Status determination of fentanyl-related substances

Fentanyls

Fentanyl is a highly potent opioid analgesic. Its analgesic potency has been reported to exceed morphine by 50-100 fold in humans^{Footnote 1} and it is highly addictive and psychoactive. Recreational use of fentanyl and its analogues is dangerous due to their ability to induce respiratory depression, and these substances have been linked to the majority of apparent opioid-related deaths in Canada between January and September 2019^{Footnote 2}. During illicit drug production, fentanyl is often added to enhance the effects of other drugs such as heroin and cocaine. As a result, large doses of fentanyl may be consumed accidentally with fatal consequences^{Footnote 3}.

Fentanyl is listed under item 16 of Schedule I to the Controlled Drugs and Substances Act (CDSA). Numerous substances structurally similar to fentanyl have been reported in the scientific literature to produce similar effects to fentanyl, including its salts, derivatives and analogues. These substances are explicitly listed under sub-items 16(1) to 16(13) of Schedule I to the CDSA. Many other structurally similar substances also have the potential to induce psychoactive and toxic effects similar to fentanyl. Therefore, these substances are also controlled under item 16 as fentanyl analogues or derivatives, even though they are not explicitly listed.

This guidance document provides a general overview of how Health Canada determines the status for fentanyl-related substances under the CDSA. Please note that this guidance is subject to change upon availability of new scientific evidence. It bears emphasis that this document is published for informational purposes only. It is not a comprehensive account of how status decisions are made, and is not a substitute for status decisions made by the Science Division of the Office of Drug Policy and Science.

In order to ensure an accurate status of any substance of interest, please contact: hc.status-demandedestatut.sc@canada.ca.

Fentanyl analogues

In order to determine whether a fentanyl-related substance is controlled under the CDSA as a fentanyl analogue, a core fentanyl structure has been defined. This core structure captures substances that are chemically related as well as potentially psychoactive. The core structure is primarily based on the structural modifications (described in peer-reviewed publications) that lead to substances that produce analgesia (ED₅₀), bind (K_i) and activate (EC₅₀) the µ-opioid receptor.

Figure 1. Fentanyl core structure

The core structure is used to determine whether a substance is an analogue of fentanyl. If the substance is captured within the outlined core structure above, it is captured under item 16 of Schedule I to the CDSA.