From the Guidelines
Mitragynine content at 2.3% and 7-hydroxymitragynine at 0.01% suggests a conversion potential to buprenorphine-like effects, but with significantly less potency and risk of respiratory depression compared to traditional opioids. When considering the management of acute pain in patients receiving maintenance buprenorphine therapy, clinical experience is limited, and treatment approaches are based on available literature, pharmacologic principles, and published recommendations 1. The high affinity of buprenorphine for the μ receptor complicates pain treatment with opioids, risking displacement of, or competition with, full opioid agonist analgesics.
Some key considerations for managing acute pain in patients on buprenorphine therapy include:
- Continuing buprenorphine maintenance therapy and titrating a short-acting opioid analgesic to effect, with caution due to potential increased sensitivity to the full agonist 1
- Dividing the daily dose of buprenorphine and administering it every 6 to 8 hours to take advantage of its analgesic properties, potentially requiring additional opioid agonist analgesics for effective analgesia in patients with opioid tolerance 1
- Monitoring level of consciousness and respiration frequently, with naloxone available due to highly variable rates of buprenorphine dissociation from the μ receptor 1
In the context of mitragynine and 7-hydroxymitragynine conversion to buprenorphine-like effects, the partial agonist properties of these alkaloids create a ceiling effect that limits both therapeutic benefits and dangerous side effects compared to full opioid agonists. This suggests that users may experience mild to moderate pain relief, mood enhancement, and potentially some withdrawal suppression if transitioning from other opioids, but with less risk of respiratory depression. However, the potency of this kratom composition is estimated to be roughly 1/10th to 1/20th that of a standard 2mg buprenorphine dose, depending on the total amount consumed.
From the Research
Mitragynine and 7-Hydroxymitragynine Conversion
- The conversion of mitragynine to 7-hydroxymitragynine is a crucial aspect of its pharmacological activity, with 7-hydroxymitragynine being a more potent mu-opioid receptor agonist 2.
- Studies have shown that mitragynine is converted to 7-hydroxymitragynine in vitro in both mouse and human liver preparations, mediated by cytochrome P450 3A isoforms 2.
- The conversion rate of mitragynine to 7-hydroxymitragynine is limited, resulting in a built-in ceiling effect for mitragynine-induced respiratory depression 3.
Pharmacokinetics of Mitragynine and 7-Hydroxymitragynine
- The pharmacokinetics of mitragynine and 7-hydroxymitragynine have been studied in humans, with mitragynine being the most abundant alkaloid in kratom leaves 4.
- The median mitragynine Tmax was 1.0-1.3 h after single and 1.0-1.7 h after multiple doses, while the median 7-hydroxymitragynine Tmax was 1.2-1.8 h and 1.3-2.0 h, respectively 4.
- Steady-state mitragynine concentrations were reached in 8-9 days, and 7-hydroxymitragynine concentrations were reached within 7 days 4.
Abuse Liability and Therapeutic Potential
- Studies have investigated the abuse liability and therapeutic potential of mitragynine and 7-hydroxymitragynine, with 7-hydroxymitragynine being found to have high abuse potential and mitragynine having limited abuse potential 5.
- The reinforcing effects of 7-hydroxymitragynine are mediated in part by μ and δ opiate receptors, and prior exposure to 7-hydroxymitragynine increased subsequent morphine intake, whereas prior exposure to mitragynine decreased morphine intake 5.
Analgesic Effects
- The analgesic effects of mitragynine are mediated by its conversion to 7-hydroxymitragynine, which is a more potent mu-opioid receptor agonist 2.
- 7-Hydroxymitragynine is formed from mitragynine in mice, and brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine 2.