additionally include burning sensations in the mouth, diarrhea, headache, dilated pupils, irregular beating of the heart, and drowsiness; coma and death most often eventually follow. There is no clear, reported correlation between the dose and mortality (see below); death often occurs after 3–6 hours. A historic, reported lethal dose of cerberin in dog is 1.8 mg/kg, and in cat 3.1 mg/kg; that is, it is very low. Hence, eating the core of a fruit from the tree is sufficient for a human to receive a lethal dose, and consumption of the raw leaves of related oleander species has resulted in death. There is significant evidence both from Cerbera and from related species, with regard to lethal poisonings. Individual cases of poisoning from Cerbera, Nerium (oleander), and related species are documented including direct and indirect, and intentional and unintentional ingestion. In one case of accidental poisoning, two vegans in Europe that were foraging for and ingesting wild plants died after consuming wild oleander. In indirect cases, human consumption of crab, where the crustacean had earlier consumed plants producing cerberin or related cardenolides, fatalities are also known. The response of humans to cardiac glycosides in general often depends on the tissue, exposure time and the dose. These toxins act mainly on the heart, either directly or through the nerves. Ouabain and digoxin have half-lives of about 20 and 40 hours, respectively, hence, for these agents, a few days with constant dosing are required before a steady state concentration is reached in tissues. The concentration of a cardioactive agent at steady state is called the therapeutic plasma concentration; for digoxin this value, in ng/mL, lies in the low single digits. When this value is exceeded, the dose can be toxic or life-threatening. Because of the long half-lives of cardiac glycosides, days might pass before plasma concentrations decrease to safe levels. The therapeutic index of cardiac glycosides is ≈2; this is quite narrow, indicating that only a small dose is needed for the compound to be toxic. There are reports that treatment with potassium ion can be used to counter the toxic effects of cerberin, and gastric lavage may also be applied. Even so, cases of direct and indirect poisoning often are fatal, even when the nature and source of the toxin are rapidly identified. Metabolism Very little is known about the metabolism of cerberin. For the related digoxin, another cardiac glycoside, it is