Kratom, derived from the plant Mitragyna speciosa, is receiving increased attention as an alternative to traditional
opiates and as a replacement
therapy for
opiate dependence.
Mitragynine (MG) and
7-hydroxymitragynine (7-HMG) are major psychoactive constituents of kratom. While MG and 7-HMG share behavioral and
analgesic properties with
morphine, their reinforcing effects have not been examined to date. 7-HMG, but not MG, substituted for
morphine self-administration in a dose-dependent manner in the rat
self-administration paradigm. Following the substitution procedure, re-assessment of
morphine self-administration revealed a significant increase following 7-HMG and a significant decrease following MG substitution. In a separate cohort, 7-HMG, but not MG, engendered and maintained intravenous
self-administration in a dose-dependent manner. The effects of pretreatment with nalxonaxine (NLXZ), a μ1
opiate receptor antagonist, and
naltrindole (NTI), a δ
opiate receptor antagonist, on 7-HMG and
morphine self-administration were also examined. Both NLXZ and NTI reduced 7-HMG
self-administration, whereas only NLXZ decreased
morphine intake. The present results are the first to demonstrate that 7-HMG is readily self-administered, and the reinforcing effects of 7-HMG are mediated in part by μ and δ
opiate receptors. In addition, prior exposure to 7-HMG increased subsequent
morphine intake whereas prior exposure to MG decreased
morphine intake. The present findings indicate that MG does not have abuse potential and reduces
morphine intake, desired characteristics of candidate
pharmacotherapies for
opiate addiction and withdrawal, whereas 7-HMG should be considered a kratom constituent with high abuse potential that may also increase the intake of other
opiates.