Kratom: Risks, Pharmacology, and the Opioid Connection
Summary
This episode of the Huberman Lab AMA addresses the short and long-term effects of kratom, a plant-derived substance from Indonesia that acts as an opioid in the body. Huberman breaks down kratom’s pharmacology, its addictive potential, and the controversial debate around its use as a tool for weaning off more potent opioids. The core message is clear: kratom is not a benign supplement, and those who have never taken it should avoid it entirely.
Key Takeaways
- Kratom is an opioid — it binds to the same mu-opioid receptors as morphine and hydrocodone, despite common claims to the contrary.
- At low doses, kratom produces mild stimulant effects; at higher doses, it becomes an analgesic and sedative with significant addiction potential.
- 10–40% of people may have a heightened response to opioids, making them especially vulnerable to kratom addiction.
- Kratom is approximately one-sixth the potency of hydrocodone, but users can and do escalate dosages to compensate.
- Some people have successfully used kratom to taper off more potent opioids, but the goal must be to eventually come off kratom as well.
- Death from kratom alone is rare but becomes more likely when combined with alcohol or other opioids due to respiratory suppression.
- The lack of standardized regulation means kratom products vary wildly in alkaloid concentration, making dosage comparisons between brands unreliable.
- If you have never taken kratom, the safest course of action is to never start.
Detailed Notes
What Is Kratom?
- Derived from the tree Mitragyna speciosa, native to Indonesia
- Has been used for hundreds of years; traditionally consumed by chewing the leaves
- Today sold over the counter as capsules or raw powder — no prescription required in the United States
- Contains multiple plant alkaloids that interact differently with the endogenous opioid system
Dose-Dependent Effects
- Low dose (stimulant range): mild energy boost, mild euphoria
- Higher dose (opioid range): analgesia (pain relief), sedation, dreamlike states
- Commonly cited “safe” range: 1–6 grams per day, but this figure is unreliable due to variable alkaloid concentrations across brands
Pharmacology: How Kratom Works
- Kratom primarily binds to the mu-opioid receptor (contrary to the popular claim that it only binds kappa-opioid receptors)
- Also binds the kappa-opioid receptor to a lesser degree
- When a mu-opioid receptor blocker is administered before kratom, all effects — euphoria, analgesia, sedation, even the mild stimulant effect — are eliminated, confirming its opioid mechanism
- Kratom indirectly activates dopamine and serotonin reinforcement circuits, contributing to its addictive potential
- Key brain region involved: the periaqueductal gray nucleus in the brainstem, which mediates pain relief
The Endogenous Opioid System
- All humans naturally produce endogenous opioids that bind to opioid receptors
- The runner’s high is a real-world example: long-duration repetitive effort triggers release of endogenous opioids, producing mild euphoria, analgesia, and altered perception
- Kratom, morphine, and hydrocodone mimic these natural compounds but at much higher potency
Addiction Risk
- Kratom meets the definition of an addictive substance: continued use despite negative consequences, and the progressive narrowing of things that bring pleasure
- An estimated 10–40% of people respond to opioids with significantly greater euphoria — these individuals are at highest risk
- Parallel noted with alcohol: roughly 8–10% of alcohol users experience heightened dopamine responses, putting them at elevated risk for alcohol use disorder
- A key indicator of addiction: anxiety or resistance at the idea of stopping use for even 7–10 days
Kratom and the Opioid Crisis
- Some people have used kratom to successfully taper off more potent opioids (morphine, oxycodone/OxyContin, hydrocodone)
- Medical professionals acknowledge this use case but only support it if the person commits to progressively lowering kratom doses and eventually stopping entirely
- Risk of substitution trap: users may escalate kratom dosage until its effects closely resemble those of the drugs they were trying to quit
Respiratory Risk and Death
- Opioids suppress the physiological sigh — an involuntary breathing pattern during sleep that reinflates the lungs and regulates oxygen/CO₂ levels
- Suppression of this reflex during sleep is a primary mechanism behind opioid-related death
- Kratom at low to moderate doses does not appear to significantly suppress respiration on its own
- However, combining kratom with alcohol or other opioids can dangerously suppress respiration
- Deaths attributed to kratom have occurred, likely involving polydrug combinations
Regulation Concerns
- Kratom supplements are not standardized — alkaloid concentrations vary significantly between brands
- One gram of one brand cannot be meaningfully compared to one gram of another
- High abuse potential combined with minimal regulatory oversight is a significant public health concern