POISONING BY AMANITA MUSCARIA.

The symptoms of poisoning by this fungus usually appear from eight to twelve hours after it has been eaten, unless it has been taken in enormous quantities, as in the cases reported by Prentiss (Phila. Med. Jour., September 24, 1898), where they came on in half an hour.

These begin with cramp-like pains in the extremities, colicky pains in the abdomen, burning thirst, vomiting and purging. The pulse may be very slow and strong at first, but later becomes rapid, small and feeble. The blood pressure is low and, as a result of this disturbance of the circulation, faintness is a common early symptom. Extreme pallor is often noticed. The secretions are increased, and the sweat and the saliva may be secreted in abnormal quantities.

The pupils are strongly contracted and dullness of the vision or double vision may be noticed early.

The respirations are slow and become shallow and stertorous when the poisoning is severe.

The mental state may be clear at first, but becomes dull, deepening into unconsciousness and deep coma if a large quantity has been taken.

Convulsions are reported to have occurred in some cases from poisoning by this toadstool in man. The dried Amanita muscaria or extracts of the fresh fail to produce convulsions in the lower animals, even in frogs, which are very susceptible. Either there is a considerable difference in the susceptibility to this poison or there is some poison present in the fresh fungus which is lost by drying.

Small amounts of the dried Amanita muscaria are said to be used by inhabitants of northern Asia for the stimulating effect upon the nervous system, producing, like other narcotic poisons, a dreamy state of intoxication, deepening into sleep (Von Boeck in Ziemssen’s Cyclopedia of Medicine, Vol. VII).

In animals the most striking effect is upon the circulation. When injected intravenously it causes tremendous inhibition of the heart’s action—a moderate amount causing the heart to beat slowly and powerfully; a large amount causing complete arrest. Even with the partial inhibition there is an enormous fall of pressure. The slowing of the heart soon passes off, and when a moderate amount has been injected, the circulation quickly returns to normal.

In one of my experiments on a dog, the heart stopped for 1¾ minutes and then began beating again, the circulation soon recovering.

Late in the poisoning the heart beats may be rapid and feeble and the blood pressure low. The lowered blood pressure is largely due to dilatation of the small blood vessels resulting from a loss of control over them by the nerve center which normally keeps the arterioles in a state of partial contraction.

The inhibition of the heart is due to the action of the well-known alkaloid muscarine upon nerve ganglia in the heart. The contraction of the pupil and the increased secretory activity of the glands are also due to this substance which was discovered by Schmideberg and Koppe in 1869.

It was soon found that although dogs recovered from the immediate or early effects (i. e., from the muscarine) of enormous quantities of toadstools, they succumbed from the late effects of much smaller quantities. Atropine fails to avert this result from the late effect, whether given before the poison, with it, or after it. The inhibition of the heart passes off long before death occurs. Late death does not appear to be due to muscarine.

All these facts put together point to the existence of some other poison or poisons in the Amanita muscaria to which atropine is not an antidote.

This peculiar poisoning causing death so late will be discussed again after considering the other poisonous mushrooms as they act similarly.

Gastro-intestinal symptoms were not as common in my experiments with Amanita muscaria as with the Amanita phalloides. Vomiting and purging occasionally occurred early, but much more frequently late in the poisoning and often not at all.

Convulsions did not occur in any of the animals poisoned by this fungus. Convulsions are recorded in some cases of poisoning in man, but not so constantly as with the A. phalloides and A. verna. Where they occurred either a large amount had been taken (as in Prentiss' case) or there is some doubt about the Amanita muscaria having been the only toadstool eaten (as in Caglieri’s cases). Frogs are very easily thrown into spasms, but no spasms were observed, even in fatal poisoning of them by this toadstool.

Regarding cerebral symptoms, little can be said except that unconsciousness and coma may come on early and persist till death. In cases terminating fatally the animal seemed to be conscious, but so depressed that it was unable to stand or even move when called.

Concerning differences in the susceptibility of different animals to the poisons of Amanita muscaria, cats seemed to be more susceptible than dogs in the earlier experiments with extracts of the fresh fungus, but more numerous experiments with the dried fungus failed to show any greater difference than can be observed between different animals of the same kind.

As to the nature of the poisons very little can be stated from the experiments, as they were undertaken as a preliminary step to chemical studies to be carried on later. The alkaloid muscarine is one of our best known poisons and nothing can be added to what is already known about it. The poisons are extracted by distilled water as well as by a solution of sodium chloride; they are soluble in glycerine and in alcohol and very little difference can be seen in the action of these extracts, unless the alcoholic extract contains more of the muscarine, while the glycerine extract contains more of the other poisons.

It is stated that muscarine is not poisonous to flies; that the Amanita muscaria contains a volatile poison which is poisonous to flies (hence the name “Fly mushroom”), and which is lost by drying; that inhabitants of northern Asia use the dried fungus (after the volatile poison has been lost) for producing intoxication (Von Boeck in Ziemssen’s Cyclopedia, Vol. VII, p. 927). My experiments have been entirely with mammals and frogs, and unfortunately those performed with the fresh toadstools were not numerous enough to enable me to draw positive conclusions as to any loss of toxicity by drying. A single experiment with a cat seemed to indicate that boiling of the fungus lessened the toxicity but subsequent experiments indicated that a boiled solution was no less toxic than one not boiled.

One thing we can state definitely; that boiling the dried A. muscaria does not destroy its toxicity. This indicates that the poison is not of an albuminous nature, which would be coagulated by heat.

Whether or not any volatile poison is lost by boiling a solution of the fresh fungus or by drying at 40° C. can not be stated definitely as the experiments made with the fresh fungus were few in number on account of the extreme difficulty in getting them perfectly fresh.

The average of six observations in which it was possible to weigh the toadstools before and after drying at 40° C. showed a loss of 84.4 per cent. of water. In other words, 1 gram of the dried equals 6.4 grams of the fresh.

Comparing the lethal doses of the dried with the lethal doses of the fresh extracted by glycerine and alcohol, it does not appear that there is any great loss of the toxicity by drying as is shown by the following: Lethal dose of dried in Experiment 31 was .085 gram. per kilo of body weight; in Experiment 55, .033 gram. per kilo caused early death, while .223 gram. of dried per kilo and .120 gram. per kilo caused death from late effects (Exps. 32 and 57). The lethal doses of the fresh were .91 gram. per kilo (Exp. 29) and 1.055 gram. per kilo (Exp. 36) when a glycerine extract of the fresh growth was used, while 1.222 gram. per kilo (Exp. 16) made from an alcoholic extract failed to kill.

It may be well to introduce here the results of an experiment which shows there is no highly poisonous volatile material given off from the A. phalloides. This is rather an important fact to determine, as the opinion is held by some that there is a volatile poison, and most of my experiments were made with the dried fungus. A 1 per cent. solution of fresh A. phalloides was distilled until three-fourths of the fluid had passed over as distillate. The latter was injected into the vein of a dog and found not at all toxic. The opportunity has not been afforded me of repeating this experiment personally, but Dr. J.P. Arnold has kindly repeated it for me, injecting the distillate into rabbits and frogs and failed to find it toxic. Certainly if there is any volatile poison in the A. phalloides it must be either in very minute quantity or very slightly toxic.