From the Guidelines
Mitragynine, the primary active alkaloid in kratom, should be discontinued due to its opioid-like properties and potential for serious adverse effects, as recommended by the Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement. This recommendation is based on the potential risks associated with mitragynine, including dependence, withdrawal symptoms, and side effects such as nausea, constipation, and sedation 1. The FDA has also warned against the use of kratom, which contains mitragynine, due to its potential for abuse and lack of regulatory oversight.
Key Considerations
- Mitragynine acts as a partial agonist at mu-opioid receptors, producing pain relief and mood enhancement effects, but its use is not FDA-approved for medical purposes.
- Regular use of mitragynine can lead to dependence and withdrawal symptoms, and higher doses may cause side effects including nausea, constipation, and sedation.
- The SPAQI consensus statement recommends discontinuing kratom, which contains mitragynine, due to its potential for serious adverse effects, including hepatotoxicity and opioid-like properties 1.
- The FDA has warned against the use of kratom, which contains mitragynine, due to its potential for abuse and lack of regulatory oversight.
Clinical Implications
- Discontinuation of mitragynine is recommended to minimize the risk of adverse effects, particularly in patients undergoing surgery or taking other medications that may interact with mitragynine.
- Patients using mitragynine should be closely monitored for signs of dependence, withdrawal symptoms, and side effects, and alternative pain management strategies should be considered.
- Healthcare providers should be aware of the potential risks associated with mitragynine and counsel patients on the safe use of kratom and other dietary supplements.
From the Research
Mitragynine Overview
- Mitragynine is the major active compound in Kratom (Mitragyna speciosa) [(2,3,4,5,6)]
- It is used for its opium- and coca-like effects, as well as for self-medication of pain, opioid withdrawal, and other conditions [(2,3,4)]
Physiological and Behavioral Effects
- Mitragynine has analgesic, muscle relaxant, anti-inflammatory, and anorectic effects [(3,4)]
- Regular consumption may lead to tolerance, dependence, and aversive withdrawal symptoms [(3,4)]
- Mitragynine's actions in the central nervous system involve μ-opioid receptors, neuronal Ca²⁺ channels, and descending monoaminergic projections [(3,4)]
Metabolism and Potency
- Mitragynine is metabolized in human liver microsomes to several metabolites, including 7-hydroxymitragynine, which is more potent and efficacious than mitragynine [(5,6)]
- The cytochrome P450 enzyme CYP3A4 plays a predominant role in the metabolic clearance of mitragynine 6
- Mitragynine pseudoindoxyl, a novel metabolite, is formed in human plasma and is even more potent than mitragynine or 7-hydroxymitragynine 5
Therapeutic and Abuse Potential
- Mitragynine has both therapeutic and abuse potential [(3,4)]
- It may be used to alleviate morphine and ethanol withdrawal effects, as well as to treat pain and opioid addiction [(3,4)]
- However, daily, high-dose use may result in kratom use disorder and opioid-like withdrawal on cessation of use 2