Health Effects & Risks of Kratom, Opioids & Other Plant-Derived Medicines
Summary
Dr. Chris McCurdy, professor of medicinal chemistry at the University of Florida, joins Andrew Huberman to discuss the complex pharmacology of kratom (Mitragyna speciosa), a Southeast Asian plant used for centuries as a stimulant, pain reliever, and mood elevator. The conversation covers kratom’s dose-dependent effects, its relationship to the opioid system, the critical differences between traditional leaf products and modern concentrated extracts/isolates, and its potential role in addressing opioid addiction — alongside serious risks, particularly for young people and those using highly processed forms.
Key Takeaways
- Not all kratom products are the same: Traditional leaf products, concentrated extracts, and semi-synthetic isolates have vastly different potency and risk profiles — yet all are sold under the same “kratom” label.
- Serving size is critical: Many kratom products contain multiple servings per bottle; consuming an entire bottle can deliver far more than intended, especially with concentrated products.
- Kratom-derived isolates (e.g., 7-hydroxymitragynine) behave like pure opioids and have been shown in animal studies to cause respiratory depression equivalent to traditional opioids — reversible with naloxone.
- Most surveyed users are NOT taking kratom to get high: The largest user surveys show people primarily use it for energy, mood elevation, and pain management.
- Kratom causes physical dependence with chronic use, ranging from caffeine-like withdrawal (headaches, fatigue) to opioid-like symptoms (restless leg syndrome) depending on the product and dose.
- Kratom has shown real-world benefit for opioid users: Many people report successfully transitioning off opioids using kratom leaf products, reporting restored energy and quality of life.
- Kratom should be avoided by those under 18–25: The developing brain is vulnerable to psychoactive substances; no data exists on kratom’s impact on brain development.
- “Less is more” among experienced leaf users: Regular users of leaf-based kratom report greater benefit at lower doses, not higher ones.
- The poison is in the dose AND the form: Traditional whole-leaf use is fundamentally different from isolated alkaloids — paralleling how coca leaf differs from cocaine, or opium poppy differs from morphine.
Detailed Notes
What Is Kratom?
- Botanical name: Mitragyna speciosa; a tree native to the border region of Peninsula Malaysia and Thailand
- Primarily grown and exported from Indonesia (~250,000 farmers); imported heavily to the United States
- Estimated 20+ million daily users in the US (based on import volume data; official survey estimates are lower at ~2–2.5 million, but considered a significant undercount)
- Sold in supermarkets, gas stations, convenience stores, and online — often in fine print on energy shot-style products
Traditional Use vs. Modern Products
Traditional use (Southeast Asia):
- Fresh leaves chewed directly or boiled into a decoction (tea) for hours
- Used by outdoor laborers for energy, stamina, heat tolerance, pain relief, and social lubrication
- Higher evening consumption produced more sedative/euphoric effects
- Also used historically to stave off heroin/opium withdrawal symptoms
Modern Western products:
- Dried, shipped leaf material — ground into powder, packed into capsules, or brewed as tea (closest to traditional use)
- Concentrated extracts: Alkaloids pre-extracted by a solvent or liquid; absorbed much faster, delivering higher exposure
- Isolates / semi-synthetics: Chemically modified compounds derived from kratom alkaloids; no longer traceable to the plant; behave as pure opioids
Analogy used: Traditional leaf ≈ light beer; concentrated extract ≈ spirits; isolate ≈ 190-proof Everclear
Kratom’s Active Compounds (Alkaloids)
- Kratom contains 20–40 alkaloids — a diverse chemical “shotgun” targeting multiple receptor systems simultaneously
- Mitragynine: The most abundant alkaloid in the leaf
- 7-Hydroxymitragynine (7-OH): A metabolite of mitragynine produced in the body; likely not synthesized by the plant itself (no biosynthetic enzymes found)
- Acts as a pure opioid agonist
- Now being chemically synthesized and sold commercially as “kratom-derived” products
- Animal data shows respiratory depression equivalent to opioids, fully reversible with naloxone/Narcan
- An alkaloid is defined as an organic molecule containing nitrogen; the nitrogen enables electrostatic binding to protein receptors in the body
Dose-Dependent Effects
| Dose Level | Primary Effects |
|---|---|
| Low dose | Stimulant, energy boost, focus, mild mood elevation |
| Moderate dose | Mood elevation, mild analgesia, social lubrication |
| High dose | Euphoria, sedation, opioid-like effects |
Who Is Using Kratom and Why?
Based on Ecological Momentary Assessment (EMA) studies conducted with Dr. Kirsten Smith at Johns Hopkins:
- Most users take kratom responsibly and purposefully, not primarily to get high
- Top reported uses:
- Energy (most common)
- Mood elevation
- Pain management (including post-workout recovery)
- Opioid substitution or withdrawal management
- Pre-workout endurance enhancement
- A subset uses it for euphoric/recreational effects, typically with more concentrated products
- Users taking leaf-based products typically dose within the first 30 minutes of waking
Physical Dependence and Addiction Risk
- Single use: Does not cause physical dependence
- Chronic use: Causes physical dependence; timeline varies and has not been studied in controlled human or animal trials
- Leaf-based dependence: Resembles caffeine withdrawal — headaches, low energy, irritability
- Higher-dose/extract dependence: Can include restless leg syndrome, more severe withdrawal — resembling opioid withdrawal
- Tolerance to pain-relieving effects develops over time, leading users to escalate dose
- The product in question (small blue bottle, kava + kratom) was noted anecdotally to escalate from 1 bottle/day to 6 bottles/day in one user
Kratom and the Opioid Crisis
- Traditional users in Southeast Asia historically increased kratom tea consumption when heroin/opium was unavailable to prevent withdrawal
- Dr. McCurdy’s lab studies kratom’s potential to help people transition off opioids
- Many users report that kratom “got them off the couch” — restored energy, family life, and functioning that opioids had destroyed
- Kratom leaf interacts with multiple receptor systems (not exclusively opioid), which distinguishes it from classical opioids
- Pure 7-OH isolates, however, interact only with opioid receptors and carry opioid-equivalent risks including respiratory depression
Risks and Safety Concerns
Young people (under 18–25):
- Brain development continues until approximately age 24–25
- No studies on kratom’s effect on the developing brain
- Dr. McCurdy recommends avoiding use until at least 18–21; personally advocates for 24–25
- Parallels drawn to cannabis research showing reduced IQ and slowed brain development with early use
Mislabeling and product confusion:
- Products labeled simply as “kratom” may contain leaf, extract, concentrate, or semi-synthetic isolates
- Consumers and emergency room physicians often cannot distinguish between product types
- Kids may inadvertently pick up kratom energy shots mistaking them for conventional energy products
Key safety rules for anyone using kratom products:
- Check serving size — never assume one bottle = one serving
- Look for “kratom-derived” or “kratom isolate” language on labels — these are functionally different and higher-risk products
- Prefer whole-leaf or minimally processed powder over extracts or isolates
- Use the lowest effective dose; experienced users report “less is more”
Broader Context: Plants, Alkaloids, and Medicine
- ~75% of FDA-approved drugs were discovered from or modified from natural products
- Examples discussed:
- Aspirin → from salicin in willow bark