From the Guidelines
Kratom and fentanyl have distinct pharmacological profiles, with kratom acting as a partial agonist at mu-opioid receptors and fentanyl being a highly potent full agonist, resulting in a higher risk of fatal overdose with fentanyl compared to kratom. Kratom contains multiple alkaloids, primarily mitragynine and 7-hydroxymitragynine, which produce less respiratory depression than full agonists and also interact with delta-opioid receptors and have activity at adrenergic and serotonergic receptors, contributing to kratom's stimulant effects at lower doses and sedative effects at higher doses 1. In contrast, fentanyl is approximately 50-100 times more potent than morphine, with strong binding affinity that results in significant respiratory depression, analgesia, and euphoria 1.
Key Differences
- Kratom's partial agonist activity at mu-opioid receptors results in a ceiling effect on respiratory depression, making it less likely to cause fatal overdoses when used alone 1.
- Fentanyl's high potency and full agonist activity at mu-opioid receptors increase the risk of fatal overdose compared to kratom 1.
- Kratom's interaction with delta-opioid receptors and adrenergic and serotonergic receptors contributes to its unique pharmacological profile, which is distinct from fentanyl's mechanism of action 1.
Clinical Implications
- The use of kratom and fentanyl should be approached with caution, taking into account their distinct pharmacological profiles and potential risks 1.
- Clinicians should be aware of the potential for dependence and withdrawal with kratom use, as well as its variable potency between products and potential interactions with other medications 1.
- Fentanyl's high potency and risk of fatal overdose make it a less desirable option for pain management, except in cases where its use is strictly necessary and closely monitored 1.
From the Research
Pharmacology of Kratom
- Kratom's primary active compounds, mitragynine and 7-hydroxymitragynine, are partial agonists that act on mu- and delta-opioid receptors in the central nervous system, producing analgesia and a sense of euphoria 2.
- The activation of opioid receptors by kratom is similar to that of opioids, but with a lower risk of overdose death, which is estimated to be >1000 times greater for opioids than for kratom 3.
Comparison to Fentanyl
- Fentanyl is a potent opioid that can cause respiratory depression and death, whereas kratom has been shown to have little of the signature respiratory depressing effects of morphine-like opioids 3.
- Kratom use can lead to addiction and adverse side effects, such as seizures, hallucinations, and coma, but the risk of death associated with kratom use is significantly lower than that of fentanyl and other opioids 4, 5, 2, 6.
Treatment of Kratom Dependence
- Buprenorphine/naloxone has been shown to be effective in treating kratom dependence and withdrawal symptoms, and may be a viable option for treating opioid use disorder complicated by kratom use, chronic pain, and depression 5, 2, 6.
- The use of buprenorphine/naloxone in treating kratom dependence may require higher levels of care and higher doses, especially in cases of polysubstance use disorders 5.