Schedules of Controlled Substances: Temporary Placement of Seven Benzimidazole-Opioids in Schedule I

DEPARTMENT OF JUSTICE <SUBAGY>Drug Enforcement Administration</SUBAGY> <CFR>21 CFR Part 1308</CFR> <DEPDOC>[Docket No. DEA-1494]</DEPDOC> <SUBJECT>Schedules of Controlled Substances: Temporary Placement of Seven Benzimidazole-Opioids in Schedule I</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Drug Enforcement Administration, Department of Justice. <HD SOURCE="HED">ACTION:</HD> Proposed amendment; notice of intent. <SUM> <HD SOURCE="HED">SUMMARY:</HD> The Acting Administrator of the Drug Enforcement Administration is issuing this notice of intent to publish a temporary order to schedule seven benzimidazole-opioid substances in schedule I of the Controlled Substances Act. When it is finalized, the temporary scheduling order will impose the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess) or propose to handle these seven specified substances. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> June 26, 2025. </EFFDATE> <HD SOURCE="HED">ADDRESSES:</HD> 8701 Morrissette Drive, Springfield, Virginia 22152. <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> Terrence L. Boos, Drug and Chemical Evaluation Section, Diversion Control Division, Drug Enforcement Administration; Mailing Address: 8701 Morrissette Drive, Springfield, Virginia 22152; Telephone: (571) 362-3249. As required by 5 U.S.C. 553(b)(4), a summary of this notice may be found in the docket (DEA-1494) for this rulemaking at <E T="03">www.regulations.gov.</E> </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> The notice of intent contained in this document is issued pursuant to the temporary scheduling provisions of 21 U.S.C. 811(h). The Drug Enforcement Administration (DEA) intends to issue a temporary scheduling order  <SU>1</SU> <FTREF/> (in the form of a temporary amendment) to add these seven benzimidazole-opioid substances, including their isomers, esters, ethers, salts, and salts of isomers, esters, and ethers whenever the existence of such isomers, esters, ethers, and salts is possible, to schedule I under the Controlled Substances Act (CSA): <FTNT> <SU>1</SU>  Though DEA has used the term “final order” with respect to temporary scheduling orders in the past, this notice of intent adheres to the statutory language of 21 U.S.C. 811(h), which refers to a “temporary scheduling order.” No substantive change is intended. </FTNT> • 2-(2-((2,3-dihydrobenzofuran-5-yl)methyl)-5-nitro-1 <E T="03">H</E> -benzimidazol-1-yl)- <E T="03">N,N</E> -diethylethan-1-amine (commonly known as, ethyleneoxynitazene), • 2-(2-(benzodioxol-5-ylmethyl)-5-nitro-1 <E T="03">H</E> -benzimidazol-1-yl)- <E T="03">N,N</E> -diethylethan-1-amine (commonly known as, methylenedioxynitazene or 3′,4′-methylenedioxynitazene), • 2-(2-(4-ethoxybenzyl)-5-methyl-1 <E T="03">H</E> -benzimidazol-1-yl)- <E T="03">N,N</E> -diethylethan-1-amine (commonly known as, 5-methyl etodesnitazene), • 2-(2-(4-ethoxybenzyl)-5-nitro-1 <E T="03">H</E> -benzimidazol-1-yl)- <E T="03">N</E> -ethylethan-1-amine (commonly known as, <E T="03">N</E> -desethyl etonitazene), • <E T="03">N</E> -ethyl-2-(5-nitro-2-(4-propoxybenzyl)-1 <E T="03">H</E> -benzimidazol-1-yl)ethan-1-amine (commonly known as, <E T="03">N</E> -desethyl protonitazene), • 2-(2-(4-ethoxybenzyl)-5-nitro-1 <E T="03">H</E> -benzimidazol-1-yl) <E T="03">-N,N</E> -dimethylethan-1-amine (commonly known as, <E T="03">N,N</E> -dimethylamino etonitazene), and • 2-(4-isopropoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1 <E T="03">H</E> -benzimidazole (commonly known as, <E T="03">N</E> -pyrrolidino isotonitazene). The temporary scheduling order will be published in the <E T="04">Federal Register</E> on or after July 28, 2025. <HD SOURCE="HD1">Legal Authority</HD> The CSA provides the Attorney General with the authority to temporarily place a substance in schedule I of the CSA for two years without regard to the evaluation requirements of 21 U.S.C. 811(b), if she finds that such action is necessary to avoid an imminent hazard to the public safety. <SU>2</SU> <FTREF/> In addition, if proceedings to control a substance are initiated under 21 U.S.C. 811(a)(1) while the substance is temporarily controlled under section 811(h), the Attorney General may extend the temporary scheduling for up to one year. <SU>3</SU> <FTREF/> <FTNT> <SU>2</SU>  21 U.S.C. 811(h)(1). </FTNT> <FTNT> <SU>3</SU>  21 U.S.C. 811(h)(2). </FTNT> Where the necessary findings are made, a substance may be temporarily scheduled if it is not listed in any other schedule under 21 U.S.C. 812, or if there is no exemption or approval in effect for the substance under section 505 of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 355. <SU>4</SU> <FTREF/> The Attorney General has delegated scheduling authority under 21 U.S.C. 811 to the Administrator of DEA (Administrator). <SU>5</SU> <FTREF/> <FTNT> <SU>4</SU>  21 U.S.C. 811(h)(1); 21 CFR part 1308. </FTNT> <FTNT> <SU>5</SU>  28 CFR 0.100. </FTNT> <HD SOURCE="HD1">Background</HD> The CSA requires the Administrator to notify the Secretary of the Department of Health and Human Services (HHS) of an intent to temporarily place a substance in schedule I of the CSA ( <E T="03">i.e.,</E> to issue a temporary scheduling order). <SU>6</SU> <FTREF/> By letter dated April 15, 2025, the Acting Administrator transmitted the required notice to place ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene, <E T="03">N</E> -desethyl etonitazene, <E T="03">N</E> -desethyl protonitazene, <E T="03">N,N</E> -dimethylamino etonitazene, and <E T="03">N</E> -pyrrolidino isotonitazene in schedule I on a temporary basis to the Assistant Secretary for Health of HHS (Assistant Secretary). <SU>7</SU> <FTREF/> On May 20, 2025, the Acting Assistant Secretary responded to this notice and advised DEA that, based on a review by the Food and Drug Administration (FDA), there are currently no investigational new drug applications (IND) or approved new drug applications (NDA) for ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene, <E T="03">N</E> -desethyl etonitazene, <E T="03">N</E> -desethyl protonitazene, <E T="03">N,N</E> -dimethylamino etonitazene, and <E T="03">N</E> -pyrrolidino isotonitazene. The Acting Assistant Secretary also stated that HHS had no objection to the temporary placement of these seven substances in schedule I of the CSA. Ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene, <E T="03">N</E> -desethyl etonitazene, <E T="03">N</E> -desethyl protonitazene, <E T="03">N,N</E> -dimethylamino etonitazene, and <E T="03">N</E> -pyrrolidino isotonitazene are not currently listed in any schedule under the CSA, and no exemptions or approvals under 21 U.S.C. 355 are in effect for these substances. <FTNT> <SU>6</SU>  21 U.S.C. 811(h)(4). </FTNT> <FTNT> <SU>7</SU>  The Secretary of HHS has delegated to the Assistant Secretary for Health of HHS the authority to make domestic drug scheduling recommendations. <E T="03">Comprehensive Drug Abuse Prevention and Control Act of 1970, Public Law 91-513, As Amended; Delegation of Authority,</E> 58 FR 35460 (July 1, 1993). </FTNT> To find that temporarily placing a substance in schedule I of the CSA is necessary to avoid an imminent hazard to the public safety, the Acting Administrator must consider three of the eight factors set forth in 21 U.S.C. 811(c): the substance's history and current pattern of abuse; the scope, duration, and significance of abuse; and what, if any, risk there is to the public health. <SU>8</SU> <FTREF/> This consideration includes any information indicating actual abuse, diversion from legitimate channels, and clandestine importation, manufacture, or distribution of ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene, <E T="03">N</E> -desethyl etonitazene, <E T="03">N</E> -desethyl protonitazene, <E T="03">N,N</E> -dimethylamino etonitazene, and <E T="03">N</E> -pyrrolidino isotonitazene. <SU>9</SU> <FTREF/> <FTNT> <SU>8</SU>  21 U.S.C. 811(h)(3). </FTNT> <FTNT> <SU>9</SU>  21 U.S.C. 811(h)(3). </FTNT> Substances meeting the statutory requirements for temporary scheduling may only be placed in schedule I. <SU>10</SU> <FTREF/> Substances in schedule I have high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision. <SU>11</SU> <FTREF/> <FTNT> <SU>10</SU>  21 U.S.C. 811(h)(1). </FTNT> <FTNT> <SU>11</SU>  21 U.S.C. 812(b)(1). </FTNT> <HD SOURCE="HD1"> Seven Benzimidazole-Opioids: Ethyleneoxynitazene, Methylenedioxynitazene, 5-Methyl Etodesnitazene, <E T="7462">N</E> -Desethyl Etonitazene, <E T="7462">N</E> -Desethyl Protonitazene, <E T="7462">N,N</E> -Dimethylamino Etonitazene, and <E T="7462">N</E> -Pyrrolidino Isotonitazene </HD> The availability of synthetic opioids in the illicit drug market continues to pose an imminent hazard to the public safety. Adverse health effects associated with the abuse of synthetic opioids and the continued evolution and increased popularity of these substances have been a serious concern in recent years. As the United States continues to experience an unprecedented epidemic of opioid misuse and abuse, the presence of new synthetic opioids with no approved medical use exacerbates the epidemic. The trafficking and abuse of new synthetic opioids are deadly new trends. The benzimidazole-opioids have a similar pharma ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 44k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━