Management Flowchart

Figure 1. Poison-center triage

Any Step 1 criterion sends the patient straight to the ED. Otherwise, the product class, then the patient's age, the size of the exposure, the product's identity, and tolerance decide home versus ED.

Figure 2. ED management

Every ED patient stays until the longest applicable observation 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.

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 opioid-reversal 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. [2–4,34; P]

Empiric naloxone given without preceding respiratory depression and without an objective opioid-reversal 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 3. High-Potency or Uncertain Product: Age, Exposure Size, and Tolerance

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. [5; 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 brief lick or taste only, at a known time; product not held, sucked, or dissolved in the mouth

• 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]

Emergency services must be readily accessible. Having naloxone available is advised but not required for this pathway. [EC]

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

Adult without current high-potency opioid tolerance:

Any more-than-trivial ingestion of a high-potency or uncertain product identified in Step 2, including 7-OH, mitragynine pseudoindoxyl, MGM compounds, concentrated kratom extracts, or unidentified enhanced products:

→ ED even if currently asymptomatic. [EC]

Adult with current high-potency opioid tolerance:

• Product explicitly identified as 7-OH, with a numerical 7-OH content declared per serving and no other modified kratom alkaloid listed → Step 4.

• Any product containing mitragynine pseudoindoxyl, MGM-15, MGM-16, 7-acetoxymitragynine, or another chemically modified kratom alkaloid, alone or combined with 7-OH; an extract or concentrate labeled only by mitragynine or total alkaloid content; or a product with uncertain composition or labeling: any more-than-trivial exposure → ED, even when tolerant. [EC]

When a product meets both descriptions, the ED rule takes precedence. Explicit 7-OH labeling does not establish actual chemical composition, dose accuracy, or safety; measured content can differ from the label. [3,4,34; P] All Step 4 criteria remain mandatory.

Important: If product identity, amount ingested, or recent opioid tolerance cannot be reliably established, use the more conservative applicable pathway. [EC]

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]

These criteria define eligibility for the Step 4 pathway only. They do not establish biological tolerance to respiratory depression, and meeting them does not make home observation safe. [EC]

Step 4. Tolerant Adult After a Labeled 7-OH Product

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

• Meets the Operational Definition of Current Opioid Tolerance

• Product explicitly identified as 7-OH, with a numerical 7-OH content per serving stated on the packaging and no other modified kratom alkaloid listed

• Completely asymptomatic

• No significant underlying respiratory disease (including obstructive sleep apnea) or frailty, and no diagnosed gastroparesis or other clinically significant gastrointestinal dysmotility; ordinary opioid-induced constipation does not exclude

• Same product and formulation as the tolerated product, verified from the packaging, with no change in brand, formulation, labeled concentration, or route of administration (for example, swallowed versus sublingual, or crushed or otherwise manipulated)

• Total amount and dosing pattern during this exposure episode no more than the patient's established usual regimen; no additional or clustered doses

• No clinically important coexposure

• No self-harm intent

• Reliable dose, time, and unit count (for gummies or edibles)

• 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. [2–4,34; P] This pathway accepts that residual risk only because established tolerance, a responsible observer, and immediate naloxone availability are all present.

If any criterion is not met → ED.

Observation Duration

Observe ≥8 hours after the last dose. [EC]

When the usual, previously tolerated product is a known delayed-release formulation, home observation is an individualized poison-center decision; if chosen, observe ≥12 hours after the last dose. Tolerance does not eliminate delayed absorption. [EC]

An uncertain formulation, a large or repeated exposure beyond the usual pattern, an uncertain amount or time, or a gummy or edible with an uncertain number of pieces or unknown concentration does not meet Step 4 → ED. [EC]

Home Monitoring

The responsible observer should remain awake and continuously available during the observation period.

The patient may sleep, but if sleeping:

• assess respiratory effort and color at least every 30 minutes;

• confirm that the patient can be readily awakened and responds normally at least hourly.

[EC]

If this degree of observation cannot be provided → ED.

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

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.

Suggested Poison-Center Follow-Up

• Callback approximately 2 hours after the initial assessment

• Final callback when the applicable 8- or 12-hour observation period is complete

• Immediate callback or ED referral for somnolence, difficulty rousing, abnormal breathing, repeated vomiting, confusion, gait abnormality, or other progression

Step 5. Identified Conventional Botanical Kratom

Asymptomatic Adult

Home observation is reasonable when all of the following are true:

• Reliable, isolated exposure without self-harm intent

• The amount and time of ingestion are known

• The amount is either within the person's usual range, or, for a first-time user or a regular user above their usual range, clearly limited, not large, and not repeated

• No concerning coingestant

• Reliable supervision is available

[EC]

An unusually large ingestion, an escalating binge, or an uncertain amount:

→ ED. [EC]

Recreational or therapeutic intentional use alone is not an ED criterion. Intentional self-harm is.

Observe for ≥6 hours after the last ingestion. [EC]

Mild Symptoms in an Adult

Home observation may remain appropriate, including for a first-time user, when symptoms are limited to:

• Mild nausea

• One isolated episode of vomiting

• Mild dizziness without gait impairment

• Mild jitteriness or anxiety

• Mild transient tachycardia without chest pain, syncope, or significant palpitations

and all of the following remain true:

• Normal mental status

• Normal spontaneous breathing

• No increasing somnolence

• No ataxia

• No repeated vomiting

• No severe agitation

• No concerning coingestant

• No self-harm intent

• Symptoms are stable or improving

• Exposure is not unusually large or uncertain

• Reliable observation is available

[EC]

For a first-time user or a regular user above their usual range, use a lower threshold for ED referral if sedation, gait abnormality, repeated vomiting, substantial tachycardia, or symptom progression develops.

Observe for ≥6 hours after the last ingestion and until mild symptoms have resolved. Worsening symptoms, or symptoms still present at the end of the observation period, warrant reassessment for ED referral. [EC]

Suggested callback:

• Approximately 2 hours after the initial symptomatic assessment

• At completion of the 6-hour period

• Immediately if symptoms progress

Child With Conventional Botanical Kratom

A clearly trivial lick or taste of identified conventional botanical material in an asymptomatic child may be observed at home for ≥6 hours after exposure. [EC]

If more than a trivial amount was swallowed, the amount is uncertain, symptoms develop, or product concentration is uncertain:

→ ED

Step 6. ED Observation Clock

Observation duration should be determined by the longest applicable clock.

Unknown Ingestion Time

When the time of ingestion cannot be reliably established, start the applicable clock at the latest possible ingestion time: usually ED arrival, or the time the patient was found if continuously observed since. For a high-potency or uncertain product, an unknown ingestion time is an unreliable exposure history: apply the ≥12-hour clock from that reference time. Extend observation when the clinical course or a suspected delayed-release formulation warrants. [EC]

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.

These botanical clocks do not apply after clinically significant opioid-type respiratory depression, inability to protect the airway, or CNS or respiratory depression with an objective opioid-reversal response to naloxone. Manage as high-potency/uncertain (Step 2, Clinical Reclassification) and apply the high-potency clocks below. [EC]

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 observation.

Naloxone given for opioid-type respiratory depression, or followed by an objective opioid-reversal response, after a high-potency/uncertain exposure or a botanical exposure managed as high-potency under Step 2: observe until the latest of:

1. ≥12 hours after the last exposure

2. ≥6 hours after the last naloxone dose

3. ≥6 hours after complete resolution of clinically meaningful symptoms, when such symptoms occurred

[EC]

Empiric naloxone administered without preceding opioid-type respiratory depression and without an objective opioid-reversal response does not independently trigger reclassification or establish a naloxone-specific observation interval. Apply the applicable product-, age-, symptom-, and coexposure-based clocks. Any naloxone administration remains an ED-referral criterion under Step 1. [EC]

If the indication for prehospital naloxone or the clinical response cannot be reliably established, apply the high-potency/uncertain observation pathway, including the after-naloxone clock, as a conservative disposition rule. This does not establish naloxone responsiveness or confirm high-potency product identity. [EC]

Examples:

• Adult, liquid 7-OH. One naloxone dose at hour 1; symptoms resolve by hour 3. Observe until at least hour 12.

• Adult, 7-OH tablet. Recurrent hypoventilation at hour 9; repeat naloxone with immediate complete response. Observe until at least hour 15, in a monitored setting (see Recurrent Respiratory Depression).

• Child, 7-OH gummy. Naloxone at hour 2; sedation resolves at hour 10. Observe until at least hour 16.

• Prehospital naloxone, indication and response undocumented, asymptomatic on arrival. Naloxone at hour 1. Observe until at least hour 12; no symptom-resolution clock applies.

• Product labeled as botanical powder, naloxone-responsive hypoventilation. Manage as high-potency/uncertain; apply the clocks above, not the 6-hour botanical clock.

• Botanical powder, empiric prehospital naloxone without respiratory depression or response. Botanical clocks apply; no naloxone-specific clock.

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 latest of:

• ≥12 hours after the last exposure

• ≥6 hours after infusion discontinuation

• ≥6 hours after complete resolution of significant symptoms

[EC]

Withdrawal During Observation

Dependent patients, including adolescents, may develop opioid withdrawal during prolonged observation. Anticipate and treat it rather than shortening the observation clock or allowing redosing. [EC]

Methods

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

Targeted literature and regulatory review completed October 5, 2026; focused PubMed/MEDLINE and Federal Register updates were performed October 8 and October 11, 2026, and Federal Register regulatory status was re-verified on November 4, 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.

Classify as A only when the Step 2 identification criteria are met.

B. Kratom Extract or Concentrate

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

Extracts and concentrates are managed as high-potency/uncertain because measured alkaloid content frequently differs from labeling and cannot be established at the time of the call, not because 7-OH content has been demonstrated in a defined proportion of these products. [2–4; P] [EC]

Products labeled as "kratom extract" and declaring 7-OH content have been found to contain synthetic-level 7-OH (22–75 mg/g), 5–28% above label claims, with chromatographic profiles inconsistent with kratom leaf. The "extract" label does not establish botanical origin, and a declared 7-OH amount does not establish actual content. [34; P]

Extracts or concentrates labeled only by mitragynine or total alkaloid content do not qualify for the Step 4 home pathway, even in tolerant adults (Step 3). [EC]

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.

Tolerance does not qualify users of these products for the Step 4 home pathway, including when they are combined with 7-OH; any more-than-trivial exposure warrants ED evaluation. [EC]

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. [6; P/DEA]

Commercial analytical studies have also identified substantial discrepancies between labeled and measured alkaloid composition. A 2026 analysis of commercial tablets, films, and liquid shots found frequent label inconsistencies, including unlisted alkaloids and listed alkaloids that were absent. [2–4; P]

Tolerance does not qualify users of these products for the Step 4 home pathway; any more-than-trivial exposure warrants ED evaluation. [EC]

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. [7,8; 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. [9; 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. [10; 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. [11; H1]

After a concentrated kratom extract standardized to 39.5% mitragynine, mitragynine and 7-OH peaked at a median of about 1.3–2.3 hours after single and repeated daily doses. Repeated dosing produced higher 7-OH-to-mitragynine ratios, and the extract gave greater mitragynine exposure than leaf powder or tea at comparable doses. [35; 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. [12,13; 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 [12,14–18; 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. [14; 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. [19; H3]

Pediatric Exposures

In a retrospective NPDS analysis of 169 single-substance kratom ingestions in children <12 years (median age 2 years; 97% unintentional), 7-OH or MP exposures had higher odds of serious respiratory effects (OR 2.5; 95% CI 1.1–5.4) and serious neurologic effects (OR 2.6; 95% CI 1.2–5.4) than mitragynine exposures, and naloxone was used approximately twice as often. [5; H2]

These data support conservative pediatric disposition but do not establish a toxic dose, a lick/taste threshold, or an observation interval.

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. [17; 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 Step 1 (Figure 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

The ED management flowchart (Figure 2) summarizes this section.

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

With supplemental oxygen, a normal SpO₂ does not exclude hypoventilation. Use capnography when available; otherwise assess respiratory rate, depth, and mental status frequently.

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. Isolated sedation with adequate ventilation is not, by itself, an indication for naloxone.

The endpoint is adequate spontaneous ventilation, not necessarily complete wakefulness. Abrupt full reversal in an opioid-dependent patient can precipitate severe withdrawal, vomiting with aspiration risk, and agitation.

Adult With Spontaneous but Inadequate Ventilation

• Naloxone 0.04–0.4 mg IV initially. Use the lower end when opioid dependence is possible.

• Escalate every 2–3 minutes according to respiratory response.

Apnea or Profound Respiratory Depression

When effective bag-mask ventilation is established and maintained:

• Ventilate first.

• Titrated naloxone remains appropriate: 0.04–0.4 mg IV, escalating every 2–3 minutes, particularly when opioid dependence is possible.

• Use larger initial doses when oxygenation cannot be maintained despite assisted ventilation.

When effective ventilation cannot be assured (prehospital, layperson response, or failed bag-mask ventilation):

• Naloxone 2 mg IV/IM, or standard intranasal naloxone, typically 4 mg/device.

• Repeat every 2–3 minutes as needed, and continue rescue breathing or assisted ventilation.

Failure of a single dose does not demonstrate naloxone resistance.

Pediatrics

Opioid-naive child:

Naloxone 0.1 mg/kg IV/IO/IM, generally maximum 2 mg for the initial dose. Repeat according to respiratory response.

Adolescent or child with possible opioid dependence (including regular 7-OH or other high-potency opioid use):

When ventilation is supported, use the adult titrated approach (0.04–0.4 mg IV, escalating every 2–3 minutes) rather than weight-based full-reversal dosing. [EC]

When effective ventilation cannot be assured, use the weight-based dose above.

Newborn of a mother with chronic kratom, 7-OH, or other opioid use:

Prioritize ventilation. Naloxone may precipitate acute neonatal withdrawal, including seizures. [EC]

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. [20; H2/extrapolated]

ACMT reports that naloxone has been effective in 7-OH respiratory depression based on animal evidence and human case reports. [1,12,13; 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.

Seizures are reported after kratom exposure itself (see Clinical Manifestations) but are 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. The mechanism of QRS widening after kratom or 7-OH exposure is not established. [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. [18; 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 Step 6 (summarized in Figure 2) 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. [21; H1]

In the same study, kratom did not meaningfully alter dextromethorphan/dextrorphan pharmacokinetics despite strong in-vitro CYP2D6 inhibition signals. [21; 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. [22; H3/forensic]

A 2017–2018 multistate outbreak linked contaminated kratom to 199 Salmonella infections across 41 states. [23; H2/public-health surveillance]

FDA testing of 30 kratom products identified concerning concentrations of lead and nickel in multiple samples. [24; 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. [25; 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. [26; 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. [27; 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

[28–30; H3]

Buprenorphine

Buprenorphine has been used successfully in published 7-OH cases and small series. [28–30; 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

[29; 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. [31; 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

For regular kratom or 7-OH users, advise return for jaundice, dark urine, pruritus, or persistent nausea; kratom-associated liver injury can present days to about 7 weeks after starting use (see Hepatotoxicity).

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 toxic-dose threshold, lick/taste threshold, or observation interval. Comparative pediatric evidence for 7-OH/MP is limited to retrospective poison-center data in children under 12 years, without prospective disposition-rule validation. [5; H2]

• 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 and concentrated extracts [35]

• No reliable way to confirm actual product composition at the time of a call; labels may be inaccurate [3,4,34]

• 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. Federal concentration and ratio criteria are legal classification thresholds; they are not safe-dose limits, overdose thresholds, poison-center referral criteria, naloxone thresholds, observation intervals, or discharge criteria.

7-Hydroxymitragynine and Mitragynine Pseudoindoxyl

On October 14, 2026, the U.S. Drug Enforcement Administration published a revised notice of intent covering both 7-hydroxymitragynine (7-OH) and mitragynine pseudoindoxyl (MGPI). The October notice superseded DEA's earlier July 2026 notice of intent for 7-OH. [33]

Under the revised proposed framework, 7-OH and MGPI would be subject to temporary Schedule I control when either substance alone, or their combined amount when both are present, meets either of the following alternative criteria: [33]

The concentration and ratio tests are alternative regulatory criteria. Meeting the ratio criterion may therefore matter even when the concentration criterion is not exceeded. [33]

The October 14 document is a notice of intent, not an effective replacement temporary scheduling order. DEA states that the new temporary scheduling order will be published no earlier than November 13, 2026. As of the November 4, 2026 regulatory review, the replacement 7-OH/MGPI threshold framework had therefore not yet taken effect. [33]

DEA also explicitly cautions that falling below the proposed regulatory threshold should not be interpreted as establishing safety for consumption. [33]

For a detailed chronology of the federal regulatory change, see DEA Revises Schedule I Plan for 7-OH and MGPI.

Current Status of Mitragynine Pseudoindoxyl

MGPI was temporarily placed in federal Schedule I on August 26, 2026, together with MGM-15 and MGM-16. [32]

The October 14 notice proposes replacing MGPI's current no-threshold temporary control with the new shared 7-OH/MGPI threshold framework. Until that replacement temporary scheduling order is published and the previous MGPI order is withdrawn—or the existing order otherwise expires—MGPI remains subject to the August 26 temporary Schedule I order. [32,33]

Accordingly, the proposed October thresholds should not be described as already governing MGPI as of November 4, 2026.

MGM-15 and MGM-16

MGM-15 and MGM-16 remain separately controlled substances and should not be folded into the new 7-OH/MGPI concentration-and-ratio framework.

DEA temporarily placed MGM-15 and MGM-16 in Schedule I on August 26, 2026. [32] On October 14, DEA published a separate notice of intent for MGM-15 and MGM-16 designed to maintain their temporary Schedule I placement without applying the new 7-OH/MGPI threshold framework to them. [36]

The August 26 control remains in effect until the applicable replacement order is published and the previous order withdrawn, or until the existing temporary order otherwise expires. [32,36]

Regulatory Timeline

Clinical interpretation: Regulatory status does not determine clinical toxicity. Continue to base poison-center referral, ED evaluation, naloxone use, airway management, observation, and disposition on the clinical framework elsewhere in this Guideline, not on whether a product is above or below a federal concentration or ratio threshold.