Schedules of Controlled Substances: Placement of N-Desethyl Isotonitazene and N-Piperidinyl Etonitazene in Schedule I

<RULE> DEPARTMENT OF JUSTICE <SUBAGY>Drug Enforcement Administration</SUBAGY> <CFR>21 CFR Part 1308</CFR> <DEPDOC>[Docket No. DEA-1143]</DEPDOC> <SUBJECT>Schedules of Controlled Substances: Placement of N-Desethyl Isotonitazene and N-Piperidinyl Etonitazene in Schedule I</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Drug Enforcement Administration, Department of Justice. <HD SOURCE="HED">ACTION:</HD> Final amendment; final order. <SUM> <HD SOURCE="HED">SUMMARY:</HD> With the issuance of this final order, the Administrator of the Drug Enforcement Administration is permanently placing <E T="03">N-</E> ethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1 <E T="03">H</E> -benzimidazol-1-yl)ethan-1-amine (other name: <E T="03">N</E> -desethyl isotonitazene) and 2-(4-ethoxybenzyl)-5-nitro-1-(2-(piperidin-1-yl)ethyl)-1 <E T="03">H</E> -benzimidazole (other names: <E T="03">N</E> -piperidinyl etonitazene; etonitazepipne), including their isomers, esters, ethers, salts, and salts of isomers, esters, and ethers whenever the existence of such isomers, esters, ethers, and salts are possible within the specific chemical designation, in schedule I under the Controlled Substances Act. This scheduling action discharges the United States' obligations under the Single Convention on Narcotic Drugs (1961). This action imposes permanent regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, import, export, engage in research or conduct instructional activities with or possess), or handle <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> Effective January 22, 2026. </EFFDATE> <HD SOURCE="HED">ADDRESSES:</HD> 8701 Morrissette Drive, Springfield, Virginia 22152. <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> Dr. Terrence L. Boos, Drug and Chemical Evaluation Section, Diversion Control Division, Drug Enforcement Administration; Telephone: (571) 362-3249. </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> <HD SOURCE="HD1">Legal Authority</HD> The United States is a party to the United Nations Single Convention on Narcotic Drugs, Mar. 30, 1961, 18 U.S.T. 1407, 520 U.N.T.S. 151 (Single Convention), as amended by the 1972 Protocol. Article 3, paragraph 7 of the Single Convention requires that if the Commission on Narcotic Drugs (Commission) adds a substance to one of the schedules of such Convention, and the United States receives notification of such scheduling decision from the Secretary-General of the United Nations (Secretary-General), the United States, as a signatory Member State, is obligated to control the substance under its national drug control legislation. Under 21 U.S.C. 811(d)(1) of the Controlled Substances Act (CSA), if control of a substance is required “by United States obligations under international treaties, conventions, or protocols in effect on October 27, 1970,” the Attorney General must issue an order controlling such drug under the schedule she deems most appropriate to carry out such obligations, without regard to the findings required by 21 U.S.C. 811(a) or 812(b), and without regard to the procedures prescribed by 21 U.S.C. 811(a) and (b). The Attorney General has delegated scheduling authority under 21 U.S.C. 811 to the Administrator of the Drug Enforcement Administration (DEA). <SU>1</SU> <FTREF/> <FTNT> <SU>1</SU>  28 CFR 0.100. </FTNT> <HD SOURCE="HD1">Background</HD> On July 29, 2024, DEA issued a temporary scheduling order, placing <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene temporarily in schedule I of the CSA. <SU>2</SU> <FTREF/> That order for <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene (codified at 21 CFR 1308.11(h)(68) and (69)) was based on findings by the then-Administrator that the temporary scheduling was necessary to avoid an imminent hazard to public safety. <SU>3</SU> <FTREF/> <FTNT> <SU>2</SU>   <E T="03">Schedules of Controlled Substances: Temporary Placement of N-desethyl isotonitazene and N-piperidinyl etonitazene in Schedule I,</E> 89 FR 60817 (July 29, 2024). </FTNT> <FTNT> <SU>3</SU>   <E T="03">Id.</E> </FTNT> On November 21, 2024, the Director-General of the World Health Organization recommended to the Secretary-General that <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene be placed in Schedule I of the Single Convention, as these substances have pharmacological effects similar to other opioid drugs that are controlled in Schedule I of the Single Convention. On June 9, 2025, the Secretariat of the United Nations informed the United States Government, by letter, that the Commission voted to place <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene in Schedule I of the Single Convention during its 68th session on March 12, 2025 (CND Mar 68/4 and 68/3). <HD SOURCE="HD1"> <E T="7462">N</E> -Desethyl Isotonitazene and <E T="7462">N</E> -Piperidinyl Etonitazene </HD> <E T="03">N</E> -Desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene are temporarily controlled in schedule I of the CSA because they pose imminent hazard to the public safety. Both <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene belong to the benzimidazole-opioid drug class, similar to etonitazene and isotonitazene. Substances of the benzimidazole-opioid drug class share similar pharmacological profile with other opioids such as morphine and fentanyl. <E T="03">N</E> -Desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene, similar to morphine and fentanyl, act as mu-opioid receptor agonists. Adverse health effects have been associated with the abuse of these benzimidazole-opioids. The abuse of <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene has been associated with several toxicology cases in the United States and in Europe. Several substances belonging to the benzimidazole-opioid drug class have been controlled in the United States, and as a class of drug in China, Canada, and the United Kingdom. The appearance of benzimidazole-opioids on the illicit drug market is similar to other synthetic opioids that are trafficked and abused for their psychoactive effects. Law enforcement reports demonstrate that <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene are being illicitly distributed and abused. According to the National Forensic Laboratory Information System (NFLIS-Drug)  <SU>4</SU> <FTREF/> database, which collects drug identification results from drug cases submitted to and analyzed by Federal, State and local forensic laboratories, there have been 151 reports for <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene between January 2022 and July 2025 (query date: July 17, 2025). Benzimidazole-opioids have been identified in counterfeit prescription tablets in the United States and other countries, including Sweden and the United Kingdom. The identification of these substances in counterfeit prescription drug products is of significant concern due to benzimidazole-opioids high potency. <FTNT> <SU>4</SU>  NFLIS-Drug represents an important resource in monitoring illicit drug trafficking, including the diversion of legally manufactured pharmaceuticals into illegal markets. NFLIS-Drug is a comprehensive information system that includes data from forensic laboratories that handle more than 96 percent of an estimated 1 million distinct annual federal, state, and local drug analysis cases. NFLIS-Drug includes drug chemistry results from completed analyses only. While NFLIS-Drug data are not direct evidence of abuse, these can lead to an inference that a drug has been diverted and abused. <E T="03">See Schedules of Controlled Substances: Placement of Carisoprodol Into Schedule IV,</E> 76 FR 77330, 77332 (Dec. 12, 2011). </FTNT> <E T="03">N</E> -Desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene have no currently accepted medical use in treatment in the United States. The Department of Health and Human Services (HHS) advised DEA, by letter dated May 11, 2023, that based on a review by the Food and Drug Administration (FDA), there were no investigational new drug applications (IND) or approved new drug applications (NDA) for <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene in the United States. Since this letter, HHS has not advised DEA of any new IND or NDA for these substances. Because <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene are not formulated or available for clinical use as approved medicinal products, all current use of these substances by individuals is based on their own initiative, rather than on the basis of medical advice from a practitioner licensed by law to administer such drugs. Consistent with 21 U.S.C. 811(d)(1), DEA concludes that <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene have no currently accepted medical use in treatment in the United States  <SU>5</SU> <FTREF/> and are most appropriately placed permanently in schedule I of the CSA, the same schedule in which they temporarily reside at present. Because control is required under the Single Convention, DEA will not be initiating regular rulemaking proceedings to permanently schedule <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene pursuant to 21 U.S.C. 811(a). <FTNT> <SU>5</SU>  There is no evidence suggesting that ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 27k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━