The Hepatic Oxidation of Mitragynine

By Victor A. Borras RN, TNCC, ENPC

K9 Handler /Contraband Educator - K9 One Detection Services

A noteworthy aspect of Kratom (Mitragynine), often overlooked in presentations by subject matter experts, is its conversion to 7-OH-Mitragynine through a process known as hepatic oxidation. This article aims to explain, clarify, and inform our readers and subscribers about the significance of understanding the actions of this substance upon ingestion.

What Hepatic Oxidation Means

“Hepatic oxidation” refers to liver enzyme–mediated metabolism — specifically, oxidation reactions that alter a drug’s chemical structure.

• The liver is the primary site of drug metabolism.

• These reactions are usually carried out by the cytochrome P450 (CYP) enzyme family.

• The goal of oxidation is to make the compound more water-soluble, so it can be eliminated by the kidneys.

Mitragynine’s Oxidative Metabolism

When mitragynine (MG) enters the liver, it is primarily oxidized by CYP3A4, and to a lesser extent by CYP2D6 and CYP2C19. The key oxidative reaction is the conversion of mitragynine to 7-hydroxymitragynine (7-OH-MG). This involves adding a hydroxyl (-OH) group to the 7th carbon on the indole ring system — hence “7-hydroxy.”

The Conversion Rate

Only a small fraction of mitragynine is converted to 7-hydroxymitragynine. Studies show roughly 1–2% of mitragynine undergoes this hepatic oxidation. Despite the low conversion, 7-OH-MG is much more potent at the μ-opioid receptor — about 10 to 13 times stronger than morphine in receptor affinity studies. So, even though little is produced, that small amount contributes disproportionately to kratom’s opioid-like effects.

Why It Matters Pharmacologically

Mitragynine itself has weak opioid activity but acts as a prodrug: its metabolite, 7-OH-MG, drives much of the analgesic and euphoric effects. Individuals with different CYP3A4 activity levels (due to genetics, other drugs, or liver health) may experience different intensity or duration of effects. This also explains variable user experiences — some people feel stronger effects from the same kratom dose.

Why is it crucial to understand the process related to Kratom?

Comprehending the hepatic oxidation of mitragynine is essential for students and the general public to make informed, science-based decisions regarding Kratom use. Here’s why it is significant:

It Clarifies Kratom's Opioid-Like Effects

Mitragynine itself exhibits limited opioid activity. However, when the liver oxidizes mitragynine into 7-hydroxymitragynine, it becomes a potent μ-opioid receptor agonist. This transformation helps explain why some users experience effects similar to opioids, such as pain relief, sedation, euphoria, or dependence. Understanding this informs students that Kratom’s risks are pharmacologically significant, rather than merely “natural and harmless.”

It Emphasizes Individual Variability in Risk

The enzymes responsible for this oxidation (CYP3A4, CYP2D6, CYP2C19) differ among individuals due to genetics, diet, and other medications. Some individuals may convert more mitragynine to 7-hydroxy, resulting in stronger effects, tolerance, or toxicity. Others may experience less, prompting them to increase dosage unsafely. Understanding this variability aids students in comprehending why Kratom’s effects vary from person to person and why it can be unpredictable.

It Links Liver Health to Drug Safety

Since hepatic oxidation occurs in the liver, students should recognize that: Liver damage (from alcohol, medications, or illness) can alter Kratom metabolism.

Combining Kratom with other drugs that affect CYP enzymes (e.g., antidepressants, antibiotics, antifungals) can enhance side effects or toxicity. Liver function is a critical safety factor in all drug metabolism, including “natural” substances like Kratom. It Reinforces the Concept of a “Prodrug.” Mitragynine functions as a prodrug, meaning its active form (7-hydroxy) emerges after metabolism. This helps students grasp basic pharmacology concepts applicable to many medications—not just Kratom. It serves as a valuable teaching example for biology, chemistry, and health science. It Increases Awareness of Dependence and Withdrawal. Since 7-hydroxymitragynine is a potent opioid agonist, repeated use can lead to:

Tolerance (requiring more for the same effect). Dependence (withdrawal if discontinued).

Cross-sensitivity with other opioids. Students who understand that the liver converts mitragynine into an opioid-like compound are more likely to comprehend why Kratom can be addictive.