Status determination of fentanyl-related substances

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• How to use this page
• About fentanyl
• Substances classified as fentanyl analogues under the CDSA

How to use this page

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 Legislative and Regulatory Affairs.

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

About fentanyl

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 various analogues. Examples of 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 even though they are not explicitly listed.

Substances classified as fentanyl analogues under the CDSA

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.

Figure 1 - Text description

The fentanyl core structure includes a 1-ethylpiperidin-4-amine skeleton whether or not substituted on the piperidine ring with carbon or non-carbon substituents (R1). The 4-amine in the skeleton is further substituted at position R2 with aromatic rings that may be further substituted, or at position R3 with variously substituted acyl groups. The ethyl moiety of the 1-ethylpiperidin-4-amine skeleton can be substituted at the α- or β-carbons. Finally, the ethyl moiety is also substituted at position R with various functional groups such as aromatic rings, monocycles, heterocycles and alkyl esters. These functional groups can be further substituted.

• R = Aromatic rings, monocycles, heterocycles and alkyl esters whether or not further substituted
  • Commonly observed substitutions include alkyl groups
• α,β-carbons, whether or not further substituted
  • Commonly observed substitutions include alkyl and hydroxyl groups
• R1 = Substitutions, if any, on the piperidine ring could include any carbon or non-carbon substituents
  • Commonly observed substitutions include alkyl groups, esters, and alkoxyl groups
• R2 = Aromatic rings whether or not further substituted
  • Commonly observed substitution of aromatic rings includes halogen, alkoxy, and alkyl groups
• R3 = Variously substituted acyl groups
  • Commonly observed substitutions of acyl group includes alkyl, alkene and cyclic groups (such as carbocycles and heterocycles, aromatic or non-aromatic.)

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.

Footnotes