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Kratom (Mitragyna speciosa Korth., Rubiaceae) is a tropical tree native to Southeast Asia whose leaves contain over 40 alkaloids. Its dominant constituent, mitragynine, activates both opioid and stimulant pathways in the brain. At low doses this produces alertness and energy; at higher doses, sedation and pain suppression dominate.

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Plant data not yet available. The article body content (when present) provides preparation and dosing details.
minlowmodhigh
Acute
Chronic
Physical
Psych.
Withdrawal
Buildupmoderate
Full reset10 days
Cross-tol.opioids
Absolute4 entries
Pre-existing liver diseasePregnancy and lactationConcurrent opioid useConcurrent CNS depressants
Relative4 entries
Respiratory compromiseHistory of psychosisRenal impairmentCYP3A4 substrates with narrow therapeutic index
Dosage varies by body weight, tolerance & metabolism · Not medical advice · Terms

Kratom has been used in Thailand and the Malay Peninsula for centuries — chewed by farm laborers to ease fatigue and manage pain.[1] The Dutch botanist Pieter Willem Korthals first formally described the plant in 1841.[2] It entered Western markets around 2005–2010 and has remained subject to unresolved regulatory debate.

Subjective effects include stimulation, mood elevation, pain relief, sedation, and euphoria — shifting from sociable energy at lower doses to opioid-like warmth and cognitive slowing at higher doses.[3] The defining quality is a dose-dependent inversion absent from conventional stimulants or opioids, though preparation type and alkaloid concentration shape the experience considerably.[4] Common unwanted effects include nausea, constipation, and pupil constriction.

Prolonged use carries significant opioid-type physical dependence risk, and kratom is a documented cause of drug-induced liver injury.[5][6] The highest-risk pattern is combining kratom with opioids or sedatives — additive opioid signaling can slow breathing to a dangerous or fatal degree.[7][8] Alkaloid concentrations vary more than 50-fold across commercial products,[4] and no formal human dose-finding trials have been completed.

History[edit]

Traditional and historical use

Kratom leaf chewing in southern Thailand and the Malay Peninsula dates to at least the mid-19th century;[1][9] Korthals formally described the plant in 1841.[2] Farm laborers chewed fresh leaves daily to combat fatigue during manual work, functioning comparably to coca leaf use in South America.[1] As opium became restricted, kratom substituted as a cheaper remedy for pain, cough, and opioid withdrawal;[10][11] in some communities it was offered to guests as a social gesture, paralleling kava.[12]

Western discovery and modern era

Kratom products entered Western markets around 2005–2010, marketed as a legal opioid alternative.[1] The first comprehensive pharmacology review appeared in 2012,[10] followed by a landmark neuropharmacology review in 2018 characterizing its G-protein-biased opioid agonism.[13] Thailand banned kratom in 1943 then legalized it again in August 2021.[14]

In the United States, the DEA proposed Schedule I classification in August 2016[15] then withdrew the notice after approximately 142,000 opposing public comments — the first such withdrawal in DEA history.[16]

Botanical Overview[edit]

Mitragyna speciosa belongs to the Rubiaceae family — the coffee family — making it a distant relative of coffee (Coffea) and Psychotria viridis, the ayahuasca admixture plant. The genus Mitragyna contains roughly ten tree species across tropical Africa and Asia. M. speciosa is the only member widely used for its psychoactive properties.

Kratom is native to a broad arc of tropical Southeast Asia — from southern Indochina through the Malay Peninsula, Sumatra, and Borneo.[1] It thrives in lowland tropical forest with heavy rainfall and rich alluvial soil; wild populations grow along riverbanks and in swamp margins. Indonesia is today the dominant source for international commerce.

The tree grows 15–25 meters tall with a straight trunk and broadly spreading crown. Leaves are large (up to 20 cm), glossy, and oval with prominent veining. Leaf vein color (red, green, or white) is widely used as a commercial cultivar marker, but the link between vein color and alkaloid profile is inconsistent and lacks peer-reviewed validation.citation needed

Alkaloid Profile[edit]

Kratom leaf contains over 40 identified alkaloids, but two dominate its pharmacology. Mitragynine makes up roughly 66% of total alkaloid content[17] — typically 0.5–1.5% of dry leaf weight. It activates opioid receptors in the brain while simultaneously engaging adrenergic (stimulant) pathways.[13] This dual action is what produces kratom's characteristic dose-dependent shift: stimulation at low doses, sedation and analgesia at higher doses.

7-Hydroxymitragynine forms in the body as mitragynine is processed by the liver.[18] It binds opioid receptors with roughly 13 times the potency of mitragynine and acts as a full opioid agonist — not partial.[19][20] Commercial extracts can contain dramatically enriched 7-hydroxymitragynine concentrations, fundamentally changing both the experience and the risk profile compared to plain leaf.[21]

Minor alkaloids — speciogynine, speciociliatine (each roughly 6–7% of total alkaloids), and paynantheine (roughly 9%) — accumulate in the body with repeated daily dosing.[22] Their individual contributions to subjective effects are poorly understood; most evidence is from laboratory studies. Mitragynine content across commercial products ranges from 0.7% to 38.7% by weight — a greater than 50-fold difference.[4]

Neuroscience[edit]

Where it acts

Mitragynine partially activates opioid receptors while simultaneously engaging adrenergic (stimulant) receptors.[13][23] At lower doses, adrenergic stimulation dominates — producing alertness and energy. At higher doses, opioid receptor engagement takes over, producing sedation, analgesia, and warmth. Kratom alkaloids also interact with serotonin and dopamine systems, contributing to mood elevation and — during withdrawal — emotional disruption.[24][25]

What it changes

With chronic use, the brain's opioid receptors adapt and tolerance builds — cross-tolerance with classical opioids is documented.[26] The partial opioid agonism of mitragynine is thought to produce less respiratory depression than a full opioid agonist, though this protection diminishes substantially with concentrated extract products.[23][27] Sustained use may disrupt neuroplasticity across opioid, serotonin, and adrenergic systems, impairing cognition.[28]

Subjective Effects[edit]

Summary

Kratom's character is defined by a dose-dependent shift. At low doses, the experience is warm, sociable stimulation — mood lifts, focus sharpens, energy builds. At higher doses, opioid-like qualities emerge: pain fades, the body feels heavy, thinking slows. Preparation type shapes the arc: leaf powder tea produces a gradual curve, while concentrated extracts compress onset and amplify the peak.

At low doses the profile resembles coca leaf — functional energy with an underpinning of mood lift. At higher doses it approaches mild opioid analgesia, comparable in warmth and body feeling to a low dose of codeine, but with a stimulant quality that conventional opioids lack. Enriched 7-hydroxymitragynine extract products produce a qualitatively different experience dominated by full opioid character — closer to a classical opioid than to traditional leaf.

Preparations[edit]

Fresh leaf (chewed)

The traditional Southeast Asian preparation. Leaves are plucked fresh, the central vein is removed, and the remaining leaf is chewed and held in the cheek.[1] Onset: 5–10 minutes. Duration: 1–2 hours. Fresh leaf is rarely available outside cultivation regions.

Dried leaf powder (oral)

The most common commercial preparation worldwide. Powder is swallowed directly with water (“toss and wash”) or mixed into juice, yogurt, or a smoothie. Onset: 20–40 minutes. Duration: 3–5 hours.[3]

Dose ranges (dried leaf powder, oral):

  • Threshold: 1–2 g
  • Common (stimulant range): 2–4 g
  • Common (sedative range): 4–6 g
  • Strong: 6–8 g

Alkaloid content varies more than 50-fold across commercial products[4] — batch-specific dose calibration is essential.

Tea (aqueous decoction)

Dried powder or crushed leaf is simmered in water for 15–30 minutes, then strained. Onset is slightly faster than powder — 15–30 minutes — because alkaloids are pre-extracted into solution. Duration: 3–5 hours. Less gastrointestinal irritation than raw powder, as insoluble plant fiber is removed.

Capsules (oral)

Pre-measured dried leaf powder, typically 0.5–1 g per capsule. Onset is delayed (30–60 minutes) due to capsule dissolution. Duration and dose ranges are equivalent to dried powder. Capsules reduce taste aversion but make flexible dose adjustment harder.

Extracts and concentrated products

Sold as resins, tinctures, and liquid shots. These carry the highest risk of any kratom preparation.[21] Commercial extracts may contain enriched 7-hydroxymitragynine at concentrations far exceeding natural leaf levels, producing a fundamentally different pharmacological and risk profile. Onset is rapid (10–20 minutes for liquid forms). No standardized potency system exists — labeling is frequently inaccurate. Start at half or less of an equivalent powder dose and titrate cautiously.

Per-preparation dose tiers, timelines, and bioavailability data are in the Dose · by preparation card on this page.

Safety[edit]

Harm
Acute toxicity
Low
Chronic toxicity
Moderate
Withdrawal
Moderate
Tolerance buildup
moderate
Tolerance reset
10 days
Dependence
Physical
High
Psychological
High
Compulsive redosing
Moderate
Dose escalation
Moderate
Cross-tol.
opioids
Risk Shape
TOXPHYPSYWDRREDTOL

Toxicity

No human lethal dose has been established. Acute toxicity from traditional leaf doses is low; chronic toxicity data are limited but raise concerns for liver and cognitive function.[29]

Kratom is a documented cause of drug-induced liver injury with a predominantly cholestatic pattern — meaning bile flow from the liver becomes blocked.[6] Jaundice, itching, and dark urine are common early signs, appearing at a median of about 20 days from first use (range 2–49 days).[6] Some cases have mimicked primary biliary cholangitis — a chronic autoimmune liver condition.[30]

Published kratom-associated fatalities nearly all involve polydrug exposure. Nine deaths in Sweden resulted from kratom powder adulterated with O-desmethyltramadol — not from kratom alkaloids alone.[8] One documented death involved kratom combined with hydromorphone; another involved a 26-year-old male where polydrug exposure was not fully excluded.[7][31] No deaths attributed solely to botanical kratom appear in Southeast Asian published literature.[9]

Commercial kratom products carry additional contaminant risks:

  • Synthetic opioid adulterants: O-desmethyltramadol documented in "Krypton" products (9 fatalities);[8] enriched 7-hydroxymitragynine in products marketed as botanical kratom[21]
  • Microbial contamination: Salmonella contamination cited by FDA as basis for import detentions[32]citation needed
  • Heavy metals: Lead and cadmium contamination is a theoretical concern for dried botanical productscitation needed
  • Labeling inaccuracy: mitragynine content ranges 0.7–38.7% w/w across commercial products[4]

No federally mandated testing program exists for commercial kratom in the United States.

Psychological Risks

Higher doses and concentrated extract products are associated with anxiety, irritability, and — in rare documented cases — psychosis.[26] Chronic use may impair cognition by disrupting neuroplasticity across opioid, serotonin, and adrenergic systems.[28][33] Patterns of use meeting diagnostic criteria for substance use disorder have been documented, with dosing frequency a stronger predictor of dependence severity than dose size.[34]

Tolerance & Dependence

Tolerance develops with prolonged use through opioid receptor adaptation. Buprenorphine can precipitate withdrawal in kratom-dependent individuals, confirming clinically significant cross-tolerance with conventional opioids.[26] Mitragynine has a half-life of approximately 23 hours.[35]

Physical dependence risk is high.[5] Studies of 150–170 regular Malaysian kratom tea users found that stopping produced mild anxiety (70%), mild depression (81%), moderate pain (84%), and sleep problems (46%).[36][37] Users consuming four or more glasses daily had higher rates of depression, pain, and sleep disturbance.[37] Withdrawal was described as milder than classical opioid withdrawal in these studies.[37]

Severe withdrawal from concentrated 7-hydroxymitragynine products — including psychosis and breathing failure requiring intubation — has been documented.[26]

Withdrawal from botanical kratom leaf at moderate doses is generally manageable without medical intervention.[37] Low-dose sublingual buprenorphine has achieved complete kratom abstinence within 3 weeks in documented cases.[38] Reducing use frequency — rather than dose size alone — may be more effective, given that frequency shows a stronger link to dependence severity.[34]

Recovery resources, crisis lines, and support pathways → View all

Drug Interactions

The highest-risk combination is opioids. Adding kratom to an opioid amplifies opioid receptor activity; fatal outcomes have been documented.[7][8] Benzodiazepines, alcohol, GHB, and ketamine carry plausible risk of additive sedation and breathing depression.safety citation needed

Kratom inhibits CYP3A4 — a liver enzyme that clears many common drugs. A clinical study found a 2 g kratom dose raised midazolam blood levels by 1.39× (90% CI: 1.23–1.57);[39] pharmacokinetic modeling predicts a 2.2–2.7× increase with direct co-administration.[40] Opioids, benzodiazepines, immunosuppressants, and statins may reach toxic blood levels when combined with kratom.

CYP2D6 inhibition is seen in laboratory studies[41] but was not clinically significant at a 2 g dose.[39] With repeated use, kratom activates a regulatory pathway that increases CYP3A4, CYP1A2, and P-glycoprotein activity 3–6-fold[42] — potentially reducing the efficacy of co-administered drugs over time.

Contraindications

Pregnancy: Contraindicated. Neonatal withdrawal syndrome has been documented with kratom use during pregnancy;[43] teratogenicity is unknown, and the opioid-like mechanism warrants avoidance during pregnancy and lactation.[44]

Liver disease: Contraindicated. Kratom is a documented cause of drug-induced liver injury and may worsen existing hepatic conditions.[6]

Concurrent opioid use: Contraindicated. Additive opioid receptor stimulation with documented fatal outcomes.[7][8]

Drugs with a narrow therapeutic index (e.g., cyclosporine, fentanyl, alprazolam): Relative contraindication. Kratom inhibits CYP3A4 at typical oral doses and can raise co-administered drug concentrations to toxic levels.[39]

Personal or family history of psychosis: Relative contraindication for concentrated extract products, which are associated with psychotic symptoms during withdrawal.[26]

Kidney impairment: Relative contraindication. Renal impairment was a contributing factor in a documented fatal polydrug case; kratom's large volume of distribution (38 L/kg) suggests altered accumulation with impaired clearance.[7][35]

Harm Reduction[edit]

Forms & Identification

Reagent ResultsNot recorded+ add reagent results
AppearanceNot recorded+ add appearance
Red FlagsNot recorded+ add red flags

Lab testing matters more for kratom than for most botanicals because alkaloid content varies more than 50-fold across commercial products.[4] Some products marketed as botanical kratom contain enriched 7-hydroxymitragynine at concentrations far exceeding natural leaf levels.[21] A Certificate of Analysis (COA) from an ISO-accredited laboratory confirms mitragynine and 7-hydroxymitragynine concentrations, screens for contaminants, and verifies absence of synthetic adulterants.

Products without a COA should be treated as unverified. In US states with Kratom Consumer Protection Act (KCPA) frameworks, testing and labeling are mandatory — KCPA-regulated vendors carry greater reliability than unregulated sources.

Full identification analysis →

Guidelines

  • Start low, go slow. Begin with 1–2 g of dried leaf powder and wait at least 60 minutes before redosing. For extracts, start at half or less of an equivalent powder dose and titrate cautiously.
  • Use lab-tested products. Purchase from vendors providing a current COA from an ISO-accredited laboratory. Verify that 7-hydroxymitragynine content is consistent with botanical leaf (typically <0.1% of dry weight) — substantially higher concentrations indicate enrichment.
  • Track dose and frequency. Dose frequency is a stronger predictor of dependence severity than dose amount.[34] Limit use to 2–3 days per week when possible to reduce dependence risk.
  • Avoid combinations. Never combine kratom with opioids, benzodiazepines, alcohol, or other CNS depressants — additive respiratory depression risk is the highest-severity interaction class.[7][8]
  • Hydrate and eat. Kratom suppresses appetite and can cause dehydration. Maintain fluid and food intake, especially with daily use.
  • Store securely. Keep all kratom products away from children and pets. Label stored powder and extracts clearly.

Set & Setting

Kratom's opioid-class pharmacology makes context important. Daily use at higher doses carries impairment risk — sedation, cognitive slowing, and reduced reaction time are dose-dependent effects. The line between stimulant and sedative dosing is narrow and varies by batch. Driving or operating machinery after higher doses carries risk comparable to mild opioid impairment.

Aftercare & integration. After higher-dose kratom use, expect a period of low energy and mild mood dip lasting several hours as effects recede — a normal pharmacological rebound effect, not a medical concern. Hydrate thoroughly; kratom is mildly diuretic and appetite-suppressing, so fluid and electrolyte replenishment supports recovery. If using kratom daily, monitor for constipation — a common opioid-class side effect — and maintain dietary fiber intake.

Recovery & Support

Kratom dependence is an opioid-class physical dependence. For users wanting to reduce or stop use:

  • Gradual taper is the first-line approach. Reduce dose by 0.5 g every 2–3 days, or reduce frequency by one session per week. Frequency reduction may be more effective than dose reduction alone.[34]
  • Medical support: Low-dose sublingual buprenorphine has achieved complete kratom abstinence within 3 weeks in documented cases.[38] Consult a physician experienced in opioid use disorder treatment.
  • Withdrawal management: Botanical kratom withdrawal is generally mild compared to classical opioid withdrawal — muscle aches, insomnia, anxiety, and irritability are common symptoms.[5][37] Withdrawal from concentrated 7-hydroxymitragynine products can be significantly more severe.[26]
  • SAMHSA National Helpline: 1-800-662-4357 (free, confidential, 24/7). Provides referrals to local treatment facilities, support groups, and community-based organizations.
  • Support communities: Online peer-support forums provide lived-experience guidance, though advice should be verified against clinical sources.

Recovery resources, crisis lines, and support pathways → View all

Emergency Response

Recognizing an emergency: Slow or stopped breathing, blue or gray lips, unresponsiveness, pinpoint pupils, or seizures after kratom use — especially with concentrated extracts or in combination with other substances — constitute a medical emergency. Treat suspected kratom overdose as an opioid overdose.

Immediate steps:

  • 1. Call emergency services immediately (911 in the US).
  • 2. If the person is not breathing or breathing very slowly, administer naloxone if available — kratom's opioid agonism is naloxone-reversible.
  • 3. Place the person in the recovery position (on their side) to prevent aspiration.
  • 4. Stay with the person until emergency responders arrive.
  • 5. Do not induce vomiting.

What to tell the dispatcher: Name the substance (kratom — specify if extract or powder), approximate amount and time of last dose, any other substances taken, and current symptoms. Good Samaritan laws in many US jurisdictions provide legal protection for individuals reporting overdoses.

Naloxone: Naloxone reverses opioid agonism from both mitragynine and 7-hydroxymitragynine. It is available over the counter in the United States. Anyone using kratom extracts regularly should keep naloxone accessible.

references

  1. [1] 
    ^abcdefCinosi E, Martinotti G, Simonato P, Singh D, Demetrovics Z, et al. (2015) Following the Roots of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries — BioMed Research International doi:10.1155/2015/968786
  2. [2] 
    ^abRoyal Botanic Gardens Kew (2024) Mitragyna speciosa Korth. - Plants of the World Online (POWO), Kew Link
  3. [3] 
    ^abSmith KE, Rogers JM, Dunn KE, Grundmann O, McCurdy CR, Schriefer D, Epstein DH (2022) Searching for a Signal: Self-Reported Kratom Dose-Effect Relationships Among a Sample of US Adults With Regular Kratom Use Histories — Frontiers in Pharmacology doi:10.3389/fphar.2022.765917
  4. [4] 
    ^abcdefSharma A, Kamble SH, Leon F et al. (2019) Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra-performance liquid chromatography-tandem mass spectrometry — Drug Testing and Analysis doi:10.1002/dta.2604
  5. [5] 
    ^abcSingh D, Muller CP, Vicknasingam BK (2014) Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users — Drug and Alcohol Dependence doi:10.1016/j.drugalcdep.2014.03.017
  6. [6] 
    ^abcdSchimmel J, Dart RC (2020) Kratom (Mitragyna Speciosa) Liver Injury: A Comprehensive Review — Drugs doi:10.1007/s40265-019-01242-6