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In rats, the median lethal dose (LD50) when administered orally is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine. The lethal dose of psilocybin when administered intravenously in mice is 285 mg/kg and in rats is 280 mg/kg.[17] When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg.[77] Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37 lb) of fresh mushrooms, would be required for a 60-kilogram (130 lb) person to reach the 280 mg/kg LD50 value of rats.[46] Based on the results of animal studies, the lethal dose of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose of 6 milligrams.[78] The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index of 641 (higher values correspond to a better safety profile); for comparison, the therapeutic indices of aspirin and nicotine are 199 and 21, respectively.[79] The lethal dose from psilocybin toxicity alone is unknown, and has rarely been documented—as of 2011, only two cases attributed to overdosing on hallucinogenic mushrooms (without concurrent use of other drugs) have been reported in the scientific literature and may involve other factors aside from psilocybin.[4