Rule2025-23717
Schedules of Controlled Substances: Placement of N-Desethyl Isotonitazene and N-Piperidinyl Etonitazene in Schedule I
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
December 23, 2025
Effective
January 22, 2026
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
With the issuance of this final order, the Administrator of the Drug Enforcement Administration is permanently placing N-ethyl-2- (2-(4-isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine (other name: N-desethyl isotonitazene) and 2-(4-ethoxybenzyl)-5-nitro- 1-(2-(piperidin-1-yl)ethyl)-1H-benzimidazole (other names: N- 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 N-desethyl isotonitazene and N-piperidinyl etonitazene.
Full Text
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<title>Federal Register, Volume 90 Issue 244 (Tuesday, December 23, 2025)</title>
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[Federal Register Volume 90, Number 244 (Tuesday, December 23, 2025)]
[Rules and Regulations]
[Pages 59969-59972]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-23717]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-1143]
Schedules of Controlled Substances: Placement of N-Desethyl
Isotonitazene and N-Piperidinyl Etonitazene 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 N-ethyl-2-
(2-(4-isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine
(other name: N-desethyl isotonitazene) and 2-(4-ethoxybenzyl)-5-nitro-
1-(2-(piperidin-1-yl)ethyl)-1H-benzimidazole (other names: N-
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 N-desethyl isotonitazene and N-piperidinyl
etonitazene.
DATES: Effective January 22, 2026.
ADDRESSES: 8701 Morrissette Drive, Springfield, Virginia 22152.
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
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
[[Page 59970]]
Drug Enforcement Administration (DEA).\1\
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\1\ 28 CFR 0.100.
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Background
On July 29, 2024, DEA issued a temporary scheduling order, placing
N-desethyl isotonitazene and N-piperidinyl etonitazene temporarily in
schedule I of the CSA.\2\ That order for N-desethyl isotonitazene and
N-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.\3\
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\2\ Schedules of Controlled Substances: Temporary Placement of
N-desethyl isotonitazene and N-piperidinyl etonitazene in Schedule
I, 89 FR 60817 (July 29, 2024).
\3\ Id.
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On November 21, 2024, the Director-General of the World Health
Organization recommended to the Secretary-General that N-desethyl
isotonitazene and N-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 N-desethyl isotonitazene and N-piperidinyl
etonitazene in Schedule I of the Single Convention during its 68th
session on March 12, 2025 (CND Mar 68/4 and 68/3).
N-Desethyl Isotonitazene and N-Piperidinyl Etonitazene
N-Desethyl isotonitazene and N-piperidinyl etonitazene are
temporarily controlled in schedule I of the CSA because they pose
imminent hazard to the public safety. Both N-desethyl isotonitazene and
N-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. N-Desethyl
isotonitazene and N-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 N-desethyl isotonitazene and N-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 N-desethyl isotonitazene
and N-piperidinyl etonitazene are being illicitly distributed and
abused. According to the National Forensic Laboratory Information
System (NFLIS-Drug) \4\ 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 N-desethyl
isotonitazene and N-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.
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\4\ 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. See Schedules of Controlled Substances: Placement of
Carisoprodol Into Schedule IV, 76 FR 77330, 77332 (Dec. 12, 2011).
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N-Desethyl isotonitazene and N-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 N-
desethyl isotonitazene and N-piperidinyl etonitazene in the United
States. Since this letter, HHS has not advised DEA of any new IND or
NDA for these substances. Because N-desethyl isotonitazene and N-
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 N-desethyl
isotonitazene and N-piperidinyl etonitazene have no currently accepted
medical use in treatment in the United States \5\ 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 N-desethyl
isotonitazene and N-piperidinyl etonitazene pursuant to 21 U.S.C.
811(a).
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\5\ There is no evidence suggesting that N-desethyl
isotonitazene or N-piperidinyl etonitazene have a currently accepted
medical use in treatment in the United States. To determine whether
a drug or other substance has a currently accepted medical use, DEA
has traditionally applied a five-part test to a drug or substance
that has not been approved by the FDA: 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.
See 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). DEA applied the traditional five-part test and concluded
the test was not satisfied. In a recent published letter in a
different context, HHS applied an additional two-part test to
determine currently accepted medical use for substances that do not
satisfy the five-part test: (1) whether there exists widespread,
current experience with medical use of the substance by licensed
health care providers operating in accordance with implemented
jurisdiction-authorized programs, where medical use is recognized by
entities that regulate the practice of medicine, and, if so, (2)
whether there exists some credible scientific support for at least
one of the medical conditions for which part (1) is satisfied. On
April 11, 2024, the Department of Justice's Office of Legal Counsel
(OLC) issued an opinion, which, among other things, concluded that
HHS's two-part test would be sufficient to establish that a drug has
a currently accepted medical use. Office of Legal Counsel,
Memorandum for Merrick B. Garland Attorney General Re: Questions
Related to the Potential Rescheduling of Marijuana at 3 (April 11,
2024). For purposes of this scheduling order, there is no evidence
that health care providers have widespread experience with medical
use of N-desethyl isotonitazene and N-piperidinyl etonitazene or
that the use of N-desethyl isotonitazene and N-piperidinyl
etonitazene are recognized by entities that regulate the practice of
medicine, so the two-part test also is not satisfied. By letter
dated May 11, 2023, DEA has been advised by HHS that there are
currently no approved new drug applications or investigational new
drug applications for N-desethyl isotonitazene and N-piperidinyl
etonitazene. Additionally, HHS communicated no objections to the
temporary placement of N-desethyl isotonitazene and N-piperidinyl
etonitazene into schedule I of the CSA.
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Conclusion
In order to meet the United States' obligation under the Single
Convention and because N-desethyl isotonitazene and N-piperidinyl
etonitazene have no currently accepted medical use in
[[Page 59971]]
treatment in the United States, the Administrator has determined that
N-desethyl isotonitazene and N-piperidinyl etonitazene including their
isomers, esters, ethers, salts, and salts of isomers, esters, and
ethers, whenever the existence of such isomers, esters, and salts are
possible within the specific 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
As discussed above, N-desethyl isotonitazene and N-piperidinyl
etonitazene have been temporarily controlled in schedule I of the CSA
since July 29, 2024. Upon the effective date of this final order, N-
desethyl isotonitazene and N-piperidinyl etonitazene will be
permanently subject to the CSA's schedule I regulatory controls and
administrative, civil, and criminal sanctions applicable to the
manufacture, distribution, dispensing, importing, exporting, 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,
reverse distributes, imports, exports, engages in research or conducts
instructional activities or chemical analysis with, or possesses), or
who desires to handle, N-desethyl isotonitazene or N-piperidinyl
etonitazene 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. N-Desethyl isotonitazene and N-piperidinyl
etonitazene 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. N-Desethyl isotonitazene and N-piperidinyl etonitazene
are subject to schedule I security requirements and must be handled and
stored pursuant to 21 U.S.C. 821, 823, and in accordance with 21 CFR
1301.71 through 1301.76. Non-practitioners handling N-desethyl
isotonitazene and N-piperidinyl etonitazene must comply with the
screening requirements of 21 CFR 1301.90 through 1301.93.
4. Labeling and packaging. All labels, labeling, and packaging for
commercial containers of N-desethyl isotonitazene and N-piperidinyl
etonitazene must comply with 21 U.S.C. 825 and 958(e) and be in
accordance with 21 CFR part 1302.
5. Quota. Only registered manufacturers are permitted to
manufacture N-desethyl isotonitazene and N-piperidinyl etonitazene 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 N-desethyl
isotonitazene or N-piperidinyl etonitazene 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(e),
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 N-desethyl
isotonitazene and N-piperidinyl etonitazene) on hand every two years
pursuant to 21 U.S.C. 827 and 958(e) 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 N-desethyl isotonitazene and N-
piperidinyl etonitazene pursuant to 21 U.S.C. 827 and 958(e), and in
accordance with 21 CFR 1301.74(b) and (c), 1301.76(b), and 1307.11 and
parts 1304, 1312, and 1317. Manufacturers and distributors must submit
reports regarding N-desethyl isotonitazene and N-piperidinyl
etonitazene 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 N-desethyl
isotonitazene or N-piperidinyl etonitazene 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
N-desethyl isotonitazene and N-piperidinyl etonitazene 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 N-desethyl isotonitazene or
N-piperidinyl etonitazene 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, 13563, 14192, and 14294
This action is not a significant regulatory action as defined by
Executive Order (E.O.) 12866 (Regulatory Planning and Review), and the
principles reaffirmed in E.O. 13563 (Improving Regulation and
Regulatory Review). DEA scheduling actions are not subject to E.O.
14192, Unleashing Prosperity Through Deregulations, or E.O. 14294,
Fighting Overcriminalization in Federal Regulations. This action makes
no change in the status quo, as N-desethyl isotonitazene and N-
piperidinyl etonitazene 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. 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.
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.\6\ If control is required pursuant
to such international treaty, convention, or protocol, the Attorney
General, as delegated to the Administrator, must issue an order
[[Page 59972]]
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.
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\6\ 21 U.S.C. 811(d)(1).
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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 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 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.\7\ 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.
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\7\ 44 U.S.C. 3501-3521.
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Unfunded Mandates Reform Act of 1995
On the basis of information contained in the ``Regulatory
Flexibility Act'' section above, DEA has determined pursuant to the
Unfunded Mandates Reform Act (UMRA) of 1995 (2 U.S.C. 1501 et seq.)
that this final rule 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.
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.
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 21 CFR 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)(76) through (117) as paragraphs (b)(78)
through (119);
0
b. Redesignate paragraphs (b)(72) through (75) as paragraphs (b)(73)
through (76);
0
c. Add new paragraphs (b)(72), (77); and
0
h. Remove and reserve paragraphs (h)(68) and (h)(69).
The additions to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(b) * * *
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* * * * * * *
(72) N-Desethyl isotonitazene (N-ethyl-2-(2-(4- 9760
isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-
amine).................................................
* * * * * * *
(77) N-Piperidinyl etonitazene (2-(4-ethoxybenzyl)-5- 9761
nitro-1-(2-(piperidin-1-yl)ethyl)-1H-benzimidazole
(other names: etonitazepipne)..........................
* * * * * * *
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* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
December 17, 2025, by Administrator Terrance Cole. 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.
Leslie Mayer,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2025-23717 Filed 12-22-25; 8:45 am]
BILLING CODE 4410-09-P
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</html>Indexed from Federal Register on December 23, 2025.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.