May 6, 2022
Health Canada published a Notice to Stakeholders today about use of psilocybin mushrooms in clinical trials or as a drug accessed through the Special Access Program (SAP). The Notice clarified, in writing, information that had been previously communicated in webinars and other industry engagement by the regulator earlier in 2022.
For both clinical trial applications and use through the SAP, Natural Psilocybin Products will face hurdles that are avoided by use of synthetic or purified psilocybin as an active pharmaceutical ingredient (API). Additional tryptamines or other compounds present in Natural Psilocybin Products complicate characterization of their API relative to Synthetic Psilocybin Products. The Notice applies equally to clinical use of flood doses and microdoses of psilocybin.
All drug products used in a clinical trial or accessed through the SAP must be manufactured in compliance with good manufacturing practices (GMP). The Notice focused on and clarified regulatory points around drug products manufactured in accordance with GMP, and that include dried psilocybin mushrooms as an API without any extraction or purification of the psilocybin (Natural Psilocybin Products).
The Notice distinguished between Natural Psilocybin Products, and drug products including purified or synthetic psilocybin as API (Synthetic Psilocybin Products). Health Canada confirmed that clinical research of psilocybin lacks good quality research-based evidence on added therapeutic benefits of using Natural Psilocybin Products instead of Synthetic Psilocybin Products. This position is consistent with communications made by Health Canada to SAP applicants requesting access to Natural Psilocybin Products.
For both clinical trials and SAP access, GMP compliance is key. Inconsistency in dosing and impurities throughout anatomical structures (e.g. caps, stems, mycelia, hyphae, scleortia, etc.) may complicate manufacturing Natural Psilocybin Products in compliance with GMP. However, Health Canada remains open to receiving evidence that a Natural Psilocybin Product could meet GMP quality requirements and recognized the possibility that from a clinical perspective, evidence may demonstrate that Natural Psilocybin Products could potentially be equivalent to, or better than, Synthetic Psilocybin Products. As with all effective and ethical clinical assessments, the evidence would speak for itself.
Use of Natural Psilocybin Products in clinical trials or through the SAP requires evidence demonstrating safety and uniformity of the proposed dosage form. Testing of microbiology, aflatoxins, residual pesticides and similar quality controls would be required in addition to usual requirements for Synthetic Psilocybin Products (data specifications, analytical methods, method validation, batch data, stability data, etc.). Species and cultivar used for the API, growing conditions, and extraction and isolation procedures (if applicable), would all have to be provided with the clinical trial application or by the manufacturer identified by a physician in an SAP application. Incidentally, the reference to extraction and isolation is seemingly at odds with Health Canada’s distinction of Natural Psilocybin Products from those based on extraction.
In summary, for both clinical trial applications and the SAP, Natural Psilocybin Products may be considered alongside Synthetic Psilocybin Products, but will be reviewed and held to the same standard. The Notice is a welcome clarification of existing policy and practices. Health Canada has signaled to stakeholders that the regulator is ready and willing to work with drug development companies trialing Natural Psilocybin Products, as well as practitioners requesting SAP access to Natural Psilocybin Products.
Health Canada Notice clarifies that Natural Psilocybin Products for use in clinical trial or SAP applications will be held to the same standards that would be applied to Synthetic Psilocybin Products. Furthermore, it is clear from the Notice that the regulator is looking for evidence that Natural Psilocybin Products carry a stronger safety and efficacy profile than a Synthetic Psilocybin Product.
The Notice also referenced a general information webpage about psilocybin and psilocin, confirming that “Magic mushrooms may cause heightened emotions and senses and people may feel happy and creative. They may laugh or giggle a lot and experience a sense of mental and emotional clarity.” These are certainly side effects, or perhaps part of the therapeutic effect, to watch for.