Decoding kratom: molecular mechanisms and epigenetic factors in use and dependence

Area of Science:

• Pharmacology
• Neuroscience
• Epigenetics

Background:

• Kratom (Mitragyna speciosa) is a traditional herb used for pain and energy.
• Its main compound, mitragynine (MG), has opioid-like and stimulant effects.
• Understanding kratom's mechanisms and safety is crucial for potential clinical use.

Purpose of the Study:

• To systematically review preclinical evidence on kratom's molecular, pharmacological, and epigenetic effects.
• To synthesize findings on receptor activity, intracellular signaling, and gene regulation.
• To identify potential therapeutic benefits and safety concerns.

Main Methods:

• Systematic review adhering to PRISMA 2020 guidelines.
• Analysis of studies indexed in Scopus and Web of Science (2000-2024).
• Focus on in vitro and in vivo models examining molecular and cellular effects.

Main Results:

• Kratom alkaloids interact with μ-opioid, adrenergic, and serotonergic receptors.
• Mitragynine (MG) demonstrates anti-inflammatory and analgesic properties.
• Evidence suggests potential cardiotoxicity, drug-drug interactions, and epigenetic changes during withdrawal.

Conclusions:

• Kratom alkaloids have diverse pharmacological actions.
• Mitragynine (MG) shows promise but has associated safety risks.
• Further human studies are needed to establish safety and efficacy for clinical applications.