The Mechanisms of Mind-Manifesting Mushrooms

© Peter Werner
Original publication: Mycena News, September 2004

Psychedelic mushrooms, such as the blue-staining Psilocybe species and Amanita muscaria, have been of enormous cultural and religious importance for many thousands of years, continuing to the present day. Most people have a vague idea that these mushrooms have neurologically active compounds that affect the central nervous system, but are less clear on exactly how these compounds act to alter consciousness.

To understand how psychoactive drugs work, one must first understand the role of neurotransmitters. The brain and the larger nervous system are made up a complex series of specialized nervous pathways. The individual neurons that make up these pathways communicate with other neurons at sites called synapses. Synapses are pairs of projections, an axon and a dendrite, each from a different neuron; between the two is a gap called the synaptic cleft. Transmission of a signal from one nerve to another involves the release of a neurotransmitter from the axon, which then disperses across the synaptic cleft and binds to receptors on the surface of the dendrite. The binding of the neurotransmitter to a receptor causes the neuron to either release or take up calcium ions, altering the neuron's electrical potential and either stimulating or inhibiting the movement of electrical pulses along the neuron to axons elsewhere on the neuron. Once an axon receives an electrical impulse, it releases neurotransmitters, continuing the chain of nervous signals.

There are many different neurotransmitters, such as serotonin, norepinephrine, dopamine, acetylcholine, GABA, and many others. Different neural centers and pathways in the brain use different arrays of neurotransmitters to transmit nervous signals. The actions and processes of the brain are determined by which of these centers and pathways are stimulated and which are inhibited.

Neuroactive compounds function by mimicking the action of specific neurotransmitters; they bind to the same receptors, where they act as either antagonists, agonists, or reuptake inhibitors. Agonists and antagonists both bind to the receptor sites of an analogous neurotransmitter, however, they differ in how they act once they bind to these sites. Agonists cause the neuron to transmit or inhibit a nerve impulse just like the actual neurotransmitter would, while antagonists simply block the binding of neurotransmitters without stimulating the neuron. A reuptake inhibitor slows the axon's reabsorption of a neurotransmitter, making the neurotransmitter available to the receptors for longer, hence prolonging an incoming nervous signal.

The blue-staining Psilocybe and Panaeolus species get their psychoactive properties from the high levels of psilocin and psilocybin that they contain. (The blue staining is directly correlated with psilocin content, as it results from the oxidation by air of an unidentified compound that is produced by the degeneration of psilocin.) Psilocin is directly resposible for the psychoactive properties of these mushrooms, as psilocybin is simply converted by the human body to psilocin by a simple dephosphorylation reaction. Psilocin is a close relative of the neurotransmitter serotonin and its resemblance to serotonin is what is responsible for its psychoactive properties. Psilocin binds to a specialized type of serotonergic receptor know as the 5-HT2a receptors, where it acts as a partial agonist, stimulating some neurons but not others.

How these nerve actions translate into the characteristic psychedelic experience is still not fully understood. One hypothesis is that the increased activity of the sensorimotor gating system of the brain, which normally functions to channel the majority of sensory stimuli from conscious awareness. The conscious mind is therefore overwhelmed by sensory stimuli and cognitive processes that are normally not consciously experienced. In fact, one of the centers of the brain through which sensorimotor stimuli are filtered is the locus coeruleus, which has a very high concentration of 5-HT2, receptors. (It should be noted, however, that there are other hallucinogens such as ketamine that do not act on the locus coeruleus.) If the sensorimotor gating hypothesis of hallucinogenic action is correct, then Aldous Huxley's restatement of Blake's dictum, "If the doors of perception were cleansed every thing would appear to man as it is: infinite" is in fact a worthwhile metaphor.

The effects of Amanita muscaria are caused by an entirely different set of compounds which act in a very different manner than psylocybin mushrooms. Amanita muscaria contains ibotenic acid and muscimol, though only muscimol is directly responsible for the mushroom's psychoactive effects; ibotenic acid is converted to muscimol when the mushroom is dried. Muscimol is a GABA agonist, and its actions on the brain are even less well understood than are the actions of psilocybin. GABA is thought to be a "master inhibitor", blocking the firing of many other neurotransmitters throughout the brain. Muscimol therefore inhibits the release other neurotransmitters at many different sites, but exactly which neural centers andpathways are affected and how this translates into the characteristic Amanita muscaria experience is not understood. The fact that muscimol acts in such a general manner in the brain is perhaps the reason why A. muscaria is associated with such a wide range of autonomic effects, such as alternations between sleep and wakefulness, as well as excessive salvation.

Fig 1: A basic diagram of synaptic action showing the release of neurotransmitter from an axon (top) to binding sites on a dendrite (bottom).

The striking effects that these mushrooms have upon awareness has lead to a great deal of fanciful speculation about their role in nature and human culture. A widespread "theory" that has gained far too much currency in recent years is the assertion by the late Terrence McKenna that Psilocybe is in fact some sort of extraterrestrial life form that has come to this planet to raise human awareness. Needless to say, there's no evidence for this assertion and quite a bit of evidence against it. It is quite clear from the study of the morphology, physiology, and molecular sequences of fungi and other organisms that Psilocybe is a perfectly ordinary agaric closely related to other agarics and that fungi as a whole fit perfectly well into the phylogeny of eukaryotes, being in fact more closely related to animals (including ourselves) than they are to any other group of organisms. An extraterrestrial organism, if we were to ever encounter one, would almost certainly have a biology that in fundamental ways would be different from the organisms of the Earth.

It is also often asserted that psychoactive compounds in plants and fungi exist as a sort of mutualistic adaptation to humans. It is reasoned that humans enjoy the effects of psychoactive plants and fungi, and therefore humans deliberately propagate them, creating an adaptive advantage for organisms that are psychoactive. This argument could be extended, of course, to any cultivated plant, and it should be obvious that there are many edible plants under far more intensive cultivation than any psychoactive plants. More importantly, such anthropocentric speculations ignore the fact that hominids have only been on this planet for a tiny portion of Earth's evolutionary history and that most groups of plants and fungi have been around far longer; humans are therefore unlikely to have played any significant role in the evolution of hallucinogenic compounds.

The role of insects and soil organisms in the evolution of such compounds is a far more likely course of events. It has been demonstrated that cocaine disrupts insect feeding behaviors and inhibits their feeding upon leaves containing cocaine; psilocin and psilocybin (which are present in mycelium as well as fruiting bodies) may very well protect fungal tissue in a similar manner. It has been observed that LSD, which acts on the same receptor sites as psilocin, causes marked behavioral changes in Drosophila.

It would seem, then, that the ability of some plants and mushrooms to alter our consciousness is simply a by-product of a much earlier process of coevolution. This of course, is true of much of the natural world – wild raspberries are tasty so that they can attract seed dispersers and orchids are showy to attract pollinators. Our own aesthetic pleasures and transcendent experiences are incidental in the larger scheme of things, but then, why should we need a grand purpose to enjoy such benefits?