[Federal Register Volume 90, Number 121 (Thursday, June 26, 2025)]
[Proposed Rules]
[Pages 27268-27273]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-11462]
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Proposed Rules
Federal Register
________________________________________________________________________
This section of the FEDERAL REGISTER contains notices to the public of
the proposed issuance of rules and regulations. The purpose of these
notices is to give interested persons an opportunity to participate in
the rule making prior to the adoption of the final rules.
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Federal Register / Vol. 90, No. 121 / Thursday, June 26, 2025 /
Proposed Rules
[[Page 27268]]
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-1494]
Schedules of Controlled Substances: Temporary Placement of Seven
Benzimidazole-Opioids in Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Proposed amendment; notice of intent.
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SUMMARY: 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.
DATES: June 26, 2025.
ADDRESSES: 8701 Morrissette Drive, Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: 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
www.regulations.gov.
SUPPLEMENTARY INFORMATION: 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 \1\ (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):
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\1\ 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.
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2-(2-((2,3-dihydrobenzofuran-5-yl)methyl)-5-nitro-1H-
benzimidazol-1-yl)-N,N-diethylethan-1-amine (commonly known as,
ethyleneoxynitazene),
2-(2-(benzodioxol-5-ylmethyl)-5-nitro-1H-benzimidazol-1-
yl)-N,N-diethylethan-1-amine (commonly known as, methylenedioxynitazene
or 3',4'-methylenedioxynitazene),
2-(2-(4-ethoxybenzyl)-5-methyl-1H-benzimidazol-1-yl)-N,N-
diethylethan-1-amine (commonly known as, 5-methyl etodesnitazene),
2-(2-(4-ethoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)-N-
ethylethan-1-amine (commonly known as, N-desethyl etonitazene),
N-ethyl-2-(5-nitro-2-(4-propoxybenzyl)-1H-benzimidazol-1-
yl)ethan-1-amine (commonly known as, N-desethyl protonitazene),
2-(2-(4-ethoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)-N,N-
dimethylethan-1-amine (commonly known as, N,N-dimethylamino
etonitazene), and
2-(4-isopropoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-
yl)ethyl)-1H-benzimidazole (commonly known as, N-pyrrolidino
isotonitazene).
The temporary scheduling order will be published in the Federal
Register on or after July 28, 2025.
Legal Authority
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.\2\ 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.\3\
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\2\ 21 U.S.C. 811(h)(1).
\3\ 21 U.S.C. 811(h)(2).
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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.\4\ The Attorney General has delegated scheduling
authority under 21 U.S.C. 811 to the Administrator of DEA
(Administrator).\5\
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\4\ 21 U.S.C. 811(h)(1); 21 CFR part 1308.
\5\ 28 CFR 0.100.
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Background
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 (i.e., to issue
a temporary scheduling order).\6\ By letter dated April 15, 2025, the
Acting Administrator transmitted the required notice to place
ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene,
N-desethyl etonitazene, N-desethyl protonitazene, N,N-dimethylamino
etonitazene, and N-pyrrolidino isotonitazene in schedule I on a
temporary basis to the Assistant Secretary for Health of HHS (Assistant
Secretary).\7\ 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, N-desethyl etonitazene, N-desethyl
protonitazene, N,N-dimethylamino etonitazene, and N-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,
[[Page 27269]]
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-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.
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\6\ 21 U.S.C. 811(h)(4).
\7\ The Secretary of HHS has delegated to the Assistant
Secretary for Health of HHS the authority to make domestic drug
scheduling recommendations. Comprehensive Drug Abuse Prevention and
Control Act of 1970, Public Law 91-513, As Amended; Delegation of
Authority, 58 FR 35460 (July 1, 1993).
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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.\8\ This consideration includes
any information indicating actual abuse, diversion from legitimate
channels, and clandestine importation, manufacture, or distribution of
ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene,
N-desethyl etonitazene, N-desethyl protonitazene, N,N-dimethylamino
etonitazene, and N-pyrrolidino isotonitazene.\9\
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\8\ 21 U.S.C. 811(h)(3).
\9\ 21 U.S.C. 811(h)(3).
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Substances meeting the statutory requirements for temporary
scheduling may only be placed in schedule I.\10\ 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.\11\
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\10\ 21 U.S.C. 811(h)(1).
\11\ 21 U.S.C. 812(b)(1).
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Seven Benzimidazole-Opioids: Ethyleneoxynitazene,
Methylenedioxynitazene, 5-Methyl Etodesnitazene, N-Desethyl
Etonitazene, N-Desethyl Protonitazene, N,N-Dimethylamino Etonitazene,
and N-Pyrrolidino Isotonitazene
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
pharmacological profile to fentanyl, morphine, and other mu-opioid
receptor agonists. Beginning in 2019, this class of synthetic opioids
known as benzimidazole-opioids, commonly referred to as ``nitazenes,''
appeared in the United States and have dominated the opioid
recreational drug market. Between August 2020 and July 2024, DEA has
temporarily controlled 10 benzimidazole-opioids because they posed a
threat to public safety.\12\ Recently, additional benzimidazole-opioids
have been identified within the rapidly expanding class of ``nitazene''
compounds in the recreational drug market. Ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-pyrrolidino isotonitazene etonitazene are some of the recently
encountered ``nitazene'' synthetic opioids identified in the illicit
drug market.
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\12\ 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); Schedules of Controlled
Substances: Temporary Placement of Isotonitazene in Schedule I, 85
FR 51342 (Aug. 20, 2020); Schedules of Controlled Substances:
Temporary Placement of N-Desethyl Isotonitazene and N-Piperidinyl
Etonitazene in Schedule I, 89 FR 60817 (Jul. 29, 2024).
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The benzimidazole-opioids have contributed to numerous fatalities.
The continued trafficking and identification of benzimidazole-opioids
in toxicology cases pose a significant threat to public health and
safety. The misuse and abuse of synthetic opioids have led to
devastating consequences including death. Preclinical pharmacology data
demonstrate that ethyleneoxynitazene, methylenedioxynitazene, 5-methyl
etodesnitazene, N-desethyl etonitazene, N-desethyl protonitazene, N,N-
dimethylamino etonitazene, and N-pyrrolidino isotonitazene have
pharmacological profiles similar to those of the potent benzimidazole-
opioids etonitazene, metonitazene, and protonitazene, schedule I opioid
substances. Thus, it is expected that these substances will have
similar harmful effects in humans. Accordingly, methylenedioxynitazene,
5-methyl etodesnitazene, N-desethyl etonitazene, N-desethyl
protonitazene, and N-pyrrolidino isotonitazene have been positively
identified in at least 37 toxicology cases. As the United States
continues to experience a high number of opioid-involved overdoses and
mortalities, the introduction of new designer opioids further
exacerbates the current opioid epidemic.
Available data and information for ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-pyrrolidino isotonitazene, summarized below, indicate that these
substances have high potentials for abuse, no currently accepted
medical uses in treatment in the United States,\13\ and a lack of
accepted safety for use under medical supervision. DEA's three-factor
analysis is available in its entirety under ``Supporting and Related
Material'' of the public docket for this action at www.regulations.gov
under Docket Number DEA-1494.
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\13\ When finding schedule I placement on a temporary basis is
necessary to avoid imminent hazard to the public, 21 U.S.C. 811(h)
does not require DEA to consider whether the substance has a
currently accepted medical use in treatment in the United States.
Nonetheless, there is no evidence suggesting that
ethyleneoxynitazene, methylenedioxynitazene, 5-methyl
etodesnitazene, N-desethyl etonitazene, N-desethyl protonitazene,
N,N-dimethylamino etonitazene, and N-pyrrolidino isotonitazene 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 notice of intent, there is no
evidence that health care providers have widespread experience with
medical use of these seven substances or that the use of these
substances is recognized by entities that regulate the practice of
medicine, so the two-part test also is not satisfied. By letter
dated May 20, 2025, DEA has been advised by HHS that there are
currently no approved new drug applications or investigational new
drug applications for seven benzimidazole-opioids. Additionally, HHS
communicated no objections to the temporary placement of these
substances into schedule I of the CSA.
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[[Page 27270]]
Factor 4. History and Current Pattern of Abuse
Benzimidazole-opioids were originally synthesized and studied for
their analgesic properties in the 1950s by the pharmaceutical research
laboratories of the Swiss chemical company Chemical Industries Basel.
The research produced a group of structurally unique benzimidazole
derivatives with analgesic properties; however, the research effort did
not produce any medically approved analgesic products. Since 2019,
there has been an emergence of benzimidazole-opioid compounds on the
illicit drug market, which have been positively identified in numerous
cases of fatal overdose events. These benzimidazole-opioid derivatives
include schedule I substances, such as synthetic opioids clonitazene,
etonitazene, and isotonitazene.
Recently, ethyleneoxynitazene, methylenedioxynitazene, 5-methyl
etodesnitazene, N-desethyl etonitazene, N-desethyl protonitazene, N,N-
dimethylamino etonitazene, and N-pyrrolidino isotonitazene have emerged
in the illicit drug market. Law enforcement officers have encountered
these seven substances in solid forms (e.g., powder and tablets) and
are often mixed with other illicit drugs. Commonly, benzimidazole-
opioids are co-detected with designer benzodiazepines, a combination
that poses significant risk to users. These substances are not approved
pharmaceutical products, and they are not approved for medical use
anywhere in the world. In a letter to DEA dated May 20, 2025, the
Acting Assistant Secretary stated that there are no FDA-approved NDAs
or INDs for ethyleneoxynitazene, methylenedioxynitazene, 5-methyl
etodesnitazene, N-desethyl etonitazene, N-desethyl protonitazene, N,N-
dimethylamino etonitazene, and N-pyrrolidino isotonitazene in the
United States; hence, there are no legitimate channels for these
substances as marketed drug products.
Reports of detection of benzimidazole-opioids in forensic casework
are on the rise. The appearance of benzimidazole-opioids on the illicit
drug market is similar to other designer opioid drugs trafficked for
their psychoactive effects. These substances are likely to be abused in
the same manner as schedule I opioids, such as etonitazene,
isotonitazene, and heroin. In 2023 and 2024, ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-pyrrolidino isotonitazene emerged on the illicit synthetic drug
market as evidenced by their identification in forensic drug seizures
and in biological samples.\14\ According to the National Forensic
Laboratory Information System (NFLIS-Drug) and DEA STARLiMS databases,
law enforcement encounters of ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-pyrrolidino isotonitazene have been identified in powder or
tablet forms.
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\14\ Gao, G., Yang, S., Wang, X., Xiang, P., Ma, L., Yan, F., &
Shi, Y. (2025). UHPLC-MS/MS-based analysis of 17 nitazenes in human
hair for practical forensic casework with simultaneous separation of
6 groups of isomers. Journal of pharmaceutical and biomedical
analysis, 257, 116707.
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Factor 5. Scope, Duration and Significance of Abuse
Ethyleneoxynitazene, methylenedioxynitazene, 5-methyl
etodesnitazene, N-desethyl etonitazene, N-desethyl protonitazene, N,N-
dimethylamino etonitazene, and N-pyrrolidino isotonitazene, similar to
etonitazene, metonitazene, and protonitazene (schedule I substances),
have been described as potent synthetic opioids, and evidence suggests
they are abused for their opioidergic effects (see Factor 6). The abuse
of these benzimidazole-opioids, similar to other synthetic opioids, has
resulted in serious adverse health effects. According to the center for
forensic science research education (CFSRE) monograph reports published
between November 2023 and December 2024, some of these benzimidazole-
opioids have been co-identified with designer benzodiazepines,
fentanyl, heroin, or another benzimidazole-opioids.\15\
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\15\ Monographs, N-desethyl etonitazene-November 30, 2023;
Monographs, 5-methyl etodesnitazene- August 26, 2024); Monographs,
Methylenedioxynitazene- August 29, 2024; Monographs- N-pyrrolidino
isotonitazene.
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Data from law enforcement suggest that ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N-pyrrolidino isotonitazene, and
N,N-dimethylamino etonitazene are being abused in the United States as
recreational drugs.\16\ Since 2023, there have been 184 exhibits
reported to the NFLIS-Drug database (which collects drug identification
results from drug cases submitted to and analyzed by federal, state,
and local forensic laboratories,) pertaining to the trafficking,
distribution, and abuse of these substances.\17\ NFLIS registered 14
encounters of ethyleneoxynitazene from 5 states; 19 encounters of
methylenedioxynitazene from 5 states; four encounters of 5-methyl
etodesnitazene from 1 state, 114 encounters of N-desethyl etonitazene
from 14 states; 9 encounters of N-desethyl protonitazene from 6 states;
12 encounters of N,N-dimethylamino etonitazene from 4 states; 12
encounters of N-pyrrolidino isotonitazene from 9 states According to
data from DEA STARLiMS database, there have been 66 identifications of
six of these substances.\18\ There have been seven identifications of
ethyleneoxynitazene, two identifications of methylenedioxynitazene, 24
identifications of N-desethyl etonitazene, seven identifications of N-
desethyl protonitazene, four identifications of N-pyrrolidino
isotonitazene and 22 identifications of N,N-dimethylamino etonitazene
in drug seizures.
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\16\ While law enforcement data are not direct evidence of
abuse, it 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).
\17\ NFLIS-Drug was queried on May 12, 2025.
\18\ There is duplication of records between NFLIS and STARLiMS.
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Because abusers of these substances are likely to obtain these
substances through unregulated sources, the identity, purity, and
quantity of these substances are uncertain and inconsistent, thus
posing significant adverse health risks to the end user. The misuse and
abuse of opioids have been demonstrated and are well-characterized.
Individuals who initiate use (i.e., use a drug for the first time) of
these benzimidazole-opioids are likely to be at risk of developing
substance use disorder, an overdose event, or death, similar to that of
other opioid analgesics (e.g., fentanyl, morphine, etc.). The
population likely to abuse these benzimidazole-opioids appears to be
the same as those abusing prescription opioid analgesics, fentanyl, and
other synthetic drugs. This is evidenced by the types of other drugs
co-identified in biological samples and law enforcement encounters. Law
enforcement and toxicology reports demonstrate that
ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene,
N-desethyl etonitazene, N-desethyl protonitazene, N,N-dimethylamino
etonitazene, and N-pyrrolidino isotonitazene are being illicitly
distributed and abused.
[[Page 27271]]
Factor 6. What, if Any, Risk There Is to the Public Health
The increase in opioid overdose deaths in the United States has
been exacerbated recently by the availability of potent synthetic
opioids on the illicit drug market. Data obtained from pre-clinical
studies demonstrate that ethyleneoxynitazene, methylenedioxynitazene,
5-methyl etodesnitazene, N-desethyl etonitazene, N-desethyl
protonitazene, N,N-dimethylamino etonitazene, and N-pyrrolidino
isotonitazene exhibit pharmacological profiles similar to that of
etonitazene, metonitazene, protonitazene, and other mu-opioid receptor
agonists.\19\ It is well established that substances that act as mu-
opioid receptor agonists have a high potential for addiction and can
induce dose-dependent respiratory depression. Consistent with any mu-
opioid receptor agonist, the potential health and safety risks for
users of these substances are high. Data obtained from trend reports
published by CFSRE, which reports on NPS opioid positivity in cases and
samples types from recreational drug use, medicolegal death
investigations, clinical intoxications, and/or driving under the
influence of drugs investigations, showed that in 2024, 5-methyl
etodesnitazene was identified in six toxicology cases;
methylenedioxynitazene in four toxicology cases; N-desethyl etonitazene
in 11 cases; N-desethyl protonitazene was identified as a metabolite of
protonitazene in eleven cases and as a parent compound in seven cases;
N-pyrrolidino isotonitazene has been identified in one toxicology
case.\20\ A study conducted to develop an analytical method for
identifying nitazenes in human hair detected the presence of N,N-
dimethylamino etonitazene in two biological samples obtained from
individuals suspected of smoking tobacco products containing
nitazenes.\21\
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\19\ DEA-VA Interagency Agreement. ``In Vitro Receptor and
Transporter Assays for Abuse Liability Testing for the DEA by the
VA''. Binding and Functional Activity at Delta, Kappa and Mu Opioid
Receptors. 2022 2024.
\20\ NPS Opioids-- 2024 Q1-Q4 reports.
\21\ Gao, G., Yang, S., Wang, X., Xiang, P., Ma, L., Yan, F., &
Shi, Y. (2025). UHPLC-MS/MS-based analysis of 17 nitazenes in human
hair for practical forensic casework with simultaneous separation of
6 groups of isomers. Journal of pharmaceutical and biomedical
analysis, 257, 116707.
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The public health risks attendant to the abuse of mu-opioid
receptor agonists are well established and have resulted in large
numbers of drug treatment admissions, emergency department visits, and
fatal overdoses. The introduction of potent synthetic opioids, such as
ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene,
N-desethyl etonitazene, N-desethyl protonitazene, N,N-dimethylamino
etonitazene, and N-pyrrolidino isotonitazene, into the illicit market
may serve as a portal to problematic opioid use for those seeking these
powerful opioids. The United States is currently experiencing an opioid
epidemic, and the presence of synthetic opioids on the illicit drug
market further exacerbates the problem. The trafficking and abuse of
new synthetic opioids are deadly trends which pose 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 has been a serious concern in recent years. Because
of the pharmacological similarities of ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-pyrrolidino isotonitazene to other schedule I opioids such as
etonitazene and protonitazene, the use of these substances presents
high risk of abuse and may negatively affect users and communities. The
positive identification of these substances in toxicology and forensic
cases demonstrates that the use of these substance is of a serious
concern to the public safety. Thus, ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-pyrrolidino isotonitazene pose imminent hazard to public safety.
Finding of Necessity of Schedule I Placement To Avoid Imminent Hazard
to Public Safety
In accordance with 21 U.S.C. 811(h)(3), based on the available data
and information summarized above, the uncontrolled manufacture,
distribution, reverse distribution, importation, exportation,
conducting of research and chemical analysis, possession, and abuse of
ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene,
N-desethyl etonitazene, N-desethyl protonitazene, N,N-dimethylamino
etonitazene, and N-pyrrolidino isotonitazene pose imminent hazards to
public safety. DEA is not aware of any currently accepted medical uses
for these substances in the United States. A substance meeting the
statutory requirements for temporary scheduling, found in 21 U.S.C.
811(h)(1), may only be placed in schedule I. Substances in schedule I
must have a 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. Available data and information for
ethyleneoxynitazene, methylenedioxynitazene, 5-methyl etodesnitazene,
N-desethyl etonitazene, N-desethyl protonitazene, N,N-dimethylamino
etonitazene, and N-pyrrolidino isotonitazene indicate that these
substances meet the three statutory criteria.
As required by 21 U.S.C. 811(h)(4), the Acting Administrator
transmitted to the Acting Assistant Secretary, via letter dated April
15, 2025, notice of DEA's intent to place ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, N-desethyl protonitazene, N,N-dimethylamino etonitazene,
and N-pyrrolidino isotonitazene in schedule I on a temporary basis. In
a letter dated May 20, 2025, the Acting Assistant Secretary for Health
did not object to the temporary placement of these substances in
schedule I.
Conclusion
This notice of intent provides the 30-day notice pursuant to 21
U.S.C. 811(h)(1) of DEA's intent to issue a temporary scheduling order.
In accordance with 21 U.S.C. 811(h)(1) and (3), the Acting
Administrator considered available data and information, herein set
forth the grounds for his determination that it is necessary to
temporarily schedule ethyleneoxynitazene, methylenedioxynitazene, 5-
methyl etodesnitazene, N-desethyl etonitazene, N-desethyl
protonitazene, N,N-dimethylamino etonitazene, and N-pyrrolidino
isotonitazene in schedule I of the CSA, and finds that placement of
these substances in schedule I is necessary to avoid an imminent hazard
to the public safety.
The temporary placement of ethyleneoxynitazene,
methylenedioxynitazene, 5-methyl etodesnitazene, N-desethyl
etonitazene, and N-desethyl protonitazene in schedule I of the CSA will
take effect pursuant to a temporary scheduling order, which will not be
issued before July 28, 2025. Because the Acting Administrator hereby
finds this temporary scheduling order necessary to avoid an imminent
hazard to the public safety, it will take effect on the date the order
is published in the Federal Register and remain in effect for two
years, with a possible extension of one
[[Page 27272]]
year, pending completion of the regular (permanent) scheduling
process.\22\ The Acting Administrator intends to issue a temporary
scheduling order as soon as possible after the expiration of 30 days
from the date of publication of this document. Upon the temporary
order's publication, ethyleneoxynitazene, methylenedioxynitazene, 5-
methyl etodesnitazene, N-desethyl etonitazene, N-desethyl
protonitazene, N,N-dimethylamino etonitazene, and N-pyrrolidino
isotonitazene will then be subject to the CSA's schedule I regulatory
controls and to administrative, civil, and criminal sanctions
applicable to their manufacture, distribution, reverse distribution,
importation, exportation, research, conduct of instructional activities
and chemical analysis, and possession.
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\22\ 21 U.S.C. 811(h)(1) and (2).
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The CSA sets forth specific criteria for scheduling drugs or other
substances. Regular scheduling actions in accordance with 21 U.S.C.
811(a) are subject to formal rulemaking procedures ``on the record
after opportunity for a hearing'' conducted pursuant to the provisions
of 5 U.S.C. 556 and 557.\23\ The regular scheduling process of formal
rulemaking affords interested parties appropriate process and the
government any additional relevant information needed to make a
determination. Final decisions that conclude the regular scheduling
process of formal rulemaking are subject to judicial review.\24\
Temporary scheduling orders are not subject to judicial review.\25\
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\23\ 21 U.S.C. 811.
\24\ 21 U.S.C. 877.
\25\ 21 U.S.C. 811(h)(6).
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Regulatory Analyses
The CSA provides for expedited temporary scheduling actions where
necessary to avoid an imminent hazard to the public safety. Under 21
U.S.C. 811(h)(1), the Administrator, as delegated by the Attorney
General, may, by order, temporarily place substances in schedule I.
Such orders may not be issued before the expiration of 30 days from:
(1) The publication of a notice in the Federal Register of the intent
to issue such order and the grounds upon which such order is to be
issued, and (2) the date that notice of the proposed temporary
scheduling order is transmitted to the Assistant Secretary, as
delegated by the Secretary of HHS.\26\
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\26\ 21 U.S.C. 811(h)(1).
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Inasmuch as section 811(h) directs that temporary scheduling
actions be issued by order and sets forth the procedures by which such
orders are to be issued, including the requirement to publish in the
Federal Register a notice of intent, the notice-and-comment
requirements of section 553 of the Administrative Procedure Act (APA),
5 U.S.C. 553, do not apply to this notice of intent. The APA expressly
differentiates between orders and rules, as it defines an ``order'' to
mean a ``final disposition, whether affirmative, negative, injunctive,
or declaratory in form, of an agency in a matter other than rule
making.'' \27\ This contrasts with permanent scheduling actions, which
are subject to formal rulemaking procedures done ``on the record after
opportunity for a hearing,'' and final decisions that conclude the
scheduling process and are subject to judicial review.\28\ The specific
language chosen by Congress indicates its intent that DEA issue orders
instead of proceeding by rulemaking when temporarily scheduling
substances. Given that Congress specifically requires the Administrator
(as delegated by the Attorney General) to follow rulemaking procedures
for other kinds of scheduling actions, see 21 U.S.C. 811(a), it is
noteworthy that, in section 811(h)(1), Congress authorized the issuance
of temporary scheduling actions by order rather than by rule.
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\27\ 5 U.S.C. 551(6) (emphasis added).
\28\ 21 U.S.C. 811(a) and 877.
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Even assuming that this notice of intent is subject to section 553
of the APA, the Acting Administrator finds that there is good cause to
forgo its notice-and-comment requirements, as any further delays in the
process for issuing temporary scheduling orders would be impracticable
and contrary to the public interest given the manifest urgency to avoid
an imminent hazard to the public safety.
Although DEA believes this notice of intent to issue a temporary
scheduling order is not subject to the notice-and-comment requirements
of section 553 of the APA, DEA notes that in accordance with 21 U.S.C.
811(h)(4), the Acting Administrator took into consideration comments
submitted by the then-Assistant Secretary in response to the notices
that DEA transmitted to the Assistant Secretary pursuant to such
subsection.
Further, DEA believes that this temporary scheduling action is not
a ``rule'' as defined by 5 U.S.C. 601(2), and, accordingly, is not
subject to the requirements of the Regulatory Flexibility Act (RFA).
The requirements for the preparation of an initial regulatory
flexibility analysis in 5 U.S.C. 603(a) are not applicable where, as
here, DEA is not required by section 553 of the APA or any other law to
publish a general notice of proposed rulemaking. As discussed above,
DEA is issuing this notice of intent pursuant to DEA's authority to
issue a temporary scheduling order.\29\ Therefore, in this instance,
since DEA believes this temporary scheduling action is not a ``rule,''
it is not subject to the requirements of the RFA when issuing this
temporary action.
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\29\ 21 U.S.C. 811(h)(1).
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In accordance with the principles of Executive Orders (E.O.) 12866,
13563 and 14192, this action is not a significant regulatory action.
E.O. 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, if regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health, and safety effects;
distributive impacts; and equity). E.O. 13563 is supplemental to and
reaffirms the principles, structures, and definitions governing
regulatory review as established in E.O. 12866. Because this is not a
rulemaking action, this is not a significant regulatory action as
defined in Section 3(f) of E.O. 12866. DEA scheduling actions are not
subject to E.O. 14192, Unleashing Prosperity Through Deregulation.
This action will 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. Therefore, in accordance with E.O. 13132, it is
determined that this action does not have sufficient federalism
implications to warrant the preparation of a Federalism Assessment.
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 proposes to amend 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, add paragraphs (h)(77-83) to read as follows:
[[Page 27273]]
Sec. 1308.11 Schedule I.
* * * * *
(h) * * *
* * * * * * *
(77) 2-(2-((2,3-dihydrobenzofuran-5-yl)methyl)-5-nitro-1H- 9770
benzimidazol-1-yl)-N,N-diethylethan-1-amine, its isomers,
esters, ethers, salts, and salts of isomers, esters and ethers
(Other name: Ethyleneoxynitazene).............................
(78) 2-(2-(benzodioxol-5-ylmethyl)-5-nitro-1H-benzimidazol-1- 9766
yl)-N,N-diethylethan-1-amine, its isomers, esters, ethers,
salts, and salts of isomers, esters and ethers (Other names:
Methylenedioxynitazene; 3',4'-methylenedioxynitazene).........
(79) 2-(2-(4-ethoxybenzyl)-5-methyl-1H-benzimidazol-1-yl)-N,N- 9767
diethylethan-1-amine, its isomers, esters, ethers, salts, and
salts of isomers, esters and ethers (Other name: 5-methyl
etodesnitazene)...............................................
(80) 2-(2-(4-ethoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)-N- 9768
ethylethan-1-amine, its isomers, esters, ethers, salts, and
salts of isomers, esters and ethers (Other name: N-desethyl
etonitazene)..................................................
(81) N-ethyl-2-(5-nitro-2-(4-propoxybenzyl)-1H-benzimidazol-1- 9769
yl)ethan-1-amine its isomers, esters, ethers, salts, and salts
of isomers, esters and ethers (Other name: N-desethyl
protonitazene)................................................
(82) 2-(2-(4-ethoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)-N,N- 9771
dimethylethan-1-amine (Other name: N,N-dimethylamino
etonitazene)..................................................
(83) 2-(4-isopropoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1- 9772
yl)ethyl)-1H-benzimidazole (Other name: N-pyrrolidino
isotonitazene)................................................
* * * * * * *
* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
June 17, 2025, by Acting Administrator Robert J. Murphy. 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.
Gregory Aul,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2025-11462 Filed 6-25-25; 8:45 am]
BILLING CODE 4410-09-P