How do traditional Kratom use and modern US products differ?

Traditional use involves fresh leaves, either chewed or brewed as a decoction. In the US, products are typically made from dried, ground leaf material (capsules, powders) or highly concentrated extracts/isolates. Concentrates are absorbed much faster and can lead to significantly higher exposure compared to traditional leaf consumption.

Is Kratom addictive or habit-forming?

Yes, kratom absolutely causes physical dependence with regular use. The withdrawal symptoms are often compared to caffeine withdrawal for leaf products but can be more severe, including restless leg syndrome, similar to opioid withdrawal, with higher doses or concentrated products.

What are the primary reasons people use Kratom in the US?

Most users in the US report using kratom for energy, mood elevation, and pain treatment, often as an alternative to opioids. A smaller population uses it to achieve euphoric or sedative effects, similar to recreational opioid use.

Should minors (under 18 or 21) use Kratom?

Dr. McCurdy strongly recommends against kratom use for anyone under 24-25, as the brain is still developing. He emphasizes unknown impacts on brain development and the increased risk-taking behavior in young individuals.

What is the risk of respiratory depression with Kratom?

While traditionally believed to cause less respiratory depression than illicit opioids, recent research indicates that 7-hydroxy mitragynine, a chemically produced metabolite sometimes labeled as 'kratom derived,' can cause respiratory depression equivalent to opioids. This is a significant public safety concern.

What are alkaloids, and what role do they play in plants like Kratom?

Alkaloids are organic molecules containing nitrogen, which allows them to interact with proteins in the body. Examples include caffeine, cocaine, morphine, and nicotine. In kratom, multiple alkaloids interact with opioid, serotonin, and adrenergic systems, contributing to its diverse effects.

Can Kratom be used to treat opioid addiction?

Anecdotal evidence suggests many individuals successfully use kratom to transition off traditional opioid drugs and manage withdrawal symptoms. However, current medical treatments for kratom dependence often involve opioid use disorder treatments like buprenorphine, which may not address all aspects of kratom's complex pharmacology.

What is the historical connection between Coca-Cola and the coca leaf?

The original Coca-Cola formula developed by pharmacist John Pemberton contained coca leaf extract. While cocaine was later removed, Coca-Cola remains a major importer of coca leaves. The leaves are processed to remove cocaine (used in pharmaceuticals), and the 'decocainized' extract is used as a flavoring agent in classic Coca-Cola and Coke Zero.

What is the difference between 'white vein,' 'red vein,' and 'brown vein' Kratom products?

These 'vein' labels primarily refer to marketing strategies and how the leaves have been cured or dried after harvesting. While the alkaloid content is generally similar across these color variations, other chemical compositions might differ, leading users to associate specific effects with certain colors.

What potential is there for natural products in medicine that are not currently being utilized?

The discussion highlights a 'slow medicine' movement, emphasizing the long history of plants providing medicinal compounds. Examples like Metformin from tree bark and GLP-1 drugs from Gila monster saliva illustrate how natural sources continue to inspire and contribute to modern pharmacology, often with complex, multi-pathway effects.

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

Andrew Huberman

Science & Technology6 min read163 min video

Jul 21, 2025|99,943 views|2,504|1,095

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TL;DR

Kratom's complex effects range from stimulant to opioid-like. Processed forms pose addiction and safety risks, especially for developing brains.

Key Insights

Kratom originates from Southeast Asia, traditionally used for energy and pain relief, with paradoxical stimulant effects at low doses and sedative effects at higher doses.

Products sold in the US differ significantly from traditional kratom leaf, with many being extracts, concentrates, or isolates, leading to altered pharmacokinetics and increased risks.

Serving size and product type (leaf vs. derivative/isolate) are critical factors; concentrated products can deliver much higher doses, increasing the risk of adverse effects and dependence.

Most kratom users surveyed use it responsibly for energy, mood elevation, and pain management, often as an alternative to opioids, rather than for a euphoric high.

Kratom contains numerous alkaloids, only some of which are well-studied, and its effects are more complex than a simple opioid interaction, involving serotonin and adrenergic systems.

The 7-hydroxy mitragynine metabolite, now synthesized and sold, acts as a potent opioid and has shown respiratory depression in animal studies, similar to traditional opioids.

ORIGINS AND TRADITIONAL USE OF KRATOM

Kratom, botanically known as Mitragyna speciosa, is a tree native to Southeast Asia. Traditionally, laborers in regions like Malaysia and Thailand chewed fresh leaves or brewed them into a decoction to boost energy, stamina, and alleviate pain. It was also used socially for mood elevation and, in some cases, to manage withdrawal symptoms from opium or heroin. Users experienced a dual effect: stimulant-like at lower doses and more sedative or euphoric, similar to opioids, at higher doses.

MODERN KRATOM PRODUCTS AND THEIR DIFFERENCES

Current kratom products available in the US and Western markets vary significantly from fresh leaves. They often consist of dried leaf material in powder or capsule form, or more concentrated extracts, tinctures, and isolates. These processed forms have already had active compounds extracted, making them more readily absorbed by the body. This concentration and altered delivery method fundamentally change the substance's interaction with the body, increasing potential risks compared to traditional leaf consumption.

DOSE AND PRODUCT FORM MATTER: THE CONCENTRATION PROBLEM

The critical distinction lies in the preparation and concentration of kratom products. While traditional leaf use might be comparable to a single serving of a less concentrated beverage, modern extracts and isolates can deliver significantly higher alkaloid concentrations. This is likened to the difference between beer and high-proof spirits. Misinterpreting serving sizes, especially on pre-packaged 'energy shots' or concentrated bottles, can lead to accidental overconsumption and a much greater exposure to kratom's active compounds, creating a 'slippery slope' toward problematic use.

DIVERSE USER MOTIVATIONS AND RESPONSIBLE USE

Research indicates that while some individuals use kratom for euphoric or sedative effects, the majority of users report using it responsibly for legitimate purposes. Common motivations include seeking increased energy, mood enhancement, pain relief, and as an alternative to traditional opioids. A significant number of users report that kratom has helped them transition away from more harmful substances, regaining energy and improving their quality of life, suggesting a potential role in harm reduction for certain populations.

THE COMPLEX ALKALOIDAL PROFILE AND DUAL ACTION

Kratom is not a single compound but contains 20-40 alkaloids, with mitragynine and 7-hydroxymitragynine being the most studied. Mitragynine has weak affinity for opioid receptors and also interacts with serotonin and adrenergic systems. The plant's effects are thought to arise from this complex interplay, potentially offering pain relief by targeting opioid, serotonin, and noradrenergic pathways simultaneously. This tripartite action contrasts with single-target pharmaceuticals and may contribute to its unique therapeutic profile and reported 'less is more' user experiences.

RISKS ASSOCIATED WITH DERIVATIVES AND ISOLATES

While leaf kratom has its own risks, synthesized derivatives and isolates, particularly 7-hydroxy mitragynine, pose greater concerns. These are essentially potent opioids that can cause respiratory depression, as shown in animal studies, on par with traditional opioids. The lack of clear labeling and differentiation between leaf products and potent synthetic derivatives contributes to confusion and potential harm. Concerns are heightened for young people whose brains are still developing, making avoidance of kratom products, especially the more potent forms, strongly recommended.

THE PHARMACEUTICAL ORIGINS OF MEDICINES AND SOFT DRINKS

Historically, many modern medicines, including aspirin and GLP-1 agonists like those in weight-loss drugs, originated from plant compounds. This exploration extends to common beverages. Coca-Cola, for instance, originally contained cocaine extract from coca leaves for flavor before alkaloid extraction. Similarly, early soft drinks like Seven Up (with lithium) and Pepsi (with pepsinogen) were marketed for well-being. This highlights a long tradition of using plant-derived compounds for therapeutic purposes, often predating their understanding as modern pharmaceuticals.

NATURAL PRODUCTS AS FUNCTIONAL PHARMACOLOGY

Plants have evolved complex chemistry, including alkaloids, to defend themselves, often resulting in compounds with potent biological effects. Kratom's alkaloids, for example, may serve as antifungal agents for the plant. This natural bounty has historically informed medicine, with animals often leading humans to identify beneficial plants. The 'slow medicine' movement, akin to 'slow food,' suggests appreciating these natural compounds in their less processed forms, recognizing that their intricate biological effects, often targeting multiple pathways, can offer benefits that highly purified, single-target drugs may miss.

UNDERSTANDING THE COLOR-CODED MARKETING OF KRATOM

Marketing terms like 'white vein,' 'red vein,' and 'brown vein' kratom primarily relate to how the leaves are cured and dried after harvesting, rather than significant inherent differences in alkaloid content. While users report varied effects, scientific analysis of alkaloid profiles for different vein colors shows them to be quite similar. This suggests that perceived differences might be influenced more by product source, processing chain of custody, and user expectation (placebo effect) rather than distinct chemical compositions, similar to cannabis strain marketing.

POTENTIAL FOR DEPENDENCE AND WITHDRAWAL

Regular kratom use, particularly of leaf material, can lead to physical dependence. Withdrawal symptoms can include headaches, lethargy, and restless leg syndrome, sometimes described as similar to caffeine withdrawal but potentially more intense and akin to opioid withdrawal. While opioid-based treatments like buprenorphine are used to help individuals withdraw from kratom, the complex pharmacology of kratom means that these treatments may not address all aspects of dependence, leaving open questions about optimal treatment strategies.

CHILDREN AND ADOLESCENTS: A HARD NO FOR KRATOM

Given that the brain continues to develop until around age 24-25, and research on cannabis shows potential negative impacts on developing brains, it is strongly advised that individuals under 18, and preferably under 21 or 25, avoid kratom. Young people, lacking fully developed prefrontal cortex executive control, are more susceptible to risks associated with psychoactive substances. The availability of kratom products in easily accessible locations like gas stations poses a significant risk for accidental or experimental use by minors.

THE HISTORICAL RELATIONSHIP BETWEEN COCA LEAF AND COCA-COLA

Coca-Cola's original formula by pharmacist John Pemberton contained both coca leaf extract and kola nut extract. Coca leaf extract, sans cocaine alkaloids, is still used as a flavoring agent in Coca-Cola and Coke Zero today, imported from Peru and processed to remove all psychoactive compounds. This decocainized extract is generally recognized as safe and provides the beverage's unique flavor. Coca leaf, when consumed as tea, is even reported to soothe the gastrointestinal tract, demonstrating a continued, albeit subtle, connection to the plant's original uses.

THE EVOLUTION OF DRUG RESEARCH AND NATURAL PRODUCTS

Dr. McCurdy's career trajectory exemplifies the journey from exploring natural products to understanding their pharmacology. His work on lobeline from Indian tobacco, researching its potential for Alzheimer's, and then Salvia Divinorum's potent hallucinogen salvionorin, led him to kratom. This path highlights how investigation into plant compounds can uncover novel mechanisms and potential therapeutic targets, driving medicinal chemistry and pharmacology forward, often revealing nature's sophisticated solutions to complex biological challenges.

Mentioned in This Episode

●Supplements

●Products

●Software & Apps

●Companies

●Organizations

●Concepts

●People Referenced

Common Questions

Kratom (Mitragyna speciosa) is a tree native to Southeast Asia, particularly Malaysia and Thailand. Traditionally, its leaves are chewed or brewed into a tea by laborers for energy, stamina, pain relief, and mood elevation. In the US, it is sold as dried leaf material or concentrated extracts.

Topics

Kratom Alkaloids Medicinal Chemistry Natural Products Coca Leaf Respiratory Depression

Mentioned in this video

productSeven Up

A soft drink that historically contained lithium and was marketed for 'mind wellness'.

supplementFadogia Agrestis

An herb mentioned as being used for vitality and hormone support.

drugGLP-1s (weight loss drugs like Wegovy/Ozempic)

A class of blockbuster weight loss drugs, originally derived from the saliva of the Gila monster, used to control glucose and promote satiety.

drug7-hydroxy mitragynine

A metabolite of mitragynine (the major alkaloid in kratom) that is chemically produced and sold in commerce, acting as a pure opioid equivalent in activity and causing respiratory depression.

drugMethadone

An opioid used as a treatment for opioid use disorder, sometimes prescribed to help individuals withdraw from kratom.

personJohn Pemberton

Pharmacist in Atlanta who developed the original Coca-Cola formula containing coca leaf and cola nut extract.

organizationUniversity of Florida

Institution where Dr. Chris McCurdy is a professor of medicinal chemistry and directs research on natural products.

drugLobeline (from Indian tobacco)

A compound derived from Indian tobacco (Lobelia inflata) that was studied as a respiratory stimulant and potential treatment for Alzheimer's disease.

personDr. Chris McCurdy

Professor of Medicinal Chemistry at the University of Florida, whose research focuses on natural products and their pharmacologic effects, especially kratom.

personDr. Kirsten Smith

Colleague of Dr. McCurdy at Johns Hopkins, involved in extensive surveying of kratom users.

productROKA Red Lens Glasses

Glasses designed to filter short-wavelength light in the evening to improve sleep, by supporting melatonin and reducing cortisol.

conceptPepsinogen

A digestive peptide that was historically an ingredient in Pepsi.

productDr. Pepper

A soft drink developed in Waco, Texas as a special formula for well-being.

drugNaloxone (Narcan)

An opioid antagonist that can reverse the respiratory depression caused by 7-hydroxy mitragynine, confirming its opioid receptor involvement.

drugCodeine

An opioid medication used for moderate pain relief and cough suppression, used as a benchmark for mitragynine's analgesic efficacy.

drugNSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

A class of drugs like ibuprofen that emerged as a safer alternative to opioids for pain relief, without addictive properties, though they have their own side effects.

supplementKava

An ingredient sometimes found in kratom products, contributing to their effects.

drugTHC tincture

A highly concentrated form of cannabis, mentioned to illustrate the difference between traditional plant use and concentrated products.

drugSalvinorin

A potent, non-nitrogen containing terpenoid hallucinogen from Salvia Divinorum, known to cause dysphoria by interacting with kappa opioid receptors.

drugBotox (Botulinum toxin)

A very potent neurotoxin that inhibits acetylcholine release, used clinically for muscle spasms, migraines, and cosmetic purposes.

drugBuprenorphine (Suboxone)

A gold-standard opioid use disorder treatment, used to help individuals get off kratom, although its efficacy for kratom's complex pharmacology is debated.

companySmith, Kline & French (now GlaxoSmithKline)

Pharmaceutical company that extensively studied mitragynine in the 1960s but shelved its development due to its limited advantages over codeine and the emergence of safer NSAIDs.

productNew Coke

A Coca-Cola product released in the 1980s without coca plant extract, which failed due to a different flavor profile.

productCoke Zero

A Coca-Cola product that successfully replicated the classic flavor by including the coca plant flavoring agent, unlike Diet Coke.

supplementMorphine

supplementHeroin

supplementOpium