Natural Compound

Kratom

Mitragyna speciosa

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

1-6 g daily

watchEffect Window

15-45 min (acute)

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Kratom (Mitragyna speciosa) contains alkaloids with stimulant and opioid-like receptor activity. It is used for pain relief, energy, and mood effects, with substantial safety and dependence concerns.

Observational reports suggest analgesic effects and increased energy at lower exposures, with more sedative effects at higher exposures. Some users report reduced opioid use, but evidence is preliminary and confounded. Minority benefits include mood enhancement and improved social functioning. Dependence, withdrawal, adulteration, and variable alkaloid content are major limiting factors for any net benefit.

MOR partial agonism with kappa/delta antagonism plus alpha2 and monoamine reuptake effects. Dose-sensitive opioid-like and adrenergic/monoaminergic activity.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Pain relief
  • Opiate withdrawal support
  • Energy/mood support

Secondary Outcomes

  • Short-cycle symptom relief
  • Sleep and alertness modulation

Safety

Contraindications and Interactions

Contraindications

  • Pregnancy or lactation
  • Severe or unstable cardiovascular/psychiatric/hepatic/renal/endocrine disease without clinician clearance
  • Seizure history or uncontrolled neurologic risk without specialist oversight

Side effects

  • Nausea
  • Constipation
  • Dizziness
  • Drowsiness/sedation
  • Reduced motivation
  • Agitation
  • Vomiting
  • Dry mouth
  • Confusion (dose-related warning)
  • Dependence with regular/daily use
  • Withdrawal symptoms after abrupt cessation

Interactions

No entries provided

Avoid if

  • Pregnancy/lactation
  • Unstable cardiovascular, psychiatric, hepatic, renal, or endocrine disease
  • Active malignancy
  • Severe anxiety or panic disorder that is not clinically stable
  • Seizure history
  • History of substance use disorder or active dose-escalation pattern
  • Concurrent high-risk CNS depressant or serotonergic polypharmacy

Evidence

Study-level References

kratom-SRC-001Human and preclinical literature review
Sourceopen_in_new

Prozialeck, W.C. et al., 2012 review

Population: Adults

Dose protocol: Source-listed

Key findings: Review discusses opioid receptor activity (MOR partial agonism, kappa/delta antagonism), alpha2 and monoamine effects, acute symptomatic benefits, and dependence/withdrawal concerns with higher-dose or sustained use.

Notes: Evidence supports biologic plausibility but real-world heterogeneity and safety uncertainty keep confidence at C.

Paper content

Review discusses opioid receptor activity (MOR partial agonism, kappa/delta antagonism), alpha2 and monoamine effects, acute symptomatic benefits, and dependence/withdrawal concerns with higher-dose or sustained use.

kratom-SRC-002Cross-sectional comparative study.
Sourceopen_in_new

La-Up A, Saengow U, Aramrattana A. Hematological and clinical-chemistry parameters of kratom users: a comparative study of users and non-users in Southern Thailand. Sci Rep. 2026. doi:10.1038/s41598-026-35524-3. PMID:41545679.

Population: Adults from Southern Thailand, a traditional kratom-endemic region.

Dose protocol: Observational, long-term traditional kratom use (no controlled dosing)

Key findings: No clinically significant hepatic or hematological toxicity in chronic users versus non-users after confounder adjustment. No clear dose-response relationship for organ toxicity.

Notes: Cross-sectional design in a traditional-use population. Findings may not apply to Western commercial products or extract-based consumption.

Paper content

This cross-sectional comparative study examined 285 kratom users and 296 non-users in Southern Thailand. After adjusting for confounders, chronic kratom use was not associated with clinically significant hepatic or hematological toxicity. Kratom users showed lower serum creatinine and higher eGFR, but these differences were attributed to lower BMI in the user group rather than pharmacological effects. No clear dose-response relationship regarding organ toxicity was observed. The study provides community-level safety data from a traditional kratom use population, though the observational design cannot rule out confounding or long-term effects not captured by a cross-sectional snapshot.

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