Notice to stakeholders: Considerations regarding the proposed use of psilocybin mushrooms in clinical trials, or as a drug accessed through the Special Access Program (SAP)

May 6, 2022
Our file number: 22-105312-974

Purpose

Health Canada is aware of the growing interest in the use of psilocybin, including psilocybin that occurs naturally in certain mushroom speciesFootnote 1 ("magic mushrooms"), for potential therapeutic purposes. In response, Health Canada is issuing this notice to provide information on the use of psilocybin mushrooms in clinical trials or as a drug requested through the Special Access Program (SAP), and to emphasize the importance of drug quality and Good Manufacturing Practices (GMP).

Considerations regarding the use of psilocybin mushrooms

Health Canada understands that some stakeholders may consider psilocybin mushrooms (i.e. whole or part of any mushroom species containing psilocybin) to be a natural or traditional form of psilocybin. Although research into the therapeutic potential of psilocybin continues to advance through several well-designed studies, there is currently limited good quality research-based evidence on the added therapeutic benefits of using psilocybin mushrooms instead of purified or synthetic psilocybin.

To obtain market authorization for a drug in Canada, evidence is required to support the drug's efficacy and safety in treating the disease. Clinical trials remain the best method to advance our knowledge about products with a possible medical benefit, but have not undergone the rigorous, science-based review process to be approved as marketed drugs. Clinical trials protect participants by providing a framework so that an experimental treatment is administered in accordance with national and international ethical, medical and scientific standards. They can also help build the evidence related to the safety and efficacy of treatment options for patients.

All clinical trials require that the administered investigational product be of consistent quality and delivers a consistent dose. This is achieved by manufacturing products according to the applicable Good Manufacturing Practices (GMP). Consistent quality and dosing is required to generate reliable clinical trial results and support good clinical decision-making. This also helps ensure that the contribution of participants is managed in an ethical manner and not wasted.

The use of psilocybin mushrooms presents challenges for clinical trials because of the potential variability in the content of the active ingredients (i.e., psilocybin and psilocin) and potential impurities among different mushroom cultivars, as well as the potential variability throughout the mushroom tissue matrix (i.e., differences across different anatomical structures). The primary implications of this are related to dosing, particularly in the determination of a dosage form that provides a consistent active ingredient, while ensuring any impurities are consistently within acceptable limits. While this inconsistency in dosing and impurities can make it difficult for psilocybin mushrooms to meet GMP requirements, Health Canada is aware of the challenges with the characteristics of this product and remains open to receiving evidence that a mushroom product could meet GMP quality requirements and be demonstrated to be equivalent to (or better than) purified or synthetic forms of psilocybin from a clinical perspective.

Clinical trials require the use of GMP-compliant drugs

There are currently several clinical trials involving psilocybin that are underway in Canada. More information on these and other clinical trials can be obtained from Health Canada's Clinical Trials Database.

Research that meets the definition of a clinical trial in the Food and Drug Regulations (FDR) is subject to Part C, Division 5, which is a set of internationally aligned regulations under the FDR that govern the sale and importation of drugs for use in clinical trials. The chemistry and manufacturing requirements set out under division 5 of the FDR require the investigational product to be of GMP qualityFootnote 2. This means that any psilocybin product, including psilocybin mushrooms, used in a clinical trial must be manufactured according to GMP standards.

An attestation should be provided in the clinical trial application (either in the Quality Overall Summary or as an attachment) to confirm that the drug product to be used in the Canadian study was manufactured according to GMP standards. GMP ensures that products are consistently produced and controlled according to quality standards. Additionally, the investigational product(s) used in clinical trials should generally approximate the product(s) that may be submitted in the future for a pre-marketing evaluation for a New Drug Submission (NDS) under Part C, Division 8 of the FDR.

Sponsors are expected to gather information that will allow physicians to prescribe the drug according to best clinical practices. This is only possible if the investigational product is of consistent and stable quality. There is an expectation that if later approved for sale in Canada, the marketed therapeutic product will have a product monograph that accurately details the appropriate use of the drug, contraindications and other safety considerations, dose and dosage regimen, and recommended monitoring.

Required information for filing a clinical trial application (CTA)

If a sponsor wishes to proceed with a CTA involving psilocybin mushrooms, the application should include a discussion covering the rationale for using mushrooms over purified or synthetic psilocybin. It should also include evidence demonstrating that the proposed dosage form provides an accurate and consistent dose (e.g., capsules filled with a uniform blend of ground psilocybin mushroom). Non-clinical and/or clinical evidence should be provided to support the safety of the proposed dosage form.

The following information should also be included in a CTA: the species/cultivar of mushroom, a description of the growing conditions, the extraction/ isolation procedures (if applicable), characterization data, specifications including a description of the analytical methods and method validation, data from the batch analysis, a description of the container-closure system and stability data. Psilocybin mushrooms would also require further testing (e.g., microbiology, aflatoxins, residual pesticides, etc.) in addition to the usual requirements for chemically-synthesized drugs.

Considerations for requests to the SAP for psilocybin mushrooms

Requests to the SAP must provide sufficient evidence to support the use of the drug for treatment of the patient's condition, including the most recent supporting evidence of safety and efficacy. During review and prior to issuing an authorization, the SAP works with the manufacturer to gather and document information about the drug, including its development and regulatory status. This, in turn, helps to ensure that practitioners have access to current and relevant information. As part of their commitment to supply the drug, manufacturers are responsible for providing all relevant information, such as an Investigator's Brochure, Product Information, treatment guidelines, medical literature, clinical trial reports, etc., and for ensuring that significant new information respecting the safety, efficacy and quality of drugs released under the SAP is made available to practitioners and the Program as soon as available.

Manufacturers are requested to provide information regarding the manufacturing of the drug under GMP principles. Drugs that do not meet pharmaceutical GMP standards may only be considered when no product of higher quality is available in the world. GMP ensures that products are consistently produced and controlled according to quality standards. It is intended to minimize the risks involved in pharmaceutical production that cannot be eliminated through testing of the final product.

There are Canadian manufacturers capable of supplying GMP-grade psilocybin through different production methods. For assistance in identifying a manufacturer that can supply psilocybin, practitioners can contact the SAP directly.

Contact info

Please contact Health Canada for more information regarding clinical trials or SAP requests involving psilocybin, and for information on additional requirements due to psilocybin being classified as a restricted drug.

Office of Clinical Trials
Health Canada
E-mail: oct.enquiries-requetes.bec@hc-sc.gc.ca

Special Access Program
Health Canada
Telephone: 613-941-2108
Fax: 613-941-3194
E-mail: sapd-pasm@hc-sc.gc.ca

Related links

Notice to Stakeholders – Clarification of Requirements under the Food and Drug Regulations and the Controlled Drugs and Substances Act When Conducting Clinical Research with Psilocybin

Guidance Document For Clinical Trial Sponsors: Clinical Trial Applications

Special Access Program for drugs: Guidance document for industry and practitioners

Psilocybin and psilocin (Magic Mushrooms)

Footnotes

Footnote 1

In the context of this document, 'psilocybin mushrooms' refers to the fruiting body (whole or part) of any mushroom species that contains psilocybin. It does not include psilocybin that has been extracted and purified from mushrooms under GMP conditions.

Return to footnote 1 referrer

Footnote 2

Section C.05.010 of the FDR states that: "Every sponsor shall ensure that a clinical trial is conducted in accordance with good clinical practices and, without limiting the generality of the foregoing, shall ensure that…"

"(j) the drug is manufactured, handled and stored in accordance with the applicable good manufacturing practices referred to in Divisions 2 to 4 except sections C.02.019, C.02.025 and C.02.026."

Return to footnote 2 referrer

Report a problem or mistake on this page
Please select all that apply:

Thank you for your help!

You will not receive a reply. For enquiries, contact us.

Date modified: