Format

Send to

Choose Destination
Psychopharmacology (Berl). 2018 Oct;235(10):2823-2829. doi: 10.1007/s00213-018-4974-9. Epub 2018 Jul 23.

Abuse liability of mitragynine assessed with a self-administration procedure in rats.

Author information

1
Wuhan Institute of Biomedical Science, Jianghan University, No. 8 Sanjiaohu Street, Wuhan, China.
2
Psychobiology Section, Molecular Neuropsychiatry Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 251 Bayview Blvd., Baltimore, MD, 21224, USA.
3
Psychobiology Section, Molecular Neuropsychiatry Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 251 Bayview Blvd., Baltimore, MD, 21224, USA. jkatz@intra.nida.nih.gov.

Abstract

RATIONALE:

Substantial use of the plant kratom for psychoactive effects has driven interest in its abuse liability. Several place conditioning studies suggest abuse liability of the active ingredient mitragynine, though studies of its self-administration have not been published.

METHODS:

Binding of mitragynine to rat brain mu, kappa, and delta opioid receptors was compared to that for heroin and morphine. Self-administration of mitragynine, heroin, methamphetamine, or saline was assessed during single-session substitutions in rats trained to self-administer methamphetamine (0.022 mg/kg/injection, i.v.) during 1-h daily sessions.

RESULTS:

Mitragynine had > 2- or ~ 16-fold greater affinity for the mu opioid receptor than, respectively, for kappa or delta opioid receptors. Its affinity for the mu receptor was ~ 200-fold less than that for morphine. In rats trained to self-administer methamphetamine, saline substitutions significantly decreased the number of responses, whereas different doses of methamphetamine (0.002-0.068 mg/kg/injection) or heroin (0.001-0.03 mg/kg/injection) maintained self-administration with maximal responding at 0.022 or 0.01 mg/kg/injection, respectively. In contrast, no dose of mitragynine maintained response rates greater than those obtained with saline. Presession mitragynine treatment (0.1 to 3.0 mg/kg) decreased response rates maintained by heroin but had little effect on responding maintained by methamphetamine across the same range of doses.

CONCLUSIONS:

These results suggest a limited abuse liability of mitragynine and potential for mitragynine treatment to specifically reduce opioid abuse. With the current prevalence of opioid abuse and misuse, it appears currently that mitragynine is deserving of more extensive exploration for its development or that of an analog as a medical treatment for opioid abuse.

KEYWORDS:

Abuse liability; Heroin; Kratom; Medical treatments; Methamphetamine; Mitragynine; Opioid abuse; Rats; Self-administration

PMID:
30039246
DOI:
10.1007/s00213-018-4974-9

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center