What is Psilocybin?

The Historical Journey of Psilocybin

• The history of hallucinogenic mushrooms, or 'magic mushrooms', is a journey spanning over 3000 years. Originating in Mexico, these mushrooms were introduced to Western science in 1957 by Robert G. Wasson and later systematically classified by Roger Heim. The main psychedelic ingredients of these mushrooms are Psilocybin and Psilocin, with content varying between 0.2% and 1% of the dry weight. This historical overview provides insight into how Psilocybin has been perceived and used over the millennia.
  
  
• In the 1960s, Psilocybin was extensively used in experimental research on mental disorders and psychotherapy. However, after its popularity as a recreational drug, it was classified as a Schedule I drug in 1970, leading to a halt in human experiments. In the late 1990s, interest in Psilocybin research was revived, pushing the boundaries of our understanding of this compound.

Chemical Characteristics of Psilocybin

• Psilocybin and its active metabolite, Psilocin, belong structurally to the tryptamine/indolamine group of hallucinogens, which are related to serotonin. The substitution of the indole core at position 4 plays a significant role in its hallucinogenic properties. This chemical structure is crucial to understanding how Psilocybin interacts with the brain, altering perception and mood.

Metabolism and Pharmacokinetics of Psilocybin

• Upon ingestion, Psilocybin is rapidly dephosphorylated to Psilocin in the intestinal mucosa. About 50% of the total volume of Psilocin is absorbed from the gastrointestinal tract. After systemic administration, tissue phosphatases play a similar role, with the kidneys being among the most active. This metabolic process is essential to understand the effects of Psilocybin on the human body.

Pharmacodynamics of Psilocybin

• Psilocybin and Psilocin primarily exhibit agonistic activity on serotonin 5HT2A/C and 5HT1A receptors. Interestingly, the affinity of Psilocybin for human 5HT2A receptors is significantly higher than in rats. This receptor interaction is key to understanding the psychedelic effects of Psilocybin.

Behavioral Effects and Dosage

• The behavioral effects of Psilocybin and Psilocin in animals have been observed in a dosage range of 0.25–10 mg/kg. Clinical studies indicate that the effective oral dose of Psilocybin is 0.045–0.429 mg/kg and 1–2 mg per adult intravenously. Understanding these dosage parameters is important for both therapeutic and research purposes.

Acute Somatic Toxicity of Psilocybin

• According to numerous toxicological and clinical studies, Psilocybin has very low toxicity. It exhibited no specific signs of toxicity in isolated organs of rats and pigs, and it is not neurotoxic. This low toxicity profile makes Psilocybin a subject of interest for medical research.

Risks and Side Effects of Psilocybin

• The safety of using Psilocybin is primarily influenced by personal expectations and the environment. Due to altered perception, hallucinations, and intensified emotions, dangerous behavior can occur during non-medical administration. Understanding these risks is essential for both users and researchers.

EEG and MEG Studies

• Electroencephalography (EEG) and Magnetoencephalography (MEG) studies have documented an increase in rapid activity, a reduction in amplitude, and desynchronization in both primates and humans after the administration of Psilocybin. These studies provide valuable insights into the neurological effects of Psilocybin.

Psilocybin as a Model of Psychosis

• Psychedelics, including Psilocybin, cause complex changes at various levels of the brain, leading to altered states of consciousness. Psilocybin is used as one of the primary acute serotonergic models of psychosis/schizophrenia due to its phenomenological and neurobiological similarities with the disorder. This application as a model offers significant opportunities for research into mental health disorders.

Therapeutic Applications and Recent Clinical Studies

• Psilocybin has shown therapeutic potential in recent clinical studies. It is considered a significant tool for understanding the etiopathogenesis of certain mental illnesses. Thousands of scientific papers published before 1965 described positive results in patients who had taken hallucinogens for therapeutic purposes. Current research continues to discover new therapeutic applications for Psilocybin, making it a promising candidate for future treatments.

Conclusion

• In summary, Psilocybin has strong research and therapeutic potential. It brings key findings about the functioning of the human brain, especially the role of the serotonergic system in complex functions like perception and emotions. Understanding Psilocybin in detail reveals much about the human psyche and potential treatments for various mental health conditions.
  
  

Source:
https://www.sciencedirect.com/science/article/abs/pii/S0924977X13003519