2-Minute on the Neuroscience of Psilocybin

What is Psilocybin?

Psilocybin is a substance found in a number of mushroom species that can be ingested to cause psychoactive effects. Although psilocybin is thought to have minimal (if any) psychoactive effects, upon ingestion it is rapidly metabolized into a highly psychoactive substance called psilocin. In the above video, the effects of psilocin on the brain are discussed.

Where to find Psilocybin

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 its effects.

Psilocin and Psilocybin

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.

What does it do?

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 the 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 different 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 magic truffles 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 the 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. These types of Psychedelics are, however, not generally considered to be addictive. On top of that is thought to be safe in terms of its effects on the body.

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