Kratom

A Southeast Asian leaf whose alkaloids (mitragynine, 7-OH-mitragynine) act on opioid receptors — stimulating at low intakes, opioid-like at higher. Millions of US users take it for energy, pain or to self-taper off opioids, mostly without knowing the receptor pharmacology.

Kratom is a tree leaf whose alkaloids act on opioid receptors, which is the fact that most of the public conversation manages to avoid. Mitragynine is the main alkaloid, but the more potent actor is 7-hydroxymitragynine, present in small amounts in the leaf and produced when the body metabolises mitragynine — it is a partial agonist at the mu-opioid receptor with far greater potency. At lower amounts the plant also has stimulant-like activity through other receptors, which is why users describe it as energising in small quantities and sedating in larger ones. The opioid activity is why dependence and withdrawal are real, and why concentrated extracts behave very differently from traditional leaf.

Human trial evidence is thin; the user-report literature is enormous. Real analgesia and real withdrawal-bridging capacity are plausible from mechanism and surveys. Nothing about its common "energy supplement" framing survives contact with the fact that it is an opioid-receptor agonist.

• There are no adequate randomised controlled trials of kratom for pain, opioid withdrawal or anything else. What exists is survey data, case reports and poison-centre statistics.
• Survey research consistently finds people use it for pain and for self-managing opioid withdrawal, and a substantial share report it helping. That is self-report from people who chose it, not trial evidence.
• Dependence and a genuine opioid-type withdrawal syndrome are well documented in case series — irritability, muscle aches, insomnia, sweating, nausea and cravings.
• Poison-centre calls rose sharply over the last decade. On deaths, the polysubstance pattern is real but does not mean kratom alone is harmless: in a CDC analysis of 152 kratom-positive deaths almost all involved other substances, yet medical examiners considered kratom a cause in 91 of them, including seven with no other positive toxicology. Later poison-centre data recorded 233 associated deaths, 49 of them reported as single-substance.
• FDA has not approved it for any use and has warned about it repeatedly, including seizures of adulterated product and a salmonella outbreak traced to contaminated supply.
• Concentrated 7-hydroxymitragynine products are a newer and materially different risk: far more potent than leaf, and the subject of specific recent regulatory concern.

Mitragynine has a long half-life, on the order of a day, which is why withdrawal from regular use tends to be drawn out rather than sharp. Effects are strongly dose-dependent and shift character as the amount rises. Alkaloid content varies enormously between products, batches and vendors, so two packets of the same nominal product are not equivalent — which is the single biggest practical hazard, since it makes any personal calibration unreliable.

Dependence and a genuine opioid-type withdrawal syndrome with daily use — the single most under-communicated fact about it. Tolerance escalation, nausea, constipation; liver injury reports; deaths almost always involve co-ingestants but exist. Concentrated 7-OH extract products sold at gas stations are a different, sharper drug than leaf powder. Unregulated supply, salmonella recalls on record.

• Anyone taking opioids, benzodiazepines or other sedatives
• Anyone with liver disease
• Anyone pregnant — neonatal withdrawal has been reported in infants of regular users
• Anyone with a history of substance dependence
• Anyone using it as a substitute for supervised opioid dependence treatment

• Opioids, benzodiazepines, alcohol and any sedative — combined respiratory depression, and polysubstance use is the pattern in most kratom-associated deaths.
• It inhibits several liver enzymes that clear other medicines, so it can raise their levels — a poorly characterised but real interaction surface.
• Serotonergic drugs including SSRIs, with case reports of serotonin syndrome.
• Stimulants, given its own stimulant-like activity at lower amounts.

• Frequency and quantity, honestly recorded, because escalation in this category is gradual and easy to miss.
• Liver symptoms — jaundice, dark urine, itching, right-sided abdominal pain — since kratom-associated liver injury is documented.
• Seizures and breathing difficulty, both identified by FDA, with respiratory depression a particular concern for concentrated 7-hydroxymitragynine products and for any combination with other sedatives.
• Product contamination: FDA has identified heavy metals and pathogens in kratom products, including a salmonella outbreak traced to contaminated supply.
• Whether use has become daily, which is the practical dividing line for dependence.
• What you actually bought: concentrated extracts and 7-hydroxymitragynine products are a different drug from leaf powder in effect and risk.

Withdrawal after regular use resembles opioid withdrawal: muscle aches, sweating, runny nose, insomnia, irritability, nausea and strong cravings, typically starting within a day and lasting several days to a week, sometimes longer given the long half-life. Severity varies, and the published evidence does not support promising it cannot become medically serious — this is an unregulated opioid-receptor product associated with seizures and serious poison-centre outcomes. It is also the reason people keep taking it. Anyone who has been using daily, and particularly anyone using concentrated extracts, should get medical support rather than white-knuckling it, and should say plainly that it is an opioid-receptor agonist so the clinician can treat it appropriately.

US: federally unscheduled but FDA-hostile; banned in several states. Sold openly elsewhere.

Papers about this compound, not proof of the claims above. A title says what was studied, which is sometimes a negative result or a different question entirely.

• The effects of kratom (Mitragyna speciosa) on metabolic syndrome-related parameters: a systematic review and meta-analysis
  Front Pharmacol, 2025
• Reported associations between kratom and seizures: a systematic review
  Front Pharmacol, 2025
• Kratom (Mitragyna speciosa) Use and Mental Health: A Systematic Review and Multilevel Meta-Analysis
  Eur Addict Res, 2024

• Kratom (Mitragyna speciosa): Friend or Foe?Prim Care Companion CNS Disord · 2020
• Kratom2012
• Kratom Dependence and Treatment Options: A Comprehensive Review of the LiteratureCurr Drug Targets · 2020
• An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerationsExpert Rev Clin Pharmacol · 2024
• Kratom (Mitragyna speciosa): worldwide issuesCurr Opin Psychiatry · 2020
• Controversies in Assessment, Diagnosis, and Treatment of Kratom Use DisorderCurr Psychiatry Rep · 2024
• Treatment of Kratom Withdrawal and Dependence With Buprenorphine/Naloxone: A Case Series and Systematic Literature ReviewJ Addict Med · 2021
• Kratom: a primer for pain physiciansCurr Opin Anaesthesiol · 2024
• Kratom: Substance of Abuse or Therapeutic Plant?Psychiatr Clin North Am · 2022
• Kratom: A Narrative Review of the Possible Clinical Uses and Dangers of This Opioid-Like PlantCureus · 2024
• The pharmacology and toxicology of kratom: from traditional herb to drug of abuseInt J Legal Med · 2016
• Kratom: A Bibliometric Analysis of Scientific PublicationsJ Psychoactive Drugs · 2024