Toadstools and toxins

When I found the mushroom Amanita muscaria being sold in candy wrappers, I uncovered legal loopholes, dangerous dosages and more

Dried caps of the mushroom Amanita muscaria. Photo by Yarphoto/Getty Images

is an associate professor at the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, US.

Edited byPam Weintraub

In late summer 2023, I found myself in a smoke shop looking at a package of ‘magic mushroom’ gummies.

That phrase, magic mushrooms, usually calls to mind one type of mushroom: those containing psilocybin, the compound showing promise as a therapy for depression, addiction and other psychopathologies. But these gummies were not psilocybin. Instead, the packaging described Amanita muscaria, the red-capped, white-spotted toadstool of fairy-tale forests, iPhone keyboards and Super Mario.

I knew a little about the folklore of Amanita muscaria. I had first seen it discussed in an episode of the show Hamilton’s Pharmacopeia (2016-21), which begins with a claim I now hear often: that Amanita muscaria may be among the oldest human intoxicants. The New York banker-turned-ethnomycologist R Gordon Wasson, whose Life magazine essay from 1957 introduced psilocybin mushrooms to a mass Western audience, certainly took this idea seriously. In his book Soma: Divine Mushroom of Immortality (1968), he argued that the Vedic soma – a ritual drink in ancient Indian religions – was made from Amanita muscaria. The mushroom has also been linked, sometimes carefully and sometimes wildly, to the origins of Santa Claus, Viking berserkers and even Christianity. Some believe its other name, ‘fly agaric’, stems from its use as a natural pesticide for house flies; the word muscaria is also derived from the Latin word musca, meaning fly. Some scholars have linked Amanita muscaria to Lewis Carroll’s mushroom scene in Alice’s Adventures in Wonderland (1865), in which the Caterpillar tells Alice that ‘one side’ of the mushroom will make her taller and the other shorter, though Carroll does not identify a species.

From the 1922 edition of Alice’s Adventures in Wonderland, illustrated by Gwynedd M Hudson. Photo by Alamy

But I wasn’t standing in that smoke shop holding one of these products as a folklorist or looking to lose myself in Carroll’s ‘golden afternoon’. I am a public-health scientist, and my questions were pragmatic: what exactly was in this package? Could it hurt someone? Were these products legal?

The first thing I did was what I usually do. I went to the scientific literature. And down the rabbit hole I tumbled.

Although manufacturers use the term ‘magic mushrooms’, the main psychoactive compound in Amanita muscaria is not pharmacologically interchangeable with psilocybin; the two drugs do not act on the brain in the same way.

The body converts psilocybin into psilocin, the substance that actually produces its psychedelic effects. Psilocin switches on serotonin 5-HT2A receptors, proteins on the surface of brain cells that respond to the chemical messenger serotonin. These receptors are concentrated in the cortex, the brain’s outer layer, and especially in the prefrontal cortex, the region behind the forehead involved in such functions as attention, perception and our sense of self. The receptors sit on the big output neurons that broadcast to the rest of the brain, and switching them on makes those cells fire harder. Brain scans of people on psilocybin show what follows: networks that normally run in step with each other come apart, and regions of the cortex that rarely signal to each other begin to. What people report from the inside is a change in perception rather than false perception – surfaces that appear to move, colours that intensify, time that stops running at a fixed rate.

Muscimol killed mice at a lower dose than nearly all psychotropic drugs we examined, including fentanyl

Amanita muscaria works through a different system. Its principal psychoactive compound, muscimol, acts primarily on GABA-A receptors – part of the brain’s main braking system – quieting neuronal activity rather than amping it up. That puts muscimol broadly on the inhibitory side of brain chemistry, the same signalling system influenced by central nervous system depressants such as benzodiazepines and alcohol. The experience is still ‘psychoactive’, but it can look quite different. Clinical reports of Amanita intoxication describe drowsiness and dream-like states, impaired balance and coordination, confusion and disorientation, sometimes alternating with agitation, as well as visual or auditory hallucinations. In severe cases, people can become profoundly sedated, delirious or lose consciousness. In other words, rather than the characteristic alterations in perception associated with psilocybin, Amanita can produce a much less orderly mixture of sedation, hallucination and confusion.

The risks are different too. When my colleagues and I began looking at the toxicology, the numbers startled me. By the crude measure toxicologists often begin with – the LD50, or the dose required to kill half the test population – published estimates suggested that muscimol administered orally killed mice at a lower dose than nearly all commonly used psychotropic drugs we examined, including fentanyl. As a vegetarian, I found the exercise grim, and translating animal doses to humans is always imperfect. But these were safety signals we took seriously.

That was the first turn in the rabbit hole. The next was dosing. If companies were selling Amanita muscaria gummies and chocolates in ordinary retail settings, then somewhere, implicitly or explicitly, someone had made a decision about dosing. A gummy contains some amount. A package contains some total amount. A label tells a consumer to take one piece, or half a piece, or perhaps more. A certificate of analysis from products submitted to a laboratory can provide an amount per gummy. Those numbers can feel reassuring simply because they are printed on a package. They also imply that someone knew enough to choose a dose for the desired effect.

I wanted to know whether that chain existed.

So, I started with a simple question: are there human studies showing what muscimol does at different doses? The best answer to this would have come from controlled studies in which multiple human participants were given standardised doses under observation, with careful reporting of effects and adverse events. I could not find that literature in the usual places. I could find toxicology estimates, case reports, historical accounts and ethnobotanical discussions. But a modern dosing study, the kind one would want before placing psychoactive candies near a cash register, was not there.

Eventually, I came across the proceedings from a symposium I had not known about: the Ethnopharmacologic Search for Psychoactive Drugs, held at the University of California, San Francisco, from 28 to 30 January 1967. The time and place stood out to me immediately. Two weeks........

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