Effects of Panax Ginseng on the Development of Morphine Tolerance and Dependence

The present study was undertaken to determine the inhibitory effects of orally administered ginseng saponins (GS), protopanaxadiol saponins(PD) and protopanaxatriol saponins(PT) on the development of morphine induced tolerance and physical dependence in mice, and to determine the increases in the loss of morphine tolerance and dependence. The study also sought to determine the hepatic glutathione contents, which are closely related to the degree of detoxication of morphinone, a novel metabolite of morphine, and the effects of ginseng saponins on morphine 6-dehydrogenase. The results of the present study showed that GS, PD and PT administered orally inhibited the development of morphine-induced tolerance and dependence. GS, PD and PT, however, increased the loss of morphine tolerance and dependence. GS, PD and PT inhibited the reduction of hepatic glutathione concentration in mice treated chronically with morphine, and the activity of morphine 6-dehydrogenase. So we hypothesized that these results were partially due to the dual action of the test drugs, the inhibition of morphine production and the activation in morphine-glutathione conjugation due to the increased glutathione level for detoxication.