Schedules of Controlled Substances: Temporary Placement of N-Desethyl Isotonitazene and N-Piperidinyl Etonitazene in Schedule I, 60817-60823 [2024-16391]

Agencies

• Drug Enforcement Administration
• Department of Justice

[Federal Register Volume 89, Number 145 (Monday, July 29, 2024)]
[Rules and Regulations]
[Pages 60817-60823]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-16391]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-1143]


Schedules of Controlled Substances: Temporary Placement of N-
Desethyl Isotonitazene and N-Piperidinyl Etonitazene in Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Temporary amendment; temporary scheduling order.

-----------------------------------------------------------------------

SUMMARY: The Administrator of the Drug Enforcement Administration is 
issuing this temporary order to schedule two synthetic benzimidazole-
opioid substances, as identified in this order, in schedule I of the 
Controlled Substances Act. This action is based on a finding by the 
Administrator that the placement of these two substances in schedule I 
is necessary to avoid imminent hazard to the public safety. This order 
imposes the regulatory controls and administrative, civil, and criminal 
sanctions applicable to schedule I controlled substances on persons who 
handle (manufacture, distribute, reverse distribute, import, export, 
engage in research, conduct instructional activities or chemical 
analysis with, or possess) or propose to handle these two specified 
controlled substances.

[[Page 60818]]


DATES: This temporary scheduling order is effective July 29, 2024, 
until July 29, 2026. If this order is extended or made permanent, DEA 
will publish a document in the Federal Register.

FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Ph.D., Drug and 
Chemical Evaluation Section, Diversion Control Division, Drug 
Enforcement Administration; Mailing Address: 8701 Morrissette Drive, 
Springfield, Virginia 22152; Telephone: (571) 362-3249.

SUPPLEMENTARY INFORMATION: The Drug Enforcement Administration (DEA) 
issues a temporary scheduling order \1\ (in the form of a temporary 
amendment) to add the following two substances, including their 
isomers, esters, ethers, salts, and salts of isomers, esters, and 
ethers whenever the existence of such isomers, esters, ethers, and 
salts is possible, to schedule I under the Controlled Substances Act 
(CSA):
---------------------------------------------------------------------------

    \1\ Though DEA has used the term ``final order'' with respect to 
temporary scheduling orders in the past, this action adheres to the 
statutory language of 21 U.S.C. 811(h), which refers to a 
``temporary scheduling order.'' No substantive change is intended.
---------------------------------------------------------------------------

     N-ethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1H-benzimidazol-
1-yl)ethan-1-amine (commonly known as N-desethyl isotonitazene), and
     2-(4-ethoxybenzyl)-5-nitro-1-(2-(piperidin-1-yl)ethyl)-1H-
benzimidazole (commonly known as either N-piperidinyl etonitazene or 
etonitazepipne).

Legal Authority

    Under 21 U.S.C. 811(h)(1), the Attorney General, as delegated to 
the Administrator of DEA (Administrator) pursuant to 28 CFR 0.100, has 
the authority to temporarily place a substance in schedule I of the CSA 
for two years without regard to the evaluation requirements of 21 
U.S.C. 811(b), if the Administrator finds that such action is necessary 
to avoid an imminent hazard to the public safety.\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\
---------------------------------------------------------------------------

    \2\ 21 U.S.C. 811(h)(1).
    \3\ 21 U.S.C. 811(h)(2).
---------------------------------------------------------------------------

    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\
---------------------------------------------------------------------------

    \4\ 21 U.S.C. 811(h)(1); 21 CFR part 1308.
---------------------------------------------------------------------------

Background

    The CSA requires the Administrator to notify the Secretary of the 
Department of Health and Human Services (HHS) of an intent to place a 
substance in schedule I of the CSA temporarily (i.e., to issue a 
temporary scheduling order).\5\ The Administrator transmitted the 
required notice to the Assistant Secretary for Health of HHS (Assistant 
Secretary),\6\ by letter dated April 3, 2023, regarding N-desethyl 
isotonitazene and N-piperidinyl etonitazene. The Assistant Secretary 
responded to this notice by letter dated May 11, 2023, and advised that 
based on a review by the Food and Drug Administration (FDA), there are 
currently no investigational new drug applications (IND) or approved 
new drug applications (NDA) for N-desethyl isotonitazene and N-
piperidinyl etonitazene. The Assistant Secretary also stated that HHS 
had no objection to the temporary placement of these substances in 
schedule I. N-Desethyl isotonitazene and N-piperidinyl etonitazene 
currently are not listed in any schedule under the CSA, and no 
exemptions or approvals under 21 U.S.C. 355 are in effect for these 
substances.
---------------------------------------------------------------------------

    \5\ 21 U.S.C. 811(h)(4).
    \6\ The Secretary of HHS has delegated to the Assistant 
Secretary for Health of HHS the authority to make domestic drug 
scheduling recommendations. 58 FR 35460 (July 1, 1993).
---------------------------------------------------------------------------

    DEA has taken into consideration the Assistant Secretary's comments 
as required by subsection 811(h)(4). DEA has found the control of N-
desethyl isotonitazene and N-piperidinyl etonitazene in schedule I on a 
temporary basis is necessary to avoid an imminent hazard to the public 
safety.
    As required by 21 U.S.C. 811(h)(1)(A), DEA published a notice of 
intent (NOI) to temporarily schedule N-desethyl isotonitazene and N-
piperidinyl etonitazene on October 25, 2023.\7\ That NOI discussed 
findings from DEA's three-factor analysis dated January 2023, which DEA 
made available on www.regulations.gov.
---------------------------------------------------------------------------

    \7\ 88 FR 73293 (Oct. 25, 2023).
---------------------------------------------------------------------------

    To find that temporarily placing a substance in schedule I of the 
CSA is necessary to avoid an imminent hazard to the public safety, the 
Administrator must consider three of the eight factors set forth in 21 
U.S.C. 811(c): the substance's history and current pattern of abuse; 
the scope, duration, and significance of abuse; and what, if any, risk 
there is to the public health.\8\ Consideration of these factors 
includes any information indicating actual abuse, diversion from 
legitimate channels, and clandestine importation, manufacture, or 
distribution of these substances.\9\
---------------------------------------------------------------------------

    \8\ 21 U.S.C. 811(h)(3).
    \9\ Id.
---------------------------------------------------------------------------

    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\
---------------------------------------------------------------------------

    \10\ 21 U.S.C. 811(h)(1).
    \11\ 21 U.S.C. 812(b)(1).
---------------------------------------------------------------------------

Two Benzimidazole-Opioids: N-desethyl isotonitazene and N-piperidinyl 
etonitazene

    The continued encounter of novel psychoactive substances (NPS) on 
the recreational drug market poses a threat to public safety. Following 
the class-wide scheduling of fentanyl-related substances,\12\ there has 
been an increase in the emergence of synthetic opioids that are not 
structurally related to fentanyl. Beginning in 2019, a new class of 
synthetic opioids known as benzimidazole-opioids, commonly referred to 
as ``nitazenes,'' emerged on the recreational drug market. This class 
of substances was first synthesized in the 1950s by CIBA 
Aktiengesellschaft in Switzerland, and it has a similar pharmacological 
profile to fentanyl, morphine, and other mu-opioid receptor agonists. 
Between August 2020 and April 2022, DEA temporarily controlled eight 
benzimidazole-opioids because they posed a threat to public safety.\13\
---------------------------------------------------------------------------

    \12\ On February 6, 2018, pursuant to 21 U.S.C. 811(h), the then 
Acting Administrator of Drug Enforcement Administration temporarily 
placed fentanyl-related substances in schedule I of the Controlled 
Substances Act (CSA) (83 FR 5188) to avoid an imminent hazard to 
public safety. Through the Temporary Reauthorization and Study of 
Emergency Scheduling of Fentanyl Analogues Act, Public Law 116-114, 
which became law on February 6, 2020, Congress extended the 
temporary control of fentanyl-related substances until May 6, 2021. 
This temporary order was subsequently extended multiple times, most 
recently through the Consolidated Appropriations Act of 2023, Public 
Law 117-328, which extended the order until December 31, 2024.
    \13\ 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).
---------------------------------------------------------------------------

    Recently, additional benzimidazole-opioids have been identified 
within the rapidly expanding class of ``nitazene'' compounds on the 
recreational drug market. N-Desethyl isotonitazene and N-piperidinyl 
etonitazene are some of the recently encountered ``nitazene''

[[Page 60819]]

 synthetic opioids identified on the illicit drug market.
    The continued trafficking and identification of benzimidazole-
opioids in toxicology cases pose a significant threat to public health 
and safety. Adverse health effects associated with the misuse and abuse 
of synthetic opioids have led to devastating consequences including 
death. Preclinical pharmacology data demonstrate that N-desethyl 
isotonitazene and N-piperidinyl etonitazene have pharmacological 
profiles similar to those of the potent benzimidazole-opioids 
etonitazene and isotonitazene, schedule I opioid substances.\14\ N-
Desethyl isotonitazene, an active metabolite of isotonitazene, has been 
positively identified in at least ten toxicology cases.\15\ N-
Piperidinyl etonitazene has been positively identified in at least 
three toxicology cases.\16\ 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.
---------------------------------------------------------------------------

    \14\ 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.
    \15\ Walton SE, Krotulski AJ, Logan BK. A Forward-Thinking 
Approach to Addressing the New Synthetic Opioid 2-
Benzylbenzimidazole Nitazene Analogs by Liquid Chromatography-Tandem 
Quadrupole Mass Spectrometry (LC-QQQ-MS). J Anal Toxicol. 2022 Mar 
21;46(3):221-231.
    \16\ Calello DP, Aldy K, Jefri M, Nguyen TT, Krotulski A, Logan 
B, Brent J, Wax P, Walton S, Manini AF; ToxIC Fentalog Study Group. 
Identification of a novel opioid, N-piperidinyl etonitazene 
(etonitazepipne), in patients with suspected opioid overdose. Clin 
Toxicol (Phila). 2022 Sep;60(9):1067-1069.
---------------------------------------------------------------------------

    Available data and information for N-desethyl isotonitazene and N-
piperidinyl etonitazene, summarized below, indicate that these 
substances have high potentials for abuse, no currently accepted 
medical uses in treatment in the United States,\17\ and a lack of 
accepted safety for use under medical supervision. N-Desethyl 
isotonitazene and N-piperidinyl etonitazene have been positively 
identified 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 Thus, the Administrator concludes that N-
desethyl isotonitazene and N-piperidinyl etonitazene meet the statutory 
requirements to be temporarily placed in schedule I under the CSA. 
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-1143.
---------------------------------------------------------------------------

    \17\ When finding that placing a substance in schedule I 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 N-
desethyl isonitazene and etonitazepipne 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 and HHS applied the traditional five-part test for 
currently accepted medical use in this matter. 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 practitioners 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 the 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 temporary scheduling 
action, there is no evidence that health care providers have 
widespread experience with medical use of N-desethyl isonitazene and 
etonitazepipne, or that the use of N-desethyl isonitazene and 
etonitazepipne is recognized by entities that regulate the practice 
of medicine under either the traditional five-part test or the two-
part test.
---------------------------------------------------------------------------

Factor 4. History and Current Pattern of Abuse

    In the late 1950s, pharmaceutical research laboratories of the 
Swiss chemical company CIBA Aktiengesellschaft synthesized a group of 
structurally unique benzimidazole derivatives with analgesic 
properties; however, the research effort did not produce any medically 
approved analgesic products. These benzimidazole derivatives include 
schedule I substances, such as synthetic opioids clonitazene, 
etonitazene, and isotonitazene.
    Since 2019, there has been an emergence of nitazene compounds on 
the illicit drug market, which have been positively identified in 
numerous cases of fatal overdose events. In August 2020, isotonitazene 
was placed in schedule I of the CSA (85 FR 51342). Subsequently, seven 
additional benzimidazole-opioids \18\ have been placed in schedule I of 
the CSA.
---------------------------------------------------------------------------

    \18\ Butonitazene, etodesnitazene, flunitazene, metodesnitazene, 
metonitazene, N-pyrrolidino etonitazene, and protonitazene. See 87 
FR 21556 (Apr. 12, 2022).
---------------------------------------------------------------------------

    Recently, two additional benzimidazole-opioids have emerged on the 
illicit drug market. Law enforcement officers have encountered N-
desethyl isotonitazene and N-piperidinyl etonitazene in several solid 
forms (e.g., powder and tablets). These substances are not approved 
pharmaceutical products and are not approved for medical use anywhere 
in the world. The Assistant Secretary in a letter to DEA dated May 11, 
2023, stated that there are no FDA-approved NDAs or INDs for N-desethyl 
isotonitazene and N-piperidinyl etonitazene in the United States. There 
are no legitimate channels for these substances as marketed drug 
products.
    The appearance of benzimidazole-opioids on the illicit drug market 
is similar to other designer opioid drugs that are 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 2022, N-desethyl isotonitazene was identified in counterfeit 
tablets in the United States and United Kingdom. Recent reporting by 
Center for Forensic Science Research and Education (CFSRE) indicates 
that in the United States, N-desethyl isotonitazene was identified in 
counterfeit oxycodone round blue tablets in Florida. Further, in 
December 2022, N-desethyl isotonitazene was co-identified in ``dope'' 
samples containing xylazine, fentanyl, para-fluorofentanyl, and 
designer benzodiazepines (e.g., flubromazepam and bromazolam).\19\
---------------------------------------------------------------------------

    \19\ CFSRE NPS Discovery Public Alert 2023. Case Example--N-
desethyl isotonitazene. January 2023.
---------------------------------------------------------------------------

    In 2021, N-piperidinyl etonitazene emerged on the illicit synthetic 
drug market, as evidenced by its identification in toxicological 
analysis of biological samples.\20\ In addition, there have been 
encounters of N-piperidinyl etonitazene in Europe. As reported in 
January 2022 by the European Monitoring Center for Drugs

[[Page 60820]]

and Drug Addiction (EMCDDA), the European Union Early Warning System 
Network identified N-piperidinyl etonitazene in Germany in October 
2021. As of January 23, 2023, a total of four European countries have 
reported identifications of N-piperidinyl etonitazene in powder form to 
the EMCDDA.\21\
---------------------------------------------------------------------------

    \20\ A partnership between the American College of Medical 
Toxicology (ACMT) and the Center for Forensic Science Research and 
Education (CFSRE) was established to comprehensively assess the role 
and prevalence of synthetic opioids and other drugs among suspected 
overdose events in the United States. CFSRE NPS Monograph. N-
Piperidinyl etonitazene. November 22, 2021.
    \21\ Email communication with EMCDDA dated January 23, 2023.
---------------------------------------------------------------------------

Factor 5. Scope, Duration and Significance of Abuse

    N-Desethyl isotonitazene and N-piperidinyl etonitazene, similar to 
etonitazene and isotonitazene (schedule I substances), have been 
described as potent synthetic opioids, and evidence suggests they are 
abused for their opioidergic effects. The abuse of these benzimidazole-
opioids, similar to other synthetic opioids, has resulted in serious 
adverse health effects. Between October 2019 and January 2020, N-
desethyl isotonitazene was positively identified as a metabolite of 
isotonitazene in 13 postmortem samples and 64 driving-under-the-
influence-of-drugs (DUID) in the United States. However, beginning in 
2023, N-desethyl isotonitazene has been identified in 10 toxicology 
cases.\22\ The pharmacological profile of N-desethyl isotonitazene 
demonstrates it is a highly potent synthetic opioid similar to 
etonitazene, isotonitazene, and fentanyl. As such, the identification 
of this substance as a parent drug in the recreational drug market is 
worrisome.
---------------------------------------------------------------------------

    \22\ CFSRE NPS Opioids Trend Report, 2023 Q1 and Q2. Accessed 
September 15, 2023.
---------------------------------------------------------------------------

    Data from law enforcement suggest that N-desethyl isotonitazene and 
N-piperidinyl etonitazene are being abused in the United States as 
recreational drugs.\23\ Since 2022, there have been 14 reports to DEA's 
National Forensic Laboratory Information System (NFLIS)-Drug \24\ 
(Federal, State, and local laboratories) database pertaining to the 
trafficking, distribution, and abuse of N-desethyl isotonitazene (n = 
5) and N-piperidinyl etonitazene (n = 9). These five encounters of N-
desethyl isotonitazene were reported to NFLIS-Drug from Pennsylvania 
(2), Florida (2) and Kansas (1). Encounters of N-piperidinyl 
etonitazene occurred in Tennessee (8) and Pennsylvania (1).
---------------------------------------------------------------------------

    \23\ 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 76 FR 77330, 77332 (Dec. 12, 2011).
    \24\ 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 the nation's drug analysis cases. NFLIS-
Drug participation rate, defined as the percentage of the national 
drug caseload represented by laboratories that have joined NFLIS-
Drug, is currently 98.5 percent. NFLIS-Drug includes drug chemistry 
results from completed analyses only. While NFLIS-Drug data is 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). NFLIS-Drug data was queried on October 2, 
2023.
---------------------------------------------------------------------------

    Based on information collected from NFLIS-Drug, N-desethyl 
isotonitazene and N-piperidinyl etonitazene were identified in tablet 
form or as residue. Reporting from CFSRE show that N-desethyl 
isotonitazene was identified in a counterfeit oxycodone tablet in 
Florida,\25\ suggesting that it might be present as a substitute for 
heroin or fentanyl and likely abused in the same manner as either of 
those substances.
---------------------------------------------------------------------------

    \25\ CFSRE NPS Discovery Public Alert January 2023. Accessed 
January 25, 2023.
---------------------------------------------------------------------------

    The population likely to be harmed by these benzimidazole-opioids 
appears to be the same as that harmed by prescription opioid 
analgesics, fentanyl, and other synthetic drugs.\26\ This is evidenced 
by the types of other drugs co-identified in biological samples and law 
enforcement reports. Law enforcement and toxicology reports demonstrate 
that N-desethyl isotonitazene and N-piperidinyl etonitazene are being 
illicitly distributed and abused. Because users of N-desethyl 
isotonitazene and N-piperidinyl etonitazene 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. Individuals 
who initiate (i.e., use a drug for the first time) use of these 
benzimidazole-opioids are likely to be at risk of developing substance 
use disorder, overdose, and/or death, similar to that of other opioid 
analgesics (e.g., fentanyl, morphine, etc.).
---------------------------------------------------------------------------

    \26\ According to the most recent data from the National Survey 
on Drug Use and Health, as of 2022, an estimated 8.9 million people 
aged 12 years or older misused opioids in the past year, including 
8.5 million prescription pain reliever misusers and 1.0 million 
heroin users. This population abusing opioids is likely to be at 
risk of abusing N-desethyl isotonitazene and N-piperidinyl 
etonitazene.
---------------------------------------------------------------------------

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 N-desethyl isotonitazene and N-piperidinyl 
etonitazene exhibit pharmacological profiles similar to that of 
etonitazene, isotonitazene, and other mu-opioid receptor agonists.\27\ 
These two benzimidazole-opioids bind to and act as an agonist at the 
mu-opioid receptors. 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.
---------------------------------------------------------------------------

    \27\ 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. Unpublished data.
---------------------------------------------------------------------------

    Consistent with any mu-opioid receptor agonist, the potential 
health and safety risks for users of N-desethyl isotonitazene and N-
piperidinyl etonitazene are high. N-Desethyl isotonitazene and N-
piperidinyl etonitazene have been positively identified in toxicology 
cases. The public health risks attendant to the abuse of mu-opioid 
receptor agonists are well established. These risks include large 
numbers of drug treatment admissions, emergency department visits, and 
fatal overdoses.
    N-Piperidinyl etonitazene was detected in suspected opioid overdose 
cases in three patients from New Jersey over a period of three days in 
July 2021. Of those patients, two reported the use of cocaine; one 
reported the use of heroin and alprazolam. Similarly, according to a 
2021 CFSRE report, N-piperidinyl etonitazene was co-identified with 
fentanyl in two cases and para-fluorofentanyl in one other case.\28\
---------------------------------------------------------------------------

    \28\ NPS Discovery Program at the Center for Forensic Science 
Research and Education: Monograph. N-Piperidinyl etonitazene 
Toxicology Analytical Report. November 22, 2021.
---------------------------------------------------------------------------

    The pharmacological profile of this substance demonstrates that it 
is a highly potent synthetic opioid similar to etonitazene, 
isotonitazene, and fentanyl. As such, the identification of this 
substance as a parent drug in the recreational drug market is 
worrisome.

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, conduct 
of research and chemical analysis, possession, and abuse of N-desethyl 
isotonitazene and N-piperidinyl etonitazene 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.

[[Page 60821]]

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 N-
desethyl isotonitazene and N-piperidinyl etonitazene indicate that 
these substances meet the three statutory criteria.
    As required by 21 U.S.C. 811(h)(4), the Administrator transmitted 
to the Assistant Secretary, via letter dated April 3, 2023, notice of 
her intent to place N-desethyl isotonitazene and N-piperidinyl 
etonitazene in schedule I on a temporary basis. HHS had no objection to 
the temporary placement of these substances in schedule I. DEA 
subsequently published a NOI in the Federal Register on October 25, 
2023.\29\
---------------------------------------------------------------------------

    \29\ Schedules of Controlled Substances: Temporary Placement of 
N-Desethyl Isotonitazene and N-Piperidinyl Etionitazene in Schedule 
I, 88 FR 73293 (Oct. 25, 2023).
---------------------------------------------------------------------------

Conclusion

    In accordance with 21 U.S.C. 811(h)(1) and (3), the Administrator 
considered available data and information, herein set forth the grounds 
for her determination that it is necessary to temporarily schedule N-
desethyl isotonitazene and N-piperidinyl etonitazene 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.
    This temporary placement of N-desethyl isotonitazene and N-
piperidinyl etonitazene in schedule I of the CSA 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 year, pending 
completion of the regular (permanent) scheduling process.\30\
---------------------------------------------------------------------------

    \30\ 21 U.S.C. 811(h)(1) and (2).
---------------------------------------------------------------------------

    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.\31\ 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.\32\ 
Temporary scheduling orders are not subject to judicial review.\33\
---------------------------------------------------------------------------

    \31\ 21 U.S.C. 811.
    \32\ 21 U.S.C. 877.
    \33\ 21 U.S.C. 811(h)(6).
---------------------------------------------------------------------------

Requirements for Handling

    Upon the effective date of this temporary order, N-desethyl 
isotonitazene and N-piperidinyl etonitazene will be subject to the 
regulatory controls and administrative, civil, and criminal sanctions 
applicable to the manufacture, distribution, reverse distribution, 
importation, exportation, possession of, and engagement in research and 
conduct of instructional activities or chemical analysis with, schedule 
I controlled substances, including the following:
    1. Registration. Any person who handles (possesses, manufactures, 
distributes, reverse distributes, imports, exports, engages in 
research, or conducts instructional activities or chemical analysis 
with) or 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, as of July 29, 2024. Any person who thereafter 
handles N-desethyl isotonitazene or N-piperidinyl etonitazene and is 
not registered with DEA must submit an application for registration and 
may not continue to handle N-desethyl isotonitazene and N-piperidinyl 
etonitazene as of July 29, 2024, unless DEA has approved that 
application for registration 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 on or after July 29, 2024 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. Any person who does not desire or is unable 
to obtain a schedule I registration to handle N-desethyl isotonitazene 
or N-piperidinyl etonitazene must surrender all currently held 
quantities of these substances.
    3. Security. N-Desethyl isotonitazene and N-piperidinyl etonitazene 
are subject to schedule I security requirements and must be handled in 
accordance with 21 CFR 1301.71-1301.93, as of July 29, 2024.
    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 21 CFR part 
1302. Current DEA registrants will have 30 calendar days from July 29, 
2024 to comply with all labeling and packaging requirements.
    5. Inventory. Every DEA registrant who possesses any quantity of N-
desethyl isotonitazene or N-piperidinyl etonitazene on the effective 
date of this order must take an inventory of all stocks of these 
substances on hand pursuant to 21 U.S.C. 827 and 958, and in accordance 
with 21 CFR 1304.03, 1304.04, and 1304.11. Current DEA registrants will 
have 30 calendar days from the effective date of this order to comply 
with all inventory requirements. After the initial inventory, every DEA 
registrant must take an inventory of all controlled substances 
(including N-desethyl isotonitazene and N-piperidinyl etonitazene) on 
hand on a biennial basis pursuant to 21 U.S.C. 827 and 958 and in 
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
    6. Records. All DEA registrants must maintain records 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 parts 1304, 
1312, and 1317, and section 1307.11. Current DEA registrants authorized 
to handle these two substances shall have 30 calendar days from the 
effective date of this order to comply with all recordkeeping 
requirements.
    7. Reports. All DEA registrants must submit reports with respect to 
N-desethyl isotonitazene and N-piperidinyl etonitazene pursuant to 21 
U.S.C. 827 and in accordance with 21 CFR parts 1304, 1312, and 1317, 
and sections 1301.74(c) and 1301.76(b), as of July 29, 2024. 
Manufacturers and distributors must also submit reports regarding these 
substances 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. All DEA registrants who distribute N-desethyl 
isotonitazene or N-piperidinyl etonitazene must comply with order form 
requirements pursuant to 21 U.S.C. 828 and in accordance with 21 CFR 
part 1305 as of July 29, 2024.
    9. Importation and Exportation. All importation and exportation of 
N-desethyl isotonitazene and N-piperidinyl etonitazene must be in 
compliance with 21 U.S.C. 952, 953, 957, and 958, and in accordance 
with 21 CFR part 1312 as of July 29, 2024.
    10. Quota. Only DEA-registered manufacturers may manufacture N-
desethyl isotonitazene and N-piperidinyl etonitazene in accordance

[[Page 60822]]

with a quota assigned pursuant to 21 U.S.C. 826 and in accordance with 
21 CFR part 1303, as of July 29, 2024.
    11. Liability. Any activity involving N-desethyl isotonitazene or 
N-piperidinyl etonitazene not authorized by or in violation of the CSA, 
occurring as of July 29, 2024, is unlawful, and may subject the person 
to administrative, civil, and/or criminal sanctions.

Regulatory Matters

    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.\34\
---------------------------------------------------------------------------

    \34\ 21 U.S.C. 811(h)(1).
---------------------------------------------------------------------------

    Inasmuch as section 811(h) directs that temporary scheduling 
actions be issued by order (as distinct from a rule) and sets forth the 
procedures by which such orders are to be issued, DEA believes the 
notice-and-comment requirements of section 553 of the Administrative 
Procedure Act (APA), 5 U.S.C. 553, which are applicable to rulemaking, 
do not apply to this temporary scheduling order. 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.'' 5 U.S.C. 551(6) (emphasis added). 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. 21 U.S.C. 811(a) and 877. 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.
    Assuming for the sake of argument that this action is subject to 
section 553 of the APA, the 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 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 
Administrator took into consideration comments submitted by the 
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. 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. Therefore, in this instance, 
since DEA believes this temporary scheduling action is not a ``rule,'' 
it is not subject to the requirements of the Regulatory Flexibility Act 
when issuing this temporary action.
    In accordance with the principles of Executive Orders (E.O.) 12866, 
13563, and 14094, 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. E.O. 12866, sec. 3(f), 
as amended by E.O. 14094, sec. 1(b), provides the definition of a 
``significant regulatory action,'' requiring review by the Office of 
Management and Budget. Because this is not a rulemaking action, this is 
not a significant regulatory action as defined in Section 3(f) of E.O. 
12866.
    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.

Signing Authority

    This document of the Drug Enforcement Administration was signed on 
July 16, 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.

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 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)(68) and (69) to read as 
follows:


Sec.  1308.11  Schedule I

* * * * *
    (h) * * *

[[Page 60823]]



------------------------------------------------------------------------
 
------------------------------------------------------------------------
 
                              * * * * * * *
(68) N-ethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1H-                  9760
 benzimidazol-1-yl)ethan-1-amine, its isomers, esters,
 ethers, salts, and salts of isomers, esters and ethers
 (Other name: N-desethyl isotonitazene).................
(69) 2-(4-ethoxybenzyl)-5-nitro-1-(2-(piperidin-1-                  9761
 yl)ethyl)-1H-benzimidazole, its isomers, esters,
 ethers, salts, and salts of isomers, esters and ethers
 (Other names: N-piperidinyl etonitazene;
 etonitazepipne)........................................
 
                              * * * * * * *
------------------------------------------------------------------------

* * * * *
[FR Doc. 2024-16391 Filed 7-26-24; 8:45 am]
BILLING CODE 4410-09-P