Health Effects & Risks of Kratom, Opioids & Other Natural Occurring Medicines | Dr. Chris McCurdy

KEYPOINTS

• 01

  Kratom is a Southeast Asian tree whose effects depend on dose

  Kratom (Mitragyna speciosa) is native to the border region of peninsular Malaysia and Thailand. There, outdoor laborers chew fresh leaves or drink a decoction boiled for hours, using it much as people use coffee to get through heat and hard work. Traditionally it is also used for pain, mood and as a 'nature's Viagra.' McCurdy describes the paradox: small amounts act as a stimulant, while larger amounts produce a more euphoric, sedative, opioid-like effect, which men in the region used socially on weekend evenings in a mostly alcohol-free Muslim culture.

• 02

  US kratom products are very different from the traditional leaf

  Western products start as dried leaf, mostly from Indonesia (roughly 250,000 farmers), exposed to sun and air and shipped around the world. Ground leaf in capsules or as powder stirred into water is the closest thing to traditional use, and absorption is slow because the body has to extract the alkaloids itself. Extracts, concentrates and isolates made with ethanol, oil or juice deliver the compounds already pulled out, so they are absorbed much faster. McCurdy compares this range to light beer versus fortified spirits.

• 03

  Read servings per bottle, not just the serving

  McCurdy's lab has tested nearly every product on the market, and a single labeled serving is broadly similar to a traditional glass of tea. The danger is in the number of servings per container: a bottle may hold 2, 9 or 15. Someone used to downing a two-serving bottle can swallow a 15-serving shot in one go, in a form that is absorbed quickly. Some shots sit next to 5-hour Energy at gas stations.

• 04

  7-hydroxymitragynine products behave like pure opioids

  The leaf contains roughly 20–40 alkaloids. The main one, mitragynine, is converted in the body into 7-hydroxymitragynine, which acts only on opioid receptors, and the plant itself has never been shown to make it. Manufacturers now synthesize it and sell semi-synthetic 'kratom-derived' products or isolates, under a dietary-ingredient loophole that treats metabolites as dietary ingredients. McCurdy's rat study (on bioRxiv, headed to the Journal of Pharmacology and Experimental Therapeutics) found these products cause respiratory depression equivalent to opioids.

• 05

  Whole-leaf kratom acts on three pain systems at once

  Mitragynine has only weak opioid-receptor affinity. Other alkaloids act strongly on serotonin, which affects mood and pain, and on adrenergic receptors, which drive stimulant activity. McCurdy calls the leaf a 'pharmaceutical shotgun' or 'symphony orchestra' that combines opioid, serotonergic and adrenergic pain relief in a way no single drug does. This may explain why some users call it the best pain relief they have had. He stresses that most of the roughly 1,000 papers on kratom, about 10% from his lab, study mitragynine alone, and 'mitragynine does not equal kratom.'

• 06

  Physical dependence is real and tolerance builds for pain relief

  A single use will not create dependence, but regular use can. Missing a morning dose brings headaches and misery similar to caffeine withdrawal, and with stronger products some users report restless legs, which looks more like opioid withdrawal. Pain-relieving effects seem to lose strength over time, pushing doses up. There are no chronic studies in humans or animals to say how quickly this happens.

• 07

  Use is widespread and mostly not for getting high

  Published estimates are 2–2.5 million US users, but sales and imports (1,950 metric tons a month in 2019) suggest over 20 million daily users. In McCurdy's ecological momentary assessment study, people logged each dose by smartphone. Most used it for energy, mood elevation and pain, including as a pre-workout or post-workout aid, and often within 30 minutes of waking. A smaller group used it to get high, probably with concentrates, and others used it to get off opioids.

• 08

  Quitting kratom has no evidence-based protocol yet

  Before COVID, addiction physicians in Gainesville saw patients improving after switching from opioids to kratom. After COVID, they saw people seeking treatment to get off kratom. Clinicians often use buprenorphine (Suboxone) or methadone, which seems to work, but McCurdy worries this addresses only the opioid component, ignores the serotonin and adrenergic effects, and may leave people dependent on a pure opioid that is harder to quit. Counseling and social support matter alongside medication.

• 09

  Vein colors are mostly marketing

  White, red, green, brown and yellow 'vein' products reflect how leaves were dried, plus sun or cold damage to trees normally grown in the shade. Alkaloid profiles across the colors are very similar in the lab's analyses, though other chemical differences cannot be ruled out. Huberman compares this to the indica-versus-sativa debate in cannabis.