Kratom
Kratom is a herbal product from the leaves of Mitragyna speciosa, a Southeast Asian tree. Its principal active alkaloids, mitragynine and 7-hydroxymitragynine, act at opioid and monoamine receptors, giving stimulant-like effects at low doses and opioid-like sedation and analgesia at higher doses. It is used for pain, energy, mood and opioid-withdrawal self-management. Regular use can cause dependence, and it interacts with opioids and other sedatives.
01 Overview
Kratom has a long history of traditional use in Southeast Asia and is now widely sold internationally as a supplement, tea or extract. A growing body of human survey, pharmacokinetic and case-report data exists, though large controlled trials are lacking. At low doses users report stimulation and alertness; at higher doses effects shift toward opioid-like analgesia, relaxation and sedation.
Regular, heavy use can produce tolerance and a physical dependence with a withdrawal syndrome resembling a mild-to-moderate opioid withdrawal (restlessness, muscle aches, irritability, insomnia). Concentrated extracts and products enriched in 7-hydroxymitragynine carry higher dependence and toxicity risk than raw leaf. Kratom has been implicated in liver injury in some cases and in deaths, most of which involved other drugs. It interacts with opioids and other CNS depressants (additive sedation and respiratory depression) and, through effects on drug-metabolising enzymes, with a range of medications.
02 Mechanism
Mitragynine and its more potent metabolite 7-hydroxymitragynine are partial agonists at the mu-opioid receptor with biased signalling, and the alkaloids also act on alpha-2 adrenergic, serotonergic and dopaminergic systems, producing the mixed stimulant-opioid profile.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Threshold | 1–2 g | Oral | Raw leaf powder; mild stimulation. |
| Common (stimulant range) | 2–5 g | Oral | Energy, alertness and mild mood lift at lower end. |
| Strong (opioid-like range) | 5–8 g | Oral | Sedation and analgesia predominate; extracts are far more potent by weight. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Stimulation and increased energyAlertness and mild euphoria at lower doses. | low doses | Observational | |
| AnalgesiaOpioid-like pain relief; a common reason for use. | higher doses | Observational | |
| Relief of opioid withdrawalWidely used to self-manage opioid withdrawal, though not a formally approved treatment. | self-reported | Observational | |
| Sedation and relaxationCalming, opioid-like sedation at higher doses. | higher doses | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Dependence and withdrawalTolerance and physical dependence develop; withdrawal resembles mild-to-moderate opioid withdrawal. | Moderate | Common with heavy regular use | Observational | |
| Additive sedation and respiratory depressionCombined with opioids, benzodiazepines or alcohol, kratom can add to sedation and respiratory depression; most kratom-associated deaths involve other substances. | Severe | Uncommon; mainly with other drugs | Observational | |
| HepatotoxicityCholestatic or mixed liver injury has been reported in a number of case reports, usually reversible on stopping. | Severe | Rare | Observational | |
| Nausea, constipation and other GI effectsOpioid-like gastrointestinal effects including nausea and constipation. | Mild | Common | Observational |