Psilocybin & Psilocin: Comprehensive Synthesis Guide

The Synthesis of Psilocybin and Psilocin: A Comprehensive Guide

Psilocybin and psilocin are naturally occurring psychedelic compounds found in certain species of mushrooms. They are known for their mind-altering effects and have been used for centuries in various cultures for spiritual and therapeutic purposes. While these compounds can be found in nature, some individuals and researchers are interested in synthesizing them for a variety of reasons, including scientific study and medical applications. In this comprehensive guide, we will delve into the synthesis of psilocybin and psilocin, their pharmacokinetics and pharmacodynamics, clinical effects, methods of administration and dosages, as well as the reagents, equipment, and laboratory requirements for their synthesis.

Synthesis of Psilocybin


Psilocybin is a naturally occurring prodrug of psilocin, meaning it is converted to psilocin in the body after ingestion. The synthesis of psilocybin involves several chemical reactions to create this psychoactive compound.


To synthesize psilocybin, the following reagents are required:

  • Tryptamine: The core structure for psilocybin synthesis.
  • Diethylamine: Used to protect the amino group in tryptamine.
  • Di-tert-butyl dicarbonate (Boc2O): A reagent for protecting the hydroxyl group.
  • Dimethyl sulfate (DMS): Used for methylation.
  • Phosphoryl chloride (POCl3): Essential for creating the phosphate ester.
  • Sodium hydroxide (NaOH): Used for deprotection.
  • Ethanol and other organic solvents: For various reaction steps.


  1. Protection of Tryptamine: Tryptamine is first reacted with diethylamine and Boc2O to protect the amino group.
  2. Methylation: The protected tryptamine is then methylated using DMS.
  3. Phosphorylation: Phosphorylation is achieved by reacting the methylated compound with POCl3.
  4. Deprotection: The Boc group is removed using NaOH to yield psilocybin.

Synthesis of Psilocin


Psilocin is the active form of psilocybin and is directly responsible for the psychedelic effects experienced. The synthesis of psilocin involves the dephosphorylation of psilocybin.


To synthesize psilocin, the following reagents are required:

  • Psilocybin: This can be obtained either from natural sources or synthesized as mentioned earlier.
  • Hydrochloric acid (HCl): Used to remove the phosphate group.


  1. Hydrolysis: Psilocybin is hydrolyzed by adding HCl, effectively removing the phosphate group and yielding psilocin.

Pharmacokinetics and Pharmacodynamics


  • Oral Consumption: Psilocybin and psilocin are typically ingested orally. Psilocybin is converted to psilocin in the stomach by enzymatic dephosphorylation.


  • Blood-Brain Barrier: Psilocin readily crosses the blood-brain barrier due to its structural similarity to serotonin, a neurotransmitter.


  • Liver Metabolism: Both psilocybin and psilocin are metabolized in the liver by various enzymes.


  • Renal Excretion: Metabolites of psilocin are excreted primarily through urine.

Clinical Effects

  • Psychedelic Experience: Psilocybin and psilocin induce altered states of consciousness, including visual hallucinations, altered perception of time, and enhanced introspection.
  • Mood Enhancement: Many users report positive mood changes, including feelings of joy and interconnectedness.
  • Therapeutic Potential: Emerging research suggests potential therapeutic applications for conditions like depression, anxiety, and PTSD.

Methods of Administration and Dosages

  • Oral Ingestion: Typically consumed in dried mushroom form or as capsules containing synthetic psilocybin.
  • Dosages: Dosages vary widely depending on the individual and the desired experience. Common doses range from 1 to 5 grams of dried mushrooms, with synthetic psilocybin doses measured in milligrams.

Laboratory Requirements

  • Reagents: High-quality reagents and chemicals for synthesis, including those listed earlier.
  • Equipment: Standard laboratory equipment, including glassware, heating apparatus, and pH meters.
  • Safety Measures: Adequate safety measures, including fume hoods and personal protective equipment.


The synthesis of psilocybin and psilocin offers insights into the chemical processes behind these fascinating compounds. While their psychedelic effects have been a subject of interest for many, it's essential to emphasize responsible use and adherence to legal regulations where applicable. The evolving field of psychedelic research continues to uncover the potential therapeutic benefits of these substances, shedding light on new possibilities for mental health treatment and human consciousness exploration.

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