Psilocybin Pharmacokinetics and Metabolism

Question 1

What is metabolism?

Answer 1

Metabolism refers to the set of life-sustaining chemical reactions in organisms that enable them to grow, reproduce, maintain their structures, and respond to their environments. These processes are broadly categorized into two types:

1. Catabolism: The breakdown of molecules to obtain energy. This involves breaking down larger, complex molecules into smaller, simpler ones, releasing energy in the process.
2. Anabolism: The synthesis of all compounds needed by the cells. It involves building up smaller molecules into larger, complex ones, which is an energy-consuming process.

Question 2

What is the process of psilocybin conversion to its active form in the body, and which enzyme is responsible for this transformation?

Answer 2

Psilocybin is rapidly dephosphorylated (removal of a phosphate group from a molecule) to an active metabolite = Psilocin. This happens in the liver, gastrointestinal tract.

Alkaline phosphates (ALP) is responsible for the enzymatic transformation of psilocybin to psilocin.

Question 3

What is the reason for considering psilocybin a prodrug, and what happens to it in the body after ingestion?

Answer 3

After ingestion, no psilocybin is detected in the blood plasma or urine. For this reason psilocybin is considered a prodrug.

Prodrug = It needs to be converted to the active molecule, psilocin for a person to feel its effect.

Question 4

What is Pharmacokinetics?

Answer 4

Pharmacokinetics is the branch of pharmacology concerned with the movement of drugs within the body. It covers how a drug is absorbed, distributed, metabolized, and eventually excreted from the body. The four key processes involved in pharmacokinetics, often summarized by the acronym ADME, are:

1. Absorption: This refers to how a drug enters the bloodstream after administration. Factors like the route of administration (oral, intravenous, etc.), the rate of absorption, and the extent to which a drug is absorbed are studied.
2. Distribution: Once in the bloodstream, a drug is distributed throughout the body. This includes understanding how the drug moves through bodily fluids and tissues, and how it binds to proteins in the blood.
3. Metabolism: This involves the chemical alteration of the drug in the body, usually in the liver. Metabolism can change a drug into an active or inactive form and often prepares the drug for excretion.
4. Excretion: The final process is the removal of the drug from the body, typically through the kidneys (urine) or in the feces. Excretion rates help determine how long a drug and its metabolites remain in the system.

Question 5

What does research indicate about the pharmacokinetics of psilocin at oral doses?

Answer 5

According to the research on the topic, oral doses tested of psilocybin (0.3 - 0.6 mg/kg), psilocin exhibited linear Pharmacokinetics.

Question 6

Outline the linear Pharmacokinetics of psilocybin?

Answer 6

After oral administration of psilocybin on an empty stomach, psilocin is detectable in significant amounts in plasma within 20- 40 minutes.

Psilocybin has a bioavailability of about 50% = only about half of the amount ingested is absorbed.

Psychological effects occur when plasma levels reach 4-6 ug/ml. Plasma concentrations peak at approximately 80 minutes.

The half-life of psilocin is roughly 2-3 hours, then the concentration curve slowly declines until ending around 360 minutes.

Overal effects last three to six hours.

Question 7

Discussing what happens in the body when you take psilocybin with a patient.

Answer 7

Let’s talk about what happens in your body when you take psilocybin, especially on an empty stomach. Within about 20 to 40 minutes, psilocin, which is what psilocybin turns into in your body, starts to show up in your blood. But keep in mind, only about half of what you take actually gets absorbed - this is what we call ‘bioavailability’.

You start to feel the effects when the level of psilocin in your blood hits a certain point, around 4-6 units per milliliter, which usually happens about 80 minutes after you take it. Psilocin has a ‘half-life’ of about 2 to 3 hours, meaning that’s how long it takes for its amount in your blood to drop by half. The level gradually decreases over about 6 hours, which is also how long the overall effects usually last. So, from start to finish, the experience lasts between three to six hours.”

Question 8

The process of excretion of Psilocin.

Answer 8

After you take psilocybin, your liver works on it to break it down into other substances, called metabolites. When you take it orally, less than 4% of one of these substances, psilocin, ends up in your urine.

This is especially important for people with liver or kidney problems because we don’t fully understand how psilocybin affects them yet.

After you take psilocybin, the highest amount of psilocin in your urine will be within 2 to 4 hours. By 24 hours, it usually can’t be detected in the urine anymore.