What are the effects of Kratom (Mitragyna speciosa)?

Effects of Kratom (Mitragyna speciosa)

Kratom should not be used due to its serious adverse effects, including opioid agonist properties with withdrawal potential, hepatotoxicity risk, neurologic complications including seizures, and documented deaths—the FDA has issued warnings against its use. 1

Pharmacologic Effects

Kratom contains over 40 alkaloids, with mitragynine and 7-hydroxymitragynine being the primary psychoactive compounds that exert effects on multiple receptor systems 2:

• Opioid receptor activity: Acts as an atypical opioid agonist on mu, delta, and kappa opioid receptors, producing analgesia and mild euphoria 2, 3
• Adrenergic effects: Alpha-2 receptor agonism contributing to stimulant properties 3, 4
• Serotonergic and dopaminergic pathway modulation 2
• Dose-dependent effects: Lower doses produce stimulant effects, while higher doses (5-15 g per day or more) produce opioid-like sedation and analgesia 1, 5

Serious Adverse Effects

Neurologic Complications

• Seizures: Chronic use may lead to seizures as a direct neurologic effect 1
• Cognitive effects: Confusion, severe confusion, and paranoia can occur 2, 3

Hepatotoxicity

• Liver damage: Kratom has been associated with hepatotoxicity, similar to concerns with other botanicals 1

Cardiovascular Effects

• Tachycardia and orthostatic hypotension may occur 3

Dependence and Withdrawal

• Physical and psychological dependence: Users develop tolerance and experience classic opioid withdrawal symptoms upon cessation 2, 3, 4
• Withdrawal syndrome: Occurs particularly in those taking more than 5-15 g per day and requires tapering rather than abrupt discontinuation 1
• Neonatal withdrawal: Withdrawal signs and symptoms have been documented in newborns of mothers using kratom 3

Common Side Effects

• Dizziness, fatigue, and dry mouth 2
• Unlike traditional opioids, respiratory depression is not commonly reported, though this does not eliminate risk 2, 4

Drug Interactions

Kratom poses significant drug interaction risks through multiple mechanisms 2, 3:

• Cytochrome P450 inhibition: Acts as both substrate and inhibitor of CYP450 enzymes, potentially altering metabolism of co-administered medications 2, 3
• P-glycoprotein and UGT enzyme modulation: May potentiate toxicity of other medications 2
• Polysubstance toxicity: Most documented deaths involved kratom combined with other substances of abuse 3, 5

Detection and Clinical Pitfalls

• Not detected on standard drug screens: Requires specialized testing like liquid chromatography-mass spectrometry 3, 6
• May go unrecognized: Especially dangerous when ingested with other substances, as kratom use may not be identified as contributing to clinical presentation 3, 4

Perioperative Considerations

The Society for Perioperative Assessment and Quality Improvement (SPAQI) explicitly recommends against kratom use and advises discontinuation if possible 1:

• Should be tapered (not abruptly stopped) due to withdrawal potential 1
• The FDA has issued specific warnings against kratom use 1

Mortality Risk

Multiple deaths have been attributed to kratom, though many cases involved polysubstance use 3, 4, 6. The growing number of hospital visits and deaths has prompted national and international regulatory attention 6.

Clinical Context

While some advocate for kratom as an alternative to opioid replacement therapy or for chronic pain management, no adequate human pharmacologic, pharmacokinetic, or clinical trials exist to establish safety, efficacy, or appropriate dosing 4. The high abuse liability, inadequate research, and mounting evidence of adverse events outweigh any theoretical benefits 3.