generation run 2026-05-10
72 min completedmodel pipeline-v5plan not recordedrun/4c1c0cb0…Selection
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The model's own caveats
4 further caveats recorded as free text — readable on the working page
Reproduce
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17 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | WebSearch | 5-MeO-AMT legal status DEA scheduling controlled substance USA UK | 10 | 1 | Critical legal status finding |
| 2 | ClinicalTrials.gov · absence | 5-MeO-AMT 5-methoxy-alpha-methyltryptamine | 0 | 0 | No clinical trials |
| 3 | PubMed · absence | 5-methoxy-alpha-methyltryptamine toxicity adverse effects case report | 0 | 0 | No results |
| 4 | OpenAlex | 5-methoxy-alpha-methyltryptamine 5-MeO-AMT | 51 | 4 | High-citation reviews directly relevant to tryptamine pharmacology and 5-MeO-AMT |
| 5 | PubMed | 5-MeO-AMT 5-methoxy-alpha-methyltryptamine pharmacology | 7 | 7 | All directly relevant to 5-MeO-AMT pharmacology |
| 6 | PubChem | 5-MeO-AMT | 1 | 1 | Primary chemical identity verification |
| 7 | WebSearch | 5-methoxy-alpha-methyltryptamine Alpha-O history synthesis first appearance | 10 | 2 | History, dose, and street name data |
| 8 | WebSearch | 5-MeO-AMT overdose cardiac arrhythmia seizure sympathomimetic toxidrome | 10 | 3 | Safety-critical information for harm reduction section |
| 9 | NDIC (National Drug Intelligence Center) | 5-MeO-AMT fast facts | 1 | 4 | Government law enforcement profile with dose/duration data |
| 10 | NCATS Inxight Drugs | 5-MeO-AMT U5XOB9AQ15 | 1 | 3 | Chemical identity and key pharmacological values |
| 11 | PubMed/NCATS | Rickli 2016 receptor interaction profiles novel psychoactive tryptamines | 1 | 1 | Critical verification of primary pharmacology source |
| 12 | WebSearch | 5-MeO-AMT legal status UK Misuse of Drugs Act Japan Australia Canada scheduling | 10 | 3 | Key legal status data for major jurisdictions |
| 13 | Release UK | 5-MeO-AMT history synthesis | 1 | 2 | Primary historical documentation of 5-MeO-AMT |
| 14 | WebSearch | 5-MeO-AMT Australia Schedule 9 Sweden Canada legal status | 10 | 3 | International legal status completion |
| 15 | PubMed | serotonin toxicity serotonergic psychedelics SSRI interaction | 5 | 1 | Drug interaction and serotonin syndrome risk |
| 16 | NCATS/Rickli 2016 | 5-MeO-AMT receptor binding affinity Ki EC50 | 3 | 1 | Critical receptor pharmacology values |
| 17 | Erowid | 5-MeO-AMT basics dose duration | 1 | 4 | Community-level dose and duration data with safety context |
54 claims by section — every cited sentence, checked against its source
safety13 · 10 ok
Claim in safety — not_supportednot supportedworking →
Claim in safety — inconclusiveinconclusiveworking →
5-MeO-AMT is a potent 5-HT₂B agonist (EC50 = 4 nM)supported
5-MeO-AMT: 5-HT2B EC50=4 nM (agonist). j.euroneuro.2016.05.001
Sustained 5-HT₂B receptor activation is mechanistically linked to cardiac valvulopathy via mitogenic and fibrotic changes in valvular interstitial cellssupported
5-HT2B activation mediates fibrotic changes in valvular tissue. a-2794-6487
Sustained 5-HT₂B receptor activation is mechanistically linked to cardiac valvulopathy via mitogenic and fibrotic changes in valvular interstitial cellssupported
Microdosing psychedelics risks cardiac fibrosis/valvulopathy via 5-HT2B. 02698811231225609
This occurred in parallel with increased 5-HT₂A mRNA in the prefrontal cortex — a compensatory transcriptional upregulation consistent with receptor-level desensitization.supported
5-MeO-AMT increased 5-HTR2a mRNA and PKC-γ phosphorylation in PFC. j.bbr.2018.07.020
De la Fuente Revenga et al. (2022) demonstrated that repeated administration of 5-HT₂A agonists decreases 5-HT₂A receptor density in the frontal cortex, providing the mechanistic basis for tolerance across the psychedelic classsupported
tolerance develops via 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Cross-tolerance with other 5-HT₂A-mediated psychedelics (lsd, psilocybin, mescaline) is expected based on this shared mechanism.supported
Cross-tolerance between psychedelics (DOI, LSD) but not between psychedelic and non-psychedelic 5-HT2A agonists. acschemneuro.2c00170
Rodent models found no conditioned place preference and no self-administration, indicating low reinforcement potentialsupported
No locomotor sensitization, CPP, or self-administration — suggesting low abuse liability. j.bbr.2018.07.020
Co-administration with SSRIs or SNRIs raises serotonin syndrome risk through additive serotonergic activitysupported
Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances (5-HT2A agonists/SERT substrates) and SSRIs/MAOIs. s00213-021-05876-x
Claim in safety — inconclusiveinconclusiveworking →
Cardiac arrhythmia or structural heart disease — the combination of sympathomimetic effects and potent 5-HT₂B agonism creates dual cardiovascular risksupported
5-MeO-AMT: 5-HT2B EC50=4 nM (agonist). j.euroneuro.2016.05.001
Concurrent SSRI or SNRI use — serotonin syndrome risksupported
Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances (5-HT2A agonists/SERT substrates) and SSRIs/MAOIs. s00213-021-05876-x
pharmacology11 · 8 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
5-MeO-AMT operates through a dual mechanism: high-potency 5-HT₂A receptor agonism mediating its psychedelic effects, and broad-spectrum monoamine transporter activity (reuptake inhibition and release of serotonin, dopamine, and norepinephrine) contributing stimulant and entactogen-adjacent properties.supported
5-MeO-AMT strongly inhibited reuptake and increased release of all three monoamines (DA, 5-HT, NE) in rat brain synaptosomes. pmid:17223101
The psychedelic component is 5-HT₂A–dependent. 5-MeO-AMT elicits dose-dependent head-twitch responses (HTR) in mice at 0.3–10 mg/kg, and this response is fully abolished by the selective 5-HT₂A antagonist ketanserinsupported
5-MeO-AMT (0.3–10 mg/kg) induced HTR in mice; repeated dosing produced tolerance. Ketanserin (5-HT2A antagonist) blocked HTR. j.bbr.2018.07.020
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Repeated administration (7 days) produces tolerance to HTR with concurrent upregulation of 5-HT₂A mRNA, suggesting compensatory transcriptional changes during receptor desensitization.supported
repeated dosing produced tolerance. Ketanserin (5-HT2A antagonist) blocked HTR. 5-MeO-AMT increased 5-HTR2a mRNA and PKC-γ phosphorylation in PFC. j.bbr.2018.07.020
Nagai et al. (2007) demonstrated that 5-MeO-AMT strongly inhibits reuptake and induces release of all three monoamines (dopamine, serotonin, norepinephrine) from rat brain synaptosomes — a mixed inhibitor/releaser profile qualitatively similar to amt but distinct from other 5-methoxytryptamines that only inhibit reuptake without causing releasesupported
5-MeO-AMT strongly inhibited reuptake and increased release of all three monoamines (DA, 5-HT, NE) in rat brain synaptosomes. Qualitatively similar to AMT but differentiated from other methoxytryptamines. pmid:17223101
In drug discrimination assays, 5-MeO-AMT produced 67% LSD-appropriate responding but did not fully substitute for DMT, DOM, LSD, cocaine, or methamphetamine, and showed only low-potency dopamine uptake blockade and low serotonin release relative to MDMA-class entactogens.partially supported
5-MeO-AMT produced 67% LSD-appropriate responding. Low serotonin release, low-potency DAT blockade. Did not substitute for cocaine or methamphetamine. jpet.111.179705
Zhutao et al. (2024) characterized rat urinary metabolites of 5-MeO-AMT using UPLC-LTQ-Orbitrap mass spectrometry, confirming a complex metabolic profilesupported
Study of metabolic characteristics of 5-MeO-AMT using UPLC-LTQ-Orbitrap in rat urine. Identifies urinary metabolites of 5-MeO-AMT for forensic toxicology purposes. 0113892002295551240628061732
By structural analogy with 5-MeO-DIPT metabolism in rat liver microsomes, the expected metabolic pathways include aromatic ring O-demethylation to 5-hydroxy-AMT (CYP2D family), side-chain N-dealkylation (CYP3A family), and aromatic ring 6-hydroxylation (CYP1A1)supported
N-dealkylation by CYP2C11/CYP3A2, O-demethylation by CYP2D2/CYP2C6, and 6-hydroxylation by CYP1A1. pmid:17980859
In humans, CYP2D6 is the expected primary enzyme for O-demethylation of 5-methoxytryptamines, based on human liver microsome studies of the structural analogue 5-MeO-DIPT.partially supported
5-MeO-DIPT metabolism by rat liver microsomes and CYPs: N-dealkylation by CYP2C11/CYP3A2, O-demethylation by CYP2D2/CYP2C6. pmid:17980859
neuroscience8 · 5 ok
CYP2D6 pharmacogenomics: How does CYP2D6 genotype affect brain exposure, subjective intensity, and adverse event risk? Given the expected dependence on CYP2D6 for primary metabolism, poor metabolizers may experience substantially different neural effects.supported
O-demethylation by CYP2D2/CYP2C6. pmid:17980859
As a potent 5-HT₂A agonist (EC50 = 2 nM), 5-MeO-AMT is expected to engage the same cortical circuit disruptions observed with other serotonergic psychedelics: activation of 5-HT₂A receptors on layer V pyramidal neurons in the prefrontal cortex, disruption of thalamocortical gating (leading to sensory flooding), dissolution of default mode network (DMN) integrity, and increased global functional connectivity and neural entropysupported
5-MeO-AMT: 5-HT2A EC50=2 nM (agonist). j.euroneuro.2016.05.001
Claim in neuroscience — inconclusiveinconclusiveworking →
Li et al. (2025) performed the most comprehensive in vivo neurochemical characterization of 5-MeO-AMT to date, measuring dopamine, serotonin, DOPAC, HVA, and 5-HIAA via HPLC-ECD in four rat brain regions (prefrontal cortex, nucleus accumbens, dorsolateral striatum, hippocampus) following acute administration at multiple dosessupported
DA, 5-HT and metabolites measured in PFC, NAc, DLS, hippocampus after administration of AMT, 5-MeO-AMT and 5-MeO-DiPT at different doses in rats using HPLC-ECD. j.neures.2025.04.006
5-MeO-AMT did not induce locomotor sensitization, conditioned place preference, or self-administration in rodentssupported
No locomotor sensitization, CPP, or self-administration — suggesting low abuse liability. j.bbr.2018.07.020
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
5-HT₂B cardiac risk quantification: What degree of chronic exposure is required to produce valvular changes? The potent 5-HT₂B EC50 (4 nM) exceeds the threshold of concern established for other 5-HT₂B agonists, but no exposure-response data exist for 5-MeO-AMT.supported
5-MeO-AMT: 5-HT2B EC50=4 nM (agonist). j.euroneuro.2016.05.001
receptor-pharmacology7 · 7 ok
The most comprehensive receptor interaction data for 5-MeO-AMT were reported by Rickli et al. (2016), who profiled novel psychoactive tryptamines at human monoamine receptors and transporters using radioligand binding and functional assays.supported
Novel tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT investigated at monoamine receptors and transporters. j.euroneuro.2016.05.001
Rickli et al. (2016) found that 5-HT₂A binding affinity across their tryptamine panel correlated with reported psychoactive doses, and all tested compounds, including 5-MeO-AMT, functioned as partial or full 5-HT₂A agonists.partially supported
All novel tryptamines were partial or full 5-HT2A agonists. j.euroneuro.2016.05.001
Sustained 5-HT₂B receptor activation is mechanistically linked to drug-induced valvular heart disease via mitogenic and fibrotic signalling in valvular interstitial cellssupported
5-HT2B activation mediates fibrotic changes in valvular tissue. a-2794-6487
Sustained 5-HT₂B receptor activation is mechanistically linked to drug-induced valvular heart disease via mitogenic and fibrotic signalling in valvular interstitial cellssupported
Microdosing psychedelics risks cardiac fibrosis/valvulopathy via 5-HT2B. 02698811231225609
Nonaka et al. (2007) ranked 5-MeO-AMT third among seven tryptamines for [³⁵S]GTPγS-stimulated G-protein activation in rat brain membranes, with the order: 5-meo-dmt > 5-MeO-DALT > 5-MeO-AMT ≥ 5-MeO-MIPT > 5-MeO-DIPT > DPT ≥ amtsupported
5-MeO-AMT ranked third among 7 tryptamines for potency of G-protein activation in rat brain membranes. Order: 5-MeO-DMT > 5-MeO-DALT > 5-MeO-AMT ≥ 5-MeO-MIPT > 5-MeO-DIPT > DPT ≥ AMT. pmid:18057721
5-MeO-AMT occupies a distinctive pharmacological position among tryptamines: it acts as both a reuptake inhibitor and a monoamine releaser at serotonin, dopamine, and norepinephrine transporterssupported
5-MeO-AMT strongly inhibited reuptake and increased release of all three monoamines (DA, 5-HT, NE) in rat brain synaptosomes. pmid:17223101
Gatch et al. (2011) confirmed SERT blockade and low-potency DAT inhibition, with serotonin release levels below those characteristic of entactogenssupported
Activity at 5-HT1A, 5-HT2A receptors and SERT blockade. Low serotonin release, low-potency DAT blockade. jpet.111.179705
summary7 · 6 ok
Its pharmacological profile combines potent 5-HT₂A agonism with triple-monoamine reuptake inhibition and release — a mixed mechanism uncommon among serotonergic psychedelics.supported
5-MeO-AMT strongly inhibited reuptake and increased release of all three monoamines (DA, 5-HT, NE) in rat brain synaptosomes. Qualitatively similar to AMT but differentiated from other methoxytryptamines. pmid:17223101
Claim in summary — inconclusiveinconclusiveworking →
5-MeO-AMT activates 5-HT₂A receptors with a functional EC50 of 2 nM and binds 5-HT₁A with Ki = 46 nMsupported
5-MeO-AMT: 5-HT1A Ki=46 nM, 5-HT2A EC50=2 nM (agonist), 5-HT2B EC50=4 nM (agonist). j.euroneuro.2016.05.001
The head-twitch response — the standard rodent proxy for hallucinogenic activity — is fully blocked by the selective 5-HT₂A antagonist ketanserin, confirming the receptor as the primary mediator of psychedelic effectssupported
Ketanserin (5-HT2A antagonist) blocked HTR. j.bbr.2018.07.020
Its potent 5-HT₂B agonism (EC50 = 4 nM) raises mechanistic concern for cardiac valvulopathy with chronic exposuresupported
5-MeO-AMT: 5-HT2B EC50=4 nM (agonist). j.euroneuro.2016.05.001
Its potent 5-HT₂B agonism (EC50 = 4 nM) raises mechanistic concern for cardiac valvulopathy with chronic exposuresupported
5-HT2B activation mediates fibrotic changes in valvular tissue. a-2794-6487
Tolerance develops through 5-HT₂A receptor downregulation, and rodent models show no self-administration or conditioned place preference, indicating low dependence liabilitypartially supported
repeated dosing produced tolerance... 5-MeO-AMT increased 5-HTR2a mRNA and PKC-γ phosphorylation in PFC. No locomotor sensitization, CPP, or self-administration — suggesting low abuse liability. j.bbr.2018.07.020
comparative-pharmacology6 · 5 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The addition of the 5-methoxy group in 5-MeO-AMT dramatically increases 5-HT₂A potency: the functional EC50 at 5-HT₂A for 5-MeO-AMT is 2 nM, while AMT ranked lowest among seven tryptamines for G-protein activation in rat brain membranessupported
5-MeO-AMT: 5-HT2A EC50=2 nM (agonist). j.euroneuro.2016.05.001
The addition of the 5-methoxy group in 5-MeO-AMT dramatically increases 5-HT₂A potency: the functional EC50 at 5-HT₂A for 5-MeO-AMT is 2 nM, while AMT ranked lowest among seven tryptamines for G-protein activation in rat brain membranessupported
Order: 5-MeO-DMT > 5-MeO-DALT > 5-MeO-AMT ≥ 5-MeO-MIPT > 5-MeO-DIPT > DPT ≥ AMT. pmid:18057721
In G-protein activation assays, 5-MeO-DMT ranked highest among seven tryptamines, above 5-MeO-AMTsupported
Order: 5-MeO-DMT > 5-MeO-DALT > 5-MeO-AMT ≥ 5-MeO-MIPT > 5-MeO-DIPT > DPT ≥ AMT. pmid:18057721
In drug discrimination studies, 5-MeO-AMT produced 67% LSD-appropriate responding but did not achieve full substitutionsupported
5-MeO-AMT produced 67% LSD-appropriate responding. jpet.111.179705
However, Gatch et al. (2011) found that 5-MeO-AMT produces much lower serotonin release than MDMA-class entactogens and does not substitute for cocaine or methamphetamine in discrimination assayssupported
Low serotonin release, low-potency DAT blockade. Did not substitute for cocaine or methamphetamine. jpet.111.179705
pharmacokinetic-detail2 · 2 ok
Zhutao et al. (2024) characterized rat urinary metabolites of 5-MeO-AMT via UPLC-LTQ-Orbitrap mass spectrometrysupported
Study of metabolic characteristics of 5-MeO-AMT using UPLC-LTQ-Orbitrap in rat urine. 0113892002295551240628061732
By structural analogy with 5-MeO-DIPT metabolism characterized in rat liver microsomes by Narimatsu et al. (2008), the expected metabolic routes include:supported
5-MeO-DIPT metabolism by rat liver microsomes and CYPs: N-dealkylation by CYP2C11/CYP3A2, O-demethylation by CYP2D2/CYP2C6, and 6-hydroxylation by CYP1A1. pmid:17980859