generation run 2026-05-14
69 min completedmodel pipeline-v5plan not recordedrun/dee8f1a4…Selection
Verification
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- seen / partial
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The model's own caveats
1 further caveat recorded as free text — readable on the working page
Reproduce
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- 34 source keys (listed under Sources)
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- none — agent transcripts are persisted from 2026-09 onward
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | Salvia divinorum detection drug testing urine blood forensic | 1 | 1 | Drug testing methodology relevant to detection section |
| 2 | PubMed | Salvia divinorum human study subjective effects dose controlled | 6 | 6 | All key human experimental studies selected |
| 3 | EUDA (European Union Drugs Agency) | Salvia divinorum EU drug profile | 1 | 1 | EU regulatory perspective on Salvia divinorum |
| 4 | PubMed | Evolution and origins Mazatec hallucinogenic sage Salvia divinorum | 1 | 1 | Important phylogenetic/botanical data |
| 5 | PubMed | Salvia divinorum cognitive impairment memory learning effects | 2 | 1 | Relevant preclinical safety data on cognitive effects |
| 6 | PubMed | Salvia divinorum pharmacology salvinorin review | 15 | 7 | Selected comprehensive reviews and landmark papers on pharmacology |
| 7 | WebSearch/WebFetch | Salvia divinorum legal status Australia UK Germany international | 10 | 2 | International legal status data |
| 8 | PubMed | salvinorin A pharmacokinetics half-life plasma | 2 | 1 | Key pharmacokinetics data |
| 9 | PubChem | salvinorin A | 1 | 1 | Confirmed chemical identity of primary active constituent |
| 10 | ClinicalTrials.gov | Salvia divinorum salvinorin | 3 | 3 | All 3 completed trials relevant |
| 11 | Plants of the World Online (POWO) | Salvia divinorum taxonomy | 1 | 1 | Authoritative taxonomy source |
| 12 | PubMed | Salvia divinorum psychiatric adverse effects psychosis hospitalization | 4 | 3 | Selected safety/adverse event case reports |
| 13 | WebSearch | Salvia divinorum legal status United States DEA scheduling states ban 2024 | 10 | 2 | Legal status overview |
| 14 | OpenAlex | Salvia divinorum salvinorin kappa opioid (sorted by citations) | 406 | 4 | Selected landmark papers by citation count |
| 15 | PubMed · absence | Salvia divinorum ethnobotany history traditional use Mazatec | 0 | 0 | Used broader searches to find ethnobotanical information |
| 16 | PubMed | salvinorin A gastrointestinal anti-inflammatory KOR CB1 colitis | 1 | 1 | Therapeutic potential data |
| 17 | Multiple | Salvinorin A dose effects duration route smoked oral buccal | 5 | 4 | Cross-reference of dose data across preparations to verify consistency |
| 18 | PubMed | kappa opioid receptor agonist dysphoria aversion depression preclinical | 5 | 2 | Key preclinical data on KOR-mediated depressive effects relevant to safety section |
| 19 | PubMed · absence | Salvia divinorum legal status scheduling controlled substance | 0 | 0 | Legal data sourced from web |
| 20 | PubMed Central | salvinorin A leaf concentration HPLC quantification commercial products | 1 | 1 | Key quantification data for alkaloid profile section |
81 claims by section — every cited sentence, checked against its source
safety28 · 7 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Commercial S. divinorum products carry labeling accuracy concerns: measured salvinorin A content deviates substantially from labeled potency claimssupported
Commercial extract potency claims do not reliably correspond to concentration. acsomega.2c06106
Claim in safety — inconclusiveinconclusiveworking →
Dysphoria is more frequently reported than euphoriasupported
Water potion of crushed leaves produced short-lasting light-headedness, dysphoria, tactile and proprioceptive sensations. pmid:23627785
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The aversive phenomenology and KOR-mediated dopaminergic suppression — rather than enhancement — are thought to underlie the substance's low abuse potentialsupported
Review of salvinorin A KOR mechanism: beta-arrestin-biased signaling, thalamocortical disruption, mesolimbic dopaminergic suppression. Low abuse potential. biomedicines14020476
The aversive phenomenology and KOR-mediated dopaminergic suppression — rather than enhancement — are thought to underlie the substance's low abuse potentialsupported
Decreased dopamine in nucleus accumbens without affecting serotonin. Supports kappa-opioid stimulation producing depressive-like effects. pmid:16223871
Claim in safety — inconclusiveinconclusiveworking →
Multiple reviews conclude that salvinorin A has low abuse potential based on aversive phenomenology, dopaminergic suppression, and absence of positive reinforcement in animal self-administration paradigms.supported
Review of salvinorin A KOR mechanism: beta-arrestin-biased signaling, thalamocortical disruption, mesolimbic dopaminergic suppression. Low abuse potential. biomedicines14020476
Claim in safety — inconclusiveinconclusiveworking →
Salvinorin A is metabolised by CYP2D6, CYP1A1, CYP2E1, and CYP2C18, with additional glucuronidation via UGT2B7, and is a P-glycoprotein substratesupported
CYP2D6, CYP1A1, CYP2E1, CYP2C18, UGT2B7 substrates. P-gp substrate. j.ejpb.2009.01.002
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Hepatic impairment: CYP enzyme involvement in salvinorin A metabolism suggests possible altered metabolism in liver disease. No published clinical data exist.supported
CYP2D6, CYP1A1, CYP2E1, CYP2C18, UGT2B7 substrates. j.ejpb.2009.01.002
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
summary19 · 9 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Its pharmacology is driven by salvinorin-a, a neoclerodane diterpenoid and the first known naturally occurring non-nitrogenous kappa-opioid receptor (KOR) agonistsupported
Salvinorin A potently and selectively inhibited kappa opioid receptors. pmid:12192085
When smoked or vaporized, effects onset within approximately 2 minutes and resolve within 15–20 minutes; traditional buccal quid preparations produce a more gradual experience lasting 30–90 minutes.partially supported
Drug strength peaked at 2 min, effects absent ~20 min after inhalation. j.drugalcdep.2010.11.005
Claim in summary — inconclusiveinconclusiveworking →
Gordon Wasson and Albert Hofmann's expedition to the Sierra Mazateca, S. divinorum has been used in Mazatec divinatory healing ceremonies for centuriessupported
In 1962 ethnopharmacologists Hofmann and Wasson undertook expedition to Oaxaca Mexico, first scientists to collect flowering specimen of Salvia divinorum allowing identification of species. j.jep.2013.11.032
The identification of salvinorin A as a selective KOR agonist in 2002 established a unique pharmacological mechanism — hallucinogenic potency without serotonin 5-HT₂A receptor involvementsupported
Salvinorin A potently and selectively inhibited kappa opioid receptors. Had no activity at 5-HT2A receptor. pmid:12192085
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Salvinorin A acts as a highly selective full agonist at KOR with no clinically significant activity at the serotonin 5-HT₂A receptor or at over 50 other screened molecular targetspartially supported
Salvinorin A potently and selectively inhibited kappa opioid receptors. Had no activity at 5-HT2A receptor. pmid:12192085
KOR activation suppresses mesolimbic dopaminergic transmission in the nucleus accumbens and disrupts thalamocortical signalling, producing the substance's characteristic dissociative and hallucinogenic effects without the euphoria or positive reinforcement associated with classical psychedelics or mu-opioid agonists.partially supported
Decreased dopamine in nucleus accumbens without affecting serotonin. Supports kappa-opioid stimulation producing depressive-like effects. pmid:16223871
KOR activation suppresses mesolimbic dopaminergic transmission in the nucleus accumbens and disrupts thalamocortical signalling, producing the substance's characteristic dissociative and hallucinogenic effects without the euphoria or positive reinforcement associated with classical psychedelics or mu-opioid agonists.supported
Review of salvinorin A KOR mechanism: beta-arrestin-biased signaling, thalamocortical disruption, mesolimbic dopaminergic suppression. Low abuse potential. biomedicines14020476
Claim in summary — inconclusiveinconclusiveworking →
Dysphoria is more frequently reported than euphoria, particularly with traditional buccal preparationssupported
Water potion of crushed leaves produced short-lasting light-headedness, dysphoria, tactile and proprioceptive sensations. pmid:23627785
Claim in summary — inconclusiveinconclusiveworking →
Salvinorin A displays low abuse potential due to KOR-mediated dopaminergic suppression and aversive phenomenology; no formal dependence syndrome or withdrawal has been describedsupported
Review of salvinorin A KOR mechanism: beta-arrestin-biased signaling, thalamocortical disruption, mesolimbic dopaminergic suppression. Low abuse potential. biomedicines14020476
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
preparations10 · 4 ok
Dried leaf material (salvinorin A concentration averaging 1.54 mg/g, range 0.89–7.8 mg/g) is smoked in a pipe or water pipesupported
Average in raw leaves: 1.54 mg/g. acsomega.2c06106
Measured salvinorin A content ranges from 13.0 to 53.2 mg/g — an 8- to 35-fold increase over plain leafsupported
Enhanced extracts: 13.0-53.2 mg/g. acsomega.2c06106
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
Onset: Approximately 2 minutes (peak effects coincide with onset at the first measured time point)supported
Drug strength peaked at 2 min. j.drugalcdep.2010.11.005
Effect character: Dose-related increases on the Hallucinogen Rating Scale and Mysticism Scale. Internal and external hallucinations, spatial disorientation, depersonalisation and derealisation, proprioceptive distortion, entity contact, revisiting of childhood memories, cartoon-like visual imagery, temporal disorientation, and amnesia for portions of the experience. Post-acute residual fatigue and mild cognitive fog lasting hours.supported
Dose-related mystical-type and hallucinogen rating scale increases. j.drugalcdep.2010.11.005
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
history8 · 4 ok
The Mazatec people of the Sierra Mazateca in Oaxaca, Mexico, have used Salvia divinorum in divinatory healing ceremonies (veladas) for centuries, where it is known as ska María pastora ("leaves of Mary the Shepherdess"), yerba de la pastora, and hojas de María Pastorasupported
Salvia divinorum is a sage endemic to a small region of Mexico used by Mazatec Indians for divination and spiritual healing. hup.2304
In 1962, Wasson and Albert Hofmann collected the first flowering specimen of S. divinorum, enabling formal botanical identification.supported
In 1962 ethnopharmacologists Hofmann and Wasson undertook expedition to Oaxaca Mexico, first scientists to collect flowering specimen of Salvia divinorum allowing identification of species. j.jep.2013.11.032
Field research conducted by Diaz between 1973 and 1983 documented three principal preparation methods: a fresh-leaf quid (crushed or rolled leaves held in the mouth for buccal absorption), a water infusion (crushed fresh leaves mixed with cold water), and direct chewing of fresh leaves with juice retained sublinguallysupported
Traditional Mazatec beliefs, ritual uses, and mental effects of Salvia divinorum from 1973-1983 field research. Water potion of crushed leaves... pmid:23627785
Claim in history — inconclusiveinconclusiveworking →
The landmark mechanistic discovery came in 2002, when Roth et al. identified salvinorin A as a potent, selective kappa-opioid receptor agonist with no activity at the serotonin 5-HT₂A receptorsupported
Salvinorin A potently and selectively inhibited kappa opioid receptors. Had no activity at 5-HT2A receptor. pmid:12192085
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
neuroscience8 · 6 ok
Salvinorin A is a selective full agonist at the kappa-opioid receptor (KOR) with no clinically significant activity at the serotonin 5-HT₂A receptor — the canonical target of classical psychedelicssupported
Salvinorin A potently and selectively inhibited kappa opioid receptors. Had no activity at 5-HT2A receptor. pmid:12192085
Claim in neuroscience — inconclusiveinconclusiveworking →
Salvinorin A displays pronounced β-arrestin-biased signalling that distinguishes it from endogenous dynorphins and classical KOR agonists, producing rapid receptor desensitisationsupported
Review of salvinorin A KOR mechanism: beta-arrestin-biased signaling, thalamocortical disruption, mesolimbic dopaminergic suppression. biomedicines14020476
KOR activation by salvinorin A engages several interconnected neural systems:supported
Review of salvinorin A KOR mechanism: beta-arrestin-biased signaling, thalamocortical disruption, mesolimbic dopaminergic suppression. biomedicines14020476
Mesolimbic dopaminergic suppression: Salvinorin A decreases extracellular dopamine in the nucleus accumbens without affecting serotonin. This suppression explains the characteristically aversive or dysphoric quality and the substance's low abuse potential.supported
Decreased dopamine in nucleus accumbens without affecting serotonin. Supports kappa-opioid stimulation producing depressive-like effects. pmid:16223871
Claim in neuroscience — inconclusiveinconclusiveworking →
Preclinical data from rats (intraperitoneal administration) provide the available quantitative parameters:supported
In vivo PK in rats: half-life 75 min (plasma), brain half-life 36 min. Vd 47.1 L/kg. Brain-to-plasma ratio 0.050. j.ejpb.2009.01.002
Human CYP isoforms metabolising salvinorin A in vitro include CYP2D6, CYP1A1, CYP2E1 (greatest effect — 31.1% decrease in concentration), and CYP2C18, with additional glucuronidation via UGT2B7partially supported
CYP2D6, CYP1A1, CYP2E1, CYP2C18, UGT2B7 substrates. j.ejpb.2009.01.002
alkaloid-profile4 · 3 ok
salvinorin-a (C₂₃H₂₈O₈; molecular weight 432.5 g/mol) is the principal psychoactive compound in S. divinorum and the first reported naturally occurring non-nitrogenous kappa-opioid receptor agonistsupported
Salvia divinorum whose main active ingredient is the neoclerodane diterpene Salvinorin A... Salvinorin A potently and selectively inhibited kappa opioid receptors. pmid:12192085
Salvinorin A contains no nitrogen atom, making it structurally unique among potent opioid receptor ligands, which typically require a basic nitrogen for receptor engagement.supported
Salvinorin A potently and selectively inhibited kappa opioid receptors. pmid:12192085
Chambers et al. (2023) quantified salvinorin A in commercial products using DART-HRMS (direct analysis in real time–high resolution mass spectrometry):supported
DART-HRMS method for quantification of salvinorin A in commercial Salvia products. acsomega.2c06106
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
botanical-overview3 · 1 ok
Claim in botanical-overview — inconclusiveinconclusiveworking →
Gordon Wasson and Albert Hofmann in the Sierra Mazatecasupported
In 1962 ethnopharmacologists Hofmann and Wasson undertook expedition to Oaxaca Mexico. j.jep.2013.11.032
Claim in botanical-overview — inconclusiveinconclusiveworking →
effects-overview1 · 0 ok
Claim in effects-overview — inconclusiveinconclusiveworking →