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| Clinical data | |
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| Other names | NBOMe-2C-D; 2C-D-NBOMe; 2,5-Dimethoxy-N-(2-methoxybenzyl)-4-methylphenethylamine;N-(2-Methoxybenzyl)-4-methyl-2,5-dimethoxyphenethylamine |
| Drug class | Serotonin5-HT2 receptoragonist;Serotonergic psychedelic;Hallucinogen |
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| Chemical and physical data | |
| Formula | C19H25NO3 |
| Molar mass | 315.413 g·mol−1 |
| 3D model (JSmol) | |
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25D-NBOMe, also known asNBOMe-2C-D and"divination", is a derivative of thephenethylamine derived hallucinogen2C-D. It acts in a similar manner to related compounds such as25I-NBOMe, which is a potentagonist at the5-HT2Areceptor.[2][3] 25D-NBOMe has been sold as a street drug since 2010 and produces similar effects in humans to related compounds such as25I-NBOMe and25C-NBOMe.[4] It was banned as aTemporary Class Drug in the UK on 10 June 2013 after concerns about its recreational use.[5]
The dose range of 25D-NBOMe has been given as 0.3 to 1.2 mg or moresublingually, with a typical dose estimate of 1.0 mg.[6]
NBOMe compounds are often associated with life-threatening toxicity and death.[7][8] Studies on NBOMe family of compounds demonstrated that the substance exhibit neurotoxic and cardiotoxic activity.[9] Reports ofautonomic dysfunction remains prevalent with NBOMe compounds, with most individuals experiencingsympathomimetic toxicity such asvasoconstriction,hypertension andtachycardia in addition to hallucinations.[10][11][12][13][14] Other symptoms oftoxidrome include agitation oraggression,seizure,hyperthermia,diaphoresis,hypertonia,rhabdomyolysis, and death.[10][14][8] Researchers report that NBOMe intoxication frequently display signs ofserotonin syndrome.[15] The likelihood of seizure is higher in NBOMes compared to other psychedelics.[9]
NBOMe and NBOHs are regularly sold as LSD in blotter papers,[8][16] which have a bitter taste and different safety profiles.[10][7] Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity.[7] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[12] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[10] 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.[17][18][10]
Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown.[10] NBOMe compounds are not active orally,[a] and are usually taken sublingually.[20]: 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.[21][22][23]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.[8][13] 5-HT2B receptors have been strongly implicated in causing drug-inducedvalvular heart disease.[24][25][26] The high affinity of NBOMe compounds foradrenergic α1 receptor has been reported to contribute to the stimulant-type cardiovascular effects.[13]
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.[9] 25C-NBOMe, including the other derivative 25D-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.[9]
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.[27][28]| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 4,510–7,100 (Ki) 5,900 (EC50Tooltip half-maximal effective concentration) 55% (EmaxTooltip maximal efficacy) |
| 5-HT1B | ND |
| 5-HT1D | 5,354 |
| 5-HT1E | ND |
| 5-HT1F | ND |
| 5-HT2A | 0.22–2.52 (Ki) 0.224–90 (EC50) 27–148% (Emax) |
| 5-HT2B | 2.05–3.89 (Ki) 32.3–100 (EC50) 22–48% (Emax) |
| 5-HT2C | 0.69–13 (Ki) 1.37–11.5 (EC50) 96–97% (Emax) |
| 5-HT3 | ND |
| 5-HT4 | ND |
| 5-HT5A | ND |
| 5-HT6 | 168.9 |
| 5-HT7 | 6,744 |
| α1A | 700 |
| α1B,α1D | ND |
| α2A | 370 |
| α2B,α2C | ND |
| β1–β3 | ND |
| D1 | 8,700 |
| D2 | 2,600 |
| D3 | 6,400 |
| D4,D5 | ND |
| H1 | 630 |
| H2–H4 | ND |
| M1–M5 | ND |
| I1 | ND |
| σ1,σ2 | ND |
| MOR | ND (Ki) >63,000 (EC50) <5–72% (Emax) |
| DOR | ND |
| KOR | ND |
| TAAR1Tooltip Trace amine-associated receptor 1 | 13,000 (Ki) (mouse) 810 (Ki) (rat) 4,000 (EC50) (mouse) 1,500 (EC50) (rat) >30,000 (EC50) (human) 67% (Emax) (mouse) 34% (Emax) (rat) |
| SERTTooltip Serotonin transporter | 1,400–1,780 (Ki) 1,024–3,900 (IC50Tooltip half-maximal inhibitory concentration) IA (EC50) |
| NETTooltip Norepinephrine transporter | 2,200–6,700 (Ki) 1,170–4,000 (IC50) IA (EC50) |
| DATTooltip Dopamine transporter | 14,000–34,500 (Ki) 106,000 (IC50) IA (EC50) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified.Refs:[29][30][31][32][33][34][35][36][37][38][39] | |
25D-NBOMe acts as anagonist of theserotonin5-HT2 receptors.[40]
The drug produces thehead-twitch response, a behavioral proxy ofpsychedelic-like effects, in rodents.[41]
25D-NBOMe has shownreinforcing effects in rodents.[40][42] This includedconditioned place preference (CPP) andself-administration.[40][42] Relatedly, the drug has been found to increasedopaminergicsignaling in thenucleus accumbens.[40][42]
25D-NBOMe was first described in thescientific literature by 2012.[43]
As of October 2015 25D-NBOMe is a controlled substance in China.[44]
Scheduled in the "government decree on prohibited psychoactive substances in consumer markets".[45]
Sveriges riksdag added 25D-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 byMedical Products Agency in their regulation LVFS 2013:15 listed as 25D-NBOMe 2-(2,5-dimetoxi-4-metylfenyl)-N-(2-metoxibensyl)etanamin.[46]
This substance is aClass A drug in the United Kingdom as a result of theN-benzylphenethylamine catch-all clause in theMisuse of Drugs Act 1971.[47]
Unregulated at a federal and state level, though arguably may contravene theFederal Analog Act under certain circumstances given its structural and functional similarity to controlled substance 2C-D.
Supplementary Table S2. Dose estimates and data sources for psychedelics.
Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT2A and 5-HT2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT2A compared with 5-HT1A. They display higher affinity for 5-HT2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT2B receptor compared to 5-HT2A or 5-HT2C.
Table 3. 5-HT2A in vitro G protein and arrestin functional activity of known 5-HT2A agonist psychedelics and novel compounds. No activity refers to no detectable curve. [...]
