Methadone, Buprenorphine, and Clonidine Attenuate Mitragynine Withdrawal in Rats
Open Access
- 12 July 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 12, 708019
- https://doi.org/10.3389/fphar.2021.708019
Abstract
Background: Kratom or Mitragyna speciosa Korth has been widely used to relieve the severity of opioid withdrawal in natural settings. However, several studies have reported that kratom may by itself cause dependence following chronic consumption. Yet, there is currently no formal treatment for kratom dependence. Mitragynine, is the major psychoactive alkaloid in kratom. Chronic mitragynine treatment can cause addiction-like symptoms in rodent models including withdrawal behaviour. In this study we assessed whether the prescription drugs, methadone, buprenorphine and clonidine, could mitigate mitragynine withdrawal effects. In order to assess treatment safety, we also evaluated hematological, biochemical and histopathological treatment effects. Methods: We induced mitragynine withdrawal behaviour in a chronic treatment paradigm in rats. Methadone (1.0 mg/kg), buprenorphine (0.8 mg/kg) and clonidine (0.1 mg/kg) were i.p. administered over four days during mitragynine withdrawal. These treatments were stopped and withdrawal sign assessment continued. Thereafter, toxicological profiles of the treatments were evaluated in the blood and in organs. Results: Chronic mitragynine treatment caused significant withdrawal behaviour lasting at least 5 days. Methadone, buprenorphine, as well as clonidine treatments significantly attenuated these withdrawal signs. No major effects on blood or organ toxicity were observed. Conclusion: These data suggest that the already available prescription medications methadone, buprenorphine, and clonidine are capable to alleviate mitragynine withdrawal signs rats. This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.This publication has 100 references indexed in Scilit:
- Antinociceptive Action of Isolated Mitragynine from Mitragyna Speciosa through Activation of Opioid Receptor SystemInternational Journal of Molecular Sciences, 2012
- Maintenance Medication for Opiate Addiction: The Foundation of RecoveryJournal of Addictive Diseases, 2012
- A comparison of methadone, buprenorphine and alpha2 adrenergic agonists for opioid detoxification: A mixed treatment comparison meta-analysisDrug and Alcohol Dependence, 2010
- Self‐treatment of opioid withdrawal using kratom (Mitragynia speciosa korth)Addiction, 2008
- Clinical chemistry and haematology historical data in control Sprague-Dawley rats from pre-clinical toxicity studiesExperimental and Toxicologic Pathology, 2006
- Toxicology and pathology of deaths related to methadone: retrospective reviewWestern Journal of Medicine, 2000
- Inhibitory effect of mitragynine, an alkaloid with analgesic effect from thai medicinal plant Mitragyna speciosa, on electrically stimulated contraction of isolated guinea-pig ileum through the opioid receptorLife Sciences, 1997
- Antinociceptive action of mitragynine in mice: Evidence for the involvement of supraspinal opioid receptorsLife Sciences, 1996
- Effect of Epidural Clonidine on Analgesia and Pharmacokinetics of Epidural Fentanyl in Postoperative PatientsAnesthesiology, 1991
- Effects of two alpha2 agonists, rilmenidine and clonidine, on the morphine withdrawal syndrome and their potential addictive properties in ratsThe American Journal of Cardiology, 1988