Potentiation of lethality and increase in body temperature by combined use of d-methamphetamine and morphine in mice

Lethality and change in body temperature in mice were examined after subcutaneous injection of d-methamphetamine and morphine alone or in combination. The LD50 values for methamphetamine and morphine were calculated to be 95 and 670 mg/kg body wt., respectively. When a non-lethal dose of morphine (300 mg/kg) was administered with various doses of methamphetamine, the LD50 for methamphetamine was reduced to 5 mg/kg, indicating a marked potentiation of toxicity by combined use of both drugs. Injection of 5 mg/kg of methamphetamine produced slight hyperthermia, while 300 mg/kg of morphine decreased the body temperature of mice. However, when both drugs were used concomitantly, a marked increase in body temperature was observed. Hyperthermia was also observed when the dose of morphine was reduced to 50 mg/kg. It is postulated that hyperthermia is probably one of the contributory factors in the potentiated toxicity by combined use of morphine and methamphetamine.