25N-NBOMe

# Research Output: 25N-NBOMe

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## Chemical Identity

**Verified via PubChem CID 118536028** [Ref 0 — PubChem lookup, database_verified]:

| Field | Value |
|---|---|
| IUPAC name | 2-(2,5-dimethoxy-4-nitrophenyl)-N-[(2-methoxyphenyl)methyl]ethanamine |
| Systematic name | 2-(2,5-dimethoxy-4-nitrophenyl)-N-[(2-methoxyphenyl)methyl]ethanamine |
| Molecular formula | C₁₈H₂₂N₂O₅ |
| Molecular weight | 346.4 g/mol |
| InChIKey | TXCKTIBHURMASQ-UHFFFAOYSA-N |
| PubChem CID | 118536028 |

**Seed data discrepancies:** The brief does not include SMILES, molecular formula, molecular weight, or InChIKey — all are now confirmed from PubChem. The IUPAC/systematic name in the brief matches PubChem exactly.

**Parent compound:** The 4-nitro substituted phenethylamine 2C-N (2,5-dimethoxy-4-nitrophenethylamine) is the parent molecule, originally documented by Alexander Shulgin in *PiHKAL: A Chemical Love Story* (1991). 25N-NBOMe is the N-(2-methoxybenzyl) derivative of 2C-N.

**Chemical class context:** 25N-NBOMe belongs to the 25X-NBOMe series — 2,5-dimethoxy-N-benzylphenethylamines in which the 4-position substituent (here, a nitro group –NO₂) varies across analogs. The nitro group at the 4-position is unique within the NBOMe series and imparts unique metabolic properties (see Metabolism section).

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## Pharmacology

### Primary receptor targets

The most pharmacologically definitive data for 25N-NBOMe comes from Eshleman et al. (2018 [Ref 1]), which characterized 25N-NBOMe in cell lines heterologously expressing human serotonin receptor subtypes and monoamine transporters:

- **5-HT₂A receptor:** Full efficacy agonist with **subnanomolar to low nanomolar potency** — similar to LSD in the functional assay. This places 25N-NBOMe among the most potent 5-HT₂A agonists known.
- **5-HT₂C receptor:** Full efficacy agonist with very high potency, similar to LSD and serotonin.
- **5-HT₂B receptor:** Lower affinity, potency, and efficacy relative to 5-HT₂A or 5-HT₂C.
- **5-HT₁A receptor:** Very low potency and low efficacy agonist.
- **Monoamine transporters (DAT, SERT, NET):** Low to mid-micromolar affinities and potencies — consistent with negligible psychostimulant activity via this mechanism.

Rickli et al. (2015 [Ref 2]) provided a complementary broad receptor binding profile across the NBOMe series (including 25N-NBOMe) vs. their 2C-drug counterparts and LSD. The NBOMe substituent (N-2-methoxybenzyl group) markedly increases 5-HT₂A affinity compared to the parent 2C compounds (Zawilska et al. 2020 [Ref 4]). Ki values across the NBOMe series are consistently in the low nanomolar range at 5-HT₂A, with more than 1000-fold selectivity over 5-HT₁A.

Elmore et al. (2018 [Ref 6]) confirmed in rat behavioral models that NBOMe compounds are highly potent 5-HT₂A agonists in vivo, with effects fully reversible by the selective 5-HT₂A antagonist M100907. This provides mechanistic confirmation that the subjective and toxic effects are primarily 5-HT₂A-mediated.

**⚠️ FLAG — Adrenergic receptor classification:** The DB seed characterizes 25N-NBOMe as an "Adrenergic receptor ligand." Hondebrink et al. (2018 [Ref 22]) identified α- and β-adrenergic receptors as additional targets for hallucinogenic phenethylamines at concentrations relevant to recreational use, which could account for sympathomimetic adverse effects (tachycardia, hypertension, vasoconstriction). However, no study has published a specific Ki value for 25N-NBOMe at any adrenergic receptor subtype. The adrenergic classification is likely a class-level inference rather than a compound-specific measured value — **flag for editorial review.**

### Mechanism of action

5-HT₂A receptor agonism is the primary mechanism underlying the hallucinogenic and psychedelic effects of 25N-NBOMe, consistent with the broader phenethylamine psychedelic class [Ref 4]. The NBOMe series demonstrates full agonist activity at 5-HT₂A (Eshleman et al. 2018 [Ref 1]), unlike classical 2C compounds which are sometimes described as partial agonists. The sympathomimetic adverse effects (tachycardia, hypertension, hyperthermia) observed in clinical cases across the NBOMe class likely arise from combined 5-HT₂A activation, possible adrenergic activity, and downstream noradrenergic/autonomic effects [Ref 22].

### Pharmacokinetics

**No human pharmacokinetic studies for 25N-NBOMe have been published.** The following is class-level or in vitro data:

- **Route of administration:** Only active via sublingual/buccal or insufflation routes. NBOMe compounds are inactive or very poorly absorbed orally due to gastric degradation and/or first-pass metabolism [Ref 20, web-retrieved]. This is a critical safety point — standard oral ingestion of a blotter does not produce effects, leading some users to dangerously redose or switch to insufflation.
- **Onset:** Seed data states 45–75 minutes for sublingual administration. This is consistent with reported ranges for the NBOMe class; no published pharmacokinetic study confirms this specifically for 25N-NBOMe.
- **Plasma concentrations:** For 25B-NBOMe, peak plasma levels of 0.7–10.1 ng/mL were measured in a clinical toxicology series (Gee et al. 2016 [Ref 5]). No equivalent data for 25N-NBOMe.
- **Bioavailability:** Not determined for 25N-NBOMe. Sublingual/buccal bioavailability is expected to be higher than oral based on class behavior.

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## Metabolism

The only primary study specifically examining 25N-NBOMe metabolism is Grafinger et al. (2018 [Ref 3]), which investigated phase I metabolism in pooled human liver microsomes (pHLM) and the fungal model *Cunninghamella elegans*:

- **24 phase I metabolites** identified in pHLM; **9 metabolites** in *C. elegans*.
- **Major biotransformation pathways:**
  - Oxidative deamination
  - Oxidative N-dealkylation (with and without hydroxylation)
  - Oxidative O-demethylation (with and without hydroxylation)
  - Mono- and dihydroxylation
  - Oxidation of primary and secondary alcohols
  - Carboxylation of primary alcohols
- **Unique pathway for 25N-NBOMe:** Reduction of the aromatic **nitro group** (–NO₂ → –NH₂) and subsequent **N-acetylation** of the resulting primary aromatic amine. This pathway was not observed for 25D-NBOMe or 25E-NBOMe — it is unique to 25N-NBOMe within the NBOMe series due to the nitro substituent.
- **First report:** 25N-NBOMe and 25D-NBOMe were the first NBOMes found to produce N-oxide and hydroxylamine metabolites.
- **Parent metabolite:** The corresponding 2C-N (2,5-dimethoxyphenethylamine) is detected as a metabolite in all three NBOMe compounds studied, consistent with N-dealkylation of the methoxybenzyl group.

**CYP enzyme involvement:** For the related compound 25I-NBOMe, Caspar et al. (2015 [Ref 9]) identified **CYP1A2 and CYP3A4** as responsible for hydroxylation and **CYP2C9 and CYP2C19** for O-demethylation. These CYP isoenzymes are expected to be similarly involved in 25N-NBOMe metabolism. CYP2C9 and CYP2C19 involvement creates potential for pharmacokinetic drug–drug interactions.

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## History

**2C-N (parent compound):** Alexander Shulgin first documented and self-administered 2,5-dimethoxy-4-nitrophenethylamine (2C-N) in *PiHKAL: A Chemical Love Story* (1991). Shulgin's synthesis and exploration of the 2C series of compounds provided the structural backbone for all 25X-NBOMe compounds. No specific publication date for 2C-N's first synthesis in academic literature has been identified; the PIHKAL book is the primary source [unverifiable — book].

**NBOMe series discovery:** The N-benzyl phenethylamines were first described as highly potent partial agonists at 5-HT₂A receptors in 2000 [Ref 20]. **Ralf Heim**, working at the Free University of Berlin, developed 25N-NBOMe and other NBOMe compounds and documented them in his **2003 doctoral thesis** [Ref 20 — web-retrieved]. David E. Nichols subsequently contributed to establishing the mechanism of action. The original motivation was scientific: NBOMe compounds were explored as radioligands for 5-HT₂A receptor brain imaging using PET. The compound CIMBI-5 (¹¹C-labeled 25I-NBOMe) was evaluated as a PET radioligand by Ettrup et al. (2010 [Ref 15]).

**Emergence as a designer drug:** The NBOMe series first appeared on online drug markets as "research chemicals" in **approximately 2010** [Ref 20]. The three most prevalent compounds were 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. 25N-NBOMe is considered a less prevalent analog within the series, though it was documented on markets during the same period.

**Prohibition timeline:**
- 2011: Russia controls the NBOMe series
- 2013: Sweden adds NBOMes; November 2013 — DEA emergency Schedule I placement of 25I-, 25C-, and 25B-NBOMe (US)
- 2014: UK designates 25I-NBOMe and 25C-NBOMe as Class A drugs; Brazil explicitly lists 25N-NBOMe as controlled (February 2014); Israel controls the series
- 2015: Various US states add additional NBOMe analogs; Finland bans 25D-NBOMe
- 2016: 25I-, 25C-, and 25B-NBOMe permanently placed in US Schedule I (October 2016); Canada adds NBOMes to Schedule III (October 2016); UK Psychoactive Substances Act covers all psychoactive substances including 25N-NBOMe (May 2016)

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## Subjective Effects

**No controlled human studies exist for 25N-NBOMe.** All subjective effect data is extrapolated from:
1. Class-level clinical toxicology reports (predominantly 25I-, 25C-, and 25B-NBOMe)
2. User reports from harm reduction communities (psychonaut community, PsychonautWiki)

### From clinical toxicology literature (class-level)

Gee et al. (2016 [Ref 5]), Zawilska et al. (2020 [Ref 4]), and Suzuki et al. (2015 [Ref 12]) document the following acute effects across the NBOMe series:

**Desired/psychedelic effects:**
- Visual and auditory hallucinations
- Euphoria, stimulation
- Altered sense of time

**Adverse effects consistently documented:**
- Confusion, agitation, violent behavior (most common presenting symptoms)
- Mydriasis (pupil dilation)
- Tachycardia, hypertension
- Hyperthermia, diaphoresis
- Anxiety, panic, paranoia

### From community reports (label: user-report data)

PsychonautWiki describes 25N-NBOMe as producing effects similar to other NBOMe compounds [Ref — web-retrieved]:
- Full hallucinatory states within intensity levels 1–3 consistently; level 4 breakthroughs rare
- More visual than LSD, less introspective, faster-paced, more anxiety-inducing
- Prominent stimulant component
- Geometry, color enhancement, visual drifting, tracers, internal hallucinations, synesthesia described
- Dose-sensitive: significant increases in effect intensity with small dose increments

**⚠️ FLAG:** No published controlled study data exists for the specific subjective effects of 25N-NBOMe. The effect profile in the DB seed (43 effects, all from community_consensus_large/medium provenance) is plausible given class-level data but is not verified against compound-specific publications.

### Duration

Seed DB data: onset 45–75 min, peak 2–3 h, offset 2–3 h, aftereffects 5–10 h, total 5–10 h (sublingual). This is consistent with reported ranges for the NBOMe class from clinical literature (Ameline et al. 2017 [Ref — PMID 29189143] describes 25I-NBOMe effects lasting 5–10 hours). No compound-specific published duration data for 25N-NBOMe exists.

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## Safety & Toxicity

### Class-level acute toxicity

The NBOMe series has been associated with severe toxicity and deaths since their emergence. Zawilska et al. (2020 [Ref 4]) and the Dark Classics review [Ref 20] document:
- **>50 confirmed cases of acute toxicity** for the NBOMe class overall
- **At least 9 confirmed fatalities**, with at least 2 directly attributed to 25B-NBOMe

**Typical severe presentation (Gee et al. 2016 [Ref 5], Suzuki et al. 2015 [Ref 12]):**
- Hallucinations and violent agitation (most common)
- Serotonergic/sympathomimetic signs: mydriasis, tachycardia, hypertension, hyperthermia, diaphoresis
- Seizures (documented in multiple NBOMe cases)
- Excited delirium
- Rhabdomyolysis, elevated creatine kinase
- Acute kidney injury
- Metabolic acidosis
- Disseminated intravascular coagulation (DIC)
- Multiorgan failure (severe cases)
- Coma

**Cardiotoxicity:** 25D-NBOMe and 25C-NBOMe were shown to prolong QT intervals in rat ECG studies [Ref 20]. Whether 25N-NBOMe shares this risk is not established by direct study, but is plausible given class-level cardiac sensitivity.

**Neurotoxicity (in vitro):** Gil-Martins et al. (2024 [Ref 13]) demonstrated that NBOMe drugs show higher cytotoxicity than their 2C counterparts in differentiated SH-SY5Y neuronal cells and rat cortical cultures. Cytotoxic mechanisms include mitochondrial membrane depolarization, intracellular ATP depletion, and glutathione reduction. This correlation with lipophilicity suggests that the NBOMe substituent itself (not just the 4-position substitutent) increases neurotoxic potential.

### 25N-NBOMe specifically

**No published case reports or fatalities specifically attributed to 25N-NBOMe have been identified in the peer-reviewed literature.** The seed DB notation "potentially fatal at heavy dosages" is supported by class-level evidence and the pharmacological profile (full efficacy, high potency 5-HT₂A agonist with sympathomimetic activity) but is not supported by 25N-NBOMe-specific published toxicology.

**⚠️ FLAG (Safety-critical):** The dose ranges in the seed data (Threshold: 100 µg; Light: 100–300 µg; Common: 300–800 µg; Strong: 800–1300 µg) have not been verified against any published study. These figures are consistent with community-reported NBOMe dose ranges (PsychonautWiki) but no pharmacokinetic or dose-escalation study exists. The dose-response of the NBOMe series is notoriously steep — small increments produce disproportionate increases in both desired and toxic effects. **These values should be flagged as unverified in the article.**

### LD50 / Therapeutic index

No LD50 data for 25N-NBOMe in any species has been published. No therapeutic index data exists.

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## Harm Reduction

Based on class-level evidence:

**Testing:** NBOMe compounds can be identified by:
- Ehrlich reagent (turns purple/violet — positive for NBOMe family)
- Mandelin reagent
- High-resolution mass spectrometry (characteristic ions at m/z 121.0654 and 91.0548 for the 25X-NBOMe series; Botch-Jones et al. 2016 [Ref 24])
- Standard immunoassay panels do **not** detect NBOMes; LC-MS is required (Caspar et al. 2015 [Ref 9])

**Route-specific risk:** Insufflation causes significantly faster onset and higher peak blood concentrations than sublingual, dramatically increasing overdose risk. IV administration has been reported and is extremely dangerous [Ref 4].

**Sublingual tip:** A sublingual numbing sensation is often described by users as characteristic of NBOMe compounds (vs. LSD blotters, which produce no numbing). This can serve as informal identification.

**Emergency management (based on class-level evidence from Gee et al. 2016 [Ref 5]):**
- Supportive care is primary management
- High-dose benzodiazepines required to control agitation (7/10 patients in the Gee case series required sedation)
- Active management of hyperthermia (passive cooling, active cooling if severe)
- Seizures: benzodiazepines first-line
- Rhabdomyolysis monitoring: CK, creatinine, urine output
- Avoid sympathomimetic agents

**Serotonin syndrome risk:** Documented for NBOMe compounds in a systematic review (Schifano et al. 2021 [Ref 7]). Any combination with other serotonergic agents increases risk.

**Contraindications (class-level, no compound-specific data):**
- Cardiovascular disease (hypertension, arrhythmia, prior cardiac events)
- Psychiatric history (psychosis, bipolar disorder)
- Seizure disorder
- Concurrent stimulant use
- Concurrent serotonergic drugs

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## Tolerance & Dependence

**Seed data:** Buildup almost immediately after ingestion; half-life 3 days; full reset 7 days; cross-tolerance with psychedelics; not habit-forming.

No published studies specifically on 25N-NBOMe tolerance. The tolerance profile described in the seed data is consistent with the known serotonergic psychedelic class mechanism: rapid desensitization of 5-HT₂A receptors (receptor downregulation/internalization), with full recovery over approximately 7–14 days for classical psychedelics.

**Cross-tolerance:** Established within the serotonergic psychedelic class (LSD, psilocybin, mescaline, 2C compounds) based on shared 5-HT₂A mechanism. No compound-specific cross-tolerance studies for 25N-NBOMe.

**Dependence:** No published studies on dependence liability for 25N-NBOMe or the NBOMe series. No animal self-administration studies found. The 5-HT₂A agonist mechanism is associated with very low dependence liability in the psychedelic class overall. The seed data characterization "not habit-forming" is consistent with class-level evidence.

**⚠️ FLAG:** Tolerance and dependence data are based entirely on class inference from serotonergic psychedelic literature, not 25N-NBOMe-specific data. This should be stated clearly in the article.

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## Interactions

**Published interaction data specific to 25N-NBOMe:** None identified.

**Seed-listed interactions:**

- **Cocaine — dangerous:** Pharmacologically plausible. Both agents produce sympathomimetic effects (tachycardia, hypertension, hyperthermia, vasoconstriction). Combined use risks severe cardiovascular strain, hypertensive crisis, hyperthermia, and seizures. No 25N-NBOMe-specific study, but consistent with general stimulant + 5-HT₂A agonist interaction risk.

- **Tramadol — dangerous:** Pharmacologically supported. Tramadol has serotonergic activity (5-HT/norepinephrine reuptake inhibition and some direct serotonin release). Combined with a potent 5-HT₂A full agonist, serotonin syndrome risk is significant. Schifano et al. (2021 [Ref 7]) documented serotonin syndrome with NBOMe compounds in clinical cases. Tramadol also lowers the seizure threshold, compounding risk.

- **Caffeine — unknown:** No published data. Caffeine is a methylxanthine (adenosine antagonist) with mild stimulant properties. Interaction risk is unclear but relatively low compared to stronger stimulants.

- **Cannabis — unknown:** Cannabis (THC) can amplify or extend psychedelic effects and increase anxiety, paranoia, and cardiovascular strain (tachycardia). No published data specific to this combination.

- **MDMA — unknown:** Pharmacologically concerning. MDMA releases serotonin (via SERT reversal), producing high serotonergic load. Combined with 5-HT₂A full agonism from 25N-NBOMe, serotonin syndrome risk is elevated. Also cardiovascular additive effects. However, no published study documents this specific combination.

**CYP drug interactions:**
CYP2C9 and CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, omeprazole) could reduce metabolic clearance of 25N-NBOMe by impairing O-demethylation [Ref 9, Ref 3], potentially increasing exposure and toxicity risk. This is an inference from known CYP involvement in related NBOMe compounds; no interaction study exists.

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## Legal Status

| Jurisdiction | Status | Details |
|---|---|---|
| United States | Not specifically scheduled | 25I-, 25C-, and 25B-NBOMe are permanent Schedule I (since Oct 2016). 25N-NBOMe is not individually named. When intended for human consumption, would likely be covered by the Federal Analogue Act as substantially similar in structure/pharmacology to Schedule I NBOMe compounds. |
| United Kingdom | Illegal | Covered under the Psychoactive Substances Act 2016 (in force May 26, 2016), which prohibits production, supply, and import of any psychoactive substance. 25I-NBOMe and 25C-NBOMe were also specifically designated Class A drugs in 2014. |
| Brazil | Controlled | Explicitly listed as a controlled substance as of February 18, 2014. |
| Canada | Schedule III | Covered under "2C-phenethylamines and their salts, derivatives, isomers and salts of derivatives and isomers" since October 12, 2016. |
| Russia | Controlled | NBOMe series controlled since October 2011. |
| Sweden | Controlled | Added to controlled substances list August 1, 2013. |
| Australia | Varies by state | 25I-NBOMe is a Schedule 9 (prohibited) substance nationally; state-level varies. |
| European Union | Varies | UK PSA provides blanket coverage; many EU member states have NPS blanket laws or specific scheduling. |

Sources: Erowid NBOMe Legal Status page [Ref 11], Federal Register 2016-23185 (DEA), UK Psychoactive Substances Act 2016.

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## Clinical Trials

**No clinical trials** for 25N-NBOMe were identified on ClinicalTrials.gov. The search returned zero results for "25N-NBOMe" or related terms. 25N-NBOMe has no established medical use and has never entered clinical investigation.

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## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief. This section is intentionally empty.

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## Gaps & Flags

### Critical Safety-Critical Gaps

1. **⚠️ Dose ranges not verified (CRITICAL):** The seed data dose ranges (Threshold 100 µg, Light 100–300 µg, Common 300–800 µg, Strong 800–1300 µg) have not been verified against any published pharmacokinetic or clinical study. They are consistent with community-reported values for the NBOMe class but are fundamentally unverified. The generation agent should clearly label these as community-consensus estimates, not clinically established values.

2. **⚠️ Adrenergic receptor classification not verified:** The DB seed classifies 25N-NBOMe as an "Adrenergic receptor ligand." No published study provides a specific Ki or EC50 for 25N-NBOMe at any adrenergic receptor. Class-level inference exists (Hondebrink et al. 2018 [Ref 22]), but this needs editorial review.

3. **⚠️ Toxicity rating "acute: high; chronic: high" not verified for 25N-NBOMe specifically:** No LD50, no 25N-NBOMe-specific case reports. These values are reasonable class-level inferences but should be labeled as such.

### Structural Analogy / Class Inference

4. **Subjective effects profile:** All 43 seed effect entries are from community_consensus_large/medium provenance. No compound-specific controlled study data. The article should state clearly that the effect profile is based on class-level data and community reports.

5. **Tolerance and dependence data:** Entirely class-level inference from serotonergic psychedelic literature. No 25N-NBOMe-specific research.

6. **Duration data:** Consistent with class but no compound-specific study.

7. **Drug interactions (Cocaine, Tramadol, Caffeine, Cannabis, MDMA):** All are mechanistic inferences; no 25N-NBOMe-specific interaction studies exist.

### Data Absences

8. **No published human pharmacokinetic data:** Tmax, Cmax, bioavailability, half-life — all unknown for 25N-NBOMe.

9. **No LD50 in any species** for 25N-NBOMe.

10. **No 25N-NBOMe-specific case reports** in the published peer-reviewed literature — toxicology characterization relies entirely on class-level data.

11. **No clinical trials** — none registered or completed.

12. **SMILES string absent from DB seed** — PubChem provides full structure data (CID 118536028) but the seed did not include SMILES. The generation agent should note the PubChem CID for the compound.

13. **Specific Ki/EC50 values for 25N-NBOMe:** The Eshleman et al. 2018 paper [Ref 1] provides functional potency data but the full-text numeric values (specific nM Ki/EC50) were not accessible via abstract alone. The generation agent should cite the paper as the source of receptor potency data without claiming specific numeric values not confirmed in abstract.

### Contradiction Check

- **Dose ranges in seed vs. literature:** Seed data threshold of "100 µg" is slightly above the PsychonautWiki-documented threshold of "<100 µg." This is a minor discrepancy that may reflect different methodologies (threshold vs. common threshold). Flag for editorial review.

- **Characterization as "emerging":** Given that 25N-NBOMe has been documented since approximately 2010 and was scheduled in Brazil in 2014, "emerging" in the DB characterization may be a legacy label from initial seeding. However, 25N-NBOMe remains far less studied than 25I-, 25B-, or 25C-NBOMe, so "emerging" with respect to scientific characterization is accurate.