An Examination of Cholinergic Symptoms Produced by the Fly Agaric Mushroom Amanita muscaria (Agaricomycetes): Revisiting the Role of Muscarine.

The English mycological and toxicological literature has, for decades, asserted that muscarine concentrations in Amanita muscaria are insignificant based on a study from the 1950s that demonstrated muscarine levels in fresh A. muscaria mushrooms at a meager 0.0003%. This position has been maintained despite frequent reports of cholinergic symptoms following consumption of this mushroom and despite the dated study upon which this position is based. To update the literature on A. muscaria's pharmacology and to address disparities between the current scientific consensus on the role of muscarine, a cholinergic compound, in A. muscaria poisonings and the frequent reports of cholinergic symptoms following its ingestion, four steps were taken: (1) surveys were collected from 53 individuals who experienced cholinergic symptoms following ingestion of A. muscaria; (2) mushroom samples were procured for HPLC-MS/MS analysis from three survey participants; (3) mushrooms were collected independently for HPLC-MS/MS analysis; and (4) commercial analyses of Amanita muscaria were compiled to illustrate a range of muscarine concentrations. Survey results demonstrated that mild-to-moderate cholinergic symptoms were experienced at doses that reflect common use of the mushroom for recreational, therapeutic, and spiritual purposes (1-20 g dried). Results of HPLC-MS/MS analyses demonstrated muscarine concentrations ranging from 0.004% up to 0.043%, significantly exceeding the consensus value. Study findings demonstrate that current understandings of muscarine concentrations in A. muscaria are inaccurate, and that the occurrence of muscarine in A. muscaria must be understood as a broad range, one that ranges from the insignificant up to physiologically significant levels.