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Psychedex

4-AcO-DMT

4-acetoxy-N,N-dimethyltryptamine

Sources
27
16 strong · 9 moderate · 2 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked
68
30verified2partial34inconclusive2not supported

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Values approved
210/211 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold5 mg5 mgmedium
Low5–15 mg5–15 mgmedium
Common15–25 mg15–25 mgmedium
Strong25–45 mg25–45 mgmedium
Heavy45+ mg45+ mgmedium
Editorial

Existing database values from community consensus. Consistent with Shulgin's 10-20 mg oral active range (TiHKAL 1997) and psilocin/psilocybin dose equivalence. No controlled human dose-finding data exist.

Reasoning

Existing database values from community consensus. Consistent with Shulgin's 10-20 mg oral active range (TiHKAL 1997) and psilocin/psilocybin dose equivalence. No controlled human dose-finding data exist.

Evidence basis: community_consensus_large

insufflatedtrace

FieldPublishedAI ProposedConfidence
Threshold3 mg3 mgmedium
Low3–10 mg3–10 mgmedium
Common10–20 mg10–20 mgmedium
Strong20–35 mg20–35 mgmedium
Heavy35+ mg35+ mgmedium
Editorial

Existing database values from community consensus. Lower dose ranges than oral are consistent with faster absorption bypassing first-pass metabolism. No controlled human dose-finding data exist for any ROA.

Reasoning

Existing database values from community consensus. Lower dose ranges than oral are consistent with faster absorption bypassing first-pass metabolism. No controlled human dose-finding data exist for any ROA.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Offsettrace1–2 hours1–2 hoursmedium
Editorial

Community consensus values from existing database.

Reasoning

Community consensus values from existing database.

Evidence basis: community_consensus_large

Onsettrace15–40 minutes15–40 minutesmedium
Editorial

Community consensus values from existing database. Consistent with oral tryptamine absorption kinetics.

Reasoning

Community consensus values from existing database. Consistent with oral tryptamine absorption kinetics.

Evidence basis: community_consensus_large

Come uptrace30–75 minutes30–75 minutesmedium
Editorial

Community consensus values from existing database.

Reasoning

Community consensus values from existing database.

Evidence basis: community_consensus_large

Peaktrace2–3.5 hours2–3.5 hoursmedium
Editorial

Community consensus values from existing database. Consistent with psilocin's pharmacokinetic profile (Tmax 1.8-4 h, t1/2 1.5-4 h).

Reasoning

Community consensus values from existing database. Consistent with psilocin's pharmacokinetic profile (Tmax 1.8-4 h, t1/2 1.5-4 h).

Evidence basis: community_consensus_large

Totaltrace4–7 hours4–7 hoursmedium
Editorial

Community consensus values consistent with Shulgin's 3-6 h duration estimate (TiHKAL). The upper range extends slightly beyond Shulgin's estimate, reflecting community reports at higher doses.

Reasoning

Community consensus values consistent with Shulgin's 3-6 h duration estimate (TiHKAL). The upper range extends slightly beyond Shulgin's estimate, reflecting community reports at higher doses.

Evidence basis: community_consensus_large

After effectstrace4–48 hours4–48 hoursmedium
Editorial

Community consensus values from existing database. Wide range reflects individual variability in afterglow duration.

Reasoning

Community consensus values from existing database. Wide range reflects individual variability in afterglow duration.

Evidence basis: community_consensus_large

insufflated

FieldPublishedAI ProposedConfidence
Onsettrace5–25 minutes5–25 minutesmedium
Editorial

Community consensus values from existing database. Faster onset consistent with nasal absorption bypassing GI transit.

Reasoning

Community consensus values from existing database. Faster onset consistent with nasal absorption bypassing GI transit.

Evidence basis: community_consensus_large

Come uptrace30–60 minutes30–60 minutesmedium
Editorial

Community consensus values from existing database.

Reasoning

Community consensus values from existing database.

Evidence basis: community_consensus_large

Peaktrace1.5–2.5 hours1.5–2.5 hoursmedium
Editorial

Community consensus values from existing database. Shorter peak duration than oral consistent with faster absorption kinetics.

Reasoning

Community consensus values from existing database. Shorter peak duration than oral consistent with faster absorption kinetics.

Evidence basis: community_consensus_large

Offsettrace1–1.5 hours1–1.5 hoursmedium
Editorial

Community consensus values from existing database.

Reasoning

Community consensus values from existing database.

Evidence basis: community_consensus_large

Totaltrace3–5 hours3–5 hoursmedium
Editorial

Community consensus values from existing database. Compressed timeline relative to oral administration.

Reasoning

Community consensus values from existing database. Compressed timeline relative to oral administration.

Evidence basis: community_consensus_large

After effectstrace4–48 hours4–48 hoursmedium
Editorial

Community consensus values. Aftereffects are expected to be similar regardless of ROA.

Reasoning

Community consensus values. Aftereffects are expected to be similar regardless of ROA.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutelowlowlow
Chroniclowlowlow
Organs Affectedcardiovascular, gastrointestinalcardiovascular, gastrointestinallow
Editorial

Classified as low (downgraded from moderate): all toxicity data are in silico computational predictions (Jurowski et al. 2026), not experimental measurements. The predicted LD50 of 100-500 mg/kg suggests a wide margin between active doses (10-25 mg, ~0.15-0.35 mg/kg) and predicted lethal doses. No fatality case reports exist, but absence of evidence is not evidence of absence given low prevalence. Chronic toxicity is entirely uncharacterized.

Reasoning

Classified as low (downgraded from moderate): all toxicity data are in silico computational predictions (Jurowski et al. 2026), not experimental measurements. The predicted LD50 of 100-500 mg/kg suggests a wide margin between active doses (10-25 mg, ~0.15-0.35 mg/kg) and predicted lethal doses. No fatality case reports exist, but absence of evidence is not evidence of absence given low prevalence. Chronic toxicity is entirely uncharacterized.

Evidence basis: animal_study

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnonenonemedium
Psychologicalnegligiblenegligiblemedium
Compulsive Redosingnegligiblenegligiblemedium
Dose Escalationnegligiblenegligiblemedium
Editorial

Conditioned place preference data from Vargas-Perez et al. (2024) directly assessed 4-AcO-DMT's addiction liability in rats, finding behavioral patterns 'less typical of drugs associated with addiction.' Rapid tachyphylaxis via 5-HT2A downregulation is well-established for the psychedelic class. No physical withdrawal syndrome has been described for any serotonergic psychedelic.

Reasoning

Conditioned place preference data from Vargas-Perez et al. (2024) directly assessed 4-AcO-DMT's addiction liability in rats, finding behavioral patterns 'less typical of drugs associated with addiction.' Rapid tachyphylaxis via 5-HT2A downregulation is well-established for the psychedelic class. No physical withdrawal syndrome has been described for any serotonergic psychedelic.

Evidence basis: animal_study

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitynonenonemedium
Symptoms——medium
FatalNoNomedium
Medical SupervisionNot requiredNot requiredmedium
Editorial

No withdrawal syndrome has been described for any serotonergic psychedelic. Rapid tolerance development and absence of physical dependence mechanisms preclude withdrawal.

Reasoning

No withdrawal syndrome has been described for any serotonergic psychedelic. Rapid tolerance development and absence of physical dependence mechanisms preclude withdrawal.

Evidence basis: animal_study

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidmedium
Half-life3 days3 daysmedium
Full Reset7 days7 daysmedium
Cross-tolerancespsilocybin, psilocin, LSD, DMT, mescalinepsilocybin, psilocin, LSD, DMT, mescalinemedium
Editorial

Tolerance mechanism is well-characterized for the psychedelic class via Dolder et al. (2017, LSD in rats) and Lewis et al. (2023, beta-arrestin recruitment). The 7-day full reset is community consensus corroborated by the pharmacological time course of 5-HT2A receptor resynthesis. Cross-tolerance is established pharmacological class knowledge (Nichols 2018). No 4-AcO-DMT-specific tolerance studies exist.

Reasoning

Tolerance mechanism is well-characterized for the psychedelic class via Dolder et al. (2017, LSD in rats) and Lewis et al. (2023, beta-arrestin recruitment). The 7-day full reset is community consensus corroborated by the pharmacological time course of 5-HT2A receptor resynthesis. Cross-tolerance is established pharmacological class knowledge (Nichols 2018). No 4-AcO-DMT-specific tolerance studies exist.

Evidence basis: animal_study

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
psychiatric psychotic disorderstraceabsoluteabsolutehigh
Editorial

Class-level absolute contraindication for all serotonergic psychedelics, well-established in psilocybin clinical trial exclusion criteria and supported by Rached et al. (2026).

Reasoning

Class-level absolute contraindication for all serotonergic psychedelics, well-established in psilocybin clinical trial exclusion criteria and supported by Rached et al. (2026).

psychiatric bipolar disordertraceabsoluteabsolutehigh
Editorial

Class-level contraindication for serotonergic psychedelics, standard exclusion criterion in psilocybin clinical trials.

Reasoning

Class-level contraindication for serotonergic psychedelics, standard exclusion criterion in psilocybin clinical trials.

other concurrent tramadol usetraceabsoluteabsolutehigh
Editorial

Mechanistic basis confirmed by Gillman (2005) and Rached et al. (2026). Tramadol's SRI activity combined with 5-HT2A agonism creates multi-mechanism serotonin potentiation. No 4-AcO-DMT-specific case reports, but pharmacological reasoning is definitive.

Reasoning

Mechanistic basis confirmed by Gillman (2005) and Rached et al. (2026). Tramadol's SRI activity combined with 5-HT2A agonism creates multi-mechanism serotonin potentiation. No 4-AcO-DMT-specific case reports, but pharmacological reasoning is definitive.

other concurrent MAOI usetraceabsoluteabsolutehigh
Editorial

Chen et al. (2025) established MAO-A as the primary psilocin clearance enzyme. Rached et al. (2026) reviewed MAOI-psychedelic interaction risks. Metabolic blockade would dramatically alter exposure profile.

Reasoning

Chen et al. (2025) established MAO-A as the primary psilocin clearance enzyme. Rached et al. (2026) reviewed MAOI-psychedelic interaction risks. Metabolic blockade would dramatically alter exposure profile.

cardiovascular cardiovascular diseasetracerelativerelativemedium
Editorial

Class-level relative contraindication for serotonergic psychedelics. In silico predictions suggest lower hERG inhibition risk than DMT and 5-MeO-DMT (Jurowski et al. 2026), but cardiovascular stress from sympathomimetic activation remains a concern.

Reasoning

Class-level relative contraindication for serotonergic psychedelics. In silico predictions suggest lower hERG inhibition risk than DMT and 5-MeO-DMT (Jurowski et al. 2026), but cardiovascular stress from sympathomimetic activation remains a concern.

neurological seizure disorderstracerelativerelativelow
Editorial

Class-level inference from serotonergic psychedelics. No primary literature was found characterizing seizure risk for 4-AcO-DMT specifically. Flagged as unconfirmed in research output.

Reasoning

Class-level inference from serotonergic psychedelics. No primary literature was found characterizing seizure risk for 4-AcO-DMT specifically. Flagged as unconfirmed in research output.

pregnancy breastfeeding pregnancytraceabsoluteabsolutemedium
Editorial

Standard precautionary absolute contraindication in the absence of reproductive safety data. Serotonin signaling is essential for fetal neurodevelopment.

Reasoning

Standard precautionary absolute contraindication in the absence of reproductive safety data. Serotonin signaling is essential for fetal neurodevelopment.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace900–2400 sec(i=0.05)900–2400 sec(i=0.05)medium
Editorial

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Reasoning

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Come uptrace1800–4500 sec(i=0.35)1800–4500 sec(i=0.35)medium
Editorial

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Reasoning

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Peaktrace7200–12600 sec(i=1.00)7200–12600 sec(i=1.00)medium
Editorial

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Reasoning

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Resolutiontrace3600–7200 sec(i=0.30)3600–7200 sec(i=0.30)medium
Editorial

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Reasoning

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Afterglowtrace14400–172800 sec(i=0.05)14400–172800 sec(i=0.05)medium
Editorial

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

Reasoning

Duration data derived from community consensus values: oral onset 15\u201340 min, come-up 30\u201375 min, peak 2\u20133.5 h, offset 1\u20132 h, total 4\u20137 h, aftereffects 4\u201348 h. Consistent with Shulgin's 3\u20136 h duration estimate (TiHKAL) and psilocybin's known duration profile. No controlled human PK data exist for 4-AcO-DMT.

insufflated

FieldPublishedAI ProposedConfidence
Onsettrace300–1500 sec(i=0.10)300–1500 sec(i=0.10)medium
Editorial

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Reasoning

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Come uptrace1800–3600 sec(i=0.40)1800–3600 sec(i=0.40)medium
Editorial

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Reasoning

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Peaktrace5400–9000 sec(i=1.00)5400–9000 sec(i=1.00)medium
Editorial

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Reasoning

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Resolutiontrace3600–5400 sec(i=0.25)3600–5400 sec(i=0.25)medium
Editorial

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Reasoning

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Afterglowtrace14400–172800 sec(i=0.05)14400–172800 sec(i=0.05)medium
Editorial

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Reasoning

Duration data from community consensus values: insufflated onset 5\u201325 min, come-up 30\u201360 min, peak 1.5\u20132.5 h, offset 1\u20131.5 h, total 3\u20135 h. Compressed timeline consistent with faster nasal absorption bypassing GI transit.

Dose Tier Summaries

thresholdtrace
medium

At threshold doses (5 mg oral), effects are subtle and easily overlooked. Mild mood elevation, slight visual brightening, enhanced colour saturation, and a gentle sense of heightened awareness may be present but remain sub-perceptual for many users. Music appreciation may deepen marginally. These doses are sometimes used in exploratory microdosing protocols, though 4-AcO-DMT's duration (4–7 h) makes it less practical for this purpose than shorter-acting compounds. Physically, slight pupil dilation may be noticeable. Mild body awareness or faint tingling can occur. Functional impairment is minimal, though subtle cognitive shifts may be apparent to the user.

Editorial

Threshold of 5 mg oral is consistent with community consensus data and aligns with the lower bound of Shulgin's 10–20 mg active range (TiHKAL). Effects described are consistent with sub-perceptual psilocin activity at 5-HT2A.

Reasoning

Threshold of 5 mg oral is consistent with community consensus data and aligns with the lower bound of Shulgin's 10–20 mg active range (TiHKAL). Effects described are consistent with sub-perceptual psilocin activity at 5-HT2A.

Evidence basis: community_consensus_large

lighttrace
medium

At light doses (5–15 mg oral), the psychedelic character becomes recognizable. Mild visual enhancement emerges — colour intensification, surface texturing, slight pattern recognition enhancement. Thought acceleration and increased associative thinking are common. Emotional sensitivity increases, and music may feel richer and more immersive. A sense of novelty or gentle wonder pervades ordinary perception. Physically, pupil dilation becomes more apparent. Mild nausea may occur during the come-up, typically resolving within 30–45 minutes. Light body load — a diffuse heaviness or tingling — is common. Yawning is frequently reported. Sleep is difficult for 4–5 hours after ingestion.

Editorial

Light dose range of 5–15 mg oral is consistent with existing database values and overlaps with the lower portion of Shulgin's 10–20 mg range (TiHKAL). Effects profile inferred from psilocin equivalence and community reports.

Reasoning

Light dose range of 5–15 mg oral is consistent with existing database values and overlaps with the lower portion of Shulgin's 10–20 mg range (TiHKAL). Effects profile inferred from psilocin equivalence and community reports.

Evidence basis: community_consensus_large

commontrace
medium

At common doses (15–25 mg oral), the full psychedelic experience unfolds. Visual effects become pronounced — geometric patterning overlaying surfaces, colour shifting and enhancement, drifting and morphing of objects and textures, and closed-eye visuals with kaleidoscopic imagery. Time distortion is significant; minutes may feel stretched or compressed. Thought connectivity increases, producing novel associations and conceptual linkages. Emotional amplification is marked — responses to music, nature, and interpersonal interaction can feel deeply meaningful. Physically, nausea during the come-up is common and may lead to vomiting in some individuals. Body load is noticeable as diffuse heaviness or waves of physical sensation. Pupil dilation is prominent. Temperature dysregulation — alternating sensations of warmth and cold — is typical. Functional impairment is substantial. Sleep is not possible for the duration of effects (4–7 h). Activities requiring coordination, concentration, or social composure are significantly impaired.

Editorial

Common dose range of 15–25 mg oral is consistent with existing database values and closely matches Shulgin's 10–20 mg active range (TiHKAL). This is the core psychedelic dose range for psilocin-equivalent compounds. Effects are well-documented in community consensus.

Reasoning

Common dose range of 15–25 mg oral is consistent with existing database values and closely matches Shulgin's 10–20 mg active range (TiHKAL). This is the core psychedelic dose range for psilocin-equivalent compounds. Effects are well-documented in community consensus.

Evidence basis: community_consensus_large

strongtrace
medium

At strong doses (25–45 mg oral), the psychedelic experience intensifies considerably. Open-eye visuals become pervasive — environments appear to breathe, flow, and transform. Closed-eye visuals may feature complex, immersive imagery. Synaesthesia — cross-modal sensory blending — becomes possible. Thought loops may occur, where the same sequence of thoughts repeats without resolution. Ego dissolution begins to emerge: the boundary between self and environment feels permeable or dissolving. Emotional responses are powerful and may shift rapidly between euphoria, awe, anxiety, and confusion. Physically, nausea is more likely during the come-up. Body load is heavy. Motor coordination is significantly impaired. Temperature dysregulation, muscle tension, and jaw clenching may occur. Psychological distress becomes a meaningful risk at this range. Anxiety, paranoia, and confusion can escalate into difficult experiences requiring support. Setting and psychological preparation become critical safety factors.

Editorial

Strong dose range of 25–45 mg oral is consistent with existing database values. Effects at this range are inferred from psilocin equivalence and large community report bases, with strong doses producing qualitatively more intense versions of common-dose effects plus emergence of ego dissolution.

Reasoning

Strong dose range of 25–45 mg oral is consistent with existing database values. Effects at this range are inferred from psilocin equivalence and large community report bases, with strong doses producing qualitatively more intense versions of common-dose effects plus emergence of ego dissolution.

Evidence basis: community_consensus_large

heavytrace
medium

At heavy doses (45+ mg oral), the experience becomes overwhelming for most individuals. Complete ego dissolution is common — the sense of being a separate self may fully dissolve into an experience of unity, void, or formless awareness. Visual perception may be entirely overridden by hallucinatory content. Thought processes become non-linear and difficult to recall. Mystical-type experiences, including feelings of cosmic significance, ineffability, and transcendence, are reported at this range. Conversely, extreme anxiety, panic, delusions, and psychotic-like symptoms can occur. Physically, nausea and vomiting are common. Complete motor incoordination may occur. Communication with others becomes difficult or impossible. Awareness of the physical body may be minimal. This dose range carries substantially elevated psychological risk. Difficult experiences at this level can be psychologically destabilizing. A trusted, sober companion and a controlled, safe environment are essential. This range is not appropriate for inexperienced users.

Editorial

Heavy dose threshold of 45+ mg oral is consistent with existing database values. Effects at this range are extrapolated from psilocin equivalence and high-dose psilocybin clinical trial reports. Psychological risks at heavy doses are well-documented for the psychedelic class.

Reasoning

Heavy dose threshold of 45+ mg oral is consistent with existing database values. Effects at this range are extrapolated from psilocin equivalence and high-dose psilocybin clinical trial reports. Psychological risks at heavy doses are well-documented for the psychedelic class.

Evidence basis: community_consensus_large

02

History

current version
published Jun 4, 2026AI-generated—
versions
1 total
publication ledger

backfill Jun 4, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correctioncontact@psychedex.org
03

Sources

16 strong · 9 moderate · 2 weak
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    moderate
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    doi.org/10.1021/acsptsci.2c00177pubmed 364079487 claims checked4 verified3 inconclusive
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    strong
    Tentative identification of in vitro metabolites of O-acetylpsilocin (psilacetin, 4-AcO-DMT) by UHPLC-Q-Orbitrap MS
    Zhai W, Li L, Zhao J, Xiang P, Liu M, Shi Y, Dang Y · 2022 · Drug Testing and Analysis
    doi.org/10.1002/dta.3255pubmed 353121668 claims checked6 verified2 inconclusive
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    moderate
    Improvements to the Synthesis of Psilocybin and a Facile Method for Preparing the O-Acetyl Prodrug of Psilocin
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    doi.org/10.1055/s-1999-34903 claims checked3 inconclusive
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    strong
    Rewarding Effects of the Hallucinogen 4-AcO-DMT Administration and Withdrawal in Rats: A Challenge to the Opponent-Process Theory
    Vargas-Perez H, Minauro-Sanmiguel F, Ting-A-Kee R, Grieder TE, Méndez-Díaz M, Próspero-García O, van der Kooy D · 2024 · Neuroscience Letters
    doi.org/10.1016/j.neulet.2023.137597pubmed 381101462 claims checked2 verified
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    moderate
    In-silico toxicity study of tryptamine, psilocin, psilocybin, N,N-dimethyltryptamine, 5'-methoxy-N,N-dimethyltryptamine and O-acetylpsilocin
    Jurowski K, Kobylarz D, Noga M · 2026 · Archives of Toxicology
    doi.org/10.1007/s00204-026-04365-4pubmed 419151863 claims checked2 verified1 inconclusive
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    strong
    Receptor Binding Profiles for Tryptamine Psychedelics and Effects of 4-Propionoxy-N,N-dimethyltryptamine in Mice
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    linkno claims checked
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    linkno claims checked
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    strong
    In vivo validation of psilacetin as a prodrug yielding modestly lower peripheral psilocin exposure than psilocybin
    Jones NT, Wagner L, Hahn MCP, Scarlett CO, Wenthur CJ · 2024 · Frontiers in Psychiatry
    doi.org/10.3389/fpsyt.2023.1303365pubmed 382646376 claims checked6 verified
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    strong
    Bis(4-acetoxy-N,N-dimethyltryptammonium) fumarate: a new crystalline form of psilacetin, an alternative to psilocybin as a psilocin prodrug
    Chadeayne AR, Golen JA, Manke DR · 2019 · Acta Crystallographica Section E Crystallographic Communications
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    moderate
    Psilocin - The 'real deal' or an extraction byproduct
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    doi.org/10.1111/1556-4029.15167pubmed 363338362 claims checked2 verified
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    strong
    Chemistry and Structure-Activity Relationships of Psychedelics.
    Nichols DE · 2018 · Current Topics in Behavioral Neurosciences
    doi.org/10.1007/7854_2017_475pubmed 284015243 claims checked3 inconclusive
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    strong
    Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor
    Kim K, Che T, Panova O, DiBerto JF, Lyu J, Krumm BE, Wacker D, Robertson MJ, Seven AB, Nichols DE, Shoichet BK, Skiniotis G, Roth BL · 2020 · Cell
    doi.org/10.1016/j.cell.2020.08.024pubmed 329467822 claims checked2 inconclusive
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    The polypharmacology of psychedelics reveals multiple targets for potential therapeutics
    Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL · 2025 · Neuron
    doi.org/10.1016/j.neuron.2025.06.012pubmed 406832472 claims checked2 inconclusive
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    Elucidating the Phase I metabolism of psilocin in vitro
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    Pharmacokinetics of Psilocybin: A Systematic Review
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    Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post-Hoc Analysis
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    doi.org/10.1007/s40262-024-01454-4pubmed 398127432 claims checked2 inconclusive
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    5-HT2A receptors in the prelimbic cortex VIP-expressing interneurons: A mechanism for psychedelic-induced innate fear attenuation
    Wang Y, Yao Y, Su R, Yan H · 2026 · British Journal of Pharmacology
    doi.org/10.1111/bph.70307pubmed 417615641 claim checked1 verified
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    Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue
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    Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells
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    Designer drugs: mechanism of action and adverse effects
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    A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects
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    Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, Calkins MM, Bautista-Carro MA, Arsenault E, Telfer A, Taghavi-Abkuh FF, Malcolm NJ, El Sayegh F, Abizaid A, Schmid Y, Morton K, Halberstadt AL, Aguilar-Valles A, McCorvy JD · 2023 · Cell Reports
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04

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary6 claims4verified2inconclusive
inconclusiveNichols and Frescas proposed it as a practical psilocybin surrogate for research in 1999, catalyzing academic interest[3]model confidence 90%
Inconclusive

Abstract not available. SCOPE confirms this is exactly what the paper is about (first peer-reviewed proposal of 4-AcO-DMT as psilocybin alternative), but cannot verify without the abstract text.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThe compound acts primarily through 5-HT₂A receptor agonism, both directly and via hydrolysis to psilocin — the dominant metabolic transformation in human liver microsomes[2]model confidence 85%
Verified

The abstract directly confirms that psilocin (via hydrolysis) is the primary metabolite in pooled human liver microsomes, supporting the 'dominant metabolic transformation' portion. The 5-HT₂A agonism is not addressed by this metabolism paper but is not contradicted either; this citation is being used to support the metabolic half of the claim.

Primary metabolite = psilocin (hydrolysis).

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedDirect 5-HT₂A activity prior to hydrolysis is confirmed by mouse head-twitch response data (ED₅₀ 0.11–0.29 mg/kg s.c., comparable to psilocin)[1]model confidence 98%
Verified

Abstract directly confirms psilacetin-induced head twitch response with ED50 ~0.11-0.29 mg/kg s.c. blocked by 5-HT2A antagonist and direct serotonin receptor activity.

Psilacetin induced head twitch response (ED50 ~0.11-0.29 mg/kg s.c.) blocked by 5-HT2A antagonist...psilacetin acts as prodrug but also displays direct serotonin receptor activity.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveSecondary 5-HT₁A agonism contributes dose-dependent hypothermia and locomotor suppression at higher doses.[6]model confidence 90%
Inconclusive

Abstract not available. SCOPE indicates paper covers receptor binding profiles for tryptamine psychedelics, which would be relevant, but cannot verify the specific 5-HT₁A hypothermia and locomotor suppression claims without the abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedNo experimental LD₅₀ data exist for any species; in silico modeling predicts oral LD₅₀ at 100–500 mg/kg with low hERG inhibition risk[5]model confidence 80%
Verified

Abstract confirms the in silico prediction of oral LD50 100-500 mg/kg. The 'low hERG inhibition risk' detail is not mentioned in the abstract but is plausibly within scope of this in silico toxicology assessment and is not contradicted.

In silico toxicological assessment of 4-AcO-DMT. Predicted oral LD50: 100-500 mg/kg (moderate-high acute toxicity).

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedConditioned place preference data in rats indicate behavioral patterns inconsistent with addiction liability[4]model confidence 95%
Verified

Abstract confirms CPP data in rats showing a motivational dynamic inconsistent with typical addiction profile.

Different motivational dynamic than typical drugs of abuse — less typical addiction profile.

checked by claude-sonnet-4-6 · Apr 19, 2026

history5 claims3verified2inconclusive
inconclusiveIn 1999, David Nichols and Stephen Frescas at Purdue University published the first peer-reviewed paper explicitly proposing 4-AcO-DMT as a practical, economical alternative to psilocybin for psychopharmacology research[3]model confidence 90%
Inconclusive

Abstract not available. SCOPE strongly confirms the paper's content matches this claim exactly, but cannot verify without the abstract text.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThe crystal structure of psilacetin fumarate was characterized in 2019, providing the first solid-state physical characterization of the compound[10]model confidence 80%
Verified

Abstract confirms the crystal structure of psilacetin fumarate salt was described. The year (2019) and 'first' characterization are not mentioned in the abstract, but the core claim about crystal structure characterization is confirmed and not contradicted.

Crystal structure of psilacetin fumarate salt described.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedA series of pharmacological studies from 2022 to 2026 have substantially expanded the evidence base: in vitro metabolite profiling identified 15 metabolites in human liver microsomes, in vivo prodrug validation confirmed conversion to psilocin in mice, comprehensive receptor binding profiling was published, and multi-model computational toxicology predictions were generated[2]model confidence 95%
Verified

Abstract directly confirms the in vitro metabolite profiling component of this multi-study claim: 15 metabolites identified in human liver microsomes.

15 metabolites identified in pooled human liver microsomes. Primary metabolite = psilocin (hydrolysis).

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedA series of pharmacological studies from 2022 to 2026 have substantially expanded the evidence base: in vitro metabolite profiling identified 15 metabolites in human liver microsomes, in vivo prodrug validation confirmed conversion to psilocin in mice, comprehensive receptor binding profiling was published, and multi-model computational toxicology predictions were generated[9]model confidence 95%
Verified

Abstract directly confirms the in vivo prodrug validation component of this multi-study claim: conversion to psilocin confirmed in mice.

First direct in vivo support for psilacetin functioning as a psilocin prodrug in C57Bl6/J mice.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveA series of pharmacological studies from 2022 to 2026 have substantially expanded the evidence base: in vitro metabolite profiling identified 15 metabolites in human liver microsomes, in vivo prodrug validation confirmed conversion to psilocin in mice, comprehensive receptor binding profiling was published, and multi-model computational toxicology predictions were generated[6]model confidence 80%
Inconclusive

Abstract not available. SCOPE indicates this paper covers comprehensive receptor binding profiling for tryptamine psychedelics, which matches the 'comprehensive receptor binding profiling' component of this multi-study claim.

checked by claude-sonnet-4-6 · Apr 19, 2026

chemistry6 claims3verified3inconclusive
verifiedThis ester functions as a hydrolyzable prodrug moiety: enzymatic cleavage yields psilocin, the pharmacologically active 4-hydroxytryptamine shared with psilocybin (4-PO₄-DMT).[2]model confidence 98%
Verified

Abstract confirms hydrolysis to psilocin as the primary metabolic transformation, supporting the prodrug/enzymatic cleavage claim.

Primary metabolite = psilocin (hydrolysis).

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThis ester functions as a hydrolyzable prodrug moiety: enzymatic cleavage yields psilocin, the pharmacologically active 4-hydroxytryptamine shared with psilocybin (4-PO₄-DMT).[9]model confidence 98%
Verified

Abstract directly confirms psilacetin functions as a psilocin prodrug via in vivo conversion.

First direct in vivo support for psilacetin functioning as a psilocin prodrug in C57Bl6/J mice.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveThe compound belongs to a structure–activity relationship series established by Nichols, in which 4-position substituents on the tryptamine scaffold modulate binding affinity at serotonin receptors: 4-OH (psilocin) > 4-AcO (psilacetin) > 4-PO₄ (psilocybin) in terms of direct receptor affinity[1]model confidence 65%
Inconclusive

Abstract confirms SAR work comparing 4-position tryptamine analogs and notes similar pharmacological effects between 4-OH and 4-AcO compounds. However, the specific binding affinity rank order (4-OH > 4-AcO > 4-PO₄) is not stated in the abstract. The abstract says effects are similar, not that 4-OH exceeds 4-AcO in binding affinity.

4-acetoxy and 4-hydroxy compounds show similar pharmacological effects.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveThe N,N-dimethyl tertiary amine configuration is essential for psychedelic-type activity; secondary and quaternary amine analogs fail to produce 5-HT₂A-mediated head-twitch responses in mice[1]model confidence 65%
Inconclusive

Abstract confirms psilacetin (N,N-dimethyl) produces HTR via 5-HT2A, but does not specifically address secondary or quaternary amine analogs failing to produce HTR. This specific SAR claim may be in the full paper but is not verifiable from the abstract.

Psilacetin induced head twitch response (ED50 ~0.11-0.29 mg/kg s.c.) blocked by 5-HT2A antagonist.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveThese structure–activity principles follow Nichols' broader framework for tryptamine hallucinogens.[12]model confidence 85%
Inconclusive

Abstract not available. As a review titled 'Chemistry and Structure-Activity Relationships of Psychedelics' with SCOPE covering SAR for tryptamines, this paper would naturally support this claim, but cannot verify without abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThe compound is commonly prepared and distributed as the fumarate salt (psilacetin fumarate), whose crystal structure was characterized by single-crystal X-ray diffraction as bis(4-acetoxy-N,N-dimethyltryptammonium) fumarate[10]model confidence 98%
Verified

Abstract confirms crystal structure of psilacetin fumarate salt was described, and the title itself is 'Bis(4-acetoxy-N,N-dimethyltryptammonium) fumarate: a new crystalline form of psilacetin', directly confirming the compound name and characterization.

Crystal structure of psilacetin fumarate salt described.

checked by claude-sonnet-4-6 · Apr 19, 2026

pharmacology16 claims8verified7inconclusive1not supported
inconclusive4-AcO-DMT exerts its psychoactive effects primarily through agonism at serotonin 5-HT₂A receptors, consistent with the mechanism shared by all classical serotonergic psychedelics[12]model confidence 85%
Inconclusive

Abstract not available. SCOPE confirms SAR for tryptamines and 5-HT2A activity context, which should cover this claim, but cannot verify without abstract text.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusive4-AcO-DMT exerts its psychoactive effects primarily through agonism at serotonin 5-HT₂A receptors, consistent with the mechanism shared by all classical serotonergic psychedelics[13]model confidence 85%
Inconclusive

Abstract not available. SCOPE indicates the paper is about structural basis for 5-HT2A receptor activation by psychedelics, which would support this claim, but cannot verify without abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThe compound functions as a prodrug of psilocin (4-HO-DMT): the acetate ester undergoes hydrolysis in vivo to yield psilocin as the primary and most abundant metabolic transformation.[2]model confidence 85%
Verified

Abstract confirms hydrolysis to psilocin as the primary metabolic transformation in human liver microsomes. This is an in vitro study, so the 'in vivo' language in the claim is a minor imprecision, but the overall prodrug-via-hydrolysis mechanism is confirmed. The paper clearly establishes psilocin as the most abundant metabolite.

Primary metabolite = psilocin (hydrolysis).

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThe compound functions as a prodrug of psilocin (4-HO-DMT): the acetate ester undergoes hydrolysis in vivo to yield psilocin as the primary and most abundant metabolic transformation.[9]model confidence 98%
Verified

Abstract directly confirms in vivo prodrug function: psilacetin fumarate converts to psilocin in C57Bl/6J mice.

First direct in vivo support for psilacetin functioning as a psilocin prodrug in C57Bl6/J mice.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedGlatfelter et al. demonstrated that psilacetin directly induces 5-HT₂A-mediated head-twitch responses (HTR) in mice — a validated behavioral proxy for psychedelic activity — with ED₅₀ values of 0.11–0.29 mg/kg s.c., comparable to psilocin itself[1]model confidence 99%
Verified

Abstract confirms all specific details: ED50 ~0.11-0.29 mg/kg s.c., 5-HT2A-mediated (blocked by antagonist), comparable to psilocin, and direct receptor activity.

Psilacetin induced head twitch response (ED50 ~0.11-0.29 mg/kg s.c.) blocked by 5-HT2A antagonist. 4-acetoxy and 4-hydroxy compounds show similar pharmacological effects.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveCryo-EM structural studies have resolved the 5-HT₂A receptor in its active state bound to psychedelic ligands, defining the molecular basis of agonist-induced conformational changes.[13]model confidence 80%
Inconclusive

Abstract not available. The title 'Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor' and SCOPE strongly suggest this paper covers structural characterization, but cannot verify without abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveCryo-EM structural studies have resolved the 5-HT₂A receptor in its active state bound to psychedelic ligands, defining the molecular basis of agonist-induced conformational changes.[14]model confidence 60%
Inconclusive

Abstract not available. SCOPE describes this as a polypharmacology study (41 psychedelics vs 318 GPCRs), which does not appear to be a structural/cryo-EM study. However, without the abstract, cannot definitively rule out that it contains structural data.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveSecondary 5-HT₁A agonism contributes dose-dependent effects including hypothermia, reduced locomotor activity, and attenuation of the head-twitch response at higher doses — producing a biphasic behavioral profile in which 5-HT₁A-mediated sedation partially counteracts 5-HT₂A-driven psychedelic activity.[6]model confidence 85%
Inconclusive

Abstract not available. SCOPE indicates paper covers receptor binding profiles for tryptamine psychedelics and behavioral effects in mice, which would be relevant to this claim.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedIn human liver microsomes, hydrolysis to psilocin is the primary metabolic transformation, accounting for the most abundant metabolite peak[2]model confidence 99%
Verified

Abstract directly confirms this: primary metabolite is psilocin via hydrolysis, identified in pooled human liver microsomes.

First comprehensive in vitro metabolism study of 4-AcO-DMT. 15 metabolites identified in pooled human liver microsomes. Primary metabolite = psilocin (hydrolysis).

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedIn vivo validation in C57Bl/6J mice confirmed that psilacetin fumarate yields approximately 70% of the peripheral psilocin area under the curve (AUC) compared to equimolar psilocybin — the first direct in vivo confirmation of the prodrug hypothesis that had previously rested on pharmacological equivalence and in vitro data.[9]model confidence 99%
Verified

Abstract directly confirms all specific details: C57Bl/6J mice, ~70% psilocin AUC vs equimolar psilocybin, and framed as first direct in vivo support.

First direct in vivo support for psilacetin functioning as a psilocin prodrug in C57Bl6/J mice. Psilacetin fumarate yields ~70% of psilocin AUC compared to equimolar psilocybin.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedOnce liberated, psilocin undergoes hepatic clearance primarily via monoamine oxidase A (MAO-A), which accounts for approximately 80.9% of total hepatic clearance[15]model confidence 99%
Verified

Abstract directly confirms MAO-A as primary enzyme in psilocin Phase I metabolism at 80.9% hepatic clearance.

MAO-A identified as primary enzyme in psilocin Phase I metabolism (80.9% hepatic clearance).

checked by claude-sonnet-4-6 · Apr 19, 2026

not supportedSecondary metabolic routes involve CYP2D6 and CYP3A4.[16]model confidence 92%
Not supported

cited source's abstract does not support this claim — flagged for editorial review

The abstract directly contradicts the claim. It states 'CYP2D6 and CYP3A4 primary metabolism, secondary MAO-A' — meaning CYP2D6/CYP3A4 are PRIMARY in this systematic review, not secondary. The claim inverts the hierarchy described in this abstract.

CYP2D6 and CYP3A4 primary metabolism, secondary MAO-A.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedPublished psilocin pharmacokinetic parameters (from the psilocybin route): t₁/₂ = 1.5–4 hours; Tmax = 1.8–4 hours oral; volume of distribution (Vd) = 277–1016 L.[16]model confidence 99%
Verified

Abstract exactly matches all three PK parameters: Tmax 1.8-4h oral, t1/2 1.5-4h, Vd 277-1016L.

Tmax 1.8-4h oral, bioavailability 52.7%, t1/2 1.5-4h, Vd 277-1016L.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusivePublished psilocin pharmacokinetic parameters (from the psilocybin route): t₁/₂ = 1.5–4 hours; Tmax = 1.8–4 hours oral; volume of distribution (Vd) = 277–1016 L.[17]model confidence 75%
Inconclusive

Abstract confirms this is a systematic review of psilocin PK after psilocybin administration but does not enumerate the specific parameter values. Cannot verify the specific numerical claims (t1/2, Tmax, Vd) from the abstract alone.

Systematic review of all published PK data for psilocin post-psilocybin administration.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveMetabolite profiling of 4-AcO-DMT itself in human liver microsomes identified 15 metabolites: 12 Phase I products (hydrolysis to psilocin [most abundant], hydroxylation, N-demethylation, oxidation) and 3 Phase II glucuronide conjugates[2]model confidence 75%
Inconclusive

Abstract confirms 15 metabolites and psilocin as primary, but does not provide the specific 12/3 Phase I/Phase II breakdown or enumerate the specific reaction types (N-demethylation, glucuronide conjugates). These details may be in the full paper but are not verifiable from the abstract.

15 metabolites identified in pooled human liver microsomes. Primary metabolite = psilocin (hydrolysis).

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThe beta-hydroxylation metabolite M2-1 is proposed as the optimal forensic biomarker for distinguishing 4-AcO-DMT consumption from psilocybin use, as psilocin itself could originate from either prodrug.[2]model confidence 90%
Verified

Abstract confirms M2-1 (beta-hydroxylation metabolite) is recommended as forensic biomarker. The reasoning (psilocin could originate from either prodrug) is implied and consistent with the abstract's framing.

Beta-hydroxylation metabolite M2-1 recommended as forensic biomarker.

checked by claude-sonnet-4-6 · Apr 19, 2026

receptor pharmacology5 claims1verified1partial3inconclusive
inconclusiveGlatfelter et al. conducted the most comprehensive receptor binding profiling of tryptamine psychedelics, including 4-AcO-DMT[6]model confidence 85%
Inconclusive

Abstract not available. SCOPE confirms this paper covers receptor binding profiles for tryptamine psychedelics, consistent with the claim.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusivePrimary targets include the 5-HT₂A receptor (mediating psychedelic effects) and the 5-HT₁A receptor (contributing sedation, hypothermia, and hypolocomotion at higher doses). Secondary targets encompass multiple additional 5-HT receptor subtypes, with differential binding at adrenergic alpha receptors, dopamine receptors, histamine receptors, and the serotonin transporter (SERT) depending on N,N-dialkyl substitution pattern.[6]model confidence 85%
Inconclusive

Abstract not available. SCOPE confirms comprehensive receptor binding profiling for tryptamine psychedelics, which would naturally contain the detailed receptor binding data claimed.

checked by claude-sonnet-4-6 · Apr 19, 2026

partialPsilocin, the primary active metabolite, interacts with the serotonin transporter (SERT) and partially with the norepinephrine transporter (NET) — a pharmacological profile more similar to mdma than to lsd, which does not interact with monoamine transporters[19]model confidence 80%
Partial

Abstract confirms psilocin binding at SERT, but does not mention NET (norepinephrine transporter) binding, nor does it make the comparison to MDMA or LSD. The SERT component is confirmed; the NET and MDMA/LSD comparative claims cannot be verified from the abstract.

Psilocin binding at 5-HT2A, 5-HT1A, SERT.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveComprehensive screening of 41 psychedelics against 318 GPCRs has revealed multiple transducer pathways activated at the 5-HT₂A receptor, with implications for distinguishing hallucinogenic from non-hallucinogenic 5-HT₂A agonists.[14]model confidence 85%
Inconclusive

Abstract not available. SCOPE confirms 'Comprehensive polypharmacology of 41 psychedelics including tryptamines against 318 GPCRs; multiple 5-HT2AR transducers', which matches the claim precisely.

checked by claude-sonnet-4-6 · Apr 19, 2026

verified4-AcO-DMT significantly reduced TNF-α and IFN-γ in a human 3D EpiIntestinal tissue model via 5-HT₂A agonism[20]model confidence 99%
Verified

Abstract directly confirms all details: 4-AcO-DMT reduces TNF-alpha and IFN-gamma in 3D intestinal tissue model via 5-HT2A.

4-AcO-DMT and psilocybin reduce TNF-alpha and IFN-gamma in 3D intestinal tissue model. Anti-inflammatory potential via 5-HT2A.

checked by claude-sonnet-4-6 · Apr 19, 2026

neuroscience1 claim1verified
verifiedWang et al. demonstrated that 4-AcO-DMT attenuates innate fear responses in rats through 5-HT₂A receptors on VIP-expressing interneurons in the prelimbic cortex[18]model confidence 99%
Verified

Abstract directly confirms all specific details: 4-AcO-DMT, fear attenuation in rats, 5-HT2A mechanism, prelimbic cortex, VIP-expressing interneurons.

4-AcO-DMT used as tool compound to investigate 5-HT2A receptor mechanism in fear attenuation in rats. Prelimbic cortex VIP-expressing interneurons identified as substrate.

checked by claude-sonnet-4-6 · Apr 19, 2026

pharmacokinetic detail7 claims3verified4inconclusive
verifiedJones et al. provided the first direct in vivo comparison: in C57Bl/6J mice, psilacetin fumarate produced approximately 70% of the peripheral psilocin AUC achieved by equimolar psilocybin administration[9]model confidence 99%
Verified

Abstract directly confirms all specific details: C57Bl/6J mice, ~70% psilocin AUC vs equimolar psilocybin, first direct in vivo support.

First direct in vivo support for psilacetin functioning as a psilocin prodrug in C57Bl6/J mice. Psilacetin fumarate yields ~70% of psilocin AUC compared to equimolar psilocybin.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveData from Meshkat et al., Otto et al., and Chen et al..[16]model confidence 60%
Inconclusive

Abstract confirms this is a systematic review of psilocybin/psilocin PK, which would include data from multiple studies, but does not specifically mention Meshkat, Otto, or Chen et al. Cannot verify these specific authors are cited.

Systematic review of psilocybin/psilocin pharmacokinetics.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveData from Meshkat et al., Otto et al., and Chen et al..[17]model confidence 60%
Inconclusive

Abstract confirms this is a systematic review of psilocin PK but does not mention the specific authors Meshkat, Otto, or Chen.

Systematic review of all published PK data for psilocin post-psilocybin administration.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveData from Meshkat et al., Otto et al., and Chen et al..[15]model confidence 50%
Inconclusive

Abstract describes psilocin Phase I metabolism study, not a compilation of PK data from multiple authors. The specific authors Meshkat, Otto, or Chen are not mentioned and this paper does not appear to be the appropriate citation for this claim.

MAO-A identified as primary enzyme in psilocin Phase I metabolism (80.9% hepatic clearance).

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveThe beta-hydroxylation metabolite M2-1 is proposed as the definitive forensic biomarker for 4-AcO-DMT consumption, as it is structurally unique to the 4-AcO-DMT metabolic pathway and cannot originate from psilocybin metabolism.[2]model confidence 70%
Inconclusive

Abstract confirms M2-1 is recommended as forensic biomarker, but the specific reason ('structurally unique to the 4-AcO-DMT metabolic pathway and cannot originate from psilocybin metabolism') is not stated in the abstract. This mechanistic reasoning may be in the full paper.

Beta-hydroxylation metabolite M2-1 recommended as forensic biomarker.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThe acetate ester is thermally stable at 200 °C (standard GC injection port temperature) but hydrolyzes under basic conditions[11]model confidence 99%
Verified

Abstract directly confirms both claims: hydrolysis under basic conditions (GC-MS artifact) and thermal stability at 200°C.

4-AcO-DMT hydrolyzes to psilocin under basic conditions (GC-MS artifact); thermally stable at 200C.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThis base-lability represents a critical forensic analytical confound: basic pre-injection reagents used in GC-MS workflows can convert 4-AcO-DMT to psilocin as a laboratory artifact, causing misidentification[11]model confidence 99%
Verified

Abstract directly confirms GC-MS artifact from base-catalyzed hydrolysis to psilocin.

4-AcO-DMT hydrolyzes to psilocin under basic conditions (GC-MS artifact); thermally stable at 200C. Confirms base-catalyzed hydrolysis mechanism.

checked by claude-sonnet-4-6 · Apr 19, 2026

safety16 claims4verified1partial10inconclusive1not supported
verifiedA multi-model in silico computational toxicity assessment yielded the following predictions:[5]model confidence 99%
Verified

Abstract directly confirms this is an in silico toxicological assessment of 4-AcO-DMT yielding multiple predictions.

In silico toxicological assessment of 4-AcO-DMT. Predicted oral LD50: 100-500 mg/kg (moderate-high acute toxicity). Cramer Class III.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveIn silico predictions indicate lower hERG inhibition risk than DMT and 5-MeO-DMT.[5]model confidence 70%
Inconclusive

Abstract does not mention hERG inhibition or any comparison to DMT or 5-MeO-DMT. The paper is an in silico toxicology study that would typically include hERG assessment, but the specific comparative claim cannot be verified from the abstract.

In silico toxicological assessment of 4-AcO-DMT. Predicted oral LD50: 100-500 mg/kg (moderate-high acute toxicity). Cramer Class III. Cardiovascular and GI systems primary targets.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedHallucinogen persisting perception disorder (HPPD) — persistent visual disturbances following psychedelic use — can arise after single or multiple exposures to serotonergic psychedelics[23]model confidence 98%
Verified

Abstract directly confirms HPPD can arise after single exposure and is linked to hallucinogenic drug use.

Review of HPPD: rare condition linked to hallucinogenic drug use. Can arise after single exposure.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveDaily LSD administration in rats for 4 days decreases frontal cortex 5-HT₂A receptor binding, and β-arrestin-mediated receptor internalization is implicated in the tolerant phenotype[24]model confidence 50%
Inconclusive

Abstract not available. Title ('A Single Dose of LSD Does Not Alter Gene Expression...in Healthy Subjects') does not align well with the claim about daily rat administration decreasing receptor binding. SCOPE mentions 5-HT2A downregulation as tolerance mechanism. Cannot confirm or deny without the abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

partialDaily LSD administration in rats for 4 days decreases frontal cortex 5-HT₂A receptor binding, and β-arrestin-mediated receptor internalization is implicated in the tolerant phenotype[25]model confidence 75%
Partial

The abstract supports the β-arrestin/receptor internalization mechanism for tolerance by inverse demonstration (2-Br-LSD lacks β-arrestin recruitment and does NOT induce tolerance), but does not directly confirm the specific claim about classic LSD daily administration for 4 days in rats decreasing frontal cortex 5-HT₂A binding.

Weak 5-HT2A beta-arrestin recruitment and receptor internalization linked to non-tolerance.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveCross-tolerance is established with all 5-HT₂A agonist psychedelics — lsd, psilocybin, dmt, mescaline — reflecting shared receptor downregulation as the underlying mechanism.[12]model confidence 80%
Inconclusive

Abstract not available. As a review of SAR and tryptamine pharmacology, the paper would likely cover cross-tolerance, but cannot verify without abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedIn conditioned place preference tests, 4-AcO-DMT produces acutely rewarding effects, but its 24-hour aftereffect is also rewarding — a motivational pattern inconsistent with the opponent-process dynamics that drive addiction[4]model confidence 99%
Verified

Abstract directly confirms all details: acutely rewarding, 24h aftereffect also rewarding, different motivational dynamic than typical drugs of abuse.

Modified test showed 4-AcO-DMT is acutely rewarding; 24h aftereffect also rewarding. Different motivational dynamic than typical drugs of abuse — less typical addiction profile.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveThe combination of tramadol's SERT inhibition with 4-AcO-DMT's serotonergic activity carries a mechanistically confirmed risk of serotonin toxicity[26]model confidence 85%
Inconclusive

Abstract not available. SCOPE indicates paper covers tramadol as SERT inhibitor and serotonin toxicity mechanism, which is directly relevant to this claim.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveMultiple fatalities have been documented from tramadol in combination with other serotonergic drugs, including MAOIs, SSRIs, and SNRIs[27]model confidence 70%
Inconclusive

Abstract not available. SCOPE mentions MAOI/serotonergic drug interactions and tramadol serotonin toxicity risk, which is partially relevant, but whether it specifically documents tramadol fatalities in combination with SSRIs/SNRIs cannot be verified.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedMAOIs inhibit MAO-A, the primary enzyme responsible for psilocin catabolism (approximately 80.9% of hepatic clearance)[15]model confidence 99%
Verified

Abstract directly confirms MAO-A is primary enzyme for psilocin Phase I metabolism at 80.9% hepatic clearance, providing the mechanistic basis for the MAOI interaction claim.

MAO-A identified as primary enzyme in psilocin Phase I metabolism (80.9% hepatic clearance).

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveNarrative review evidence indicates that some classic hallucinogens may be compatible with MAOI treatment under careful clinical monitoring, but the full risk profile in individual patients is uncertain.[27]model confidence 75%
Inconclusive

Abstract not available. SCOPE covers MAOI/serotonergic drug interactions, which is relevant, but cannot verify the nuanced compatibility claim without the abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusive4-AcO-DMT is not detectable by standard immunoassay drug screening panels.[22]model confidence 65%
Inconclusive

Abstract not available. SCOPE mentions 'detection challenges' which is relevant, but cannot verify this specific claim without the abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusivePsychedelics can precipitate or exacerbate psychotic episodes through 5-HT₂A-mediated disruption of prefrontal cortical gating.[27]model confidence 40%
Inconclusive

Abstract not available. SCOPE is about MAOI/serotonergic drug interactions and tramadol toxicity, which does not appear to cover psychedelic-induced psychosis risk. This citation may not support this claim, but cannot confirm without the abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveAbsolute contraindication.[26]model confidence 80%
Inconclusive

Abstract not available. SCOPE covers tramadol as SERT inhibitor and serotonin toxicity mechanism, which would provide mechanistic basis for absolute contraindication, but cannot verify without abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveRelative-to-absolute contraindication depending on clinical context and monitoring capacity.[27]model confidence 65%
Inconclusive

Abstract not available. SCOPE is about MAOI/serotonergic drug interactions. Even if available, the abstract would need to contain explicit clinical risk stratification language to support this specific contraindication classification.

checked by claude-sonnet-4-6 · Apr 19, 2026

not supportedRelative-to-absolute contraindication depending on clinical context and monitoring capacity.[15]model confidence 90%
Not supported

cited source's abstract does not support this claim — flagged for editorial review

The abstract describes psilocin metabolic pathway (MAO-A as primary enzyme, 80.9% hepatic clearance) — this is mechanistic/pharmacological data, not clinical guidance. The claim is a clinical risk classification that cannot be derived from metabolic enzyme data alone. The abstract contains no information about contraindication classifications or clinical monitoring.

MAO-A identified as primary enzyme in psilocin Phase I metabolism (80.9% hepatic clearance). MAO-A converts psilocin to 4-HIA intermediate, then AO/ALDH to terminal metabolite 4-HIAA.

checked by claude-sonnet-4-6 · Apr 19, 2026

clinical evidence2 claims1verified1inconclusive
inconclusiveNichols and Frescas first proposed 4-AcO-DMT as a synthetically accessible and economical alternative to psilocybin for psychopharmacology research in 1999[3]model confidence 90%
Inconclusive

Abstract not available. SCOPE directly confirms this is the paper that first proposed 4-AcO-DMT as an economical/synthetically accessible alternative to psilocybin, but cannot verify without abstract text.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedThis rationale has been partially validated at the preclinical level: Glatfelter et al. confirmed equivalent 5-HT₂A-mediated behavioral responses in mice, and Jones et al. demonstrated in vivo conversion to psilocin with approximately 70% of the AUC achieved by psilocybin.[1]model confidence 95%
Verified

Abstract confirms the Glatfelter portion of the claim: equivalent 5-HT₂A-mediated behavioral effects with similar ED50 values to psilocin. The Jones et al. portion is covered by a separate citation.

4-acetoxy and 4-hydroxy compounds show similar pharmacological effects; psilacetin acts as prodrug but also displays direct serotonin receptor activity.

checked by claude-sonnet-4-6 · Apr 19, 2026

comparative pharmacology4 claims2verified2inconclusive
verifiedData from Jones et al., Glatfelter et al., and Erowid.[9]model confidence 95%
Verified

Abstract confirms this is the Jones et al. in vivo prodrug study, supporting the Jones et al. component of this multi-source citation.

First direct in vivo support for psilacetin functioning as a psilocin prodrug in C57Bl6/J mice. Psilacetin fumarate yields ~70% of psilocin AUC compared to equimolar psilocybin.

checked by claude-sonnet-4-6 · Apr 19, 2026

verifiedData from Jones et al., Glatfelter et al., and Erowid.[1]model confidence 95%
Verified

Abstract confirms this is the Glatfelter SAR study, supporting the Glatfelter et al. component of this multi-source citation.

SAR study testing psilacetin (4-AcO-DMT) alongside psilocin, psilocybin.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveAmong 4-substituted tryptamines characterized by Glatfelter et al., binding affinity at serotonin receptors follows the order: 4-OH (psilocin) > 4-AcO (psilacetin) > 4-PO₄ (psilocybin)[1]model confidence 65%
Inconclusive

Abstract describes SAR work with these compounds but notes 'similar pharmacological effects' between 4-OH and 4-AcO, not a rank-ordered difference. The specific binding affinity rank order is not stated and may even be inconsistent with the 'similar effects' language.

4-acetoxy and 4-hydroxy compounds show similar pharmacological effects; psilacetin acts as prodrug but also displays direct serotonin receptor activity.

checked by claude-sonnet-4-6 · Apr 19, 2026

inconclusiveAmong 4-substituted tryptamines characterized by Glatfelter et al., binding affinity at serotonin receptors follows the order: 4-OH (psilocin) > 4-AcO (psilacetin) > 4-PO₄ (psilocybin)[6]model confidence 70%
Inconclusive

Abstract not available. SCOPE confirms comprehensive receptor binding profiling, which would contain binding affinity data, but cannot verify the specific rank order without the abstract.

checked by claude-sonnet-4-6 · Apr 19, 2026

05

Coverage & Gaps

effect links
171 links · 170 approved · 73 audited1/171 with evidence basis
interactions
2 approved pairs0/2 graded