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Mitragynine and 7-Hydroxymitragynine: Bidirectional Effects on Breathing in Rats
Julio D Zuarth Gonzalez1, Alexandria K Ragsdale1, Sushobhan Mukhopadhyay2
1Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX.
Biorxiv : the Preprint Server for Biology
|June 6, 2025
Summary
7-hydroxymitragynine (7-HMG) in kratom causes respiratory depression reversible by naloxone, similar to opioids. Mitragynine (MG) from kratom, however, stimulates breathing through non-opioid pathways.
Area of Science:
- Pharmacology
- Respiratory Physiology
- Toxicology
Background:
- Kratom use is rising for pain and opioid withdrawal, with products often containing 7-hydroxymitragynine (7-HMG).
- Understanding the respiratory effects of kratom alkaloids, 7-HMG and mitragynine (MG), and naloxone's potential to reverse them is crucial.
Purpose of the Study:
- To evaluate the respiratory depressant effects of 7-HMG and MG.
- To determine if naloxone can reverse the respiratory effects of these kratom alkaloids.
Main Methods:
- Respiratory parameters were measured in rats using whole-body plethysmography.
- Drugs including morphine, 7-HMG, and MG were administered intravenously.
Main Results:
- Morphine and 7-HMG significantly depressed respiration (reduced frequency, tidal, and minute volume).
- MG unexpectedly increased respiratory frequency.
- Naloxone reversed morphine and 7-HMG respiratory depression but not MG's stimulant effect.
Conclusions:
- 7-HMG causes opioid-like respiratory depression antagonized by naloxone.
- MG exhibits respiratory stimulant effects via non-opioid mechanisms.
- Kratom products high in 7-HMG pose risks, while MG may have a safer respiratory profile.
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