Abstract
Abstract
Rationale
Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway.
Objectives
Compare the respiratory effects of oral mitragynine to oral oxycodone in rats with the study design previously published by US Food and Drug Administration (FDA) scientists for evaluating the respiratory effects of opioids (Xu et al., Toxicol Rep 7:188–197, 2020).
Methods
Blood gases, observable signs, and mitragynine pharmacokinetics were assessed for 12 h after 20, 40, 80, 240, and 400 mg/kg oral mitragynine isolate and 6.75, 60, and 150 mg/kg oral oxycodone hydrochloride.
Findings
Oxycodone administration produced significant dose-related respiratory depressant effects and pronounced sedation with one death each at 60 and 150 mg/kg. Mitragynine did not yield significant dose-related respiratory depressant or life-threatening effects. Sedative-like effects, milder than produced by oxycodone, were evident at the highest mitragynine dose. Maximum oxycodone and mitragynine plasma concentrations were dose related.
Conclusions
Consistent with mitragynine’s pharmacology that includes partial µ-opioid receptor agonism with little recruitment of the respiratory depressant activating β-arrestin pathway, mitragynine produced no evidence of respiratory depression at doses many times higher than known to be taken by humans.
Funder
American Kratom Association
Publisher
Springer Science and Business Media LLC
Reference75 articles.
1. Ahmad I, Prabowo WC, Arifuddin M, Fadraersada J, Indriyanti N, Herman H, Purwoko RY, Nainu F, Rahmadi A, Paramita S, Kuncoro H, Mita N, Narsa AC, Prasetya F, Ibrahim A, Rijai L, Alam G, Mun’im A, Dej-adisai S, (2022) Mitragyna species as pharmacological agents: from abuse to promising pharmaceutical products. Life 12:193. https://doi.org/10.3390/life12020193
2. American Kratom Association (2019) The increase in consumer use of kratom in the United States, June 2019. https://assets.website-files.com/61858fcec654303987617512/619dd9d68bd48315873c4952_Kratom_Population_2019.pdf. Accessed 19 Oct 2022
3. Artsy E, McCarthy DC, Hurwitz S, Pavlova MK, Dworetzky BA, Lee JW (2012) Use of modafinil in patients with epilepsy. Epilepsy Behav 23(4):405–408. https://doi.org/10.1016/j.yebeh.2012.02.011
4. Avery BA, Boddu SP, Sharma A, Furr EB, Leon F, Cutler SJ (2019) McCurdy CR (2019) Comparative pharmacokinetics of mitragynine after oral administration of Mitragyna speciosa (Kratom) leaf extracts in rats. Planta Med 85(4):340–346. https://doi.org/10.1055/a-0770-3683
5. Bahramnjead E, Kazemi Roodsari S, Rahimi N, Etemadi P, Aghaei I, Dehpour AR (2018) Effects of modafinil on clonic seizure threshold induced by pentylenetetrazole in mice: involvement of glutamate, nitric oxide, GABA, and serotonin pathways. Neurochem Res 43:2025–2037. https://doi.org/10.1007/s11064-018-2623-7
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