Management Flowchart

Kratom/7-OH management flowchart: triage, ED care, observation, discharge

Any Step 1 criterion sends the patient straight to the ED; otherwise product class, then tolerance, decides home versus ED, and every ED patient stays until the longest applicable clock has run.

Step 1. Does an Immediate ED Criterion Apply?

Recommend ED evaluation now for any of the following:

• Apnea, cyanosis, or visibly inadequate ventilation

• Respiratory rate <10/min in an adolescent or adult, or otherwise abnormally low for age

• Oxygen saturation <94% on room air in a patient without known chronic hypoxemia, or a clinically meaningful decrease below the patient's documented baseline.

• Inability to remain awake or protect the airway

• New confusion or severe ataxia

• Any naloxone administration

• Seizure

• Syncope

• Severe agitation or hyperthermia

• Chest pain

• Significant palpitations

• Persistent or severe vomiting

• Hypotension

• Significant ECG abnormality or dysrhythmia

• Intentional self-harm exposure

• Clinically important opioid, benzodiazepine, alcohol, gabapentinoid, sedative-hypnotic, or other respiratory-depressant coexposure

[EC]

If YES → ED.
If NO → Step 2.

Step 2. Identify the Product

High-Potency or Uncertain Product

Includes:

• 7-OH

• Mitragynine pseudoindoxyl

• MGM-15

• MGM-16

• 7-acetoxymitragynine

• Concentrated kratom extracts

• Other chemically modified kratom alkaloids

• Any unidentified or “enhanced” kratom product

If product identity or concentration cannot be established, manage it as a high-potency/uncertain product. [EC]

Commercial 7-OH products vary widely in dose per serving; see Product Classification below.

→ Proceed to Step 3.

Confirmed Conventional Botanical Kratom

Leaf, powder, tea, or conventional capsules without evidence of alkaloid concentration or enhancement.

→ Proceed to Step 5.

Step 3. Child or Not Currently Tolerant to High-Potency Opioid Effects?

Clearly Trivial Exposure

A witnessed lick or taste with no appreciable amount swallowed, no symptoms, and a reliable exposure history may be considered for individualized poison-center-directed home observation. [EC]

If the amount swallowed cannot be confidently classified as trivial, apply the age- and tolerance-based criteria below.

Child <18 years:

Any oral exposure to a high-potency or uncertain product identified in Step 2, including a lick or taste:

→ ED regardless of current symptoms. [EC]

In children <12 years, poison-center data show higher odds of serious respiratory and neurologic effects after 7-OH or MP than after mitragynine. [31; H2] Extension of this rule to adolescents 12–17 years is expert consensus. [EC]

Adult: Clearly Trivial Exposure

An adult exposure is clearly trivial only when all of the following are true:

• Witnessed or reliably reported lick or taste only

• No bite, chew, or swallowed portion of a tablet, capsule, gummy, or edible

• No swallowed liquid

• No product unaccounted for

• Completely asymptomatic

• No clinically important coexposure

• No self-harm intent

An adult meeting all criteria may be considered for individualized poison-center-directed home observation for ≥8 hours after exposure, using the Step 4 Home Monitoring requirements. [EC]

If any criterion is not met or cannot be established, the exposure is not trivial. Apply the tolerance-based criteria below.

OPERATIONAL DEFINITION: CURRENT OPIOID TOLERANCE — OPTION A APPLIED

Operational Definition: Current Opioid Tolerance

For this algorithm, an adult is currently tolerant only when all of the following are true:

• Reliable history of use of the same high-potency product and formulation on approximately ≥5 of the preceding 7 days

• Last use of that product <72 hours ago

• None of the following loss-of-tolerance factors:

  • Recent detoxification

  • Incarceration or hospitalization interrupting use

  • Significant deliberate taper or dose reduction

  • Treatment that substantially reduced opioid exposure

  • Uncertain recent use history

[EC]

Tolerance to another μ-opioid agonist, or regular botanical kratom use, does not qualify a patient for the Step 4 home pathway. [EC]

A person returning to a previously tolerated dose after ≥72 hours without that product does not qualify. [EC]

Step 4. Tolerant Adult After High-Potency Product

Home observation may be considered only when all of the following are true:

• Meets the Operational Definition of Current Opioid Tolerance

• Completely asymptomatic

• Same product and formulation as the tolerated product, with no change in brand, formulation, or labeled concentration

• No more than the current usual dose

• No clinically important coexposure

• No self-harm intent

• Reliable dose and time

• Responsible adult observer present

• Naloxone immediately available

• Emergency services readily accessible

[EC]

Same product does not guarantee same dose, because commercial products vary in measured content. [2–4,30; P] This pathway accepts that residual risk only because established tolerance, a responsible observer, and immediate naloxone availability are all present.

Keep the existing If any criterion is not met → ED, Observation Duration, and Suggested Poison-Center Follow-Up text unchanged.

At the end of Home Monitoring, immediately after:

“No further kratom, 7-OH, opioids, alcohol, benzodiazepines, sleep medications, or other sedatives should be used during observation.”

Add:

In a dependent patient, opioid withdrawal may emerge during the observation period. Advise a poison-center callback rather than redosing; manage withdrawal as in Dependence, Withdrawal, and MOUD Linkage.

Step 5. Identified Conventional Botanical Kratom

Product composition cannot be confirmed from telephone history. Classify an exposure as conventional botanical kratom only when all of the following are true:

• Leaf, powder, tea, or conventional capsule

• Packaging is available or the product is otherwise reliably identified

• Not labeled or marketed as an extract, concentrate, liquid shot, resin, or “enhanced,” “fortified,” or “extra-strength” product

• No 7-OH, 7-HMG, mitragynine pseudoindoxyl, MGM compound, or other modified alkaloid listed

If any criterion is not met → manage as high-potency/uncertain → Step 3. [EC]

→ Otherwise, proceed to Step 5.

Clinical Reclassification

After a product identified as conventional botanical kratom, manage the exposure as high-potency/uncertain and apply the high-potency observation clocks in Step 6 when any of the following occurs:

• Clinically significant opioid-type respiratory depression (bradypnea, apnea, or hypoventilation-related hypoxemia)

• Inability to protect the airway

• CNS or respiratory depression with an objective response to naloxone

[EC]

This is a disposition rule, not a determination of product identity. Adulteration and label-content discrepancies are documented in commercial kratom products. [2,3,30; P]

Empiric naloxone given without preceding respiratory depression and without an objective clinical response does not by itself trigger reclassification. When the indication for prehospital naloxone or the response cannot be reliably established, see Step 6, After Naloxone.

Step 6. ED Observation Clock

Observation duration should be determined by the longest applicable clock.

Asymptomatic Conventional Botanical Exposure

≥6 hours after the last ingestion. [EC]

Symptomatic Conventional Botanical Exposure

For a botanical exposure with clinically meaningful symptoms evaluated in an ED or other healthcare facility, observe until the later of:

• ≥6 hours after the last ingestion; or

• ≥4 hours after complete resolution of clinically meaningful symptoms.

[EC]

Longer observation may be required when a coingestant or clinical complication dictates.

Asymptomatic Adult After High-Potency Product

≥8 hours after the last ingestion. [EC]

Use ≥12 hours for delayed-release or uncertain formulation, large, repeated, or otherwise uncertain exposure, or other factors likely to delay absorption.

A gummy or edible with an uncertain number of pieces or unknown concentration should be treated as an uncertain exposure. [EC]

Also use ≥12 hours when any of the following is present:

• Gastrointestinal hypomotility

• Significant underlying respiratory disease

• Older or frail patient

• Unreliable product composition

• Unreliable exposure history

[EC]

Child After High-Potency Product

≥12 hours after the last ingestion. [EC]

Favor overnight monitored admission when:

• Amount or timing is uncertain

• A whole tablet, gummy, or potentially substantial amount was swallowed

• Any clinically meaningful symptom occurred

• Important coexposure is present

• Safe post-discharge observation cannot be ensured

Clinically Meaningful Symptoms After High-Potency Exposure

For high-potency exposure with CNS depression, ataxia, respiratory abnormality, repeated vomiting, clinically important cardiovascular effects, or other significant toxicity, even when naloxone was not required, observe until the later of:

• ≥12 hours after the last exposure; or

• ≥6 hours after complete resolution of clinically meaningful symptoms.

[EC]

Longer observation may be required when the coingestant or clinical complication dictates.

After Naloxone

Naloxone never shortens the underlying product- or age-specific observation interval.

Observe until the latest of:

1. ≥6 hours after the last naloxone dose

2. Completion of the applicable product- and age-specific interval

3. If significant symptoms occurred, ≥6 hours after complete symptom resolution

[EC]

Examples:

• Adult liquid 7-OH exposure requiring naloxone for respiratory depression: observe until the latest of ≥12 hours after exposure, ≥ 6 hours after the last naloxone dose, or ≥6 hours after complete resolution of clinically meaningful symptoms.

• Adult high-potency exposure meeting a ≥12-hour criterion, plus naloxone: at least 12 hours after exposure and at least 6 hours after the final naloxone dose.

• Child after any high-potency product, plus naloxone: at least 12 hours after exposure and at least 6 hours after the final naloxone dose.

• Persistent sedation resolving late in the course: continue until at least 6 hours after full clinical resolution.

Recurrent Respiratory Depression

Any clinically important recurrence requiring additional naloxone or assisted ventilation warrants monitored admission. [EC]

A single recurrence that responds promptly and remains stable may be managed in a step-down or equivalent monitored setting only when all of the following are available:

• Continuous pulse oximetry

• Preferably continuous capnography

• Frequent bedside nursing assessment

• Immediate naloxone availability

• Immediate airway support

Use ICU-level care for:

• Repeated respiratory recurrence

• Naloxone infusion

• Assisted ventilation

• Escalating naloxone requirements

• Persistent substantial sedation

• Hemodynamic instability

• Significant pulmonary complication

• Lack of an appropriate high-acuity monitored unit

After Naloxone Infusion

Observe until the later of:

• ≥6 hours after infusion discontinuation

• Completion of the applicable product/age interval

• ≥6 hours after complete resolution of significant symptoms

[EC]

Methods

This is a rapid evidence-informed poison-center guideline rather than a formal systematic review or GRADE guideline.

Literature search updated through October 5, 2026. The targeted literature and regulatory review used PubMed/MEDLINE and authoritative primary sources including ACMT, CDC/MMWR, FDA, DEA, HHS, and the Federal Register.

Search concepts included kratom, Mitragyna speciosa, mitragynine, 7-hydroxymitragynine, 7-OH, 7-HMG, mitragynine pseudoindoxyl, MGM-15, MGM-16, poisoning, overdose, respiratory depression, naloxone, pharmacokinetics, cardiac, pulmonary, seizure, interaction, liver injury, pregnancy, neonatal withdrawal, psychosis, withdrawal, and buprenorphine.

Evidence Tags

• [H1] Controlled/prospective human experimental evidence.

• [H2] Observational human evidence. Prospective cohorts, poison-center studies, surveillance datasets, and pharmacokinetic derivation studies without controlled clinical outcome testing.

• [H3] Human case-level evidence.

• [H3-SR] Systematic review of case-level evidence. Systematic synthesis does not elevate the underlying case reports to controlled evidence.

• [M] Mechanistic evidence. Animal, receptor, or in-vitro evidence.

• [P] Product/market-analysis evidence. Analytical chemistry, label-content studies, stability testing, contaminant testing, or systematic product-market characterization.

• [EC] Expert consensus/extrapolation.

Professional or regulatory authority is identified separately, for example [ACMT guidance], [FDA], or [DEA], rather than treated as an evidence grade.

No validated toxic-dose threshold, pediatric threshold, prospective poison-center triage rule, or validated observation interval currently exists for 7-OH.

Product Classification

A. Conventional Botanical Kratom

Leaf, powder, tea, or conventional capsules without evidence of alkaloid concentration or enhancement.

B. Kratom Extract or Concentrate

Liquid shots, concentrated extracts, resins, or products advertising enhanced alkaloid content.

C. 7-OH Product

Any formulation marketed as containing 7-hydroxymitragynine, 7-OH, or 7-HMG.

D. Other Modified Kratom Alkaloid Product

Includes products marketed as containing:

• Mitragynine pseudoindoxyl

• MGM-15

• MGM-16

• 7-acetoxymitragynine

• Other chemically modified kratom alkaloids

Human toxicity and relative potency cannot be assumed to be equivalent among these compounds.

E. Unknown or Enhanced Product

If the composition or concentration cannot be confidently established, manage it as a high-potency/uncertain product. [EC]

This approach is supported by extreme variability in the commercial 7-OH market. DEA reports that the concentration of commercial 7-OH products varied significantly, ranging from 1 mg to 700 mg in a single dose or serving. [4; P/DEA]

Commercial analytical studies have also identified substantial discrepancies between labeled and measured alkaloid composition. [2,3; P]

Pharmacology and Toxicokinetics

Mitragynine is the predominant alkaloid in conventional botanical kratom. Experimental studies describe relatively low-efficacy or partial μ-opioid receptor agonism together with activity at adrenergic and serotonergic systems. [5,6; M]

7-OH has substantially greater μ-opioid activity than mitragynine.

Mitragynine undergoes CYP3A-mediated metabolism to 7-OH. A controlled human itraconazole study demonstrated reduced 7-OH formation and increased mitragynine exposure, supporting an important CYP3A contribution. [7; H1]

7-OH can convert in human plasma in vitro to mitragynine pseudoindoxyl, a potent μ-opioid agonist. The clinical contribution of this conversion following commercial 7-OH exposure remains uncertain. [8; M]

After oral botanical kratom, mitragynine and 7-OH generally reach peak plasma concentrations within approximately 1–2 hours. Mitragynine has a substantially longer terminal elimination phase than the period of peak clinical effect, so terminal half-life should not independently determine disposition. [9; H1]

Respiratory-Ceiling Misconception

Experimental findings suggesting that mitragynine may produce less respiratory depression than conventional full μ-opioid agonists should not be extrapolated to concentrated 7-OH.

7-OH causes substantial respiratory depression in animal models, with naloxone reversal demonstrated experimentally, and severe naloxone-responsive human toxicity has now been reported. [10,11; H3 + M]

Clinical Manifestations

Possible acute findings include:

• Nausea or vomiting

• Dizziness

• Drowsiness

• Miosis

• Ataxia

• Tremor

• Anxiety

• Agitation

• Diaphoresis

• Tachycardia

• Hypertension

Severe toxicity may include:

• Profound CNS depression

• Bradypnea or apnea

• Hypoxemia

• Coma

• Aspiration

• Seizure

• Hypotension

• QTc prolongation

• QRS widening

• Ventricular dysrhythmia

• Brugada-pattern ECG abnormality

• Hyperthermia

• Rhabdomyolysis

• Acute kidney injury

• Respiratory failure

[10,12–16; H2/H3]

In national poison-center surveillance from 2015–2025, multiple substances were involved in 184 of 233 reported kratom-associated deaths. The dataset does not reliably distinguish botanical kratom from concentrated 7-OH or semisynthetic products, so it cannot establish formulation-specific mortality. [12; H2]

Psychosis and delirium have been reported after prolonged heavy 7-OH use and cessation, but this currently remains case-level evidence rather than an established common overdose phenotype. [17; H3]

Pulmonary Toxicity

Central opioid-type respiratory depression is the most clinically important acute pulmonary effect.

A 2026 systematic review of case reports and forensic series proposed additional pulmonary phenotypes including:

• ARDS/diffuse acute lung injury

• Diffuse alveolar hemorrhage

• Eosinophilic or hypersensitivity pneumonitis

• Pulmonary edema/congestion

• Central respiratory depression

These remain case-level associations rather than established kratom-specific pulmonary syndromes. [15; H3-SR]

Persistent hypoxemia after restoration of adequate ventilation should prompt evaluation for aspiration, pulmonary edema, ARDS, alveolar hemorrhage, infection, pulmonary embolism, and other causes of acute lung injury.

Poison-Center Triage

The authoritative ED-referral criteria for this guideline are contained in the Page-One Algorithm, Step 1.

This section deliberately does not reproduce a second list.

If any Step 1 criterion is present → Recommend ED evaluation.

Steps 2–5 define disposition when no immediate ED criterion is present.

ED Evaluation

For clinically important exposures:

• Continuous pulse oximetry

• Frequent respiratory assessment

• Cardiac monitoring when appropriate

• Serial mental-status examination

• Consider continuous capnography with significant sedation

• Temperature monitoring with agitation, seizure, or hyperthermia

ECG

Obtain an ECG for:

• Moderate or severe poisoning

• Seizure

• Syncope

• Chest pain

• Significant palpitations

• Symptomatic high-potency exposure

• Important cardiotoxic coingestant

• Relevant electrolyte abnormality

Repeat when abnormal or when clinical status changes.

Laboratory Testing

Testing should be severity-directed. Consider:

• Point-of-care glucose

• Electrolytes

• Magnesium

• Creatinine

• Blood gas for significant hypoventilation

• Lactate in severe poisoning

• CK after seizure, hyperthermia, severe agitation, or prolonged immobilization

• AST, ALT, alkaline phosphatase, bilirubin, and INR when hepatic injury is suspected

• Acetaminophen concentration after intentional or uncertain overdose

• Salicylate concentration when clinically appropriate

• Pregnancy testing when relevant

Routine opioid immunoassays generally do not detect mitragynine or 7-OH.

A negative routine opioid screen does not exclude kratom-derived opioid toxicity.

Airway and Ventilation

Ventilation takes priority over antidote administration.

Provide:

• Airway positioning

• Suction

• Supplemental oxygen

• Bag-mask ventilation when spontaneous ventilation is inadequate

• Endotracheal intubation when ventilation or airway protection cannot otherwise be maintained

Do not delay ventilation while waiting for naloxone.

Naloxone

Use naloxone for clinically significant opioid-type respiratory depression or apnea.

The endpoint is adequate spontaneous ventilation, not necessarily complete wakefulness.

Adult With Spontaneous but Inadequate Ventilation

If opioid dependence is possible:

• Naloxone 0.04–0.4 mg IV initially

• Escalate every 2–3 minutes according to respiratory response

Apnea or Profound Respiratory Depression

• Naloxone 2 mg IV/IM, or

• standard intranasal naloxone, typically 4 mg/device

Continue assisted ventilation and repeat naloxone as clinically necessary.

Failure of a single dose does not demonstrate naloxone resistance.

Pediatrics

Naloxone 0.1 mg/kg IV/IM, generally maximum 2 mg for the initial parenteral dose.

Repeat according to respiratory response.

Continuous Infusion

When repeated boluses are necessary, a reasonable starting infusion is approximately two-thirds of the total effective reversal bolus per hour.

This dosing approach derives from naloxone pharmacokinetic modeling and established opioid-toxicology practice rather than kratom-specific trials. [18; H2/extrapolated]

ACMT reports that naloxone has been effective in 7-OH respiratory depression based on animal evidence and human case reports. [1,10,11; H3 + M, ACMT guidance]

Seizures and Agitation

Treat seizures with benzodiazepines according to standard toxicologic seizure management.

Because concurrent opioid-type respiratory depression may be present:

• continuously reassess ventilation;

• use pulse oximetry;

• prefer capnography with substantial sedation;

• maintain immediate readiness for assisted ventilation.

Seizure is atypical for an uncomplicated pure opioid toxidrome.

Evaluate for:

• Tramadol/O-desmethyltramadol

• Bupropion

• Stimulants

• Serotonergic drugs

• Adulterants

• Hypoglycemia

• Electrolyte abnormalities

• Hypoxemia

Benzodiazepines may also be used for clinically significant agitation, with the same respiratory precautions.

Cardiovascular Toxicity

Hypotension

• Isotonic crystalloid initially

• Norepinephrine for persistent clinically significant hypotension after appropriate volume assessment [EC]

QT Prolongation

• Correct potassium, magnesium, and calcium abnormalities

• Avoid additional QT-prolonging drugs when feasible

• Continue cardiac monitoring

Torsades de Pointes

• Adults: magnesium sulfate 2 g IV

• Children: magnesium sulfate 25–50 mg/kg IV, maximum 2 g

Defibrillate unstable or pulseless patients.

For recurrent acquired pause-dependent torsades despite correction and magnesium, consider overdrive pacing or isoproterenol with cardiology/medical-toxicology input. [EC]

QRS Widening

No kratom-specific trial supports sodium bicarbonate.

For progressive QRS widening from baseline, or QRS ≥100 ms with a terminal R wave in aVR or another ECG feature consistent with sodium-channel blockade, or ventricular dysrhythmia suggesting sodium-channel blockade:

• Sodium bicarbonate 1–2 mEq/kg IV is reasonable while obtaining medical-toxicology consultation. [EC]

• Compare with any available baseline ECG and evaluate for coexposure, since a QRS of 100–120 ms may reflect pre-existing conduction disease rather than acute sodium-channel blockade.

• Repeat according to ECG response while monitoring potassium and systemic pH.

Do not administer bicarbonate solely for QTc prolongation or an isolated Brugada-pattern ECG without evidence of conduction delay. [16; H3]

Gastrointestinal Decontamination

Activated charcoal is generally not indicated for isolated kratom or 7-OH ingestion. [EC]

Potential benefit is uncertain, while evolving opioid-type sedation creates an aspiration risk.

Consider charcoal primarily when a separate dangerous coingestant independently warrants gastrointestinal decontamination and the airway is reliably protected.

If used:

Activated charcoal approximately 1 g/kg, maximum 50 g.

Do not induce vomiting.

There is no routine role for gastric lavage, whole-bowel irrigation, or multidose activated charcoal.

Enhanced Elimination

There is no established role for hemodialysis, hemoperfusion, or urinary manipulation solely to increase elimination of mitragynine, 7-OH, or related compounds.

Use extracorporeal therapy only for another established indication.

Observation and Level of Care

Observation intervals are expert-consensus operational recommendations rather than validated prediction rules.

Use Page-One Algorithm, Step 6 as the single source of truth for observation clocks.

After recurrent respiratory depression, monitored step-down care is acceptable only when continuous respiratory monitoring and immediate airway intervention are available.

Use ICU-level care for repeated recurrence, naloxone infusion, assisted ventilation, escalating antidote requirements, hemodynamic instability, major pulmonary complications, or lack of an appropriate high-acuity monitored unit.

Drug Interactions

Pharmacodynamic interactions with other respiratory depressants are the immediate clinical concern.

Alcohol, conventional opioids, benzodiazepines, sedative-hypnotics, and other CNS depressants can increase respiratory risk.

A controlled human crossover study using 2 g of kratom tea increased midazolam AUC by approximately 39% and Cmax by approximately 50%, supporting intestinal CYP3A inhibition at that exposure. [19; H1]

In the same study, kratom did not meaningfully alter dextromethorphan/dextrorphan pharmacokinetics despite strong in-vitro CYP2D6 inhibition signals. [19; H1]

Therefore:

• Human evidence supports a CYP3A interaction signal.

• Clinically meaningful CYP2D6 inhibition was not demonstrated at the studied human dose.

• Different effects after larger doses, chronic exposure, or concentrated extracts cannot be excluded.

Adulterants and Contaminants

Unexpected toxicity should prompt consideration of adulteration or contamination.

The marketed preparation Krypton contained O-desmethyltramadol and was associated with fatal intoxications. [20; H3/forensic]

A 2017–2018 multistate outbreak linked contaminated kratom to 199 Salmonella infections across 41 states. [21; H2/public-health surveillance]

FDA testing of 30 kratom products identified concerning concentrations of lead and nickel in multiple samples. [22; P/FDA]

Consider another substance or contaminant when the presentation includes:

• Seizure

• Serotonergic toxicity

• Unexpectedly prolonged opioid toxicity

• Fever and diarrhea suggesting infectious disease

• Subacute neurologic or hematologic findings

• Findings inconsistent with the labeled product

Whenever possible, document:

• product name;

• manufacturer;

• lot number;

• photograph of the packaging;

• labeled alkaloid concentrations;

• whether remaining product is available.

Hepatotoxicity

Kratom-associated drug-induced liver injury is among the better-characterized non-opioid complications of repeated kratom use.

In the prospective U.S. Drug-Induced Liver Injury Network, 11 adjudicated cases were attributed to kratom. Median latency to symptoms was 14 days (range 5–28 days). Six had mixed injury, two cholestatic injury, and three hepatocellular injury. All developed jaundice, most required hospitalization, and all ultimately recovered. [23; H2]

A broader review of the earlier literature found a median symptom latency of approximately 20.6 days, with reported cases ranging from 2 to 49 days after exposure. [24; H3-SR]

Accordingly, a compatible history may extend from a few days to approximately 7 weeks after starting kratom, although presentation around the second to fourth week is more typical.

A 2026 systematic review identified 32 patients across 31 published studies. The accumulated case literature was predominantly cholestatic, and four reported patients progressed to liver transplantation. [25; H3-SR]

Evaluate for kratom-associated liver injury when patients develop:

• Jaundice

• Dark urine

• Pruritus

• Persistent nausea

• Right-upper-quadrant discomfort

• Unexplained fatigue

• Evidence of impaired hepatic synthetic function

Management includes:

• Discontinue the suspected product

• Evaluate competing causes of liver injury

• Trend AST/ALT, alkaline phosphatase, bilirubin, and INR as appropriate

• Obtain hepatology consultation for significant synthetic dysfunction, severe jaundice, encephalopathy, or progressive injury

Routine serial liver testing is not required after a small isolated asymptomatic acute exposure. [EC]

Dependence, Withdrawal, and MOUD Linkage

Regular kratom use, and particularly concentrated 7-OH use, can produce tolerance, craving, physical dependence, opioid-like withdrawal, and substance use disorder.

Withdrawal may include:

• Restlessness

• Anxiety

• Myalgias

• Diaphoresis

• Rhinorrhea

• Abdominal cramping

• Nausea or vomiting

• Diarrhea

• Insomnia

• Tachycardia

• Hypertension

[26–28; H3]

Buprenorphine

Buprenorphine has been used successfully in published 7-OH cases and small series. [26–28; H3]

For standard induction, wait for objective opioid withdrawal.

A COWS score around 8–12 or greater may support initiation, but there is no validated kratom- or 7-OH-specific threshold. [EC]

Low-dose buprenorphine initiation may be considered when there is concern for precipitated withdrawal, including:

• Heavy high-potency 7-OH use

• Uncertain duration of opioid effect

• Concurrent fentanyl or methadone exposure

• Previous precipitated withdrawal

• Inability to tolerate abstinence

[27; H3]

Methadone

ACMT notes successful treatment of kratom/7-OH dependence using medications for opioid use disorder including buprenorphine and methadone. [1; ACMT guidance]

Methadone treatment for OUD should follow the applicable regulated treatment pathway.

Adjunctive Treatment

Symptom-directed options may include:

• clonidine when hemodynamically appropriate;

• ondansetron;

• loperamide;

• NSAIDs;

• acetaminophen.

Discharge Linkage

Patients with dependence, escalating use, recurrent overdose, or OUD should be offered:

• Buprenorphine when appropriate

• Methadone-treatment referral when appropriate

• Addiction-medicine follow-up

• Take-home naloxone

• Harm-reduction counseling

Do not simply advise a heavily dependent patient to abruptly stop high-dose 7-OH without addressing withdrawal and access to treatment.

Pregnancy, Newborns, and Lactation

Maternal stabilization takes priority.

Do not withhold naloxone from a pregnant patient with clinically important opioid-type respiratory depression.

Published prenatal-exposure literature supports a neonatal opioid-withdrawal signal after chronic maternal kratom use. Available evidence remains limited to case-level literature and does not establish incidence. [29; H3-SR]

Newborns with substantial chronic prenatal kratom or 7-OH exposure should be monitored according to local neonatal withdrawal protocols.

Human lactation pharmacokinetic and safety data remain inadequate.

Kratom and concentrated kratom-derived opioid products should generally be avoided while breastfeeding. [EC]

Discharge Criteria

Before ED discharge confirm:

• Baseline mental status

• Normal spontaneous ventilation

• Stable room-air oxygenation or established baseline

• Stable vital signs

• Completion of the applicable observation period

• No recurrent toxicity

• No clinically significant unresolved ECG abnormality

• Safe ambulation

• Adequate oral intake when appropriate

• Psychiatric assessment after self-harm exposure

After clinically significant opioid-type toxicity:

• Provide take-home naloxone

• Review respiratory-depressant interactions

• Screen for dependence or OUD

• Offer MOUD linkage when appropriate

Reporting and Surveillance

For significant, unusual, or emerging toxicity:

• Record exact product/formulation

• Photograph packaging

• Record labeled alkaloid concentrations

• Record manufacturer and lot

• Record dose and timing

• Record current tolerance and any recent interruption in use

• Record coexposures

• Report through the regional poison center

• Consider FDA MedWatch for serious product-related adverse events

Product-level documentation is important because surveillance datasets frequently cannot distinguish conventional botanical kratom from concentrated or semisynthetic products.

Evidence Limitations

Major limitations include:

• No validated toxic dose for botanical kratom or 7-OH

• No validated pediatric threshold

• No validated home-triage rule

• No prospective disposition rule

• No validated observation duration

• No controlled clinical naloxone trial specific to kratom/7-OH

• Limited human pharmacokinetic data for purified 7-OH

• Major commercial-product variability

• Frequent polysubstance exposure

• Limited evidence for newer modified alkaloids

• Cardiac and pulmonary complications supported predominantly by mechanistic or case-level evidence

• Pregnancy evidence limited to case reports

• MOUD literature for 7-OH limited primarily to case reports and small retrospective series

The [EC] recommendations in this guideline are explicit operational decisions made where poison-center practice requires a disposition despite incomplete direct evidence.

Federal Regulatory Context

This section is informational and does not define toxic doses or clinical disposition thresholds.

Mitragynine Pseudoindoxyl, MGM-15, and MGM-16

DEA temporarily placed these three substances into federal Schedule I effective August 26, 2026 through August 26, 2028, unless the order is extended or superseded. [30]

7-Hydroxymitragynine

DEA published a July 6, 2026 notice of intent concerning temporary Schedule I placement of 7-OH above a specified threshold.

The proposed threshold includes:

• Botanical Mitragyna speciosa material containing >0.050% 7-OH on a dry-weight basis

• Synthetic or processed alternative articles containing >0.050% 7-OH by the applicable concentration measure or >1.00 mg of 7-OH per article

[4]

The same notice also documents wide per-serving variability in commercial 7-OH products.

HHS extended the threshold-related comment period through September 10, 2026. [31]

At the October 5, 2026 literature-search date, no subsequently published Federal Register temporary scheduling order for 7-OH itself was identified in the sources reviewed.

Regulatory thresholds are not toxicity thresholds and should not be used to determine home versus ED disposition.