Why do Mushrooms Make Psilocybin?
Written by Elyas Stephens on 2/17/2022
Written by Elyas Stephens on 2/17/2022
As psilocybin's medical potential gains attention, an ever-increasing number of people are drawn to the question: why exactly would a mushroom evolve to produce a compound with its effects? The prevailing answer to this is a hypothesis formed by a team of researchers at the Ohio State University. In their article, they proposed psilocybin acted as an insect-repellant in the fungi. Though it was this that grabbed headlines, the study's primary goal was to find a means by which such a diverse set of fungi developed such a complex trait -spoiler: horizontal gene transfer- and offered the hypothesis as part of their explanation for why the mushrooms would share and conserve this specific trait. There have not been any studies exploring psilocybin's effect on insects, but the idea that psilocybin suppresses their appetites may have come from the action of Massospora cicadina on cicadas. The psilocybin-producing fungus replaces the insect's abdomen and inundates it with potent psychoactive chemicals, compelling it to mate constantly and spread the fungus to more hosts. However, most articles on the subject omit or downplay the fungus' additional production of cathinone. As a stimulant, it is more likely to induce symptoms like hypersexuality and anorexia than psilocybin.
Even if the lack of evidence is disregarded, the hypothesis -in its current form- has a couple of flaws that I believe decrease its viability. The first is that despite their complex methods of spore dispersal, mushrooms often benefit from being consumed¹, as it increases the chances of their spores being deposited in an ideal location. The idea would be more plausible if psilocybin were produced in greater quantities by the subterranean portion of the fungus rather than the fruiting body. If that were the case, acting as a repellant could serve as a means of protecting the health of the fungus, as the mycelial network is the portion of the organism essential to its survival. It also does not benefit from being consumed and deposited elsewhere by an insect, as portions of the mushroom inundated with spores do.
Additionally, if the fungus doesn’t want its mushrooms consumed, there are other chemicals better equipped to stop that from happening. An example of this is camphor, an insect-repelling compound produced by a tree of the same name. It is so effective that some modern mothball manufacturers decide to use it instead of creating a proprietary compound. A perhaps even more obvious form of protection is poison. If the fungus doesn’t want to be eaten, why would the organism decrease the appetites of insects that eat it when it can simply kill them? Killing insects without a predisposition to avoid the mushrooms could artificially pressure the species to evolve an avoidance response to the fungal body. If the increased number of fatalities is not great enough to apply pressure, the fungus would still benefit more from killing the insects than repelling them. Doing so within the mycelial network's range will also increase the nutritional value of the substrate in which it resides, decreasing the amount of energy and risk required to find food. Interestingly, just such a poison is thought to be the evolutionary precursor to psilocybin: muscarine. The organophosphate group to which it belongs is comprised entirely of poisonous compounds, any of which would be far better at defending the mushroom. If psilocybin did develop from muscarine, it indicates the compound has a more important role than repelling insects -although this may still be a part of its function. I would like to propose a more complex hypothesis building on this idea:
Psilocybin production evolved in fungi as a means of artificially selecting which organisms interact with their mushrooms. Its presence discourages interaction from suboptimal organisms and facilitates interaction with those who would benefit the proliferation of the fungus most.
Fruits and fruiting bodies evolved to allow stationary organisms to create distance between themselves and their offspring. There are two primary advantages offered by this:
1. The younger organisms will not compete with their more developed progenitors for resources, which would lead to their development being hindered or kill them.
2. Distance decreases the chances of inbreeding and accidentally passing on harmful recessive traits. Motile organisms have the advantage of moving away or even selecting their mate themselves, but organisms that reproduce passively do not have such luxury.
Given how important these are to a species' survival and reproduction, organisms that can move spores furthest while also providing them with an ideal environment for growth would be the most advantageous to attract, though any interaction is still beneficial.
If this is the case, it makes sense for a fungus to develop a compound that does little more than suppress the appetites of insects, rather than one that outright kills them or repels them prior to contact. The insects can still eat the fruiting body -and by doing so, spread its spores- but they won’t partake frequently. Their lack of appetite may also cause the them to travel further before landing to eat, increasing the distance of the spores from the mushroom. Minimizing insect consumption will allow the mushrooms to sustain little damage over the time it takes for a more optimal animal to find them. If the mushrooms were completely consumed by insects, they would be harder for better carriers to spot in fields or along the forest floor. Even if they did not consume the entirety of the mushroom, many other animals will avoid eating something that appears rotten and covered with insects.
Additionally, the animals most likely to eat spore-laden insects are birds, lizards, and amphibians -many of which inhabit areas too dry or wet for the development of club fungi. The acidity of their stomachs is often extremely low -sometimes close to 1pH- which would kill ingested spores. Assuming any survived the digestive tract, even spores dropped on a suitable location by a mid-air guano release would have difficulty growing to maturity as the aging excrement’s acidity increases over time, rendering the area uninhabitable for developing mycelium. This indicates that the animals psilocybin targets must be terrestrial in nature with relatively alkaline stomachs: large herbivorous mammals.
In addition to having brains better suited for interaction with psilocybin, these animals will often consume the mushroom itself rather than a secondary carrier of the spores. They also inhabit more suitable locations for fungal growth, and generate far more and far better substrate in which the fungus can grow. The pH of many mammalian herbivore’s digestive systems is closer to neutral, limiting or eliminating damage to the spores. This remains true for their waste, the larger quantity of which provides more resources to the developing mycelium and a greater thermal mass to protect it from fluctuations in temperature. The tendency of such animals toward social behavior is another benefit to the fungus as well, as it will be provided with even more waste matter in a given location and its spores have a better chance of being carried externally. Though the relationship between P. cubensis and cows is the only modern example of this, psilocybin developed up to 20 million years ago during the miocene epoch. At the time, there was a greater number and diversity of large herbivores, many of them possessing more basic -in both senses of the word- digestive systems. It was also a period in which many forests began to give way to grasslands, leading to the development of more grazing and herding animals.
Psilocybin mushrooms often prefer to grow in substrate that experiences frequent disturbances, which one would assume to be detrimental to the fungus’ growth. Remember though, the end result of natural selection is not increasing the lifespan of an organism, but increasing the species ability to successfully reproduce. Considering this, even extensive damage to an individual mycelial network is a minimal price to pay for the organism’s spores to be consumed or stepped on and spread by a suitable animal.
Those spores serve as yet more support for this hypothesis. Many psilocybin mushrooms have dark spores, which are produced most often by fungi that benefit from being deposited far from their source. The dark coloration protects their DNA from being degraded by ultraviolet radiation. This selection towards protecting their DNA from mutation may also indicate how important the fungus’ current method of operation is to the species’ survival. Mushrooms with suboptimal traits will likely have lighter spores as an increased mutation rate will increase the chances of a desirable trait emerging.
If the ability to act on serotonin receptors through oral consumption is the reason for these mushrooms developing a psychedelic, why did psilocybin specifically emerge? Why not another orally-active compound or set of compounds, like DMT and an MAOI, or one of the many lysergamides found in both plants and fungi? It’s most likely because creating these is a more complex process than creating psilocybin. Increasing the number of steps it takes for an organism to produce a compound usually decreases the chances it will be selected for in the long run. The increased points of failure and energy cost of adding additional steps decrease the trait’s chances of being inherited unless the new compound being produced through that addition provides a greater advantage. However, even this doesn’t fully explain why psilocybin was produced instead of another orally-active psychedelic already found in nature. The answer might be in a secondary trait of the compound: color.
Although psilocybin itself does not contribute to the coloration of a mushroom, the aforementioned active metabolite psilocin will polymerize to form a brilliant blue bruising when the mushroom is damaged. The rarity of blue in nature will make the fungus’ mushrooms more easily identifiable and may intrigue curious animals, increasing the chances of that particular organism’s spores being carried than those of an adjacent, non-bruising fungus. This may be an additional reason why reducing -but not eliminating- insect interaction is beneficial to the mushroom. A small amount of damage to the fruiting body by insects will cause it to bruise, increasing its noticeability without rendering it unappealing. This begs the question that completes the puzzle: If psilocin is the coloring agent and the active compound, why did these fungi develop the additional phosphorylation step required to create psilocybin? The answer lies in the relative stability of the compounds. Psilocin is far more prone to decomposition than psilocybin, and its polymer form is inactive. Retaining the psychedelic’s structure is important as significant degradation would render the entire synthesis process a waste.
My hypothesis is, of course, not without its own flaws -ones we may never resolve, given our profound lack of time machines. The first of these is the distinct lack of interaction between psilocin and the dopamine, endocannabinoid, or opioid networks. One would assume a fungus that benefits most from interaction would evolve to produce a compound that rewards such behavior as directly and effectively as possible. While the lack of cannabinoids and opioids can be explained by their larger and more complex structures, many of the most powerful dopaminergic compounds are both simpler and less chemically "expensive" than tryptamines. Some psilocybin mushrooms already produce trace but measurable quantities of phenethylamine -a dopaminergic compound that serves as a base for the structures of many addictive compounds, including methamphetamine. Such compounds increase dopamine levels, which feels rewarding to the animal consuming it, and would encourage interaction to a much greater degree. A stimulant specifically would also encourage increased travel and decreased food intake, meaning the spores would be carried further before being deposited. One admittedly weak response to this is that average gut pH typically decreases after substantial durations without food. If an organism were to eat a huge amount of stimulant-containing mushrooms, the subsequent appetite suppression may render their digestive system uninhabitable for spores.
Considering the fungi are capable of making phenethylamines but heavily favor tryptamines, there must be a reason for evolution favoring one over the other. This could be a direct advantage offered to tryptamine-producing fungi through a difference in action, but external availability of compounds that make production simpler could be another solution. If the mushrooms could take advantage of a precursor to tryptamine alkaloids, modifying its active groups might provide a beneficial tryptamine more efficiently than producing a phenethylamine from scratch. For example, if the fungi evolved alkaloid production in an area saturated with a cyanobacterium such as A. Plantesis (spirulina), they would have access to an abundance of tryptophan, which can be converted to serotonin (by humans) in as little as two steps. Given that serotonin's structure differs from psilocin's only in the position of the hydroxyl group -on carbon 5 instead of 4- it would likely be similarly simple for a fungus to evolve efficient psilocin production. They could develop the phosphorylation step necessary for longer-term storage later, once the presence of psilocin proved advantageous. However, the fungi may not have possessed the ability to absorb and use tryptophan present in their environment. This is supported by a study on Claviceps purpurea (ergot), which produces the aforementioned -and far more complex- tryptamines known as lysergamides. Specimens were grown in a variety of substrates -including some saturated with tryptophan- to test if the presence of precursors would have an effect on alkaloid production. Unfortunately for the viability of this explanation, the amount of tryptamine in the substrate had no significant impact on alkaloid production. Another issue is the climate of the miocene epoch during which psilocybin production is thought to have evolved, which is believed to have been relatively warm and dry, discouraging the presence of aquatic cyanobacteria. To cap off this flaw, the effects of psilocybin consumption by non-humans is not known, meaning support for any incentive offered by psilocybin consumption is -at this time- limited to hypotheses based on its action in humans.
Another issue is the lack of animals with low-acidity digestive systems to propagate the fungus. Even considering a higher average gut pH in earlier animals, the production of psilocybin must have remained beneficial or neutral to each species of fungus’ survival for it to be conserved for such a long duration. As with the previous issue, there is little that can be said in response. Many early herbivorous species that existed for millions of years -including the Gigantopithecus apes and Megaloceros giganteus- only became extinct recently -perhaps too recently for production of psilocybin to evolve out of the fungi. Hominid interaction with the fungi could be another factor. The pH of an omnivore’s stomach is not ideal for fungal development, but their natural curiosity, strong group behavior, extreme travel distances, and perhaps even purposeful cultivation of psilocybin mushrooms could have aided in the trait’s survival.
Though we may never learn the true role psilocybin plays in the lives of fungi, it is still an interesting and worthwhile endeavor to try and find it. I believe my hypothesis is a viable explanation based our current knowledge of the fungi, despite its flaws, and can't wait to see if new evidence emerges that changes how we think about psychedelics in the context of evolution.
If you've enjoyed reading this article, consider ordering a copy of The Book of Psychedelics -it’s an in-depth exploration of psychedelics over 350 pages in length!
https://pringlelab.botany.wisc.edu/documents/GOLAN_Long-Distance%20Dispersal%20of%20Fungi.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662758/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519257/
https://psychedelicreview.com/phenylethylamine-overlooked-active-magic-mushrooms/
https://pubmed.ncbi.nlm.nih.gov/15680483/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC251757/
Disclaimer: The proposed method of integration follows a reductionist and scientific view of the psychedelic experience and its therapeutic potential that some readers may disagree with. Additionally, it is a proposal for a future technique and is designed to be implemented in a therapeutic setting, not to be taken as guidance on how to use psychedelics illegally. It is not medical advice and should not be taken as such. The author does not condone the illegal use of any compound.