Dr. Chris McCurdy on Huberman Lab: Why Kratom Misleads

Traditional kratom use in Southeast Asia involves freshly picked leaves chewed or long-boiled into a weak decoction, with the body extracting alkaloids slowly and inefficiently. In the U.S., most products are dried leaf powders (closer to traditional use), concentrated extracts/shots, or semi-synthetic isolates (e.g., 7‑hydroxymitragynine) dissolved in efficient vehicles. Once the plant alkaloids are pre-extracted into liquids or concentrates, absorption is much faster and peak brain levels higher, fundamentally changing risk profile—much like jumping from beer to Everclear. Consumers and even clinicians often lump all of this together as “kratom,” which obscures major differences in potency and danger.

McCurdy’s lab has analyzed many commercial products and found that labeled “servings” can vary wildly; a tiny bottle might contain 2 servings or 15+ servings of kratom extract, with similar packaging. Many users simply down the whole bottle, unaware they are consuming a multi-serving, highly concentrated dose—analogous to doing several tequila shots instead of sipping one light beer. This is especially dangerous for naive users and youth, and when kratom shots are merchandised right next to energy shots, creating opportunities for accidental high dosing. Anyone using these products should explicitly check: (1) serving size in mL or capsules, (2) number of servings per container, and (3) whether the product is leaf-based or an extract/isolate.

The kratom tree (Mitragyna speciosa) contains 20–40 identified alkaloids, not just mitragynine. Mitragynine has weak μ-opioid receptor activity plus actions at serotonergic and adrenergic receptors; other leaf alkaloids hit serotonin and adrenaline systems more strongly. As a result, whole-leaf kratom acts like a ‘pharmaceutical shotgun’ or symphony, providing analgesia via opioid and serotonin pathways and stimulation/endurance via adrenergic pathways. At lower doses, users often experience stimulation and mood elevation; at higher doses, more opioid-like sedation and euphoria can appear. Critically, many lab studies use only pure mitragynine and do not reflect the full plant’s multi-receptor reality.

Regular daily users—especially of leaf or powder—commonly report headache, lethargy, and feeling “off” without their morning kratom, analogous to caffeine dependence. At higher doses and with more potent products (strong extracts or isolates), reports include restless legs and more classic opioid-type withdrawal symptoms. McCurdy emphasizes that while a single use will not cause dependence, chronic use very likely will for many people, and the time course and severity are poorly quantified because there are no robust long-term human or animal dependence studies. Clinically, addiction physicians are now seeing patients seeking treatment to get off kratom, often using buprenorphine or methadone, which may resolve opioid-like aspects but not necessarily the serotonergic/adrenergic components.

In the plant, mitragynine is the major alkaloid; the body metabolizes some of it into 7‑hydroxymitragynine, which is a much more potent μ-opioid agonist. Chemists now manufacture 7‑hydroxymitragynine directly and sell it as “kratom-derived” or “isolates,” sometimes blended into products available wherever leaf kratom is sold. McCurdy’s group showed in rats that 7‑hydroxymitragynine produces respiratory depression comparable to conventional opioids and that this effect is reversible with naloxone, confirming opioid receptor mediation. These products exploit a regulatory loophole (metabolites of a dietary ingredient) and are marketed as harm-reduction or “safer,” despite behaving pharmacologically like strong opioids. He views them as qualitatively different and substantially more dangerous than leaf products.