So-called “magic mushrooms” have been used for millennia for spiritual and healing purposes — here’s what you should know about their powerful effects.
Psilocybin is a tryptamine alkaloid that is found in over 180 species of psychoactive mushrooms. With approximately 117 species, the genus Psilocybe from the family Hymenogastraceae is the most common among all genera.
Psilocybe mushrooms, commonly called “magic mushrooms” or “shrooms”, are mostly found in humid subtropical forests, however, they also grow in Alaska, Australia, New Zealand, Hawaii, Europe, Siberia, Japan, and Southeast Asia.
Evidence from wall art indicates that humans have been using different varieties of so-called shrooms for medicinal and spiritual purposes for millennia. For instance, the ‘Selva Pascuala’ mural in Cuenca, Spain dating back to 6000-4000 BCE depicts Psilocybe hispanica and Psilocybe semilanceata.
Indigenous groups, including the Aztecs — a Mesoamerican culture that flourished in central Mexico from 1300 to 1521 AD — and the Mazatecs and Zapotecs of Oaxaca, Mexico, have revered magic mushroom-induced visionary experiences for centuries. These cultures still use psilocybin in ritual ceremonies today as a portal to spiritual realms, particularly for healing and communicating with the spirits of the deceased to acquire ancient ancestral knowledge.
In the Aztec language of Nahuatl, the term for these sacred mushrooms is teonanácatl, which translates to “flesh of the gods.”
Once psilocybin is ingested, it is absorbed, dephosphorylated, and converted into its most prominent metabolite, psilocin. Psilocin then enters the bloodstream and brain where it begins to exert its psychedelic effects.
Psilocin then undergoes two phases of metabolism — phase-I and phase-II. During phase-I metabolism, psilocin is oxidized to 4-hydroxyindole-3- acetaldehyde, which is then further oxidized to 4-hydroxyindole-3-acetic acid, or reduced to 4-hydroxytryptophol.
In phase II, metabolism of psilocybin in the small intestine and the liver produces a psilocin O-glucuronide conjugate. These psilocin metabolites are then excreted via the kidneys. A study from 2017 found the elimination half-life of psilocin to be approximately 3 hours.
Psilocybin has proven itself as perhaps one of the most efficacious treatments for depression, but what makes it so? Well, because it is quite a pharmacologically complex molecule, the answer to this question has thus far resided beyond the reach of determined researchers.
We know that psychedelics produce their psychoactive effects via action at 5-HT2A serotonin receptors. But psilocin appears to exhibit a polypharmacy effect, whereby it uniquely acts on a cluster of different brain receptors.
In addition to the profoundly meaningful phenomenology of the psychedelic experience, beneficial effects of pharmaceutical-grade psilocybin and recreationally-ingested shrooms may also be associated with the following mechanisms of action:
While the induction of the psychedelic experience is primarily due to psilocin’s agonism at the 5-HT2A receptor, the drug’s broad spectrum polypharmacy effect is responsible for the unique psychedelic profile observed in recreational users and clinical study participants alike.
The following mechanisms of action also likely influence the subtleties of the psilocybin experience:
Inhibitory activity in the DRN may also have implications as to why psilocin seemingly disintegrates typical functional connectivity. For example, the administration of psilocybin has been shown to disrupt an interconnected network of brain areas called the default mode network. Some researchers believe that this mechanism is behind the often inexplicable or “ineffable” nature of the psychedelic experience, as well as psilocybin’s clinical efficacy, while others have expressed concern about placing too much emphasis on this as-yet unproven hypothesis.
The full duration of a psilocybin-containing mushroom experience is approximately four to seven hours. The stages of a traditional experience are as follows:
After-effects, which typically last 1-24 hours, are very much dose-dependent. However, they are generally characterized by profoundly positive feelings and enhanced mindfulness. As such, the positive after-effects of psilocybin are often referred to as an "afterglow".
As with the duration, the subjective effects of magic mushrooms are largely dependent on the dose, the user's mindset, and the physical and social environment in which the experience takes place.
Dosages of pure pharmaceutical-grade psilocybin are as follows:
Dosages of dry psilocybin-containing mushrooms are as follows:
Importantly, the concentration of psilocybin in shrooms varies depending on the species, how well they are preserved, and whether they are fresh or have been dried.
Subjective effects may include physiologic, perceptual, psychological, transpersonal, and synesthetic effects (stimulation of one sensation causing simultaneous involuntary stimulation of another sensation).
Also, the subjective effects of a low dose differ significantly from those of a higher dose. For example, high doses are much more visually and physiologically stimulating with significant perceptual distortion, may be spiritual or religious and be perceived as mystical, and often involve the temporary dissolution of one's ego.
Low doses, on the other hand, produce a mildly sedating, relaxing body high that is typically accompanied by sensory enhancement.
A 2018 review published in the peer-reviewed scientific journal Chemical Neuroscience very elegantly provides the most commonly experienced subjective effects of psilocybin. They are as follows:
Psilocybin and its most prominent metabolite, psilocin, were identified as the psychoactive components of Psilocybe mushrooms in 1958 by the legendary chemist Albert Hofmann, previously of LSD fame. Hofmann synthesized psilocybin a year later, and Sandoz Pharmaceuticals, Hofmann’s employer, began marketing the psychedelic for scientific research under the brand name ‘Indocybin’.
Clinical studies conducted during the golden age of psychedelic research in the 1960s-1970s demonstrated that psilocybin produces non-ordinary states of consciousness — characterized by perceptual distortions, mood elevation, creative thinking, transcendence of time and space, and reconceptualization of the self — that were shown to be of profound therapeutic utility.
However, shrooms soon gained popularity as a recreational drug which ultimately led to psilocybin's unfortunate and unjustified classification as a Schedule I substance in 1970. All psilocybin use was made illegal, including scientific research investigating the drug’s evident potential as a therapeutic aid.
Thankfully, some courageous researchers revived human research on psilocybin in the 1990s. Today it is perhaps the most widely used classic psychedelic in human studies due to its relative safety (estimated lethal dose of around 1000 times greater than the effective dose of 6 milligrams), low toxicity rate, and good absorption in humans.
Psilocybin has continued to demonstrate strong therapeutic potential with recent studies showing varying degrees of clinical efficacy for substance use disorders, depression, anxiety, OCD, and chronic pain conditions.
Test Answer 222
Test Answer 2
Content from the community
Test Answer 3
Test Answer 2