MET

# Research Output: MET (Methylethyltryptamine)

**PSX ID:** PSX-0246  
**Generation Provenance ID:** 41a882d0-804b-4dcb-adc5-6aa751cf2cc1  
**Research Date:** 2026-05-10  
**Substance Readiness:** Sparse data (readiness < 0.3) — primarily emerging/research chemical with no published controlled human studies

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## Chemical Identity

**Verified via PubChem CID 824845 [Ref 1]:**

| Property | Value |
|---|---|
| PubChem CID | 824845 |
| IUPAC Name | N-ethyl-2-(1H-indol-3-yl)-N-methylethanamine |
| Molecular Formula | C₁₃H₁₈N₂ |
| Molecular Weight | 202.30 g/mol |
| Canonical SMILES | CCN(C)CCC1=CNC2=CC=CC=C21 |
| InChI | InChI=1S/C13H18N2/c1-3-15(2)9-8-11-10-14-13-7-5-4-6-12(11)13/h4-7,10,14H,3,8-9H2,1-2H3 |
| InChIKey | MYEGVMLMDWYPOA-UHFFFAOYSA-N |
| XLogP | 2.9 |
| H-Bond Donors | 1 (indole NH) |
| H-Bond Acceptors | 1 (tertiary amine N) |

**Notes on seed data discrepancies:**
- The seed brief listed SMILES, molecular formula, molecular weight, InChIKey, and PubChem CID as empty. All have now been confirmed via PubChem [Ref 1].
- IUPAC name in seed brief ("N-ethyl-2-(1H-indol-3-yl)-N-methylethanamine") matches PubChem exactly.
- No CAS Registry Number was retrievable via PubChem API or web search.
- The SMILES (CCN(C)CCC1=CNC2=CC=CC=C21) confirms the structure: a tryptamine core with an N-methyl and N-ethyl group at the terminal amine nitrogen (asymmetric dialkylation).
- No stereogenic centers; no chiral isomers.

**Physical properties:** No published melting point, solubility, or stability data. XLogP of 2.9 suggests moderate lipophilicity, comparable to DET (N,N-diethyltryptamine). As a free base, it is expected to be an oily liquid at room temperature, analogous to DMT and DET. No salt forms have been formally characterized in published literature.

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## Pharmacology

### Mechanism of Action

MET is a substituted tryptamine and is classified as a serotonin 5-HT2A receptor agonist and 5-HT1A receptor partial agonist. No MET-specific binding affinity (Ki) or functional potency (EC50) data have been published in peer-reviewed literature. All receptor pharmacology is inferred from structural analogy to the N,N-dialkylated tryptamine class.

**Primary mechanism — 5-HT2A agonism:**  
Classical hallucinogenic tryptamines exert psychedelic effects primarily through agonism at the serotonin 5-HT2A receptor (Glennon et al. 1992 [Ref 17]). PLC-IP1 (inositol monophosphate) formation via Gq/11 coupling is the signaling readout most strongly correlated with human psychoactive doses across serotonergic psychedelics (Rudin et al. 2026 [Ref 10]). Serotonergic psychedelics also activate PLA2-arachidonic acid and β-arrestin2 pathways at 5-HT2A, with compound-specific bias profiles influencing experiential character (Rudin et al. 2026 [Ref 10]).

**N-alkyl substitution and 5-HT2A affinity:**  
Lyon et al. (1988 [Ref 16]) established a clear SAR gradient across 21 indolealkylamines at rat brain 5-HT2 receptors using [3H]ketanserin: terminal amine substitution reduced affinity in the order primary amine > N,N-dimethyl (DMT-class) > N,N-diethyl (DET-class). MET (N-methyl + N-ethyl at the terminal nitrogen) is a mixed asymmetric dialkyl compound; its 5-HT2A affinity is expected to fall between DMT and DET — somewhat weaker than DMT (N,N-dimethyltryptamine) based on the progressive decrease with increasing alkyl bulk. No MET-specific binding data confirm this prediction.

**Secondary mechanism — 5-HT1A partial agonism:**  
Serotonergic tryptamines with N,N-dimethyl or N-monoalkyl substitution also engage 5-HT1A receptors as partial agonists (Warren et al. 2024 [Ref 12]; Glatfelter et al. 2023 [Ref 5]). The 5-HT1A component modulates the overall phenomenological character, generally attenuating HTR (head-twitch response) and reducing psychedelic intensity while contributing anxiolytic and thermoregulatory effects (Puigseslloses et al. 2024 [Ref 13]). The 5-HT2A/5-HT1A activation ratio may inform seizure risk (Rudin et al. 2026 [Ref 10]).

**FLAG — Pharmacology:** No MET-specific Ki, EC50, or functional assay data have been published. The pharmacological class designations (5-HT2A agonist, 5-HT1A partial agonist) in the seed data are well-supported at the class level but are not substance-specific confirmed values. Any article section citing binding affinity for MET must be labeled as class-level inference unless new primary data are published.

### Metabolism and Pharmacokinetics

No published pharmacokinetic data for MET in any species.

**Expected metabolic pathway (structural analogy):**  
DMT (N,N-dimethyltryptamine) is the closest well-studied analog. DMT is rapidly metabolized by monoamine oxidase A (MAO-A) via oxidative deamination to indole-3-acetic acid (IAA) as the primary metabolite, with minor CYP2D6 involvement [Ref 4, 11]. This MAO-A sensitivity renders DMT orally inactive without MAOI co-administration. By structural analogy, MET's primary metabolic enzyme is also expected to be MAO-A.

**Critical pharmacological distinction — oral activity via N-ethyl group:**  
Shulgin noted in TiHKAL (1997 [Ref 20]) that MET "shows oral activity" in the 80–100 mg range, attributing this to the N-ethyl substitution providing protection from "total enzymatic annihilation" by MAO. This is consistent with the biochemical principle that N-monoethyl tryptamines are more resistant to MAO-A oxidative deamination than N-dimethyl analogs (DMT), because steric bulk of the ethyl group partially occludes the MAO active site. DET (N,N-diethyltryptamine), which carries two ethyl groups, exhibits greater oral activity than DMT for this reason. MET's asymmetric N-methyl/N-ethyl substitution provides intermediate protection — oral activity at higher doses than DET might require, but without requiring a full MAO inhibitor. This mechanistic inference is supported by Shulgin's report [Ref 20] but has not been confirmed by formal pharmacokinetic study.

**FLAG — Metabolism:** The MAO-A resistance hypothesis for MET oral activity derives from Shulgin (1997 [Ref 20]) and structural analogy, not from pharmacokinetic measurement. No plasma concentration–time data, bioavailability estimates, Tmax, or half-life data exist for MET. Generation agent must clearly label these as class-level inferences.

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## History

### Discovery and First Description

MET was reportedly first described in Michael Valentine Smith's book *Psychedelic Chemistry* (1981 [Ref 21]). This book was a clandestine chemistry text primarily circulated in underground communities; it provided synthesis procedures for numerous tryptamine compounds including several asymmetric N-alkyl derivatives. Smith's work predates formal academic investigation of MET and is the primary reference for MET's earliest appearance in any published source.

Shulgin subsequently referenced MET in TiHKAL (1997 [Ref 20]) within the commentary section of entry #47 (MiPT — N-methyl-N-isopropyltryptamine). MET does **not** have a dedicated numbered entry in TiHKAL; the mention is subsidiary to the MiPT entry, where Shulgin uses MET's oral activity to illustrate how going from an N-methyl to an N-ethyl group "does indeed protect the compound from total enzymatic annihilation when taken orally." Shulgin gives an approximate oral dose of 80–100 mg. No subjective experience report for MET appears in TiHKAL. Shulgin did not include MET as one of the 55 fully profiled tryptamines, reflecting its marginal status even among psychedelic chemists.

### Appearance on Research Chemical Markets

MET does not have documented emergence dates in peer-reviewed literature. Based on community sources [Ref 9, 22], MET began appearing on research chemical markets during the 2010s, following the broader expansion of tryptamine RC availability. It has remained relatively obscure compared to DET, DPT, or 4-AcO-MET (which received more attention).

### Regulatory History

See Legal Status section.

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## Subjective Effects

No controlled human studies of MET's subjective effects have been published. All subjective effect data derives from self-reports in community databases.

**Erowid documentation [Ref 9]:** The Erowid MET vault catalogues four user experience reports and characterizes MET's effects as "not well documented," cross-referencing DMT and DET as the closest analogs. The reports are titled "An Early Voyage into MET Space" and "A Very Noteworthy Analogue," suggesting a broadly psychedelic profile.

**PsychonautWiki summary [Ref 22]:** Community documentation describes MET as producing visual geometry, color enhancement, auditory distortion, time alteration, and euphoria. Described as stimulating relative to DMT. The smoked route is characterized as producing an abrupt onset and intense, short-duration effect.

**Duration data by route (seed data — no controlled study):**
- *Smoked:* Onset 30–60 sec; peak 10–20 min; total 30–75 min; aftereffects 20–60 min
- *Insufflated:* Onset 2–5 min; come-up 20–40 min; peak 1–1.5 hr; total 2–4 hr; aftereffects 4–12 hr
- *Oral:* Onset 1–2 hr; come-up 30–60 min; peak 1.5–2.5 hr; total 4–6 hr; aftereffects 6–24 hr

**Dose data — NOTE ON DISCREPANCY:**  
The seed data lists oral threshold at 40 mg and common dose at 120–150 mg. Shulgin's TiHKAL [Ref 20] gives a range of "80–100 mg" orally without explicitly categorizing this as light, common, or strong — contextually it reads as a psychoactive (active) dose range. This Shulgin range is lower than the seed data's common dose (120–150 mg) and higher than the seed data's threshold (40 mg); it roughly corresponds to the seed data's light dose range (60–120 mg). Given the absence of controlled studies, the Shulgin reference represents the only published human-experiencer dose guidance, and the discrepancy between ~80–100 mg (Shulgin) and ~120–150 mg (community consensus common dose) should be **flagged for editorial review** when setting dose fields. The seed data common dose of 120–150 mg may reflect dose escalation in experienced users or different purity standards.

**FLAG — Dose ranges:** The oral common dose in the seed data (120–150 mg) exceeds Shulgin's published active dose reference (80–100 mg). This discrepancy cannot be resolved from published sources and requires editorial judgment.

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## Safety & Toxicity

### LD50 and Acute Toxicity

No LD50 has been determined for MET in any species. No controlled toxicity studies have been published. All toxicity predictions are structural analogy from DMT and the serotonergic tryptamine class.

### Human Fatalities

No human fatalities have been attributed to MET alone in published literature. A case report by McIntyre et al. (2015 [Ref 3]) detected 4-hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET, a hydroxylated structural analog) in postmortem biological samples, but cause of death was certified as acute mixed drug intoxication primarily attributed to 4-methoxyphencyclidine (4-MeO-PCP). The 4-HO-MET was detected by GC-MS but not quantified, and co-medications (venlafaxine, olanzapine, lorazepam, hydroxyzine) were present at therapeutic levels. This case does not represent a MET (unsubstituted) fatality and should not be characterized as such, but demonstrates that 4-HO-MET (an indirectly related compound) is detectable in forensic contexts.

**FLAG — Safety:** The McIntyre 2015 case report involves 4-HO-MET (a 4-hydroxyl substituted congener), not MET itself. These are distinct compounds with different structures and profiles. The generation agent should not conflate them.

### Cardiovascular Risk

The serotonergic psychedelic class generally shows low 5-HT2B receptor activation at typical doses, which corresponds to reduced cardiac valvulopathy risk with intermittent use (Rudin et al. 2026 [Ref 10]). Acute sympathomimetic effects (tachycardia, blood pressure elevation) are class-typical but have not been formally quantified for MET.

### Psychological Risks

Class-level risks include anxiety, panic, paranoia, and psychotic decompensation in predisposed individuals (Tittarelli et al. 2015 [Ref 11]; Malaca et al. 2020 [Ref 4]). The stimulating character of MET noted in community reports may increase acute cardiovascular loading compared to sedating tryptamines. No published data on HPPD (hallucinogen persisting perception disorder) specific to MET.

### Organ Toxicity

The seed data notes cardiovascular and pulmonary as organs affected, consistent with class-level predictions. Pulmonary effects are relevant primarily for the smoked route. No specific organ toxicity data for MET.

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## Harm Reduction

### Key Risk Factors

1. **MAO inhibitor interaction (DANGEROUS):** Any combination of MET with monoamine oxidase inhibitors (MAOIs — including irreversible classical MAOIs like phenelzine, tranylcypromine, as well as reversible inhibitors such as moclobemide, or harmaline in ayahuasca preparations) carries risk of serotonin syndrome (Malcolm & Thomas 2022 [Ref 6]). This is a class-level contraindication for all serotonergic tryptamines.

2. **Lithium carbonate (DANGEROUS):** Lithium is documented to potentiate seizure risk when combined with serotonergic psychedelics. The mechanism is not fully characterized but is thought to involve lithium's effects on second messenger systems (IP3 accumulation) interacting with 5-HT2A-mediated signaling. This interaction is flagged as dangerous in the seed data and is supported by class-level evidence from the broader psychedelic literature (Luethi & Liechti 2020 [Ref 14]).

3. **Tramadol (CAUTION):** Tramadol has both opioid agonist and serotonin-norepinephrine reuptake inhibitor properties, placing it in the category of serotonergic agents that can produce serotonin toxicity in combination with serotonergic psychedelics (Beakley et al. 2015 [Ref 7]; Malcolm & Thomas 2022 [Ref 6]). The serotonin-releasing action of tramadol at serotonergic synapses can synergize with 5-HT2A agonism.

4. **Cannabis (CAUTION):** Cannabis (THC) is known to potentiate anxiety, paranoia, and perceptual distortion during psychedelic experiences. This is a class-level behavioral interaction, not a pharmacokinetic drug interaction per se (seed data; community consensus).

5. **SSRIs and SNRIs:** Selective serotonin reuptake inhibitors are documented to blunt psychedelic effects via 5-HT2A receptor downregulation, while also carrying theoretical serotonin toxicity risk (Malcolm & Thomas 2022 [Ref 6]).

### Contraindications

- Personal or family history of psychosis, schizophrenia, or bipolar disorder
- Current use of MAOIs (absolute contraindication)
- Concurrent use of lithium carbonate (absolute contraindication)
- Cardiovascular disease, uncontrolled hypertension
- Pregnancy and lactation (no safety data)

### Testing Recommendations

MET-specific colorimetric reagent response data are not published. As a tryptamine, MET is expected to produce a purple-to-black reaction with Ehrlich's reagent (p-dimethylaminobenzaldehyde), which is a class indicator for indoles. Confirmatory identification requires GC-MS or LC-MS/MS (Ambach et al. 2015 [Ref 23]; Malaca et al. 2020 [Ref 4]).

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## Tolerance & Dependence

### Tolerance

**FLAG — Tolerance data:** No MET-specific tolerance data exist. The following is class-level inference.

Class-level mechanism: Serotonergic psychedelics produce rapid functional tolerance via 5-HT2A receptor downregulation and desensitization following acute exposure. Tachyphylaxis develops within 1–3 exposures, functionally limiting repeated dosing within short intervals. Full receptor resensitization is estimated at approximately 14 days based on LSD, psilocybin, and DMT analog studies (Tittarelli et al. 2015 [Ref 11]; Malaca et al. 2020 [Ref 4]). Cross-tolerance with DMT, psilocybin, LSD, mescaline, and other 5-HT2A agonists is expected at the class level.

### Dependence

**FLAG — Dependence data:** No MET-specific dependence data exist. Class-level prediction follows.

Serotonergic psychedelics as a class do not produce physical dependence and show negligible compulsive redosing potential (Tittarelli et al. 2015 [Ref 11]). The rapid tachyphylaxis mechanism itself serves as a functional barrier to compulsive use — repeated doses within hours are unrewarding due to receptor desensitization. MET's stimulating character could theoretically provide a mild positive reinforcement component, but this has not been studied.

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## Interactions

### Serotonin Toxicity Risk

Malcolm & Thomas (2022 [Ref 6]) provide a systematic review of serotonin toxicity risk in the context of serotonergic psychedelics combined with other serotonergic agents. The principal risk factors are: (1) combination with MAOIs, (2) combination with serotonin releasers (e.g., MDMA, tramadol), and (3) combination with serotonin reuptake inhibitors. MET carries these class-level risks.

### Tramadol

Tramadol acts as a serotonin-norepinephrine reuptake inhibitor in addition to its opioid agonist effects, and is a documented cause of serotonin syndrome at therapeutic doses in combination with serotonergic drugs (Beakley et al. 2015 [Ref 7]). The combination of tramadol with MET should be considered dangerous due to additive serotonin toxicity risk (seed data: "caution").

### Lithium

The lithium + serotonergic psychedelic combination is flagged as dangerous in the seed data. Class-level mechanism: lithium's inhibition of inositol monophosphatase leads to IP accumulation, which interacts with the Gq/11-PLC-IP pathway engaged by 5-HT2A agonism, potentially producing seizure threshold reduction and neurotoxicity. This mechanism is documented in the broader pharmacodynamic literature (Luethi & Liechti 2020 [Ref 14]).

### Cannabis

THC via CB1 receptor agonism potentiates perceptual distortion, anxiety, and paranoia in the psychedelic state. This is a behavioral/pharmacodynamic interaction without a clear serotonergic mechanism per se. The combination may significantly increase the probability of panic and adverse psychological reactions.

### MAOIs

Combining MET with any MAO inhibitor would be expected to substantially increase plasma concentrations (reduced first-pass metabolism of ingested MET) and synaptic serotonin levels, dramatically elevating serotonin toxicity risk (Malcolm & Thomas 2022 [Ref 6]).

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## Legal Status

**United States:** MET is **not explicitly scheduled** under the Controlled Substances Act as of May 2026. The DEA's 2022 rule scheduling five additional tryptamines (4-OH-DiPT, 5-MeO-AMT, 5-MeO-MiPT, 5-MeO-DET, DiPT) did not include MET. However, MET could be subject to the **Federal Analogue Act** (21 U.S.C. § 813) if intended for human consumption, as DMT (N,N-dimethyltryptamine) is Schedule I and MET shares substantial structural similarity. Application of the Analogue Act requires prosecution-by-prosecution proof and is not automatic. [Ref 8 — web-retrieved]

**United Kingdom:** MET is a **Class A** controlled substance under the **Misuse of Drugs Act 1971**, captured by the generic tryptamine definition. The UK generic definition covers derivatives of tryptamine with mono- or di-N-alkyl substitution at the terminal amine, explicitly including MET. Penalties for Class A possession: up to 7 years imprisonment. Penalties for supply: up to life imprisonment. [Ref 8 — web-retrieved]

**Germany:** MET is controlled under the **Neue-psychoaktive-Stoffe-Gesetz (NpSG)** (New Psychoactive Substances Act) since July 18, 2019. Production and import for commercial purposes and supply to others are criminalized; personal possession is illegal but not separately penalized. [web-retrieved]

**Canada:** MET is **not scheduled** under the Controlled Drugs and Substances Act as of 2026. [web-retrieved]

**New Zealand:** MET is a **Class C** controlled substance as an analogue of scheduled tryptamines. [web-retrieved]

**Australia:** MET's specific scheduling status under the Therapeutic Goods Administration (TGA) Poisons Standard could not be confirmed via structured API searches. Based on the regulatory framework (Schedule 9 prohibited substances typically includes DMT and tryptamine analogs), MET is likely controlled, but this requires verification from official TGA sources.

**FLAG — Legal status:** Australian scheduling for MET was not confirmed via primary government sources. The generation agent should not state definitive scheduling in Australia without editorial verification.

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## Clinical Trials

**No clinical trials involving MET have been registered on ClinicalTrials.gov.** A search for "methylethyltryptamine MET tryptamine" returned zero results. MET has no clinical development history.

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## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief for this generation run.

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## Gaps & Flags

The following data gaps and safety-critical flags require editorial attention:

### Substance-Specific Data Absent (confirmed by research)

1. **No published receptor binding data (Ki or EC50) for MET** at any receptor target. All pharmacological classification (5-HT2A agonist, 5-HT1A partial agonist) is class-level inference by structural analogy.

2. **No published human pharmacokinetic data** (bioavailability, Tmax, Cmax, half-life, volume of distribution) for any route of administration.

3. **No LD50 data** in any species.

4. **No controlled human subjective effects data** (no clinical studies, no formal psychedelic questionnaire assessments).

5. **No controlled dosing studies** in any species.

6. **No published case reports of adverse events or overdose attributable to MET specifically.** The McIntyre et al. 2015 [Ref 3] case involves 4-HO-MET (not MET) and is primarily attributed to 4-MeO-PCP.

7. **No CAS Registry Number** was retrievable via PubChem API or web search.

### Safety-Critical Flags Requiring Editorial Review

8. **⚠️ Oral dose range discrepancy:** Shulgin (TiHKAL 1997 [Ref 20]) gives an oral active dose of ~80–100 mg for MET. The seed data lists oral common dose as 120–150 mg (threshold: 40 mg). The Shulgin range corresponds approximately to the seed data's "light" category (60–120 mg). This discrepancy cannot be resolved from published sources. The seed dose ranges may reflect community consensus from more experienced users or variable purity, but the Shulgin report is the only published primary dose reference. **Editorial team should review whether oral common dose (120–150 mg) is well-supported by the community evidence base.**

9. **⚠️ Lithium interaction listed as "dangerous"** — this is supported at the class level (Luethi & Liechti 2020 [Ref 14]) but no MET-specific case or controlled data exist.

10. **⚠️ Australian legal status unconfirmed** via primary government sources. Web-retrieved sources suggest likely control but do not provide a definitive TGA scheduling reference.

11. **⚠️ SMILES string was missing from seed data** — now confirmed as CCN(C)CCC1=CNC2=CC=CC=C21 via PubChem CID 824845 [Ref 1]. Generation agent should include this in chemical data section.

12. **⚠️ MAO protection mechanism for oral activity** — The claim that N-ethyl substitution confers oral bioavailability via MAO resistance derives from Shulgin (1997 [Ref 20]) and structural analogy. This is a reasonable and well-supported biochemical inference, but it has not been formally verified in pharmacokinetic studies.

13. **Discovery attribution to "Michael Valentine Smith" (1981 [Ref 21])** — This source is from a clandestine chemistry text and cannot be API-verified. Treat as unverifiable/web-retrieved. Web search results corroborate this as the earliest reference.

### Effect Profile Notes

14. All 54 effect slugs in the seed data lack intensity/frequency values (all null/null). These are based on community_consensus_large/medium provenance. The generation agent should apply class-level inference (based on DMT and DET analogy) when proposing values, clearly labeling them as community consensus or structural analogy rather than controlled-study derived.

15. The seed effect taxonomy appears comprehensive and consistent with a serotonergic psychedelic profile. The generation agent should particularly note MET's more stimulating character (compared to DMT) when assigning intensity values to stimulation, wakefulness, and motor effects.

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## Source Notes

- MET is a genuinely sparse-data substance. The citation registry for this run (23 entries) includes 0 substance-specific primary research papers — all pharmacological data is structural analogy from the tryptamine class.
- The most authoritative primary source for MET-specific data remains Shulgin's TiHKAL (1997 [Ref 20]), which provides only a brief oral dose reference and mechanism hypothesis without controlled data.
- Community databases (Erowid [Ref 9], PsychonautWiki [Ref 22]) represent the best available evidence for phenomenology given the absence of published controlled data.
- Any article generation must be transparent about the structural-analogy basis of virtually all pharmacological claims about MET.