Psilocybin is a psychedelic compound found in over 200 species of mushrooms that are distributed across the planet, with the most famous and potent of the psilocybin mushrooms being from the genus Psilocybe.  Though psilocybin is the most well known compound, it is not directly responsible for the hallucinogenic effects or perceptual distortions.  The most prominent use of this compound was by the Mexican Indians, specifically the Aztec and the Maya, and it has gained prominence as an entheogen, allowing its user to interact with the divine.  For example, psilocybin mushrooms played an important part in the culture and religion, for both divination and healing.

Spanish conquistadors were the first Europeans to observe the ritualistic use of mushrooms by the Aztec, who called psilocybe “teonanáctal” meaning “flesh of the gods”.  There was extensive use in mesoamerica, and psilocybin’s ritualistic uses are still in existence.  The amateur mycologist Gordon Wasson documented the most famous interaction with such ritualistic uses in 1955, and brought attention to this hallucinogen to the modern western world.  During a trip to Mexico, Wasson met a curandera named Maria Sabina.  She would become famous as a mushroom shaman, and used the mushrooms properties to guide her patients into the spirit world for healing.  In Wasson’s later writings he describes the experience:

As your body lies there, your soul is free, with no sense of time, alert as never before, living an eternity in a night, seeing infinity in a grain of sand… The divine mushroom introduces ecstasy to us.  Your very soul is seized and shaken until it tingles, until you fear that you will never recover your equilibrium.  After all, who will choose to feel undiluted awe, or to float through that door yonder into the Divine Presence?     

This experience sparked interest by Americans, who would later flood the region, and destroy the cultural importance of the experience.  Maria Sabina said “the lack of respect and the total disrespect which the foreigners displayed towards her "saint children" shook the very foundations of her wisdom, strength, and world. Like the ancient mysteries of the "temple of Dionysus" where silence of the ancient rites was golden, María Sabina claimed that before Wasson came, "nobody spoke so openly about the `saint children'. No Mazatec before ever revealed what he or she knew about this matter” (Erowid).  Now, Psilocybin is one of the most prevalent entheogens, but is rarely used as such and is almost exclusively used for recreational purposes. 

Psilocybin trips vary from person to person as well as with dose.  With lower doses, thoughts become more introspective and auditory and visual senses become more pronounced.  As the dose increases, distortions become more prominent, potentially yielding full visual and auditory hallucinations.  The effects of psilocybin take effect within 30-45 minutes, and reach peak intensity by about 2 hours.  The experience lasts about 4 hours, with the compound being completely metabolized within 24 hours (Passie et al).

Though psilocybin is the most well known component, it is not the hallucinogenic compound; its metabolite, psilocin is the bioactive species in the central nervous system (Perrine, 278).  Psilocybin is metabolized mainly in the liver via dephosphorylation to psilocin. 

Psilocin’s bioactivity comes from its N,N-dimethyltriptamine moiety, which is present in many psychotropic compounds.  This structure is very similar to 5-hydroxytryptamine (5-HT) or Serotonin, which gives indoleamine hallucinogens their bioactivity, as they act as agonists for 5-HT receptors in the CNS. The 5-HT1A receptor is found in blood vessels and the CNS, and regulate functions such as anxiety, blood pressure, heart rate, impulsivity, mood, memory, sociability, and other physiological changes.  The 5-HT2A receptors are located in the CNS, blood vessels and platelets, and in smooth muscle.  This receptor regulates similar functions as the 5-HT1A but with the addition of cognition, imagination, learning, and perception.  Although indoleamine hallucinogens can bind to various serotonin receptors, the primary hallucinogenic and cognitive effects are a result of the 5-HT2A receptor (Umbricht, et al).  The specific affinity of indoleamine moieties for the 5-HT2A receptor gives psilocin its ability to act as an agonist for dopamine, as well as inducing excessive release of glutamate (Umbricht et al.)  With continual use, downregulation of 5-HT receptors occurs, resulting in the development of tolerance (Spinella).

Psilocybin/psilocin has 1/200th the potency of LSD, another indoleamine hallucinogen, and yields similar effects.  Psilocin produces mood changes, altered thought, visual hallucinations, and impaired ego or conceptualizations of the “self”.  The last effect, impaired ego, leads to feelings of depersonalization, which is associated with a person’s “openness” and has been a subject of interest regarding psilocybin’s “psychic” effects.  A curious area of study involving psilocybin is the psychology of religious experiences.  There is a longstanding relationship between psilocybin and religious experiences, as it has been used as an entheogen, recorded as early as the Aztec but probably used ritualistically around the world much earlier.   In one study observing the effects of psilocybin on a religious experience, theology students were led through an experience in a religious setting and it was noted that expectations and preparation played an important part in the experience, and its long-term effects (Perrine, 287).  The conclusion from this study was that the drug was not the cause of a religious experience, but acts as a facilitator, that is, the drug is necessary for such a profound experience, but it is not sufficient (Perrine, 281). 

Works cited

Erowid Psilocybin Mushroom Vault: Maria Sabina: Saint Mother of the Sacred Mushrooms.

Passie, Torsten, Juergen Seifert, Udo Schneider, and Hinderk M. Emrich. "The Pharmacology of Psilocybin." Addiction Biology 7.4 (2002): 357-64. Print.

Perrine, Daniel M. The Chemistry of Mind-altering Drugs: History, Pharmacology, and Cultural Context. Washington, DC: American Chemical Society, 1996. Print.

Spinella, Marcello. The Psychopharmacology of Herbal Medicine: Plant Drugs That Alter Mind, Brain, and Behavior. Cambridge, MA: MIT, 2001. Print.

Umbricht, Daniel., Vollenweider, et al. Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia. Neuropshycopharmacology, 2003, 28, 179-181. doi:10.1038/sj.npp.1300005