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| Other names | 2C-H-NBOMe; NBOMe-2C-H; DMPEA-NBOMe;N-(2-Methoxybenzyl)-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-N-(2-methoxybenzyl)phenethylamine |
| Drug class | Serotonin5-HT receptoragonist;Serotonergic psychedelic;Hallucinogen |
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| Formula | C18H23NO3 |
| Molar mass | 301.386 g·mol−1 |
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25H-NBOMe, also known asNBOMe-2C-H, is a derivative of thephenethylaminehallucinogen2C-H, which acts as a highlypotentfull agonist for thehuman5-HT2Areceptor.[2]
The active dose range of 25H-NBOMe in humans has not been reported and hence is unknown.[3] This is in notable contrast to many other NBOMe drugs.[3]
NBOMe compounds are often associated with life-threatening toxicity and death.[4][5] Studies on NBOMe family of compounds demonstrated that the substance exhibit neurotoxic and cardiotoxic activity.[6] Reports ofautonomic dysfunction remains prevalent with NBOMe compounds, with most individuals experiencingsympathomimetic toxicity such asvasoconstriction,hypertension andtachycardia in addition to hallucinations.[7][8][9][10][11] Other symptoms oftoxidrome include agitation oraggression,seizure,hyperthermia,diaphoresis,hypertonia,rhabdomyolysis, and death.[7][11][5] Researchers report that NBOMe intoxication frequently display signs ofserotonin syndrome.[12] The likelihood of seizure is higher in NBOMes compared to other psychedelics.[6]
NBOMe and NBOHs are regularly sold as LSD in blotter papers,[5][13] which have a bitter taste and different safety profiles.[7][4] Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity.[4] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[9] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[7] 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.[14][15][7]
Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown.[7] NBOMe compounds are not active orally,[a] and are usually taken sublingually.[17]: 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.[18][19][20]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.[5][10] 5-HT2B receptors have been strongly implicated in causing drug-inducedvalvular heart disease.[21][22][23] The high affinity of NBOMe compounds foradrenergic α1 receptor has been reported to contribute to the stimulant-type cardiovascular effects.[10]
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.[6] 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.[6]
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.[24][25]| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 4,520–6,973 (Ki) 28,400 (EC50Tooltip half-maximal effective concentration) 52% (EmaxTooltip maximal efficacy) |
| 5-HT1B | ND |
| 5-HT1D | ND |
| 5-HT1E | ND |
| 5-HT1F | ND |
| 5-HT2A | 2.83–49.4 (Ki) 11.0–490 (EC50) 38–144% (Emax) |
| 5-HT2B | 62.9 (Ki) 340–463 (EC50) 11–38% (Emax) |
| 5-HT2C | 16.4–130 (Ki) 13.8 (EC50) 96% (Emax) |
| 5-HT3 | ND |
| 5-HT4 | ND |
| 5-HT5A | ND |
| 5-HT6 | ND |
| 5-HT7 | ND |
| α1A | 550 |
| α1B,α1D | ND |
| α2A | 530 |
| α2B,α2C | ND |
| β1–β3 | ND |
| D1 | 14,000 |
| D2 | 7,700 |
| D3 | 20,000 |
| D4,D5 | ND |
| H1 | 4,100 |
| H2–H4 | ND |
| M1–M5 | ND |
| I1 | ND |
| σ1,σ2 | ND |
| MOR | ND |
| DOR | ND |
| KOR | ND |
| TAAR1Tooltip Trace amine-associated receptor 1 | >20,000 (Ki) (mouse) 1,400–1,500 (Ki) (rat) 6,100 (EC50) (mouse) 3,000 (EC50) (rat) >10,000 (EC50) (human) 53% (Emax) (mouse) 37% (Emax) (rat) |
| SERTTooltip Serotonin transporter | 2,220–2,300 (Ki) 2,080–12,000 (IC50Tooltip half-maximal inhibitory concentration) IA (EC50) |
| NETTooltip Norepinephrine transporter | 5,500–16,300 (Ki) 3,650–10,000 (IC50) IA (EC50) |
| DATTooltip Dopamine transporter | 35,000–81,400 (Ki) 120,000 (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:[26][27][28][29][30][31] [32][33][34][35][36][37] | |
25H-NBOMe acts as anagonist of theserotonin5-HT2 receptors.[38][28]
Itsaffinity for the serotonin5-HT2A receptor (Ki = 2.83 nM) was 133-fold higher than that of2C-H and 24-fold higher than that of25H-NB (N-benzyl-2C-H), whereas it was 4-fold lower than that of2C-I and 64-fold lower than that of25I-NBOMe.[28] In terms ofactivationalpotency at the receptor, the drug's potency (EC50Tooltip half-maximal effective concentration = 15.3 nM) was 67-fold higher than that of 2C-H, whereas it was 6-fold lower than that of 2C-I and 35-fold lower than that of 25I-NBOMe.[28] Hence, unlike other NBOMe drugs, 25H-NBOMe appears to have affinity and activational potency at the serotonin 5-HT2A receptor more in line with the2C psychedelics like 2C-I and much lower than NBOMe drugs like 25I-NBOMe.[28]
25H-NBOMe produceshyperlocomotion, astimulant-like effect, and thehead-twitch response, a behavioral proxy ofpsychedelic effects, in rodents.[32][38][39] Its potency in inducing the head-twitch response was variably lower than that of other NBOMe drugs like25I-NBOMe and25B-NBOMe.[38][32] Conversely, its potency in inducing hyperlocomotion was about the same as that of 25I-NBOMe and25C-NBOMe.[38] The drug has also been found to produceantidepressant-like effects in rodents.[39] 25H-NBOMe has shownreinforcing effects in rodents.[38][40] This includedconditioned place preference (CPP) andself-administration.[38][40]
25H-NBOMe was first described in thescientific literature by Ralf Heim at theFree University of Berlin by 2003.[27]
The Riksdag added 25H-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 25H-NBOMe, and 2-(2,5-dimetoxifenyl)-N-(2-metoxibensyl)etanamin.[41]
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.[42]
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 5.1: Agonistic potency (pEC50) and intrinsic activity (Emax) of 5-HT2AR partial agonistic arylethylamines (indole, methoxybenzene and quinazolinedione derivatives) used in the study. [...] [Compound] 229 [...]
