Attenuation of Morphine Dependence by Ganoderma lucidum Extract in Mice

Background: Opioids are the principal drugs of choice for managing acute severe pain; however, physical dependence is still reported as one of the main limiting factors in the clinical application of these drugs. In the present study, the effect of Ganoderma lucidum was assessed on morphine dependence in mice. Methods: A19-day administration schedule was applied to induce morphine dependence in male adult NMRI mice. The mice were given intraperitoneal (i.p.) morphine sulfate once daily in an increasing dose of 10, 20, and 40 mg/kg. Then, G. lucidum hydroalcoholic extract (12.5, 25, and 50 mg/kg, i.p.) was given to the mice from days 10 to 18. Another group of mice received single doses of the extract (50, 100, and 200 mg/kg, i.p.) only on the 19th day. Naloxone (3 mg/kg, i.p.) was used to precipitate withdrawal syndrome. Normal saline and diazepam (0.25 mg/kg) were used as the negative and positive controls, respectively. Results: The administration of single doses of G. lucidum extract (100 and 200 mg/kg, i.p.) significantly decreased the number of jumps, leanings, and diarrhea in mice subjected to morphine dependence. The repeated administration of G. lucidum extract (25 and 50 mg/kg for nine days) significantly attenuated the number of jumps, leanings, and diarrhea in morphine-dependent mice. Conclusions: Overall, G. lucidum extract attenuates induced morphine dependence and inhibits withdrawal syndrome symptoms in mice.