7-Hydroxymitragynine

Sources

25 strong · 6 moderate · 14 weak

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

Values approved

82/82 (100%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

oraltrace

Field	Published	AI Proposed	Confidence
Threshold	—	—	low
Low	—	—	low
Common	—	—	low
Strong	—	—	low
Heavy	—	—	low
Editorial	No published human dose-finding data for isolated 7-hydroxymitragynine exist. Animal antinociceptive doses (2.5-10 mg/kg s.c., 5-10 mg/kg oral in mice; Matsumoto 2004) cannot be directly extrapolated to human doses due to species differences in metabolism (7-HMG converts to more potent mitragynine pseudoindoxyl in human plasma to a far greater extent than in rodents). Semi-synthetic products exist in various formulations but no standardized human dose ranges have been published. All numeric tier values intentionally omitted — proposing with confidence=low to flag the complete absence of human dose data.
	ReasoningReasoning No published human dose-finding data for isolated 7-hydroxymitragynine exist. Animal antinociceptive doses (2.5-10 mg/kg s.c., 5-10 mg/kg oral in mice; Matsumoto 2004) cannot be directly extrapolated to human doses due to species differences in metabolism (7-HMG converts to more potent mitragynine pseudoindoxyl in human plasma to a far greater extent than in rodents). Semi-synthetic products exist in various formulations but no standardized human dose ranges have been published. All numeric tier values intentionally omitted — proposing with confidence=low to flag the complete absence of human dose data. Evidence basis: animal_study

sublingualtrace

Field	Published	AI Proposed	Confidence
Threshold	—	—	low
Low	—	—	low
Common	—	—	low
Strong	—	—	low
Heavy	—	—	low
Editorial	No published human dose data for sublingual 7-HMG. Case reports describe use of sublingual 7-HMG films (Reif et al. 2025) but provide no dose-response characterization. Sublingual delivery bypasses hepatic first-pass metabolism, increasing bioavailability relative to oral — dose requirements would be expected to be lower than oral but cannot be quantified from available evidence.
	ReasoningReasoning No published human dose data for sublingual 7-HMG. Case reports describe use of sublingual 7-HMG films (Reif et al. 2025) but provide no dose-response characterization. Sublingual delivery bypasses hepatic first-pass metabolism, increasing bioavailability relative to oral — dose requirements would be expected to be lower than oral but cannot be quantified from available evidence. Evidence basis: single_case_report

Duration

oral

Field	Published	AI Proposed	Confidence
Onsettrace	20–45 minutes	20–45 minutes	low
Editorial	Inferred from PK Tmax of 1.2-1.8h for metabolically derived 7-HMG (Huestis 2024). Onset of subjective effects precedes Tmax; estimated at 20-45 minutes based on opioid class analogy and the metabolic formation pathway from mitragynine via CYP3A.
	ReasoningReasoning Inferred from PK Tmax of 1.2-1.8h for metabolically derived 7-HMG (Huestis 2024). Onset of subjective effects precedes Tmax; estimated at 20-45 minutes based on opioid class analogy and the metabolic formation pathway from mitragynine via CYP3A. Evidence basis: structural_analogy
Peaktrace	1.5–3 hours	1.5–3 hours	low
Editorial	Inferred from PK Tmax ~1.5h and single-dose T½ 4.7h (Huestis 2024). Peak duration estimated by opioid class analogy with morphine, adjusted for 7-HMG's PK parameters. No controlled human subjective duration data exist.
	ReasoningReasoning Inferred from PK Tmax ~1.5h and single-dose T½ 4.7h (Huestis 2024). Peak duration estimated by opioid class analogy with morphine, adjusted for 7-HMG's PK parameters. No controlled human subjective duration data exist. Evidence basis: structural_analogy
Offsettrace	2–4 hours	2–4 hours	low
Editorial	Inferred from single-dose elimination half-life of 4.7h (Huestis 2024). Offset duration estimated from opioid class pharmacodynamic-pharmacokinetic relationships. Note: with chronic dosing, T½ extends to 24.7h, which would substantially prolong offset.
	ReasoningReasoning Inferred from single-dose elimination half-life of 4.7h (Huestis 2024). Offset duration estimated from opioid class pharmacodynamic-pharmacokinetic relationships. Note: with chronic dosing, T½ extends to 24.7h, which would substantially prolong offset. Evidence basis: structural_analogy
Totaltrace	4–8 hours	4–8 hours	low
Editorial	Estimated total subjective duration based on sum of onset through offset phases, informed by single-dose T½ of 4.7h and opioid class analogy. This represents acute single-dose subjective experience only. With chronic dosing and T½ extension to 24.7h, subjective duration may be substantially longer. NOT derived from half-life alone — inferred from morphine pharmacodynamic analogy.
	ReasoningReasoning Estimated total subjective duration based on sum of onset through offset phases, informed by single-dose T½ of 4.7h and opioid class analogy. This represents acute single-dose subjective experience only. With chronic dosing and T½ extension to 24.7h, subjective duration may be substantially longer. NOT derived from half-life alone — inferred from morphine pharmacodynamic analogy. Evidence basis: structural_analogy
After effectstrace	6–24 hours	6–24 hours	low
Editorial	Wide range reflects the dramatic T½ extension from 4.7h (single dose) to 24.7h (steady state) documented by Huestis 2024, suggesting significant accumulation and prolonged sub-threshold effects with repeated dosing. Upper bound based on the steady-state elimination half-life.
	ReasoningReasoning Wide range reflects the dramatic T½ extension from 4.7h (single dose) to 24.7h (steady state) documented by Huestis 2024, suggesting significant accumulation and prolonged sub-threshold effects with repeated dosing. Upper bound based on the steady-state elimination half-life. Evidence basis: structural_analogy

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	high	high	medium
Chronic	moderate	moderate	medium
Organs Affected	pulmonary, hepatic, cardiovascular, renal	pulmonary, hepatic, cardiovascular, renal	medium
Editorial	Acute toxicity rated high based on 4.5× morphine respiratory depression potency (rat IV, Zuarth Gonzalez 2025) and documented fatalities. Chronic toxicity rated moderate based on hepatotoxicity case reports and cardiomegaly findings in postmortem studies (Iuteri 2026). Confidence is medium because respiratory depression ratio is from rat IV data only, fatality data reports mitragynine not 7-HMG concentrations, and hepatotoxicity involves full kratom alkaloid mixture.
	ReasoningReasoning Acute toxicity rated high based on 4.5× morphine respiratory depression potency (rat IV, Zuarth Gonzalez 2025) and documented fatalities. Chronic toxicity rated moderate based on hepatotoxicity case reports and cardiomegaly findings in postmortem studies (Iuteri 2026). Confidence is medium because respiratory depression ratio is from rat IV data only, fatality data reports mitragynine not 7-HMG concentrations, and hepatotoxicity involves full kratom alkaloid mixture. Evidence basis: published_case_series

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	high	high	high
Psychological	high	high	high
Compulsive Redosing	high	high	high
Dose Escalation	high	high	high
Editorial	Animal dependence data robust (Matsumoto 2005: tolerance, cross-tolerance, precipitated withdrawal in mice). Human case evidence consistent — multiple independent case reports document OUD from 7-HMG products (Reif 2025, Hendler 2026, Lybik 2026, Stanciu 2026). Self-administration substitutes for morphine (Hemby 2019).
	ReasoningReasoning Animal dependence data robust (Matsumoto 2005: tolerance, cross-tolerance, precipitated withdrawal in mice). Human case evidence consistent — multiple independent case reports document OUD from 7-HMG products (Reif 2025, Hendler 2026, Lybik 2026, Stanciu 2026). Self-administration substitutes for morphine (Hemby 2019). Evidence basis: published_case_series

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	severe	severe	high
Symptoms	anxiety, myalgia, lacrimation, rhinorrhea, piloerection, diarrhea, insomnia, restlessness, nausea, vomiting, diaphoresis	anxiety, myalgia, lacrimation, rhinorrhea, piloerection, diarrhea, insomnia, restlessness, nausea, vomiting, diaphoresis	high
Fatal	No	No	high
Medical Supervision	Required	Required	high
Editorial	Opioid-typical withdrawal confirmed in both animal models (naloxone-precipitated, Matsumoto 2005) and human case reports. COWS scores up to 31 documented (Stanciu 2026), indicating severe withdrawal. Early onset reported in case reports. Treatment with buprenorphine and methadone documented. Withdrawal is not typically fatal but medical supervision recommended given severity.
	ReasoningReasoning Opioid-typical withdrawal confirmed in both animal models (naloxone-precipitated, Matsumoto 2005) and human case reports. COWS scores up to 31 documented (Stanciu 2026), indicating severe withdrawal. Early onset reported in case reports. Treatment with buprenorphine and methadone documented. Withdrawal is not typically fatal but medical supervision recommended given severity. Evidence basis: published_case_series

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	moderate	moderate	medium
Half-life	—	—	medium
Full Reset	—	—	medium
Cross-tolerances	morphine, mu-opioid agonists (class)	morphine, mu-opioid agonists (class)	medium
Editorial	Animal tolerance data robust (Matsumoto 2005: bidirectional cross-tolerance with morphine in mice). Human tolerance kinetics unknown — no controlled studies. Clinical case reports suggest rapid escalation. Buildup rated moderate-to-rapid per work-notes; 'moderate' selected as the schema value. Confidence medium because human tolerance kinetics are uncharacterized.
	ReasoningReasoning Animal tolerance data robust (Matsumoto 2005: bidirectional cross-tolerance with morphine in mice). Human tolerance kinetics unknown — no controlled studies. Clinical case reports suggest rapid escalation. Buildup rated moderate-to-rapid per work-notes; 'moderate' selected as the schema value. Confidence medium because human tolerance kinetics are uncharacterized. Evidence basis: animal_study

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
respiratory Concurrent CNS depressant usetrace	absolute	absolute	high
Editorial	Established by epidemiological fatality data (156 deaths, 87% polysubstance) and pharmacological mechanism (additive respiratory depression). Safety-critical.
	ReasoningReasoning Established by epidemiological fatality data (156 deaths, 87% polysubstance) and pharmacological mechanism (additive respiratory depression). Safety-critical.
hepatic Severe hepatic impairmenttrace	absolute	absolute	medium
Editorial	CYP3A-dependent metabolism confirmed; hepatotoxicity documented in case reports with kratom. 7-HMG-specific hepatotoxicity not isolated but CYP-dependent clearance makes hepatic impairment a pharmacokinetic risk.
	ReasoningReasoning CYP3A-dependent metabolism confirmed; hepatotoxicity documented in case reports with kratom. 7-HMG-specific hepatotoxicity not isolated but CYP-dependent clearance makes hepatic impairment a pharmacokinetic risk.
respiratory Severe respiratory diseasetrace	absolute	absolute	high
Editorial	Respiratory depression is the primary acute lethal mechanism for 7-HMG. The 4.5× morphine potency ratio (rat IV) and full naloxone reversibility confirm MOR-mediated respiratory suppression.
	ReasoningReasoning Respiratory depression is the primary acute lethal mechanism for 7-HMG. The 4.5× morphine potency ratio (rat IV) and full naloxone reversibility confirm MOR-mediated respiratory suppression.
other CYP3A4 inhibitor co-administrationtrace	relative	relative	medium
Editorial	Human PK data (Mongar et al. 2024) and rat behavioral data (Kamble et al. 2023) both confirm significant CYP3A4 interaction. Net clinical effect for pre-formed 7-HMG is unpredictable — safety-critical flag.
	ReasoningReasoning Human PK data (Mongar et al. 2024) and rat behavioral data (Kamble et al. 2023) both confirm significant CYP3A4 interaction. Net clinical effect for pre-formed 7-HMG is unpredictable — safety-critical flag.
pregnancy breastfeeding Pregnancytrace	relative	relative	low
Editorial	Class extrapolation from mu-opioid agonist pharmacology. No substance-specific data exists. Confidence is low because this is entirely structural analogy.
	ReasoningReasoning Class extrapolation from mu-opioid agonist pharmacology. No substance-specific data exists. Confidence is low because this is entirely structural analogy.
psychiatric Active substance use disordertrace	relative	relative	high
Editorial	Animal self-administration data (Hemby 2019) and multiple human case reports (Reif 2025, Hendler 2026, Stanciu 2026) confirm high abuse liability and reinforcement.
	ReasoningReasoning Animal self-administration data (Hemby 2019) and multiple human case reports (Reif 2025, Hendler 2026, Stanciu 2026) confirm high abuse liability and reinforcement.
hepatic Moderate hepatic impairmenttrace	relative	relative	low
Editorial	Pharmacokinetic inference from CYP3A substrate status and the demonstrated 5-fold half-life extension with chronic dosing in healthy volunteers. No hepatic impairment PK studies exist.
	ReasoningReasoning Pharmacokinetic inference from CYP3A substrate status and the demonstrated 5-fold half-life extension with chronic dosing in healthy volunteers. No hepatic impairment PK studies exist.
other Paralytic ileustrace	absolute	absolute	low
Editorial	Standard opioid-class contraindication. Class extrapolation from morphine; 7-HMG is a confirmed MOR partial agonist with bidirectional cross-tolerance with morphine.
	ReasoningReasoning Standard opioid-class contraindication. Class extrapolation from morphine; 7-HMG is a confirmed MOR partial agonist with bidirectional cross-tolerance with morphine.
neurological Head injury with raised intracranial pressuretrace	absolute	absolute	low
Editorial	Class extrapolation from morphine/opioid pharmacology. No 7-HMG-specific data on intracranial pressure effects exist.
	ReasoningReasoning Class extrapolation from morphine/opioid pharmacology. No 7-HMG-specific data on intracranial pressure effects exist.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Onsettrace	1200–2700 sec(i=0.20)	1200–2700 sec(i=0.20)	low
Editorial	All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture.
	ReasoningReasoning All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture. Evidence basis: structural_analogy
Peaktrace	5400–10800 sec(i=0.80)	5400–10800 sec(i=0.80)	low
Editorial	All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture.
	ReasoningReasoning All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture. Evidence basis: structural_analogy
Resolutiontrace	7200–14400 sec(i=0.40)	7200–14400 sec(i=0.40)	low
Editorial	All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture.
	ReasoningReasoning All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture. Evidence basis: structural_analogy
Afterglowtrace	14400–43200 sec(i=0.05)	14400–43200 sec(i=0.05)	low
Editorial	All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture.
	ReasoningReasoning All phase descriptions are inferred from PK data (Huestis 2024: Tmax 1.2-1.8h, T½ 4.7h single dose) and opioid class analogy. No controlled human timeline data for isolated 7-HMG exist. Duration ranges estimated from morphine pharmacodynamic analogy adjusted for 7-HMG PK parameters. Most human experiential data derives from kratom preparations containing the full alkaloid mixture. Evidence basis: structural_analogy

Dose Tier Summaries

lighttrace

low

Light doses produce clearly perceptible opioid effects: noticeable pain suppression, a warm body high spreading from the core outward, and mild euphoria with anxiolysis. Mood elevation is gentle but distinct — a sense of contentment and reduced worry. Thought deceleration becomes apparent, with a pleasant cognitive softening. Physically, pupil constriction is evident. Mild sedation and muscle relaxation emerge. Nausea may occur, particularly in opioid-naive individuals. Appetite suppression and dry mouth are possible. Motor control remains largely intact but reflexes may slow. Functional impairment is mild but present. Driving and complex task performance should be avoided.

Editorial

No published human dose data for pure 7-HMG. Description inferred from mu-opioid agonist class pharmacology (morphine reference) and kratom user survey reports of low-dose effects.

Reasoning

No published human dose data for pure 7-HMG. Description inferred from mu-opioid agonist class pharmacology (morphine reference) and kratom user survey reports of low-dose effects.

Evidence basis: structural_analogy

thresholdtrace

low

At threshold doses, the first perceptible effects are subtle: a faint warmth spreading through the body, mild pain suppression barely distinguishable from placebo, and a slight softening of ambient anxiety. Cognitive function remains essentially intact, with perhaps a gentle slowing of thought tempo. Physical effects are minimal — slight pupil constriction may be detectable, and a mild heaviness in the limbs may be noticed. Nausea is unlikely at this level. Duration of perceptible effects is expected to be brief relative to higher doses. No human dose-finding data for isolated 7-hydroxymitragynine exist. This description is inferred entirely from mu-opioid agonist class pharmacology using morphine as the reference compound.

Editorial

No published human dose data for pure 7-HMG. Entire description inferred from opioid class analogy (morphine as reference). Work-notes explicitly flag all dose tier summaries as sparse-evidence.

Reasoning

No published human dose data for pure 7-HMG. Entire description inferred from opioid class analogy (morphine as reference). Work-notes explicitly flag all dose tier summaries as sparse-evidence.

Evidence basis: structural_analogy

commontrace

low

Common doses produce the characteristic opioid experience: substantial pain suppression, pronounced euphoria and cognitive euphoria, and marked anxiety suppression. A warm body high and tactile euphoria dominate the physical experience. Sedation becomes prominent, with a heavy, comfortable bodily heaviness and strong muscle relaxation. Nausea is common, particularly on the come-up. Constipation, pupil constriction, and respiratory depression are pharmacologically expected at this level. Spontaneous body sensations including itching may occur. Dry mouth and appetite suppression are typical. Motor control impairment and thought deceleration are functionally significant. Compulsive redosing urge may emerge. Duration of effects is expected to last several hours. Emotional suppression and dreaming suppression are likely with evening dosing.

Editorial

No published human dose data for pure 7-HMG. Description inferred from mu-opioid agonist class pharmacology, kratom survey data, and the documented 13× morphine potency. Work-notes rate effects profile values at this tier with mixed confidence.

Reasoning

Evidence basis: structural_analogy

strongtrace

low

Strong doses intensify all opioid effects substantially: near-complete pain suppression, heavy sedation approaching somnolence, and intense euphoria that may include a dissociative-like emotional detachment. Bodily heaviness is pronounced, and voluntary movement requires deliberate effort. Cognitive impairment is significant — focus suppression, thought deceleration, and decision impairment are marked. Respiratory depression becomes a tangible clinical risk at this level. Nausea and vomiting are common. Severe constipation, pronounced pupil constriction (miosis), and dizziness are expected. Physical fatigue is heavy. Motor control is significantly impaired. Compulsive redosing urge is strong. Risk of accidental overdose increases, particularly with concurrent CNS depressants. Naloxone should be immediately accessible.

Editorial

No published human dose data for pure 7-HMG. Description inferred from mu-opioid class pharmacology at strong-dose levels, considering 7-HMG's 4.5× morphine respiratory depression potency (rat IV) and documented case reports of severe presentations.

Reasoning

Evidence basis: structural_analogy

heavytrace

low

Heavy doses carry immediate life-threatening risk. Respiratory depression may progress to respiratory arrest — this is the primary lethal mechanism for 7-HMG, with 4.5-fold greater potency than morphine demonstrated in animal models. Profound sedation approaching unconsciousness, severe miosis, and loss of protective reflexes (cough, gag) are expected. Nausea, vomiting (with aspiration risk in obtunded patients), severe hypotension, and bradycardia may occur. Rhabdomyolysis has been reported following kratom overdose. All respiratory depression is fully reversed by naloxone — standard opioid overdose response protocols apply. This dose range should never be approached intentionally. Multiple naloxone doses may be required. Emergency medical services should be contacted immediately if respiratory depression is observed.

Editorial

No published human dose data for pure 7-HMG. Description based on opioid overdose pharmacology, 7-HMG respiratory depression potency (4.5× morphine, rat IV, Zuarth Gonzalez 2025), documented fatality data (Corkery 2019, Iuteri 2026), and rhabdomyolysis case report (Tobarran 2021).

Reasoning

Evidence basis: structural_analogy

History

current version

published Oct 6, 2026system—

versions

3 total · since previous: +0 / −0 citations

publication ledger

publish Oct 6, 2026 · by agent-psx

publish Oct 2, 2026 · by agent-psx

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 correction contact@psychedex.org

Sources

25 strong · 6 moderate · 14 weak

[1]
strong
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moderate
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[3]
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[4]
strong
7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects
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[5]
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Kamble SH, Leon F, King TI, Berthold EC, Lopera-Londono C, Siva Rama Raju K, Hampson AJ, Sharma A, Avery BA, McMahon LR, McCurdy CR · 2020 · ACS Pharmacology & Translational Science
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[6]
weak
Substance Use Disorder Following Consumption of a Novel Synthetic 7-Hydroxymitragynine Product.
Reif B, Adkins A, Boyer EW, Kanumuri SRR, Sharma A, Smith KE · 2025 · Journal of Addiction Medicine
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[7]
moderate
De facto opioids: Characterization of novel 7-hydroxymitragynine and mitragynine pseudoindoxyl product marketing.
Hill K, Boyer EW, Grundmann O, Smith KE · 2025 · Drug and Alcohol Dependence
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[8]
weak
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US Food and Drug Administration · 2025
linkno claims checked
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strong
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[10]
strong
Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.
Kruegel AC, Gassaway MM, Kapoor A, Varadi A, Majumdar S, Filizola M, Javitch JA, Sames D · 2016 · Journal of the American Chemical Society
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Kruegel AC, Grundmann O · 2017 · Neuropharmacology
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[12]
strong
Mitragynine and 7-hydroxymitragynine: Bidirectional effects on breathing in rats.
Zuarth Gonzalez JD, Ragsdale AK, Mukhopadhyay S, McCurdy CR, McMahon LR, Obeng S, Wilkerson JL · 2025 · Journal of Pharmacology and Experimental Therapeutics
doi.org/10.1016/j.jpet.2025.103720 pubmed 41106041no claims checked
[13]
moderate
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[14]
strong
Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa.
Matsumoto K, Horie S, Takayama H, Ishikawa H, Aimi N, Ponglux D, Murayama T, Watanabe K · 2005 · Life Sciences
pubmed 16169018no claims checked
[15]
weak
A Case of 7-Hydroxymitragynine Use Disorder Treated With Buprenorphine.
Hendler R, Karavolis Z, Kim J, Gonzalez G · 2026 · Journal of Addiction Medicine
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Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine.
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Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous Plant, Mitragyna speciosa
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A Descriptive Assessment of Products Containing the Opioid Receptor Stimulator Mitragynine Pseudoindoxyl.
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[21]
weak
Complicating Factors Surrounding Concurrent Use of Kratom and a Novel 7-hydroxymitragynine Product Among a Participant Enrolled in a Kratom Clinical Trial.
Smith KE, Rama Raju Kanumuri S, Sharma A, Rattenni R, LeComte R, McCurdy CR, Boyer EW, Strain EC · 2025 · Journal of Addiction Medicine
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[22]
weak
An accidental poisoning with mitragynine
Karinen R, Fosen JT, Rogde S, Vindenes V · 2014 · Forensic Science International
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[23]
strong
Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions
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[24]
strong
Interactive Effects of mu-Opioid and Adrenergic-alpha2 Receptor Agonists in Rats.
Obeng S, Leon F, Patel A, et al. · 2022 · Journal of Pharmacology and Experimental Therapeutics
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[25]
strong
Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine.
Hemby SE, McIntosh S, Leon F, Cutler SJ, McCurdy CR · 2019 · Addiction Biology
doi.org/10.1111/adb.12639 pubmed 29949228no claims checked
[26]
strong
Effects of Itraconazole on Pharmacokinetics of Mitragynine and 7-Hydroxymitragynine in Healthy Volunteers.
Mongar P, Jaisi A, Inkviya T, Wungsintaweekul J, Wiwattanawongsa K · 2024 · ACS Pharmacology & Translational Science
doi.org/10.1021/acsptsci.3c00335 pubmed 38481700no claims checked
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strong
Pharmacokinetic and Pharmacodynamic Consequences of Cytochrome P450 3A Inhibition on Mitragynine Metabolism in Rats.
Kamble SH, Obeng S, Leon F, et al. · 2023 · Journal of Pharmacology and Experimental Therapeutics
doi.org/10.1124/jpet.122.001525 pubmed 37019472no claims checked
[28]
strong
Translating Kratom-Drug Interactions: From Bedside to Bench and Back
Tanna RS, Cech NB, Oberlies NH, Rettie AE, Thummel KE · 2023 · Drug Metabolism and Disposition
doi.org/10.1124/dmd.122.001005 pubmed 37286363no claims checked
[29]
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Effects of kratom alkaloids on mesolimbic dopamine release.
Manus JP, Crenshaw RC, Ringer LC, Towers SA, Paige NB, Leon F, McCurdy CR, Lester DB · 2025 · Neuroscience Letters
doi.org/10.1016/j.neulet.2025.138153 pubmed 39923979no claims checked
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strong
Physiologically Based Pharmacokinetic Model for Clinical Translation and Prediction of Drug Interaction of the Major Kratom Alkaloid, Mitragynine
Chiang YH, Kanumuri SRR, Berthold EC, Kamble SH, et al. · 2026 · ACS Pharmacology & Translational Science
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Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats.
Berthold EC, Kamble SH, Kanumuri SRR, et al. · 2024 · Pharmaceutics
doi.org/10.3390/pharmaceutics16030318 pubmed 38543213no claims checked
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weak
A Case of 7-OH Mitragynine Use Requiring Inpatient Medically Managed Withdrawal.
Wightman RS, Hu D · 2025 · Journal of Addiction Medicine
doi.org/10.1097/adm.0000000000001558 pubmed 40758956no claims checked
[33]
weak
Management of acute withdrawal from 7-hydroxymitragynine following high-dose chronic use: A case report.
Lybik N, Cone B, Skelton S, Elfessi Z · 2026 · Journal of the American Pharmacists Association
doi.org/10.1016/j.japh.2026.103047 pubmed 41690384no claims checked
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Severe Early-Onset Withdrawal Following Intentional Use of Mitragynine Pseudoindoxyl: A Case Report and Emerging Clinical Considerations.
Stanciu CN · 2026 · Cureus
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Treatment of Kratom Use Disorder With Methadone in an Opioid Treatment Program.
Sherrick RC · 2026 · Journal of Addiction Medicine
doi.org/10.1097/adm.0000000000001666 pubmed 41673921no claims checked
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Treatment of obsessive compulsive disorder and Kratom dependence with buprenorphine and supportive care.
Teixeira F, Ajewole O, Picior M, Roberts E · 2025 · BMJ Case Reports
doi.org/10.1136/bcr-2025-265834 pubmed 40518266no claims checked
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Case Control study of mitragynine deaths in Florida.
Iuteri CM, Sawyers RJ, Byrne CM, Trojano M, Thundiyil J · 2026 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bkag017 pubmed 41837384no claims checked
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Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa)
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Kratom induced severe cholestatic liver injury histologically mimicking primary biliary cholangitis: A case report.
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Hepatotoxicity Induced by the 3Ks: Kava, Kratom and Khat
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Pressure Necrosis Requiring Fasciotomy After Kratom Overdose.
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Kratom as an opioid alternative: harm, or harm reduction? A systematic review of literature.
Stanciu C, Ahmed S, Gnanasegaram S, Gibson S, Penders T, Grundmann O, McCurdy C · 2022 · The American Journal of Drug and Alcohol Abuse
doi.org/10.1080/00952990.2022.2111685 pubmed 36001875no claims checked
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An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerations.
McCurdy CR, Sharma A, Smith KE, Veltri CA, Weiss ST, White CM, Grundmann O · 2024 · Expert Review of Clinical Pharmacology
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Evaluation of the rewarding effects of mitragynine and 7-hydroxymitragynine in an intracranial self-stimulation procedure in male and female rats.
Behnood-Rod A, Chellian R, Wilson R, Hiranita T, Sharma A, Leon F, McCurdy CR, McMahon LR, Bruijnzeel AW · 2020 · Drug and Alcohol Dependence
doi.org/10.1016/j.drugalcdep.2020.108235 pubmed 32889450no claims checked
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weak
Two Single-Drug Fatal Intoxications by Mitragynine.
Behonick GS, Vu C, Czarnecki L, El-Ters M, Shanks KG · 2022 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bkac016 pubmed 35285475no claims checked

Claim Verification

No claim verification has run for this version.

Coverage & Gaps

effect links

53 links · 53 approved · 0 audited0/53 with evidence basis

7-Hydroxymitragynine

Value Provenance

Dosing

oraltrace →

sublingualtrace →

Duration

oral

Safety

Toxicity Profiletrace →

Dependence Profiletrace →

Withdrawal Profiletrace →

Tolerance Profiletrace →

Effects & Profile

Contraindications

Timeline Phases

oral

Dose Tier Summaries

History

Sources

Claim Verification

Coverage & Gaps

oraltrace

sublingualtrace

Toxicity Profiletrace

Dependence Profiletrace

Withdrawal Profiletrace

Tolerance Profiletrace