2C-E

# Research Output: 2C-E

**Substance:** 2C-E (PSX-0031)
**Research date:** 2026-04-20
**Evidence density:** Sparse–moderate (limited dedicated human studies; rich comparative literature)

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## Chemical Identity

### Confirmed Data (PubChem CID 24729233) [Ref 1 — via PubChem lookup]

| Field | Value | Source |
|-------|-------|--------|
| PubChem CID | 24729233 | PubChem API [Ref 1 — database_lookup] |
| IUPAC name | 2-(4-ethyl-2,5-dimethoxyphenyl)ethanamine | PubChem [Ref 1] |
| Systematic name | 2-(4-ethyl-2,5-dimethoxyphenyl)ethanamine | PubChem [Ref 1] |
| Molecular formula | C₁₂H₁₉NO₂ | PubChem [Ref 1] |
| Molecular weight | 209.28 g/mol | PubChem [Ref 1] |
| InChIKey | VDRGNAMREYBIHA-UHFFFAOYSA-N | PubChem [Ref 1] |
| SMILES | Not returned by PubChem API; retrieve directly from CID 24729233 | — |

**Notes on seed data:**
- The brief lists SMILES, molecular formula, molecular weight, and InChIKey as empty. PubChem confirms formula (C₁₂H₁₉NO₂) and MW (209.28) — these should be populated.
- The IUPAC name in the brief ("2-(4-ethyl-2,5-dimethoxyphenyl)ethanamine") matches PubChem exactly — confirmed correct.
- PubChem CID 24729233 confirmed — brief listed this as empty and should be populated.
- InChIKey VDRGNAMREYBIHA-UHFFFAOYSA-N should be populated in the DB.
- CAS number commonly cited in literature as **71539-34-9** (web-retrieved; not verified via API — flag for editorial confirmation).

**⚠️ FLAG:** SMILES string was not returned by the PubChem MCP tool for this compound. Generation agent should retrieve canonical SMILES directly from CID 24729233 via PubChem web interface before finalising the article's chemical data block.

---

## Pharmacology

### Mechanism of Action

2C-E is a **partial agonist at serotonin 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors**, and a **weak inhibitor of norepinephrine (NE) and serotonin (5-HT) reuptake** (Papaseit et al. 2020 [Ref 1]). The 5-HT₂A receptor is the primary mediator of psychedelic effects (Aghajanian & Marek 1999 [Ref 11]; Nichols 2004 [Ref 10]). 5-HT₂A agonism on neocortical pyramidal cells leads to enhanced non-synchronous glutamatergic excitatory postsynaptic potentials, with downstream effects on thalamocortical connectivity and prefrontal cortical metabolism (Aghajanian & Marek 1999 [Ref 11]).

As a phenethylamine (2C-series) compound, 2C-E has **lower intrinsic activity at 5-HT₂A** than its phenylisopropylamine analogues (DO-series), reflecting the general structure-activity relationship for this compound class (Parrish et al. 2005 [Ref 26]).

### Receptor Binding Profile

Published binding affinity data for 2C-E is available from three primary sources:

1. **Ray (2010) [Ref 5]** — NIMH Psychoactive Drug Screening Program (NIMH-PDSP) data for 2C-E at 51 receptors, transporters, and ion channels. 2C-E showed affinity across 42 of 49 sites tested, consistent with the broad receptor interaction profile of phenylalkylamines. Specific Ki values are tabulated in the paper; abstracts do not reproduce individual values.

2. **Rickli et al. (2015) [Ref 4]** — Compared 2C-drug receptor profiles (including 2C-E) against NBOMe derivatives and LSD at multiple receptor subtypes and monoamine transporters. 2C-E shows moderate 5-HT₂A and 5-HT₂C affinity; NBOMe derivatives show dramatically higher affinity at 5-HT₂A (low nanomolar vs. 2C compounds' higher Ki values).

3. **Eshleman et al. (2014) [Ref 3]** — In vitro receptor and transporter binding data for 2C-E alongside 2C-C, 2C-D, 2C-I, 2C-T-2, and DOC. Includes transporter binding function; full Ki table in paper.

**⚠️ FLAG:** Specific numerical Ki/EC₅₀ values for 2C-E at 5-HT₂A, 5-HT₂B, and 5-HT₂C are published in tabulated form in Refs [3], [4], and [5] but are not extractable from abstracts alone. The generation agent should retrieve these values from the full papers before quoting specific Ki figures in the article.

**Secondary receptor interactions:** In rat brain membranes, 2C-E stimulated G protein binding at serotonin receptors in cortical membranes (Nonaka et al. 2007 [Ref 8]). At monoamine transporters, 2C-E exerts weak effects on dopamine, serotonin, and NE reuptake compared to classical stimulants — the drug's primary activity is receptor-mediated rather than transporter-mediated (Nagai et al. 2007 [Ref 9]).

### Pharmacokinetics

**The only published human pharmacokinetic study is Papaseit et al. (2020) [Ref 1]**, an observational study conducted in Spain in n=10 recreational psychedelic users. Key findings:

- **Route studied:** Oral self-administration
- **Dose range:** 6.5, 8, 10, 15, or 25 mg
- **Saliva (oral fluid) Tmax:** ~2 hours post-oral administration
- **Bioavailability (absolute):** Not published
- **Half-life:** Not published
- **Volume of distribution:** Not published
- **Protein binding:** Not published
- **Plasma Cmax:** Not published (saliva concentration measured, not plasma)

**⚠️ FLAG:** No full human PK study (plasma pharmacokinetics, bioavailability, half-life, Vd) has been published for 2C-E as of research date. The Papaseit 2020 study used saliva as a pharmacokinetic matrix, which approximates free plasma drug levels but is not equivalent to formal plasma pharmacokinetics.

### Metabolism

Metabolism of 2C-E is reviewed in Meyer & Maurer (2010) [Ref 7]. The primary metabolic pathways for 2C compounds are:
- **O-demethylation** at the 2- and 5-methoxy positions
- **Hydroxylation** of the ethyl side chain at position 4
- **Deamination** of the ethylamine moiety
- Phase II conjugation (glucuronidation, sulphation) of hydroxylated metabolites

CYP enzyme involvement: the Meyer & Maurer review discusses CYP-dependent metabolism for the 2C class generally; specific CYP isoforms responsible for 2C-E biotransformation have not been individually characterised in published studies.

The recent 25E-NBOH metabolism study (Vágnerová et al. 2026 [Ref 18]) confirmed 2C-E as a metabolite of 25E-NBOH via N-debenzylation, with identity verified using a commercial reference standard. This confirms the structural identity of 2C-E and supports the predicted O-demethylation metabolic pathways.

**⚠️ FLAG:** Specific CYP isoform data for 2C-E metabolism has not been published. The generation agent should not cite specific isoforms (e.g., CYP2D6) without primary source verification.

---

## History

### Discovery and Synthesis

2C-E was **first synthesised by Alexander T. Shulgin** (American pharmacologist, 1925–2014), approximately **1977**, as part of his systematic exploration of phenethylamine psychedelics. The compound was first publicly documented in **PiHKAL: A Chemical Love Story** (Shulgin & Shulgin, 1991 [Ref 16]), where it appears as **entry #24**.

Shulgin designated 2C-E as one of the **"magical half-dozen"** — his six most significant phenethylamine psychedelics — alongside mescaline, DOM, 2C-B, 2C-T-2, and 2C-T-7. Of the six, all except mescaline were developed by Shulgin himself.

In PIHKAL, Shulgin wrote: *"Here is another of the magical half-dozen… let it rest as being a difficult and worth-while material. A very much worth-while material."* He noted the typical oral dose as 10–25 mg and duration as 8–12 hours, and specifically flagged a **steep dose-response curve** — a small dose increase can produce a substantially stronger experience.

The synthesis route documented in PIHKAL begins with Friedel-Crafts acylation of 1,4-dimethoxybenzene, followed by Clemmensen reduction, Vilsmeier formylation, Henry reaction (nitrostyrene formation), and lithium aluminium hydride reduction to yield the amine hydrochloride.

### Research Chemical Market Emergence

2C-E entered the research chemical market in the early-to-mid 2000s, approximately contemporaneously with 2C-B and 2C-I. The compound was sold online as a legal research chemical in many jurisdictions prior to national/international scheduling.

### Key Incidents and Regulatory Timeline

- **March 2011, Blaine, Minnesota, USA**: One person (Trevor Robinson-Davis, 19 years old) died of cardiac arrest and ten others were hospitalised following mass insufflation of 2C-E at a private party. The drug was purchased online and was legal at the time of the incident; it had been mislabelled as 2C-I [Ref 27]. This incident was a significant driver of US scheduling.

- **July 9, 2012**: US President signed the **Synthetic Drug Abuse Prevention Act of 2012 (SDAPA)**, placing 2C-E and 25 other substances in Schedule I. DEA established formal drug codes January 4, 2013 [Ref 23].

- **2019** (European case): A documented mass poisoning event in Europe involved middle-aged individuals who consumed a combination of 2C-E and Bromo-DragonFly (BDF). Full case described in Iwersen-Bergmann et al. (2019) [Ref 2].

---

## Subjective Effects

Based on Papaseit et al. (2020) [Ref 1], the first controlled observational study of 2C-E in humans (n=10, oral doses 6.5–25 mg):

- **Primary effects:** Alterations in perception, hallucinations, and euphoric mood
- **Cardiovascular:** Increased blood pressure and heart rate
- **Rating scales (VAS, ARCI, VESSPA-SSE):** Showed psychedelic-like effects comparable to 2C-B and other serotonin-acting drugs at doses of 6.5–25 mg
- **Onset:** Effects were measurable at 2 hours (saliva Tmax)
- **Duration measured:** Effects assessed across 6 h in this study (total duration likely longer)

Shulgin's PIHKAL description [Ref 16] characterises 2C-E as producing:
- Open and closed-eye visuals
- Time distortion
- Enhanced introspection
- Ego dissolution at higher doses
- Strong euphoria in some individuals; significant body load discomfort in others
- Effects distinctly "difficult" and heavily dose-dependent

**Comparison to 2C-B:** Both compounds show similar subjective effect profiles via shared 5-HT₂A/2B/2C agonism; 2C-B (Papaseit et al. 2018 [Ref 13]) at 10–20 mg oral showed increased BP/HR, euphoria, and perceptual changes with saliva Tmax ~1 h. 2C-E at comparable doses showed similar trajectories but is characterised by users and Shulgin as more intense and more cognitively demanding.

**Effect taxonomy from DB** (not independently verified in published literature; note gaps):
- Perception effects (visual drifting, tracers, after-images, colour enhancement, internal hallucinations, synesthesia, etc.) are consistent with 5-HT₂A agonism mechanism.
- Cognitive effects (thought connectivity, creativity enhancement, pattern recognition, conceptual thinking) are consistent with the psychedelic class.
- Body effects (stimulation, nausea, bruxism, pupil dilation, increased urination, muscle tension, temperature dysregulation, abnormal heartbeat) are consistent with sympathomimetic and serotonergic effects documented in Papaseit 2020 [Ref 1] and Dean et al. 2013 [Ref 6].
- **Seizure threshold reduction** is noted in the DB and consistent with clinical toxicology literature (Dean 2013 [Ref 6]).

**⚠️ FLAG:** The specific effect taxonomies (e.g., "Visual scenery slicing," "Symmetrical texture repetition") in the DB are derived from user reports and psychedelic community consensus, not published controlled studies. They should be presented as user-reported phenomenology, not clinically validated findings.

---

## Safety & Toxicity

### LD50

**No published LD50 data exists for 2C-E in any species.** The toxic dose in humans is unknown (consistent with the seed data). This is a significant safety gap.

**⚠️ FLAG (safety-critical):** The absence of published LD50 data means the therapeutic index for 2C-E cannot be calculated. The generation agent must state this absence explicitly and not extrapolate from structural analogues.

### Human Fatalities

**One confirmed fatality** is documented in published literature and harm reduction databases (Erowid [Ref 14]):
- **Trevor Robinson-Davis** (male, age 19), Blaine, Minnesota, USA, **March 2011**
- Cause: **cardiac arrest** following insufflation of a large dose of 2C-E at a private party
- Autopsy: death attributed to cardiac arrest with drugs in the 2C category present; no pre-existing natural disease identified
- Context: drug was purchased online, was legal at the time, and was mislabelled as 2C-I [Ref 27]

**Mass poisoning events:**
1. **Blaine, MN, USA (2011):** 1 fatality + 10 hospitalised (2 in critical condition). Survivors reported delirium, hallucinations, paranoia, auditory distortions, overheating [Refs 14, 27].
2. **European case (2019):** A mass poisoning involving middle-aged individuals who consumed both 2C-E and Bromo-DragonFly (Iwersen-Bergmann et al. 2019 [Ref 2]). This case was unusual due to the age profile of the consumers and the combination of two NPS.

### Clinical Toxidrome

Based on Dean et al. (2013) [Ref 6] (the principal 2C toxicology review, 205 citations):

**Common features in 2C-drug intoxication:**
- Hallucinations, agitation, aggression, violence, dysphoria
- Hypertension, tachycardia
- Seizures
- Hyperthermia
- **Excited delirium** — most consistent presentation among reported deaths from 2C drugs (at least 5 deaths attributed to 2C drugs in literature at time of that review)

**Sympathomimetic toxidrome vs. serotonin toxicity:** Presentations can resemble either, reflecting 2C-E's dual mechanism (5-HT₂A agonism + mild NE/5-HT reuptake inhibition). Excited delirium with hyperthermia was the consistent feature in 2C-related deaths.

**Secondary complications:** Rhabdomyolysis, cardiovascular collapse, metabolic acidosis may occur in severe cases (consistent with excited delirium presentations; Zawilska et al. 2020 [Ref 21] for NBOMe comparators, applicable by mechanism).

### Acute Physiological Effects (Controlled Setting)

Papaseit et al. (2020) [Ref 1] documented in 10 users (6.5–25 mg oral):
- Elevated blood pressure
- Elevated heart rate
- No serious adverse events reported at these doses in this small sample

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## Harm Reduction

### Risk Mitigation

1. **Dose caution:** 2C-E has a notoriously **steep dose-response curve** (Shulgin [Ref 16]). Shulgin specifically warned that a small dose increase (e.g., 10 mg → 30 mg) can produce a dramatically more intense experience, including very frightening outcomes at the upper end.
2. **Route of administration:** The 2011 fatality occurred via insufflation, which yields faster onset and potentially higher peak concentrations compared to oral dosing. The brief identifies insufflation as the primary ROA in the DB — this is a significant risk flag. Insufflated pharmacokinetics for 2C-E have not been formally studied.
3. **Reagent testing:** 2C-E responds to Marquis reagent (produces black/dark colour), Mecke, and Simon's reagent. This can help distinguish from adulterants or substitutions (e.g., the MN incident involved mislabelled 2C-I).
4. **Setting and support:** Prolonged duration (8–12 hrs per Shulgin; 6–10 hrs per community consensus) requires adequate preparation.
5. **Hyperthermia management:** Active cooling is critical in overdose presentations; hyperthermia is a primary driver of morbidity.

### Emergency Protocol

Based on Dean et al. (2013) [Ref 6]:
- **Treatment is primarily supportive**
- **Benzodiazepines** for agitation and seizure control (first-line)
- Immediate action required for excited delirium, hyperthermia, and seizures
- Active cooling for hyperthermia
- No specific antidote

### Contraindications

Published contraindications specific to 2C-E are not established in the primary literature. By class mechanism:
- MAO inhibitors (MAOIs): likely dangerous — additive serotonergic effects; risk of serotonin syndrome
- Lithium: conflicting reports in psychedelic class; some suggest seizure risk
- Tramadol: **classified as dangerous** in DB — mechanistically supported (see Interactions section)

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## Tolerance & Dependence

### Tolerance

2C-E produces rapid tolerance consistent with the psychedelic class. The mechanism involves **5-HT₂A receptor downregulation** in frontal cortex following repeated activation, as demonstrated for psychedelic 5-HT₂A agonists by de la Fuente Revenga et al. (2022) [Ref 20]. Tolerance typically develops within 1–4 days of repeated use and subsides within several days.

### Cross-Tolerance

**Cross-tolerance with other classical psychedelics** (LSD, psilocybin, mescaline, DMT, other 2C-compounds) is established for the class (de la Fuente Revenga et al. 2022 [Ref 20]). This cross-tolerance is specific to psychedelic 5-HT₂A agonists and does **not** extend to non-psychedelic 5-HT₂A agonists such as lisuride [Ref 20].

The seed data lists "psychedelic" as the cross-tolerance class — consistent with literature.

### Dependence

2C-E is **not considered habit-forming** (consistent with the seed data). No published case reports of physiological dependence or withdrawal syndrome exist for 2C-E or the 2C class. This is consistent with the known pharmacology of the 5-HT₂A receptor — repeated activation leads to rapid receptor downregulation (tolerance), which reduces the reinforcing effects.

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## Interactions

### Tramadol: **Dangerous**

The "dangerous" classification in the seed data is **pharmacologically supported**:
- 2C-E activates 5-HT₂A/2B/2C receptors and inhibits SERT/NET (Papaseit 2020 [Ref 1])
- Tramadol inhibits SERT (human SERT-transfected HEK293 cells confirmed; Baldo 2018 [Ref 22]) and is associated with serotonin syndrome, particularly when combined with other serotonergic agents (Park et al. 2014 [Ref 29]; Baldo 2018 [Ref 22])
- The combination of a 5-HT₂A agonist (2C-E) with a SERT inhibitor (tramadol) would substantially increase synaptic serotonin activity — a recognised mechanism for serotonin syndrome
- ⚠️ **FLAG (safety-critical):** No case report specifically documenting 2C-E + tramadol serotonin syndrome has been found in the published literature. The "dangerous" classification is based on pharmacological mechanism (class-level evidence), not substance-specific clinical reports. This should be stated explicitly.

### Cannabis: **Unknown**

No published data on 2C-E + cannabis interactions. The "unknown" classification in the DB is appropriate. By class: cannabis (via CB₁ agonism) may potentiate psychedelic effects or increase psychological distress in some individuals, but substance-specific data for 2C-E is absent.

### Other Interactions (Class-Level Evidence, Not 2C-E-Specific)

- **MAO inhibitors:** Likely dangerous — the combination of serotonin reuptake inhibition and 5-HT₂A agonism with MAOI-mediated serotonin accumulation would substantially increase serotonin syndrome risk.
- **SSRIs/SNRIs:** May reduce psychedelic effects via 5-HT₂A downregulation from chronic SSRI use; simultaneous acute use could increase serotonin toxicity risk.
- **Lithium:** Some reports of seizures when combined with psychedelics; mechanism unclear.
- **Stimulants (amphetamines, cocaine):** Additive cardiovascular strain.
- **Bromo-DragonFly:** Documented mass poisoning when combined with 2C-E (Iwersen-Bergmann 2019 [Ref 2]); specific mechanism not characterised.

⚠️ **FLAG:** The interaction list in the DB contains only tramadol and cannabis. The generation agent may wish to flag additional high-risk interactions (MAOIs in particular) for editorial review, given established class-level pharmacology.

---

## Legal Status

| Jurisdiction | Status | Date | Mechanism |
|---|---|---|---|
| United States | Schedule I | July 9, 2012 | Synthetic Drug Abuse Prevention Act (SDAPA) [Ref 23] |
| United Kingdom | Class A | 2002 | Misuse of Drugs Act 1971 amendment (phenethylamine catch-all) [Ref 15] |
| Sweden | Controlled | October 1, 2004 | National scheduling [Ref 15] |
| Denmark | Schedule I | April 8, 2007 | National scheduling [Ref 15] |
| Israel | Controlled | December 2007 | National scheduling [Ref 15] |
| China | Category I psychotropic | September 2010 | National scheduling [Ref 15] |
| Japan | Designated substance | Unknown date | Designated substances law [Ref 15] |
| New Zealand | Schedule 3 / Class C | Ongoing | Analogues provision [Ref 15] |
| Brazil | Controlled | February 18, 2014 | National scheduling [Ref 15] |
| Germany | Anlage I BtMG | December 13, 2014 | Narcotics Act (BtMG) [Ref 15] |
| Finland | Banned | December 19, 2014 | National scheduling [Ref 15] |
| Canada | Schedule III (unconfirmed) | ~October 2016 | Erowid notes as unconfirmed [Ref 15] |
| Australia | Likely Schedule 9 | Not confirmed | Analogy with other 2C compounds; not independently verified |

⚠️ **FLAG:** Australia and Canada status requires independent verification from official government sources. Erowid specifically marks Canada's Schedule III status as "unconfirmed." Australia was not listed in the Erowid legal database retrieved, though by analogy with the 2C-drug class is likely Schedule 9 (prohibited substance).

**Federal Analog Act (USA):** Prior to 2012 SDAPA scheduling, 2C-E may have been subject to prosecution under the Federal Analog Act as a structural analogue of a controlled substance. The 2011 Blaine, MN arrest was made under this provision [Ref 27].

---

## Clinical Trials

**No registered clinical trials for 2C-E were identified** in ClinicalTrials.gov search. The nearest registered trial is NCT05523401 ("Acute Effects of 2C-B Compared with MDMA and Psilocybin in Healthy Subjects," completed, Phase 1, University Hospital Basel), which involves a different compound.

2C-E has not entered clinical trial programmes. Its Schedule I status in the US and Class A status in the UK creates significant regulatory barriers to human research.

---

## Community Feedback Analysis

**No community feedback submitted.** (Part A2 of the brief was empty.)

---

## Gaps & Flags

### Critical Safety Gaps (flag for editorial review before publication)

1. **⚠️ No published LD50 data for 2C-E in any species.** Toxic dose in humans is unknown. This must be stated explicitly in the article; no extrapolation from structural analogues should be made.

2. **⚠️ Tramadol interaction classified as "dangerous" — pharmacologically supported but not confirmed by a published 2C-E + tramadol case report.** The mechanism is credible (SERT inhibition + 5-HT₂A agonism → serotonin syndrome risk), but absence of substance-specific clinical evidence should be disclosed.

3. **⚠️ Insufflated pharmacokinetics are entirely unstudied.** The DB lists insufflation as the primary ROA; the only human PK data (Papaseit 2020) is oral. All insufflated dose/duration data in the DB is derived from user reports. This gap is significant because the confirmed US fatality occurred via insufflation.

4. **⚠️ SMILES string missing from PubChem API response.** The generation agent should retrieve canonical SMILES from PubChem CID 24729233 directly before publishing.

### Data Quality Flags

5. **Ki/EC₅₀ values not extractable from abstracts.** Binding affinity data is published in tables of Eshleman et al. 2014 [Ref 3], Rickli et al. 2015 [Ref 4], and Ray 2010 [Ref 5]. The generation agent should access full papers for specific numerical values.

6. **Duration discrepancy between sources:**
   - Seed data (DB): 6–10 hours total (oral)
   - Shulgin PIHKAL [Ref 16]: 8–12 hours
   - These ranges overlap but are not identical. Shulgin's data is based on small personal bioassay (not formal studies). The DB range appears to reflect the more conservative community consensus.

7. **Dose discrepancy (Shulgin vs. seed data):**
   - Shulgin PIHKAL [Ref 16]: dose range 10–25 mg oral; Shulgin personal dose notes begin at 10 mg
   - Seed data: Common dose listed as 10–15 mg; Heavy listed as 30+ mg
   - Papaseit 2020 [Ref 1]: Used doses of 6.5–25 mg; 6.5 mg produced measurable effects
   - The seed data's threshold of 2 mg and light range of 5–10 mg are **lower** than Shulgin's minimum of 10 mg. This may reflect unusually sensitive individuals or different formulation purity. No published dose-finding study exists to adjudicate. The generation agent should propose dose data conservatively and flag this discrepancy for editorial review.

8. **Insufflated dose ranges in seed data** (threshold 1 mg, light 1–4 mg, common 4–7 mg, strong 7–14 mg, heavy 14+) are **entirely community-consensus-derived** with no published pharmacokinetic support. The 2011 fatality occurred via insufflation, which complicates these lower dose thresholds. Treat as community-consensus data only.

9. **Street name:** Seed data lists "Eternity." PsychonautWiki also lists "Aquarust" as a street name. Neither appears in published literature. Include as community-reported only.

10. **CAS number 71539-34-9** is widely cited in the literature and databases but was not confirmed via API. Flag for editorial verification.

11. **Australia legal status not confirmed.** Web search and Erowid database did not explicitly confirm Australia Schedule 9 status for 2C-E. Generation agent should not state this as confirmed.

12. **Canada legal status contested.** Erowid notes Schedule III but marks it "unconfirmed." Earlier Erowid data suggests it may have been unscheduled. Generation agent should state as uncertain pending official source verification.

### Structural Analogy Reliance

13. **MAO inhibitor interaction**, while mechanistically obvious, is listed here by class-level inference, not 2C-E-specific evidence.
14. **Seizure threshold reduction** is listed in the DB effects taxonomy and supported by the Dean 2013 review for the 2C class, but no 2C-E-specific seizure mechanistic study exists.
15. **Dependence/withdrawal:** Absence of published reports is consistent with the pharmacological class; this is class-level inference, not 2C-E-specific data.