Metonitazene

Substance identification
Metonitazene (IUPAC chemical name: N,N-diethyl-2-(2-(4-methoxybenzyl)- 5-nitro-1H-benzo[d]imidazol-1-yl)ethan-1-amine) belongs to the series of 2-benzylbenzimidazole opioid compounds. It is a white, off-white, beige or coloured powder and is sometimes crystalline. Reports suggest that it is used intranasally and by iv injection.

WHO review history
Metonitazene has not been formally reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention that this substance is manufactured clandestinely, poses a risk to public health and has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
Metonitazene is a chemical analogue of etonitazene and isotonitazene, both of which are Schedule I compounds under the Single Convention on Narcotic Drugs, 1961. Metonitazene is a potent opioid analgesic with rapid onset of action and greater potency than fentanyl and hydromorphone. Limited early clinical research demonstrated that metonitazene produces analgesia and typical opioid adverse effects, including sedation, respiratory depression, nausea and vomiting. The effects of metonitazene have been shown to be reversed by an opioid antagonist.

Dependence potential
Studies in animals show that metonitazene suppresses opioid withdrawal and has potent µ-opioid agonist effects. No controlled human studies have been reported on the dependence potential of metonitazene, but, as it is a potent µ-opioid agonist, it would be expected to produce dependence similarly to other opioids.

Actual abuse and/or evidence of likelihood of abuse
No controlled studies have been reported on the abuse potential of metonitazene, but, as it is a potent µ-opioid agonist, it would be expected to have high abuse liability. Online reports by people who have used metonitazene describe its euphoric and opioid-like effects.

A number of deaths have been reported in association with use of metonitazene. In many of these cases, metonitazene was used in combination with other opioids or benzodiazepines; however, in some fatalities, metonitazene was the sole substance identified in analysed biological samples.

Trafficking and use of metonitazene have been reported from a number of countries in several regions.

Therapeutic usefulness
Metonitazene is not known to have any therapeutic use.

Recommendation
The mechanism of action and effects of metonitazene indicate that it is liable to have abuse potential and ill effects similar to those of opioids that are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. Its use has been reported in a number of countries and been associated with adverse effects, including death. Metonitazene has no known therapeutic use and is likely to cause substantial harm.

Recommendation: The Committee recommended that metonitazene (IUPAC chemical name: N,N-diethyl-2-(2-(4-methoxybenzyl)-5-nitro-1H- benzo[d]imidazol-1-yl)ethan-1-amine) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.