Mushroom Metabolism: Understanding The Process And Its Intricacies

Magic mushrooms, or psilocybin mushrooms, are naturally occurring psychedelic drugs that can induce hallucinations and alter a person's thinking, sense of time, and emotions. The active ingredient in magic mushrooms, psilocybin, is metabolized by the body into psilocin, which is the chemical responsible for the psychoactive properties of the drug. Psilocybin is dephosphorylated by alkaline phosphatase to psilocin, which then binds to receptors in the brain. The duration of the psychedelic effects depends on factors such as dosage and body weight. Mushrooms also contain biologically active metabolites and have been used in traditional medicine for their various health benefits.

How does the body metabolise psilocybin?

Psilocybin, the naturally occurring psychedelic found in certain types of mushrooms, is metabolised by the body in the following way. When psilocybin is ingested, it is absorbed into the bloodstream through the stomach and intestine. It then travels to the liver, where it is converted into psilocin through the removal of a phosphate group from the organic compound (psilocybin) by hydrolysis. This process is called dephosphorylation and is facilitated by enzymes called alkaline phosphatase or alkaline phosphates. Psilocin is the active compound that causes the psychedelic effects associated with magic mushrooms. It is about 1.4 times more potent than psilocybin due to its lower molecular weight.

Psilocin then interacts with receptors in the brain, specifically acting as an agonist or partial agonist at 5-hydroxytryptamine (5-HT)2A subtype receptors. This interaction results in the various physiological and psychological effects commonly associated with psilocybin ingestion, such as hallucinations, perceptual changes, altered thinking, and emotional responses. The duration of these effects typically lasts between 4 to 8 hours, depending on factors such as dosage, body weight, fat percentage, metabolism rate, and the psilocybin and psilocin content of the mushrooms.

After the initial psychedelic experience, psilocin undergoes further metabolism. It is broken down by the enzyme monoamine oxidase into O-Glucoronide and 4-Hydroxy-indoline-3-acetaldehyde. O-Glucoronide is the main urinary metabolite of psilocin and is clinically and forensically relevant in diagnosis. 4-Hydroxy-indoline-3-acetaldehyde is further metabolised into 4-Hydroxy-indole-3-acetic acid and 3-Hydroxytryptophole.

It is important to note that the use of magic mushrooms can vary greatly in effect from person to person. Factors such as mood, environment, previous encounters with psychedelic drugs, and expectations can influence the overall experience. Additionally, magic mushrooms can sometimes lead to negative experiences or "bad trips," and in rare cases, they may result in life-threatening symptoms if a large amount or a strong batch is consumed.

Psilocybin's transformation into psilocin

Psilocybin, the naturally occurring psychedelic found in certain types of mushrooms, is metabolised in the body to induce brain effects. When psilocybin is taken, it is converted in the body to psilocin, which is the chemical with psychoactive properties. Psilocybin is a prodrug of psilocin, meaning it is biologically inactive but quickly converted by the body to psilocin.

Psilocybin is transformed into psilocin by dephosphorylation mediated via phosphatase enzymes. Dephosphorylation is the removal of a phosphate group from an organic compound (in this case, psilocybin) by hydrolysis. Hydrolysis is the chemical reaction by which a water molecule ruptures the chemical bond, thus separating the phosphate group. Psilocybin is dephosphorylated into its active form, psilocin, in the body. Psilocybin is primarily dephosphorylated by alkaline phosphatase to the active metabolite psilocin.

The transformation of psilocybin into psilocin occurs in the liver, and psilocin then binds to receptors in the brain. The psychedelic experience lasts anywhere from 4 to 8 hours, depending on factors such as dosage and the amount of psilocybin and psilocin in the mushrooms. The effects of magic mushrooms usually begin within 30 minutes when eaten, or within 5–10 minutes when taken as a soup or tea. Psilocybin's effects can be subjectively perceived at a dose as low as 3 mg per 70 kg body weight.

The role of alkaline phosphatase

Mushrooms are metabolised in the human body through a process that involves the liver and the intestine. The key ingredient in magic mushrooms, psilocybin, is converted in the body to psilocin, which is the chemical with psychoactive properties. Psilocybin is transformed (dephosphorylated) to psilocin through the action of enzymes called alkaline phosphatases.

Alkaline phosphatase is an enzyme that plays a crucial role in the metabolism of mushrooms, specifically in the dephosphorylation of psilocybin to psilocin. This process involves the removal of a phosphate group from the psilocybin molecule by hydrolysis. Hydrolysis is a chemical reaction where a water molecule ruptures the chemical bond, separating the phosphate group from the rest of the molecule.

Furthermore, alkaline phosphatase has been implicated in bone metabolism. Studies have shown that extracts from the mushroom Pleurotus eryngii increased alkaline phosphatase activity in osteoblasts and positively impacted bone mineral density.

In summary, alkaline phosphatase plays a vital role in the metabolism of mushrooms, particularly in the conversion of psilocybin to its active form, psilocin. Additionally, it has been linked to assessing liver damage in mushroom poisoning cases and positively influencing bone metabolism.

Psilocybin's effects on the liver

Psilocybin, the naturally occurring psychedelic found in certain types of mushrooms, is metabolised in the liver and intestines. When psilocybin is consumed, it is converted in the body to psilocin, the chemical with psychoactive properties. Psilocybin is transformed (dephosphorylated) into its active form, psilocin, through the action of enzymes called alkaline phosphatases. Psilocybin is a prodrug of psilocin, meaning the compound itself is biologically inactive but is quickly converted by the body to psilocin.

Psilocybin is usually ingested orally, and its onset is about 20 to 50 minutes, with peak effects occurring after around 60 to 90 minutes. The duration of psilocybin's effects is typically between 4 and 8 hours, depending on dosage and other factors such as body weight, fat percentage, and metabolism rate.

Psilocybin's effects on the body include perceptual changes, such as visual and auditory hallucinations, as well as changes in heart rate, blood pressure, and stretch reflex. Psilocybin can also cause adverse reactions such as nausea, vomiting, and panic attacks. However, a study found that administration of gradually increasing dosages of psilocybin daily for 21 days had no measurable effect on electrolyte levels, blood sugar levels, or liver toxicity tests. This suggests that psilocybin does not have significant toxic effects on the liver, at least in the short term.

While psilocybin use rarely results in life-threatening symptoms, it is important to note that it can affect everyone differently. The use of psilocybin mushrooms may be associated with an increased risk of negative experiences, such as a "'bad trip'" or flashbacks involving previous psilocybin experiences. These flashbacks can be disturbing and can occur weeks, months, or even years after the last use of psilocybin.

The pharmacological effects of mushroom metabolites

Mushrooms have been used traditionally in herbal medicine and are now being studied for their pharmacological effects. Some mushrooms contain metabolites with drug-like structures, making them a potential source of new medicines. The metabolites in mushrooms have been found to have antioxidant, antifungal, cytotoxic, and antineurodegenerative properties. For example, the Coriolus versicolor mushroom has pharmacologically active secondary metabolites that belong to small molecular weight compounds, in addition to minerals and major macromolecules such as carbohydrates, lipids, and proteins.

One of the most well-known pharmacological effects of mushroom metabolites is their ability to induce a psychedelic experience. Psilocybin, the active ingredient in magic mushrooms, is metabolized by the body into psilocin, which is the compound responsible for the psychedelic effects. Psilocybin is first dephosphorylated into psilocin in the acidic environment of the stomach or through the action of alkaline phosphatase (ALP) and non-specific esterases in tissues and fluids. Psilocybin can also be metabolized by the liver. Psilocin is then further metabolized by monoamine oxidase (MAO), specifically monoamine oxidase A (MAO-A), into 4-hydroxyindole-3-acetaldehyde (4-HIAL or 4-HIA). 4-HIAL is then further oxidized into one of two compounds: 4-hydroxyindole-3-acetic acid (4-HIAA) or 4-hydroxytryptophol (4-HTOL or 4-HTP). The psychedelic experience typically lasts from 4 to 8 hours, depending on factors such as dosage and individual differences.

The pharmacological effects of psilocybin include perceptual changes, such as visual and auditory hallucinations, changes in heart rate and blood pressure, nausea, tremors, and dysmetria. Psilocybin's sympathomimetic or cardiovascular effects, including increased heart rate and blood pressure, are usually mild. However, temporary increases in blood pressure can be a risk factor for users with pre-existing hypertension. Psilocybin's effects can also vary depending on a person's mood, expectations, and environment. Some people may experience negative effects or a "bad trip," and flashbacks involving previous magic mushroom experiences can occur weeks, months, or even years later.

In addition to their psychedelic effects, psilocybin mushrooms have been used in Indigenous American cultures and Western group therapies for their perceived spiritual and therapeutic benefits. Some scholars suggest that the mystical experiences induced by psilocybin are similar to those achieved through non-drug techniques such as meditation. Psilocybin has been studied for its potential therapeutic effects in treating anxiety and paranoia. However, the safety and efficacy of psilocybin and other psychedelic mushrooms are still being evaluated, and more research is needed to understand their long-term effects fully.

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