Research and analysis

Sixth addendum to ACMD report on the use and harms of 2-benzyl benzimidazole (‘nitazene’) and piperidine benzimidazolone (‘brorphine-like’) opioids, 21 October 2025 (accessible)

Updated 21 October 2025

21 October 2025

The ACMD has continued to monitor and assess detections of newly identified nitazenes that fall outside the scope of the current generic control.

On 8 November 2024, the ACMD published its fifth addendum to the advice on 2-benzyl benzimidazole (nitazene) and piperidine benzimidazolone (‘brorphine-like’) opioids.

Since the publication of this addendum, the ACMD has continued to review international approaches to nitazene generic controls as they became available.

The ACMD has recently been alerted to the detection of new 2-benzyl benzimidazole compounds:

• Ethylene etonitazene
• Ethylene isotonitazepyne (N-pyrrolidino ethylene isotonitazene)

These compounds would not be captured by the generic published on 8 November 2024. Owing to their potential harms, the ACMD has modified Recommendation 3 to capture ethylene etonitazene, ethylene isotonitazepyne and associated phenethyl variants that may appear in the future.

Therefore, the ACMD recommends that the proposed generic definition (Recommendation 3) be updated to encompass additional 2-benzyl benzimidazoles (nitazenes) of this type that may be identified in the future.

Updated Recommendation 3

The ACMD recommends that a consultation should be undertaken with stakeholders, including academia and the chemical and pharmaceutical industries on the introduction of a generic control on 2- benzyl benzimidazole variants, as new examples may be encountered and could present a serious risk of harm. Following this consultation, materials covered by the generic should be added to Class A of the Misuse of Drugs Act 1971, consistent with the classification of other potent opioids and other nitazenes. As these materials have no medical use, it is recommended that they should be placed in Schedule 1 of the Misuse of Drugs Regulations 2001 (as amended) and the Misuse of Drugs (Designation) (England, Wales, and Scotland) Order 2015, Northern Ireland 2001. The proposed wording for the generic for addition to the Misuse of Drugs Act is as follows (amended text in bold):

Any compound (not being a compound for the time being specified in sub- paragraph (a) above), with a maximum molecular mass of 500 atomic mass units, structurally derived from 2-(2-benzyl-benzimidazol-1-yl)ethanamine by modification in any of the following ways, that is to say:

i) By substitution at the nitrogen of the ethanamine to any extent by alkyl substituents containing up to three carbon atoms or alkenyl substituents containing up to three carbon atoms or by inclusion of the nitrogen atom (and no other atoms of the side chain) in a cyclic structure.

ii) By substitution in the phenyl ring of the benzyl system to any extent by alkyl or haloalkyl containing up to six carbon atoms, alkoxy or haloalkoxy containing up to five carbon atoms, acetyloxy, hydroxy, cyano, halogen, thioalkyl containing up to five carbon atoms or alkylsulphonyl containing up to five carbon atoms.

iii) By substitution at the 5- or 6- positions of the benzimidazole system by nitro, acetyl, amino, cyano, methoxy, trifluoromethyl, trifluoromethoxy or halogen substituents.

iv) By substitution at the benzylic carbon by a methyl group or by a carbamoyl group.

v) By replacement of the benzylic carbon or of a carbon atom of an ethyl link between the benzimidazole system and the phenyl ring by a nitrogen, oxygen or sulphur atom.

vi) By substitution in the phenyl ring of the benzyl system by an ethoxy group linked back to the phenyl ring to form a dihydrobenzofuran structure.

vii) By replacement of the phenyl ring of the benzyl system by methylenedioxyphenyl.

viii) By replacement of the methyl group of the benzyl system by an ethyl group to form a phenethyl system.