Tolerance in psilocybin use refers to the body’s reduced response to the substance after repeated exposure, requiring higher doses to achieve the same effects. This occurs as the brain’s serotonin receptors, particularly 5-HT2A, become less sensitive to psilocin, the active compound in psilocybin. Tolerance develops quickly, often within a few days of consecutive use, but typically resets after a break, completely in about 3 weeks. This phenomenon encourages spaced-out usage to maintain effectiveness and minimize potential risks.