[Federal Register Volume 89, Number 71 (Thursday, April 11, 2024)]
[Rules and Regulations]
[Pages 25514-25517]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-07684]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-900]


Schedules of Controlled Substances: Placement of Etodesnitazene, 
N-Pyrrolidino Etonitazene, and Protonitazene in Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Final amendment; final order.

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SUMMARY: With the issuance of this final order, the Administrator of 
the Drug Enforcement Administration is permanently placing 2-(2-(4-
ethoxybenzyl)-1H-benzimidazol-1-yl)-N,N-diethylethan-1-amine (other 
names: etodesnitazene; etazene), 2-(4-ethoxybenzyl)-5-nitro-1-(2-
(pyrrolidin-1-yl)ethyl)-1H-benzimidazole (other names: N-pyrrolidino 
etonitazene; etonitazepyne), and N,N-diethyl-2-(5-nitro-2-(4-
propoxybenzyl)-1H-benzimidazol-1-yl)ethan-1-amine (other name: 
protonitazene), 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 of 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 
etodesnitazene, N-pyrrolidino etonitazene, and protonitazene.

DATES: Effective April 11, 2024.

FOR FURTHER INFORMATION CONTACT: Dr. Terrence L. Boos, Drug and 
Chemical Evaluation Section, Diversion Control Division, Drug 
Enforcement Administration; Telephone: (571) 362-3249.

SUPPLEMENTARY INFORMATION:

Legal Authority

    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 he 
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).\1\
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    \1\ 28 CFR 0.100.
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Background

    On April 12, 2022, DEA issued a temporary scheduling order, placing 
etodesnitazene, N-pyrrolidino etonitazene, and protonitazene, along 
with four other substances,\2\ temporarily in schedule I of the 
Controlled Substances Act (CSA).\3\ That order for etodesnitazene, N-
pyrrolidino etonitazene, and protonitazene (codified at 21 CFR 
1308.11(h)(51), (55), and (56)) was based on findings by the 
Administrator that the temporary

[[Page 25515]]

scheduling was necessary to avoid an imminent hazard to the public 
safety.\4\
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    \2\ Those four other substances, [butonitazene, flunitazene, 
metodesnitazene, metonitazene], will not be discussed further in 
this final order.
    \3\ Schedules of Controlled Substances: Temporary Placement of 
Butonitazene, Etodesnitazene, flunitazene, Metodesnitazene, 
Metonitazene, N-Pyrrolidino etonitazene, and Protonitazene in 
Schedule I, 87 FR 21556 (Apr. 12, 2022).
    \4\ Id.
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    On November 24, 2022, the Director-General of the World Health 
Organization recommended to the Secretary-General that etodesnitazene, 
N-pyrrolidino etonitazene, and protonitazene be placed in Schedule I of 
the Single Convention, as these substances have opioid-agonist 
mechanism of action similar to drugs that are controlled in Schedule I 
of the Single Convention (i.e., etodesnitazene, N-pyrrolidino 
etonitazene, and protonitazene are similar to drugs such as 
isotonitazene and fentanyl) and has dependence and abuse potential. On 
May 17, 2023, the United States government was informed by the 
Secretariat of the United Nations, by letter, that during its 66th 
session in March 2023, the Commission voted to place etodesnitazene, N-
pyrrolidino etonitazene, and protonitazene in Schedule I of the Single 
Convention (CND Mar/66/2, 66/3, and 66/4).

Etodesnitazene, N-Pyrrolidino Etonitazene, and Protonitazene

    As discussed in the background section, etodesnitazene, N-
pyrrolidino etonitazene, and protonitazene are temporarily controlled 
in schedule I of the CSA upon the Administrator's finding they pose 
imminent hazard to the public safety. Etodesnitazene, N-pyrrolidino 
etonitazene, and protonitazene share a pharmacological profile with 
etonitazene (schedule I), isotonitazene (schedule I), and other 
schedule I and II synthetic opioids that act as mu-opioid receptor 
agonists. The use of these substances presents a high risk of abuse and 
have negatively affected users and communities due to their 
pharmacological similarities with etonitazene and isotonitazene (potent 
mu-opioid agonists). The abuse of etodesnitazene, N-pyrrolidino 
etonitazene, and protonitazene has been associated with at least 46 
toxicology cases in the United States between January 2021 and April 
2023. The positive identification of these substances in toxicology 
cases is a serious concern to the public safety.
    Law enforcement reports demonstrate that etodesnitazene, N-
pyrrolidino etonitazene, and protonitazene are being illicitly 
distributed and abused. The illicit use and distribution of these 
substances are similar to that of isotonitazene (schedule I) and 
prescription opioid analgesics. According to the National Forensic 
Laboratory Information System (NFLIS-Drug) database, which collects 
drug identification results from drug cases submitted to and analyzed 
by Federal, State and local forensic laboratories, there has been 596 
reports for etodesnitazene, N-pyrrolidino etonitazene, and 
protonitazene between January 2020 and May 2023 \5\ (query date: May 
15, 2023).
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    \5\ Reports to NFLIS-Drug are still pending for 2023.
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    DEA is not aware of any claims or of any medical or scientific 
literature suggesting that etodesnitazene, N-pyrrolidino etonitazene, 
and protonitazene have a currently accepted medical use in treatment in 
the United States. In addition, the Department of Health and Human 
Services (HHS) advised DEA, by letters dated July 7 and September 10, 
2021, that there were no investigational new drug applications (IND) or 
approved new drug applications (NDA) for etodesnitazene, N-pyrrolidino 
etonitazene, and protonitazene in the United States. Since September 
10, 2021, HHS has not advised DEA of any new IND or NDA for any of 
these substances. Because etodesnitazene, N-pyrrolidino etonitazene, 
and protonitazene 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 
etodesnitazene, N-pyrrolidino etonitazene, and protonitazene have no 
currently accepted medical use in treatment in the United States \6\ 
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 
etodesnitazene, N-pyrrolidino etonitazene, and protonitazene pursuant 
to 21 U.S.C. 811(a).
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    \6\ HHS and DEA both applied a five-part test for currently 
accepted medical use as part of this scheduling action. Under that 
test, with respect to a drug that has not been approved by the Food 
and Drug Administration, to have a currently accepted medical use in 
treatment in the United States, all of the following must be 
demonstrated: i. the drug's chemistry must be known and 
reproducible; ii. there must be adequate safety studies; iii. there 
must be adequate and well-controlled studies proving efficacy; iv. 
the drug must be accepted by qualified experts; and v. the 
scientific evidence must be widely available. Marijuana Scheduling 
Petition; Denial of Petition; Remand, 57 FR 10499 (Mar. 26, 1992), 
pet. for rev. denied, Alliance for Cannabis Therapeutics v. Drug 
Enforcement Admin., 15 F.3d 1131, 1135 (D.C. Cir. 1994).
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Conclusion

    In order to meet the United States' obligations under the Single 
Convention and because etodesnitazene, N-pyrrolidino etonitazene, and 
protonitazene have no currently accepted medical use in treatment in 
the United States, the Administrator has determined that 
etodesnitazene, N-pyrrolidino etonitazene, and protonitazene, 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, should be 
placed permanently in schedule I of the CSA.

Requirements for Handling

    Etodesnitazene, N-pyrrolidino etonitazene, and protonitazene have 
been controlled in schedule I of the CSA since April 12, 2022. Upon the 
effective date of this final order, etodesnitazene, N-pyrrolidino 
etonitazene, and protonitazene will be permanently subject to the CSA's 
schedule I regulatory controls and administrative, civil, and criminal 
sanctions applicable to the manufacture of, distribution of, 
importation of, exportation of, engagement in research or conduct of 
instructional activities with, and possession of, schedule I controlled 
substances, including the following:
    1. Registration. Any person who handles (manufactures, distributes, 
imports, exports, engages in research or conducts instructional 
activities with, or possesses), or who desires to handle, 
etodesnitazene, N-pyrrolidino etonitazene, or protonitazene 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. Etodesnitazene, N-pyrrolidino etonitazene, 
and protonitazene 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. Etodesnitazene, N-pyrrolidino etonitazene, and 
protonitazene are subject to schedule I security requirements and must 
be handled and stored pursuant to 21 U.S.C. 823, and in accordance with 
21

[[Page 25516]]

CFR 1301.71 through 1301.76. Non-practitioners handling etodesnitazene, 
N-pyrrolidino etonitazene, or protonitazene must comply with the 
employee screening requirements of 21 CFR 1301.90 through 1301.93.
    4. Labeling and packaging. All labels, labeling, and packaging for 
commercial containers of etodesnitazene, N-pyrrolidino etonitazene, and 
protonitazene 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 etodesnitazene, N-pyrrolidino etonitazene, and 
protonitazene in accordance with a quota assigned pursuant to 21 U.S.C. 
826, and in accordance with 21 CFR part 1303.
    6. Inventory. Every DEA registrant who possesses any quantity of 
etodesnitazene, N-pyrrolidino etonitazene, or protonitazene has been 
required to keep an inventory of all stocks of these substances on hand 
as of April 12, 2022, pursuant to 21 U.S.C. 827, and in accordance with 
21 CFR 1304.03, 1304.04, and 1304.11.
    7. Records and Reports. DEA registrants must maintain records and 
submit reports with respect to etodesnitazene, N-pyrrolidino 
etonitazene, and protonitazene pursuant to 21 U.S.C. 827, and in 
accordance with 21 CFR 1301.74(b) and (c), 1301.76(b), and 1307.11 and 
21 CFR parts 1304, 1312, and 1317. Manufacturers and distributors must 
submit reports regarding etodesnitazene, N-pyrrolidino etonitazene, and 
protonitazene to the Automation of Reports and Consolidated Order 
System (ARCOS) pursuant to 21 U.S.C. 827 and in accordance with 21 CFR 
parts 1304 and 1312.
    8. Order Forms. All DEA registrants who distribute etodesnitazene, 
N-pyrrolidino etonitazene, or protonitazene must continue to comply 
with order form requirements pursuant to 21 U.S.C. 828 and in 
accordance with 21 CFR part 1305.
    9. Importation and Exportation. All importation and exportation of 
etodesnitazene, N-pyrrolidino etonitazene, and protonitazene must 
continue to comply with 21 U.S.C. 952, 953, 957, and 958, and in 
accordance with 21 CFR part 1312.
    10. Liability. Any activity involving etodesnitazene, N-pyrrolidino 
etonitazene, or protonitazene not authorized by, or in violation of the 
CSA, 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)

    This action is not a significant regulatory action as defined by 
Executive Order (E.O.) 12866 (Regulatory Planning and Review), section 
3(f), as amended by E.O. 14094, section 1(b), and the principles 
reaffirmed in E.O. 13563 (Improving Regulation and Regulatory Review); 
and, accordingly, this action has not been reviewed by the Office of 
Management and Budget (OMB). This action makes no change in the status 
quo, as etodesnitazene, N-pyrrolidino etonitazene, and protonitazene 
are already listed as schedule I controlled substances.

Executive Order 12988, Civil Justice Reform

    This action 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 action does not have federalism implications warranting the 
application of E.O. 13132. This action does not have substantial direct 
effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This action does not have tribal implications warranting the 
application of E.O. 13175. The action 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.

Administrative Procedure Act

    The CSA provides for an expedited scheduling action where control 
is required by the United States' obligations under international 
treaties, conventions, or protocols. 21 U.S.C. 811(d)(1). If control is 
required pursuant to such international treaty, convention, or 
protocol, the Attorney General, as delegated to the Administrator, must 
issue an order controlling such drug under the schedule he deems most 
appropriate to carry out such obligations, and ``without regard to'' 
the findings and rulemaking procedures otherwise required for 
scheduling actions in 21 U.S.C. 811(a) and (b). Id.
    In accordance with 21 U.S.C. 811(d)(1), scheduling actions for 
drugs that are required to be controlled by the United States' 
obligations under international treaties, conventions, or protocols in 
effect on October 27, 1970, shall be issued by order (as opposed to 
scheduling by rule pursuant to 21 U.S.C. 811(a)). Therefore, DEA 
believes that the notice and comment requirements of section 553 of the 
Administrative Procedure Act (APA), 5 U.S.C. 553, do not apply to this 
scheduling action.

Regulatory Flexibility Act

    The Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612) applies to 
rules that are subject to notice and comment under section 553(b) of 
the APA or any other law. As explained above, the CSA exempts this 
final order from notice and comment. Consequently, the RFA does not 
apply to this action.

Paperwork Reduction Act of 1995

    This action does not impose a new collection of information 
requirement under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-
3521. Also, this action does not impose new or modify existing 
recordkeeping or reporting requirements on State or local governments, 
individuals, businesses, or organizations. However, this action does 
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.

Unfunded Mandates Reform Act of 1995

    In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995, 
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 UMRA of 1995.

[[Page 25517]]

Congressional Review Act

    This order is not a major rule as defined by the Congressional 
Review Act (CRA), 5 U.S.C. 804. However, DEA is submitting reports 
under the CRA to both Houses of Congress and to the Comptroller 
General.

List of Subjects in 21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.

Signing Authority

    This document of the Drug Enforcement Administration was signed on 
April 5, 2024, by Administrator Anne Milgram. That document with the 
original signature and date is maintained by DEA. For administrative 
purposes only, and in compliance with requirements of the Office of the 
Federal Register, the undersigned DEA Federal Register Liaison Officer 
has been authorized to sign and submit the document in electronic 
format for publication, as an official document of DEA. This 
administrative process in no way alters the legal effect of this 
document upon publication in the Federal Register.

Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.

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

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for part 1308 continues to read as follows:

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


0
2. In Sec.  1308.11:
0
a. Redesignate paragraphs (b)(95) through (103) as paragraphs (b)(98) 
through (106);
0
b. Redesignate paragraphs (b)(69) through (94) as paragraphs (b)(71) 
through (96);
0
c. Redesignate paragraphs (b)(40) through (68) as paragraphs (b)(41) 
through (69);
0
d. Add new paragraph (b)(40), (70), and (97); and
0
e. Remove and reserve paragraphs (h)(51), (55), and (56).
    The addition reads as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (b) * * *

 
                              * * * * * * *
(40) 2-(2-(4-ethoxybenzyl)-1H-benzimidazol-1-yl)-N,N-               9765
 diethylethan-1-amine (Other names: etodesnitazene; etazene)....
 
                              * * * * * * *
(70) 2-(4-ethoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-    9758
 benzimidazole (Other names: N-pyrrolidino etonitazene;
 etonitazepyne).................................................
 
                              * * * * * * *
(97) N,N-diethyl-2-(5-nitro-2-(4-propoxybenzyl)-1H-benzimidazol-    9759
 1-yl)ethan-1-amine (Other name: protonitazene).................
 

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[FR Doc. 2024-07684 Filed 4-10-24; 8:45 am]
BILLING CODE 4410-09-P