Psychedex is in open beta. We are still fine-tuning the generation and review process. Please double-check sources.
Kratom
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.
Kratom (''Mitragyna speciosa'' Korth., Rubiaceae) is a tropical tree native to Southeast Asia whose leaves contain over 40 indole alkaloids. Its dominant constituent, mitragynine, is a G-protein-biased partial agonist at the μ-opioid that also engages α₂-adrenergic receptors.[1] Mitragynine produces its principal effects by partially activating opioid and adrenergic pathways, generating a dose-dependent spectrum from mild stimulation to opioid-like sedation.
Psychedex is in open beta. We are still fine-tuning the generation and review process. Please double-check sources.
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]
Between 2009 and 2011, a kratom-based product marketed as "Krypton" was linked to nine unintentional deaths in Sweden.[8] Forensic analysis revealed the powder was adulterated with O-desmethyltramadol — the active metabolite of tramadol. Deaths resulted from combined opioid receptor stimulation, not from kratom alkaloids alone. The incident remains the first documented mass-casualty kratom-associated event and underscores the critical distinction between botanical kratom and adulterated commercial products.
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]
The relative contribution of adrenergic versus opioid signaling to the stimulant-to-sedative dose shift has not been resolved. Pharmacokinetics for extracts and enriched 7-hydroxymitragynine products remain uncharacterized in controlled human studies. No neuroimaging studies using kratom preparations in human subjects have been published.
Subjective Effects[edit]
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.
First described by Pieter Willem Korthals in 1841,[2] kratom was used for centuries as a work aid and folk medicine in Thailand and Peninsular Malaysia.[3] The plant entered Western markets around 2005–2010 and became a focus of regulatory debate after the US DEA proposed — then withdrew — Schedule I classification in 2016.
Subjective effects include stimulation, mood elevation, analgesia, sedation, and euphoria, shifting from functional energy at lower doses to opioid-like warmth and cognitive slowing at higher doses.[4] The defining quality is a dual adrenergic-opioid character absent from conventional opioids, though preparation type and alkaloid content — which varies more than 50-fold across commercial products — profoundly shape the experience.[5] Common unsought effects include nausea, constipation, and pupil constriction.
Prolonged use carries clinically significant opioid-type dependence risk, with a withdrawal marked by myalgia, insomnia, anxiety, and irritability.[6] Hepatotoxicity — predominantly cholestatic — has been documented at a median latency of roughly three weeks.[7] The principal contemporary safety concern is the divergence between botanical leaf and commercially enriched 7-Hydroxymitragynine products, which carry substantially greater respiratory depression and dependence risk;[8] no formal human dose-finding trials have been completed, and long-term safety data remain limited to observational studies and case reports.
History[edit]
Traditional and historical use
''Mitragyna speciosa'' was first described by the Dutch botanist Pieter Willem Korthals in 1841 during surveys of the Dutch East Indies.[2] Korthals named the genus for the resemblance of its stipules to a bishop's mitre; earlier European accounts of leaf chewing in Peninsular Malaysia appear in the work of Low, dating to 1836.[3][9]
Kratom — กระท่อม (krathom) in Thai, ketum in Malay — has been used in southern Thailand and the Malay Peninsula for centuries as a traditional work aid and folk remedy.[3][10] Farm laborers chewed fresh leaves daily to combat fatigue during manual work, functioning analogously to coca leaf use in South America.[3] As opium became expensive or restricted, kratom served as a cheaper substitute for managing pain, cough, diarrhea, and eventually opioid withdrawal.[11][12] In some communities, kratom tea was offered to guests as a social gesture, paralleling kava hospitality in Pacific island cultures.[10]
Western discovery and research
Kratom products appeared in Western retail and online markets around 2005–2010, marketed as a legal opioid alternative and a self-treatment for opioid withdrawal.[3] Prozialeck, Jivan, and Andurkar published the first widely cited English-language pharmacology review in 2012,[11] and Kruegel and Grundmann followed in 2018 with a comprehensive neuropharmacology review characterizing the G-protein-biased opioid agonism of kratom alkaloids.[1] By 2025, hundreds of peer-reviewed publications had addressed the plant's pharmacology, toxicity, and abuse liability.
Modern era
Thailand banned kratom in 1943 under the Kratom Act B.E. 2486 — paradoxically, while simultaneously profiting from opium taxation — and classified it as a Category 5 narcotic in 1979.[13] On August 24, 2021, Thailand reversed course, removing kratom from its narcotics list.[13]
In the United States, the DEA published a notice of intent on August 31, 2016 to temporarily place mitragynine and 7-hydroxymitragynine into Schedule I.[14] The agency withdrew the notice on October 13, 2016 — the first such withdrawal in DEA history — following approximately 142,000 public comments opposing scheduling.[15]
Between 2009 and 2011, a kratom-based product marketed as "Krypton" was linked to nine unintentional deaths in Sweden.[16] Forensic analysis revealed the powder was adulterated with O-desmethyltramadol, the active metabolite of tramadol — deaths resulted from synergistic dual μ-opioid agonism, not from kratom alkaloids alone. The incident remains the first documented mass-casualty kratom-associated event and underscores the critical distinction between botanical kratom and adulterated commercial products.
Botanical Overview[edit]
Mitragyna speciosa Korth. belongs to the family Rubiaceae — the coffee family — making it a distant botanical relative of Coffea (coffee) and Psychotria (the genus containing the ayahuasca admixture Psychotria viridis). The genus Mitragyna contains roughly ten species of trees distributed across tropical Africa and Asia; M. speciosa is the only member widely used for its psychoactive properties.
Kratom is native to a broad swath of tropical Southeast Asia, from southern Indochina through the Malay Peninsula, Sumatra, Borneo, and as far east as New Guinea.[3] It thrives in lowland tropical forest with heavy rainfall, rich alluvial soils, and partial to full sun. Wild populations grow along riverbanks and in swamp margins. Today it is widely cultivated in Thailand, Indonesia, and Malaysia, with Indonesia the dominant source for international commerce.
The tree reaches 15–25 meters at maturity with a straight trunk and broadly spreading crown. Leaves are the pharmacologically relevant organ: large (up to 20 cm long), glossy, ovate, with prominent pinnate venation. Leaf vein color — red, green, or white — is the primary commercial cultivar marker, though the relationship between vein color and alkaloid profile is inconsistent and poorly validated in peer-reviewed literature.citation needed Flowers are deep yellow, globular, and clustered in heads, giving rise to the genus name (mitra = mitre, for the shape of the stipules).
For psychoactive use, leaves are harvested at maturity when alkaloid content is highest. Traditional preparation involves chewing fresh leaves with the tough central vein removed. For commercial sale, leaves are dried, powdered, and sometimes further extracted. Drying method, leaf maturity, and post-harvest processing all influence final alkaloid concentration.
Alkaloid Profile[edit]
Kratom leaf contains over 40 identified indole alkaloids, but its pharmacology is dominated by two: mitragynine and its hepatic metabolite 7-Hydroxymitragynine.
Mitragynine constitutes approximately 66% of total alkaloid content[17] and typically represents 0.5–1.5% of dry leaf weight. It acts as a partial agonist at μ-opioid receptors with G-protein-biased signaling and simultaneously engages α₂-adrenergic receptors.[1] This dual mechanism is proposed to explain the stimulant character at low doses (adrenergic dominance) and opioid-like sedation at higher doses (μ-opioid dominance).
7-Hydroxymitragynine occurs at trace levels in unprocessed leaf but is also produced in vivo through hepatic CYP3A4 metabolism of mitragynine.[18] It binds μ-opioid receptors with roughly 13-fold greater potency than mitragynine and acts as a full agonist without significant α₂-adrenergic activity.[19][20] Commercially enriched extracts contain dramatically higher 7-hydroxymitragynine concentrations than botanical leaf, producing a fundamentally different pharmacological and risk profile.[8]
Minor alkaloids include speciogynine and speciociliatine (both diastereomers of mitragynine, each approximately 6–7% of total alkaloid content) and paynantheine (roughly 9%). These accumulate in plasma with repeated daily dosing[21] but their individual contributions to subjective effects remain poorly characterized — most evidence is in vitro.
Alkaloid concentrations vary enormously across commercial products. A survey of retail kratom found mitragynine content ranging from 0.7% to 38.7% w/w — a greater-than-50-fold difference.[5] Growing conditions, leaf maturity at harvest, drying method, and post-harvest extraction all contribute to this variability. Vein color (red, green, white) is marketed as a reliable potency indicator but lacks consistent peer-reviewed validation.citation needed
Neuroscience[edit]
Where it acts
Kratom's mixed pharmacology explains its unusual dose-dependent character. Mitragynine partially activates μ-opioid receptors with G-protein-biased signaling — meaning it does not significantly recruit β-arrestin-2 — and simultaneously agonizes α₂-adrenergic receptors.[1][22] At lower doses, adrenergic stimulation predominates, producing alertness and energy; at higher doses, opioid receptor engagement overtakes it, producing sedation and analgesia. Kratom alkaloids additionally interact with serotonergic, dopaminergic, and noradrenergic systems, contributing to mood elevation and, during withdrawal, affective disturbance.[23][24]
What it changes
The G-protein-biased agonism of mitragynine is proposed to preserve analgesic efficacy while reducing β-arrestin-2-mediated adverse effects such as respiratory depression and rapid tolerance.[22] However, respiratory depression risk is reduced rather than eliminated, particularly with concentrated 7-hydroxymitragynine preparations.[25] Chronic use leads to opioid-receptor adaptation and tolerance, with documented cross-tolerance to classical opioids.[26] Cognitive effects with sustained use are attributed to disruption of neuroplasticity across opioid, serotonergic, and adrenergic systems.[27]
The relative contribution of α₂-adrenergic versus μ-opioid agonism to the stimulant-to-sedative dose shift has not been resolved. Preparation-specific pharmacokinetics for extracts and enriched 7-hydroxymitragynine products remain uncharacterized in controlled human studies. No neuroimaging studies using kratom preparations in human subjects have been published.
Subjective Effects[edit]
Kratom's experiential character is defined by a dose-dependent inversion: at lower doses, a warm, sociable stimulation with mood elevation and enhanced focus; at higher doses, opioid-like analgesia, bodily heaviness, and cognitive slowing. The stimulant range carries a quality distinct from caffeine — attributed to concurrent adrenergic and partial opioid receptor activity — while the sedative range approaches the analgesic warmth of codeine. Preparation type is the primary modifier: leaf powder tea produces a gentler arc than concentrated extracts, which compress onset and amplify peak intensity. Set, setting, and individual opioid tolerance strongly shape the experience.
Pharmacologically, kratom occupies a position between stimulant plants and classical opioids. Its low-dose profile resembles coca leaf — functional energy with mood lift — while its higher-dose profile approaches mild opioid analgesia, distinguished by reduced respiratory depression risk and a dual adrenergic-opioid quality absent from conventional opioids. Enriched 7-hydroxymitragynine products produce a qualitatively different experience dominated by full μ-opioid agonism, closer to classical opioid character than to traditional leaf preparations.
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]
- Acute toxicity
- Low
- Chronic toxicity
- Moderate
- Withdrawal
- Moderate
- Tolerance buildup
- moderate
- Tolerance reset
- 10 days
- Physical
- High
- Psychological
- High
- Compulsive redosing
- Moderate
- Dose escalation
- Moderate
- Cross-tol.
- opioids
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]
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
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.
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.
Legal Status[edit]
Kratom is not listed under any UN drug control treaty. In 2021 the WHO reviewed kratom and found insufficient evidence to recommend international scheduling.[45] In the United States, kratom is federally unscheduled but banned in several states — Alabama, Arkansas, Indiana, Vermont, and Wisconsin — while Rhode Island transitioned from a ban to a regulated framework in April 2026.[46] The FDA authorizes detention of imported kratom products under Import Alert 54-15.[32] Thailand legalized kratom in 2021 after banning it since 1943.[14] Malaysia prohibits it under the Poison Act 1952.[47] Australia lists kratom as Schedule 9 (prohibited) since 2003.[48] The UK banned it in 2016 under the Psychoactive Substances Act;[48] France banned it in 2020;[48] Sweden prohibited it in 2011.[48] Germany and the Netherlands remain unscheduled at the federal level.[48] Kratom alkaloids are not detected by standard immunoassay drug screening panels.[49]
Legal status changes frequently. This overview reflects the status as of May 2026 and is not legal advice. Verify current law in the relevant jurisdiction before acting on this information.
Preparations[edit]
Fresh leaf (chewed)
Fresh leaf is the traditional Southeast Asian preparation. Leaves are plucked, the tough central vein is removed, and the remaining lamina is chewed and held in the cheek. Onset occurs within 5–10 minutes; effects last 1–2 hours. Typical traditional use involves 1–3 leaves per session.[3] Fresh leaf is rarely available outside cultivation regions.
Dried leaf powder (oral — toss-and-wash or mixed)
Dried leaf powder is the most common commercial preparation worldwide. Users swallow measured powder directly with water ("toss and wash") or mix it into juice, yogurt, or a smoothie. Onset is 20–40 minutes; total duration 3–5 hours.[4] Dose ranges are preparation-specific:
- 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,[5] making batch-specific dose calibration essential.
Tea (oral, aqueous decoction)
Kratom tea is prepared by simmering dried leaf powder or crushed leaf in water for 15–30 minutes and straining the plant material. Onset is slightly faster than powder (15–30 minutes) due to pre-extraction of alkaloids into solution; duration is comparable at 3–5 hours. Dose ranges parallel dried powder by weight of starting material. Tea produces a somewhat smoother onset curve with less gastrointestinal irritation than raw powder, as insoluble plant fiber is removed.
Capsules (oral)
Capsules contain 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 powder. Capsules reduce taste aversion but make dose titration less flexible.
Extracts and concentrated products
Extracts — sold as resins, tinctures, and liquid "shots" — concentrate kratom alkaloids well beyond natural leaf levels. These products carry the highest risk of any kratom preparation. Commercial extracts marketed as botanical kratom may contain dramatically enriched 7-hydroxymitragynine concentrations, producing a fundamentally different pharmacological profile from leaf.[8] Onset is rapid (10–20 minutes for liquid extracts); duration varies by concentration. Dose equivalence between extracts and leaf powder is unreliable — labeling is frequently inaccurate, and no standardized potency system exists. Start at half or less of the dose a user would take in powder form and titrate cautiously.
Per-preparation dose tiers, timelines, and bioavailability data are in the Dose · by preparation card on this page.
Safety[edit]
- Acute toxicity
- Low
- Chronic toxicity
- Moderate
- Withdrawal
- Moderate
- Tolerance buildup
- moderate
- Tolerance reset
- 10 days
- Physical
- High
- Psychological
- High
- Compulsive redosing
- Moderate
- Dose escalation
- Moderate
- Cross-tol.
- opioids
Toxicity
No human lethal dose has been established for mitragynine or any kratom preparation. Animal studies document hepatic, renal, pulmonary, and CNS toxicity at high doses.[28] Acute toxicity from traditional leaf doses is considered low; chronic toxicity data are limited but raise concerns for liver and cognitive function.[28]
Kratom is a documented cause of drug-induced liver injury (DILI) with a predominantly cholestatic pattern.[7] A comprehensive review found a median latency of 20.6 days from first use to symptom onset (range 2–49 days), with jaundice, pruritus, and dark urine as common presenting features.[7] Causality assessment concluded that kratom "likely causes liver injury based on totality of evidence".[7] Individual cases have demonstrated cholestatic injury mimicking primary biliary cholangitis.[29]
Published fatalities attributed in whole or part to kratom involve polydrug exposures in nearly all cases. Nine deaths in Sweden resulted from "Krypton" — kratom powder adulterated with O-desmethyltramadol.[16] A fatal case involving hydromorphone and kratom attributed death to hydromorphone toxicity with mitragynine as a contributing factor.[30] A 26-year-old male died of cardiorespiratory failure following suspected kratom use, though polydrug exposure was not fully excluded.[31] No deaths attributed solely to botanical kratom appear in published Southeast Asian literature.[9]
Contaminant and adulterant risk is a distinct safety concern for commercial kratom products:
- Synthetic opioid adulterants: O-desmethyltramadol was documented in "Krypton" products (9 fatalities);[16] semi-synthetic 7-hydroxymitragynine enrichment appears in products marketed as botanical kratom[8]
- Microbial contamination: FDA Import Alert 54-15 cites Salmonella contamination risk as a basis for detaining imported products[32]citation needed
- Heavy metals: Lead, cadmium, and other heavy metal contamination is a theoretical concern for dried botanical products; no published validated surveys specific to kratom products were identifiedcitation needed
- Labeling inaccuracy: Mitragynine content ranges 0.7–38.7% w/w across commercial products[5]
No ISO/IEC-accredited mandatory federal testing program exists for commercial kratom products in the United States. Some US states implementing Kratom Consumer Protection Act (KCPA) frameworks require testing and labeling standards.
Psychological Risks
Higher doses and concentrated 7-hydroxymitragynine products are associated with anxiety, irritability, and — in rare documented cases — psychosis.[26] Chronic kratom use may adversely affect cognitive performance through disruption of neuroplasticity via opioid, serotonergic, and adrenergic receptor interactions.[27] Epigenetic mechanisms have been implicated in withdrawal-associated cognitive impairment in animal models.[33] Kratom use patterns meeting DSM-5 substance use disorder criteria have been documented, with dose frequency showing a stronger association with dependence severity than dose amount.[34]
Tolerance & Dependence
Tolerance develops with prolonged use through μ-opioid mechanisms. Cross-tolerance with classical opioids is documented; buprenorphine can precipitate withdrawal in kratom-dependent individuals, confirming clinically significant opioid cross-tolerance.[26] The mitragynine half-life is approximately 23 hours;[35] specific tolerance recovery timelines have not been validated in published studies.
Physical dependence liability is high.[6] In studies of 150–170 regular Malaysian kratom tea users, cessation produced mild anxiety (70%), mild depression (81%), moderate pain intensity (84%), moderate pain interference (70%), and sleep problems (46%).[36][37] Severity was dose-dependent — users consuming ≥4 glasses daily had higher odds of more severe depression, pain interference, and sleep problems.[37] Withdrawal was characterized as "relatively mild" compared to classical opioid analgesic withdrawal in these studies.[37]
Severe withdrawal from concentrated 7-hydroxymitragynine products — including psychosis and respiratory compromise requiring intubation — has been documented in case reports.[26]
Recovery resources, crisis lines, and support pathways → View all
Drug Interactions
Kratom is both a CYP enzyme substrate and inhibitor/inducer, creating complex herb–drug interaction liability.
CYP3A4 inhibition is the best-characterized mechanism: a single 2 g dose of kratom tea increased midazolam AUC by 1.39× (90% CI: 1.23–1.57) and Cmax by 1.50× in 12 healthy adults.[39] PBPK modeling predicts mitragynine increases midazolam exposure 2.2–2.7× with co-administration.[40] Drugs extensively metabolized by CYP3A4 — including many opioids (oxycodone, fentanyl), benzodiazepines (midazolam, alprazolam), immunosuppressants (cyclosporine, tacrolimus), and statins — may reach toxic levels with concurrent kratom use.
CYP2D6 inhibition is demonstrated in vitro[41] but was not clinically significant at a 2 g kratom dose.[39] Significance at higher doses remains uncharacterized.
PXR-mediated enzyme induction with repeated kratom use (CYP3A4, CYP1A2, P-glycoprotein; 3–6-fold activation)[42] creates a paradoxical combination of acute CYP inhibition and chronic CYP induction, potentially reducing efficacy of co-administered drugs during sustained use.
Pharmacodynamic synergy with opioids and CNS depressants is the highest-risk interaction class. Fatal outcomes have been documented with kratom and hydromorphone[30] and kratom products adulterated with O-desmethyltramadol.[16] Combinations with alcohol, GHB/GBL, benzodiazepines, or ketamine carry pharmacodynamically plausible risk of additive CNS and respiratory depression.safety citation needed
Contraindications
Pregnancy: Contraindicated. Neonatal abstinence syndrome has been documented with kratom use during pregnancy;[43] teratogenicity is unknown. The opioid-like mechanism warrants avoidance during pregnancy and lactation.[44]
Hepatic impairment: Contraindicated. Kratom is a documented cause of drug-induced liver injury and may worsen pre-existing hepatic conditions.[7]
Concurrent opioid use: Contraindicated. Additive μ-opioid receptor agonism with documented fatal outcomes in polydrug contexts.[30][16]
Concurrent CYP3A4 substrates with narrow therapeutic index: Relative contraindication. Kratom inhibits intestinal CYP3A at typical oral doses, potentially elevating co-administered drug concentrations to toxic levels.[39]
Psychiatric history (psychosis): Relative contraindication for concentrated 7-hydroxymitragynine products, which have been associated with psychotic symptoms during withdrawal.[26]
Renal impairment: Relative contraindication. Renal impairment was present as a contributing factor in a documented fatal kratom-polydrug case;[30] the large volume of distribution (38 L/kg) suggests altered accumulation with impaired clearance.[35]
Harm Reduction[edit]
Forms & Identification
Lab testing matters more for kratom than for most botanical preparations because alkaloid content varies more than 50-fold across commercial products[5] and because some products marketed as botanical kratom contain enriched 7-hydroxymitragynine at concentrations far exceeding natural leaf levels.[8] A Certificate of Analysis (COA) from an ISO-accredited laboratory confirms mitragynine and 7-hydroxymitragynine concentrations, screens for heavy metals and microbial contaminants, and verifies absence of synthetic adulterants. Products sold without a COA should be treated as unverified. In US states that have enacted Kratom Consumer Protection Act (KCPA) frameworks, testing and labeling are mandatory — products from KCPA-regulated vendors carry greater reliability than unregulated sources.
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 who provide 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.[30][16]
- 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 especially important. Daily use in workplace settings carries impairment risk at higher doses — sedation, cognitive slowing, and impaired reaction time are dose-dependent effects. Users who take kratom for functional stimulation should be aware that 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. Social or solitary use at sedating doses should occur in a safe, stable environment.
Aftercare & integration. After higher-dose kratom use, expect a period of low energy and mild mood dip lasting several hours as effects recede — this is a normal pharmacological rebound effect, not a medical concern. Hydrate thoroughly; kratom is mildly diuretic and appetite-suppressing, so fluid and electrolyte replenishment (water, broth, potassium-rich foods) supports recovery. If using kratom daily, monitor for constipation — a common opioid-class side effect — and maintain dietary fiber intake. Next-day grogginess is more likely with evening dosing of sedating doses; plan accordingly.
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 — myalgia, insomnia, anxiety, and irritability are common symptoms.[6][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 μ-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 μ-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.
Legal Status[edit]
Mitragynine and 7-hydroxymitragynine are not listed under any of the three major UN drug control treaties. In 2021, the WHO Expert Committee on Drug Dependence reviewed kratom and found insufficient evidence to recommend international scheduling.[45] This absence of treaty-level control has produced a patchwork of national and subnational regulations. In the United States, kratom is federally unscheduled but banned in several states, while a growing number of states have adopted Kratom Consumer Protection Act (KCPA) frameworks that regulate rather than prohibit.
| Jurisdiction | Scheduling status | Notes |
|---|---|---|
| United States (federal) | Unscheduled | Not listed under the Controlled Substances Act. DEA proposed Schedule I placement August 31, 2016; withdrew October 13, 2016 following approximately 142,000 public comments.[15] FDA Import Alert 54-15 authorizes detention of imported kratom products; kratom is not lawfully marketed as a drug, dietary supplement, or food additive.[32] |
| US — Alabama | Schedule I (2016) | Mitragynine and 7-hydroxymitragynine listed as Schedule I[46] |
| US — Arkansas | Schedule VI (2016) | Banned[46] |
| US — Indiana | Schedule I (2014) | Among the earliest US state bans[46] |
| US — Vermont | Banned | Sale and possession prohibited[46] |
| US — Wisconsin | Schedule I | Banned[46] |
| US — Rhode Island | KCPA regulated (April 2026) | Historically banned; signed Kratom Consumer Protection Act July 2025, effective April 1, 2026 — transitioning from ban to regulated framework with age restrictions, labeling, and testing requirements[46] |
| Thailand | Legal (2021) | Banned 1943 (Kratom Act B.E. 2486); Category 5 narcotic 1979. Legalized August 24, 2021[13] |
| Malaysia | Illegal | Prohibited under Poison Act 1952[47] |
| Australia | Schedule 9 (Prohibited) | Listed under the Poisons Standard (SUSMP) since 2003[48] |
| United Kingdom | Banned (2016) | Prohibited under Psychoactive Substances Act 2016[48] |
| Netherlands | Legal | Unscheduled; available through licensed retail outlets[48] |
| Sweden | Banned (2011) | Prohibited[48] |
| France | Banned (2020) | Prohibited[48] |
| Germany | Unscheduled (federal) | No federal ban; individual state regulations may vary[48] |
Several US states have enacted KCPA frameworks imposing age restrictions (typically 21+), labeling requirements, and testing standards rather than outright prohibition. This regulatory approach represents a middle path between federal inaction and state-level criminalization.
Detection
Kratom alkaloids are not detected by standard immunoassay drug screening panels, including standard opioid immunoassays.[49] Detection requires specific LC-MS/MS or GC-MS analytical methods. No commercially available kratom-specific rapid test validated for point-of-care use has been identified in the published literature.
Frequently asked questions
What is Kratom?
Kratom is a tropical tree (Mitragyna speciosa) of the Rubiaceae family whose leaves produce dose-dependent stimulant and opioid-like effects. Its primary alkaloid mitragynine acts as a G-protein-biased partial μ-opioid receptor agonist with α₂-adrenergic activity.
What are dangerous combinations with Kratom?
The highest-severity documented interactions for Kratom: Alpha-2 adrenergic receptor antagonist (Dangerous), Anticholinergics (Dangerous), Antipsychotics (Dangerous), Atypical antipsychotics (Dangerous), Benzodiazepines (Dangerous). See the interactions section for the full list with mechanisms and severity levels.
Is Kratom addictive?
Psychedex records tolerance and dependence data rather than a yes/no rating. Recorded tolerance indicators for Kratom: tolerance builds moderate; full reset takes 10 days; cross-tolerance develops with opioids. See the article's dependence and safety sections for recorded dependence data.
experience reports
No experience reports yet. Be the first to contribute.
First-person accounts of subjective effects, timing, and outcomes — submitted for harm reduction.
references
- [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]
- [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]
- [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] ^abcdSchimmel J, Dart RC (2020) Kratom (Mitragyna Speciosa) Liver Injury: A Comprehensive Review — Drugs doi:10.1007/s40265-019-01242-6
references
- [1] ^abcdKruegel AC, Grundmann O (2017) The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse — Neuropharmacology doi:10.1016/j.neuropharm.2017.08.026
- [2]
- [3] ^abcdefgCinosi 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
- [4] ^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
- [5]
- [6] ^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