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Mitragynine Facts

Opioid; Indole alkaloid; Mu-opioid receptor agonist

Description

Mitragynine is a naturally-occurring opioid of the indole alkaloid class. It activates opioid receptors, but depends on a liver-generated metabolite to produce most of its pain-relieving effects.[1]

Subjective effects include stimulation, heightened focus, pain suppression, warm mood elevation, and sedation. Low doses feel like strong coffee with added warmth; higher doses shift into opioid sedation and heavy-limbed calm.

Physical dependence develops with regular use; stopping brings withdrawal — muscle aches, insomnia, anxiety, and low mood.[2] The dominant danger is combination: 87% of kratom-associated deaths involved other substances,[3] and mixing with opioids or benzodiazepines multiplies respiratory failure risk.

Dose and durationby route · individual sensitivity varies

Oral(mg)
Threshold< 5 mgLight5 – 15 mgCommon15 – 40 mgStrong40 – 80 mgHeavy80+ mg

Starts in 15 – 30 minLasts 2 – 5 hoursAfter-effects 2 – 6 hours

Body and dependence

Acute toxicity
Moderate
Chronic toxicity
Moderate
Physical dependence
Moderate
Psychological dependence
Moderate
Withdrawal
Moderate
Compulsive redosing
Moderate

Tolerance

Builds
Moderate
Fully resets after
21 days
Carries over to
morphine; oxycodone; heroin; other mu-opioid receptor agonists

Effectslikely at a common dose

Perception
none likely · 6 possible, including Spatial disorientation, Vestibular distortion, Visual acuity suppression
Body
Body high; Pain suppression; Pupil constriction; +28 possible, including Nausea, Diarrhea, Dizziness
Thinking
none likely · 13 possible, including Compulsive redosing urge, Cognitive impairment, Information processing suppression
Feeling
none likely · 8 possible, including Anxiety, Anhedonia, Depression
Self
none likely · 5 possible, including Craving

Who shouldn't take it

Absolute
Concurrent full opioid agonists; Pregnancy
Relative
Hepatic impairment; Renal impairment; Concurrent CNS depressants (benzodiazepines, alcohol, gabapentinoids); CYP3A substrates with narrow therapeutic index; Perioperative setting

Combinations60 recorded

Lethal (4)
Benzodiazepines, Barbiturates; GHB, Baclofen; GHB, GBL; Local anesthetics
Dangerous (28)
Alpha-2 adrenergic receptor antagonist; Amphetamines; Anticholinergics; Antihistamines; Antipsychotics; Benzodiazepines; Buprenorphine, Kratom; Cannabis, THC; Clonidine, Guanfacine; Gabapentin, Pregabalin; MAOIs; MDMA, Amphetamines; MDMA, MDA; Naltrexone; NRIs; SNRIs; SSRIs; Stimulants; Synthetic cannabinoids; THC; Caffeine; CBD; Glutamate modulator; Huperzine A; and 4 more, see full page
Caution (19)
See full page: psychedex.org/substances/mitragynine
Not graded (9)
Not listed never means safe.

Seek help immediately if

  • Unresponsive / can't be woken, even to a firm sternal rub
  • Slow, shallow, or stopped breathing
  • Pinpoint pupils
  • Blue/grey lips, fingertips, or skin (cyanosis)
  • Limp body; pale, clammy skin
  • Choking or gurgling sounds ("death rattle")
  • Slow, erratic, or absent pulse

What to do

  1. Try to wake them — shout their name, firm sternal rub
  2. Call emergency services immediately
  3. Administer naloxone if available
  4. Give rescue breaths (or CPR if there is no pulse)
  5. Place them in the recovery position
  6. Stay with them; re-dose naloxone every 2–3 minutes if there is no response
Reversal agent
Naloxone (Narcan) — opioid antagonist. May require repeated doses; its effect can wear off before the opioid does.

With prompt naloxone and rescue breathing, reversal is usually rapid. Because naloxone can wear off before the opioid — especially with long-acting opioids (methadone) or high-potency ones (fentanyl) — a period of monitoring is needed even after the person revives.

988 Suicide & Crisis LifelineFireside Project: 62-FIRESIDE

Version r1 · Not medical advice

References

  1. [1]
    ^Kruegel AC, Uprety R, Grinnell SG, Langreck C, Pekarskaya EA, et al. (2019) 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects — ACS Central Science doi:10.1021/acscentsci.9b00141
  2. [2]
    ^Singh D, Narayanan S, Vicknasingam BK, Prozialeck WC, et al. (2018) Severity of Pain and Sleep Problems during Kratom (Mitragyna speciosa Korth.) Cessation among Regular Kratom Users — Journal of Psychoactive Drugs doi:10.1080/02791072.2018.1443234
  3. [3]
    ^Corkery J, Streete P, Claridge H, et al. (2019) Characteristics of deaths associated with kratom use — Journal of Psychopharmacology doi:10.1177/0269881119862530
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