generation run 2026-05-11
65 min completedmodel pipeline-v5plan not recordedrun/6c1de0ae…Selection
Verification
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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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- 13 source keys (listed under Sources)
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20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | methallylescaline | 1 | 1 | Only result; confirms chemical identity data from seed brief. |
| 2 | PubMed | mescaline analog 4-alkoxy substitution serotonin receptor psychedelic potency | 1 | 1 | Direct comparison of mescaline analog potency including escaline family. |
| 3 | PubMed | methallylescaline MAL phenethylamine psychedelic | 1 | — | — |
| 4 | ClinicalTrials.gov · absence | methallylescaline mescaline analog | 0 | — | — |
| 5 | WebSearch | NDEWS methallylescaline 2024 alert | 10 | — | — |
| 6 | OpenAlex | methallylescaline pharmacology psychedelic | 6 | — | — |
| 7 | Erowid PiHKAL | MAL methallylescaline PiHKAL entry #99 | 1 | — | — |
| 8 | WebSearch | methallylescaline synthesis CAS 207740-41-8 SMILES | 10 | — | — |
| 9 | WebSearch | methallylescaline MAL pharmacology effects dose PiHKAL Shulgin | 10 | 4 | Multiple converging sources confirm PiHKAL origin and 2021 pharmacology paper. |
| 10 | PMC/Frontiers in Pharmacology | Kolaczynska 2021 MAL methallylescaline receptor data | 1 | — | — |
| 11 | WebSearch | methallylescaline MAL legal status scheduling UK US EU | 10 | — | — |
| 12 | Erowid | methallylescaline hospital trip report | 1 | 1 | — |
| 13 | PubMed | get_pubmed_article PMID 30789291 | 1 | 1 | — |
| 14 | Multiple sources | methallylescaline dose duration cross-reference PiHKAL vs Kolaczynska 2021 vs seed data | 3 | 3 | — |
| 15 | PubMed | get_pubmed_article PMID 39587436 39349427 37231080 | 3 | 3 | — |
| 16 | PubMed | serotonin toxicity serotonergic psychedelics drug interaction SSRI MAOI | 1 | 1 | — |
| 17 | WebSearch | methallylescaline allylescaline escaline potency comparison mescaline 4-alkoxy PiHKAL | 10 | — | — |
| 18 | PubMed | mescaline human dose subjective effects clinical controlled crossover study | 2 | — | — |
| 19 | PMC/Frontiers in Pharmacology | Kolaczynska 2021 MAL allylescaline mescaline comparative data | 1 | 2 | — |
| 20 | Erowid | methallylescaline hospital trip case report 130mg | 1 | — | — |
69 claims by section — every cited sentence, checked against its source
safety18 · 9 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Nausea and vomiting are prominent adverse effects, particularly at higher doses, consistent with the mescaline classsupported
Nausea and emesis frequent at 800 mg s41398-024-03116-2
Claim in safety — inconclusiveinconclusiveworking →
Hallucinogen persisting perception disorder (HPPD) — persistent visual disturbances following psychedelic use have been documented with potent 5-HT₂A agonist novel psychoactive substances. No MAL-specific HPPD cases have been published, but the risk is presumed to exist on pharmacological grounds.supported
5-HT2A receptor agonists (e.g. 25I-NBOMe) pose risks of acute intoxication and long-term adverse effects including HPPD, derealization, and depersonalization j.biopha.2021.112295
MAL, consistent with all characterized serotonergic psychedelics, is not habit-forming and carries no physical dependence liabilitysupported
Generally considered physiologically safe and do not lead to dependence or addiction pr.115.011478
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Cross-tolerance extends to other 5-HT₂A agonists including LSD, psilocybin, mescaline, and DOx-series compounds.partially supported
Cross-tolerance between DOI and LSD but not nonpsychedelic 5-HT2AR agonist lisuride acschemneuro.2c00170
Monoamine oxidase inhibitors (MAOIs). The combination of MAOIs with serotonergic psychedelics carries risk of serotonin toxicitysupported
Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs/MAOIs s00213-021-05876-x
SSRIs and SNRIs. Selective serotonin reuptake inhibitors may attenuate psychedelic effects through chronic 5-HT₂A receptor downregulation and can, in some combinations, raise serotonin toxicity risksupported
Evaluates drug-drug interaction risks and serotonin toxicity between psychedelic serotonergic substances and SSRIs/MAOIs s00213-021-05876-x
CYP2D6 and CYP3A4 inhibitors. MAL is metabolized by CYP2D6, CYP2J2, CYP1A2, and CYP3A4supported
CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes responsible msl.2018.9.3.86
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Concurrent MAOI use. Risk of serotonin toxicity.supported
serotonin toxicity between psychedelic serotonergic substances and SSRIs/MAOIs s00213-021-05876-x
Hepatic impairment. MAL is metabolized by multiple CYP enzymes; impaired hepatic function could reduce clearance and increase exposuresupported
CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes responsible msl.2018.9.3.86
pharmacology13 · 9 ok
In the only published pharmacological characterization, Kolaczynska and colleagues determined a 5-HT₂A binding affinity of Ki = 550 ± 190 nM and a functional activation EC50 of 79 ± 12 nM with 85 ± 5% efficacy relative to serotonin, classifying MAL as a potent full agonist at this targetsupported
Ki 550±190 nM, EC50 79±12 nM, efficacy 85±5% fphar.2021.794254
Near-equivalent affinity at 5-HT₂C (Ki = 520 ± 150 nM) and markedly lower affinity at 5-HT₁A (Ki = 5,100 ± 500 nM) produce a selectivity ratio of approximately 9.3-fold for 5-HT₂A over 5-HT₁A.supported
5-HT2C Ki 520±150 nM, 5-HT1A Ki 5100±500 nM fphar.2021.794254
Activation of 5-HT₂A receptors expressed on the apical dendrites of layer V pyramidal neurons in the prefrontal cortex is the established primary mechanism for serotonergic psychedelic effectssupported
agonists or partial agonists at brain serotonin 5-HT2A receptors, particularly on apical dendrites of neocortical pyramidal cells in layer V pr.115.011478
This mechanism is confirmed by blocking studies: the selective 5-HT₂A antagonist ketanserin attenuates the subjective effects of mescaline in controlled human settings, establishing that 5-HT₂A agonism is both necessary and sufficient for mescaline-class psychedelic activity.supported
Ketanserin attenuated effects confirming 5-HT2A primary mechanism s41398-024-03116-2
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Mescaline reaches peak plasma concentration (Tmax) at approximately 2 hours after oral administration, with a plasma elimination half-life of approximately 3.5 hourssupported
Tmax ~2h, t1/2 ~3.5h s41398-024-03116-2
Claim in pharmacology — inconclusiveinconclusiveworking →
Total duration ranges from 8–16 hours depending on dose — Shulgin reported 12–16 hours at doses of 40–65 mg, while Kolaczynska and colleagues cite 8–12 hourssupported
duration 8-12 h fphar.2021.794254
The sole published metabolic study employed in vitro incubation of MAL with human hepatocytes, analyzed by liquid chromatography–high resolution mass spectrometry (LC-HRMS)supported
MAL metabolized... in human hepatocytes... Liquid Chromatography-High Resolution Mass Spectrometry msl.2018.9.3.86
The metabolizing enzymes identified are CYP2D6, CYP2J2, CYP1A2, and CYP3A4supported
CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes responsible msl.2018.9.3.86
CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) and CYP3A4 inhibitors (ketoconazole, grapefruit juice) could increase MAL plasma concentrations through competitive metabolic inhibition.supported
CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes responsible msl.2018.9.3.86
comparative-pharmacology12 · 7 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Duration: MAL's total duration (8–16 hours) overlaps with mescaline's (mean 11.1 hours at 500 mg in Ley et al.), though PiHKAL suggests the upper range of MAL may exceed mescaline's typical duration.supported
Mescaline longest duration (11.1h) s41386-023-01607-2
Kolaczynska and colleagues characterized a systematic series of 4-alkoxy-3,5-dimethoxy-phenethylamines, enabling direct comparison of MAL to its structural siblings:supported
mescaline derivatives including methallylescaline (MAL) at 5-HT2A fphar.2021.794254
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Nausea: Both produce nausea as a prominent adverse effect at higher doses, a consistent feature of the mescaline class.supported
Nausea and emesis frequent at 800 mg s41398-024-03116-2
Clinical data: Mescaline has been characterized in controlled double-blind trials. MAL has none.supported
Randomized double-blind crossover study in 16 healthy subjects receiving mescaline 100-800 mg s41398-024-03116-2
Clinical data: Mescaline has been characterized in controlled double-blind trials. MAL has none.supported
RCT comparing mescaline (300/500 mg), LSD (100 µg) and psilocybin (20 mg) in 32 healthy participants s41386-023-01607-2
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Cross-tolerance between MAL and tryptamine psychedelics is expected on the basis of shared 5-HT₂A agonism.supported
Cross-tolerance between DOI and LSD... Tolerance involves 5-HT2AR downregulation in frontal cortex acschemneuro.2c00170
A 2025 follow-up study by Kolaczynska and colleagues expanded receptor profiling to psi-derivatives (4-alkoxy-2,6-dimethoxyphenethylamines), providing additional comparative context for the alkoxy-mescaline pharmacological spacesupported
4-substituted 2,6-dimethoxyphenethylamines and amphetamines compared to 2,4,5- and 3,4,5-substituted analogs fphar.2025.1703480
pharmacokinetic-detail6 · 5 ok
Pharmacokinetic table: Oral Tmax (estimated) — Unknown, mescaline Tmax ~2 hours; Plasma half-life — Unknown, mescaline t½ ~3.5 hours; Oral bioavailability — Not determined; Primary metabolizing enzymes — CYP2D6, CYP2J2, CYP1A2, CYP3A4; Identified metabolites — M1–M3 (mono-OH), M4 (di-OH)supported
Tmax ~2h, t1/2 ~3.5h s41398-024-03116-2
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Pharmacokinetic table: Primary metabolizing enzymes — CYP2D6, CYP2J2, CYP1A2, CYP3A4; Identified metabolites — M1–M3 (mono-OH), M4 (di-OH) — all hydroxylation at methallyl moiety; Phase II conjugation — Not observed in vitrosupported
MAL metabolized to 3 mono-hydroxylated (M1-M3) and 1 di-hydroxylated (M4) metabolite... CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes responsible msl.2018.9.3.86
Pharmacokinetic table (duplicate entry): Primary metabolizing enzymes — CYP2D6, CYP2J2, CYP1A2, CYP3A4; Identified metabolites — M1–M3 (mono-OH), M4 (di-OH) — all hydroxylation at methallyl moiety; Phase II conjugation — Not observed in vitrosupported
MAL metabolized to 3 mono-hydroxylated (M1-M3) and 1 di-hydroxylated (M4) metabolite... CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes responsible msl.2018.9.3.86
Kim and colleagues identified four cytochrome P450 isoforms contributing to MAL's oxidative metabolism: CYP2D6, CYP2J2, CYP1A2, and CYP3A4supported
CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes responsible msl.2018.9.3.86
The Kim et al. (2018) study was developed explicitly to support forensic and clinical toxicology screeningsupported
Framework for forensic toxicology screening msl.2018.9.3.86
summary6 · 5 ok
MAL displays approximately six-fold greater 5-HT₂A binding affinity than mescaline (Ki = 550 ± 190 nM vs low-µM range), with an oral duration of 8–16 hours depending on dose, placing it among the longer-acting members of its class.partially supported
duration 8-12 h fphar.2021.794254
Claim in summary — inconclusiveinconclusiveworking →
MAL acts as a potent full agonist at the human 5-HT₂A receptor (EC50 = 79 ± 12 nM, 85% efficacy) with near-equal 5-HT₂C affinity (Ki = 520 ± 150 nM) and negligible activity at 5-HT₂B, monoamine transporters, and dopamine D2 receptorssupported
EC50 79±12 nM, efficacy 85±5%, 5-HT2C Ki 520±150 nM fphar.2021.794254
This selectivity profile is consistent with a classical serotonergic psychedelic mechanism, and 5-HT₂A antagonism blocks mescaline-class effects in controlled settings.supported
Ketanserin attenuated effects confirming 5-HT2A primary mechanism s41398-024-03116-2
MAL is not habit-forming and carries no physical dependence liability consistent with its classsupported
Generally considered physiologically safe and do not lead to dependence or addiction pr.115.011478
Tolerance develops rapidly via 5-HT₂A receptor downregulation, with cross-tolerance to other serotonergic psychedelicssupported
Cross-tolerance between DOI and LSD... Tolerance involves 5-HT2AR downregulation in frontal cortex acschemneuro.2c00170
chemistry4 · 1 ok
This places MAL alongside allylescaline (AL, bearing an unsubstituted allyloxy group), escaline (ethyloxy), and proscaline (propyloxy) within a systematic structure-activity series exploring the effect of 4-alkoxy chain length and branching on psychedelic potency and duration.supported
mescaline derivatives including methallylescaline (MAL) fphar.2021.794254
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
receptor-pharmacology4 · 3 ok
The receptor interaction profile of methallylescaline was characterized in a single comprehensive study by Kolaczynska and colleagues, who tested MAL (compound #32 in their series) across serotonin, dopamine, adrenergic, and trace amine-associated receptor (TAAR) targets using radioligand displacement binding and functional activation assays.supported
receptor binding profiles (Ki) and functional activation (EC50)... at 5-HT2A, 5-HT2C, 5-HT1A, TAAR1, adrenergic and dopaminergic receptors fphar.2021.794254
The 85% efficacy classifies MAL as a full agonist by the conventions of this assay system (referenced to serotonin).supported
efficacy 85±5% fphar.2021.794254
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
This profile predicts classical psychedelic phenomenology without stimulant, empathogenic, or cardiac valvulopathic properties — predictions consistent with the available human subjective reports.supported
5-HT2A Ki 550±190 nM, EC50 79±12 nM, efficacy 85±5% fphar.2021.794254
clinical-evidence2 · 2 ok
The compound's closest pharmacological relative with clinical data is mescaline, for which Klaiber and colleagues published acute dose-dependent effects in healthy participants in a double-blind, placebo-controlled designsupported
Randomized double-blind crossover study in 16 healthy subjects receiving mescaline 100-800 mg s41398-024-03116-2
and Ley and colleagues compared mescaline to LSD and psilocybin in a randomized crossover studysupported
RCT comparing mescaline (300/500 mg), LSD (100 µg) and psilocybin (20 mg) in 32 healthy participants s41386-023-01607-2
history2 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Separately, Kim and colleagues (2018) published the only study of MAL's metabolic fate, identifying four hydroxylated metabolites via in vitro hepatocyte incubation to support forensic detection.supported
MAL metabolized to 3 mono-hydroxylated (M1-M3) and 1 di-hydroxylated (M4) metabolite in human hepatocytes... Framework for forensic toxicology screening msl.2018.9.3.86
neuroscience2 · 1 ok
As a full agonist at cortical 5-HT₂A receptors (EC50 = 79 nM, 85% efficacy), MAL is predicted to engage the same neural mechanisms established for other serotonergic psychedelics:supported
EC50 79±12 nM, efficacy 85±5% fphar.2021.794254
Claim in neuroscience — inconclusiveinconclusiveworking →