Psilocybin: The Chemistry, Effects, and Brain Science

By Tessa Eskin

Across the world, there exist over 180 species of mushrooms that naturally produce psilocybin – the ingredient that makes some mushrooms ‘magic’. Scientists believe this to be a defense strategy, dampening the appetite of ants before they eat through the entire mushroom. But when ingested by humans, psilocybin has a much more interesting effect. For thousands of years, these mushrooms have been used in religious ritual to induce an altered state of consciousness or mystical experience.

These unearthly mushrooms chemically alter perception, thought, and emotions, inducing a sense of profound unity, bliss, and decentralization of ego. Many experience deep insights brought on by a fresh perspective on their internal and external world. Psilocybin appears to gives the brain a full-on makeover, a psychological reset that can prompt positive life changes. It has been used to this effect throughout human history by shamans and priests under the veil of religious mystery. Long before the west had even developed the concept of human psychology, our ancestors were conducting group therapy, assisted by natural psychedelics.

Psilocybin American History

American mushroom enthusiast R. Gordon Wasson brought psilocybin awareness to the US mainstream in the 1950s, when he was invited to an indigenous mushroom ceremony in Mexico. The experience inspired him to send samples of Psilocybe mexicana to chemist Albert Hoffman (of LSD fame). Hoffman isolated psilocybin in 1957, and went on to produce a synthetic version a year later.

In 1970, psilocybin became a casualty of the war on drugs when the DEA classified it as a Schedule 1 substance. This was despite the fact that psilocybin is neither addictive, dangerous, nor without medicinal use. On the contrary, research confirms psilocybin as an effective treatment for depression, addiction, and near-death anxiety of cancer patients. After rigorous testing decades later, the FDA recently granted psilocybin treatment as a “breakthrough therapy”, accelerating the drug development and review process. This allowed researchers to further understand how psilocybin works its magic on the human mind.

You’ve Just Had Some Kind of Mushroom

Psilocybin is an indolalkylamine hallucinogen, with a high affinity to serotonin 5-HT (monoamine neurotransmitters modulating our mood and behavior). The intensity of its effects depends largely on species, location, and handling. Though the taste is rather unpleasant, they are always ingested—fresh, dried, in pill form, or brewed in a tea. This is because psilocybin works through the gut. The acidic environment of the stomach converts it into psilocin, which binds to serotonin receptors called 2A.

The hallucinogenic effects usually begin within 20 to 40 minutes and last around 3 to 6 hours. Colors change, patterns appear, and the senses become distorted and enhanced, while intense emotions arise. Time speeds up, slows down, or halts completely. Many experience a shift in perception of their place in the universe. They feel communion with a higher power, harking back to psilocybin’s traditional use as the ‘plant of the gods’. 

An Orchestra of the Mind

What is actually happening within the brain is a process scientists call neuronal avalanching, a domino effect of neurological changes. Psilocybin creates a feedback loop of neuron activity and neurotransmitter release. As individual brain networks destabilize, psilocybin creates a “global” network across the brain. New pathways spring forth, inducing new insights for old problems. 

Johns Hopkins University Professor Dr. Matthew Johnson likens this to an orchestra. Generally, the brain has separate areas that act as different musical groups playing independently. Psilocybin acts as a conductor, communicating between regions usually strictly compartmentalized. This is what makes psilocybin so effective in a therapeutic context, allowing psychological movement for breakthroughs and emotional exploration.  

What’s even more fascinating is that mushrooms perform the same function in the plant world. Mycelium helps plants and trees communicate by conveying messages, nutrients, and electrical impulses from one to another. Much like psilocybin creates a global network in the human mind, all mushrooms act as the global network of plant life.

The Science of Psychedelics

Consciousness and the human mind are among the greatest scientific mysteries to this day. While research is still underway as to the exact effects of psilocybin on the brain, scientists have posed several theories. We know that psilocybin directly inhibits the dorsal raphe nucleus (DRN) by binding to presynaptic inhibitory 5-HT1A receptors. The DRN is the primary region of the brain that produces and synthesizes serotonin before sending it through the entire central nervous system.  

The DNR is also indirectly inhibited by the stimulation of 5-HT2A receptors on GABAergic interneurons in the periaqueductal gray. This is the brain region that regulates autonomic function, motivated behavior, and responses to threatening stimuli. Both these mechanisms decrease overall “serotonergic tone”, inducing the hallucinogenic effect on 5HT2A receptors in the cortex. This also disinhibits the “noradrenergic nucleus locus coeruleus” and dopaminergic neurons, resulting in a high release of norepinephrine and dopamine. It is this surge of LC that induces the feelings of novelty and wonder experienced on psychedelics. 

The Seat of Consciousness

Researchers at Johns Hopkins University recently compared brain scans of participants after taking a placebo, and then after taking psilocybin. They found that the claustrum was significantly less active on psilocybin. The claustrum is the part of the brain responsible for setting attention and switching tasks. It’s the thin sheet of neurones within the cortex that reach out to every other region of the brain.

Francis Crick, who discovered DNA, believed this area to be the seat of consciousness, awareness, and sense of self. It consists of a large number of receptors that are targeted by psychedelics. This could explain why psilocybin inspires feelings of interconnectivity and reduces the sense of self, or ego. 

Together, these effects create a state of mind enhancing the potential for therapeutic progress. We are left with new insights and a fresh take on our sense of self and our place in the world. It’s no wonder there is such a rich tradition of psychedelic mushroom use throughout human history. In a therapeutic environment, psilocybin can lead to deep psychological revelation, healing, and greater wellbeing. It turns out these mystical mushrooms are truly magical after all.