm potential

NBOMe compounds are often associated with life-threatening toxicity and death. Studies on NBOMe family of compounds demonstrated that the substance exhibit neurotoxic and cardiotoxic activity. Reports of autonomic dysfunction remains prevalent with NBOMe compounds, with most individuals experiencing sympathomimetic toxicity such as vasoconstriction, hypertension and tachycardia in addition to hallucinations. Other symptoms of toxidrome include agitation or aggression, seizure, hyperthermia, diaphoresis, hypertonia, rhabdomyolysis, and death. Researchers report that NBOMe intoxication frequently display signs of serotonin syndrome. The likelihood of seizure is higher in NBOMes compared to other psychedelics.
NBOMe and NBOHs are regularly sold as LSD in blotter papers, which have a bitter taste and different safety profiles. Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity. Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD, and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently". While most fatalities are due to the physical effects of the drug, there have also been reports of death due to self-harm and suicide under the influence of the substance.

### Neurotoxic and cardiotoxic actions

Many of the NBOMe compounds have high potency agonist activity at additional 5-HT receptors and prolonged activation of 5-HT$_{2B}$ can cause cardiac valvulopathy in high doses and chronic use. 5-HT$_{2B}$ receptors have been strongly implicated in causing drug-induced valvular heart disease. The high affinity of NBOMe compounds for adrenergic α$_1$ receptor has been reported to contribute to the stimulant-type cardiovascular effects.
In vitro studies, 25C-NBOMe has been shown to exhibit cytotoxicity on neuronal cell lines SH-SY5Y, PC12, and SN471, and the compound was more potent than methamphetamine at reducing the visibility of the respective cells; the neurotoxicity of the compound involves activation of MAPK/ERK cascade and inhibition of Akt/PKB signaling pathway. 25C-NBOMe, including the other derivative 25D-NBOMe, reduced the visibility of cardiomyocytes H9c2 cells, and both substances downregulated expression level of p21 (CDC24/RAC)-activated kinase 1 (PAK1), an enzyme with documented cardiac protective effects.

### Emergency treatment
## Drug prohibition laws
### Canada

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

### Israel

The NBOMe series of psychoactives became controlled in Israel in May, 2013.

### New Zealand

25C-NBOMe was sold as a designer drug in New Zealand in early 2012, but was withdrawn from sale after a statement by Associate Health Minister Peter Dunne that 25C-NBOMe would be considered to be substantially similar in chemical structure to the illegal hallucinogen DOB, and was therefore a Class C controlled drug analogue.

### Russia

Russia became the first country to regulate the NBOME class. The entire NBOMe series of psychoactives became controlled in the Russian Federation starting October, 2011.

### Sweden

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

### United Kingdom

This substance is a Class A drug in the United Kingdom as a result of the N-benzylphenethylamine catch-all clause in the Misuse of Drugs Act 1971.

### United States

Several NBOMe series compounds will be temporarily scheduled in the United States for 2 years. The temporary scheduling applies to 25C-NBOMe, 25B-NBOMe, and 25I-NBOMe. In November 2015, the temporary scheduling was extended for another year.

### China

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

### Czech Republic

25C-NBOMe is banned in the Czech Republic.

## Analogues and derivatives

Analogues and derivatives of 2C-C:
25C-NB*:
* 25C-NBF
* 25C-NBMD
* 25C-NBOH
* 25C-NBOMe (NBOMe-2CC)
* 25C-NB3OMe
* 25C-NB4OMe
N-(2C)-fentanyl:
* N-(2C-C)-fentanyl