Does chronic Mitragyna speciosa (kratom) use lead to hypogonadism (low testosterone) and decreased serotonin levels, and what is its elimination half-life after discontinuation?

From the Guidelines

Chronic kratom use is likely to cause low testosterone and affect serotonin levels in some users, and it is recommended to discontinue its use due to potential serious adverse effects, as warned by the FDA 1.

Key Points to Consider

• Regular, heavy use of kratom has been associated with hormonal changes, including decreased testosterone levels in men, which may lead to reduced libido, fatigue, and mood changes.
• Kratom's active compounds interact with various neurotransmitter systems, including serotonergic pathways, potentially disrupting normal serotonin function with long-term use.
• The primary active compounds (mitragynine and 7-hydroxymitragynine) typically have a half-life of about 24 hours, meaning they are substantially cleared from the body within 5-7 days.
• Complete normalization of hormone levels and neurotransmitter systems may take longer, typically several weeks to months depending on the duration and intensity of use.
• Some users report that testosterone levels begin to recover within 2-4 weeks after stopping kratom, though this varies considerably between individuals.

Recommendations for Discontinuation and Follow-Up

• If experiencing symptoms of hormonal imbalance or mood disorders after kratom use, consulting with a healthcare provider is recommended for appropriate testing and potential treatment options.
• Given the potential for withdrawal, tapering off kratom use is advised, as recommended by the Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement 1.
• It is essential to prioritize discontinuation of kratom use due to its potential for serious adverse effects, as highlighted in the Mayo Clinic Proceedings 1.

From the Research

Chronic Kratom Use and Hormone Levels

• There is limited research on the effects of chronic kratom use on testosterone and serotonin levels.
• However, a study on the effects of testosterone on mood, behavior, and quality of life suggests that low testosterone concentrations can be associated with depressive symptoms and anxiety 2.
• Kratom's potential impact on hormone levels is not well understood, and more research is needed to determine its effects on testosterone and serotonin levels.

Kratom Use and Serotonin Syndrome

• A case report suggests that kratom use in combination with prescription psychotropic medications can increase the risk of serotonin syndrome 3.
• Serotonin syndrome is a potentially life-threatening condition caused by excessive levels of serotonin in the body.
• Kratom's inhibition of cytochrome P450 isozymes can increase systemic exposure to serotonin, potentially leading to serotonin syndrome.

Kratom's Duration of Action

• The duration of kratom's action in the body is not well understood, and there is limited research on its pharmacokinetics.
• A review of kratom's pharmacology and clinical utility notes that there are no published human pharmacologic, pharmacokinetic, or drug interaction studies on kratom or its active ingredients 4.
• More research is needed to determine how long kratom stays in the system after use is discontinued.

Kratom's Potential Health Effects

• Kratom has been associated with various health effects, including addiction, withdrawal, and adverse interactions with other substances 4, 5, 6.
• The potential benefits and risks of kratom use are not well understood, and more research is needed to inform its safe use and potential clinical applications.