When dealing with pharmaceuticals, it’s widely accepted that the product available on the shelf is guaranteed to contain a defined number of doses, and each dose has a defined quantity of the active substance. This stands in stark contrast to the inherent variability found in nature, where apples vary in size, grapes in color, and coffee beans in caffeine content. This natural variability is further complicated by differences in growth conditions, from one plant to another, one crop to the next, and from year to year. If the goal is to make natural products into drugs, how do manufacturers ensure consistency in these naturally occurring products?
With natural psychedelics like psilocybin-containing mushrooms, mescaline-containing cacti, or even 5-MeO-DMT-containing bufo toads, considering the variability of these substances becomes particularly crucial. This is because these active ingredients can induce potent psychological effects even at extremely low doses. To make these potentially therapeutic substances practical for widespread use, it’s essential to ensure a consistent dosage of the active substance, down to the milligram level. The unprocessed forms of these plants and animal sources simply cannot provide the consistency, nor the dosage control, to make them viable therapeutic tools on their own.
For hundreds, and possibly thousands, of years, Psilocybe cubensis mushrooms have been ingested in their raw, dried state. Recreational users commonly consume these dried mushrooms, sometimes portioning them into ‘stems’ and ‘caps’ to control the dosage they receive. On average, some of the most prevalent strains of these mushrooms contain approximately 0.5% to 1% psilocybin by dry weight. However, from one mushroom to another, this psilocybin content can fluctuate by up to four to five times. This means that a person consuming one gram of dried mushrooms might ingest 5 mg of psilocybin on one occasion, and from the same batch of dried mushrooms, another individual could ingest 10 mg of psilocybin on another occasion. While the absolute difference in psilocybin quantity consumed is relatively small (just a 5 mg difference), at these dosages, the effects of these two distinct doses could be significantly different.
Both the illicit and legal psychedelic mushroom industries have attempted to address this issue by transforming mushrooms into a uniform powder and subsequently measuring the psilocybin content for each “batch” to determine the precise psilocybin dose per gram of powder. While this method can be effective, it represents a quantified product, not a standardized one. The distinction lies in the fact that for the quantified product to deliver the correct dosage of psilocybin, each batch must undergo measurement, and the administered powder amount would vary based on the batch results. This approach is a temporary fix to the problem, as the final product can never achieve true consistency. People who consume these products consistently ingest different product quantities, potentially impacting their experience due to variations in metabolism, increased nausea, or discomfort associated with consuming varying amounts of powder.
A more definitive solution to the problems of consistency in these mushrooms comes in the form of extraction, concentration, measurement and then dilution. This allows for the psilocybin content to be controlled into a solid dosage form that is the same size and content every time. For most clinical trials, the typical dose used is 25 mg of psilocybin per dose, usually in a hard shell capsule. With an extracted standardized natural product, a small size 2 hardshell capsule containing an equivalent extract administering 25 mg of psilocybin is possible, whereas using mushroom powder, a patient would need to consume between 2-6 g of mushroom powder, a different amount every time.
The natural drug extraction landscape
The pharmaceutical industry exhibits reluctance to embrace the botanical drug model, despite the availability of approved botanical drugs for US consumers like Veregen® and Mytesi®. The count of botanical Investigational New Drugs (INDs) has consistently risen from 1984 to 2018, and it’s anticipated that this sector will continue to grow due to the general preference for natural compounds over synthetic alternatives.
Psychedelics present an almost ideal case for botanical drug candidates, given that many of these substances have long been used by the broader population in their natural forms rather than their synthetic counterparts. These substances do indeed induce psychological effects, but whether their therapeutic potential will be fully realized remains to be seen. For example, at Filament Health, we have entered naturally-extracted psilocybin drug candidates into several FDA clinical trials and hope to determine their efficacy for treating a number of mental health conditions.
So, where is the market headed?
Predicting the future direction of the market for these substances is challenging, given their federal-level regulation. Over the past five years, there have been significant shifts in the landscape of psychedelics. This began when the FDA granted breakthrough status to psilocybin in 2018, prompting many jurisdictions to move away from strict scheduling of these substances toward more medicinal access models. In January 2022, Health Canada modified its Special Access Program to include psilocybin, while Oregon started permitting psilocybin therapy access in January 2023. Australia’s Authorized Prescriber program also commenced in July 2023. These developments collectively suggest that psilocybin and “magic mushrooms” are increasingly being viewed as more than just a recreational choice, potentially offering solutions to the growing mental health and drug crises observed in much of the Western world.
Ryan Moss
Ryan Moss has over ten years of research and development experience in all aspects of industrial process chemistry and the scale-up of extraction, purification, and standardization of natural products. Ryan has brought more than 20 products from bench-scale to commercialized products in the food, cosmetic and nutraceutical industries. This includes 19 patents involving commercial-scale extraction, purification processes, composition of matter, as well as drug delivery. In his role as CSO at Filament Health, Ryan oversees CMC development, IP generation, as well as manufacturing activities. Ryan holds a Bachelor of Science in Chemistry and a Master of Science in Chemistry, both from the University of British Columbia.
