Schedules of Controlled Substances: Placement of Butonitazene, Flunitazene, and Metodesnitazene Substances in Schedule I

SUPPLEMENTARY INFORMATION:

In this final rule, the Drug Enforcement Administration (DEA) permanently schedules the following three controlled substances in schedule I of the Controlled Substances Act (CSA), 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 within the specific chemical designation:

• Butonitazene (2-(2-(4-butoxybenzyl)-5-nitro-1H -benzimidazol-1-yl)- N,N -diethylethan-1-amine),
• Flunitazene (N,N -diethyl-2-(2-(4-fluorobenzyl)-5-nitro-1 H -benzimidazol-1-yl)ethan-1-amine),
• Metodesnitazene (N,N -diethyl-2-(2-(4-methoxybenzyl)-1 H -benzimidazol-1-yl)ethan-1-amine).

Legal Authority

The CSA provides that proceedings for the issuance, amendment, or repeal of the scheduling of any drug or other substance may be initiated by the Attorney General (delegated to the Administrator of DEA pursuant to 28 CFR 0.100) on his own motion, at the request of the Secretary of Health and Human Services (HHS), or on the petition of any interested party. This action is supported, inter alia, by a recommendation from the Assistant Secretary for Health of HHS (Assistant Secretary for HHS or Assistant Secretary) and an evaluation of all other relevant data by DEA. This action continues the imposition of the regulatory controls and administrative, civil, and criminal sanctions of schedule I controlled substances on any person who handles (manufactures, distributes, imports, exports, engages in research, or conducts instructional activities or chemical analysis with, or possesses) or proposes to handle butonitazene, flunitazene, and metodesnitazene.

Background

On April 12, 2022, pursuant to 21 U.S.C. 811(h)(1), DEA published an order in the Federal Register temporarily placing butonitazene, flunitazene, metodesnitazene, and four additional benzimidazole-opioids in schedule I of the Controlled Substances Act (CSA) based upon a finding that these substances pose an imminent hazard to the public safety. That temporary order was effective upon the date of publication. Under 21 U.S.C. 811(h)(2), the temporary scheduling of a substance expires at the end of two years from the date of issuance of the scheduling order, except that DEA may extend temporary scheduling of that substance for up to one year during the pendency of permanent scheduling proceedings under 21 U.S.C. 811(a)(1) with respect to the substance. Pursuant to 21 U.S.C. 811(h)(2), the temporary scheduling of butonitazene, flunitazene, and metodesnitazene was set to expire on April 12, 2024. However, on April 11, 2024, the DEA Administrator extended the temporary order in a separate action. On the same day, the Administrator, on her own motion pursuant to 21 U.S.C. 811(a), initiated scheduling proceedings and published a notice of proposed rulemaking (NPRM) to permanently control butonitazene, flunitazene, and metodesnitazene in schedule I of the CSA. Specifically, DEA proposed to add these substances to the opiates list under 21 CFR 1308.11(b).

DEA and HHS Eight Factor Analyses

On November 15, 2023, the Assistant Secretary submitted HHS's scientific and medical evaluation and scheduling recommendation for butonitazene, flunitazene, metodesnitazene, and three other benzimidazole-opioids and their salts to the Administrator, which recommended placing butonitazene, flunitazene, and metodesnitazene and their salts in schedule I of the CSA. In accordance with 21 U.S.C. 811(c), upon receipt of the scientific and medical evaluation and scheduling recommendation from HHS, DEA reviewed the documents and all other relevant data, and conducted its own eight-factor analysis of the abuse potential of these three substances. Please note that both the DEA and HHS eight-factor analyses are available in their entirety under the tab “Supporting Documents” of the public docket for this action at http://www.regulations.gov under Docket Number “DEA-900N.”

Determination To Permanently Schedule Butonitazene, Flunitazene, and Metodesnitazene

After review of the available data including the scientific and medical evaluation and the scheduling recommendation from HHS, DEA published an NPRM in the Federal Register on April 11, 2024, which proposed the placement of butonitazene, flunitazene, and metodesnitazene in schedule I of the CSA. The NPRM provided an opportunity for interested persons to file a request for a hearing in accordance with DEA regulations on or before May 13, 2024. DEA received no hearing requests. The NPRM also provided an opportunity for interested persons to submit comments on the proposed rule on or before May 13, 2024.

Comments Received

DEA received two comments on the proposed rule to control butonitazene, flunitazene, and metodesnitazene in schedule I of the CSA. One commenter provided support for the rule. This commenter noted that permanent placement of these substances would be beneficial to the community safety. DEA appreciates the support for this rulemaking. The second commenter commended the proposed rule but noted that a class control action for the nitazene drug class would be more appropriate as opposed to individually scheduling substances in the benzimidazole-opioid drug class. DEA appreciates this comment as a potential alternative for consideration. However, due to the current threat of these specific substances, DEA will continue with solely scheduling these three substances.

Scheduling Conclusion

After consideration of the relevant matters presented through public comments, the scientific and medical evaluation and accompanying scheduling recommendation of HHS, and DEA's own eight-factor analysis, DEA finds that these facts and all relevant data constitute substantial evidence of potential for abuse of butonitazene, flunitazene, and metodesnitazene. DEA is therefore permanently scheduling these three benzimidazole-opioids as schedule I controlled substances under the CSA.

Determination of Appropriate Schedule

The CSA establishes five schedules of controlled substances known as schedules I, II, III, IV, and V. The CSA also outlines the findings required to place a drug or other substance in any particular schedule. After consideration of the analysis and recommendation of the Assistant Secretary for HHS and review of all other available data, the Administrator of DEA, pursuant to 21 U.S.C. 811(a) and 21 U.S.C. 812(b)(1), finds that:

(1) Butonitazene, flunitazene, and metodesnitazene have a high potential for abuse. Butonitazene, flunitazene, and metodesnitazene, similar to etonitazene and fentanyl, are mu-opioid receptor agonists. These three benzimidazole-opioids have analgesic effects, and these effects are mediated by mu-opioid receptor agonism. HHS states that substances that produce mu-opioid receptor agonist effects in the central nervous system are considered as having a high potential for abuse ( e.g. morphine and fentanyl). Data obtained from drug discrimination studies indicate that butonitazene, flunitazene, and metodesnitazene fully substituted for the discriminative stimulus effects of morphine.

(2) Butonitazene, flunitazene, and metodesnitazene have no currently accepted medical use in the United States. There are no FDA-approved drug products for butonitazene, flunitazene, and metodesnitazene in the United States. There are no known therapeutic applications for these benzimidazole-opioids, and DEA is not aware of any currently accepted medical uses for these substances in the United States.

(3) There is a lack of accepted safety for use of butonitazene, flunitazene, and metodesnitazene under medical supervision. Because these substances have no FDA-approved medical use and have not been investigated as new drugs, their safety for use under medical supervision is not determined.

Based on these findings, the Administrator of DEA concludes that butonitazene, flunitazene, and metodesnitazene, 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 within the specific chemical designation, warrant continued control in schedule I of the CSA.

Requirements for Handling Butonitazene, Flunitazene, and Metodesnitazene

As discussed above, these three substances are currently subject to a temporary scheduling order, which added them to schedule I. Butonitazene, flunitazene, and metodesnitazene will continue to be subject to the CSA's schedule I regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, reverse distribution, dispensing, importation, exportation, engagement in research, and conduct of instructional activities or chemical analysis with, and possession of schedule I substances, including the following:

1. Registration. Any person who handles (manufactures, distributes, reverse distributes, dispenses, imports, exports, engages in research, or conducts instructional activities or chemical analysis with, or possesses) or who desires to handle butonitazene, flunitazene, and metodesnitazene must be registered with DEA to conduct such activities pursuant to 21 U.S.C. 822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 and 1312. Retail sales of schedule I controlled substances to the general public are not allowed under the CSA. Possession of any quantity of these substances in a manner not authorized by the CSA is unlawful and those in possession of any quantity of these substances may be subject to prosecution pursuant to the CSA.

2. Disposal of stocks. Butonitazene, flunitazene, and metodesnitazene must be disposed of in accordance with 21 CFR part 1317, in addition to all other applicable federal, state, local, and tribal laws.

3. Security. Butonitazene, flunitazene, and metodesnitazene are subject to schedule I security requirements and must be handled and stored pursuant to 21 U.S.C. 821, 823, and 871(b), and in accordance with 21 CFR 1301.71-1301.76. Non-practitioners handling these three substances also must comply with the screening requirements of 21 CFR 1301.90-1301.93.

4. Labeling and Packaging. All labels and labeling for commercial containers of butonitazene, flunitazene, and metodesnitazene must comply with 21 U.S.C. 825 and be in accordance with 21 CFR part 1302.

5. Quota. Only registered manufacturers are permitted to manufacture butonitazene, flunitazene, and metodesnitazene in accordance with a quota assigned pursuant to 21 U.S.C. 826, and in accordance with 21 CFR part 1303.

6. Inventory. Any person registered with DEA to handle butonitazene, flunitazene, and metodesnitazene must have an initial inventory of all stocks of controlled substances (including these substances) on hand on the date the registrant first engages in the handling of controlled substances pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.

After the initial inventory, every DEA registrant must take a new inventory of all stocks of controlled substances (including butonitazene, flunitazene, and metodesnitazene) on hand every two years pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.

7. Records and Reports. Every DEA registrant must maintain records and submit reports with respect to butonitazene, flunitazene, and metodesnitazene, pursuant to 21 U.S.C. 827, 832(a), and 958(e), and in accordance with 21 CFR 1301.74(b) and (c) and 1301.76(b) and parts 1304, 1312, and 1317. Manufacturers and distributors would be required to submit reports regarding butonitazene, flunitazene, and metodesnitazene to the Automation of Reports and Consolidated Order System pursuant to 21 U.S.C. 827, and in accordance with 21 CFR parts 1304 and 1312.

8. Order Forms. Every DEA registrant who distributes butonitazene, flunitazene, and metodesnitazene must comply with the order form requirements, pursuant to 21 U.S.C. 828 and 21 CFR part 1305.

9. Importation and Exportation. All importation and exportation of butonitazene, flunitazene, and metodesnitazene must comply with 21 U.S.C. 952, 953, 957, and 958, and be in accordance with 21 CFR part 1312.

10. Liability. Any activity involving butonitazene, flunitazene, and metodesnitazene not authorized by, or in violation of, the CSA or its implementing regulations is unlawful, and may subject the person to administrative, civil, and/or criminal sanctions.

Regulatory Analyses

Executive Orders 12866 (Regulatory Planning and Review), 13563 (Improving Regulation and Regulatory Review), and 14094 (Modernizing Regulatory Review)

In accordance with 21 U.S.C. 811(a), this final scheduling action is subject to formal rulemaking procedures done “on the record after opportunity for a hearing,” which are conducted pursuant to the provisions of 5 U.S.C. 556 and 557. The CSA sets forth the criteria for scheduling a drug or other substance. Such actions are exempt from review by the Office of Management and Budget (OMB) pursuant to section 3(d)(1) of Executive Order (E.O.) 12866 and the principles reaffirmed in E.O. 13563. E.O. 14094 modernizes the regulatory review process to advance policies that promote the public interest and address national priorities.

Executive Order 12988, Civil Justice Reform

This regulation meets the applicable standards set forth in sections 3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors and ambiguity, minimize litigation, provide a clear legal standard for affected conduct, and promote simplification and burden reduction.

Executive Order 13132, Federalism

This rulemaking does not have federalism implications warranting the application of E.O. 13132. The rule does not have substantial direct effects on the states, on the relationship between the national government and the States, or the distribution of power and responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal Governments

This rule does not have tribal implications warranting the application of E.O. 13175. It does not have substantial direct effects on one or more Indian tribes, on the relationship between the Federal government and Indian tribes, or on the distribution of power and responsibilities between the Federal government and Indian tribes.

Regulatory Flexibility Act

The Administrator, in accordance with the Regulatory Flexibility Act, 5 U.S.C. 601-612, has reviewed this rule and, by approving it, certifies that it will not have a significant economic impact on a substantial number of small entities.

On April 12, 2022, DEA published an order to temporarily place seven benzimidazole-opioids in schedule I of the CSA pursuant to the temporary scheduling provisions of 21 U.S.C. 811(h). DEA estimates that all entities handling or planning to handle butonitazene, flunitazene, and metodesnitazene have already established and implemented systems and processes required to handle these substances.

There are currently 45 registrations authorized to specifically handle butonitazene, flunitazene, or metodesnitazene, as well as 1,239 registered analytical labs and 861 researchers that are authorized to handle schedule I controlled substances generally. These 45 registrations represent 31 entities. A review of the 45 registrations indicates that all entities that currently handle butonitazene, flunitazene, and metodesnitazene also handle other schedule I controlled substances and have established and implemented (or maintained) systems and processes required to handle these substances. Therefore, DEA anticipates this final rule will impose minimal or no economic impact on any affected entities; and thus, will not have a significant economic impact on any affected small entity. Therefore, DEA has concluded that this rule will not have a significant economic impact on a substantial number of small entities.

Unfunded Mandates Reform Act of 1995

In accordance with the Unfunded Mandates Reform Act of 1995 (UMRA), 2 U.S.C. 1501 et seq., DEA has determined and certifies that this action would not result in any Federal mandate that may result “in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any 1 year . . . .” Therefore, neither a Small Government Agency Plan nor any other action is required under the UMRA.

Paperwork Reduction Act of 1995

This rule would not impose a new collection or modify an existing collection of information under the Paperwork Reduction Act of 1995. Also, this rule would not impose new or modify existing recordkeeping or reporting requirements on state or local governments, individuals, businesses, or organizations. However, this rule would require compliance with the following existing OMB collections: 1117-0003, 1117-0004, 1117-0006, 1117-0008, 1117-0009, 1117-0010, 1117-0012, 1117-0014, 1117-0021, 1117-0023, 1117-0029, and 1117-0056. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number.

For the reasons set out above, DEA amends 21 CFR part 1308 as follows:

1. The authority citation for 21 CFR part 1308 continues to read as follows:

Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise noted.

2. In § 1308.11:

a. Redesignate paragraphs (b)(62) through (106) as (b)(65) through (109)

b. Redesignate paragraphs (b)(44) through (61) as (b)(46) through (63);

c. Redesignate paragraphs (b)(24) through (43) as (b)(25) through (44);

d. Add new paragraphs (b)(24), (b)(45), and (b)(64); and

e. Remove and reserve paragraphs (h)(50), (52), and (53).

The additions to read as follows:

(b) * * *