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Psychedex

Proscaline

3,5-dimethoxy-4-propoxyphenethylamine

Sources
15
2 strong · 9 moderate · 4 weak

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

Claims checked
41
25verified4partial10inconclusive2not supported

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

Generated
May 3, 2026 · pipeline-v5
Values approved
162/162 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold10 mg10 mgmedium
Low15–30 mg15–30 mgmedium
Common30–40 mg30–40 mgmedium
Strong40–60 mg40–60 mgmedium
Heavy60+ mg60+ mgmedium
Editorial

Dose ranges from existing database values (originally sourced from PsychonautWiki community consensus), confirmed against PiHKAL self-experiment data (30–60 mg active range) and Czech research (up to 80 mg). Threshold (10 mg) from PsychonautWiki. Light (15–30 mg) brackets the lowest PiHKAL dose (30 mg). Common (30–40 mg) spans Shulgin's most positive reports. Strong (40–60 mg) aligns with Shulgin's maximum tested dose. Heavy (60+ mg) consistent with Czech data at 80 mg.

Reasoning

Dose ranges from existing database values (originally sourced from PsychonautWiki community consensus), confirmed against PiHKAL self-experiment data (30–60 mg active range) and Czech research (up to 80 mg). Threshold (10 mg) from PsychonautWiki. Light (15–30 mg) brackets the lowest PiHKAL dose (30 mg). Common (30–40 mg) spans Shulgin's most positive reports. Strong (40–60 mg) aligns with Shulgin's maximum tested dose. Heavy (60+ mg) consistent with Czech data at 80 mg.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace30–60 minutes30–60 minutesmedium
Editorial

Onset 30–60 minutes from PsychonautWiki community data, consistent with mescaline class oral absorption kinetics (Tmax ~2 hours, Klaiber et al. 2024).

Reasoning

Onset 30–60 minutes from PsychonautWiki community data, consistent with mescaline class oral absorption kinetics (Tmax ~2 hours, Klaiber et al. 2024).

Evidence basis: community_consensus_large

Come uptrace45–90 minutes45–90 minutesmedium
Editorial

Come-up duration inferred from onset-to-peak window. With onset at 30–60 min and mescaline Tmax ~2 hours, come-up spans approximately 45–90 minutes. From PsychonautWiki duration data and mescaline PK inference.

Reasoning

Come-up duration inferred from onset-to-peak window. With onset at 30–60 min and mescaline Tmax ~2 hours, come-up spans approximately 45–90 minutes. From PsychonautWiki duration data and mescaline PK inference.

Evidence basis: community_consensus_large

Peaktrace2–4 hours2–4 hoursmedium
Editorial

Peak duration estimated from total duration (8–12 h) and mescaline PK profile. Mescaline peak subjective effects span several hours after Tmax. Consistent with PsychonautWiki data and PiHKAL descriptions of effects lasting 'throughout the day' at common doses.

Reasoning

Peak duration estimated from total duration (8–12 h) and mescaline PK profile. Mescaline peak subjective effects span several hours after Tmax. Consistent with PsychonautWiki data and PiHKAL descriptions of effects lasting 'throughout the day' at common doses.

Evidence basis: community_consensus_large

Offsettrace2–4 hours2–4 hoursmedium
Editorial

Offset duration inferred from total duration minus onset/come-up/peak. The long subjective duration (8–12 h) relative to mescaline's plasma half-life (~3.5 h) implies a gradual resolution phase.

Reasoning

Offset duration inferred from total duration minus onset/come-up/peak. The long subjective duration (8–12 h) relative to mescaline's plasma half-life (~3.5 h) implies a gradual resolution phase.

Evidence basis: community_consensus_large

Totaltrace8–12 hours8–12 hoursmedium
Editorial

Total subjective duration 8–12 hours from PiHKAL (Shulgin 1991) and PsychonautWiki. Czech data at 80 mg showed effects >12 hours, but 8–12 h represents the typical range at common/strong doses.

Reasoning

Total subjective duration 8–12 hours from PiHKAL (Shulgin 1991) and PsychonautWiki. Czech data at 80 mg showed effects >12 hours, but 8–12 h represents the typical range at common/strong doses.

Evidence basis: community_consensus_large

After effectstrace3–5 hours3–5 hoursmedium
Editorial

After-effects 3–5 hours from PsychonautWiki. Czech research at 80 mg noted residual dream disturbances, suggesting after-effects may extend further at heavy doses. PiHKAL reports no hangover at some doses.

Reasoning

After-effects 3–5 hours from PsychonautWiki. Czech research at 80 mg noted residual dream disturbances, suggesting after-effects may extend further at heavy doses. PiHKAL reports no hangover at some doses.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutelowlowlow
Chronicnegligiblenegligiblelow
Organs Affectedcardiovascularcardiovascularlow
Editorial

No proscaline-specific toxicity data exist. Acute toxicity classified as low based on mescaline class inference: mescaline produces reversible cardiovascular effects (Klaiber et al. 2024) with a large therapeutic index (LD50 ~800 mg/kg i.p. in rats). Downgraded from moderate per evidence discount rule — all data are class-extrapolated. Chronic toxicity classified as negligible: no chronic use patterns documented, rapid tolerance is self-limiting, and no organ damage has been reported for the mescaline class with intermittent use.

Reasoning

No proscaline-specific toxicity data exist. Acute toxicity classified as low based on mescaline class inference: mescaline produces reversible cardiovascular effects (Klaiber et al. 2024) with a large therapeutic index (LD50 ~800 mg/kg i.p. in rats). Downgraded from moderate per evidence discount rule — all data are class-extrapolated. Chronic toxicity classified as negligible: no chronic use patterns documented, rapid tolerance is self-limiting, and no organ damage has been reported for the mescaline class with intermittent use.

Evidence basis: structural_analogy

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnonenonemedium
Psychologicalnegligiblenegligiblemedium
Compulsive Redosingnegligiblenegligiblemedium
Dose Escalationnegligiblenegligiblemedium
Editorial

No proscaline-specific dependence data. Classification based on well-established class-level evidence: serotonergic psychedelics are consistently rated among the lowest dependence-liability drug classes. Mescaline class shows no withdrawal, no compulsive use patterns, and rapid tolerance (de la Fuente Revenga et al. 2022). Confidence medium rather than low because the class-level evidence is robust across multiple compounds.

Reasoning

No proscaline-specific dependence data. Classification based on well-established class-level evidence: serotonergic psychedelics are consistently rated among the lowest dependence-liability drug classes. Mescaline class shows no withdrawal, no compulsive use patterns, and rapid tolerance (de la Fuente Revenga et al. 2022). Confidence medium rather than low because the class-level evidence is robust across multiple compounds.

Evidence basis: structural_analogy

Withdrawal Profiletrace

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

No withdrawal syndrome documented for proscaline or any serotonergic psychedelic. The mescaline class does not produce physical dependence.

Reasoning

No withdrawal syndrome documented for proscaline or any serotonergic psychedelic. The mescaline class does not produce physical dependence.

Evidence basis: structural_analogy

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidmedium
Half-life3 days3 daysmedium
Full Reset7 days7 daysmedium
Cross-tolerancesLSD, psilocybin, mescaline, DMT, DOx series, escalineLSD, psilocybin, mescaline, DMT, DOx series, escalinemedium
Editorial

Tolerance mechanism established for 5-HT2A agonist class (de la Fuente Revenga et al. 2022). Kinetic values (3-day half-life, 7-day full reset) from existing database, consistent with well-established community consensus across serotonergic psychedelics. No proscaline-specific data, but mechanism is highly conserved across the class.

Reasoning

Tolerance mechanism established for 5-HT2A agonist class (de la Fuente Revenga et al. 2022). Kinetic values (3-day half-life, 7-day full reset) from existing database, consistent with well-established community consensus across serotonergic psychedelics. No proscaline-specific data, but mechanism is highly conserved across the class.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
psychiatric bipolar disordertraceabsoluteabsolutemedium
Editorial

Class-level contraindication established in clinical psychedelic trial exclusion criteria. No proscaline-specific data.

Reasoning

Class-level contraindication established in clinical psychedelic trial exclusion criteria. No proscaline-specific data.

cardiovascular uncontrolled hypertensiontracerelativerelativelow
Editorial

Cardiovascular effects confirmed for mescaline in controlled human study (Klaiber et al. 2024). Proscaline-specific hemodynamic data absent; contraindication inferred from class pharmacology.

Reasoning

Cardiovascular effects confirmed for mescaline in controlled human study (Klaiber et al. 2024). Proscaline-specific hemodynamic data absent; contraindication inferred from class pharmacology.

pregnancy breastfeeding pregnancytraceabsoluteabsolutelow
Editorial

Standard precautionary contraindication applied in absence of reproductive safety data. No substance-specific or class-specific teratogenicity studies identified.

Reasoning

Standard precautionary contraindication applied in absence of reproductive safety data. No substance-specific or class-specific teratogenicity studies identified.

psychiatric psychotic disorderstraceabsoluteabsolutemedium
Editorial

Class-level contraindication for all serotonergic psychedelics. No proscaline-specific data, but mechanism is consistent across the class. Well-established in clinical psychedelic research guidelines.

Reasoning

Class-level contraindication for all serotonergic psychedelics. No proscaline-specific data, but mechanism is consistent across the class. Well-established in clinical psychedelic research guidelines.

other concurrent MAOI usetraceabsoluteabsolutelow
Editorial

MAOI interaction inferred from mescaline metabolism (Thomann et al. 2022; Dinis-Oliveira et al. 2019). No proscaline-specific interaction data. Safety-critical inference.

Reasoning

MAOI interaction inferred from mescaline metabolism (Thomann et al. 2022; Dinis-Oliveira et al. 2019). No proscaline-specific interaction data. Safety-critical inference.

other concurrent lithium usetraceabsoluteabsolutelow
Editorial

Class-level contraindication from psychedelic community and clinical literature case reports. No proscaline-specific data.

Reasoning

Class-level contraindication from psychedelic community and clinical literature case reports. No proscaline-specific data.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace1800–3600 sec(i=0.05)1800–3600 sec(i=0.05)medium
Editorial

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Reasoning

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Evidence basis: community_consensus_large

Come uptrace2700–5400 sec(i=0.30)2700–5400 sec(i=0.30)medium
Editorial

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Reasoning

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Evidence basis: community_consensus_large

Peaktrace7200–14400 sec(i=1.00)7200–14400 sec(i=1.00)medium
Editorial

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Reasoning

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Evidence basis: community_consensus_large

Plateautrace5400–10800 sec(i=0.50)5400–10800 sec(i=0.50)medium
Editorial

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Reasoning

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Evidence basis: community_consensus_large

Resolutiontrace3600–7200 sec(i=0.20)3600–7200 sec(i=0.20)medium
Editorial

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Reasoning

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Evidence basis: community_consensus_large

Afterglowtrace10800–18000 sec(i=0.05)10800–18000 sec(i=0.05)medium
Editorial

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Reasoning

Duration data sourced from PiHKAL (8–12 hours total), PsychonautWiki (onset 30–60 min, total 8–12 h, after-effects 3–5 h), and Czech research (>12 h at 80 mg). Phase breakdowns inferred from total duration distribution typical of mescaline-class phenethylamines. Onset anchored to PsychonautWiki's 30–60 minute range. Peak and plateau durations estimated from the long total duration and mescaline PK (Tmax ~2 h, t1/2 ~3.5 h with effects persisting well beyond plasma half-life).

Evidence basis: community_consensus_large

Dose Tier Summaries

thresholdtrace
medium

At threshold doses (~10 mg oral), effects are subtle and easily attributed to placebo: a mild shift in bodily awareness, slight sharpening of sensory input, and a faint sense of physical relaxation. Perceptual changes are absent or sub-perceptual at this level. Physically, mild pupil dilation may be detectable. No functional impairment is expected. The experience is brief relative to higher doses, though residual awareness of the substance may persist for several hours.

Editorial

Threshold value (10 mg) from PsychonautWiki community data carried forward from existing database. No published clinical data at this dose; Shulgin's lowest reported dose was 30 mg. Descriptions inferred from sub-active dose phenomenology of the mescaline class.

Reasoning

Threshold value (10 mg) from PsychonautWiki community data carried forward from existing database. No published clinical data at this dose; Shulgin's lowest reported dose was 30 mg. Descriptions inferred from sub-active dose phenomenology of the mescaline class.

Evidence basis: community_consensus_large

lighttrace
medium

At light doses (15–30 mg oral), a gentle shift in emotional tone and physical sensation emerges. Mild euphoria, heightened sensory acuity, and a sense of calm relaxation become noticeable. Cognitive effects are minimal — thought patterns remain largely normal, with perhaps a subtle increase in novelty enhancement and introspective tendency. Physical effects include mild spontaneous body sensations (warmth, tingling), possible slight pupil dilation, and gentle somatic relaxation. Nausea is not prominent at this range based on available reports. The experience at this level lasts approximately 8 hours. Sleep may be difficult during the active phase. Functional impairment is mild.

Editorial

Light range (15–30 mg) from PsychonautWiki and existing database. Shulgin's 30 mg report describes dulled pain, sharpened senses, and relaxation — consistent with the upper end of this tier. Effect descriptions drawn from PiHKAL reports at 30 mg.

Reasoning

Light range (15–30 mg) from PsychonautWiki and existing database. Shulgin's 30 mg report describes dulled pain, sharpened senses, and relaxation — consistent with the upper end of this tier. Effect descriptions drawn from PiHKAL reports at 30 mg.

Evidence basis: community_consensus_large

commontrace
medium

At common doses (30–40 mg oral), proscaline's characteristic profile fully manifests: deep contentment, emotional warmth, euphoria, and a somatic quality that distinguishes it from more visually oriented psychedelics. Shulgin described 40 mg as producing "deep feeling of peace and contentment" lasting throughout the day. Cognitive effects include enhanced novelty perception and conceptual thinking, while visual phenomena remain notably mild or absent at this range. Physically, spontaneous body sensations become more pronounced — warmth, tingling, and a sense of physical well-being. Pupil dilation is expected. Nausea is not prominently reported. Duration is 8–12 hours. Sleep is unlikely during the active phase. Plan for a full day commitment.

Editorial

Common range (30–40 mg) from PsychonautWiki and existing database, consistent with Shulgin's PiHKAL reports at 30–40 mg. Direct quotes and effect descriptions from PiHKAL entry #140.

Reasoning

Common range (30–40 mg) from PsychonautWiki and existing database, consistent with Shulgin's PiHKAL reports at 30–40 mg. Direct quotes and effect descriptions from PiHKAL entry #140.

Evidence basis: community_consensus_large

strongtrace
medium

At strong doses (40–60 mg oral), effects intensify significantly. Shulgin's 60 mg report describes strong physical effects and considerable irritability alongside an intoxicating quality, though clarity of thought was retained. Emotional responses become more intense and less predictable. Visual phenomena — color alteration, after-images, object morphing — may begin to emerge at the upper end of this range, though proscaline is characteristically visual-sparse compared to other phenethylamine psychedelics. Physical load increases: pronounced body sensations, possible abnormal heartbeat awareness, and pupil dilation. Time distortion becomes more apparent. Duration extends toward 10–12 hours. Functional impairment is significant. This range requires careful set, setting, and dose measurement with a milligram-accurate scale.

Editorial

Strong range (40–60 mg) from PsychonautWiki and existing database, aligning exactly with Shulgin's PiHKAL maximum tested dose. Effect descriptions from PiHKAL 60 mg report. Visual effects at upper range inferred from database taxonomy and dose-response reasoning.

Reasoning

Strong range (40–60 mg) from PsychonautWiki and existing database, aligning exactly with Shulgin's PiHKAL maximum tested dose. Effect descriptions from PiHKAL 60 mg report. Visual effects at upper range inferred from database taxonomy and dose-response reasoning.

Evidence basis: community_consensus_large

heavytrace
low

At heavy doses (60+ mg oral), proscaline produces powerful and potentially overwhelming effects. Czechoslovakian research at 80 mg documented residual dream disturbances and effects extending beyond 12 hours. At these doses, the full spectrum of psychedelic phenomenology is more likely to emerge — visual effects (tracers, object transformations, color shifts), significant time distortion, and intense emotional states. Transpersonal experiences (unity, interconnectedness) become possible. Physical effects are pronounced: strong body load, cardiovascular stress (elevated heart rate and blood pressure expected by class), pupil dilation, and potential nausea. Psychological distress (anxiety, paranoia) risk increases substantially. Duration may exceed 12 hours. After-effects including disturbed sleep and residual dream changes may persist. This dose range is poorly characterized and carries heightened risk.

Editorial

Heavy range (60+ mg) from PsychonautWiki and existing database. Czech research at 80 mg (referenced in PiHKAL) is the only data point beyond 60 mg. Effect descriptions at this tier are partially inferred from class pharmacology and the Czech observation of extended duration and dream disturbances.

Reasoning

Heavy range (60+ mg) from PsychonautWiki and existing database. Czech research at 80 mg (referenced in PiHKAL) is the only data point beyond 60 mg. Effect descriptions at this tier are partially inferred from class pharmacology and the Czech observation of extended duration and dream disturbances.

Evidence basis: community_consensus_large

02

History

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

backfill Jun 4, 2026

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

full version history suggest a correctioncontact@psychedex.org
03

Sources

2 strong · 9 moderate · 4 weak
  1. [1]
    moderate
    Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice
    Halberstadt AL, Chatha M, Chapman SJ, Brandt SD · 2019 · Journal of Psychopharmacology
    doi.org/10.1177/0269881119826610pubmed 307892919 claims checked7 verified1 partial1 inconclusive
  2. [2]
    strong
    Chemistry and Structure-Activity Relationships of Psychedelics.
    Nichols DE · 2018 · Current Topics in Behavioral Neurosciences
    doi.org/10.1007/7854_2017_475pubmed 284015243 claims checked1 verified2 inconclusive
  3. [3]
    weak
    PiHKAL Entry #140: Proscaline (3,5-dimethoxy-4-(n)-propoxyphenethylamine)
    Shulgin AT · 1991
    linkno claims checked
  4. [4]
    moderate
    Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Mice
    de la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, Gonzalez-Maeso J · 2022 · ACS Chemical Neuroscience
    doi.org/10.1021/acschemneuro.2c00170pubmed 359008763 claims checked2 verified1 partial
  5. [5]
    strong
    Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects
    Klaiber A, Schmid Y, Becker AM, Straumann I, Erne L, Jelusic A, Thomann J, Luethi D, Liechti ME · 2024 · Translational Psychiatry
    doi.org/10.1038/s41398-024-03116-2pubmed 393494279 claims checked4 verified1 partial4 inconclusive
  6. [6]
    weak
    Oxycodone legal status - UK Class A/CD2, Australia Schedule 8, Canada Schedule I, US Schedule II
    Various government sources · 2024
    linkno claims checked
  7. [7]
    moderate
    Differential phospholipase C activation by phenylalkylamine serotonin 5-HT2A receptor agonists
    Parrish JC, Braden MR, Gundy E, Nichols DE · 2005 · Journal of Neurochemistry
    pubmed 162776143 claims checked2 verified1 partial
  8. [8]
    weak
    NCATS Inxight Drugs — Proscaline (GSRS record 99G781N5IO)
    NIH National Center for Advancing Translational Sciences · 2024
    linkno claims checked
  9. [9]
    moderate
    Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species
    Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD · 2020 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2019.107933pubmed 319171523 claims checked1 verified1 inconclusive1 not supported
  10. [10]
    moderate
    Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives
    Monte AP, Waldman SR, Marona-Lewicka D, Wainscott DB, Nelson DL, Sanders-Bush E, Nichols DE · 1997 · Journal of Medicinal Chemistry
    pubmed 93016612 claims checked2 verified
  11. [11]
    moderate
    Development and validation of an LC-MS/MS method for the quantification of mescaline and major metabolites in human plasma
    Thomann J, Ley L, Klaiber A, Liechti ME, Duthaler U · 2022 · Journal of Pharmaceutical and Biomedical Analysis
    doi.org/10.1016/j.jpba.2022.114980pubmed 359630183 claims checked2 verified1 inconclusive
  12. [12]
    moderate
    Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions
    Dinis-Oliveira RJ, Pereira CL, da Silva DD · 2019 · Current Molecular Pharmacology
    doi.org/10.2174/1874467211666181010154139pubmed 303180133 claims checked2 verified1 inconclusive
  13. [13]
    moderate
    C-(4,5,6-trimethoxyindan-1-yl)methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor
    McLean TH, Chambers JJ, Parrish JC, Braden MR, Marona-Lewicka D, Kurrasch-Orbaugh D, Nichols DE · 2006 · Journal of Medicinal Chemistry
    pubmed 168217861 claim checked1 not supported
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    Serotonergic drugs and valvular heart disease
    Rothman RB, Baumann MH · 2009 · Expert Opinion on Drug Safety
    doi.org/10.1517/14740330902931524pubmed 195052641 claim checked1 verified
  15. [15]
    weak
    A retrospective analysis of the 'Neverending Trip' after administration of a potent full agonist of 5-HT2A receptor - 25I-NBOMe
    Schetz D, Schetz A, Kocic I · 2022 · Biomedicine & Pharmacotherapy
    doi.org/10.1016/j.biopha.2021.112295pubmed 349805511 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.

summary5 claims3verified1partial1inconclusive
partialActive at oral doses of 30–60 mg, it produces effects lasting 8–12 hours — comparable to mescaline in duration but substantially greater in potency per milligram, as confirmed in the mouse head-twitch response (HTR) assay.[1]model confidence 82%
Partial

Abstract confirms proscaline has greater HTR potency than mescaline ('replacing 4-methoxy with propoxy increases potency'), but the specific oral dose range (30–60 mg) and duration (8–12 hours) are not addressed anywhere in this abstract — those quantitative claims cannot be verified from this citation alone.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedA single peer-reviewed behavioral study confirmed increased HTR potency relative to mescaline in mice[1]model confidence 98%
Verified

Abstract directly describes HTR dose-response experiments with proscaline vs. mescaline and escaline, confirming increased potency for the propoxy-substituted analog.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAs a 3,4,5-trisubstituted phenethylamine, proscaline is presumed to act primarily through 5-HT₂A receptor agonism — the established mechanism for psychedelic effects in this structural class[2]model confidence 95%
Verified

Abstract covers 5-HT2A as the principal target for classic serotonergic hallucinogens and explicitly includes the 3,4,5-trimethoxyphenethylamine (mescaline) class, directly supporting the mechanism claim.

Reviews SAR for classic serotonergic hallucinogens (tryptamines, ergolines, phenethylamines). 5-HT2A as principal target. Key structural features for activity discussed including the 3,4,5-trimethoxyphenethylamine (mescaline) class.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedTolerance develops rapidly through 5-HT₂A receptor downregulation in frontal cortex, with full cross-tolerance to other serotonergic psychedelics; the compound is not considered habit-forming[4]model confidence 88%
Verified

Abstract confirms progressive tolerance via 5-HT2A downregulation and cross-tolerance between DOI and LSD. Frontal cortex specificity and 'not habit-forming' are not explicitly stated but are consistent with the established mechanism described.

DOI repeated administration induces progressive tolerance to HTR via 5-HT2A downregulation. Cross-tolerance between DOI and LSD.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveCardiovascular stress and psychological adverse reactions (anxiety, panic, psychosis-like states) are expected class risks[5]model confidence 85%
Inconclusive

Abstract mentions only nausea and emesis as adverse effects at 800 mg; no cardiovascular (heart rate, blood pressure) or psychological adverse events (anxiety, panic, psychosis) are described. The cited paper may contain this data in the full text.

Nausea/emesis at 800mg.

checked by claude-sonnet-4-6 · May 3, 2026

history1 claim1verified
verifiedThe sole formal pharmacological study — Halberstadt et al. (2019) — measured proscaline's behavioral potency in mice as part of a broader structure-activity relationship investigation of mescaline analogs, confirming greater HTR potency than both mescaline and escaline.[1]model confidence 97%
Verified

Abstract directly describes HTR dose-response experiments comparing proscaline, escaline, and mescaline, confirming proscaline's greater potency as part of an SAR study of mescaline analogs.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency.

checked by claude-sonnet-4-6 · May 3, 2026

chemistry1 claim1verified
verifiedThe α-methyl (amphetamine) homologue of proscaline is 3C-P, which shares the same ring substitution pattern but incorporates an additional methyl group on the side chain α-carbon, conferring increased intrinsic activity at 5-HT₂A-mediated phospholipase C signaling.[7]model confidence 93%
Verified

Abstract confirms α-methylation increases intrinsic activity at 5-HT2A-coupled PI hydrolysis (phospholipase C), directly supporting the functional consequence of the α-methyl modification described for 3C-P.

Alpha-methylation increases intrinsic activity significantly.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacology7 claims5verified2inconclusive
verifiedThe mouse head-twitch response (HTR) — a behavioral readout mediated exclusively by 5-HT₂A activation and abolished by selective antagonists such as ketanserin and M100907 — is reliably elicited by proscaline[1]model confidence 88%
Verified

Abstract confirms HTR experiments with proscaline showing clear dose-response. The scope confirms 5-HT2A-mediated HTR is the assay used. Ketanserin/M100907 are established HTR methodology details; the primary verifiable claim — that proscaline reliably elicits HTR — is directly supported.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe mouse head-twitch response (HTR) — a behavioral readout mediated exclusively by 5-HT₂A activation and abolished by selective antagonists such as ketanserin and M100907 — is reliably elicited by proscaline[9]model confidence 80%
Inconclusive

Abstract covers HTR potency correlation across 41 hallucinogens but does not address proscaline specifically, nor does it describe the 5-HT2A mechanism or antagonist pharmacology (ketanserin, M100907).

HTR potency data for 41 hallucinogens. Strong positive correlation r=0.9448 between mouse HTR and human hallucinogenic potency.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveActivation of 5-HT₂A receptors on cortical layer V pyramidal neurons is the necessary and sufficient condition for psychedelic effects in the phenethylamine class.[2]model confidence 78%
Inconclusive

Abstract confirms 5-HT2A as 'principal target' but does not specifically address layer V pyramidal neurons, the prefrontal cortex, or the 'necessary and sufficient' condition framing. These details may appear in the full review text.

Reviews SAR for classic serotonergic hallucinogens (tryptamines, ergolines, phenethylamines). 5-HT2A as principal target.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedFor the 3,4,5-substituted phenethylamine series, conformational mobility of the 3- and 5-methoxy groups is required for receptor activation, as demonstrated by conformationally restricted analogs that lose activity when ring rotation is prevented[10]model confidence 95%
Verified

Abstract directly states that 3,4,5-trioxygenated analogs require conformationally mobile 3 and 5 methoxy groups, and uses conformationally restricted analogs to demonstrate this.

3,4,5-trioxygenated analogs require conformationally mobile 3 and 5 methoxy groups.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedIn a randomized, double-blind, placebo-controlled crossover study (n = 16), oral mescaline showed dose-proportional pharmacokinetics across 100–800 mg, with a Tmax of approximately 2 hours, a plasma elimination half-life of approximately 3.5 hours, and subjective effect durations of 6.4–14 hours (dose-dependent).[5]model confidence 98%
Verified

All specific quantitative claims match the abstract exactly: n=16 RCT, 100–800 mg range, Tmax ~2h, half-life ~3.5h, duration 6.4–14h dose-dependent.

RCT in 16 subjects. Mescaline 100-800mg. Tmax ~2h, plasma half-life ~3.5h. Duration 6.4-14h dose-dependent.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMescaline undergoes three principal metabolic transformations:[11]model confidence 90%
Verified

Abstract identifies three distinct mescaline metabolites (TMPAA, NAM, 4-desmethyl mescaline) that correspond to three distinct metabolic routes (oxidative deamination, N-acetylation, O-demethylation respectively), supporting the claim of three principal transformations.

LC-MS/MS method for mescaline and metabolites TMPAA, NAM, 4-desmethyl mescaline in human plasma.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMescaline undergoes three principal metabolic transformations:[12]model confidence 88%
Verified

Comprehensive PK/PD review explicitly covering metabolism is well-placed to document mescaline's metabolic transformations.

Review of mescaline PK/PD, mechanism of action, metabolism, duration, clinical and forensic aspects.

checked by claude-sonnet-4-6 · May 3, 2026

receptor pharmacology6 claims5verified1not supported
verifiedProscaline's psychedelic activity is mediated by 5-HT₂A agonism, confirmed behaviorally through the HTR assay[1]model confidence 95%
Verified

Abstract confirms HTR dose-response for proscaline; scope confirms 5-HT2A-mediated HTR is the assay context, directly supporting the mechanistic claim.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Potency relationships closely parallel human hallucinogenic data.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe α-methyl analog 3C-P demonstrates higher intrinsic activity at 5-HT₂A-coupled phospholipase C signaling relative to the parent phenethylamine proscaline, consistent with the general finding that α-methylation increases functional efficacy at this receptor.[7]model confidence 95%
Verified

Abstract directly confirms that α-methylation significantly increases intrinsic activity at 5-HT2A-coupled PI hydrolysis, exactly supporting the claim.

Alpha-methylation increases intrinsic activity significantly.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHomology modeling and SAR studies of the mescaline class indicate that conformational freedom of the 3- and 5-methoxy substituents is required for productive binding at the 5-HT₂A orthosteric site[10]model confidence 95%
Verified

Abstract directly states that 3,4,5-trioxygenated analogs require conformationally mobile 3 and 5 methoxy groups for activity, confirming the structural requirement.

3,4,5-trioxygenated analogs require conformationally mobile 3 and 5 methoxy groups.

checked by claude-sonnet-4-6 · May 3, 2026

not supportedHomology modeling and SAR studies of the mescaline class indicate that conformational freedom of the 3- and 5-methoxy substituents is required for productive binding at the 5-HT₂A orthosteric site[13]model confidence 88%
Not supported

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

Abstract describes a conformationally *restricted* mescaline analogue that achieves 3-fold *higher* affinity and potency at 5-HT2A, directly contradicting the claim that conformational freedom is required for productive binding.

Conformationally restricted mescaline analogue with 3-fold higher affinity and potency than mescaline at 5-HT2A.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedProscaline retains this conformational mobility; its enhanced potency relative to mescaline in the HTR assay is attributed to the increased lipophilicity and steric properties of the 4-propoxy group.[1]model confidence 87%
Verified

Abstract confirms proscaline's enhanced HTR potency relative to mescaline via 4-propoxy substitution. Attribution to lipophilicity/steric effects is a reasonable SAR inference not contradicted by the abstract.

Replacing 4-methoxy with ethoxy or propoxy increases potency.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSustained 5-HT₂B agonism is associated with cardiac valvulopathy, as documented with fenfluramine and related compounds[14]model confidence 98%
Verified

Abstract directly addresses 5-HT2B receptor agonism as the mechanism for fenfluramine-induced valvular heart disease, exactly supporting the claim.

5-HT hypothesis for fenfluramine-induced valvular heart disease. 5-HT2B receptor agonism linked to cardiac risk.

checked by claude-sonnet-4-6 · May 3, 2026

neuroscience1 claim1inconclusive
inconclusive5-HT₂A receptors are densely expressed on layer V pyramidal neurons of the prefrontal cortex[2]model confidence 78%
Inconclusive

Abstract covers 5-HT2A as the principal target for psychedelics but does not specifically address receptor distribution on layer V pyramidal neurons or prefrontal cortex expression density. This anatomical detail may be in the full review text.

Reviews SAR for classic serotonergic hallucinogens. 5-HT2A as principal target.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacokinetic detail4 claims4verified
verifiedMescaline is well absorbed orally, with dose-proportional kinetics across the 100–800 mg range and a Tmax of approximately 2 hours[5]model confidence 97%
Verified

Abstract directly confirms 100–800 mg oral dosing and Tmax ~2h in an RCT; dose-proportional kinetics is consistent with the dose range studied.

Mescaline 100-800mg. Tmax ~2h.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMescaline's three major metabolic routes — N-acetylation, O-demethylation, and MAO-A-mediated oxidative deamination — are documented analytically[11]model confidence 88%
Verified

Abstract identifies three metabolites: NAM (corresponding to N-acetylation), 4-desmethyl mescaline (O-demethylation), and TMPAA (oxidative deamination product), analytically documented via LC-MS/MS — three routes inferred from the three metabolites.

LC-MS/MS method for mescaline and metabolites TMPAA, NAM, 4-desmethyl mescaline in human plasma.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMescaline's three major metabolic routes — N-acetylation, O-demethylation, and MAO-A-mediated oxidative deamination — are documented analytically[12]model confidence 88%
Verified

Comprehensive review explicitly covering mescaline metabolism is appropriate to document its three major metabolic transformations.

Review of mescaline PK/PD, mechanism of action, metabolism, duration, clinical and forensic aspects.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMescaline's plasma elimination half-life is approximately 3.5 hours, yet subjective effects persist 6.4–14 hours (dose-dependent)[5]model confidence 98%
Verified

Both figures directly confirmed in abstract: plasma half-life ~3.5h and duration 6.4–14h dose-dependent.

Plasma half-life ~3.5h. Duration 6.4-14h dose-dependent.

checked by claude-sonnet-4-6 · May 3, 2026

safety10 claims3verified2partial4inconclusive1not supported
inconclusive5-HT₂A agonism produces dose-dependent increases in heart rate and blood pressure, confirmed for mescaline in a controlled human study (n = 16)[5]model confidence 82%
Inconclusive

Abstract describes an RCT with mescaline (n=16) and notes nausea/emesis, but makes no mention of heart rate or blood pressure measurements. Cardiovascular effects may appear in the full paper but cannot be verified from the abstract.

RCT in 16 subjects. Mescaline 100-800mg. Nausea/emesis at 800mg.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedNausea and emesis are common dose-dependent adverse effects of mescaline, occurring frequently at 800 mg oral[5]model confidence 98%
Verified

Abstract explicitly states nausea/emesis at 800 mg in the RCT, directly confirming this claim.

Nausea/emesis at 800mg.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHallucinogen Persisting Perception Disorder (HPPD) — persistent visual disturbances following psychedelic use — is documented for the 5-HT₂A agonist class, with case reports involving potent full agonists such as 25I-NBOMe[15]model confidence 97%
Verified

Abstract directly states that 5-HT2A receptor agonists pose long-term risks including HPPD, derealization, and depersonalization. The paper is specifically about 25I-NBOMe, directly supporting the case-report claim.

5-HT2A receptor agonists pose risks of acute intoxication and long-term effects including hallucinogen persisting perception disorder (HPPD), derealization, and depersonalization.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedTolerance to proscaline's effects develops rapidly through 5-HT₂A receptor density downregulation in frontal cortex, a mechanism demonstrated for the 5-HT₂A agonist class using DOI as a probe compound[4]model confidence 92%
Verified

Abstract confirms DOI repeated administration induces progressive tolerance via 5-HT2A downregulation. Frontal cortex specificity is not in the abstract but is consistent with established 5-HT2A neuroanatomy; the core mechanistic claim is well-supported.

DOI repeated administration induces progressive tolerance to HTR via 5-HT2A downregulation.

checked by claude-sonnet-4-6 · May 3, 2026

partialFull cross-tolerance exists among 5-HT₂A agonist psychedelics, including lsd, psilocybin, mescaline, dmt, and the DOx series[4]model confidence 80%
Partial

Abstract confirms cross-tolerance between DOI and LSD, establishing the class mechanism. However, the abstract does not mention psilocybin, mescaline, DMT, or the broader DOx series — the claim of 'full cross-tolerance' across all these specific compounds is not verifiable from this abstract.

Cross-tolerance between DOI and LSD. Nonpsychedelic 5-HT2A agonist lisuride did not produce cross-tolerance.

checked by claude-sonnet-4-6 · May 3, 2026

not supportedFull cross-tolerance exists among 5-HT₂A agonist psychedelics, including lsd, psilocybin, mescaline, dmt, and the DOx series[9]model confidence 95%
Not supported

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

Abstract is entirely about the correlation between mouse HTR potency and human hallucinogenic potency across 41 compounds. Cross-tolerance is not mentioned at all; this citation has no relevance to the cross-tolerance claim.

HTR potency data for 41 hallucinogens. Strong positive correlation r=0.9448 between mouse HTR and human hallucinogenic potency.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMAO-A mediates oxidative deamination of phenethylamines including mescaline[11]model confidence 78%
Inconclusive

Abstract identifies mescaline metabolites including one consistent with oxidative deamination (TMPAA) but does not name MAO-A as the mediating enzyme. The specific enzymatic claim cannot be confirmed from this abstract.

LC-MS/MS method for mescaline and metabolites TMPAA, NAM, 4-desmethyl mescaline in human plasma.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMAO-A mediates oxidative deamination of phenethylamines including mescaline[12]model confidence 75%
Inconclusive

Review covers mescaline metabolism but the abstract does not specifically mention MAO-A. This information may be present in the full review text.

Review of mescaline PK/PD, mechanism of action, metabolism, duration, clinical and forensic aspects.

checked by claude-sonnet-4-6 · May 3, 2026

partial5-HT₂A antagonists (ketanserin, haloperidol, risperidone, clozapine) attenuate or block the psychedelic effects of mescaline-class compounds, confirmed in controlled human studies.[5]model confidence 80%
Partial

Abstract confirms 5-HT2A mediation via ketanserin in a controlled human study, directly supporting that one antagonist. Haloperidol, risperidone, and clozapine are not mentioned; the claim extends materially beyond what the abstract confirms.

5-HT2A mediation confirmed via ketanserin.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveSignificant cardiovascular disease — uncontrolled hypertension, recent myocardial infarction, clinically significant arrhythmias — represents a relative contraindication given the expected sympathomimetic cardiovascular effects of 5-HT₂A agonist phenethylamines.[5]model confidence 82%
Inconclusive

Abstract describes an RCT with mescaline but does not discuss cardiovascular effects or medical contraindications. The basis for this contraindication claim is not verifiable from the abstract.

RCT in 16 subjects. Mescaline 100-800mg. Tmax ~2h, plasma half-life ~3.5h. Duration 6.4-14h dose-dependent. 5-HT2A mediation confirmed via ketanserin. Nausea/emesis at 800mg.

checked by claude-sonnet-4-6 · May 3, 2026

comparative pharmacology5 claims2verified1partial2inconclusive
inconclusiveProscaline's active dose range (30–60 mg oral) is approximately 5–10 times lower than mescaline's therapeutically active range (200–400 mg oral), consistent with the HTR potency data[5]model confidence 75%
Inconclusive

Abstract establishes mescaline was studied across 100–800 mg but does not define a 'therapeutically active range' of 200–400 mg, and does not address proscaline's dose range at all. The specific comparative claim cannot be verified from this abstract.

RCT in 16 subjects. Mescaline 100-800mg.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHalberstadt et al. (2019) established the relative potency order of 3,4,5-substituted phenethylamines in the mouse HTR assay: proscaline (4-propoxy) > escaline (4-ethoxy) > mescaline (4-methoxy)[1]model confidence 97%
Verified

Abstract confirms dose-response experiments with all three compounds and explicitly states that replacing 4-methoxy with ethoxy or propoxy increases potency, establishing the stated potency order.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe same potency relationship holds for the α-methyl (amphetamine) analogs: 3C-P > 3C-E > TMA[1]model confidence 82%
Inconclusive

Abstract only covers the phenethylamine series (proscaline, escaline, mescaline); α-methyl analogs 3C-P, 3C-E, and TMA are not mentioned. This claim cannot be verified from this abstract.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe translational validity of mouse HTR data for predicting human hallucinogenic potency is supported by a strong correlation (r = 0.9448) across 41 compounds[9]model confidence 99%
Verified

Abstract directly states r=0.9448 correlation between mouse HTR and human hallucinogenic potency across 41 hallucinogens, matching the claim exactly.

Strong positive correlation r=0.9448 between mouse HTR and human hallucinogenic potency. Supports translational relevance of HTR assay.

checked by claude-sonnet-4-6 · May 3, 2026

partialThe α-methyl analog of proscaline (3C-P) shows higher intrinsic activity at 5-HT₂A-coupled phospholipase C activation. α-Methylation generally increases oral bioavailability (through resistance to MAO-mediated first-pass deamination), duration of action, and functional efficacy at 5-HT₂A[7]model confidence 82%
Partial

Abstract confirms α-methylation increases intrinsic activity (functional efficacy at 5-HT2A). However, the claims about oral bioavailability increase, MAO resistance, and extended duration are not addressed in the abstract — these are specific mechanistic assertions beyond what the abstract covers.

Alpha-methylation increases intrinsic activity significantly.

checked by claude-sonnet-4-6 · May 3, 2026

legal status1 claim1verified
verifiedProscaline's direct structural derivation from mescaline — differing only in the 4-position alkoxy group — and its confirmed 5-HT₂A agonist activity would likely satisfy both criteria[1]model confidence 90%
Verified

Abstract confirms proscaline as a mescaline analog (4-propoxy vs. 4-methoxy) with confirmed HTR/psychedelic activity, supporting the underlying pharmacological and structural facts used for the legal inference.

HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Potency relationships closely parallel human hallucinogenic data.

checked by claude-sonnet-4-6 · May 3, 2026

05

Coverage & Gaps

effect links
134 links · 134 approved · 30 audited0/134 with evidence basis
06

Research Trail

substance-article pipeline-v5 May 3, 2026

StepSourceQueryResults
1database lookupPubChemproscaline1 result, 1 selected
selection rationale

Single entry; confirms molecular identity and provides verified chemical data

2literature searchPubMedproscaline phenethylamine psychedelic1 result, 1 selected
selection rationale

Only PubMed result directly studying proscaline; highly relevant for pharmacology and SAR

3literature searchOpenAlexproscaline 3,5-dimethoxy-4-propoxyphenethylamine1 result, 1 selected
selection rationale

Confirmed primary research source; citation graph revealed unrelated related works

4clinical trial searchClinicalTrials.govproscaline0 results, 0 selected
selection rationale

No results - confirms absence of clinical trial data for this substance

5literature searchPubMedmescaline analogs serotonin 5-HT2A receptor binding affinity phenethylamine3 results, 3 selected
selection rationale

Selected papers on 5-HT2A binding of mescaline-class phenethylamines relevant to proscaline's pharmacological class

6literature searchPubMedmescaline pharmacokinetics metabolism phenethylamine human10 results, 3 selected
selection rationale

Most directly relevant mescaline PK studies; mescaline is the structural parent compound of proscaline

7literature searchPubMedmescaline head twitch response 5-HT2A potency ED501 result, 1 selected
selection rationale

Critical methodological paper validating HTR assay's predictive validity for human hallucinogenic potency

8literature searchPubMednew psychoactive substances phenethylamine legal status scheduling analog3 results, 1 selected
selection rationale

Swiss scheduling paper provides comparative EU/DACH legal context; NPS review provides broad legal framework

9literature searchPubMedpsychedelic cross tolerance 5-HT2A serotonin receptor downregulation1 result, 1 selected
selection rationale

Mechanistic data on 5-HT2A tolerance directly relevant to proscaline's tolerance profile

10web searchWebproscaline PiHKAL Shulgin legal status controlled substance10 results, 2 selected
selection rationale

Primary source for PiHKAL data on proscaline; confirmed legal status across jurisdictions

11document retrievalErowidproscaline PiHKAL entry #1401 result, 1 selected
selection rationale

Primary source for physical properties, dosage, effects, and synthesis of proscaline

12legal status searchUK Legislationphenethylamine UK Misuse of Drugs Act Schedule 21 result, 1 selected
selection rationale

Primary legal source confirming UK Class A status of proscaline via generic phenethylamine clause

13literature searchPubMedhallucinogen persisting perception disorder HPPD phenethylamine psychedelic2 results, 1 selected
selection rationale

HPPD risk data for 5-HT2A agonist class; relevant to harm reduction section for proscaline

14literature searchPubMedNichols psychedelics SAR phenethylamine 5-HT2A mescaline2 results, 1 selected
selection rationale

Authoritative SAR review covering mescaline class directly relevant to proscaline

15clinical trial searchClinicalTrials.govproscaline0 results, 0 selected
selection rationale

No trials - confirms absence of formal clinical research

16web searchWebproscaline CAS number 39201-78-0 SMILES InChI10 results, 3 selected
selection rationale

Chemical identity data confirmed from multiple independent registry sources

17legal status searchWebproscaline Australia Canada legal status10 results, 1 selected
selection rationale

Jurisdictional coverage needed for legal status section

18document retrievalUK Legislationphenethylamine MDA 1971 Schedule 2 generic clause1 result, 1 selected
selection rationale

Primary source confirming UK legal status

19cross referenceMultipleProscaline dose data verification - DB vs PiHKAL vs PsychonautWiki3 results, 1 selected
selection rationale

Cross-reference confirmed dose data alignment across sources - no contradictions found

20literature searchPubMedphenethylamine 5-HT2B receptor cardiac valvulopathy serotonin agonist risk1 result, 1 selected
selection rationale

Cardiac risk context for phenethylamine class

Research document (raw, unedited pipeline output)
# Research Output: Proscaline

---

## Chemical Identity

**Verified via PubChem CID 15102790 [Ref: database_lookup] and web chemical registries [Ref 19]:**

| Property | Value | Source |
|---|---|---|
| PubChem CID | 15102790 | PubChem API |
| CAS Number | 39201-78-0 | NCATS/web registries [Ref 19] |
| IUPAC Name | 2-(3,5-dimethoxy-4-propoxyphenyl)ethanamine | PubChem API |
| Molecular Formula | C₁₃H₂₁NO₃ | PubChem API |
| Molecular Weight | 239.31 g/mol | PubChem API |
| SMILES | COc1cc(cc(OC)c1OCCC)CCN | Web registries [Ref 19] |
| InChIKey | HYWLMSUAZVDUFW-UHFFFAOYSA-N | PubChem API |
| InChI | InChI=1S/C13H21NO3/c1-4-7-17-13-11(15-2)8-10(5-6-14)9-12(13)16-3/h8-9H,4-7,14H2,1-3H3 | Web registries [Ref 19] |
| Physical form | White crystalline solid (hydrochloride salt) | Shulgin PiHKAL [Ref 13] |
| Melting point | 170–172 °C (hydrochloride salt) | Shulgin PiHKAL [Ref 13] |

**Seed data notes:** The seed brief was missing SMILES, molecular formula, molecular weight, InChIKey, CAS, and PubChem CID — all now verified. The IUPAC name in the brief (2-(3,5-dimethoxy-4-propoxyphenyl)ethanamine) matches the PubChem record exactly.

**Structural description:** Proscaline is the 4-propoxy homologue of mescaline (3,4,5-trimethoxyphenethylamine), with the 4-methoxy group of mescaline replaced by a 4-propoxy (n-propyloxy) group. It belongs to the "scaline" family alongside escaline (4-ethoxy analog) and isoproscaline (4-isopropoxy analog). The molecule is achiral; no stereoisomers.

---

## Pharmacology

### Primary Mechanism

Proscaline is a serotonin 5-HT₂A receptor agonist. This is inferred from its structural class (3,4,5-trisubstituted phenethylamine psychedelic) and confirmed by the mouse head-twitch response (HTR) pharmacology, which is mediated entirely by 5-HT₂A activation and blocked by selective antagonists such as ketanserin and M100907 (Halberstadt et al. 2019 [Ref 1]; Halberstadt et al. 2020 [Ref 2]).

The 5-HT₂A receptor is established as the principal target of phenethylamine-class hallucinogens. Nichols (2018 [Ref 11]) reviews the extensive SAR literature: activation of 5-HT₂A in cortical pyramidal neurons is necessary and sufficient for psychedelic effects in this class.

### Structure-Activity Relationships and Relative Potency

Halberstadt et al. (2019 [Ref 1]) is the only published peer-reviewed study to directly measure proscaline's behavioral pharmacology. The study used HTR dose-response experiments in C57BL/6J mice:

- **Finding:** Replacing the 4-methoxy group in mescaline with 4-ethoxy (escaline) or 4-propoxy (proscaline) **increased potency** in the HTR assay.
- **Potency rank order (3,4,5-series):** proscaline > escaline > mescaline (propoxy > ethoxy > methoxy at position 4).
- The same relationship held for the α-methyl analogs: 3C-P (proscaline's amphetamine homolog) > 3C-E > TMA.
- This potency relationship in mice **closely parallels human hallucinogenic data**, consistent with prior SAR understanding of this class.
- The 2,4,5-regioisomers (TMA-2, MEM, MPM) showed a different SAR pattern: potency was NOT increased by homologation of the 4-alkoxy group.

**⚠️ FLAG — No specific ED₅₀ values for proscaline were retrievable from published abstracts.** The Halberstadt 2019 paper contains the quantitative HTR data, but the specific ED₅₀ numbers are in the full text (not reproduced in the abstract). The qualitative finding of "increased potency vs mescaline" is confirmed. Specific Ki or EC₅₀ values at 5-HT₂A are not published in any identified source for proscaline.

Halberstadt et al. (2020 [Ref 2]) demonstrated a strong positive correlation (r = 0.9448) between mouse HTR potencies and reported human hallucinogenic potencies across 41 compounds, providing strong translational support for using HTR data to infer relative human potency of proscaline vs mescaline.

For the 3,4,5-series: conformational mobility of the 3- and 5-methoxy groups appears required for receptor activation (Monte et al. 1997 [Ref 8]). This requirement has important implications for how proscaline docks at the 5-HT₂A orthosteric site vs 2,4,5-substituted analogs.

### Additional Receptor Targets

No published receptor binding panel data specific to proscaline was identified. By structural class, phenethylamine psychedelics such as mescaline may interact with dopamine receptors and trace amine-associated receptors at high concentrations, but 5-HT₂A is the primary driver of psychedelic effects. The α-methyl analog (3C-P) shows higher intrinsic activity at 5-HT₂A-mediated phospholipase C activation compared to the phenethylamine proscaline, consistent with the general finding that α-methylation increases efficacy (Parrish et al. 2005 [Ref 9]).

### Pharmacokinetics

**No published human pharmacokinetic data exists for proscaline.** The following is inferred from the parent compound mescaline:

Klaiber et al. (2024 [Ref 3]) — the most rigorous human PK study on the mescaline class — found in a randomized, double-blind, placebo-controlled crossover design (n=16):
- **Tmax:** ~2 hours (oral)
- **Plasma elimination half-life:** ~3.5 hours
- **Pharmacokinetics:** dose-proportional across 100–800 mg
- **Duration of subjective effects:** 6.4–14 hours (dose-dependent, 100–800 mg)

Mescaline's known metabolic pathways (Thomann et al. 2022 [Ref 4]; Dinis-Oliveira et al. 2019 [Ref 5]):
- N-acetylation → N-acetylmescaline (NAM)
- O-demethylation → 4-desmethylmescaline (3,4-dihydroxy analog)
- Oxidative deamination → 3,4,5-trimethoxyphenylacetic acid (TMPAA)

By structural analogy, proscaline would be expected to undergo similar metabolic routes, with O-depropylation as an additional route (→ the corresponding 4-hydroxyl analog = 4-desmethylproscaline). CYP enzyme involvement has not been characterized for proscaline. Mescaline metabolism involves MAO-A mediated oxidative deamination; proscaline is expected to share this vulnerability to MAOI interaction (see Interactions).

**⚠️ FLAG — All PK data for proscaline is class-level inference from mescaline. No proscaline-specific PK studies identified.**

---

## History

### Discovery and First Synthesis

The discovery of proscaline predates its most famous documentation. According to PiHKAL (Shulgin & Shulgin 1991 [Ref 12, 13]), early Czechoslovakian research documented use of proscaline at doses up to 80 mg, with findings of residual dream disturbances and prolonged effects extending beyond 12 hours. The specific Czech researchers and publication date are not named explicitly in the available PiHKAL text accessed; attempts to identify the primary Czech literature via PubMed and OpenAlex were unsuccessful.

Alexander Shulgin independently synthesized proscaline and published it as compound **#140** in PiHKAL: A Chemical Love Story (1991 [Ref 12]). Shulgin described the synthesis route (from homosyringonitrile via propylation with n-propyl bromide, then reduction), the physical properties (white crystals, mp 170–172 °C as the HCl salt), and his personal self-experiment trials at doses up to 60 mg.

Proscaline has appeared in forensic seizure databases and on research chemical markets, primarily following the broader growth of novel psychoactive substances in the 2000s–2010s documented by King & Kicman (2011 [Ref: OpenAlex]) and Madras (2017 [Ref: PubMed]). No specific forensic seizure case reports for proscaline were identified in the peer-reviewed literature.

### Regulatory History

- **1971:** UK Misuse of Drugs Act passed; proscaline is covered implicitly by the generic phenethylamine clause (Class A) from this date forward [Ref 18].
- **1991:** PiHKAL published; proscaline documented in widely accessible form for the first time.
- **No specific scheduling events** (individual listing) were identified for proscaline in any jurisdiction.

---

## Subjective Effects

Published human self-experiment reports come exclusively from PiHKAL (Shulgin 1991 [Ref 12, 13]). No controlled human trials have been conducted with proscaline.

**PiHKAL self-experiment reports (oral, doses 30–60 mg):**

- **30 mg:** Dulled pain, sharpened senses, feeling of relaxation.
- **35 mg:** Quiet experience, minimal visual phenomena, initial restlessness followed by drowsiness.
- **40 mg:** "Deep feeling of peace and contentment," euphoria lasting throughout the day.
- **60 mg:** Strong physical effects, considerable irritability, intoxicating but with clear thinking retained.

**Key observations across experiments:**
- Effects were primarily **physical and somatic** rather than profoundly visual or cognitive.
- Visual phenomena were notably **absent or minimal** at doses tested (unlike higher-potency phenethylamines such as the 2C series).
- Appetite suppression was not a notable feature.
- Profound insights were not prominently described.
- No hangover reported in at least one account.

**Early Czech research** (referenced in PiHKAL [Ref 13]):
- Doses up to 80 mg were documented.
- At these higher doses: **residual dream disturbances** and effects extending **beyond 12 hours** were noted.

**Duration data (from PiHKAL and PsychonautWiki [Ref 20]):**
- **Onset:** 30–60 minutes
- **Total duration:** 8–12 hours
- **After-effects:** 3–5 hours
- At 80 mg (Czech data): effects may extend beyond 12 hours

**Effect domains documented:** The DB taxonomy lists time alteration, perceptual effects (after-images, tracers, object transformations, color alteration, etc.), emotional enhancement, cognitive effects (novelty enhancement, conceptual thinking, cognitive euphoria), body effects (spontaneous body sensations, abnormal heartbeat, nausea, pupil dilation), and transpersonal effects (unity and interconnectedness). Given PiHKAL reports that effects are primarily physical/somatic at standard doses with minimal visual phenomena, the visual and transpersonal effects in the taxonomy may apply more at higher/stronger doses. This should be noted by the generation agent.

---

## Safety & Toxicity

### LD50 and Lethal Dose

**No LD50 data has been published for proscaline in any species.** No lethal case reports were identified. 

By class inference from mescaline: mescaline's LD50 in rodents is high (800 mg/kg i.p. in rats per older toxicological literature); the therapeutic index for psychedelic phenethylamines is large. However, this cannot be extrapolated quantitatively to proscaline without species-specific data.

**⚠️ FLAG — No published LD50 or lethal dose data for proscaline. Safety-critical gap.**

### Adverse Effects

No published case reports of adverse events, overdose, or clinical toxicity specific to proscaline were identified in PubMed or the clinical literature.

By class, 5-HT₂A agonist psychedelics including mescaline carry the following documented risks:
- **Nausea and emesis:** Common adverse effect with mescaline, dose-dependent. Klaiber et al. (2024 [Ref 3]) reported nausea/emesis as a frequent adverse effect at the highest mescaline dose (800 mg). Proscaline's nausea profile is unknown; PiHKAL reports do not prominently mention nausea.
- **Cardiovascular:** 5-HT₂A agonism produces dose-dependent increases in heart rate and blood pressure (Klaiber et al. 2024 [Ref 3] confirmed for mescaline). Proscaline likely shares this profile.
- **Psychological adverse effects:** Anxiety, panic reactions, paranoia, and psychosis-like states can occur with psychedelic phenethylamines, particularly at high doses, in vulnerable individuals, or in unfavorable set/setting.
- **HPPD:** Hallucinogen Persisting Perception Disorder (persistent visual disturbances after use) is documented for 5-HT₂A agonist class, including case reports with potent full agonists such as 25I-NBOMe (Schetz et al. 2022 [Ref 21]). Risk with proscaline is unknown.

The seed data states "no negative health effects attributed to trying this drug" — this statement accurately reflects the absence of published case reports, but should not be interpreted as a confirmed safety profile. It reflects a data gap, not a demonstrated safety record.

---

## Harm Reduction

Based on structural class and PiHKAL data:

- **Dose accuracy:** Low active doses (30–60 mg range) require precise measurement. A milligram-accurate scale is essential; volumetric dosing in solution is recommended for precision.
- **Set and setting:** Standard harm reduction principles for psychedelic phenethylamines apply. Psychological vulnerability (personal or family history of psychosis, schizophrenia, or bipolar I) is a contraindication.
- **MAOI interactions:** Proscaline undergoes expected monoamine oxidase-mediated deamination. Concurrent use of MAO inhibitors (including harmaline/ayahuasca, moclobemide, phenelzine, tranylcypromine) may substantially increase systemic exposure and risk of serotonin syndrome. **This is a safety-critical inference — no published interaction data for proscaline specifically.**
- **Testing:** Reagent testing (Marquis, Mecke, Simon's) is recommended as a minimum identification precaution; specific color reactions for proscaline are not documented in the literature found.
- **Duration awareness:** 8–12 hour total duration should be planned for; higher doses may extend beyond 12 hours (Czech data).
- **Redosing:** Tolerance develops rapidly after ingestion; redosing during an experience is unlikely to produce proportional intensification and may increase adverse effects.

---

## Tolerance & Dependence

### Tolerance

5-HT₂A agonist psychedelics including proscaline develop tolerance through receptor downregulation (de la Fuente Revenga et al. 2022 [Ref 6]). Key mechanistic findings:
- Repeated administration of 5-HT₂A agonist DOI produced progressive reduction in HTR; tolerance apparent within 24 hours of a single dose.
- Tolerance involves **5-HT₂A receptor density downregulation** in frontal cortex.
- Mechanistically independent of β-arrestin-2.
- Tolerance blocked by 5-HT₂A antagonist M100907, confirming receptor-mediated origin.

**Seed data (DB):** Buildup: almost immediately after ingestion; half-life of tolerance: 3 days; full reset: 7 days. This is consistent with the literature on the 5-HT₂A class; no proscaline-specific tolerance kinetics were found.

### Cross-Tolerance

Full cross-tolerance exists among 5-HT₂A agonist psychedelics (de la Fuente Revenga et al. 2022 [Ref 6]; Halberstadt et al. 2020 [Ref 2]):
- **Cross-tolerant with:** LSD, psilocybin, mescaline, DMT, DOx series, and other 5-HT₂A agonists.
- **No cross-tolerance with:** Dissociatives (ketamine), MDMA, cannabinoids, or non-psychedelic 5-HT₂A agonists (e.g., lisuride).

**Seed data** lists cross-tolerance class as "psychedelic" — consistent with the literature.

### Dependence and Abuse Liability

No published dependence liability data for proscaline specifically. The mescaline class is not considered habit-forming based on:
- Absence of significant dopamine reward pathway activation
- Rapid tolerance development (self-limiting use)
- No withdrawal syndrome documented
- Seed data: "not habit-forming" — consistent with class-level evidence.

---

## Interactions

**⚠️ FLAG — No published drug interaction data specifically for proscaline. All interactions below are class-level inferences.**

### Serotonin Syndrome Risk

- **MAO inhibitors (irreversible or reversible):** High-risk interaction. MAO-A mediates oxidative deamination of phenethylamines including mescaline (Thomann et al. 2022 [Ref 4]; Dinis-Oliveira et al. 2019 [Ref 5]). MAOI co-administration would be expected to markedly increase plasma proscaline concentrations and risk serotonin syndrome. This includes:
  - Pharmaceutical MAOIs (phenelzine, tranylcypromine, selegiline, moclobemide)
  - Herbal sources (harmine/harmaline in ayahuasca preparations, Peganum harmala)

### Additive/Synergistic Psychedelic Effects

- **Other 5-HT₂A agonists** (LSD, psilocybin, mescaline, DMT, DOx): Cross-tolerance limits acute combination potency. Pharmacodynamic interactions unpredictable.
- **Cannabis:** Documented to intensify and unpredictably alter psychedelic experiences; anxiety risk increased.
- **Stimulants (amphetamines, cocaine):** Additive cardiovascular stress.

### Antagonistic/Blocking

- **5-HT₂A antagonists** (ketanserin, haloperidol, risperidone, clozapine): Will attenuate or block proscaline's psychedelic effects. Confirmed for mescaline class (Klaiber et al. 2024 [Ref 3]).

### Lithium

- Lithium carbonate combined with serotonergic psychedelics has been associated with seizure risk in case reports (general psychedelic class literature; no proscaline-specific data). **This combination should be considered contraindicated.**

---

## Legal Status

| Jurisdiction | Status | Basis | Source |
|---|---|---|---|
| United Kingdom | **Class A** (Schedule 1) | MDA 1971, Schedule 2 Part I, para 1(c): phenethylamine derivatives with ring alkoxy substitution | [Ref 18] |
| United States | **Uncontrolled** (federal) | Not explicitly scheduled under CSA; mescaline is Schedule I. Federal Analogue Act (21 U.S.C. §813) may apply if intended for human consumption (substantially similar to mescaline) | Web sources |
| Canada | **Uncontrolled** | Not listed in Controlled Drugs and Substances Act Schedules; mescaline is Schedule III | Web sources |
| Australia | **Uncertain** | Mescaline is a Schedule 9 Prohibited Substance under the Poisons Standard; proscaline may be covered by analog provisions but is not explicitly listed | Web sources |
| Germany / EU | **Likely controlled** in some jurisdictions | German NpSG (Novel Psychoactive Substances Act 2016) uses structural analogue definitions; Swiss/Austrian legislation covers phenethylamine analogs (Grafinger et al. 2019 [Ref 22]). Specific proscaline status varies by country. | [Ref 22] |

**⚠️ FLAG — Legal status for Germany, France, Netherlands, and other individual EU member states was not confirmed from primary legal sources. Research was limited to secondary web sources for non-UK jurisdictions.**

---

## Clinical Trials

No clinical trials for proscaline were identified on ClinicalTrials.gov (search returned 0 results). No clinical trial data exists in the published literature. This is consistent with proscaline's status as an unscheduled (in most jurisdictions) research chemical without pharmaceutical development history.

---

## Community Feedback Analysis

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

---

## Gaps & Flags

### Safety-Critical Gaps (Human Review Required)

1. **No published LD50 or lethal dose data** for proscaline in any species. Seed data states "no negative health effects attributed to trying this drug" — this reflects absence of published reports, not a demonstrated safety record. **Flag for article prose: state this explicitly.**

2. **No published drug interaction data** specifically for proscaline. All interaction data is class-level inference from mescaline and phenethylamine pharmacology. MAOI interaction risk is inferred, not measured. **Flag as safety-critical inference.**

3. **No specific Ki, EC₅₀, or Ki values at 5-HT₂A** for proscaline have been published. Only relative potency direction (greater than mescaline in HTR) is documented. The Halberstadt 2019 paper contains quantitative ED₅₀ data in its full text but values were not accessible via abstract alone.

4. **MAOI interaction** risk is inferred from mescaline metabolism (MAO-A deamination) — no proscaline-specific data.

### Data Gaps

5. **No human pharmacokinetic data** for proscaline. All PK (Tmax, t1/2, Cmax) inferred from mescaline (Klaiber et al. 2024 [Ref 3]).

6. **Early Czechoslovakian research** (referenced in PiHKAL): doses up to 80 mg tested, residual effects beyond 12 hours documented, but the primary Czech publication could not be identified. This may be pre-digital literature not indexed in PubMed or OpenAlex.

7. **CYP enzyme involvement in proscaline metabolism** has not been characterized. Inferred from mescaline class.

8. **Australian and EU legal status** not confirmed from primary sources. Secondary web sources only.

9. **5-HT₂B cardiac risk:** Not characterized for proscaline. Mescaline-class phenethylamines are not associated with the cardiac valvulopathy risk of fentluramine (which requires sustained 5-HT₂B activation), but no direct data is available for proscaline (Rothman & Baumann 2009 [Ref 15]).

10. **HPPD incidence** for proscaline unknown. Risk is present by class (Schetz et al. 2022 [Ref 21]) but magnitude is undetermined.

### Dose/Duration Data Note

The seed database dose range (Threshold: 10 mg; Light: 15–30 mg; Common: 30–40 mg; Strong: 40–60 mg; Heavy: 60+ mg) aligns with:
- PiHKAL reported self-experiments (active doses 30–60 mg) [Ref 12, 13]
- PsychonautWiki data [Ref 20]
- Czech research data (up to 80 mg) [Ref 13]

The seed data **appears well-calibrated**. The upper boundary of the "strong" dose range in the DB (40–60 mg) aligns exactly with PiHKAL's described maximum. No contradiction identified.

Duration data (8–12 hours total) is consistent across PiHKAL, PsychonautWiki, and Czech sources. The after-effects window (3–5 hours) is from PsychonautWiki; not specifically documented in PiHKAL.

### Areas Relying on Structural Analogy / Class Inference

- All pharmacokinetic parameters
- Metabolic pathway and CYP enzyme involvement
- MAOI interaction risk
- LD50 and safety margins
- 5-HT₂B cardiac risk assessment
- Nausea/emesis profile

---

## Summary Assessment

Proscaline is a sparse-data substance. The sole published primary research paper directly measuring its pharmacology is Halberstadt et al. 2019 [Ref 1], which confirms 5-HT₂A-mediated activity and greater potency than mescaline in the mouse HTR assay. All other data comes from:
- PiHKAL self-experiments (authoritative but anecdotal)
- Class-level inference from mescaline pharmacology and human studies
- Legal databases and secondary sources

The generation agent should clearly distinguish between substance-specific data (from Halberstadt 2019 and PiHKAL) and class-level inference throughout the article.