Huberman LabDr. Chris McCurdy on Huberman Lab: Why Kratom Misleads
How kratom alkaloids differ across leaf, extract, and isolate forms; McCurdy maps opioid and serotonin effects, addiction risk, and harm reduction tools.
CHAPTERS
- 0:00 – 7:10
Introduction and Framing: Why Kratom Matters Now
Huberman introduces Dr. Chris McCurdy, his background in medicinal chemistry, and sets the agenda: understanding kratom’s mechanisms, benefits, risks, and how Western products differ from traditional use. They preview key topics such as addiction risk, kratom’s role in opioid transition, and how plant alkaloids have shaped modern medicines and even soft drinks.
- •McCurdy is a medicinal chemist at the University of Florida focused on natural products, especially kratom.
- •Kratom use is rapidly increasing in the U.S., with products widely available in gas stations, convenience stores, and online.
- •Episode aims: mechanistic understanding, dose–response effects, differences between traditional leaf vs. Western derivatives, and addiction/harm reduction potential.
- •Contextualizes kratom within a broader history of plant-derived medicines like cocoa, coca, and early formulations of Coca-Cola and 7UP.
- 7:10 – 27:20
Traditional Kratom: The Leaf, The Tree, And Rural Use
McCurdy explains what kratom is biologically and culturally: a Southeast Asian tree whose leaves are chewed or boiled into a tea by rural laborers for stamina, mood elevation, and social relaxation. He describes the classic dose-dependent profile—stimulant at low doses, sedative/euphoric at higher doses—and how anecdotal reports of using kratom to stave off opioid withdrawal first drew his research interest.
- •Kratom tree: Mitragyna speciosa, native to border region of peninsular Malaysia and Thailand.
- •Traditional preparations: fresh leaf chewed or long-boiled decoction; used like morning coffee for energy and endurance in hot, humid environments.
- •At low doses: stimulant, mood-elevating, increased stamina; at higher doses: sedative, euphoric, “opioid-like.”
- •Used socially on evenings/weekends as alcohol substitute in predominantly Muslim communities.
- •Reports from Southeast Asia: users increase kratom intake when they run out of heroin/opium to prevent withdrawal, sparking McCurdy’s opioid-related interest.
- 27:20 – 44:30
From Tree to Shot: Western Kratom Products and Dose Pitfalls
The discussion shifts to U.S. kratom products: dried leaf powders, capsules, and especially concentrated ‘energy shots’ and tonics. McCurdy explains how pre-extraction into liquids changes pharmacokinetics, allowing much faster and higher absorption compared to eating leaf or tea, and why unlabeled or misunderstood serving sizes create serious overdose and dependence risks, especially for youth.
- •U.S. supply largely from Indonesian dried leaf, shipped globally; ~250,000 kratom farmers estimated.
- •Leaf powder in capsules or spooned into warm water is closest to traditional use, but still drier, older material.
- •Water is an inefficient extractor; body must work to pull alkaloids from leaf; extracts pre-do that work, accelerating absorption.
- •Energy shots and tonics may contain multiple ‘servings’ in one tiny bottle; consumers often drink the whole container.
- •Children/teens could confuse kratom shots with 5-Hour Energy, take full bottles, and then redose before effects hit, compounding risk.
- •McCurdy uses alcohol analogy: leaf ~ light beer, mid-strength extracts ~ wine/spirits, isolates ~ Everclear.
- •Lack of standardized categories means everything is marketed simply as ‘kratom,’ masking huge potency differences.
- 44:30 – 52:00
Who Uses Kratom in the U.S. and Why?
Drawing on survey and ecological momentary assessment data, McCurdy outlines major user groups and motivations. Most self-selected respondents report using kratom responsibly for energy, mood, and pain rather than euphoria; a subset use it as pre/post-workout support; and another subset uses it socially for intoxication. He also notes that estimated daily users likely exceed 20 million in the U.S.
- •Survey work with Johns Hopkins shows many users track dosing via smartphone apps, reporting reasons and effects.
- •Primary reported motives: energy, mood elevation, pain relief, and as an alternative to opioids.
- •Some use kratom as pre-workout for endurance and post-workout for pain relief.
- •A smaller subgroup uses it explicitly to get ‘high’ or for weekend euphoria/relaxation.
- •Contrary to assumptions, there may be more mood/energy users than pure opioid-transition users, though hard data are limited.
- •Industry import data (2019): ~1,950 metric tons/month; estimates suggest >20 million daily U.S. users, not 2–3 million.
- 52:00 – 1:07:00
Dependence, Tolerance, and Youth Risk
They dig into physical dependence: how daily users can experience caffeine-like withdrawal symptoms from leaf products, and how higher-potency preparations can produce more opioid-like withdrawal profiles. McCurdy strongly advises age limits due to unknown impacts on developing brains and warns about kids inadvertently buying kratom shots in gas stations.
- •McCurdy states kratom ‘absolutely’ can cause physical dependence over time, though severity and timeline are unknown.
- •Leaf-based daily users report headaches and malaise without their dose, similar to caffeine withdrawal.
- •More potent products (strong extracts/isolates) are linked anecdotally to restless legs and more classic opioid-like withdrawal.
- •No chronic human or animal studies yet quantify dependence mechanisms or timecourses.
- •He supports at least 18–21 age limits, ideally 24–25, consistent with brain maturation and other substance policies.
- •He expresses personal concern as a parent about youth grabbing kratom shots near energy drinks and misusing them.
- 1:07:00 – 1:19:00
Plant Alkaloids 101: How Nitrogen-Containing Molecules Hit Our Brains
McCurdy explains what alkaloids are chemically and why nitrogen atoms make them so biologically active. Using dopamine, serotonin, nicotine, morphine, and cocaine as examples, he describes how charged nitrogens act like ‘tractor beams’ to bind protein receptors, and how natural products historically revealed entire neurotransmitter systems before their endogenous ligands were known.
- •Alkaloids are organic molecules containing nitrogen; many also include oxygen; they form the basis of many neurotransmitters and drugs.
- •Nitrogen can accept a proton and carry a positive charge, allowing strong electrostatic interactions with negatively charged sites on proteins.
- •This charge attraction is like magnet poles or a ‘tractor beam,’ helping the molecule lock into receptors and transporters.
- •Classic examples: dopamine, serotonin, morphine, cocaine, caffeine, nicotine.
- •Nicotine led to discovery and naming of nicotinic acetylcholine receptors long before acetylcholine’s role was fully mapped.
- •Natural products and animal self-medication behavior historically guided discovery of pharmacologically active plants and compounds.
- 1:19:00 – 1:49:30
Nature, Medicine, and the Problem of Concentration
The conversation broadens to natural vs. synthetic medicines, emphasizing that most modern drugs descend from plant or animal products. Huberman and McCurdy discuss aspirin from willow, GLP‑1 analogues from Gila monster saliva, metformin/berberine, and how industrial extraction and marketing (sugar, processed foods, cannabis edibles, etc.) transform subtle natural tools into potent, sometimes harmful, agents.
- •About 75% of FDA-approved drugs are either natural products or derivatives thereof.
- •Examples: aspirin from willow bark (salicin/salicylic acid), GLP‑1 drugs inspired by Gila monster saliva peptides, metformin from plant guanidines/berberine, local anesthetics from cocaine.
- •Modern reductionist drug development favors single-target, high-selectivity molecules, but human physiology often depends on multi-system modulation.
- •Food analog: natural sugar vs. refined, hyper-palatable, ultra-processed foods that exploit innate drives for sweetness and calories.
- •Cannabis: users titrate inhaled flower relatively well, but edibles with delayed onset cause many ER visits through overconsumption.
- •Huberman floats the idea of a ‘slow medicine’ movement, analogous to slow food: maintaining contact with source materials rather than jumping straight to hyper-concentrates.
- 1:49:30 – 2:02:00
Kratom’s Multi-System Mechanism: Opioid, Serotonin, and Adrenergic Targets
McCurdy details kratom’s known pharmacology. Rather than being a ‘pure opioid,’ whole kratom contains dozens of alkaloids, some mildly opioid, others strongly serotonergic or adrenergic. He frames whole-plant kratom as a tri-pronged analgesic—simultaneously engaging opioid, serotonin, and adrenergic systems—in a way no approved single drug or cocktail currently does, which may explain why some users get strong pain relief without heavy intoxication.
- •Kratom leaf has at least 20–40 alkaloids; mitragynine is the major one, but many others are pharmacologically active.
- •Mitragynine shows weak μ-opioid receptor affinity and modest analgesic effect; it also modulates serotonergic and adrenergic systems.
- •Other kratom alkaloids more strongly target serotonin receptors (mood, satiety, chronic pain modulation) and adrenergic receptors (stimulation, fight-or-flight, some pain aspects).
- •This creates a ‘pharmaceutical shotgun’ or orchestra: modest hits on several pain-related systems instead of a sledgehammer on one.
- •McCurdy notes that pain medicine has never clinically targeted opioid, serotonin, and adrenergic systems together in a single agent the way kratom does.
- •He highlights user mantra ‘less is more’: many report better benefit and fewer psychoactive effects at lower doses.
- 2:02:00 – 2:10:20
The Dark Edge: 7‑Hydroxymitragynine and Respiratory Depression
Here McCurdy draws a sharp line between whole-plant kratom and kratom-derived isolates, focusing on 7‑hydroxymitragynine, a potent mitragynine metabolite now synthesized and sold directly. His lab’s recent animal work shows this compound can cause opioid-level respiratory depression reversible by naloxone, making these products functionally akin to strong opioids despite ‘natural’ branding.
- •7‑hydroxymitragynine is a metabolite of mitragynine formed in humans; some disputable claims that plants produce it directly.
- •Semi-synthetic production now allows manufacturers to sell 7‑hydroxymitragynine as ‘kratom-derived’ or isolate products.
- •In rat studies, 7‑hydroxymitragynine produces respiratory depression comparable to classical opioids; naloxone reverses it, confirming opioid receptor involvement.
- •Whole-plant kratom likely has a lower respiratory depression risk, but rigorous human data are lacking.
- •Regulatory loophole: metabolites of dietary ingredients can themselves be sold as dietary ingredients, facilitating these isolate products.
- •McCurdy and colleagues are actively warning clinicians and regulators, arguing these isolates should not be conflated with traditional kratom or left unregulated.
- 2:10:20 – 2:35:20
Kratom, Alcohol, and Polydrug Concerns
They touch on kratom–alcohol interactions and harm reduction potential. While formal interaction studies are scarce, anecdotal reports suggest kratom can reduce alcohol desire or intake. NIAAA is now funding studies on kratom for alcohol use disorder, but McCurdy cautions that mixing kratom (especially opioid-like isolates) with heavy drinking could plausibly magnify respiratory risks, as seen with opioid–alcohol combinations.
- •Some users anecdotally report kratom reduces their interest in alcohol or their tendency to drink heavily.
- •NIAAA has funded research into kratom as a potential harm reduction tool for alcohol use disorder.
- •Separately, combining opioids with alcohol is well known to raise fatal overdose risk via synergistic respiratory depression.
- •No robust data yet exist on kratom–alcohol interactions, especially for different product types.
- •Prudence suggests avoiding kratom with significant alcohol or sedatives, particularly with extracts or isolates.
- 2:35:20 – 2:53:20
Getting Off Kratom: Clinical Realities and Unknowns
In response to listener concerns about dependence, McCurdy describes addiction physicians using buprenorphine or methadone to transition kratom-dependent patients, but questions whether treating a multi-system agent with pure opioids is optimal. He underscores that there is no standardized protocol for kratom cessation and stresses the importance of medical supervision and psychosocial support rather than DIY tapering with other drugs.
- •Addiction physicians report an increasing caseload of people now seeking treatment to quit kratom, not just opioids.
- •Standard practice: treat kratom dependence similarly to opioid use disorder with buprenorphine/Suboxone or methadone.
- •Problem: kratom affects opioid, serotonin, and adrenergic systems; opioid-only treatments may not fully address the non-opioid components.
- •There are no evidence-based, kratom-specific detox protocols or long-term outcome data.
- •McCurdy worries that moving someone from kratom to a pure opioid maintenance drug could complicate eventual full abstinence.
- •He advises anyone seriously dependent to seek professional help, not self-medicate withdrawal with other psychoactives.
- 2:53:20 – 3:21:40
Coca Leaf, Cacao, and the Soft Drink Pharmacology Backstory
The episode widens to other plant medicines. McCurdy discusses coca leaf as a nutritious, non-abuse-prone traditional plant that was overshadowed by purified cocaine; cacao’s theobromine and mood effects; and the pharmacologic origins of Coca‑Cola, Pepsi, 7UP, and Dr Pepper. He explains how Coca‑Cola still legally imports coca leaf, removes cocaine for pharmaceutical use, and uses the de-cocainized extract as a flavoring agent.
- •Coca leaf is nutrient-rich (calcium, vitamins) and has long been used safely in Andean cultures; WHO is reviewing removing it from global bans.
- •Concentrating coca’s main alkaloid into cocaine made it highly addictive and overshadowed beneficial aspects of the leaf.
- •Cacao contains theobromine (a xanthine like caffeine), which mildly stimulates and aids respiration, plus compounds that engage dopaminergic reward systems.
- •Soft drink history: ‘soft’ because non-alcoholic but originally pharmacological tonics; 7UP contained lithium; Pepsi had pepsin; Dr Pepper was a physician’s formula.
- •Coca‑Cola historically contained cocaine; when cocaine was removed, flavor suffered, so they maintained coca leaf extract minus alkaloids.
- •Today, a New Jersey company imports Peruvian coca leaf, strips cocaine (sold pharmaceutically as a local anesthetic), and sends de-cocainized extract to Coca‑Cola as a GRAS flavoring.
- •Coke syrup was sold in pharmacies for nausea; coca leaf tea is still valued for GI soothing effects in traditional settings.
- 3:21:40 – 3:51:00
McCurdy’s Path: From Pharmacy Counter to Natural Products Chemist
In the final segment, McCurdy shares his personal journey: from underperforming high school student to pharmacist, then PhD student and medicinal chemist specializing in natural products. He recounts how work on nicotine-like compounds for Alzheimer’s and on Salvia divinorum’s kappa-opioid hallucinogen led him to kratom’s underexplored literature, particularly a shelved 1970s SmithKline & French program on mitragynine.
- •Grew up with a pharmacist father and a science-educator mother; initially an indifferent student, later drawn to pharmacy.
- •Early independent project quantifying caffeine in sodas; later hooked on medicinal chemistry through a mentor.
- •Practiced pharmacy while in graduate school, realized he could have more impact by training pharmacists and doing research than at the counter.
- •Postdoctoral work on opioids at University of Minnesota; then natural products research at University of Mississippi, including Salvia divinorum.
- •Salvinorin A, a potent kappa-opioid hallucinogen, expanded his interest in plant-based kappa and mu ligands.
- •While preparing a talk on natural analgesics, he found 1960s–70s SmithKline & French data on mitragynine: effective as codeine but abandoned once NSAIDs rose.
- •This ‘abandoned’ kratom literature convinced him the plant warranted modern, rigorous study, launching his now-prolific kratom research program.
- 3:51:00
Closing Reflections: Nuance, Regulation, and Public Education
The episode closes with Huberman summarizing key distinctions—leaf vs. isolate, youth vs. adult, harm reduction vs. recreational use—and praising McCurdy’s nuanced, evidence-driven approach. McCurdy reiterates that kratom has real therapeutic potential and real harms, insisting on better labeling, categorization, and clinical research, plus public education, rather than simplistic ‘good’ or ‘bad’ narratives.
- •Huberman highlights serving size vigilance, product type (leaf vs. extract vs. isolate), and user intent (energy vs. analgesia vs. intoxication vs. opioid taper) as core axes of risk.
- •McCurdy emphasizes his goal is neither to promote nor to ban kratom, but to clarify its pharmacology, benefits, and dangers so policy can be rational and users informed.
- •They agree youth should avoid kratom entirely, and adults should approach it, if at all, with the same seriousness they would potent pharmacological agents.
- •They underscore the broader lesson: ‘natural’ does not equal ‘safe’; concentration, context, and human manipulation determine much of the risk.
- •McCurdy thanks Huberman for the platform, noting the need for nuanced science communication in a polarized, anecdote-driven kratom debate.
