Schedules of Controlled Substances: Temporary 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: Temporary 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> Temporary amendment; temporary scheduling order. <SUM> <HD SOURCE="HED">SUMMARY:</HD> The Administrator of the Drug Enforcement Administration is issuing this temporary order to schedule two synthetic benzimidazole-opioid substances, as identified in this order, in schedule I of the Controlled Substances Act. This action is based on a finding by the Administrator that the placement of these two substances in schedule I is necessary to avoid imminent hazard to the public safety. This order imposes 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 with, or possess) or propose to handle these two specified controlled substances. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> This temporary scheduling order is effective July 29, 2024, until July 29, 2026. If this order is extended or made permanent, DEA will publish a document in the <E T="04">Federal Register</E> . </EFFDATE> <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> Terrence L. Boos, Ph.D., Drug and Chemical Evaluation Section, Diversion Control Division, Drug Enforcement Administration; Mailing Address: 8701 Morrissette Drive, Springfield, Virginia 22152; Telephone: (571) 362-3249. </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> The Drug Enforcement Administration (DEA) issues a temporary scheduling order  <SU>1</SU> <FTREF/> (in the form of a temporary amendment) to add the following two 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 action 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> • <E T="03">N-</E> ethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1 <E T="03">H</E> -benzimidazol-1-yl)ethan-1-amine (commonly known as <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 (commonly known as either <E T="03">N</E> -piperidinyl etonitazene or etonitazepipne). <HD SOURCE="HD1">Legal Authority</HD> Under 21 U.S.C. 811(h)(1), the Attorney General, as delegated to the Administrator of DEA (Administrator) pursuant to 28 CFR 0.100, has 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 the Administrator 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/> <FTNT> <SU>4</SU>  21 U.S.C. 811(h)(1); 21 CFR part 1308. </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 place a substance in schedule I of the CSA temporarily ( <E T="03">i.e.,</E> to issue a temporary scheduling order). <SU>5</SU> <FTREF/> The Administrator transmitted the required notice to the Assistant Secretary for Health of HHS (Assistant Secretary), <SU>6</SU> <FTREF/> by letter dated April 3, 2023, regarding <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene. The Assistant Secretary responded to this notice by letter dated May 11, 2023, and advised 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 <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene. The Assistant Secretary also stated that HHS had no objection to the temporary placement of these substances in schedule I. <E T="03">N</E> -Desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene currently are not 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>5</SU>  21 U.S.C. 811(h)(4). </FTNT> <FTNT> <SU>6</SU>  The Secretary of HHS has delegated to the Assistant Secretary for Health of HHS the authority to make domestic drug scheduling recommendations. 58 FR 35460 (July 1, 1993). </FTNT> DEA has taken into consideration the Assistant Secretary's comments as required by subsection 811(h)(4). DEA has found the control of <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene in schedule I on a temporary basis is necessary to avoid an imminent hazard to the public safety. As required by 21 U.S.C. 811(h)(1)(A), DEA published a notice of intent (NOI) to temporarily schedule <E T="03">N</E> -desethyl isotonitazene and <E T="03">N</E> -piperidinyl etonitazene on October 25, 2023. <SU>7</SU> <FTREF/> That NOI discussed findings from DEA's three-factor analysis dated January 2023, which DEA made available on <E T="03">www.regulations.gov.</E> <FTNT> <SU>7</SU>  88 FR 73293 (Oct. 25, 2023). </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 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/> Consideration of these factors includes any information indicating actual abuse, diversion from legitimate channels, and clandestine importation, manufacture, or distribution of these substances. <SU>9</SU> <FTREF/> <FTNT> <SU>8</SU>  21 U.S.C. 811(h)(3). </FTNT> <FTNT> <SU>9</SU>   <E T="03">Id.</E> </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">Two Benzimidazole-Opioids: N-desethyl isotonitazene and N-piperidinyl etonitazene</HD> The continued encounter of novel psychoactive substances (NPS) on the recreational drug market poses a threat to public safety. Following the class-wide scheduling of fentanyl-related substances, <SU>12</SU> <FTREF/> there has been an increase in the emergence of synthetic opioids that are not structurally related to fentanyl. Beginning in 2019, a new class of synthetic opioids known as benzimidazole-opioids, commonly referred to as “nitazenes,” emerged on the recreational drug market. This class of substances was first synthesized in the 1950s by CIBA Aktiengesellschaft in Switzerland, and it has a similar pharmacological profile to fentanyl, morphine, and other mu-opioid receptor agonists. Between August 2020 and April 2022, DEA temporarily controlled eight benzimidazole-opioids because they posed a threat to public safety. <SU>13</SU> <FTREF/> <FTNT> <SU>12</SU>  On February 6, 2018, pursuant to 21 U.S.C. 811(h), the then Acting Administrator of Drug Enforcement Administration temporarily placed fentanyl-related substances in schedule I of the Controlled Substances Act (CSA) (83 FR 5188) to avoid an imminent hazard to public safety. Through the Temporary Reauthorization and Study of Emergency Scheduling of Fentanyl Analogues Act, Public Law 116-114, which became law on February 6, 2020, Congress extended the temporary control of fentanyl-related substances until May 6, 2021. This temporary order was subsequently extended multiple times, most recently through the Consolidated Appropriations Act of 2023, Public Law 117-328, which extended the order until December 31, 2024. </FTNT> <FTNT> <SU>13</SU>  Schedules of Controlled Substances: Temporary Placement of Butonitazene, Etodesnitazene, flunitazene, Metodesnitazene, Metonitazene, <E T="03">N</E> -Pyrrolidino etonitazene, and Protonitazene in Schedule I, 87 FR 21556 (Apr. 12, 2022); Schedules of Controlled Substances: Temporary Placement of Isotonitazene in Schedule I, 85 FR 51342 (Aug. 20, 2020). </FTNT> Recently, additional benzimidazole-opioids have been identified within the rapidly expanding class of “nitazene” co ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 45k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━