Supplement
Kratom is a leaf from a Southeast Asian tree whose main compounds, mitragynine and 7-hydroxymitragynine, partly activate the brain's opioid receptors. People mostly look at it for pain relief, and surveys and reviews reported relief, but the evidence is very limited because no rigorous human trials have tested it. Reviews and case reports also found that regular use led to physical dependence and opioid-like withdrawal.
Sources: PMID 31308789; PMID 38251400
- Updated
- How we grade
- 4 studies cited
- Best evidence
- Grade D
- Conditions studied
- 0
- Outcomes
- 4
- Graded outcomes
- 0004
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
General
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Physical Dependence and Withdrawal Risk Multiple reviews and case reports document that regular kratom use causes physical dependence and a withdrawal syndrome (anxiety, insomnia, irritability, pain) similar to opioid withdrawal. FDA has issued public health warnings. Deaths have been reported, typically involving polysubstance use. | Worsens (the measure goes up) | Large effect | 4 studies | 2 people | ||
Studies that measured physical dependence and withdrawal risk | ||||||
| Opioid Withdrawal Symptom Management A case report of 2 pregnant women documented kratom-related opioid dependence and withdrawal (PMID:30204686). Narrative reviews note widespread self-use for opioid withdrawal management, but this is NOT an FDA-approved treatment and may substitute one dependence for another. No controlled trials exist. | Changes; see studies | Moderate effect | 3 studies | 2 people | ||
Studies that measured opioid withdrawal symptom management | ||||||
| Drug Interaction Risk A 2025 review (PMID:40522665) analyzing published literature and FDA FAERS data found that kratom alkaloids inhibit CYP3A4 and CYP2D6 enzymes, creating pharmacokinetic interactions with co-administered medications. Pharmacodynamic interactions with other CNS depressants (opioids, benzodiazepines, alcohol) increase risk of respiratory depression. | Changes; see studies | Moderate effect | 3 studies | |||
Studies that measured drug interaction risk | ||||||
| Pain Relief Mitragynine and 7-hydroxymitragynine act as partial mu-opioid receptor agonists, providing a clear mechanistic basis for analgesia. User surveys and narrative reviews report pain relief at higher doses (5-15g), but no rigorous clinical trials have evaluated kratom for pain in humans. | Improves (the measure goes down) | Moderate effect | 2 studies | |||
Studies that measured pain relief | ||||||
Key findings
- Physical Dependence and Withdrawal RiskWorsens (the measure goes up)
- Opioid Withdrawal Symptom ManagementChanges; see studies
- Drug Interaction RiskChanges; see studies
Safety notes in the studies
- Pharmacodynamic interactions with other CNS depressants (opioids, benzodiazepines, alcohol) increase risk of respiratory depression.
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- Grade D
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Studies cited
4 studies from PubMed