Pharmacology
Psilocybin is rapidly dephosphorylated in the body to psilocin which then acts as a partial agonist at the 5-HT2A serotonin receptor in the brain where it mimics the effects of serotonin (5-HT). Psilocin is an 5-HT1A and 5-HT2A/2C agonist.
Toxicity
The toxicity of psilocybin is relatively low; in rats, the oral LD50 is 280mg/kg, approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5mg/kg (however rabbits are extremely intolerant to the effects of most psychoactive drugs). The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has never been documented. Psilocybin makes up roughly 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms of dried mushrooms, or 17 kilograms of fresh mushrooms, would be required for a 60kg person to reach the 280mg/kg LD50 rate of rats.
Physiology
Psilocybin is absorbed through the lining of the mouth and stomach. Effects begin 10–40 minutes after ingestion of psilocybin-containing mushrooms, and last from 2–6 hours depending on dose, species, and individual metabolism.[21] A typical recreational dosage is from 10–50 mg psilocybin. However, a very small number of people are unusually sensitive to psilocybin's effects, where a normally threshold dose of around 2 mg of psilocybin can result in effects usually associated with medium and high doses. Likewise, there are some people who require relatively high doses of psilocybin to gain low-dose effects. Individual brain chemistry and metabolism play a large role in determining a person's response to psilocybin.
Psilocybin is metabolized mostly in the liver where it becomes psilocin. It is broken down by the enzyme monoamine oxidase. MAO inhibitors have been known to sustain the effects of psilocybin for longer periods of time; people who are taking an MAOI for a medical condition or are seeking to potentiate the mushroom experience may experience highly potentiated effects.
Mental and physical tolerance to psilocybin builds and dissipates quickly. Taking psilocybin more than three or four times in a week (especially on consecutive days) can result in diminished effects. Tolerance dissipates after a few days, so frequent users often keep doses spaced five to seven days apart to avoid the effect.
Psilocybin is rapidly dephosphorylated in the body to psilocin which then acts as a partial agonist at the 5-HT2A serotonin receptor in the brain where it mimics the effects of serotonin (5-HT). Psilocin is an 5-HT1A and 5-HT2A/2C agonist.
Toxicity
The toxicity of psilocybin is relatively low; in rats, the oral LD50 is 280mg/kg, approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5mg/kg (however rabbits are extremely intolerant to the effects of most psychoactive drugs). The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has never been documented. Psilocybin makes up roughly 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms of dried mushrooms, or 17 kilograms of fresh mushrooms, would be required for a 60kg person to reach the 280mg/kg LD50 rate of rats.
Physiology
Psilocybin is absorbed through the lining of the mouth and stomach. Effects begin 10–40 minutes after ingestion of psilocybin-containing mushrooms, and last from 2–6 hours depending on dose, species, and individual metabolism.[21] A typical recreational dosage is from 10–50 mg psilocybin. However, a very small number of people are unusually sensitive to psilocybin's effects, where a normally threshold dose of around 2 mg of psilocybin can result in effects usually associated with medium and high doses. Likewise, there are some people who require relatively high doses of psilocybin to gain low-dose effects. Individual brain chemistry and metabolism play a large role in determining a person's response to psilocybin.
Psilocybin is metabolized mostly in the liver where it becomes psilocin. It is broken down by the enzyme monoamine oxidase. MAO inhibitors have been known to sustain the effects of psilocybin for longer periods of time; people who are taking an MAOI for a medical condition or are seeking to potentiate the mushroom experience may experience highly potentiated effects.
Mental and physical tolerance to psilocybin builds and dissipates quickly. Taking psilocybin more than three or four times in a week (especially on consecutive days) can result in diminished effects. Tolerance dissipates after a few days, so frequent users often keep doses spaced five to seven days apart to avoid the effect.
Pharmacology of psilocybin.pdf