A Southeast Asian leaf whose compounds act partly like opioids and partly like stimulants, with dose deciding which. Less pain, more energy and steadier mood are consistently described but barely measured. The costs are better established: dependence with withdrawal on stopping, nausea and constipation, uncommon but occasionally severe liver injury. Nearly every death involved other depressant substances. (Full Review)

Protocol

Dose form and amount

Whole dried leaf powder, 2–3 g

The studied form; measured United States intake runs 25–31 mg mitragynine per serving, 50–135 mg daily.

Single versus split dosing

A single daily dose

Most users split into two or three daily doses; splitting raises total intake and accumulation, which a single dose better limits.

Best time of day

Daytime, low dose in the morning

Low doses are favored in the morning for energy; late-afternoon and evening dosing is most associated with disrupted sleep.

Time to effect

Pain tolerance

1 hour

Tolerance to cold-induced pain rose one hour after leaf decoction in regular users.

Stimulation and energy

15–30 minutes

Subjective effects begin within 15–30 minutes and peak near one hour.

Full blood-level accumulation

8–9 days

Blood levels continue rising for eight to nine days of repeated dosing; mean terminal half-life 43–68 hours.

Benefits

Medium: Increased pain tolerance and analgesia; more favorable lipid and body-weight profile; low-dose stimulation and sustained attention

Low: Self-managed reduction of opioid and other substance use; mood and anxiety self-management; delayed ejaculation and sexual function

Speculative: Anti-inflammatory and antioxidant activity

Contraindications

Pregnancy and breastfeeding, at any dose

Established liver disease (Child-Pugh Class B or C cirrhosis), or unexplained liver enzymes above three times the upper reference limit

Epilepsy or any seizure disorder, and people taking medicines that lower seizure threshold

Congenital or acquired long QT syndrome, corrected QT interval above 470 ms in men or 480 ms in women, or myocardial infarction within 90 days

Current opioid use disorder being treated with buprenorphine or methadone

Anyone on full opioid agonists, benzodiazepines, or with an active alcohol use disorder

Adolescents and adults under 21

Key Interactions

CYP3A4 substrates with narrow margins (midazolam, quetiapine, tacrolimus, simvastatin)

CYP2D6 substrates (metoprolol, codeine, tamoxifen, many antidepressants)

CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin, grapefruit juice)

P-glycoprotein substrates (digoxin, dabigatran, edoxaban)

Alcohol

Z-drugs (zolpidem)

Sedating antihistamines (diphenhydramine, doxylamine) and dextromethorphan

Loperamide

Sedating botanicals (kava, valerian, passionflower, melatonin, cannabidiol)

Supplements adding opioid-side-effect burden (magnesium, iron, calcium)

St John’s wort

Risk & Side Effects

High: Physical dependence and withdrawal on cessation; dose-dependent acute adverse effects

Medium: Cholestatic liver injury; QT prolongation and cardiac rhythm risk

Low: Seizures; hallucinations and psychosis; respiratory depression and death in polysubstance exposure; direct lung injury; concentrated 7-hydroxymitragynine products; contaminated products; neonatal withdrawal in pregnancy; memory impairment at heavy intake; skin hyperpigmentation; raised prolactin and suppressed testosterone

Speculative: Long-term organ toxicity at sustained high exposure

Monitoring

Marker	Target	Why
Alanine aminotransferase	Under 25 U/L men, 20 U/L women	Cell-injury component of liver toxicity
Alkaline phosphatase with total bilirubin	40–90 U/L; bilirubin under 1.0 mg/dL	The cholestatic pattern kratom injury takes
Gamma-glutamyl transferase	Under 20 U/L men, 15 U/L women	Bile-duct versus bone cause of a raised alkaline phosphatase
LDL-C	Under 2.6 mmol/L (100 mg/dL)	Whether the cohort-level metabolic difference appears individually
Resting heart rate and blood pressure	50–70 per minute; under 120/80 mmHg	The commonest cardiovascular effects
Corrected QT interval (electrocardiogram)	Under 450 ms men, 460 ms women	Mitragynine lengthens electrical recovery time, dose-dependently
Prolactin and total testosterone (men)	Prolactin under 15 ng/mL; testosterone 600–900 ng/dL	Opioid activity can suppress the hormonal axis
Creatinine with estimated glomerular filtration rate	Above 90 mL/min/1.73 m²	Kidney reserve, clearance, heavy-metal exposure

Cadence: Baseline panel before any use; liver enzymes and bilirubin at 6 weeks; blood pressure and heart rate at 4 weeks; full repeat panel with lipids and electrocardiogram at 6 months, then every 6 to 12 months while use continues. Jaundice, dark urine or itching triggers immediate testing.

Qualitative Assessment

Sleep onset latency and number of night wakings, recorded on the same scale each week
Daytime energy and mental clarity, especially in the hours after a dose
Bowel regularity, the earliest and most persistent adverse effect
Pain intensity and pain interference with daily activity
Mood, irritability and anxiety, rated at a fixed time of day rather than immediately after dosing
Whether dosing is still driven by a stated purpose or has shifted to avoiding withdrawal
Total grams per day and days used per week, written down rather than estimated

Kratom for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment