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

The conversation opens with Huberman framing kratom as both a mass-consumer phenomenon and a live research problem. He introduces his guest, Dr. Chris McCurdy, a professor of medicinal chemistry at the University of Florida who directs research on natural products and their pharmacologic effects, and describes kratom as a plant-derived compound that is readily sold in the US and around the world and now used daily by tens of millions of people, with those numbers increasing fast. McCurdy's research is said to focus on how kratom interacts with the nervous system and affects physiology and behavior, including its potential for addiction.

Huberman lays out the episode's agenda in unusual detail. The discussion will cover kratom's complex effects and its relationship to the opioid system, how its active compounds work in the brain, and why it shares certain similarities to opioid drugs. Critically, he flags that products available in the US and elsewhere are largely derivatives and isolates of the leaf, producing effects very different from traditional leaf products, and that this has confused and in many cases harmed consumers. The promised scope includes dose- and source-dependent effects: kratom as a stimulant, as a focus enhancer, as a painkiller, and as a source of euphoria, but also its strong potential for addiction. He adds that kratom has been shown effective for helping people transition off traditional opioid drugs, while announcing that the episode will also explain potential harms, particularly in young people whose brains are still developing and in people with no prior opioid addiction.

The framing deliberately widens beyond kratom. Huberman points toward other plant alkaloids with medicinal properties, including those in cocoa and a hundred percent chocolate, and toward the history of soft drinks such as Coca-Cola, Pepsi, 7Up and Dr Pepper, described as originally developed as pharmacologic tools before becoming the ultra-popular beverages familiar today. He stresses that whatever listeners already know, kratom products are now essentially everywhere — supermarkets, convenience stores and online — sold under the pretense of specific effects related to energy, pain management or mood, and that the goal is a thorough understanding of how the plant compound actually works, its potential effects and its serious risks.

Turning to the guest, Huberman characterizes McCurdy's compounds as several very controversial ones that are all affecting health and society in a major way, especially in the United States. He notes that while some listeners know kratom well and others not at all, nearly everyone has seen a kratom product, often tucked into fine print, and asks for a plain description of what kratom is, where it is found in nature and in the US, and what effects people seek from it.

McCurdy starts from first principles rather than from the supplement aisle. Kratom is a tree native to Southeast Asia — specifically, he says, to the border where peninsular Malaysia and Thailand connect, which he describes as ground zero for where the species came from. He describes that region as very rural, populated by farmers and outdoor laborers, which matters because the traditional use he goes on to describe is specifically a working, agrarian one.

In Thailand, those laborers chew the leaves directly, or prepare a tea that is more technically a decoction because the leaves are boiled for hours; fresh leaves are harvested and the liquid is drunk much as one would drink a morning coffee, to provide energy, to sustain them through the day, and to tolerate heat, humidity and a harsh tropical environment. The stamina to get through the workday is the core of traditional use, but McCurdy adds that the leaves have also been used to treat pain, to treat erectile dysfunction — described as a kind of natural Viagra — and primarily for mood elevation.

The social setting completes the picture. Because the local population is Muslim and consumes essentially no alcohol, kratom functions as a socially lubricating product; on Friday and Saturday evenings men gather and increase their tea consumption to reach a more sedative-like effect. This gives rise to what McCurdy calls a paradoxical description of the plant: a stimulant effect at lower doses or smaller amounts, and a more euphoric or sedative, opioid-like effect at higher doses. Traditionally, then, the same material is used like coffee to get moving in the morning and, in larger weekend amounts, as a social beverage.

What drew McCurdy to the plant, as an opioid researcher and pain researcher, was a set of reports that it was used when people ran out of heroin or raw opium so that they would not go into withdrawals; users would increase consumption to stave off withdrawals. He explicitly ties that observation to the potential to help with the opioid crisis the US is in, and says it is what drove his group to begin studying kratom.

McCurdy's central distinction is that the Western product is not the traditional leaf from day one. Traditional use involves freshly picked leaves chewed directly off the tree or brewed right away, whereas material reaching the US and the wider Western world is dried leaf that has been exposed to air, sun and other environmental factors and then shipped across the world, with Indonesia named as the primary country where most of it is grown. He cites a figure of about 250,000 kratom farmers in Indonesia, as of a year before the conversation, producing and exporting raw material around the globe but primarily to the United States. That leaf is then ground into capsules or sold as a powder that people measure in tablespoons or grams in warm water.

Even powdered leaf, McCurdy argues, is the closest a Western user can get to traditional use, and it is already pharmacokinetically different. Water is described as the worst, least efficient extractor of chemicals from plant material, and when leaf is taken internally the body has to work incredibly hard to pull the active ingredients out — an active process for humans and for the animals most of the research has come from. The decisive change comes with tonics, concentrates and extracts: there, the compounds have already been pulled out of the leaf by a solvent or liquid vehicle, whether ethanol, oil or something else. McCurdy notes that the pineapple-juice vehicle of the product Huberman mentioned is less efficient than oil or a solvent, but the principle holds — the compounds are already out of the leaf and are absorbed much faster into the body, which totally changes the dynamics of what the body is exposed to.

McCurdy anchors the problem in a dose argument, going back to Paracelsus hundreds of years ago and the idea that the poison is in the dose, and he describes a spectrum that runs from leaf material toward concentrates, extracts and finally isolates. Isolates are, in his framing, a whole other discussion, because they are no longer even kratom products, and his claim is that the majority of relatively non-problematic use has been with leaf material closer to traditional use.

the poison is in the dose

To make the spectrum concrete, McCurdy reaches for an alcohol analogy. Seltzers or light beers are, in his comparison, closer to traditional kratom use, while a product like Everclear at 190 proof, or 95 percent alcohol, stands in for the isolates. The alcohol industry classifies its products along that whole span — beer, wine, cider, craft beer, spirits, fortified beverages — but the kratom space has no such delineation, and every kratom product is dumped into a single bucket. The practical consequence is that a product close to traditional use and something highly concentrated sit side by side: a shot might be 15 milliliters and the bottle may say nine servings, but nobody reads that part and just downs the entire bottle.

Huberman presses the comparison directly, using a popular small blue bottle whose primary ingredients are kava and kratom, and declaring he has no financial relationship to the company and turned down a chance to be an early investor. He asks how concentrated such a bottle is relative to a typical adult user in Malaysia drinking a mug of the decoction, and whether the two are even the same compound — likening the gap to smoked cannabis versus a highly concentrated THC tincture, where the same chemical structure at some point changes the pharmacokinetics, engages different brain circuits and bodily organs, and becomes a different experience altogether.

McCurdy clarifies that the little blue bottle is actually more similar to a traditional beverage exposure in what is dosed, roughly one bottle. Huberman then offers a telling anecdote: an acquaintance's assistant said she started by drinking one bottle, was now drinking six a day, and could not whittle it back — dropping to three produced headaches, anxiety and generally feeling unwell, a pattern he reads as addictive or habit-forming and compares to nicotine pouches, where someone starts at three milligrams, moves to six, and ends up at a tin or canister a day. One bottle of the kava-kratom product, he concludes, is comparable to the plant use.

McCurdy's group, he says, has tested almost every product in the marketplace and analyzed alkaloid content against what the label calls a serving. Per serving, the products are pretty much all equivalent; the variable is how many servings a single bottle contains — one, two, nine or fifteen. If someone is accustomed to consuming the two-serving blue bottle all at once and then picks up a smaller bottle that holds ten times more servings and drinks the whole thing, they get a much greater exposure immediately, in a vehicle the body absorbs more readily. Not attending to the actual serving is, in his view, exactly where problems begin, and he calls the resulting product landscape a very slippery slope.

He grounds the risk in a retail detail: at a Murphy USA gas station, Walmart's gas station, kratom energy shots sat right next to five-hour Energy shots, so a hurried buyer could grab the wrong one. The worry is kids taking a whole multi-serving bottle, feeling nothing right away, being told they will get high, taking another, and then having all of it absorbed and hit them harder almost at once. His light-beer analogy makes the point in the source's own terms: a 12-ounce beer at 3.5 percent alcohol drunk quickly gives little alcohol exposure, whereas three shots of tequila in the same timeframe deliver significantly more. When a serving is dialed in to equal a traditional full glass of tea, the product can still be very, very concentrated.

McCurdy extends the point beyond concentration to chemical identity: semi-synthetics are chemically modified into other things that are, in some cases, still called kratom products, or else kratom-derived products, and are no longer traceable back to the plant material. Huberman draws out two practical consequences from the discussion so far — that anyone considering kratom products needs to look carefully at serving size, with packaging print so fine he jokes it needs a compound microscope, and that buyers should distinguish kratom-derived or kratom-extracted products from actual plant material. He is explicit that the conversation is not recommending use, but that many people already use and will use these products, so it matters to understand that the category is not one thing.

Huberman steps back to the dose-dependent pharmacology, restating that at lower dosages kratom is a bit of a stimulant that may even have aphrodisiac qualities — which he speculates, as a non-medicinal-chemist, could imply dopaminergic, cholinergic or vasodilation activity — while at higher doses it becomes more sedative. He then asks whether US users of derivatives and processed products such as the blue bottle or energy shots are seeking that stimulant, aphrodisiac effect or the sedative, numbing-out effect, since these are two very different things.

I don't think we have good, strong definitive data.

McCurdy is candid about the evidence base. He does not claim good, strong definitive data, and describes survey work done with his colleague Dr. Kirsten Smith at Johns Hopkins and others on their team, in which users volunteer themselves into studies rather than being random people stopped on the street — a sampling limitation he names explicitly. In the largest study they had done to date, he says, most users were using kratom in a very responsible, directed way, not to get a high, euphoria or a sedative feel; Huberman asks him to repeat the point because he thinks it needs to be heard.

On prevalence, McCurdy openly contrasts estimates. The most recent literature report he cites was around 2 million to two and a half million users, but product sales and manufacturer conversations put the estimate well over 20 million users in the United States, and availability of product suggests the higher number is closer. Huberman confirms this is a daily figure, not an annual one. The firmer anchor is 2019 import data: 1,950 metric tons per month coming into the US and then manufactured.

The strongest self-report instrument he describes is an ecological momentary assessment, or EMA study, in which smartphone apps monitor people at every single dose, capturing what they are feeling, why they are taking it and when. The majority of participants in those studies were using it in an appropriate, not-to-get-high way. When Huberman asks what they use it for, the answers are mostly energy, mood elevation and pain treatment, often as an alternative to opioids.

McCurdy adds a revealing surprise: his team expected far more people using kratom to get off opioids, and while people do that and he receives emails almost weekly from individuals saying it got them off the couch and helped them get their families and lives back by restoring energy they lacked on opioids, he is not sure that is the largest group. The bigger reported cluster is mood elevation and a general energy boost — used as a pre-workout stimulant for endurance, much like the traditional use in hot outdoor labor, and as a post-workout pain treatment for lactic-acid soreness. He insists the largest reported effect is a general good feeling rather than a high, and says they asked explicitly whether people were using it to get high.

general good feeling, not a high feeling