The therapeutic use of psilocybin, the active hallucinogenic compound in certain mushrooms, is gaining global attention for its potential to treat mental health conditions such as depression, PTSD, and anxiety. As demand for psilocybin rises, scientists have developed a synthetic version of the compound, but how does it compare to the natural form found in magic mushrooms?

What is psilocybin?

Psilocybin is the psychoactive component in “magic mushrooms,” a term for over 180 species of fungi that have been used for centuries in indigenous ceremonies. When consumed, psilocybin is converted into psilocin in the body, which interacts with serotonin receptors, particularly the 5-HT2A receptor, causing alterations in perception, mood, and cognition. Its ability to induce powerful psychological experiences, often described as ego dissolution or expanded consciousness, has made it a subject of research for its potential to treat mental health disorders.

In recent years, synthetic psilocybin has been created to meet growing demand and to facilitate controlled research and therapeutic applications. However, a major question remains: is synthetic psilocybin as effective as its natural counterpart?

How is synthetic psilocybin made?

Synthetic psilocybin is produced in a laboratory setting through a chemical process that replicates the molecular structure of the natural compound. This lab-based production offers precise control over the purity and dosage of the substance, which is a significant advantage in research and clinical settings.

“Some argue that synthetic psilocybin can offer a more controlled therapeutic experience, reducing the risks associated with natural variability,” said Gabe Charalambides, CEO of Odyssey, one of the first U.S. providers of guided psilocybin experiences, though at his facility, they choose to exclusively go natural for a number of reasons, among them the fact that it is possible to accurately test and verify the amount of natural psilocybin found in mushrooms.

Bassem Mostafa, the lead market analyst at Globemonitor, further adds that “synthetic psilocybin offers a higher level of consistency in dosing and purity compared to its natural counterpart.” He explains that the natural variability of mushroom-derived psilocybin, affected by environmental factors like species variation and harvest timing, makes synthetic psilocybin an attractive alternative for medical use.

The consistency of synthetic psilocybin has made it a preferred choice in clinical trials, ensuring that participants receive the exact same dosage. This accuracy is vital for developing new psychiatric medications based on psilocybin, as scientists explore how to tailor its effects for specific mental health conditions like depression and PTSD.

The therapeutic use of natural and synthetic psilocybin

Both natural and synthetic psilocybin interact similarly with the brain’s serotonin receptors, leading to the altered states of consciousness associated with psychedelics. Studies have shown that both forms can promote neuroplasticity, the brain’s ability to rewire itself, which is crucial for treating mental health disorders. However, recent research suggests that natural psilocybin may have an edge over synthetic psilocybin in certain therapeutic applications.

A study conducted by the Hebrew University Hadassah Medical Center found that natural psilocybin extracts had a more potent and long-lasting effect on synaptic plasticity than synthetic psilocybin in mice1. This enhanced neuroplasticity is crucial for the treatment of psychiatric disorders, as it allows the brain to form new neural connections, offering a path to recovery for patients with treatment-resistant conditions such as depression and OCD.

This difference may be attributed to the “entourage effect,” as Charalambides describes, a phenomenon where multiple compounds in a natural extract work together to produce a stronger effect than any single compound alone. Magic mushrooms contain additional psychoactive compounds, such as baeocystin and norbaeocystin, which may contribute to the overall therapeutic experience.

While synthetic psilocybin offers consistency, some believe that the holistic nature of natural mushrooms provides a more effective therapeutic experience. “There’s a ceremonial aspect to the ingestion of natural mushrooms that doesn’t exist for synthetic,” Charalambides explains, emphasizing the cultural and aesthetic preference for natural psilocybin in therapeutic settings.

Differences in therapeutic application

In therapeutic settings, both natural and synthetic psilocybin are used in guided sessions designed to help individuals explore and resolve deep emotional or psychological issues. Psilocybin-assisted therapy typically involves consuming the compound in a safe, controlled environment under the supervision of a therapist or guide. The aim is to facilitate introspection, emotional release, and, in many cases, a shift in perspective that can lead to lasting improvements in mental health.

One significant advantage of synthetic psilocybin in these settings is its predictability. With synthetic psilocybin, therapists can administer a precise dose, which may reduce the risk of negative reactions. This is particularly important in research, where controlled variables are essential. However, natural psilocybin is also rigorously tested for potency and purity before being used in therapeutic settings like those offered by Odyssey in Oregon. Mostafa’s research indicates that synthetic psilocybin reduced variability in patient outcomes by as much as 30%, largely due to its purity and controlled production process.

Despite these benefits, the entourage effect of natural psilocybin may provide an edge for those seeking a more comprehensive therapeutic experience. Natural psilocybin’s unique combination of compounds may lead to greater neuroplasticity, as shown in the study at Hebrew University, which could result in more significant and longer-lasting therapeutic effects.

Which is better?

The debate over natural versus synthetic psilocybin is far from settled. Both forms have proven therapeutic potential, offering significant benefits for mental health treatment. Synthetic psilocybin’s consistency and precision make it ideal for clinical research and controlled therapeutic settings, yet natural psilocybin can also be precisely dosed and may offer additional benefits through the entourage effect and its cultural and ceremonial significance.

As research continues to evolve, it’s likely that both natural and synthetic psilocybin will play important roles in the future of mental health treatment. The choice between the two may ultimately come down to personal preference, therapeutic goals, and the specific context in which the compound is being used. What remains clear is that psilocybin, in any form, has the potential to revolutionize mental health care and offer new hope to those suffering from treatment-resistant conditions.

References

  1. Shahar, Orr, Alexander Botvinnik, Amit Shwartz, Elad Lerer, Peretz Golding, Alex Buko, Ethan Hamid et al. “Effect of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract on Molecular and Metabolic Profiles in Mouse Brain.” Molecular Psychiatry 29, no. 7 (2024): 2059-2073. https://doi.org/10.1038/s41380-024-02477-w. ↩︎