儘管毒蠅傘含有毒性,但因誤食而中毒致死的案例非常罕見。將這種蘑菇用水煮(英语:Parboiling)兩次可以降低其毒性,並分解其中的迷幻成分。在歐洲、亞洲及北美的部分地區,人們會食用這種經過處理的蘑菇。所有毒蠅傘變種,尤其是A. muscaria var. muscaria,都因其致幻作用而聞名,其主要迷幻成分為蠅蕈素及其神經毒性前體鵝膏蕈胺酸。此外,西伯利亞原住民也曾使用當地的毒蠅傘作為迷幻藥物及宗教儀式中的致幻劑[6][7]。
英國真菌學家約翰·蘭斯巴騰發表文章,說明毒蠅傘曾在英國和瑞典被用來除蟲,且毒蠅傘的其中一個英文名稱,bug agaric,是古老的非傳統名稱[12]。法國真菌學家皮埃爾·布雅德在他的研究《Histoire des plantes vénéneuses et suspectes de la France》中,試著去複製毒蠅傘的殺蠅性質,但沒有成功,而且還因此提議一個新的生物學名Agaricus pseudo-aurantiacus[18]。從真菌裡面分離出來的其中一個化合物是1,3-雙油酸甘油酯(1,3-diolein),事實上是一種昆蟲吸引物質[19]。另外有學著提出另一個名稱起源,表示「fly-」這個字頭不只同樣表示昆蟲,還暗示吃下毒蠅傘之後會導致精神錯亂。這是基於一個中世紀的迷信,相信如果蒼蠅進入一個人的頭,就會導致心理疾病[20]。此迷信常發現於各地區關於此物種的俗名當中;同樣的情形發生在另一個物種橙蓋鵝膏菌,種名有「瘋狂」(mad-)或「愚笨」(fool's)的意思。因此在加泰羅尼亞語,毒蠅傘稱為「瘋狂的鸝」(oriol foll),類似命名的還有圖盧茲的「mujolo folo」,法國南部阿韋龍省部分地區的「concourlo fouolo」,義大利特倫托自治省的「ovolo matto」。瑞士弗里堡州的一個本地方言,對毒蠅傘的稱呼則為「tsapi de diablhou」,意義為「邪惡的帽子[21]」。
毒蠅傘在形態學上變化很大,並且很多專家在毒蠅傘的範圍內辨認出一定數目的亞種或變種。在《The Agaricales in Modern Taxonomy》書中,德國真菌學家洛夫·辛格列出3個亞種,雖然沒有詳盡的描述:A. muscariassp.muscaria、A. muscariassp.americana和A. muscariassp.flavivolvata[22]。
離生的蕈褶呈現白色,孢印也是同樣的顏色。卵圓形的孢子測量後有9-13 x 6.5-9微米大,並且沒有澱粉質,這表示說,用梅澤試劑染色後不會變成藍色[37]。蕈柄為白色,5-20公分(2-8英吋)高,1-2公分(0.4-0.8英吋)寬,有典型大型菇類的微脆,纖維狀組織。蕈柄基部膨大球莖狀,上面有2到4個環狀物,這些環狀物是由外蕈幕的殘留物所形成的。在蕈柄基部和蕈褶之間有一個白色的環狀物,這個蕈環是由內蕈幕(在成長階段覆蓋在蕈褶上面)的殘留物所形成的。環狀構造會隨著年齡變寬且不結實。除了有輕微的土質氣味之外,沒有其他的氣味[38][39]。
基督教作家約翰·C·金恩(John C. King)於1970年著作《A Christian View of the Mushroom Myth》,針對阿列佐的理論加以進一步辯駁;他指出,毒蠅傘與其棲木並沒有在中東發現到,即使香柏與松樹在此發現,並強調聖經與蘇美人姓名間關連性是由阿列佐杜撰,且其關連性非常薄弱。金恩總結,如果這個理論正確,毒蠅傘的用途就會是「世界上最需保護的秘密」,並且會完好保密2,000多年[111][112]。
在北美洲,也存在使用毒蠅傘作為食物來源。食用毒蠅傘的一個經典描述,為美國植物學家弗雷德里克·弗農·科維爾(英语:Frederick Vernon Coville)所提及,描述在19世紀後期,於華盛頓特區的非裔美洲商人會銷售毒蠅傘作為食用用途。在這個案例中,會將毒蠅傘滾水川燙,浸泡在醋裡面,變成蘑菇牛排醬汁使用[115]。毒蠅傘也被日本部分地區當作食物來食用,其中最知名的地區為長野縣。在當地,食用的方式為用鹽進行醃製[116]。
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^Sacred Weeds: Fly Agaric, BBC documentary presented by 安德魯·謝拉特博士(英语:Andrew Sherratt), The Reader in European Pre-History at the University of Oxford (prior to his resignation, formerly Professor of Archaeology, University of Oxford). Documentary released 1998-08-10. Relevant material about 06:30–07:00 minutes. Transcription: I then moved on to the appearance of the fly agaric mushroom in our own culture. This is the famous example from Lewis Carrol's Alice in Wonderland, the caterpillar sitting on the mushroom. Alice bites a little piece of this to get larger / smaller. So there is some evidence that Lewis Carrol himself was aware of some of the properties of eating these mushrooms, and the way in which it altered perception. And so the image of the fly agaric became very common in Victorian literature, especially associated with faeries and little people sitting on mushrooms and toadstools.