Is mitragynine (primary active component of Kratom) safe for medical use?

Mitragynine (Kratom) Is Not Safe for Medical Use

Mitragynine and kratom should not be used for any medical purpose due to serious documented adverse effects including opioid-like withdrawal, hepatotoxicity, seizures, and deaths—the FDA has explicitly warned against its use. 1

Why Kratom Is Unsafe

Serious Adverse Effects Profile

• Seizures represent a documented neurologic complication of chronic kratom use 1
• Hepatotoxicity has been associated with kratom consumption, similar to other problematic botanical supplements 1
• Deaths have been documented in association with kratom use, with the FDA issuing specific warnings against its consumption 1
• Opioid toxidrome requiring naloxone reversal has been reported, demonstrating its potent opioid agonist effects 2

Addiction and Withdrawal Potential

• Physical and psychological dependence develops with regular use, producing classic opioid withdrawal symptoms upon cessation 3
• Withdrawal syndrome occurs particularly in those consuming more than 5-15 grams per day 1
• Abrupt discontinuation is contraindicated—kratom must be tapered due to withdrawal risk 1
• Animal studies demonstrate locomotor sensitization, conditioned place preference, and severe somatic withdrawal signs developing after 12 hours, with increased anxiety evident after 24 hours 4

Cognitive Impairment

• Acute mitragynine impairs passive avoidance learning, memory consolidation, and retrieval 4
• Chronic administration leads to impaired passive avoidance and object recognition learning 4
• These cognitive effects are mediated by disruption of cortical oscillatory activity, including suppression of delta and theta rhythms 4

Pharmacologic Mechanism of Harm

Opioid Receptor Activity

• Mitragynine and 7-hydroxymitragynine act as partial agonists at μ-opioid receptors and antagonists at κ- and δ-opioid receptors 5
• They produce dose-dependent effects: stimulant effects at lower doses, but opioid-like sedation and analgesia at higher doses (5-15 g per day or more) 1
• The compounds also affect adrenergic, serotonergic, and dopaminergic pathways, increasing complexity and unpredictability of effects 3

Drug Interaction Risks

• Kratom alkaloids are inhibitors of CYP2D6 and to a lesser degree CYP2C19 and CYP3A4 5
• This creates potential for potentiating toxicity of coadministered medications through modulation of cytochrome P450, P-glycoprotein, and uridine diphosphate glucuronosyltransferase enzymes 3

Clinical Context and Common Pitfalls

Why People Use It (Despite Dangers)

• Users seek kratom as an inexpensive, legal alternative to methadone and buprenorphine for opioid use disorder 3
• Other reported uses include chronic pain management, achieving a "legal high," and treating anxiety, depression, and PTSD 3
• In Southeast Asia, traditional use involves enhancing tolerance for hard work or self-treating opiate addiction 6

Critical Distinction: Western vs. Southeast Asian Use

• Kratom-associated mortality and morbidity in Western countries are quantitatively and qualitatively different from Southeast Asia, where traditional use is not a public health problem 5
• Reasons for increased Western harm include: polysubstance use (more prevalent in Western countries), higher dosages, adulterations and contaminations of commercial products, pharmacokinetic interactions, and higher concentrations of 7-hydroxymitragynine in dried leaves (typically consumed in West) versus fresh leaves (consumed in Southeast Asia) 5

Perioperative Risk

• The Society for Perioperative Assessment and Quality Improvement (SPAQI) explicitly recommends against kratom use and advises discontinuation if possible 1
• If discontinuation occurs, tapering is required rather than abrupt cessation due to withdrawal potential 1

Regulatory Status and Future Concerns

• In 2016, the US Drug Enforcement Administration attempted to classify kratom as a federal Schedule I medication but withdrew the plan due to public resistance 3
• Kratom currently remains legal and unregulated as a dietary supplement, leaving users at risk from unpredictable potencies and effects 2
• The lack of standardized dosing and quality control represents an ongoing public health hazard 2

Bottom Line for Clinical Practice

Do not recommend kratom for any medical indication. 1 The documented risks of seizures, hepatotoxicity, cognitive impairment, addiction, and death outweigh any potential therapeutic benefits. Patients using kratom should be counseled on these serious risks and offered evidence-based alternatives for pain management, opioid use disorder treatment, or psychiatric conditions. If a patient is currently using kratom, coordinate a supervised taper rather than abrupt cessation to avoid withdrawal complications. 1