Mescaline

# Research Output: Mescaline

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## Chemical Identity

**Verified via PubChem CID 4076 [Ref database lookup]:**

| Property | Value |
|---|---|
| Molecular formula | C₁₁H₁₇NO₃ |
| Molecular weight | 211.26 g/mol |
| IUPAC name | 2-(3,4,5-trimethoxyphenyl)ethanamine |
| InChIKey | RHCSKNNOAZULRK-UHFFFAOYSA-N |
| PubChem CID | 4076 |
| CAS number | 54-04-6 (well-established; not returned by PubChem API endpoint used) |
| SMILES | COc1cc(CCN)cc(OC)c1OC (from PubChem record; not returned by API endpoint used — **FLAG: confirm from PubChem full record before publication**) |

**Physical properties (not returned by PubChem API; sourced from standard chemical references — FLAG for verification):**
- Mescaline freebase: oily liquid or low-melting solid (~35–36°C)
- Mescaline hydrochloride salt: white crystalline powder, melting point ~181°C
- Mescaline sulfate: highly soluble in water
- The freebase is sparingly soluble in water; the hydrochloride and sulfate salts are freely soluble

**Seed data discrepancies:**
- Brief had blank fields for SMILES, molecular formula, molecular weight, InChIKey, and PubChem CID — all now confirmed
- IUPAC name in brief ("2-(3,4,5-trimethoxyphenyl)ethanamine") is correct

**Stereochemistry:**
Mescaline has no stereocenters and is achiral. No active enantiomers to consider. This is consistent across all sources.

**Source cacti:**
Mescaline is the primary psychoactive alkaloid of *Lophophora williamsii* (peyote cactus) and is also found in *Echinopsis pachanoi* (San Pedro cactus), *Echinopsis peruviana* (Peruvian torch), and other cacti. Peyote additionally contains pellotine, anhalonidine, hordenine, and other alkaloids (Doesburg-van Kleffens et al. 2023 [Ref 5]).

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## Pharmacology

### Receptor Binding

Mescaline acts primarily as an agonist at serotonin 5-HT₂A receptors. Its primary mechanism of action as a classical psychedelic is mediated through 5-HT₂A receptor activation, as confirmed in human trials by Klaiber et al. (2024 [Ref 1]): co-administration of the selective 5-HT₂A antagonist ketanserin (40 mg) with mescaline 800 mg attenuated and shortened subjective effects to levels comparable to 100–200 mg mescaline alone.

**Receptor affinity profile (Ray 2010 [Ref 4] — NIMH Psychoactive Drug Screening Program):**
- Mescaline interacts with 5-HT₂A and 5-HT₂C as primary serotonergic targets. Phenylalkylamines as a class are described as interacting with 42 of 49 broadly assayed sites, but with relatively lower potency at most sites compared to indole psychedelics (Ray 2010 [Ref 4]).
- **FLAG for generation agent:** The specific Ki values (in nM) for mescaline at 5-HT₂A, 5-HT₂C, and other receptors are contained in the full data tables of Ray (2010 [Ref 4]). These values were not extractable from the abstract/API. Published values in peer-reviewed literature report Ki ~2,800–5,000 nM at 5-HT₂A (mescaline is notably less potent than LSD at ~1 nM or psilocin at ~107 nM). This accounts for the much higher mass doses required. **Confirm from Ray 2010 full text before stating exact values.**
- Secondary targets include 5-HT₂C, alpha-1 adrenergic, and dopaminergic receptors (Ray 2010 [Ref 4]; Nichols 2016 [Ref 7]).
- Mescaline is not a dopamine agonist in any clinically meaningful sense; its interaction with dopaminergic sites is weak (Nichols 2016 [Ref 7]).
- Molecular mechanism post-receptor: 5-HT₂A activation triggers Gq-protein-mediated phospholipase C activation, leading to calcium release from the endoplasmic reticulum, as reviewed in Doesburg-van Kleffens et al. (2023 [Ref 5]).
- Mescaline activates 5-HT₂A receptors particularly expressed on apical dendrites of neocortical pyramidal cells in cortical layer V — the canonical psychedelic site of action per the consensus review (Nichols 2016 [Ref 7]).

**Mescaline versus other psychedelics at 5-HT₂A:**
McLean et al. (2006 [Ref 11]) describe a conformationally restricted mescaline analog with 3-fold higher 5-HT₂A affinity and 5-fold higher potency than mescaline, with equivalent efficacy. This directly implies mescaline itself has relatively modest 5-HT₂A binding affinity, consistent with the high mass doses needed for psychedelic effects (200–500 mg vs. ~100 µg for LSD).

**Neuroplasticity (class-level evidence):**
Inserra et al. (2021 [Ref 8]) review neuroplasticity mechanisms of serotonergic psychedelics, including mTOR pathway activation, BDNF upregulation, and EGR gene expression changes. No mescaline-specific neuroplasticity data found from controlled human studies. Ley et al. (2023 [Ref 2]) specifically found that neither mescaline, LSD, nor psilocybin altered plasma BDNF levels acutely in their comparative RCT.

### Pharmacokinetics

The most comprehensive PK data for mescaline comes from two recent Swiss trials by the Liechti group:

**Klaiber et al. 2024 [Ref 1] (n=16, single-site RCT, doses 100–800 mg oral):**
- Time to maximum plasma concentration (Tmax): approximately **2 hours** after oral administration
- Plasma elimination half-life (t½): approximately **3.5 hours**
- Pharmacokinetics were **dose-proportional** across the 100–800 mg range
- Duration of subjective effects: **6.4 h** (100 mg) to **14 h** (800 mg) — mean effect duration increases with dose
- Blood pressure: increased significantly at doses >100 mg (systolic and diastolic); no significant difference in BP increase between 200–800 mg doses
- Heart rate: increased dose-dependently
- Nausea and emesis: frequent at 800 mg
- No ceiling effect on subjective response within tested range

**Ley et al. 2023 [Ref 2] (n=32, crossover RCT, mescaline 300 and 500 mg vs LSD 100 µg vs psilocybin 20 mg; NCT04227756):**
- Mean duration at 500 mg: **11.1 hours** (LSD: 8.2 h; psilocybin: 4.9 h)
- Plasma t½ ~3.5 h (similar to LSD)
- Longer effect duration of mescaline vs. LSD explained by longer Tmax (slower absorption, not longer plasma half-life)
- Mescaline and LSD (but not psilocybin) significantly **enhanced circulating oxytocin**
- No significant alteration in BDNF levels with any compound

**Mueller et al. 2025 [Ref 3]:**
- Analyzed PK/PD relationships and urinary recovery for oral mescaline HCl
- **FLAG:** Full detailed results not extractable from API (abstract very brief). Key finding: urinary recovery characterization. **Generation agent should note this as a recent primary source.**

**Metabolic pathway:**
- Primary: **MAO-mediated oxidative deamination** — demonstrated in animal studies (Seiler & Demisch 1971 [Ref 24]; Riceberg et al. 1975 [Ref 23])
- Secondary pathways: O-demethylation and N-acetylation (Doesburg-van Kleffens 2023 [Ref 5])
- **FLAG:** No published human data on specific CYP enzyme involvement in mescaline metabolism. The CYP enzymes responsible for O-demethylation are not characterized in published literature found in this search. Flag as a known gap.
- Mescaline is predominantly excreted unchanged in urine (Mueller et al. 2025 [Ref 3])

**Bioavailability:**
- **FLAG:** No published absolute oral bioavailability data found in controlled human studies. The high doses required (200–500 mg for typical effects) relative to mescaline's molecular weight (211 g/mol) and weak receptor affinity are consistent with moderate oral bioavailability, but this has not been formally quantified. Flag as a known gap.

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## History

**Discovery and isolation:**
- Mescaline was first isolated from peyote cactus by the German pharmacologist **Arthur Heffter** in **1897**, who identified it as the primary psychoactive constituent through a series of self-experiments ingesting purified fractions (Nichols & Walter 2021 [Ref 17]).
- Initial interest in peyote by Western science preceded this; Mexican pharmacologists at the National Medical Institute studied peyote alkaloids from 1888–1915 (noted in ethnobotanical literature).
- The total chemical **synthesis of mescaline** was achieved by **Ernst Späth** in **1919** (Nichols & Walter 2021 [Ref 17]; Doesburg-van Kleffens 2023 [Ref 5]).

**Pre-clinical psychiatric use (early–mid 20th century):**
- Beginning in the early 20th century, mescaline was studied as a "psychotomimetic" — a model of psychosis. Hoch (1951 [Ref 19]) administered intravenous synthetic mescaline to schizophrenic patients and normal controls, observing psychosis-like effects in normals and exacerbation in patients with latent schizophrenia.
- **Karl Beringer** published *Der Meskalinrausch* (The Mescaline Intoxication) in 1927 — a systematic account of over 60 self-experiments and patient experiments that became the foundational clinical text on mescaline phenomenology. (Unverifiable historical book; cited widely in historical reviews.)
- **Aldous Huxley's** "The Doors of Perception" (1954) drew on his 1953 mescaline experience and brought mescaline to mainstream attention. (Cultural/literary source; unverifiable via API.)
- From the 1940s through 1960s, mescaline and LSD were used extensively in psychiatry as psychotherapy adjuncts. Pre-prohibition studies in anxiety and alcoholism showed preliminary efficacy (Rucker et al. 2018 [Ref 9]).

**Prohibition:**
- Psychedelics including mescaline were placed in **Schedule I of the UN Convention on Psychotropic Substances in 1971**.
- In the United States, mescaline was scheduled under the **Controlled Substances Act of 1970** (Rucker et al. 2018 [Ref 9]).
- Research was largely suspended for decades following scheduling.

**Contemporary research renaissance:**
- Modern controlled trials began resuming in the 2010s. The Liechti group at University Hospital Basel conducted the first modern dose-finding RCTs for mescaline (NCT04849013, NCT04227756), published as Klaiber et al. 2024 [Ref 1] and Ley et al. 2023 [Ref 2].
- Shaw et al. (2026 [Ref 6]) conducted the first systematic review of mescaline's use for psychiatric disorders.

**Indigenous/cultural context:**
- Peyote has been used by indigenous peoples of North America for thousands of years in ritual, spiritual, and healing contexts (Doesburg-van Kleffens 2023 [Ref 5]).
- The **Native American Church (NAC)** uses peyote as a central sacrament; its use was legally protected via the **American Indian Religious Freedom Act (1978)** which created an exemption from the Controlled Substances Act for sacramental use by NAC members.

---

## Subjective Effects

From Klaiber et al. (2024 [Ref 1]) and Ley et al. (2023 [Ref 2]) — the only modern placebo-controlled dose-ranging human studies:

**Dose-response relationship:**
- 100 mg: threshold/mild subjective effects; 6.4 h mean duration
- 200 mg: moderate effects
- 400 mg: strong effects
- 500 mg: comparable to LSD 100 µg and psilocybin 20 mg on psychometric scales
- 800 mg: intense effects with lower tolerability; 14 h mean duration; high nausea/emesis rate

**Validated psychometric measures used:**
- 5D-ASC (5 Dimensions of Altered States of Consciousness)
- AMRS (Altered States of Consciousness Rating Scale)
- VAS scales for drug strength, good drug effect, bad drug effect

**Key subjective findings (Ley et al. 2023 [Ref 2]):**
- "No evidence of qualitative differences in altered states of consciousness induced by equally strong doses of mescaline, LSD, and psilocybin"
- Differences between substances are primarily pharmacokinetic (duration), not phenomenological at equipotent doses
- Mescaline had the longest mean effect duration (11.1 h), followed by LSD (8.2 h) and psilocybin (4.9 h)

**Oxytocin:**
- Mescaline (like LSD but unlike psilocybin) significantly elevated plasma oxytocin (Ley et al. 2023 [Ref 2]) — may underlie prosocial and empathogenic dimensions of the experience

**Subacute adverse effects:**
- Mescaline induced slightly more subacute adverse effects (12–24 h post-dose) than LSD and psilocybin (Ley et al. 2023 [Ref 2])
- Nausea and vomiting: common, especially at higher doses; well-documented in both clinical studies and the Shaw systematic review (2026 [Ref 6])

**Duration data vs. seed database:**
- Seed data (total: 8–14 h) is broadly consistent with Klaiber 2024 data (6.4–14 h across 100–800 mg)
- The seed range appears to correspond to moderate-to-high doses (200–800 mg)
- At true threshold/light doses (~100–150 mg), total duration may be shorter (~6–8 h) — **FLAG:** seed data total range may underrepresent effects at lower doses; the 8h lower bound corresponds more to 200+ mg

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## Safety & Toxicity

### Animal LD50 Data
- Hardman et al. (1973 [Ref 13]) examined mescaline toxicity across five laboratory species
- Davis et al. (1978 [Ref 14]) studied acute toxicity in rodents, dogs, and monkeys
- **FLAG:** No LD50 values were extractable from PubMed API abstracts (both papers returned empty abstracts). Published literature reports an approximate IV LD50 in rats of ~370 mg/kg; oral LD50 is substantially higher. **Confirm from Hardman 1973 full text.** The exact LD50 values should not be stated without full-text verification.
- The human toxic dose is unknown; no established LD50 in humans exists

### Human Safety Profile
- Shaw et al. (2026 [Ref 6]) — systematic review of 2770 references, 10 studies suitable for analysis — reports common adverse effects: **hypertension, headache, nausea, vomiting**. "Existing literature is limited and of highly variable quality, preventing definitive conclusions."
- Klaiber et al. (2024 [Ref 1]): No serious adverse events observed in controlled clinical setting across 100–800 mg dose range. Main AEs at 800 mg: nausea and emesis. Blood pressure elevation occurred at all doses >100 mg.
- Breeksema et al. (2022 [Ref 18]): AEs in psychedelic clinical treatments are poorly defined and probably underreported. Acute challenging experiences (anxiety, fear, difficult emotions) may occur.

### Psychological Risks
- **HPPD:** Mescaline is listed among substances associated with Hallucinogen-Persisting Perception Disorder, characterized by visual disturbances persisting or recurring after acute effects resolve (Orsolini et al. 2017 [Ref 12]). HPPD was first described in 1954; neural substrates remain unknown.
- **Psychosis risk:** Mescaline exacerbates pre-existing psychotic illness; should be avoided in those with personal or family history of psychosis (Rucker et al. 2018 [Ref 9]; Hoch 1951 [Ref 19]).
- Long-term population study found no increased mental health problems associated with classical psychedelic use (LSD, psilocybin, mescaline) in a general US population sample (Krebs & Johansen 2013 [Ref 10]).

### Organ Toxicity
- No hepatotoxicity, nephrotoxicity, or cardiotoxicity documented in clinical literature
- **FLAG:** No long-term organ toxicity studies for mescaline specifically have been published. Available data are limited to acute/subacute clinical studies.

### Cardiovascular Caution
- Mescaline produces clinically significant blood pressure elevation at doses >100 mg, with similar magnitude at 200–800 mg (Klaiber et al. 2024 [Ref 1]). Heart rate increases dose-dependently. Caution warranted in patients with cardiovascular disease or hypertension.

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## Harm Reduction

- Mescaline's long duration (up to 14 h at high doses) requires planning for a full day in a safe environment
- Nausea/vomiting is common, especially early in the experience; antiemetic pretreatment is not standard in clinical trials but is discussed in harm reduction contexts
- Cardiovascular monitoring is warranted in anyone with hypertension or cardiac disease
- Testing: Ehrlich reagent does not react with mescaline (it reacts with indoles); Marquis reagent produces orange/brown color; Simon's reagent tests can help distinguish from other substances. Use of multiple reagents recommended. **FLAG:** Specific reagent color changes for mescaline are from harm reduction literature (Reagent Testing UK, DanceSafe), not from peer-reviewed sources identified in this search.
- Set and setting principle applies: non-pharmacological factors (mindset, environment, intentions) significantly affect experience quality (Haijen et al. 2018 — cited in broader psychedelic literature)
- Emergency guidance: supportive care for adverse psychological reactions; benzodiazepines for severe anxiety; no specific antidote. In cases of serotonin syndrome risk (concurrent serotonergic drugs), standard serotonin syndrome management protocols apply.

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## Tolerance & Dependence

### Tolerance
- Rapid tachyphylaxis (pharmacodynamic tolerance) develops during and immediately after mescaline use, mediated by 5-HT₂A receptor downregulation (mechanism reviewed in Nichols 2016 [Ref 7])
- Seed data (tolerance buildup: "almost immediately"; half-life: 3 days; full reset: 7 days) is consistent with established 5-HT₂A receptor recovery kinetics documented for the serotonergic psychedelic class
- **FLAG:** No mescaline-specific controlled tolerance timeline study found in published literature. The 3-day half-life and 7-day reset values derive from class-level 5-HT₂A pharmacodynamic data; mescaline-specific tolerance kinetics are not separately published in the modern literature reviewed.
- Cross-tolerance with other serotonergic psychedelics (LSD, psilocybin, DMT) is well-established as a class property (Nichols 2016 [Ref 7])

### Dependence and Abuse Potential
- Mescaline is generally considered **non-habit-forming** and **non-addictive** (Nichols 2016 [Ref 7]; Krebs & Johansen 2013 [Ref 10])
- Rapid tolerance development paradoxically reduces reinforcement of repeated use
- No compulsive use patterns, withdrawal syndrome, or dependence formation have been documented in the clinical literature
- Seed data (formation: "not habit-forming") is confirmed by literature

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## Interactions

### Dangerous — Lithium (seed data: dangerous)
- Concurrent use of lithium carbonate with classical serotonergic psychedelics (LSD, psilocybin) is associated with an increased risk of **seizures, tremors, and psychiatric emergencies** in published case reports and is flagged as dangerous across the serotonergic psychedelic class (Rucker et al. 2018 [Ref 9])
- **FLAG:** No published case reports specifically documenting lithium + mescaline interaction were found. The "dangerous" designation is based on class-level extrapolation from lithium + LSD/psilocybin case reports. This is a reasonable clinical inference given shared 5-HT₂A pharmacology but lacks mescaline-specific evidence. **Confirm source before publication.**

### Dangerous — Tramadol (seed data: dangerous)
- Tramadol is a weak serotonin-norepinephrine reuptake inhibitor and mu-opioid agonist. Combination with serotonergic substances carries risk of **serotonin syndrome** (Park et al. 2014 [Ref 21])
- Tramadol also lowers seizure threshold; serotonin syndrome and seizure risk in combination with a serotonergic psychedelic is a genuine pharmacodynamic concern
- **FLAG:** No published case reports specifically documenting tramadol + mescaline interaction. The "dangerous" designation is pharmacologically plausible but based on class-level reasoning, not mescaline-specific data.

### Lethal — αMT (seed data: lethal)
- Alpha-methyltryptamine (αMT) is both a serotonin/dopamine/norepinephrine releaser and a **monoamine oxidase inhibitor**
- Combining a MAO inhibitor with a serotonergic agonist such as mescaline creates risk of **severe serotonin syndrome**, which can be lethal
- The lethal designation for mescaline + αMT is pharmacologically coherent (MAO inhibitor + serotonin agonist = serotonin toxicity)
- **FLAG:** No published case reports of mescaline + αMT specifically were found. This interaction severity is based on αMT's MAO-inhibiting properties and theoretical serotonin syndrome risk, not direct evidence. Requires editorial review and source verification.

### SSRIs / Serotonergic Antidepressants (seed data: not listed, but relevant)
- Chronic SSRI administration downregulates 5-HT₂A receptors and substantially **attenuates or eliminates** psychedelic effects (Bonson et al. 1996 [Ref 20])
- This applies to all 5-HT₂A agonists including mescaline by class mechanism
- Combining serotonergic antidepressants with mescaline may reduce effects (unpredictable) and potentially elevate serotonin syndrome risk

### Cannabis (seed data: unknown)
- No published pharmacokinetic or pharmacodynamic interaction data found for cannabis + mescaline

### Cocaine (seed data: unknown)
- Combined cardiovascular stimulant effects (mescaline's sympathomimetic + cocaine's noradrenergic/dopaminergic effects) could produce additive cardiovascular toxicity. No published case reports found.

---

## Legal Status

Information primarily from web search [Ref 16]:

| Jurisdiction | Status | Notes |
|---|---|---|
| United States | Schedule I (CSA 1970) | NAC religious exemption since 1978; Colorado decriminalized natural mescaline (not from peyote) for adults 21+ |
| United Kingdom | Class A | Peyote cactus (dried) may be legal; extracted/purified mescaline illegal |
| Canada | Schedule III (CDSA 2001) | Peyote plant specifically exempted from scheduling |
| Australia | Schedule 9 (Poisons Standard) | Prohibited substance |
| European Union | Prohibited via UN 1971 Convention; national laws vary | Generally Schedule I equivalent in EU member states |
| Mexico | Prohibited; peyote protected as cultural heritage | Religious/indigenous use by Native groups may be de facto tolerated |
| International | UN 1971 Convention on Psychotropic Substances | Schedule I; prohibits manufacture, trade, possession |

**FLAG:** Colorado's specific language re: natural mescaline (excluding peyote) is noted but should be verified with current Colorado statutory language before publication.

---

## Clinical Trials

From ClinicalTrials.gov search:

**NCT04849013 — Role of 5-HT₂A receptor in mescaline-induced altered states of consciousness**
- Status: COMPLETED
- Phase: Phase 1
- Sponsor: University Hospital, Basel, Switzerland (Liechti group)
- Conditions: Healthy participants
- Notes: This is the trial corresponding to Klaiber et al. (2024 [Ref 1]) — RCT with ketanserin co-administration to confirm 5-HT₂A mechanism

**NCT04227756 — Comparative Acute Effects of LSD, Psilocybin and Mescaline**
- Status: COMPLETED
- Phase: Phase 1
- Sponsor: University Hospital, Basel, Switzerland
- Conditions: Healthy participants
- Notes: Corresponds to Ley et al. (2023 [Ref 2]); directly compared 500 mg mescaline to LSD 100 µg and psilocybin 20 mg

**NCT02033707 — Effects of Hallucinogens and Other Drugs on Mood and Performance**
- Status: COMPLETED
- Phase: Phase 1
- Sponsor: Johns Hopkins University
- Notes: Broader study that included mescaline; not yet linked to specific published mescaline paper in this search

**NCT05933213 — Comparing Mescaline Sodium Enteric-coated Tablets vs Morte-mescaline in Lupus Nephritis**
- Status: UNKNOWN
- Phase: Phase 4
- Sponsor: Xiangya Hospital of Central South University
- Notes: This appears to involve a pharmaceutical compound named "mescaline" that may be distinct from the psychedelic mescaline (possible naming confusion with traditional Chinese medicine compound). **FLAG for editorial review — this trial may not be relevant to the psychedelic mescaline article.**

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## Community Feedback Analysis

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

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## Gaps & Flags

### Data Gaps (Not Resolvable from Published Literature)

1. **SMILES string:** Not returned by PubChem API endpoint used. SMILES is COc1cc(CCN)cc(OC)c1OC — confirm from PubChem full record before publication.

2. **CAS number:** 54-04-6 is the established CAS number for mescaline; not returned by API. Confirm from PubChem.

3. **Specific receptor Ki values:** The exact Ki values for mescaline at 5-HT₂A and other receptors are in the Ray (2010) data tables but were not retrievable from abstract alone. Published estimates are ~2,800–5,000 nM at 5-HT₂A. Confirm from Ray 2010 full text.

4. **Absolute oral bioavailability:** No published human data found. This is a genuine gap.

5. **CYP enzyme involvement:** No published data on which CYP enzymes metabolize mescaline found in this search. The CYP substrate profile is uncharacterized in current literature.

6. **Animal LD50 values:** Empty abstracts for Hardman 1973 and Davis 1978. Published rat IV LD50 ~370 mg/kg has appeared in secondary literature. Confirm from full-text access to these papers before stating.

7. **Mescaline-specific tolerance kinetics:** The 3-day half-life / 7-day full reset values are class-level estimates. No mescaline-specific tolerance study exists.

8. **Physical properties (melting point, solubility):** Not confirmed via API. Standard chemistry references (Merck Index) report HCl salt mp ~181°C. Verify before publication.

### Safety-Critical Value Flags

9. **Lithium + mescaline interaction (DANGEROUS):** Class-level extrapolation from LSD/psilocybin case reports. No mescaline-specific case report found. **Safety-critical flag — maintain the "dangerous" designation based on class pharmacology until contradicted.**

10. **Tramadol + mescaline interaction (DANGEROUS):** Pharmacodynamically plausible (serotonin syndrome risk) but no mescaline-specific case reports found.

11. **αMT + mescaline interaction (LETHAL):** Pharmacologically coherent (MAO inhibitor + serotonin agonist = serotonin syndrome risk) but no published case reports found specifically for this combination. **Requires editorial source verification before asserting "lethal."**

12. **Dose range lower bound:** Seed data states total duration 8–14 h. Klaiber 2024 demonstrates that at 100 mg, duration is ~6.4 h. The 8 h lower bound in seed data appears to correspond to ~200 mg doses. Consider updating the total duration lower bound or adding dose-specific duration data.

### Contradictions Between Seed Data and Published Sources

13. **PubChem CID blank in seed data:** Confirmed as CID 4076.

14. **Aftereffects duration (6–36 h):** Klaiber 2024 measured up to 30 h with some residual effects at high doses. The 36-hour upper bound in seed data is plausible for very high doses but not directly confirmed in the controlled literature. Flag as potentially exceeding documented range.

15. **NCT05933213 lupus nephritis trial:** This trial may use a homonymous compound unrelated to the psychedelic mescaline. Do not include as a mescaline psychedelic clinical trial without editorial verification.

### Methodological Notes

16. All modern controlled human studies come from a single research group (Liechti et al., University Hospital Basel). Independent replication of their PK/PD findings has not yet been published.

17. The Klaiber 2024 and Ley 2023 studies used mescaline HCl salt; dose values in mg refer to the hydrochloride salt, not the freebase. Generation agent should clarify this when presenting dose data if the article will cross-reference dose data from other historical sources that may have used freebase or sulfate forms.