Kratom
Mitragyna speciosa
An opioid-acting leaf — its effects and serious risks are both real.
Evidence tier
Mixed
Research weight
Citations
21 verified / 21
Classification
Banned & Harmful
❝
What the evidence says. Conflicting results across studies; benefit uncertain.
⚠
Health warning. Kratom's alkaloids act on opioid receptors. It carries real risks of dependence, withdrawal, liver toxicity, seizures and — especially with concentrated 7-OH products — death. Legal status varies and some regions ban it.
What is Kratom?
Kratom (Mitragyna speciosa) is a banned or harmful substance used for (used for) pain relief, energy, opioid-withdrawal self-treatment. NutriDex grades the human evidence as Mixed. Kratom is a Southeast-Asian tree whose alkaloids — mitragynine and the far more potent 7-hydroxymitragynine — bind mu-opioid receptors, producing stimulant effects at low doses and opioid-like sedation at higher ones. People use it for pain, energy and to self-manage opioid withdrawal, but it carries genuine opioid-type risks. The FDA warns against it, citing dependence, liver toxicity, seizures and deaths, and has moved to schedule concentrated 7-OH products.
Purported Benefits
✓(Used for) pain relief, energy, opioid-withdrawal self-treatment
✓(Claimed) mood lift
Dosing & Compounds
Typical Dose
No safe established dose; effects are dose-dependent and risk rises sharply with concentrated/adulterated products.
Active Compounds
Safety & Cautions
⚠ Dependence and opioid-like withdrawal, liver injury, seizures, and death (especially with high-potency 7-OH products or mixed with other drugs). Unregulated and often adulterated. Legal status varies by region. Educational only — always check with your doctor or pharmacist before combining Kratom with any medicine.
Kratom drug interactions
Known or theoretical interactions between Kratom and common medications — educational, not exhaustive. Always check with your doctor or pharmacist before combining Kratom with any medicine.
Avoid
Opioids, benzodiazepines, alcohol
Additive sedation and respiratory depression; kratom is implicated in many overdose deaths.
Kratom alkaloids act on opioid receptors; with depressants they intensify sedation and respiratory suppression. NIDA — Kratom · FDA — Kratom
Key Studies ★ 21 studies
Systematic review of case reports
Acute adverse effects review
✓ Full text
A 2025 systematic review of case reports (95 patients) concluded current evidence is insufficient to show kratom alone causes severe acute harm, as confounding substances were present in 32 deceased and 7 surviving cases, implicating polypharmacy.
Systematic review
Kratom and seizures review
✓ Full text
A 2025 systematic review (11 articles, 20 patients; plus 481 FAERS and 221,178 CAERS reports) found insufficient evidence that kratom causes seizures, with only one case having confirmed drug-level testing and no dose-response relationship.
Meta-analysis
Frontiers in Pharmacology 2025 (metabolic meta-analysis)
✓ Full text
Meta-analysis of five cross-sectional studies (1,458 adults; PROSPERO CRD42024600702) found kratom use associated with lower LDL-cholesterol (MD -0.21 mmol/L; 95% CI -0.39, -0.02), lower triglycerides (MD -0.17 mmol/L; 95% CI -0.25, -0.09), and lower BMI (MD -1.52 kg/m2; 95% CI -2.81, -0.23), while total cholesterol and blood sugar effects were not statistically significant.
Systematic review
Frontiers in Pharmacology 2025 (acute adverse-effect case review)
✓ Full text
Evaluation of 95 case-report patients (55 toxicologically confirmed; 35 deceased with mitragynine 3.5-7,500 ng/mL, 20 living 5-340 ng/mL) found confounding substances present in 32 deceased and 7 surviving cases, concluding the literature provides insufficient evidence that kratom alone increases the risk of severe acute adverse effects.
Meta-analysis
Rayanakorn 2025 (Front Pharmacol)
✓ PubMed
Systematic review and meta-analysis of 5 cross-sectional studies (1,458 adults). Kratom use associated with significantly lower LDL-c (MD -0.21 to -0.25 mmol/L), triglycerides (MD -0.17 mmol/L), and BMI (MD -1.52 kg/m2), and higher HDL-c (MD +0.07 mmol/L); total cholesterol and blood glucose changes not significant. Suggests a protective association against some metabolic risk factors. (per PubMed; DOI 10.3389/fphar.2025.1587528)
Meta-analysis
Yang 2024 (Eur Addict Res)
✓ PubMed
Multilevel meta-analysis of 36 studies. Kratom use showed a very small positive association with negative mental-health indicators (r=0.092, 95% CI 0.020-0.164) and a small correlation with externalizing disorders (r=0.201); no significant association with positive mental-health indicators, quality of life, or internalizing disorders. The substance-use-disorder association was stronger in Malaysian samples and among those not co-using other drugs. (per PubMed; DOI 10.1159/000539338)
Systematic review
Prenatal exposure systematic review
✓ Full text
A systematic review of prenatal kratom exposure (Wright et al., J Perinatol 2021; 6 infants from 5 case reports) found 5 of 6 (83%) neonates developed neonatal abstinence syndrome requiring morphine, with withdrawal onset from 6-8 hours to 4 days after birth.
Agency / regulator
FDA 2025 (7-OH press announcement)
✓ Source
On July 29, 2025 the FDA issued seven warning letters and recommended scheduling concentrated 7-hydroxymitragynine (7-OH) under the Controlled Substances Act, citing poison-center and law-enforcement surveillance showing rising serious adverse events and overdoses tied to concentrated 7-OH products.
RCT
Prevete 2024 (Psychopharmacology)
✓ PubMed
Phase 1 placebo-controlled single-blind within-subjects trial of isolated mitragynine (5/10/20 mg in 8 volunteers; 40 mg in 7 volunteers). Mitragynine did not affect most outcomes; the low 5 mg dose increased subjective arousal/attention and sustained-attention accuracy, while 40 mg increased subjective amnesia ratings and produced mild psychopathological symptoms. Vital signs unaffected; only mild, transient side effects; doses up to 40 mg well tolerated. (per PubMed; DOI 10.1007/s00213-024-06734-2)
RCT
Tanna 2022 (Pharmaceutics)
✓ PubMed
First comprehensive clinical pharmacokinetic characterization of kratom alkaloids: single 2 g oral dose of a well-characterized product in 6 healthy adults, best fit by a two-compartment model. The 3S alkaloids (mitragynine, speciogynine, paynantheine) showed shorter Tmax (1-2 h), lower AUC, longer terminal half-life (24-45 h), and larger volume of distribution than 3R alkaloids, providing foundational human PK data for safety evaluation. (per PubMed; DOI 10.3390/pharmaceutics14030620)
Agency / regulator
FDA warnings
✓ Source
Linked to dependence, liver toxicity, seizures and deaths; 7-OH proposed for Schedule I.
Retrospective toxicology study
Kratom in overdose deaths
✓ PubMed
A 2024 retrospective coroner toxicology review (4 of 214 opioid overdose deaths had mitragynine detected) found kratom was never present alone, with combined fentanyl/opioid use most associated with fatal outcomes.
Clinical trial (Phase 1 RCT)
Phase 1 mitragynine trial
✓ Full text
In a placebo-controlled Phase 1 study (n=15), single oral mitragynine doses up to 40 mg were well tolerated with only mild transient effects; low doses (5 mg) enhanced attention while high doses (40 mg) increased subjective amnesia and mild psychopathological symptoms.
Randomized controlled trial
Dose-escalation RCT safety
✓ PubMed
A randomized, double-blind, placebo-controlled dose-escalation trial in 116 healthy volunteers (49 kratom, 67 placebo) found mitragynine/7-OH peak concentrations rose dose-proportionally with single and 15 daily doses, supporting tolerability of dried kratom leaf powder in this range.
Cohort
Hill 2024 (J Addict Med)
✓ PubMed
Large cross-sectional survey of 2,061 US kratom consumers applying DSM-5 criteria. 25.5% met criteria for kratom use disorder (KUD), most mild-to-moderate; most common symptoms were tolerance (81.3%) and withdrawal (68.0%). A concurrent other substance use disorder conferred 2.83x higher odds of KUD (95% CI 2.19-3.67); KUD was associated with male sex, younger age, frequent daily use, and psychiatric/substance comorbidity. (per PubMed; DOI 10.1097/ADM.0000000000001290)
Prospective cohort (DILIN)
US DILIN liver injury cohort
✓ PubMed
A prospective US Drug-Induced Liver Injury Network analysis (Ahmad et al., Drug Alcohol Depend 2021) identified 11 cases of kratom-associated hepatotoxicity (median age 40, mostly male), with jaundice developing at a median latency of 14 days; most were hospitalized but all eventually recovered.
Cross-sectional survey
US prevalence survey
✓ PubMed
A quota-sampled US cross-sectional survey of 1,842 adults aged 18-59 (Covvey et al., J Addict Dis 2020) found 6.1% (112) reported lifetime kratom use, with users predominantly male, aged 25-44, and 71-92% reporting concurrent use of other substances.
Case report
Neonatal abstinence case (AAP)
✓ Source
A case report in Pediatrics (Eldridge et al., 2018) documented neonatal abstinence syndrome in an infant after maternal kratom use, presenting with excessive crying, increased tone, tachypnea and poor feeding, and managed with oral morphine.
Study
Withdrawal data
✓ PubMed
Chronic use causes tolerance and opioid-like withdrawal.
NIH authoritative database
NIH LiverTox hepatotoxicity
✓ Full text
The NIH LiverTox database states kratom causes rare but clinically apparent acute liver injury, typically cholestatic or mixed, arising 1-8 weeks after starting use; most patients recover after discontinuation, though severe cases (bilirubin >20 mg/dL) and rare progression to transplant occur.
Mechanism
Pharmacology
✓ Full text
Mitragynine & 7-OH act on mu-opioid receptors — opioid-like effects and dependence.