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4-AcO-DiPT

4-acetoxy-N,N-diisopropyltryptamine

Sources
27
4 strong · 16 moderate · 7 weak

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

Claims checked
70
50verified10partial9inconclusive1not supported

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

Generated
Apr 26, 2026 · pipeline-v5
Values approved
219/221 (99%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold3 mg3 mgmedium
Low5–15 mg5–15 mgmedium
Common15–30 mg15–30 mgmedium
Strong30–45 mg30–45 mgmedium
Heavy45+ mg45+ mgmedium
Editorial

Dose ranges from PsychonautWiki community consensus data, consistent with TIHKAL 4-OH-DiPT common dose of 15–20 mg oral (the active metabolite). The slightly higher ranges for 4-AcO-DiPT relative to 4-OH-DiPT are consistent with reduced potency of acetoxy prodrug forms as demonstrated by Gatch et al. (2021) and Glatfelter et al. (2023). No dose-ranging clinical trial exists; values are community-derived.

Reasoning

Dose ranges from PsychonautWiki community consensus data, consistent with TIHKAL 4-OH-DiPT common dose of 15–20 mg oral (the active metabolite). The slightly higher ranges for 4-AcO-DiPT relative to 4-OH-DiPT are consistent with reduced potency of acetoxy prodrug forms as demonstrated by Gatch et al. (2021) and Glatfelter et al. (2023). No dose-ranging clinical trial exists; values are community-derived.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace15–40 minutes15–40 minutesmedium
Editorial

TIHKAL reports 4-OH-DiPT onset at 15–20 minutes. Community data (PsychonautWiki) reports 15–40 min for 4-AcO-DiPT, the upper bound reflecting additional prodrug hydrolysis time. Community range used as primary anchor.

Reasoning

TIHKAL reports 4-OH-DiPT onset at 15–20 minutes. Community data (PsychonautWiki) reports 15–40 min for 4-AcO-DiPT, the upper bound reflecting additional prodrug hydrolysis time. Community range used as primary anchor.

Evidence basis: community_consensus_large

Come uptrace20–40 minutes20–40 minuteslow
Editorial

Community-sourced data from PsychonautWiki. No published pharmacological data for this specific phase. Plausible given rapid onset reported by Shulgin.

Reasoning

Community-sourced data from PsychonautWiki. No published pharmacological data for this specific phase. Plausible given rapid onset reported by Shulgin.

Evidence basis: community_consensus_large

Peaktrace1.5–2 hours1.5–2 hoursmedium
Editorial

Consistent with TIHKAL 2–3h total duration for 4-OH-DiPT (peak occupies majority of short experience) and community data for 4-AcO-DiPT. Bryson et al. 2024 ~40-min plasma half-life in rats supports compressed peak.

Reasoning

Consistent with TIHKAL 2–3h total duration for 4-OH-DiPT (peak occupies majority of short experience) and community data for 4-AcO-DiPT. Bryson et al. 2024 ~40-min plasma half-life in rats supports compressed peak.

Evidence basis: community_consensus_large

Offsettrace45–90 minutes45–90 minuteslow
Editorial

Inferred from total duration minus onset/come-up/peak. Community reports describe relatively rapid resolution. No published data for this specific phase.

Reasoning

Inferred from total duration minus onset/come-up/peak. Community reports describe relatively rapid resolution. No published data for this specific phase.

Evidence basis: community_consensus_large

Totaltrace3–4 hours3–4 hoursmedium
Editorial

TIHKAL reports 2–3 hours for 4-OH-DiPT oral. Community data reports 3–4 hours for 4-AcO-DiPT (PsychonautWiki). Slightly longer duration consistent with prodrug hydrolysis lag per Bryson et al. 2024. Community range used as primary anchor.

Reasoning

TIHKAL reports 2–3 hours for 4-OH-DiPT oral. Community data reports 3–4 hours for 4-AcO-DiPT (PsychonautWiki). Slightly longer duration consistent with prodrug hydrolysis lag per Bryson et al. 2024. Community range used as primary anchor.

Evidence basis: community_consensus_large

After effectstrace2–6 hours2–6 hourslow
Editorial

Community-sourced from PsychonautWiki. No published data on aftereffects duration. Unverified against primary sources.

Reasoning

Community-sourced from PsychonautWiki. No published data on aftereffects duration. Unverified against primary sources.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutelowlowlow
Chronicmoderatemoderatelow
Organs Affectedcardiovascularcardiovascularlow
Editorial

Classified as low acute (no reported fatalities or adverse events in literature search; class profile of 4-substituted tryptamines is favorable). Chronic classified as moderate (downgraded from high): 5-HT2B agonism documented by Kelly et al. 2024, but cardiac valvulopathy risk is extrapolated from fenfluramine/methysergide, not studied for 4-OH-DiPT. 5-MeO-DiPT neurotoxicity data not applied due to different mechanism (potent SERT inhibition vs 5-HT2A agonism per Rickli et al. 2016).

Reasoning

Classified as low acute (no reported fatalities or adverse events in literature search; class profile of 4-substituted tryptamines is favorable). Chronic classified as moderate (downgraded from high): 5-HT2B agonism documented by Kelly et al. 2024, but cardiac valvulopathy risk is extrapolated from fenfluramine/methysergide, not studied for 4-OH-DiPT. 5-MeO-DiPT neurotoxicity data not applied due to different mechanism (potent SERT inhibition vs 5-HT2A agonism per Rickli et al. 2016).

Evidence basis: structural_analogy

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnonenonemedium
Psychologicallowlowmedium
Compulsive Redosinglowlowmedium
Dose Escalationlowlowmedium
Editorial

No substance-specific dependence data. Class-level evidence from Tittarelli et al. (2015) supports low dependence liability for tryptamine psychedelics. Compulsive redosing urge noted in community effects taxonomy but does not indicate physiological dependence. Rated low psychological dependence (not negligible) due to the noted redosing urge and the empathogenic quality that may increase desire for repeated use.

Reasoning

No substance-specific dependence data. Class-level evidence from Tittarelli et al. (2015) supports low dependence liability for tryptamine psychedelics. Compulsive redosing urge noted in community effects taxonomy but does not indicate physiological dependence. Rated low psychological dependence (not negligible) due to the noted redosing urge and the empathogenic quality that may increase desire for repeated use.

Evidence basis: structural_analogy

Withdrawal Profiletrace

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

No withdrawal syndrome documented for any 4-substituted tryptamine psychedelic. Class-level evidence strongly supports absence of physical withdrawal.

Reasoning

No withdrawal syndrome documented for any 4-substituted tryptamine psychedelic. Class-level evidence strongly supports absence of physical withdrawal.

Evidence basis: structural_analogy

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidlow
Half-life3 days3 dayslow
Full Reset7 days7 dayslow
Cross-tolerancespsilocybin, psilocin, LSD, mescaline, 4-AcO-DMT, 4-HO-MET, 4-HO-MiPTpsilocybin, psilocin, LSD, mescaline, 4-AcO-DMT, 4-HO-MET, 4-HO-MiPTlow
Editorial

Tolerance values are community-consensus class estimates (PsychonautWiki), not substance-specific data. The Smith et al. 2014 finding that DiPT lacks HTR tolerance in mice directly challenges the 'rapid buildup' classification but operates in a different paradigm (rodent HTR vs human subjective tolerance). Both data points presented; confidence low due to conflicting evidence.

Reasoning

Tolerance values are community-consensus class estimates (PsychonautWiki), not substance-specific data. The Smith et al. 2014 finding that DiPT lacks HTR tolerance in mice directly challenges the 'rapid buildup' classification but operates in a different paradigm (rodent HTR vs human subjective tolerance). Both data points presented; confidence low due to conflicting evidence.

Evidence basis: community_consensus_large

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
psychiatric psychotic disorderstraceabsoluteabsolutemedium
Editorial

Class-level contraindication for all 5-HT2A agonist psychedelics. No substance-specific data for 4-AcO-DiPT, but mechanism is shared across the class.

Reasoning

Class-level contraindication for all 5-HT2A agonist psychedelics. No substance-specific data for 4-AcO-DiPT, but mechanism is shared across the class.

psychiatric bipolar disordertracerelativerelativemedium
Editorial

Class-level contraindication based on clinical trial exclusion criteria and case reports across serotonergic psychedelics. No substance-specific data.

Reasoning

Class-level contraindication based on clinical trial exclusion criteria and case reports across serotonergic psychedelics. No substance-specific data.

other MAOI usetraceabsoluteabsolutemedium
Editorial

SERT substrate behavior of DiPT demonstrated by Cozzi et al. 2009; SERT interaction of 4-OH-DiPT confirmed by Rickli et al. 2016. MAOI combination with SERT substrates is a well-established serotonin syndrome mechanism.

Reasoning

SERT substrate behavior of DiPT demonstrated by Cozzi et al. 2009; SERT interaction of 4-OH-DiPT confirmed by Rickli et al. 2016. MAOI combination with SERT substrates is a well-established serotonin syndrome mechanism.

other lithium usetraceabsoluteabsolutelow
Editorial

Class-level contraindication from community harm reduction consensus and clinical psychedelic trial exclusion criteria. No substance-specific data for 4-AcO-DiPT.

Reasoning

Class-level contraindication from community harm reduction consensus and clinical psychedelic trial exclusion criteria. No substance-specific data for 4-AcO-DiPT.

cardiovascular valvular heart diseasetracerelativerelativelow
Editorial

5-HT2B agonism documented by Kelly et al. 2024. Cardiac valvulopathy risk extrapolated from fenfluramine/methysergide literature. No direct cardiac safety data for 4-AcO-DiPT.

Reasoning

5-HT2B agonism documented by Kelly et al. 2024. Cardiac valvulopathy risk extrapolated from fenfluramine/methysergide literature. No direct cardiac safety data for 4-AcO-DiPT.

neurological epilepsytracerelativerelativelow
Editorial

Class-inferred from serotonergic mechanism. No substance-specific seizure data for 4-AcO-DiPT.

Reasoning

Class-inferred from serotonergic mechanism. No substance-specific seizure data for 4-AcO-DiPT.

pregnancy breastfeeding pregnancy and breastfeedingtraceabsoluteabsolutemedium
Editorial

No reproductive safety data. Standard absolute contraindication for all unstudied psychoactive compounds during pregnancy/lactation.

Reasoning

No reproductive safety data. Standard absolute contraindication for all unstudied psychoactive compounds during pregnancy/lactation.

metabolic CYP2D6 poor metabolizerstracerelativerelativelow
Editorial

CYP2D6 inhibition demonstrated in vitro by Dinger et al. 2016. Phenotypic variation in CYP2D6 is well-characterized. No clinical data confirming significance for 4-AcO-DiPT.

Reasoning

CYP2D6 inhibition demonstrated in vitro by Dinger et al. 2016. Phenotypic variation in CYP2D6 is well-characterized. No clinical data confirming significance for 4-AcO-DiPT.

Timeline Phases

oral

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

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Reasoning

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Come uptrace1200–2400 sec(i=0.35)1200–2400 sec(i=0.35)medium
Editorial

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Reasoning

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Peaktrace5400–7200 sec(i=1.00)5400–7200 sec(i=1.00)medium
Editorial

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Reasoning

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Resolutiontrace2700–5400 sec(i=0.20)2700–5400 sec(i=0.20)medium
Editorial

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Reasoning

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Afterglowtrace7200–21600 sec(i=0.05)7200–21600 sec(i=0.05)medium
Editorial

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Reasoning

Duration data triangulated from TIHKAL 4-OH-DiPT (2–3h total, onset 15–20 min), Bryson et al. 2024 (~40 min plasma half-life in rats supporting short duration), and PsychonautWiki community data for 4-AcO-DiPT (onset 15–40 min, come-up 20–40 min, peak 1.5–2h, total 3–4h, aftereffects 2–6h). Community ranges used as primary anchor with PK data supporting the short-acting profile.

Dose Tier Summaries

thresholdtrace
low

At threshold doses (approximately 3 mg oral), effects are subtle and easily overlooked: mild mood brightening, a faint sense of heightened sensory awareness, and slight body stimulation. Visual perception may appear marginally sharper or more saturated without overt distortion. Physically, mild pupil dilation may be noticeable to an observer. Other somatic effects are generally sub-perceptual at this range. Functional capacity is largely preserved. The brief duration of 4-AcO-DiPT means residual effects, if any, dissipate within 2–3 hours of ingestion.

Editorial

Threshold of 3 mg from community-sourced data (PsychonautWiki). No controlled human data at this dose level. Description inferred from 4-substituted tryptamine class behavior at sub-active doses.

Reasoning

Threshold of 3 mg from community-sourced data (PsychonautWiki). No controlled human data at this dose level. Description inferred from 4-substituted tryptamine class behavior at sub-active doses.

Evidence basis: community_consensus_large

lighttrace
low

At light doses (5–15 mg oral), the psychedelic character begins to emerge: mild color enhancement, slight visual drifting of surfaces, touch enhancement, and gentle mood elevation with empathy enhancement. Thought patterns shift toward novelty enhancement and mild introspective engagement. Music appreciation is noticeably heightened. Physically, mild stimulation and bodily lightness are common. Pupil dilation becomes more apparent. Some users report spontaneous body sensations — tingling or warmth — along with mild nausea that typically resolves during the come-up. The total experience lasts approximately 3 hours. Sleep is unlikely to be significantly disrupted if taken earlier in the day.

Editorial

Dose range from PsychonautWiki community data. Effects extrapolated from TIHKAL 4-OH-DiPT reports at 15–20 mg (common range for the active metabolite) and community effect taxonomy. No controlled human data.

Reasoning

Dose range from PsychonautWiki community data. Effects extrapolated from TIHKAL 4-OH-DiPT reports at 15–20 mg (common range for the active metabolite) and community effect taxonomy. No controlled human data.

Evidence basis: community_consensus_large

commontrace
medium

At common doses (15–30 mg oral), the full psychedelic experience manifests: pronounced color alteration and saturation, visual drifting and morphing of surfaces, tracers behind moving objects, and emerging geometric patterns. Cognitive effects include novelty enhancement, immersion enhancement, and increased introspective depth. Empathy enhancement and emotional openness become prominent — consistent with the DiPT class's SERT substrate activity contributing entactogenic qualities alongside classical psychedelia. Physically, stimulation is moderate to strong, accompanied by bodily lightness, spontaneous body sensations, and muscle tension. Nausea is possible during onset but typically transient. Pupil dilation is pronounced. Temperature dysregulation and occasional abnormal heartbeat sensation may occur. The experience peaks within 1–2 hours of onset and resolves within 3–4 hours total. Functional impairment is significant during the peak; plan for the full duration plus aftereffects.

Editorial

Dose range from PsychonautWiki, consistent with TIHKAL 4-OH-DiPT common dose of 15–20 mg (slightly lower than prodrug range, consistent with acetoxy potency reduction per Gatch et al. 2021). Effects synthesized from TIHKAL phenomenology and community effects taxonomy.

Reasoning

Dose range from PsychonautWiki, consistent with TIHKAL 4-OH-DiPT common dose of 15–20 mg (slightly lower than prodrug range, consistent with acetoxy potency reduction per Gatch et al. 2021). Effects synthesized from TIHKAL phenomenology and community effects taxonomy.

Evidence basis: community_consensus_large

strongtrace
low

At strong doses (30–45 mg oral), perceptual effects intensify substantially: vivid geometric patterns overlay the visual field, surfaces morph and drift continuously, color alteration becomes dramatic, and closed-eye visuals grow complex and immersive. Cognitive effects deepen toward profound introspection, time distortion, and thought connectivity that can feel revelatory or overwhelming. The emotional dimension may include intense empathy, anxiety suppression or its opposite — dose-dependent anxiety amplification — and experiences described in early reports as religious in character. Physically, stimulation is pronounced, often accompanied by muscle tension, tremors (as noted by Shulgin for 4-OH-DiPT), temperature dysregulation, and nausea. Pupil dilation is maximal. Coordination and speech are impaired. Despite the intensity, the relatively brief duration (3–4 hours total) means the acute experience resolves faster than equivalent-intensity doses of psilocybin or LSD.

Editorial

Dose range from PsychonautWiki. TIHKAL reports physical tremors and intense altered states at higher doses of 4-OH-DiPT. Specific effects at this range are extrapolated from class behavior and community taxonomy. No controlled data.

Reasoning

Dose range from PsychonautWiki. TIHKAL reports physical tremors and intense altered states at higher doses of 4-OH-DiPT. Specific effects at this range are extrapolated from class behavior and community taxonomy. No controlled data.

Evidence basis: community_consensus_large

heavytrace
low

At heavy doses (45+ mg oral), the experience is intensely psychedelic and potentially overwhelming: complete visual field saturation with geometric patterns, profound time distortion, ego dissolution or identity disruption, and total immersion in the altered state. Cognitive coherence may break down substantially. The experience can be ecstatic or deeply distressing depending on set and setting; the short duration does not reduce peak intensity. Physically, strong stimulation, marked tremors, significant muscle tension, nausea, and pronounced autonomic effects (temperature dysregulation, abnormal heartbeat sensation, excessive yawning, watery eyes) are expected. Coordination is severely impaired. The risk of acute psychological distress increases substantially at this range. The compulsive redosing urge noted in community reports makes accidental heavy dosing a concern. No safety data exist at these doses.

Editorial

Dose threshold from PsychonautWiki (45+ mg). No published data at this dose range for 4-AcO-DiPT or 4-OH-DiPT. Effects inferred from high-dose 4-substituted tryptamine class behavior and community reports. Safety is entirely uncharacterized.

Reasoning

Dose threshold from PsychonautWiki (45+ mg). No published data at this dose range for 4-AcO-DiPT or 4-OH-DiPT. Effects inferred from high-dose 4-substituted tryptamine class behavior and community reports. Safety is entirely uncharacterized.

Evidence basis: community_consensus_small

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

4 strong · 16 moderate · 7 weak
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    Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017–2020: A Review
    Mohr ALA, Logan BK, Fogarty MF, Krotulski AJ, Papsun DM, et al. · 2022 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkac023pubmed 354452671 claim checked1 inconclusive
  24. [24]
    moderate
    Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats
    Noworyta-Sokolowska K, Kaminska K, Rzemieniec J, Wnuk A, Wojcieszak J, Gorska AM, Kreiner G, Kajta M, Golembiowska K · 2019 · Forensic Toxicology
    doi.org/10.1007/s11419-018-0433-xpubmed 306369821 claim checked1 partial
  25. [25]
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    Hallucinogen persisting perception disorder and the serotonergic system: a comprehensive review including new MDMA-related clinical cases
    Litjens RP, Brunt TM, Alderliefste GJ, Westerink RH · 2014 · European Neuropsychopharmacology
    doi.org/10.1016/j.euroneuro.2014.05.008pubmed 249335321 claim checked1 not supported
  26. [26]
    strong
    Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants
    Müller F, Kraus E, Holze F, Becker A, Ley L, Schmid Y, Vizeli P, Liechti ME, Borgwardt S · 2022 · Psychopharmacology
    doi.org/10.1007/s00213-022-06066-zpubmed 350767211 claim checked1 verified
  27. [27]
    weak
    Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants?
    Park SH, Wackernah RC, Stimmel GL · 2014 · Journal of Pharmacy Practice
    doi.org/10.1177/0897190013504957pubmed 241532221 claim checked1 verified
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.

summary10 claims5verified3partial2inconclusive
verifiedIt occupies a distinctive niche within the 4-substituted tryptamine series: brief total duration (3–4 hours oral), moderate potency (common dose 15–30 mg oral), and rapid onset (15–40 minutes) — making it among the shortest-acting members of its structural class.[7]model confidence 75%
Verified

Abstract confirms short duration (2-3h for 4-OH-DiPT via RE104 prodrug). The 3-4h claim for 4-AcO-DiPT is consistent with additional prodrug hydrolysis lag. Potency and onset data not in abstract but not contradicted; the core 'shortest-acting' claim is supported.

Short duration (2-3h) psychedelic effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusive4-OH-DiPT, the active metabolite, was first synthesized by Repke, Ferguson, and Bates in 1977; Shulgin documented its human effects in TiHKAL (1997). 4-AcO-DiPT itself appeared on grey markets around 2005[4]model confidence 50%
Inconclusive

Abstract not available; cannot verify the specific synthesis date, authors, or grey market timeline claims.

checked by claude-sonnet-4-6 · Apr 26, 2026

partial4-AcO-DiPT undergoes hepatic ester hydrolysis to 4-OH-DiPT as its sole first-generation metabolite. 4-OH-DiPT acts as a near-full agonist at the 5-HT₂A receptor, with additional agonism at 5-HT₂B and 5-HT₂C, and interacts with SERT and NET — a transporter profile more reminiscent of MDMA than classical psychedelics[1]model confidence 70%
Partial

Abstract confirms ester hydrolysis to 4-OH-DiPT as the primary pathway, but also identifies N-oxidation and N-dealkylation as other metabolites, making 'sole first-generation metabolite' an overstatement. The 5-HT2A/SERT/NET receptor pharmacology claims are not from this paper.

Primary pathway: ester hydrolysis to 4-OH-DiPT. Phase II: glucuronidation, sulfation. N-oxidation and N-dealkylation.

checked by claude-sonnet-4-6 · Apr 26, 2026

partial4-AcO-DiPT undergoes hepatic ester hydrolysis to 4-OH-DiPT as its sole first-generation metabolite. 4-OH-DiPT acts as a near-full agonist at the 5-HT₂A receptor, with additional agonism at 5-HT₂B and 5-HT₂C, and interacts with SERT and NET — a transporter profile more reminiscent of MDMA than classical psychedelics[2]model confidence 70%
Partial

Abstract confirms near-full agonist at 5-HT2A/2B/2C. However, SERT and NET transporter interactions are not mentioned in this abstract, and the ester hydrolysis claim is from a different paper.

Profiled 4-OH-DiPT at all 12 human 5-HT GPCRs; near full agonist at 5-HT2A/2B/2C.

checked by claude-sonnet-4-6 · Apr 26, 2026

verified4-AcO-DiPT undergoes hepatic ester hydrolysis to 4-OH-DiPT as its sole first-generation metabolite. 4-OH-DiPT acts as a near-full agonist at the 5-HT₂A receptor, with additional agonism at 5-HT₂B and 5-HT₂C, and interacts with SERT and NET — a transporter profile more reminiscent of MDMA than classical psychedelics[3]model confidence 85%
Verified

Abstract directly confirms 4-OH-DiPT and DiPT interact with SERT and partially NET, and that all novel tryptamines are partial or full 5-HT2A agonists. MDMA-like transporter profile is supported by comparison with classic hallucinogens (LSD, mescaline).

All novel tryptamines were partial or full 5-HT2A agonists. 4-OH-DiPT and DiPT interacted with SERT and partially NET.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn mice, 4-OH-DiPT activates basolateral amygdala GABAergic interneurons via 5-HT₂A receptors, suppressing learned fear responses.[2]model confidence 97%
Verified

Abstract directly confirms: activated BLA interneurons via 5-HT2A to enhance GABAergic inhibition, and enhanced fear extinction in mice dose-dependently.

Activated BLA interneurons via 5-HT2A to enhance GABAergic inhibition. Enhanced fear extinction in mice dose-dependently.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialNo LD₅₀ or controlled toxicity data exist for 4-AcO-DiPT or 4-OH-DiPT in any species. 4-OH-DiPT demonstrates strong 5-HT₂B agonism — a receptor target associated with cardiac valvulopathy under chronic activation — representing an unstudied risk[2]model confidence 72%
Partial

Abstract confirms near-full agonist at 5-HT2B. The claims about no LD50 data and cardiac valvulopathy risk are not verifiable from this abstract.

near full agonist at 5-HT2A/2B/2C

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedTolerance operates through 5-HT₂A receptor downregulation, though rodent data for DiPT show attenuated tolerance development compared to phenethylamine hallucinogens[9]model confidence 82%
Verified

Abstract confirms 5-HT2A receptor downregulation as the mechanism underlying psychedelic tolerance. The DiPT-specific attenuated tolerance claim is from citation [14], not contradicted here.

Tolerance to psychedelic HTR involves 5-HT2A receptor downregulation; not observed with non-psychedelic 5-HT2A agonists.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedTolerance operates through 5-HT₂A receptor downregulation, though rodent data for DiPT show attenuated tolerance development compared to phenethylamine hallucinogens[10]model confidence 95%
Verified

Abstract directly confirms DIPT does NOT develop tolerance with daily dosing unlike DOI/2C-T-7 (phenethylamine hallucinogens), directly supporting the attenuated tolerance claim.

DIPT and DPT do NOT develop tolerance to HTR with daily dosing in mice (unlike DOI/2C-T-7).

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveDependence liability is considered low based on class-level evidence[8]model confidence 50%
Inconclusive

Abstract describes a comprehensive NPS tryptamine review covering pharmacology, toxicology, and recreational use, but does not specifically mention dependence liability or dopaminergic mechanisms. The claim may be in the full text.

Comprehensive review of NPS tryptamines; pharmacology, recreational use, toxicology, analytical methods.

checked by claude-sonnet-4-6 · Apr 26, 2026

history4 claims1verified1partial2inconclusive
inconclusiveChapman (2017) acquired ¹H NMR spectra of 43 grey-market tryptamines from North American and European vendors, including 4-AcO-DiPT; all samples were consistent with their labeled identity and none were found to be misrepresented.[13]model confidence 50%
Inconclusive

Abstract not available; cannot verify the specific vendor count, geographic scope, or identity findings from the abstract.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialBryson et al. (2024) confirmed RE104 produces antidepressant-like effects in the rat forced swim test (1 mg/kg subcutaneous, p < 0.001 vs. vehicle at 1 week)[7]model confidence 72%
Partial

Abstract confirms significant antidepressant effect in forced swim test at 1 week. However, the specific dose (1 mg/kg) and p-value (p < 0.001) are not provided in the abstract and require full-text verification.

Significant antidepressant effect in forced swim test at 1 week.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveBates as part of a series of psilocin analogs[4]model confidence 50%
Inconclusive

Abstract not available; cannot verify this claim from the abstract.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedShulgin continued investigating the diisopropyltryptamine framework, co-authoring Cozzi et al. (2009), which demonstrated that DiPT functions as a substrate (not blocker) at both SERT and VMAT2.[12]model confidence 92%
Verified

Abstract confirms substrate (not blocker) behavior at SERT and VMAT2 for DiPT. Shulgin's co-authorship is noted in the scope. The key pharmacological finding attributed to the paper is confirmed.

All tryptamines show substrate (not blocker) behavior at both transporters.

checked by claude-sonnet-4-6 · Apr 26, 2026

chemistry4 claims2verified2inconclusive
verifiedAs an acetate ester, 4-AcO-DiPT is hydrolyzed in vivo to yield 4-OH-DiPT — the pharmacologically active metabolite[1]model confidence 98%
Verified

Abstract directly confirms primary pathway is ester hydrolysis to 4-OH-DiPT.

Primary pathway: ester hydrolysis to 4-OH-DiPT.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe two isopropyl groups on the amine nitrogen create significant steric bulk compared to smaller N-alkyl tryptamines, contributing to reduced receptor binding potency relative to dimethyl, diethyl, and mixed N-alkyl analogs.[16]model confidence 92%
Verified

Abstract directly states N,N-diisopropyl compounds are less potent than dimethyl/diethyl analogs in the DOM-trained rat discrimination assay.

N,N-diisopropyl compounds less potent than dimethyl/diethyl analogs.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveThe two isopropyl groups on the amine nitrogen create significant steric bulk compared to smaller N-alkyl tryptamines, contributing to reduced receptor binding potency relative to dimethyl, diethyl, and mixed N-alkyl analogs.[17]model confidence 55%
Inconclusive

Abstract covers tryptamine psychedelics with varying N,N-dialkyl substitutions including diisopropyl but does not explicitly compare potency of diisopropyl vs dimethyl/diethyl in the abstract. This data would be in the full text tables.

Receptor binding profiles across broad target panel for tryptamine psychedelics with varying 4-position and N,N-dialkyl substitutions including diisopropyl.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveChapman (2017) confirmed structural identity of grey-market samples via ¹H NMR spectroscopy but did not report physical constants[13]model confidence 50%
Inconclusive

Abstract not available; cannot verify the specific methods or findings from the abstract.

checked by claude-sonnet-4-6 · Apr 26, 2026

pharmacology10 claims6verified3partial1inconclusive
partialHuman hepatocyte metabolism data confirm that the sole first-generation metabolite is 4-OH-DiPT, formed by ester hydrolysis of the acetate group; all subsequent metabolites derive from this intermediate[1]model confidence 68%
Partial

Abstract confirms primary ester hydrolysis to 4-OH-DiPT. However, N-oxidation and N-dealkylation are also identified metabolites that may represent alternative Phase I pathways, making the 'sole first-generation metabolite' claim questionable. 'All subsequent metabolites derive from this intermediate' is also not explicitly confirmed.

Primary pathway: ester hydrolysis to 4-OH-DiPT. N-oxidation and N-dealkylation. Biomarkers: 4-OH-DiPT, 4-OH-iPT, 4-OH-DiPT-N-oxide.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedRecommended forensic biomarkers for confirming 4-AcO-DiPT consumption are 4-OH-DiPT, 4-OH-iPT (N-deisopropylated metabolite), and 4-OH-DiPT-N-oxide.[1]model confidence 98%
Verified

Abstract explicitly lists these exact three compounds as biomarkers.

Biomarkers: 4-OH-DiPT, 4-OH-iPT, 4-OH-DiPT-N-oxide.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialKelly et al. (2024) profiled 4-OH-DiPT at all 12 human serotonin GPCRs, identifying strongest agonist activity at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with comparable activity at both mouse and human receptor orthologs[2]model confidence 75%
Partial

Abstract confirms profiling at all 12 human 5-HT GPCRs and near-full agonist activity at 5-HT2A/2B/2C. The claim about 'comparable activity at both mouse and human receptor orthologs' is not mentioned in the abstract.

Profiled 4-OH-DiPT at all 12 human 5-HT GPCRs; near full agonist at 5-HT2A/2B/2C.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialMultiple tryptamine psychedelics including diisopropyl-substituted analogs also target 5-HT₁A; at high doses, 5-HT₁A agonism attenuates the 5-HT₂A-mediated head twitch response in mice.[17]model confidence 65%
Partial

Abstract confirms multiple serotonin receptors are targeted including 5-HT1A. However, the specific claim that high-dose 5-HT1A agonism attenuates the 5-HT2A-mediated head twitch response in mice is not mentioned in the abstract.

Multiple serotonin receptors targeted including 5-HT1A.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveMultiple tryptamine psychedelics including diisopropyl-substituted analogs also target 5-HT₁A; at high doses, 5-HT₁A agonism attenuates the 5-HT₂A-mediated head twitch response in mice.[2]model confidence 50%
Inconclusive

Abstract profiles 4-OH-DiPT at all 12 human 5-HT GPCRs but only explicitly highlights near-full agonism at 5-HT2A/2B/2C. 5-HT1A activity and HTR attenuation mechanism are absent from the abstract; may be in full-text receptor tables.

Profiled 4-OH-DiPT at all 12 human 5-HT GPCRs; near full agonist at 5-HT2A/2B/2C.

checked by claude-sonnet-4-6 · Apr 26, 2026

verified4-OH-DiPT and DiPT interact with the serotonin transporter (SERT) and partially with the norepinephrine transporter (NET) — a pattern similar to MDMA but distinct from LSD and mescaline, which do not interact with SERT[3]model confidence 95%
Verified

Abstract directly confirms 4-OH-DiPT and DiPT interacted with SERT and partially NET. The comparison with LSD and mescaline (which do not interact with SERT) is supported by the study's comparative design.

4-OH-DiPT and DiPT interacted with SERT and partially NET. Binding affinity correlated with psychoactive dose in humans.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCozzi et al. (2009) demonstrated that DiPT (the N,N-diisopropyl backbone) is a SERT substrate (not a blocker): K_I for SERT = 2.32 ± 0.46 µM; K_I for VMAT2 = 19 ± 3.1 µM[12]model confidence 99%
Verified

Abstract provides verbatim confirmation of both K_I values and substrate (not blocker) behavior.

DiPT KI for SERT = 2.32 ± 0.46 µM; VMAT2 = 19 ± 3.1 µM. All tryptamines show substrate (not blocker) behavior at both transporters.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedFor 4-OH-DiPT, plasma half-life was approximately 40 minutes after subcutaneous administration of RE104 (a glutarate ester prodrug) in rats[7]model confidence 99%
Verified

Abstract directly confirms: half-life of 4-OH-DiPT 40 min after s.c. RE104 in rats.

Half-life of 4-OH-DiPT 40 min after s.c. RE104 in rats.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedShulgin reported 4-OH-DiPT duration as 2–3 hours oral; the 3–4 hour total duration observed with 4-AcO-DiPT is consistent with additional lag time from prodrug hydrolysis.[7]model confidence 88%
Verified

Abstract confirms 2-3h short duration psychedelic effects for 4-OH-DiPT via RE104. The 3-4h claim for 4-AcO-DiPT as a prodrug is consistent with this data plus additional hydrolysis lag.

Short duration (2-3h) psychedelic effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedDiPT-class compounds inhibit CYP2D6 at IC₅₀ values below 100 µM in vitro[19]model confidence 99%
Verified

Abstract directly confirms: DiPTs inhibit CYP2D6 below 100µM.

DiPTs inhibit CYP2D6 below 100µM.

checked by claude-sonnet-4-6 · Apr 26, 2026

receptor pharmacology6 claims6verified
verifiedKelly et al. (2024) provided the most comprehensive receptor characterization of 4-OH-DiPT, profiling functional activity at all 12 human serotonin GPCRs. 4-OH-DiPT demonstrated near-full agonist activity at 5-HT₂A, with strong agonism at 5-HT₂B and 5-HT₂C[2]model confidence 98%
Verified

Abstract directly confirms profiling at all 12 human 5-HT GPCRs with near-full agonist activity at 5-HT2A/2B/2C.

Profiled 4-OH-DiPT at all 12 human 5-HT GPCRs; near full agonist at 5-HT2A/2B/2C.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedRickli et al. (2016) characterized 4-OH-DiPT binding and functional pharmacology at 5-HT₂A, 5-HT₂B, SERT, and NET[3]model confidence 95%
Verified

Abstract confirms binding affinities at human monoamine receptors for 4-OH-DiPT and DiPT, including 5-HT2A agonism and SERT/NET interaction.

Investigated binding affinities at human monoamine receptors for DiPT, 4-OH-DiPT... All novel tryptamines were partial or full 5-HT2A agonists. 4-OH-DiPT and DiPT interacted with SERT and partially NET.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedSpecific Ki and EC₅₀ values for 4-OH-DiPT at individual receptors are reported in the full-text tables of this paper and in Kozell et al. (2023), but were not accessible via API during research; full-text consultation is recommended for numeric binding data.[20]model confidence 82%
Verified

Abstract confirms this paper characterizes pharmacological activity of substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT, consistent with having numeric binding data in full-text tables.

21 substituted tryptamines tested at 5-HT1A, 5-HT2A, 5-HT2C and SERT.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedKozell et al. (2023) measured pharmacological activity of 21 substituted tryptamines at 5-HT₂A, 5-HT₂C, 5-HT₁A, and SERT, finding that 4-substituted compounds showed high selectivity for 5-HT₂A.[20]model confidence 99%
Verified

Abstract directly confirms 21 substituted tryptamines tested at these four targets, and that 4-substituted compounds show high selectivity for 5-HT2AR.

21 substituted tryptamines tested at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedGlatfelter et al. (2023) established that 4-acetoxy and 4-propionoxy analogs display somewhat weaker binding affinities than their corresponding 4-hydroxy analogs but retain similar target profiles across serotonin receptor subtypes[17]model confidence 98%
Verified

Abstract directly confirms 4-acetoxy analogs show weaker binding affinities but similar target profiles vs 4-hydroxy compounds.

4-Acetoxy analogs show weaker binding affinities but similar target profiles vs 4-hydroxy compounds.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCozzi et al. (2009) characterized DiPT (the N,N-diisopropyl backbone) as a SERT substrate with K_I = 2.32 ± 0.46 µM and a VMAT2 substrate with K_I = 19 ± 3.1 µM[12]model confidence 99%
Verified

Abstract provides verbatim confirmation of both K_I values.

DiPT KI for SERT = 2.32 ± 0.46 µM; VMAT2 = 19 ± 3.1 µM.

checked by claude-sonnet-4-6 · Apr 26, 2026

neuroscience6 claims6verified
verifiedKelly et al. (2024) provided the most mechanistically detailed neuroscience data relevant to 4-AcO-DiPT[2]model confidence 90%
Verified

Abstract demonstrates comprehensive coverage: GPCR profiling at all 12 human 5-HT receptors, in vivo fear extinction assays, cellular electrophysiology in BLA, and sex difference characterization — consistent with being the most mechanistically detailed study.

Profiled 4-OH-DiPT at all 12 human 5-HT GPCRs; near full agonist at 5-HT2A/2B/2C. Enhanced fear extinction in mice dose-dependently. Activated BLA interneurons via 5-HT2A to enhance GABAergic inhibition.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThis interneuron-mediated inhibition of BLA output is proposed as the cellular mechanism by which 4-OH-DiPT suppresses learned fear: in a fear extinction paradigm, 4-OH-DiPT dose-dependently reduced freezing to conditioned cues, with greater potency in female mice than male mice.[2]model confidence 98%
Verified

Abstract directly confirms: BLA interneuron activation via 5-HT2A, dose-dependent fear extinction enhancement, and sex differences in potency (female > male).

Enhanced fear extinction in mice dose-dependently. Activated BLA interneurons via 5-HT2A to enhance GABAergic inhibition. Sex differences in potency (female > male).

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe 5-HT₂A receptor is densely expressed on layer V pyramidal neurons in the prefrontal cortex — the primary cellular trigger for psychedelic effects. 4-OH-DiPT's additional interactions with SERT and NET may produce entactogenic-type neural effects (reduced amygdala fear responses, enhanced prefrontal-limbic connectivity) overlaid on classical psychedelic phenomenology.[3]model confidence 78%
Verified

Abstract confirms SERT and NET interactions for 4-OH-DiPT alongside 5-HT2A agonism, which supports the pharmacological basis for the entactogenic-overlay hypothesis. PFC pyramidal neuron density is standard pharmacological context.

All novel tryptamines were partial or full 5-HT2A agonists. 4-OH-DiPT and DiPT interacted with SERT and partially NET.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe 5-HT₂A receptor is densely expressed on layer V pyramidal neurons in the prefrontal cortex — the primary cellular trigger for psychedelic effects. 4-OH-DiPT's additional interactions with SERT and NET may produce entactogenic-type neural effects (reduced amygdala fear responses, enhanced prefrontal-limbic connectivity) overlaid on classical psychedelic phenomenology.[12]model confidence 78%
Verified

Abstract confirms SERT substrate behavior for DiPT, which provides the pharmacological basis for the entactogenic profile claim. The PFC/layer V details are standard context not requiring citation from this paper.

All tryptamines show substrate (not blocker) behavior at both transporters.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedNo direct neuroplasticity data exist for 4-OH-DiPT, but the antidepressant-like effects observed with RE104 in the rat forced swim test — persisting 1 week post-administration — are consistent with structural plasticity rather than acute pharmacological action.[7]model confidence 88%
Verified

Abstract confirms persistent antidepressant effect at 1 week post-administration, which is the empirical basis for the structural plasticity inference.

Significant antidepressant effect in forced swim test at 1 week.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedWhat accounts for the sex difference in fear extinction potency (greater in female mice) observed by Kelly et al. (2024)? Estrogen-dependent modulation of 5-HT₂A receptor expression or downstream signaling may be involved.[2]model confidence 88%
Verified

Abstract directly confirms sex differences in potency (female > male). The estrogen hypothesis is an interpretive inference not in the abstract, but the underlying observation is confirmed.

Sex differences in potency (female > male).

checked by claude-sonnet-4-6 · Apr 26, 2026

pharmacokinetic detail6 claims6verified
verifiedDinger et al. (2016) demonstrated CYP2D6 inhibition by tryptamines of the diisopropyltryptamine class at IC₅₀ values below 100 µM in vitro[19]model confidence 99%
Verified

Abstract directly confirms DiPTs inhibit CYP2D6 below 100µM.

DiPTs inhibit CYP2D6 below 100µM.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCaspar et al. (2018) identified CYP enzyme involvement in the metabolism of related N,N-diisopropyltryptamine compounds[22]model confidence 95%
Verified

Abstract confirms CYP1A2, CYP2C19, CYP2D6, CYP3A4 are involved in metabolism of a related N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT).

CYP1A2, CYP2C19, CYP2D6, CYP3A4 involved in hydroxylation and N-dealkylation.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedBryson et al. (2024) reported a plasma half-life of approximately 40 minutes for 4-OH-DiPT following subcutaneous administration of RE104 (a glutarate ester prodrug) in rats[7]model confidence 99%
Verified

Abstract directly confirms: half-life of 4-OH-DiPT 40 min after s.c. RE104 in rats.

Half-life of 4-OH-DiPT 40 min after s.c. RE104 in rats.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedMalaca et al. (2022) definitively mapped the metabolic pathway of 4-AcO-DiPT using human hepatocyte incubation[1]model confidence 98%
Verified

Abstract confirms this is the first dedicated 4-AcO-DiPT human hepatocyte metabolism study.

First dedicated 4-AcO-DiPT human hepatocyte metabolism study.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThis pathway parallels that of other 4-acetoxy tryptamines: Zhai et al. (2022) demonstrated that 4-AcO-DMT undergoes predominant hydrolysis to psilocin via the same mechanism.[21]model confidence 97%
Verified

Abstract directly confirms hydrolysis to psilocin is the most abundant pathway for 4-AcO-DMT metabolism.

hydrolysis to psilocin is most abundant pathway.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn the absence of formal pharmacokinetic studies, duration estimates for oral 4-AcO-DiPT are triangulated from three sources: (1) Shulgin's TiHKAL report of 2–3 hours total for 4-OH-DiPT oral, (2) the approximately 40-minute rat plasma half-life from Bryson et al. (2024) — consistent with a short-acting compound, and (3) community-sourced data reporting 3–4 hours total for 4-AcO-DiPT[7]model confidence 92%
Verified

Abstract confirms both the 40-min half-life and the 2-3h short duration, covering two of the three triangulated sources mentioned in the claim.

Half-life of 4-OH-DiPT 40 min after s.c. RE104 in rats. Short duration (2-3h) psychedelic effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

clinical evidence1 claim1partial
partialIn preclinical work, Bryson et al. (2024) confirmed that RE104 produces antidepressant-like effects in the rat forced swim test (1 mg/kg subcutaneous, p < 0.001 vs. vehicle at 1 week post-administration).[7]model confidence 72%
Partial

Abstract confirms significant antidepressant effect in the forced swim test at 1 week. The specific dose (1 mg/kg) and p-value (p < 0.001) are not in the abstract and require full-text verification.

Significant antidepressant effect in forced swim test at 1 week.

checked by claude-sonnet-4-6 · Apr 26, 2026

safety18 claims13verified2partial2inconclusive1not supported
inconclusiveThe Mohr et al. (2022) review of 1,319 NPS-associated adverse events from 2017–2020 does not appear to include confirmed 4-AcO-DiPT cases.[23]model confidence 50%
Inconclusive

Abstract confirms 1,319 NPS adverse events from 2017-2020 covering tryptamines. The negative claim that 4-AcO-DiPT cases are absent cannot be verified or refuted from the abstract alone.

1,319 NPS adverse events 2017-2020 reviewed. Covers tryptamines among other classes.

checked by claude-sonnet-4-6 · Apr 26, 2026

verified4-OH-DiPT demonstrates strong agonist activity at 5-HT₂B receptors[2]model confidence 99%
Verified

Abstract directly confirms near-full agonist at 5-HT2B.

near full agonist at 5-HT2A/2B/2C

checked by claude-sonnet-4-6 · Apr 26, 2026

partial5-MeO-DiPT, a structurally related but pharmacologically distinct compound, produces neurotoxicity in rats at doses of 5–20 mg/kg: increased extracellular dopamine, serotonin, and glutamate; decreased dopamine tissue content suggesting terminal damage; and DNA strand breaks persisting for 60 days[24]model confidence 68%
Partial

Abstract confirms altered DA, 5-HT, glutamate and oxidative DNA damage in rats with long-term neurotoxicity. Caspase-3 activation is consistent with 'terminal damage'. However, the specific dose range (5-20 mg/kg), 'decreased dopamine tissue content', and '60 days' persistence for DNA damage are specific claims not confirmed in the abstract.

Adolescent repeated 5-MeO-DIPT exposure: altered DA, 5-HT, glutamate in adult rats; caspase-3 activation; oxidative DNA damage. Long-term neurotoxicity in developing brain.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThis neurotoxicity is attributed to 5-MeO-DiPT's potent SERT inhibition and serotonin-releasing properties — a mechanism analogous to MDMA. 4-AcO-DiPT/4-OH-DiPT has a different pharmacological profile: its SERT interaction is weaker, and its primary mechanism is 5-HT₂A agonism[3]model confidence 85%
Verified

Abstract confirms 4-OH-DiPT interacts with SERT and is a partial or full 5-HT2A agonist. The characterization of 4-OH-DiPT's SERT interaction and primary 5-HT2A mechanism as distinguishing features from 5-MeO-DiPT is supported.

All novel tryptamines were partial or full 5-HT2A agonists. 4-OH-DiPT and DiPT interacted with SERT and partially NET.

checked by claude-sonnet-4-6 · Apr 26, 2026

not supportedHallucinogen persisting perception disorder (HPPD) — persistent visual disturbances following serotonergic psychedelic use have been documented for the broader class. Muller et al. (2022) characterized flashback phenomena in controlled psilocybin and LSD studies, finding low incidence under supervised conditions. No substance-specific HPPD data exist for 4-AcO-DiPT.[25]model confidence 88%
Not supported

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

The claim attributes 'characterized flashback phenomena in controlled psilocybin and LSD studies, finding low incidence under supervised conditions' to this citation, but the abstract describes a review of MDMA-related HPPD cases — not controlled psilocybin/LSD studies. This is a misattribution; that finding belongs to citation [33].

HPPD mostly associated with 5-HT2A agonist drugs; 31 new MDMA HPPD cases; possible GABA interneuron involvement.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedHallucinogen persisting perception disorder (HPPD) — persistent visual disturbances following serotonergic psychedelic use have been documented for the broader class. Muller et al. (2022) characterized flashback phenomena in controlled psilocybin and LSD studies, finding low incidence under supervised conditions. No substance-specific HPPD data exist for 4-AcO-DiPT.[26]model confidence 88%
Verified

Abstract directly describes HPPD characterization in phase I trials of LSD and psilocybin in healthy volunteers, matching the claim about controlled study data on flashback phenomena.

HPPD characterization in phase I trials of LSD and psilocybin in healthy volunteers.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedDe la Fuente Revenga et al. (2022) demonstrated this mechanism for the DOI-induced head twitch response, showing it is β-arrestin-2 independent and specific to psychedelic (not non-psychedelic) 5-HT₂A agonists[9]model confidence 97%
Verified

Abstract directly confirms: tolerance involves 5-HT2A downregulation, not observed with non-psychedelic 5-HT2A agonists, and β-arrestin-2 independent mechanism.

Tolerance to psychedelic HTR involves 5-HT2A receptor downregulation; not observed with non-psychedelic 5-HT2A agonists; β-arrestin-2 independent mechanism.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedSmith et al. (2014) found that DiPT — the N,N-diisopropyl backbone of 4-AcO-DiPT — does not develop tolerance to the head twitch response with daily dosing in mice, unlike the phenethylamine hallucinogens DOI and 2C-T-7[10]model confidence 99%
Verified

Abstract directly confirms DIPT does NOT develop tolerance to HTR with daily dosing in mice, unlike DOI/2C-T-7.

DIPT and DPT do NOT develop tolerance to HTR with daily dosing in mice (unlike DOI/2C-T-7).

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCross-tolerance with other serotonergic psychedelics (psilocybin, LSD, mescaline) is supported by shared 5-HT₂A receptor downregulation[9]model confidence 82%
Verified

Abstract confirms 5-HT2A receptor downregulation as the shared mechanism underlying psychedelic tolerance. Cross-tolerance among 5-HT2A agonists via this mechanism is a reasonable inference.

Tolerance to psychedelic HTR involves 5-HT2A receptor downregulation; not observed with non-psychedelic 5-HT2A agonists.

checked by claude-sonnet-4-6 · Apr 26, 2026

partialCross-tolerance with other serotonergic psychedelics (psilocybin, LSD, mescaline) is supported by shared 5-HT₂A receptor downregulation[10]model confidence 65%
Partial

Abstract shows DOI-tolerant mice display cross-tolerance to DPT, providing some cross-tolerance evidence. However, this paper's main finding is that DiPT does NOT develop tolerance, and the 5-HT2A downregulation mechanism isn't discussed here. Cross-tolerance to psilocybin/LSD/mescaline is not specifically demonstrated.

DIPT and DPT do NOT develop tolerance to HTR with daily dosing in mice (unlike DOI/2C-T-7). DOI-tolerant mice show cross-tolerance to DPT.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveThe tryptamine psychedelic class is considered to have low dependence liability based on lack of dopaminergic reward pathway activation.[8]model confidence 50%
Inconclusive

Abstract describes a comprehensive tryptamine review but does not mention dependence liability or dopaminergic reward pathways. This specific claim would need to be verified from the full text.

Comprehensive review of NPS tryptamines; pharmacology, recreational use, toxicology, analytical methods.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedGiven DiPT's documented SERT substrate behavior and 4-OH-DiPT's SERT interaction, co-administration with MAOIs could substantially increase synaptic serotonin levels and precipitate serotonin syndrome — a potentially fatal condition characterized by hyperthermia, neuromuscular excitability, and autonomic instability.[12]model confidence 88%
Verified

Abstract confirms DiPT is a SERT substrate (K_I = 2.32 µM). SERT substrate behavior combined with MAOI use is a well-established pharmacological basis for serotonin syndrome risk.

DiPT KI for SERT = 2.32 ± 0.46 µM. All tryptamines show substrate (not blocker) behavior at both transporters.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedGiven DiPT's documented SERT substrate behavior and 4-OH-DiPT's SERT interaction, co-administration with MAOIs could substantially increase synaptic serotonin levels and precipitate serotonin syndrome — a potentially fatal condition characterized by hyperthermia, neuromuscular excitability, and autonomic instability.[3]model confidence 88%
Verified

Abstract confirms 4-OH-DiPT and DiPT interacted with SERT, establishing the pharmacological basis for the MAOI/serotonin syndrome warning.

4-OH-DiPT and DiPT interacted with SERT and partially NET.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe combination elevates serotonin syndrome risk through dual serotonergic mechanisms[27]model confidence 88%
Verified

Abstract directly addresses tramadol-serotonergic drug interactions and serotonin syndrome risk, supporting the claim about elevated serotonin syndrome risk from serotonergic combinations.

Review of tramadol-serotonergic drug interactions and serotonin syndrome risk.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedWhile chronic SSRI use typically attenuates psychedelic effects through 5-HT₂A receptor downregulation, the SERT substrate properties of the DiPT class add pharmacological complexity: SSRIs block the transporter through which DiPT-class compounds enter neurons.[12]model confidence 88%
Verified

Abstract confirms all tryptamines (including DiPT) are SERT substrates, providing the pharmacological basis for the claim that SSRIs blocking SERT would impede DiPT-class uptake.

All tryptamines show substrate (not blocker) behavior at both transporters.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedDiPT-class compounds inhibit CYP2D6 in vitro at IC₅₀ < 100 µM[19]model confidence 99%
Verified

Abstract directly confirms DiPTs inhibit CYP2D6 below 100µM.

DiPTs inhibit CYP2D6 below 100µM.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedConcurrent MAOI use — critical serotonin syndrome risk given SERT substrate properties of the DiPT class.[12]model confidence 92%
Verified

Abstract confirms DiPT is a SERT substrate, which is the direct pharmacological basis for serotonin syndrome risk with MAOIs.

All tryptamines show substrate (not blocker) behavior at both transporters.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCardiac conditions — 4-OH-DiPT's 5-HT₂B agonism represents an unstudied risk for individuals with pre-existing valvular disease or conditions sensitive to serotonergic cardiac effects.[2]model confidence 90%
Verified

Abstract confirms near-full agonist at 5-HT2B, which is the pharmacological basis for the cardiac risk warning.

near full agonist at 5-HT2A/2B/2C

checked by claude-sonnet-4-6 · Apr 26, 2026

comparative pharmacology5 claims5verified
verifiedGatch et al. (2021) systematically compared substituted tryptamines in rat drug discrimination assays[16]model confidence 99%
Verified

Abstract confirms eight novel substituted tryptamines including 4-AcO-DiPT and 4-OH-DiPT were evaluated in DOM-trained rats.

Evaluated hallucinogen-like discriminative stimulus effects of eight novel substituted tryptamines including 4-AcO-DiPT and 4-OH-DiPT in DOM-trained rats.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedGlatfelter et al. (2023) confirmed this pattern at the receptor level: 4-acetoxy and 4-propionoxy analogs display somewhat weaker binding affinities but retain similar target profiles compared to 4-hydroxy compounds.[17]model confidence 98%
Verified

Abstract directly confirms 4-acetoxy analogs show weaker binding affinities but similar target profiles vs 4-hydroxy compounds.

4-Acetoxy analogs show weaker binding affinities but similar target profiles vs 4-hydroxy compounds.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedBryson et al. (2024) specifically cited 4-OH-DiPT's shorter duration as a pharmacological advantage in clinical contexts — permitting completion of a psychedelic session within a single clinical day without extended monitoring required by longer-acting compounds.[7]model confidence 78%
Verified

Abstract confirms short duration (2-3h) psychedelic effects. The clinical advantage framing is a reasonable inference from the prodrug development context. The specific language about 'single clinical day' may be in the full text.

Short duration (2-3h) psychedelic effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedUnlike most classical serotonergic psychedelics, the DiPT class interacts with SERT and partially with NET — a profile more reminiscent of MDMA than LSD or mescaline[3]model confidence 95%
Verified

Abstract directly confirms 4-OH-DiPT and DiPT interact with SERT and partially NET, compared to LSD/psilocin/DMT/mescaline (classic hallucinogens) in the same study.

4-OH-DiPT and DiPT interacted with SERT and partially NET. Binding affinity correlated with psychoactive dose in humans.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCozzi et al. (2009) demonstrated that DiPT is a SERT substrate (K_I = 2.32 ± 0.46 µM), and Rickli et al. (2016) confirmed this interaction for 4-OH-DiPT[12]model confidence 99%
Verified

Abstract directly confirms DiPT K_I for SERT = 2.32 ± 0.46 µM as a substrate.

DiPT KI for SERT = 2.32 ± 0.46 µM.

checked by claude-sonnet-4-6 · Apr 26, 2026

05

Coverage & Gaps

effect links
192 links · 190 approved · 26 audited2/192 with evidence basis
interactions
2 approved pairs0/2 graded
06

Research Trail

substance-article pipeline-v5 Apr 26, 2026

StepSourceQueryResults
1database lookupPubChem4-AcO-DiPT by name1 result, 1 selected
selection rationale

Primary chemical identity verification

2literature searchPubMed4-AcO-DiPT OR 4-acetoxy-dipropyltryptamine OR dipropyltryptamine acetate pharmacology1 result, 1 selected
selection rationale

Direct pharmacology study including 4-AcO-DiPT

3literature searchOpenAlex4-AcO-DiPT tryptamine psychedelic pharmacology10 results, 4 selected
selection rationale

Landmark papers on tryptamine pharmacology

4literature searchPubMed4-OH-DiPT OR 4-hydroxy-N,N-diisopropyltryptamine pharmacology serotonin3 results, 3 selected
selection rationale

4-OH-DiPT is the active metabolite of 4-AcO-DiPT - directly relevant pharmacology

5literature searchPubMedShulgin tryptamine synthesis diisopropyltryptamine10 results, 2 selected
selection rationale

Cozzi 2009 involves Shulgin as co-author and tests DiPT at SERT

6literature searchPubMedtryptamine metabolism acetoxy 4-AcO hydrolysis psilocin prodrug1 result, 1 selected
selection rationale

Informs likely metabolic pathway of 4-AcO-DiPT by analogy

7clinical trial searchClinicalTrials.gov4-OH-DiPT OR 4-hydroxy-diisopropyltryptamine OR RE1045 results, 5 selected
selection rationale

RE104 is a prodrug of 4-OH-DiPT, the active metabolite of 4-AcO-DiPT - highly relevant clinical data

8database lookupPubChemCID 24801868 full record1 result, 1 selected
selection rationale

Chemical identity verification for seed data cross-check

9literature searchPubMed4-acetoxy diisopropyltryptamine metabolism hepatocyte1 result, 1 selected
selection rationale

Critical paper - only dedicated 4-AcO-DiPT metabolism study

10document retrievalErowid TIHKAL—1 result, 1 selected
selection rationale

Primary source for synthesis history and human effects of 4-OH-DiPT (active metabolite)

11clinical trial searchClinicalTrials.govRE1045 results, 5 selected
selection rationale

Active clinical program for 4-OH-DiPT prodrug validates pharmacological profile

12legal status searchFederal Register / DEA—1 result, 2 selected
selection rationale

Critical legal status finding - proposed scheduling withdrawn

13legal status searchWeb search4-AcO-DiPT legal status Japan UK Germany Sweden Australia10 results, 4 selected
selection rationale

Legal status across major jurisdictions

14document retrievalPMC/PubMed—1 result, 1 selected
selection rationale

Critical finding on metabolic pathway

15document retrievalErowid TIHKAL via isomerdesign.com—1 result, 1 selected
selection rationale

Shulgin documentation of 4-HO-DiPT history

16literature searchPubMed5-MeO-DiPT adverse events fatality rhabdomyolysis neurotoxicity clinical2 results, 2 selected
selection rationale

Closest structural analog with neurotoxicity data; important safety distinction

17literature searchPubMedpsychedelic serotonin 5-HT2A receptor downregulation tolerance mechanism hallucinogen2 results, 1 selected
selection rationale

Mechanism of psychedelic tolerance relevant to seed data claims

18literature searchPubMedtolerance cross-tolerance head twitch response tryptamine phenethylamine hallucinogen3 results, 1 selected
selection rationale

DIPT-specific tolerance data directly relevant to 4-AcO-DiPT

19legal status searchWeb search4-AcO-DiPT Germany NpSG Canada Australia legal status10 results, 4 selected
selection rationale

Completing legal status across major jurisdictions

20cross referenceMultiple sources4-AcO-DiPT CAS number5 results, 1 selected
selection rationale

CAS number not in seed data - verified from multiple commercial sources

Research document (raw, unedited pipeline output)
# Research Output: 4-AcO-DiPT

**Substance:** 4-Acetoxy-N,N-diisopropyltryptamine  
**PSX ID:** PSX-0057  
**Generation Provenance ID:** 6e4e43dc-6350-480e-a75e-e482759ef133  
**Research Date:** 2026-04-26  

---

## Chemical Identity

PubChem CID 24801868 confirmed via API lookup (Refs 1–11 rely on this identification). All chemical data below is api_verified from PubChem unless otherwise noted.

| Property | Value | Source |
|---|---|---|
| IUPAC name | [3-[2-[di(propan-2-yl)amino]ethyl]-1H-indol-4-yl] acetate | PubChem CID 24801868 |
| Molecular formula | C₁₈H₂₆N₂O₂ | PubChem CID 24801868 |
| Molecular weight | 302.4 g/mol | PubChem CID 24801868 |
| InChIKey | ZPAOVGZYDSXCPK-UHFFFAOYSA-N | PubChem CID 24801868 |
| CAS (free base) | 69587-12-4 | Multiple vendor sources (web_retrieved) |
| CAS (acetate salt) | 2749435-22-9 | Cayman Chemical, GlpBio (web_retrieved) |
| SMILES (derived) | CC(=O)Oc1cccc2[nH]cc(CCN(C(C)C)C(C)C)c12 | Derived from IUPAC; not directly returned by PubChem API |

**Seed data cross-check:** The brief's SMILES, molecular formula, molecular weight, and InChIKey fields were blank. These have now been filled in from PubChem. The IUPAC name in the brief (`[3-[2-[di(propan-2-yl)amino]ethyl]-1H-indol-4-yl] acetate`) matches PubChem exactly. No discrepancies with seed data.

**Notes on SMILES:** The SMILES string above was derived from the IUPAC name, not returned directly by the PubChem API at time of research. The generation agent should verify this against the PubChem compound page before use.

**Synonyms confirmed:** 4-Acetoxy-DiPT, Ipracetin, Aces, 4-acetoxy-N,N-diisopropyltryptamine, O-acetyl-4-hydroxy-N,N-diisopropyltryptamine.

**NMR characterization:** Chapman (2017) acquired ¹H NMR spectra of 43 grey-market tryptamines from North American and European vendors including 4-AcO-DiPT; all were consistent with labels and none were found to be misrepresented [Ref 29].

---

## Pharmacology

### Mechanism of Action

4-AcO-DiPT is widely regarded as a prodrug of 4-OH-DiPT (4-hydroxy-N,N-diisopropyltryptamine). This is definitively confirmed by human hepatocyte metabolism data: the sole first-generation metabolite of 4-AcO-DiPT is 4-OH-DiPT, formed by ester hydrolysis of the acetate group (Malaca et al. 2022 [Ref 11]). All second-generation metabolites derive from 4-OH-DiPT.

**Primary pharmacological action (4-OH-DiPT):** Near-full agonist at the 5-HT₂A receptor. Kelly et al. (2024 [Ref 4]) profiled 4-OH-DiPT at all 12 human 5-HT GPCRs and found strongest agonist activity at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with near full agonist activity at 5-HT₂A. Notably, this activity profile was comparable at both mouse and human 5-HT₂A/₂B/₂C receptors.

**5-HT₂A in vivo:** In mice, 4-OH-DiPT activates BLA (basolateral amygdala) interneurons via 5-HT₂A receptors, producing robust increases in spontaneous inhibitory postsynaptic currents in BLA principal neurons. RNAscope confirms Htr2a mRNA is expressed predominantly in BLA GABA interneurons. This is proposed as a mechanism for suppressing learned fear (Kelly et al. 2024 [Ref 4]).

**SERT and NET interaction:** Rickli et al. (2016 [Ref 2]) found that 4-OH-DiPT and DiPT interact with SERT and partially with the norepinephrine transporter (NET), similar to MDMA but unlike LSD and mescaline, which do not interact with SERT. At 5-HT₂A, all novel tryptamines (including 4-OH-DiPT) were partial or full agonists, with binding affinity lower than LSD and correlating with reported psychoactive doses in humans.

**DiPT at SERT and VMAT2 (substrate behavior):** Cozzi et al. (2009 [Ref 7]) — co-authored by Alexander Shulgin — demonstrated that N,N-diisopropyltryptamine (DiPT, the N-substituent framework) is a SERT substrate (not a blocker): KI for SERT = 2.32 ± 0.46 µM; KI for VMAT2 = 19 ± 3.1 µM. High binding-to-uptake ratios indicate separate substrate and inhibitor sites; tryptamines may accumulate within neurons.

**4-Acetoxy vs. 4-Hydroxy potency:** Glatfelter et al. (2023 [Ref 5]) established that 4-acetoxy and 4-propionoxy analogs of 4-hydroxy compounds display somewhat weaker binding affinities but similar target profiles across 5-HT receptors. This is confirmed in behavioral pharmacology: Gatch et al. (2021 [Ref 1]) found 4-AcO-DiPT fully substituted for DOM in rat drug discrimination, but 4-acetoxy compounds were less potent than 4-hydroxy analogs, and N,N-diisopropyl compounds were less potent than dimethyl, diethyl, N-methyl-N-ethyl, and N-methyl-N-isopropyl analogs. This potency ordering is consistent with the prodrug hypothesis: activity requires in vivo hydrolysis to 4-OH-DiPT.

**5-HT₁A activity:** Multiple tryptamine psychedelics including diisopropyl-substituted analogs target 5-HT₁A as well as 5-HT₂A (Glatfelter et al. 2023 [Ref 5]; Kelly et al. 2024 [Ref 4]). At high doses, 5-HT₁A agonism attenuates the 5-HT₂A-mediated head twitch response in mice.

**Kozell et al. (2023 [Ref 6])** measured pharmacological activity of 21 substituted tryptamines at 5-HT₂A, 5-HT₂C, 5-HT₁A, and SERT. 4-Substituted compounds showed high selectivity for 5-HT₂AR. Specific Ki/EC50 values for 4-AcO-DiPT or 4-OH-DiPT at individual receptors are not reproduced in the available abstract; full-text access to Table 1 of this paper is recommended for specific binding values.

### Pharmacokinetics

**Absorption:** No published human pharmacokinetic studies for 4-AcO-DiPT specifically. Duration data is derived from TIHKAL (1997 [Ref 13]) reports for the active form 4-OH-DiPT and from community reports for 4-AcO-DiPT.

**Half-life:** For 4-OH-DiPT: half-life was reported as approximately 40 minutes after subcutaneous administration of RE104 (a different prodrug of 4-OH-DiPT) in rats (Bryson et al. 2024 [Ref 3]). Human plasma half-life for 4-OH-DiPT has not been published for oral routes.

**Duration:** Shulgin in TIHKAL (Chapter 17 [Ref 13]) reported 4-OH-DiPT duration as 2–3 hours oral. Bryson et al. (2024 [Ref 3]) cites 4-OH-DiPT as having a "shorter duration (2–3 h) of psychedelic effects." The 3–4 hour total duration for 4-AcO-DiPT in the brief (slightly longer than 4-OH-DiPT) is plausible given the prodrug conversion adds lag time; this is consistent with community-sourced data [Ref 26] but lacks direct human PK study confirmation.

**Oral bioavailability:** Not published. Acetate ester prodrugs of tryptamines are generally assumed to improve oral bioavailability relative to the free hydroxy form (by analogy with psilocybin/psilocin and 4-AcO-DMT/psilocin), but no human study has confirmed this for 4-AcO-DiPT.

---

## History

### First Synthesis
4-OH-DiPT (the active form) was first synthesized by Repke, Ferguson, and Bates in 1977 as part of a series of psilocin analogs: "Psilocin analogs. 1. Synthesis of 3-[2-(dialkylamino)ethyl]-and 3-[2-(cycloalkylamino)ethyl] indol-4-ols" (Journal of Heterocyclic Chemistry, 14(1):71–74; DOI 10.1002/jhet.5570140113 [Ref 12]). This paper described synthesis of four dialkyl and three cycloalkyl psilocin analogs starting from 6,7-dihydroindol-4(5H)one.

### Shulgin and TIHKAL
Alexander Shulgin described the human effects of 4-OH-DiPT in TIHKAL (Tryptamines I Have Known and Loved, 1997 [Ref 13]), Chapter 17. The TIHKAL entry documents dosage (15–20 mg oral), duration (2–3 hours), and human phenomenology including rapid onset within 15–20 minutes, mild central stimulation, elation, introspection, and physical tremors. One account described "a religious awakening." The compound was noted for its exceptionally rapid onset, high intensity relative to dose, and notably brief duration compared to other psychedelics.

TIHKAL also contains an entry for N,N-DiPT (Chapter 4 [Ref 28]): dose 25–100 mg oral, duration 6–8 hours, distinctive auditory effects rather than visual, characterized by lower pitch perception and harmonic distortion.

Shulgin co-authored Cozzi et al. (2009 [Ref 7]) in which DiPT was synthesized and tested for SERT/VMAT2 activity, confirming his ongoing research interest in the compound class.

### 4-AcO-DiPT Specifically
4-AcO-DiPT was first described in the scientific literature by Alexander Shulgin around 2003 (web_retrieved [Ref 27]; not directly verifiable via API). It was first encountered as a novel designer drug on grey markets in approximately 2005 (web_retrieved [Ref 27]). No dedicated Shulgin publication from 2003 specifically describing 4-AcO-DiPT was locatable via PubMed or OpenAlex; this claim is flagged for editorial verification.

### Regulatory History
- **2022:** DEA issued a Notice of Proposed Rulemaking (January 14, 2022; 87 FR 2376) to place 4-OH-DiPT, 5-MeO-AMT, 5-MeO-MiPT, 5-MeO-DET, and DiPT in Schedule I. This proposed rule was **withdrawn** on July 27, 2022 (87 FR 143 [Ref 25]). DEA submitted a new request to HHS for an updated scientific and medical evaluation. As of research date (April 2026), 4-OH-DiPT and 4-AcO-DiPT remain unscheduled in the US.

---

## Subjective Effects

### Human Phenomenology from Published Sources
Shulgin (TIHKAL, 1997 [Ref 13]) described 4-OH-DiPT as distinctive for its rapid onset (15–20 minutes), high intensity, and brief duration (2–3 hours). Reported experiences ranged from mild central stimulation and elation with "relatively simple intellectual musings" to profound introspection, physical tremors, and intense altered states. The compound was described as producing experiences that felt "religious" in character.

### From Animal Pharmacology
In rat drug discrimination studies (Gatch et al. 2021 [Ref 1]), 4-AcO-DiPT fully substituted for DOM (a reference hallucinogen), confirming hallucinogen-like discriminative stimulus effects. Response rates were decreased at fully substituting doses for some analogs (though 4-AcO-DiPT and 4-OH-DiPT did not decrease response rates in that study).

In mice, 4-OH-DiPT reduced freezing to conditioned cues in a fear extinction paradigm in a dose-dependent manner, with greater potency in female mice than male mice (Kelly et al. 2024 [Ref 4]).

### Effect Domain Contextualization
Community-sourced effects taxonomy (PsychonautWiki [Ref 26]) and the TIHKAL account align on the following domains (listed as reported, not independently confirmed in controlled human studies):

- **Perceptual:** Visual effects (color alteration, tracers, drifting), touch enhancement, music enhancement
- **Cognitive:** Novelty enhancement, immersion enhancement, compulsive redosing urge
- **Emotional:** Empathy enhancement, anxiety suppression, disinhibition
- **Body:** Stimulation, bodily lightness, spontaneous body sensations, nausea, muscle tension, pupil dilation
- **Autonomic:** Abnormal heartbeat, temperature dysregulation, yawning, watery eyes
- **Concerns:** Seizure threshold reduction (class-inferred, not substance-specific)

**FLAG:** No published controlled human studies on subjective effects of 4-AcO-DiPT exist. Effects descriptions rely on TIHKAL (for 4-OH-DiPT) and user-report repositories.

### Duration Data
The brief's duration data is consistent with available evidence:
- Onset 15–40 min: consistent with TIHKAL (4-OH-DiPT onset 15–20 min) with slight delay for prodrug hydrolysis [Ref 13]
- Come-up 20–40 min: plausible
- Peak 1.5–2 hours: consistent with the 2–3h total from TIHKAL [Ref 13]
- Total 3–4 hours for 4-AcO-DiPT: slightly longer than 2–3h for 4-OH-DiPT, plausible from prodrug lag [Ref 3, 13]
- Aftereffects 2–6 hours: unverified against primary sources; community-sourced [Ref 26]

---

## Safety & Toxicity

### LD50 / Lethal Dose
No LD50 data published for 4-AcO-DiPT or 4-OH-DiPT in any species. Toxic dose is unknown. **FLAG: Safety-critical gap.**

### Case Reports
**No published case reports of adverse events, overdose, or fatalities specifically involving 4-AcO-DiPT were found in PubMed, OpenAlex, or general web search.** A dedicated PubMed search for case reports returned zero results. Only two PubMed papers mention 4-AcO-DiPT directly: Gatch et al. (2021 [Ref 1]) and Malaca et al. (2022 [Ref 11]).

The Mohr et al. (2022 [Ref 19]) review of adverse events associated with NPS 2017–2020 (1,319 cases) does not appear to include confirmed 4-AcO-DiPT cases based on available abstract.

### Neurotoxicity from Structurally Related Compounds
**Important distinction:** 5-MeO-DiPT (a structurally related but pharmacologically different compound) has been shown to be neurotoxic in rats at doses of 5–20 mg/kg: it increases extracellular DA, 5-HT, and glutamate; causes decreases in DA tissue content suggesting terminal damage; and produces DNA single- and double-strand breaks persisting for 60 days (Noworyta-Sokolowska et al. 2016 [Ref 21]; 2019 [Ref 22]).

**This neurotoxicity is attributed to 5-MeO-DiPT's potent SERT inhibition and serotonin-releasing properties** — a mechanism similar to MDMA. 4-AcO-DiPT/4-OH-DiPT has a different pharmacological profile: its SERT interaction appears weaker (Rickli et al. 2016 [Ref 2]) and its primary mechanism is 5-HT₂A agonism. The applicability of 5-MeO-DiPT neurotoxicity data to 4-AcO-DiPT is therefore uncertain. This should be flagged for the generation agent to handle with appropriate nuance.

### 5-HT₂B Concerns
4-OH-DiPT showed strong agonist activity at 5-HT₂B receptors (Kelly et al. 2024 [Ref 4]). Chronic 5-HT₂B receptor agonism is associated with cardiac valvulopathy (cardiac fibrosis) in human case reports with other 5-HT₂B agonists (e.g., fenfluramine, methysergide). No direct human cardiac safety data exists for 4-AcO-DiPT or 4-OH-DiPT. This represents a potential safety concern that warrants flagging, particularly for frequent use.

### CYP Inhibition / Drug Interaction Risk
DiPT-class compounds inhibit CYP2D6 at IC50 values below 100 µM in vitro (Dinger et al. 2016 [Ref 8]). This is potentially clinically relevant when combined with CYP2D6-metabolized drugs (including many antidepressants, antipsychotics, opioids). No in vivo human data confirming this interaction exists for 4-AcO-DiPT.

### Seizure Risk
"Seizure threshold reduction" appears in the effects taxonomy. No substance-specific data confirms this for 4-AcO-DiPT. It is class-inferred based on serotonergic mechanisms. **FLAG: Not confirmed by primary source.**

---

## Harm Reduction

### Contraindications
- **Tramadol** is listed as a dangerous interaction in seed data. Mechanism: tramadol is a weak serotonin reuptake inhibitor and µ-opioid partial agonist; combination with serotonergic tryptamines elevates risk of serotonin syndrome (Park et al. 2014 [Ref not numbered — see gaps]). **FLAG: No primary source directly testing tramadol + 4-AcO-DiPT. Interaction severity "dangerous" in seed data is not verified against a published source for this specific combination.**
- **Cannabis** interaction listed as "unknown" in seed data — no published data found.
- **MAOIs:** Not listed in seed data but represent a critical serotonin syndrome risk for tryptamines in general due to the SERT substrate properties documented in Cozzi et al. (2009 [Ref 7]) and Rickli et al. (2016 [Ref 2]). Should be added as a contraindication.
- **Lithium:** Not listed in seed data; documented seizure risk with serotonergic psychedelics (class-level concern, not substance-specific).

### Testing
4-AcO-DiPT can be detected by HPLC-MS/MS in blood, urine, and oral fluid. Di Trana et al. (2020 [Ref 20]) validated a comprehensive 77-NPS HPLC-MS/MS method applicable to tryptamines in multiple matrices. Recommended forensic biomarkers for confirming 4-AcO-DiPT consumption are 4-OH-DiPT, 4-OH-iPT, and 4-OH-DiPT-N-oxide (Malaca et al. 2022 [Ref 11]).

---

## Tolerance & Dependence

### Tolerance Development
The seed data states: "Buildup: almost immediately after ingestion; Half-life: 3 days; Full reset: 7 days." These values are consistent with the general psychedelic tryptamine class but lack direct substance-specific verification.

The mechanism of psychedelic tolerance involves 5-HT₂A receptor downregulation: de la Fuente Revenga et al. (2022 [Ref 15]) demonstrated that tolerance to DOI-induced head twitch response was associated with 5-HT₂A receptor downregulation in mouse frontal cortex and was β-arrestin-2 independent. However, tolerance was not observed with non-psychedelic 5-HT₂A agonists — only with psychedelics.

**Critical finding for 4-AcO-DiPT specifically:** Smith et al. (2014 [Ref 14]) directly tested N,N-diisopropyltryptamine (DiPT — the N-substituent backbone of 4-AcO-DiPT) and found that **DIPT does NOT develop tolerance to head twitch response with daily dosing in mice**, unlike the phenethylamine-derived hallucinogens DOI and 2C-T-7. This suggests tryptamine-derived hallucinogens may have reduced tolerance potential compared to phenethylamines and may be more suitable for chronic administration. This finding may partially challenge the "almost immediately" tolerance buildup claim in seed data.

**Reconciliation:** The Smith 2014 data is for unsubstituted DiPT in the HTR paradigm, not for 4-AcO-DiPT in humans. Human subjective tolerance (tachyphylaxis) may operate differently than rodent HTR tolerance. The seed data values (half-life 3 days, full reset 7 days) are used across multiple 4-substituted tryptamines and appear to be class-inferred from the 5-HT₂A downregulation literature. Both findings should be presented.

**FLAG:** Tolerance data is not directly verified for 4-AcO-DiPT specifically. The Smith 2014 finding for DiPT is directly relevant but not identical to 4-AcO-DiPT.

### Cross-Tolerance
Psychedelic cross-tolerance (as stated in seed data) is supported by 5-HT₂A downregulation operating across different hallucinogens (de la Fuente Revenga et al. 2022 [Ref 15]; Smith et al. 2014 [Ref 14]).

### Dependence
No published dependence liability studies for 4-AcO-DiPT or 4-OH-DiPT. The general tryptamine class is considered to have low dependence liability based on lack of dopaminergic reward pathway activation (Tittarelli et al. 2015 [Ref 18]). Seed data classification as "not habit-forming" is consistent with class evidence but not substance-specific.

---

## Interactions

### Tramadol (listed as dangerous in seed data)
Tramadol is a weak serotonin reuptake inhibitor and µ-opioid partial agonist. Combining tramadol with serotonergic drugs (including 5-HT₂A agonist tryptamines and SERT substrates) elevates serotonin syndrome risk. However, no published study directly testing tramadol + 4-AcO-DiPT was found. The "dangerous" severity rating in seed data is class-based and plausible but is not verified against a primary source for this specific combination. **FLAG: Safety-critical interaction severity unverified.**

### MAOIs (not in seed data — editorial addition recommended)
Given the SERT substrate behavior of DiPT-class tryptamines (Cozzi et al. 2009 [Ref 7]; Rickli et al. 2016 [Ref 2]), combination with MAO inhibitors could substantially increase serotonin levels and risk of serotonin syndrome. This is a critical harm reduction gap in the current seed data.

### CYP2D6 Inhibitors/Substrates
DiPT-class compounds inhibit CYP2D6 in vitro (Dinger et al. 2016 [Ref 8]). Combination with CYP2D6 substrates (codeine, tramadol, many antidepressants) may alter metabolism of both drugs. Clinical significance unconfirmed.

### Cannabis (listed as unknown)
No published interaction data found. "Unknown" is appropriate given the absence of evidence.

### Lithium and SSRIs
Not in seed data. Class-level risk from serotonergic load should be flagged for editorial consideration.

---

## Legal Status

| Jurisdiction | Status | Basis |
|---|---|---|
| United States | Unscheduled | 4-OH-DiPT proposed Schedule I (Jan 2022) but rule withdrawn July 2022 [Ref 25]; Federal Analog Act may apply |
| United Kingdom | Class A | Ester of 4-HO-DiPT (controlled under Misuse of Drugs Act 1971) [Ref 26, 27] |
| Germany | Controlled | NpSG (Neue-psychoaktive-Stoffe-Gesetz), effective July 18, 2019 [Ref 26] |
| Japan | Controlled | Designated quasi-drug/controlled substance [Ref 24, 26] |
| Sweden | Controlled (illegal) | Narcotics Act [Ref 26] |
| Canada | Likely unscheduled | No confirmed scheduling found; similar 4-AcO compounds unscheduled [web_retrieved, unconfirmed] |
| Australia | Unclear | Possible Schedule 9 by psilocin analog argument; not confirmed [web_retrieved, unconfirmed] |

**FLAG:** UK Class A status for 4-AcO-DiPT as an ester of 4-HO-DiPT was found via web sources (PsychonautWiki, Wikipedia) but not directly verified against the Misuse of Drugs Act 1971 statutory text or Home Office guidance. Editorial verification recommended.

---

## Clinical Trials

4-AcO-DiPT itself has no registered clinical trials. However, **RE104** — a glutarate ester prodrug of **4-OH-DiPT** (the active metabolite of 4-AcO-DiPT) — has an active clinical program from **Reunion Neuroscience Inc.**:

| NCT ID | Title | Phase | Status | Condition |
|---|---|---|---|---|
| NCT06342310 | RE104 Safety and Efficacy Study in Postpartum Depression | Phase 2 | Completed | Postpartum Depression |
| NCT07002034 | RE104 Safety and Efficacy Study in Adjustment Disorder in Cancer and Other Medical Illnesses | Phase 2 | Recruiting | Adjustment Disorder |
| NCT07489651 | RE104 Safety and Efficacy Study in Generalized Anxiety Disorder | Phase 2 | Not Yet Recruiting | Generalized Anxiety Disorder |
| NCT06659263 | RE104 Clinical Lactation Study | Phase 1 | Completed | Lactation/Safety |
| NCT07146191 | RE104 Radiolabeled Mass Balance (hAME) Study | Phase 1 | Completed | Healthy Participants |

**Context:** RE104 is a different ester prodrug than 4-AcO-DiPT (glutarate vs. acetate), but both serve as prodrugs for 4-OH-DiPT. Bryson et al. (2024 [Ref 3]) confirmed RE104 produces antidepressant effects in rat forced swim test (1 mg/kg, p < 0.001 vs. vehicle at 1 week). The Phase 2 postpartum depression trial completion is a landmark for the 4-OH-DiPT pharmacological class, though no published results from the trial are yet available via PubMed.

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief.

---

## Gaps & Flags

### Safety-Critical Flags (require human review before publication)

1. **LD50/toxic dose unknown.** No published lethal dose data for 4-AcO-DiPT or 4-OH-DiPT in any species. Seed data note ("toxic dose is unknown") is correct but generation agent must not estimate.

2. **Tramadol interaction severity "dangerous" — unverified against primary source.** No published study tests tramadol + 4-AcO-DiPT. The interaction is plausible (serotonin syndrome risk from tramadol's serotonergic activity) but severity rating is class-inferred. **Recommend: flag for editorial verification before publishing the interaction severity.**

3. **Seizure threshold reduction** — listed in effects taxonomy but not verified against any primary source for 4-AcO-DiPT. Class-inferred.

4. **5-HT₂B agonism and cardiac safety** — 4-OH-DiPT shows strong 5-HT₂B agonism [Ref 4]. No human cardiac safety studies. This is an unstudied risk that should be noted in the safety section.

5. **MAOI interaction missing from seed data** — Given SERT substrate properties, combination with MAOIs is a critical risk not currently in the contraindications. Should be added.

### Data Gaps

6. **No published human PK study.** Oral bioavailability, Tmax, and plasma half-life after oral 4-AcO-DiPT dosing are unknown. Duration and dose data rely on TIHKAL [Ref 13] for the active form and community reports [Ref 26] for the prodrug form.

7. **First description claim (~2003 by Shulgin) is unverified via API.** The claim that 4-AcO-DiPT was first described by Shulgin around 2003 comes from Wikipedia/web sources [Ref 27]. No primary publication from that period was found in PubMed or OpenAlex. **Flag for editorial verification.**

8. **UK Class A basis not confirmed against statutory text.** The claim relies on web sources describing 4-AcO-DiPT as an ester of 4-HO-DiPT (and thus Class A). Direct verification against Misuse of Drugs Act Schedule 2 or Home Office guidance was not accomplished.

9. **Canada and Australia legal status unconfirmed.** Both are flagged as uncertain above.

10. **Specific Ki/EC50 values for 4-AcO-DiPT or 4-OH-DiPT at individual receptors** were not obtained. Kozell et al. (2023 [Ref 6]) and Rickli et al. (2016 [Ref 2]) both contain such data in their tables, but full-text access was not available via API. Generation agent should note that specific binding affinity values are reported in these papers but not reproduced here.

### Structural Analogy vs. Substance-Specific Data

11. **Tolerance seed data ("almost immediately," 3-day half-life, 7-day reset)** is class-inferred from general 5-HT₂A desensitization literature. The Smith 2014 data [Ref 14] specifically showing that DiPT (the backbone) does NOT develop HTR tolerance in mice introduces nuance — tryptamine tolerance may be less robust than seed data implies. This is a substance-class discrepancy flagged for editorial attention.

12. **Neurotoxicity:** 5-MeO-DiPT neurotoxicity data [Refs 21, 22] should NOT be applied to 4-AcO-DiPT without explicit qualification. The mechanism (potent SERT inhibition + serotonin release) is different from 4-AcO-DiPT's primary 5-HT₂A agonism mechanism.

13. **CYP enzyme involvement in 4-AcO-DiPT metabolism** is inferred from related N,N-diisopropyltryptamine compounds [Ref 17] and general tryptamine CYP inhibition data [Ref 8]. No direct CYP phenotyping study for 4-AcO-DiPT exists.

### Dose Data Note
The brief's dose data (threshold 3 mg, light 5–15 mg, common 15–30 mg, strong 30–45 mg, heavy 45+ mg) is consistent with PsychonautWiki [Ref 26] and with TIHKAL data for the active form 4-OH-DiPT (15–20 mg oral for a common dose [Ref 13]). The slightly higher ranges for 4-AcO-DiPT vs. 4-OH-DiPT are consistent with reduced potency of acetoxy forms [Ref 1, 5] and prodrug conversion. No dose-ranging clinical trial exists to validate these values. They are appropriate for publication with community-consensus labeling.