generation run 2026-05-08
87 min completedmodel pipeline-v5plan not recordedrun/5661411c…Selection
Verification
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- seen / partial
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The model's own caveats
- sparse_evidence
- note
Reproduce
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- 52 source keys (listed under Sources)
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- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
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- none — agent transcripts are persisted from 2026-09 onward
23 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | mitragynine | 1 | 1 | Primary chemical identity verification |
| 2 | ClinicalTrials.gov | mitragynine kratom | 8 | 6 | All relevant clinical trials |
| 3 | PubMed | mitragynine pharmacokinetics bioavailability human metabolism CYP | 1 | 1 | Only PK systematic review found |
| 4 | PubMed | mitragynine toxicity overdose adverse effects case report | 9 | 7 | Safety-critical case reports for toxicity section |
| 5 | OpenAlex | mitragynine kratom pharmacology | 15 | 8 | High-citation landmark papers in mitragynine pharmacology |
| 6 | PubMed | mitragynine pharmacology opioid receptor binding | 15 | 5 | Core pharmacology papers on receptor binding and signaling profiles |
| 7 | WebSearch | kratom DEA Schedule I 2016 withdrawal regulatory history United States legal status 2025 | 10 | 2 | Legal/regulatory history not in academic databases |
| 8 | PubMed | kratom mitragynine subjective effects dose human study | 2 | 2 | Only published human controlled dose studies |
| 9 | PubMed | kratom Mitragyna speciosa neonatal abstinence withdrawal pregnancy | 3 | 2 | Neonatal harm data |
| 10 | PubMed | mitragynine kratom dependence withdrawal syndrome symptoms | 12 | 7 | Key dependence and withdrawal literature |
| 11 | ClinicalTrials.gov | mitragynine kratom | 8 | 5 | Active and completed clinical trials |
| 12 | OpenAlex | kratom mitragynine scheduling legal status FDA DEA regulation | 8 | 3 | Regulatory and legal history papers |
| 13 | PubMed | kratom mitragynine human plasma pharmacokinetics clinical | 10 | 6 | Human PK characterization studies |
| 14 | WebSearch | mitragynine kratom legal status UK Australia Canada EU scheduled countries 2025 | 10 | 3 | Jurisdictional legal status data |
| 15 | WebSearch | mitragynine first isolation history 1921 Field kratom alkaloid discovery | 10 | 3 | Historical isolation and structure elucidation history |
| 16 | OpenAlex | kratom user survey United States motivations opioid pain management | 8 | 2 | User survey and regulatory data |
| 17 | PubMed get_pubmed_article | PMID 28521200 | 1 | 1 | Verification of key epidemiology paper |
| 18 | WebSearch | kratom DEA Schedule I 2016 withdrawal regulatory history United States legal status | 10 | 2 | US legal history and current status |
| 19 | Multiple sources · absence | mitragynine Ki MOR KOR DOR binding affinity values | 0 | 0 | Safety-critical gap flagged for editorial review |
| 20 | PubMed get_pubmed_article | PMID 31263758 | 1 | 1 | Key metabolite mechanism paper verification |
| 21 | WebSearch | mitragynine kratom legal status UK Australia Canada EU countries 2025 | 10 | 2 | International legal landscape |
| 22 | PubMed get_pubmed_article | PMID 25995615 | 1 | 1 | First human PK study data verification |
| 23 | OpenAlex | mitragynine stereochemistry diastereomers chemical structure | 8 | 2 | Stereochemistry and diastereomer pharmacology data |
128 claims by section — every cited sentence, checked against its source
safety52 · 27 ok
Multiple reviews cite seizures as a recognized adverse event.supported
hepatotoxicity, seizures; CYP inhibition interactions. jcph.2001
Treatment of kratom dependence most commonly employs buprenorphine-naloxone (Suboxone) for both acute detoxification and maintenancesupported
buprenorphine-naloxone as treatment 1389450121666200719011653
Claim in safety — inconclusiveinconclusiveworking →
The largest mortality series — 156 kratom-associated deaths — found mitragynine implicated as the sole intoxicant in only 23% of cases; 87% involved co-exposure to other psychoactive substances.supported
156 deaths: mitragynine alone implicated in 23% of cases; poly-substance use in 87% 0269881119862530
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
A comprehensive scoping review identified 26 case reports, 7 DILI Network cases, and 25 FDA database casessupported
Scoping review of 26 case reports + 7 DILI Network cases + 25 FDA database + 27 internet cases. s40265-019-01242-6
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Perioperative concerns include hemodynamic instability and agitation in surgical patients with kratom use history.supported
Perioperative concerns with kratom: hemodynamic instability, agitation, pain management difficulty, withdrawal aorn.70077
Animal data confirm significantly less respiratory depression than morphine at equianalgesic dosespartially supported
Animal study comparing respiratory effects of mitragynine vs oxycodone; mitragynine partial agonist at MOR without beta-arrestin-2 signaling; reduced respiratory depression. s00213-022-06244-z
Claim in safety — inconclusiveinconclusiveworking →
Three published case reports document NAS in infants born to mothers using kratom, with symptoms including oral intolerance, restlessness, irritability, and vomitingsupported
Case report of NAS in infant born to mother who used kratom daily to self-treat opioid dependence. peds.2018-1839
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
In the only controlled human study, 40 mg mitragynine produced increased ratings of amnesia and mild psychopathological symptoms, though the clinical significance at this dose is unclear.supported
At 40 mg: amnesia ratings, mild psychopathological symptoms. Vital signs unaffected. Well tolerated up to 40 mg. s00213-024-06734-2
User reports and survey data describe anxiety, irritability, and depressed mood as dose-dependent or withdrawal-associated phenomenasupported
70% mild anxiety, 81% mild depression on cessation 02791072.2018.1511879
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
In humans, consumption exceeding approximately 4 glasses of kratom tea per day (76–115 mg/day mitragynine equivalent) is associated with higher withdrawal severity.supported
76-115 mg mitragynine/day in 4+ glasses; moderate pain and sleep problems on cessation 02791072.2018.1443234
Withdrawal symptoms include myalgia, joint pain, lacrimation, rhinorrhea, yawning, insomnia (46% report increased sleep problems on cessation), diarrhea, feverish sensations, appetite loss, tremors, and nauseapartially supported
moderate pain and sleep problems on cessation 02791072.2018.1443234
Psychological symptoms include depressed mood (81% report mild depression), anxiety (70% report mild anxiety), restlessness, irritability, and tension.supported
70% mild anxiety, 81% mild depression on cessation 02791072.2018.1511879
Cessation from regular kratom use produces withdrawal symptoms rated as milder than those of classical opioid analgesics in user reports, consistent with preclinical findings that kratom alkaloids produce significantly less naloxone-precipitated withdrawal than morphine at equieffective doses.supported
effects milder than opioid analgesics. 02791072.2018.1443234
Cessation from regular kratom use produces withdrawal symptoms rated as milder than those of classical opioid analgesics in user reports, consistent with preclinical findings that kratom alkaloids produce significantly less naloxone-precipitated withdrawal than morphine at equieffective doses.supported
kratom alkaloid extract, mitragynine, and mitragynine pseudoindoxyl show significantly fewer naloxone-precipitated withdrawal signs than morphine s10571-020-01034-7
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Mitragynine's time-dependent CYP3A inhibition (KI ≈ 4 μM; kinact ≈ 0.07 min⁻¹) increases exposure to CYP3A substrates with narrow therapeutic indicessupported
Mitragynine is time-dependent CYP3A inhibitor: KI ~4 uM, kinact ~0.07 min-1. cpt.2891
PBPK modelling predicts midazolam exposure increases of 2.2–2.7×.supported
midazolam exposure increases 2.2-2.7x acsptsci.5c00718
Claim in safety — inconclusiveinconclusiveworking →
Reciprocally, CYP3A inhibitors (azole antifungals, macrolide antibiotics, ritonavir) reduce 7-HMG formation from mitragynine, potentially attenuating opioid effects while increasing parent compound exposure.supported
CYP3A4 inhibitors reduce 7-HMG formation. acsptsci.5c00718
The majority of kratom-associated deaths involved concurrent CNS depressant use.partially supported
poly-substance use in 87% 0269881119862530
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Mitragynine inhibits P-gp-mediated efflux, relevant for drugs with significant P-gp-dependent intestinal absorption or blood-brain barrier efflux (digoxin, dabigatran, certain chemotherapeutics).supported
Mitragynine inhibits CYP2D6, CYP3A, and P-glycoprotein. dmd.122.001005
Mitragynine inhibits CYP2D6 in vitro, though clinical effects at typical kratom doses are minimal (no significant change in dextromethorphan disposition with 2 g kratom tea)supported
No effect on dextromethorphan (CYP2D6). cpt.2891
Higher doses or sensitive CYP2D6 substrates may present interaction risk.supported
Mitragynine inhibits CYP2D6, CYP3A, and P-glycoprotein. dmd.122.001005
Claim in safety — inconclusiveinconclusiveworking →
Specific LC-MS/MS methods are required for identification; a validated 11-alkaloid plasma assay has been published.supported
Validated LC-MS/MS assay for 11 kratom alkaloids in human plasma. s00216-024-05689-9
Neonatal abstinence syndrome has been documented in three published case reportssupported
Case report of NAS in infant born to mother who used kratom daily to self-treat opioid dependence. peds.2018-1839
Claim in safety — inconclusiveinconclusiveworking →
Hepatic impairment: Pre-existing liver disease increases risk of drug-induced liver injury and impairs clearance of both mitragynine and the CYP3A-generated metabolite 7-HMGpartially supported
Kratom likely causes liver injury based on totality of evidence. s40265-019-01242-6
The majority of kratom-associated fatalities involve poly-substance exposuresupported
poly-substance use in 87% 0269881119862530
CYP3A substrates with narrow therapeutic index: Mitragynine's time-dependent CYP3A inhibition can increase plasma concentrations of co-administered CYP3A substrates to toxic levelssupported
Mitragynine is time-dependent CYP3A inhibitor: KI ~4 uM, kinact ~0.07 min-1. cpt.2891
Claim in safety — inconclusiveinconclusiveworking →
Perioperative use warrants specific clinical attention due to risks of hemodynamic instability, agitation, pain management difficulty, and withdrawal precipitation in surgical patients.supported
Perioperative concerns with kratom: hemodynamic instability, agitation, pain management difficulty, withdrawal aorn.70077
pharmacology24 · 14 ok
The active metabolite 7-HMG appears in plasma with Tmax of 1.2–2.0 h, and its half-life increases from 4.7 h (single dose) to 24.7 h (multiple doses)supported
7-HMG Tmax 1.2-1.8 h; T1/2 4.7 h single, 24.7 h multiple. molecules29050984
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Time to steady state is 8–9 days for mitragynine and approximately 7 days for 7-HMG.partially supported
Steady-state in 8-9 days. molecules29050984
Mitragynine and 7-HMG demonstrate functional selectivity (biased agonism) for G-protein (Gᵢ) signaling with no measurable recruitment of β-arrestin-2 in vitro. β-Arrestin-2 recruitment is the primary intracellular pathway mediating respiratory depression, constipation, and rapid analgesic tolerance with classical opioidssupported
Mitragynine and 7-HMG: G-protein biased MOR partial agonists with no measurable beta-arrestin recruitment. s41598-020-76119-w
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Interactions with serotonergic receptors and neuronal calcium channels have been reported in multiple reviews, though specific Ki/EC₅₀ values at individual serotonin receptor subtypes have not been systematically publishedsupported
mitragynine and 7-OH-MG mechanisms, adrenergic, serotonergic, dopaminergic pathways jcph.2001
Claim in pharmacology — inconclusiveinconclusiveworking →
Mitragynine is rapidly absorbed after oral administration, reaching peak plasma concentrations (Tmax) within approximately 1 hour (range 0.8–1.7 h across studies).supported
Tmax 0.83 +/- 0.35 h dddt.s79658
Mitragynine is rapidly absorbed after oral administration, reaching peak plasma concentrations (Tmax) within approximately 1 hour (range 0.8–1.7 h across studies).supported
Tmax 1.0-1.3 h single, 1.0-1.7 h multiple. molecules29050984
Mitragynine is rapidly absorbed after oral administration, reaching peak plasma concentrations (Tmax) within approximately 1 hour (range 0.8–1.7 h across studies).supported
Mitragynine Tmax 1-2 h pharmaceutics14030620
The terminal elimination half-life is remarkably long: 23.2 ± 16.1 h after single doses in chronic users, up to 43.4 h in single-dose pharmacokinetic studies in opioid-naive participants, and 67.9 h with multiple daily dosingsupported
terminal half-life 23.24 +/- 16.07 h dddt.s79658
The terminal elimination half-life is remarkably long: 23.2 ± 16.1 h after single doses in chronic users, up to 43.4 h in single-dose pharmacokinetic studies in opioid-naive participants, and 67.9 h with multiple daily dosingsupported
Terminal half-life up to 43.4 h single, 67.9 h multiple dose. molecules29050984
The apparent volume of distribution is large (38.0 ± 24.3 L/kg), indicating extensive tissue distributionsupported
Vd 38.04 +/- 24.32 L/kg dddt.s79658
Urinary excretion of unchanged mitragynine accounts for only 0.14% of the administered dose, consistent with near-complete hepatic first-pass metabolism.supported
urine excretion of unchanged form 0.14% dddt.s79658
Claim in pharmacology — inconclusiveinconclusiveworking →
A single 2 g kratom dose increased midazolam AUC by 1.39× and Cmax by 1.50× in a clinical drug interaction study, consistent with intestinal rather than hepatic CYP3A inhibitionsupported
2g kratom tea + midazolam (CYP3A probe): AUC increased 1.39x, Cmax 1.50x. Primarily intestinal CYP3A inhibition. cpt.2891
Mitragynine also inhibits P-glycoprotein (P-gp)-mediated efflux.supported
Mitragynine inhibits CYP2D6, CYP3A, and P-glycoprotein. dmd.122.001005
Oral bioavailability (F%) of pure mitragynine has not been directly measured in healthy human volunteers. In silico predictions suggest fractional absorption exceeding 75% based on physicochemical properties, but human confirmation is lacking.supported
Most kratom alkaloids fall into BCS Class I-II (>75% oral absorption). Predicted high permeability and oral bioavailability. jat.4617
summary12 · 7 ok
Oral effects peak within 1–2 hours and persist for approximately 2–5 hours, though terminal elimination extends to 23–67 hours depending on dosing chronicity.partially supported
Tmax 0.83 +/- 0.35 h; terminal half-life 23.24 +/- 16.07 h dddt.s79658
Oral effects peak within 1–2 hours and persist for approximately 2–5 hours, though terminal elimination extends to 23–67 hours depending on dosing chronicity.partially supported
Tmax 1.0-1.3 h single, 1.0-1.7 h multiple. Terminal half-life up to 43.4 h single, 67.9 h multiple dose. molecules29050984
First isolated by Ellen Field at the University of Edinburgh in 1921, mitragynine has become a compound of major pharmacological interest due to its G-protein-biased μ-opioid agonism — it does not recruit β-arrestin-2, the intracellular pathway primarily mediating respiratory depression and rapid tolerance with classical opioidssupported
Mitragynine and 7-HMG: G-protein biased MOR partial agonists with no measurable beta-arrestin recruitment. s41598-020-76119-w
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Physical dependence develops with regular use exceeding approximately 76–115 mg/day mitragynine, with withdrawal symptoms rated milder than classical opioid withdrawalsupported
76-115 mg mitragynine/day in 4+ glasses; moderate pain and sleep problems on cessation; effects milder than opioid analgesics. 02791072.2018.1443234
No human LD₅₀ has been established; 87% of kratom-associated deaths involve poly-substance exposuresupported
poly-substance use in 87% 0269881119862530
Hepatotoxicity — predominantly cholestatic, mean latency 21 days — is a recognized adverse effectsupported
Latency 20.6 days (mean). Predominantly cholestatic histology. s40265-019-01242-6
Mitragynine's time-dependent CYP3A inhibition (KI ≈ 4 μM) creates clinically significant drug interaction potential with co-administered CYP3A substratessupported
Mitragynine is time-dependent CYP3A inhibitor: KI ~4 uM, kinact ~0.07 min-1. cpt.2891
receptor-pharmacology7 · 2 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Both mitragynine and 7-HMG demonstrate G-protein-biased agonism: they activate Gᵢ-mediated signaling without measurable β-arrestin-2 recruitment in vitrosupported
Mitragynine and 7-HMG: G-protein biased MOR partial agonists with no measurable beta-arrestin recruitment. s41598-020-76119-w
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Multiple reviews report mitragynine interactions with serotonergic receptors and neuronal Ca²⁺ channelssupported
mitragynine and 7-OH-MG mechanisms, adrenergic, serotonergic, dopaminergic pathways jcph.2001
pharmacokinetic-detail6 · 5 ok
The largest human pharmacokinetic study employed a randomized, double-blind, placebo-controlled design with 500–4000 mg dried kratom leaf powder (6.65–53.2 mg mitragynine equivalent) across multiple cohorts:partially supported
Largest human PK study. 500-4000 mg dried leaf (6.65-53.2 mg mitragynine). molecules29050984
Clinical confirmation: a single 2 g kratom tea dose increased midazolam (CYP3A probe substrate) AUC by 1.39× and Cmax by 1.50×, with no change in midazolam half-life — consistent with pre-systemic intestinal CYP3A inhibition rather than hepatic inhibitionsupported
AUC increased 1.39x, Cmax 1.50x. Primarily intestinal CYP3A inhibition. cpt.2891
CYP2D6 inhibition is demonstrable in vitro but produced minimal clinical effects on dextromethorphan (CYP2D6 probe) at a 2 g kratom tea dose.supported
No effect on dextromethorphan (CYP2D6). cpt.2891
The data fit a two-compartment pharmacokinetic model with linear kinetics: Tmax 0.83 ± 0.35 h, terminal half-life 23.24 ± 16.07 h, apparent volume of distribution 38.04 ± 24.32 L/kg, and urinary recovery of unchanged mitragynine 0.14%.supported
Two-compartment model. Tmax 0.83 +/- 0.35 h; terminal half-life 23.24 +/- 16.07 h; Vd 38.04 +/- 24.32 L/kg; urine excretion of unchanged form 0.14%. Linear PK. dddt.s79658
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Mitragynine also inhibits P-glycoprotein (P-gp)-mediated efflux, potentially increasing oral bioavailability and CNS penetration of co-administered P-gp substrates.supported
Mitragynine inhibits CYP2D6, CYP3A, and P-glycoprotein. dmd.122.001005
chemistry5 · 1 ok
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
The 3S alkaloid series (mitragynine, speciogynine, paynantheine) exhibits shorter time to peak concentration (Tmax 1–2 h vs. 2.5–4.5 h) and longer terminal half-life (24–45 h vs. 12–18 h) compared to the 3R series (speciociliatine, mitraciliatine, isopaynantheine)partially supported
Mitragynine Tmax 1-2 h, half-life 24-45 h. Two-compartment model. 3S vs 3R alkaloid stereoisomer PK differences documented. pharmaceutics14030620
comparative-pharmacology5 · 4 ok
Naloxone-precipitated withdrawal in animal models is significantly less severe for mitragynine and kratom alkaloid extract than for morphine at equieffective analgesic doses.supported
kratom alkaloid extract, mitragynine, and mitragynine pseudoindoxyl show significantly fewer naloxone-precipitated withdrawal signs than morphine s10571-020-01034-7
Buprenorphine-naloxone is the most-studied pharmacological treatment for kratom dependence.supported
buprenorphine-naloxone as treatment 1389450121666200719011653
Classical opioid respiratory depression is primarily mediated through β-arrestin-2 signaling; mitragynine's absence of arrestin engagement in vitro and reduced respiratory depression in rodent models suggest a wider therapeutic window, though this advantage has not been confirmed in controlled human studies.supported
Mitragynine and 7-HMG: G-protein biased MOR partial agonists with no measurable beta-arrestin recruitment. s41598-020-76119-w
Classical opioid respiratory depression is primarily mediated through β-arrestin-2 signaling; mitragynine's absence of arrestin engagement in vitro and reduced respiratory depression in rodent models suggest a wider therapeutic window, though this advantage has not been confirmed in controlled human studies.supported
Animal study comparing respiratory effects of mitragynine vs oxycodone; mitragynine partial agonist at MOR without beta-arrestin-2 signaling; reduced respiratory depression. s00213-022-06244-z
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
neuroscience5 · 2 ok
The absence of β-arrestin-2 recruitment by mitragynine is predicted to slow receptor internalization and reduce the rate of analgesic tolerance development — a hypothesis supported by the observation that kratom alkaloids produce less naloxone-precipitated withdrawal than morphine at equieffective dosessupported
kratom alkaloid extract, mitragynine, and mitragynine pseudoindoxyl show significantly fewer naloxone-precipitated withdrawal signs than morphine s10571-020-01034-7
Mitragynine's partial agonist efficacy at MOR predicts a lower ceiling on dopamine release compared to full agonists, consistent with the milder euphoria and lower abuse potential reported in user surveys and regulatory analyses.supported
Comprehensive review of kratom abuse potential by CSA 8-factor analysis; recommends against Schedule I; lower respiratory depression than classical opioids; biased agonism. s00213-017-4813-4
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
clinical-evidence4 · 3 ok
Experienced heavy users consume an estimated 76–115 mg/day mitragynine equivalent, indicating the study did not evaluate the full dose range encountered in naturalistic use.supported
76-115 mg mitragynine/day in 4+ glasses 02791072.2018.1443234
A clinical drug interaction study using 2 g kratom tea with midazolam (CYP3A probe) and dextromethorphan (CYP2D6 probe) in healthy participants confirmed clinically relevant intestinal CYP3A inhibition (midazolam AUC increase 1.39×, Cmax increase 1.50×) with minimal effect on CYP2D6 metabolism.supported
2g kratom tea + midazolam (CYP3A probe): AUC increased 1.39x, Cmax 1.50x. No effect on dextromethorphan (CYP2D6). Primarily intestinal CYP3A inhibition. cpt.2891
The only published placebo-controlled clinical study of pure mitragynine in healthy human volunteers was a Phase 1, single-blind, within-subjects design in 15 participants across two parts:supported
Phase 1 placebo-controlled study in 15 healthy volunteers. s00213-024-06734-2
Claim in clinical-evidence — inconclusiveinconclusiveworking →
alkaloid-profile3 · 1 ok
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
Claim in alkaloid-profile — not_supportednot supportedworking →
The stereochemistry-dependent pharmacokinetic differences between the 3S series (mitragynine, speciogynine, paynantheine — shorter Tmax, longer half-life) and 3R series (speciociliatine, mitraciliatine — longer Tmax, shorter half-life) are substantial and have been characterized in human pharmacokinetic studies.supported
3S vs 3R alkaloid stereoisomer PK differences documented. pharmaceutics14030620
history3 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
The discovery of biased agonism at the μ-opioid receptor — G-protein signaling without β-arrestin-2 recruitment — by Varadi et al. in 2016 and Todd et al. in 2020 positioned mitragynine alkaloids as potential leads for safer analgesic development.supported
Mitragynine and 7-HMG: G-protein biased MOR partial agonists with no measurable beta-arrestin recruitment. s41598-020-76119-w