Natural vs. Synthetic Psilocybin: The Potency Problem

March 23, 2022


  • For thousands of years, psychedelics have been used by humans for a variety of reasons – including medicinal use
  • A psychedelic renaissance has begun
  • Many companies are now creating synthetic psychedelics for therapeutic use, however these present many challenges that have yet to be addressed
  • Natural psychedelics may prove to be beneficial over synthetic for reasons including the possibility of the Entourage Effect and consumer preference

A short history of psychedelics

The history of natural psychedelics spans thousands of years.

Psychoactive plants and fungi have shaped religions and been used in cultural ceremonies by non-western peoples all over the world (1). They have been used as an aid during hunting and have been associated with increased information processing and consciousness. Cave paintings from Algeria show the use of psychedelic mushrooms dating back 7000 years!

So why did these powerful substances seemingly disappear for hundreds of years?

Upon contact with indigenous communities, use of psychedelic plants was suppressed by Western colonizers and dismissed for centuries. It wasn’t until 1958 when these substances – and their potential power – were rediscovered by Albert Hofman to be used in therapy. Following a long ban due to political reasons in the 1970s, psychedelic research has resumed at a rapid pace.

The psychedelic renaissance has begun.

mushrooms growing in the Filament Health lab

So if natural psychedelics were used for thousands of years, why are most psychedelic companies developing synthetic variants?

The answer primarily comes down to variable psilocybin content. Psilocybin is complex – magic mushrooms contain many “secondary metabolites” that are present in varying concentrations. Mushrooms are living organisms that have a natural variability in psilocybin content between mushrooms and harvests, even when cultivated in controlled conditions. As a result of this variability, the final dried, consumable-form of magic mushrooms can differ by a magnitude of up to four times! Bigwood and Beug’s (2) research found that psilocin, the pharmacologically active component of psilocybin, increased to its maximum potency by the fourth flush of mushrooms. The previous three batches of mushrooms in that series contained less psilocin and therefore had a lower potency than the fourth, and final, growth. Varying potencies between growths is problematic for two reasons:

  1. Recreational Use: People ingesting mushrooms recreationally have no way of anticipating their psilocybin strength and therefore are more likely to have an unpredictable experience.
  2. Medical Use: Psilocybin with inconsistent levels of hallucinogenic effect cannot be used for therapeutic or medical uses, which require standardized doses.

The solution to this problem has traditionally been the development of synthetic psilocybin, whereby the potency levels can be controlled. Several companies, including Compass Pathways and Mind Medicine, are developing synthetic psilocybin compounds in order to produce consistent and reliable doses for therapy.

However, this may present a missed opportunity.

Synthetic variants could be missing potential additional benefits contained in natural psychedelics. For example, synthetic psychedelics are composed of single-compound molecules, whereas natural psychedelics contain a host of secondary metabolites. Research has found that the presence of these secondary metabolites could contribute to the therapeutic benefit of these substances – a concept termed the “entourage effect”. Additionally, natural psychedelics have been ingested safely by humans for thousands of years, meaning that these natural substances are well tolerated by the human body and therefore safe for future therapeutic use. Lastly, research has shown that consumers show a preference for natural products in regard to medical treatments. Providing the option for natural psychedelic therapy may increase the likelihood of widespread adoption and further the therapeutic benefit of psychedelics.

Synthetic psychedelic compounds solve the problem of varying potency between different natural psychedelic growths – but could there be a better alternative?

mushrooms being cut

The Natural Approach

Filament Health has solved the issue of psilocybin variability by unlocking the ability to produce safe and standardized natural psychedelic medicines. Through its patent-protected processes, Filament has developed extraction, purification, standardization, and stabilization technologies which extract the psychoactive alkaloids from the magic mushroom and standardize them to a precisely known quantity, all while preserving naturally occurring spectrum and ratio of psychoactive alkaloids.

In non-technical terms – each dose created has identical potency!

These natural psychedelics have already been approved for various clinical trials including a Phase 2 microdose study for depression at the University of Toronto, a Phase 1 study for psilocin at the University of California San Francisco and a Phase 1 study for chronic pain and depression with EntheoTech Bioscience.

Through its clinical trials, Filament’s exploration of natural drug development may produce undiscovered benefits such as through the previously mentioned entourage effect. Additionally, these efforts will contribute to the widespread adoption of safe psychedelic medical treatments by consumers and patients in the future.

With psychedelic medicines starting to receive mainstream attention for their therapeutic use, it’s important to be producing medicines that are repeatable, safe, and time-tested. Natural psychedelics may be just what is needed.

About Filament Health:

​​Filament Health is a clinical-stage natural psychedelic drug development company. We believe that safe, standardized, naturally-derived psychedelic medicines can improve the lives of many, and our mission is to see them in the hands of everyone who needs them as soon as possible. Filament’s platform of proprietary intellectual property enables the discovery, development, and delivery of natural psychedelic medicines for clinical development. We are paving the way with the first-ever natural psychedelic drug candidates.


  1. Evans Schultes, Hofmann and Ratsch (1998) Plants of the Gods. Healing Arts Press.
  2. Bigwood, J., Beug, M. (1982). Variation of psilocybin and psilocin levels with repeated flushes (harvests) of mature sporocarps of Psilocybe cubensis (earle) singer. Journal of Ethnopharmacology. 5(3), 287-291.