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Psilocybin is a substance found in a number of mushroom species that can be ingested to
cause psychoactive effects.
It is considered a psychedelic or hallucinogenic drug with some similarities to LSD in terms
of effects.
Psilocybin itself is not thought to be very psychoactive, but soon after it is ingested
it is metabolized into a substance called psilocin, which is highly psychoactive.
Psilocybin is thus considered a prodrug, or a substance that is inactive until converted
into an active drug after administration.
Although we have some understanding of the activity of psilocin in the brain, it is not
fully understood how this activity leads to the subjective experiences people have while
taking psilocybin.
Regardless, it is thought that psilocin’s activity at a subtype of serotonin receptor
known as the 5-HT2A receptor is critical to the drug’s psychedelic effects.
Psilocin is thought to act as a partial agonist at the 5-HT2A receptor, which means that it
binds to the 5-HT2A receptor and causes a response that is a fraction of what the natural
ligand, serotonin, does.
Psilocin also interacts with other targets, like other serotonin receptor subtypes, some
subtypes of dopamine, histamine, and adrenergic receptors, and the serotonin transporter.
The role of these other targets in the effects of psilocybin, however, is not very clear.
Like many other psychedelic drugs, repeated administration of psilocybin over multiple
days leads to rapid tolerance and substantially reduced effectiveness.
This tolerance is thought to be associated with the down-regulation, or decrease in number,
of 5-HT2A serotonin receptors.
Psilocybin also exhibits cross-tolerance with LSD, meaning that if someone develops tolerance
to one of these drugs, they may display tolerance to the other---regardless of their history
with the other drug.
Psilocybin, however, is not generally considered to be addictive and is thought to be safe
in terms of its effects on the body.