Description

Fentanyl analogues are a group of short-acting, highly potent synthetic opioids with narcotic analgesic properties. Fourteen fentanyl analogues are currently under Schedule I and/or Schedule IV of the Single Convention on Narcotic Drugs of 1961. While four fentanyl analogues (alfentanil, remifentanil, sufentanil and fentanyl itself) have been approved for medical use to manage severe pain and in anaesthesia, many fentanyl analogues are derived from substances that have been researched for pharmaceutical use but have never been marketed.


Chemical structure

Fentanyl analogues can be described as having the 4-anilinopiperidine structure as its core, with four possible sites of modification (Figure 1).

Figure 1: Generic structural representation of fentanyl analogues obtained by modification of the highlighted key regions and using fentanyl as the template



Source: UNODC, The challenge of New Psychoactive Substances - A technical update (United Nations publication, 2024).


More than 80 fentanyl analogues have been reported to UNODC (Figure 2).

Figure 2: Common fentanyl analogues NPS


Note: Structural differences are highlighted in red.

Source: UNODC, The challenge of New Psychoactive Substances - A technical update (United Nations publication, 2024).


Commonly used forms

Fentanyl analogues appear to be used through the most common routes of administration normally accessible to users. Fentanyl can be injected, snorted/sniffed, smoked, taken orally by pill or tablet, and spiked onto blotter paper. Analogues are typically seen in powder form, which can be used as it is or mixed with another substance and then smoked or taken by the intranasal or intravenous route. They can also be pressed into tablets, often as falsified forms of other pharmaceuticals opioid products or mixed into an intranasal spray. Figure 3 shows opioid receptor agonists commonly used forms.


Figure 3: Opioid receptor agonists commonly used forms



Source: UNODC, The challenge of New Psychoactive Substances - A technical update (United Nations publication, 2024).


Reported adverse effects

The typical side effect profile of opioid agonist use includes euphoria, pupillary constriction, decreased consciousness, impairment of cognition, respiratory depression, sedation, sleepiness, dizziness, nausea, vomiting, fatigue, headache, constipation and hallucinatory or dissociative effects. Tolerance to the analgesic and euphoric effects of opioids can develop quickly and the euphoric effects of opioids can lead to habituation and dependence. Cessation of opioid agonist use leads to a withdrawal syndrome, characterized by drug craving, dysphoria, anxiety, insomnia, irregular heart rate, loss of appetite, diarrhoea, sweating, nausea, and vomiting. The main mechanism of fatal opioid overdose is respiratory depression, leading to pathological indicators such as froth in the airways, and cerebral and pulmonary oedema. As fentanyl and its analogues have high potency compared to morphine, poor control of dose, polydrug use, and patterns of repeated use are most likely contributors to the high rates of overdose, respiratory depression, and death associated with these drugs. Figure 4 shows reported effects of opioid receptor agonists.

Figure 4: Reported effects of opioid receptor agonists



Source: UNODC, The challenge of New Psychoactive Substances - A technical update (United Nations publication, 2024).

References

UNODC, The challenge of New Psychoactive Substances - A technical update (United Nations publication, 2024).

UNODC, Terminology and Information on Drugs, Third Edition (United Nations publication Sales No. E.16.XI.8)

UNODC, Early Warning Advisory on New Psychoactive Substances Dashboard, accessed 27 September 2024.

Last update: 30/09/2024