Kratom - Drug Monograph

Introduction

Kratom (Mitragyna speciosa) is a tropical tree native to Southeast Asia whose leaves contain psychoactive compounds. While traditionally used in its native regions for medicinal purposes and as a stimulant, kratom has gained popularity in Western countries as an unregulated botanical substance. It is currently classified by the FDA as a dietary supplement, though it has no approved medical uses in the United States.

Mechanism of Action

Kratom's primary active alkaloids are mitragynine and 7-hydroxymitragynine, which act as partial agonists at mu-opioid receptors and antagonists at kappa- and delta-opioid receptors. Additionally, kratom alkaloids interact with adrenergic, serotonergic, and dopaminergic systems. Mitragynine also displays affinity for alpha-2 adrenergic receptors and various serotonin receptor subtypes, contributing to its complex pharmacological profile.

Indications

Kratom has no FDA-approved medical indications. Traditional uses in Southeast Asia have included:

• Fatigue reduction
• Pain relief
• Management of opioid withdrawal symptoms
• Mood enhancement
• Diarrhea treatment

Dosage and Administration

Kratom is typically consumed as:

• Dried leaves (chewed or brewed as tea)
• Powder (often encapsulated or mixed with liquids)
• Extracts and tinctures

Dosage varies significantly:

• Low dose (1-5 g): Stimulant effects
• Moderate dose (5-15 g): Analgesic effects
• High dose (>15 g): Sedative effects

There are no established dosing guidelines for special populations.

Pharmacokinetics

Contraindications

• Known hypersensitivity to kratom or its components
• Severe hepatic impairment
• Pregnancy and breastfeeding
• Concomitant use with other CNS depressants
• History of substance use disorder

Warnings and Precautions

• Risk of dependence and addiction with chronic use
• Potential for hepatotoxicity
• May cause QT prolongation
• Not recommended for patients with cardiac conditions
• High abuse potential
• Withdrawal syndrome similar to opioid withdrawal
• Lack of quality control in commercial products

Drug Interactions

• Opioids: Additive CNS depression
• Benzodiazepines: Increased sedation risk
• Alcohol: Enhanced CNS depression
• CYP3A4 inhibitors (e.g., ketoconazole): Increased mitragynine levels
• CYP3A4 inducers (e.g., rifampin): Decreased mitragynine levels
• Serotonergic drugs: Potential serotonin syndrome

Adverse Effects

• Nausea and vomiting
• Constipation
• Dry mouth
• Increased urination
• Itching
• Sweating
• Dizziness

• Seizures
• Hepatotoxicity
• Respiratory depression (particularly with high doses)
• Psychiatric symptoms (anxiety, psychosis)
• Tachycardia and hypertension
• Coma (in overdose)

Monitoring Parameters

• Liver function tests (baseline and periodically)
• ECG monitoring for QT prolongation
• Respiratory rate (particularly with higher doses)
• Mental status assessment
• Signs of dependence or withdrawal
• Renal function

Patient Education

• Kratom is not FDA-approved for any medical use
• Potential for addiction and dependence with regular use
• Do not combine with alcohol, opioids, or other CNS depressants
• Be aware of withdrawal symptoms with discontinuation
• Report any signs of liver problems (jaundice, dark urine, abdominal pain)
• Inform healthcare providers of kratom use before procedures or prescriptions
• Products may be contaminated with other substances
• Not recommended during pregnancy or breastfeeding

References

1. FDA (2022). FDA and Kratom. U.S. Food and Drug Administration 2. Prozialeck WC, et al. (2021). Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. Journal of the American Osteopathic Association 3. National Institute on Drug Abuse (2022). Kratom Drug Facts 4. Grundmann O, et al. (2018). Patterns of kratom use and health impact in the US. Drug and Alcohol Dependence 5. Eggleston W, et al. (2019). Kratom use and toxicities in the United States. Pharmacotherapy 6. Warner ML, et al. (2016). The pharmacology and toxicology of kratom. Journal of the American Academy of Neurology 7. FDA MedWatch (2022). Adverse Events Associated with Kratom Use 8. World Health Organization (2021). Critical Review of Mitragynine