Schedules of Controlled Substances: Placement of 2-Methyl AP-237 in Schedule I
| Published date | 15 March 2024 |
| Record Number | 2024-05543 |
| Citation | 89 FR 18793 |
| Court | Drug Enforcement Administration |
| Section | Rules and Regulations |
Federal Register, Volume 89 Issue 52 (Friday, March 15, 2024)
[Federal Register Volume 89, Number 52 (Friday, March 15, 2024)]
[Rules and Regulations]
[Pages 18793-18796]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-05543]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-1245]
Schedules of Controlled Substances: Placement of 2-Methyl AP-237
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 1-(2-methyl-
4-(3-phenylprop-2-en-1-yl)piperazin-1-yl)butan-1-one (commonly known as
2-methyl AP-237), including its optical and geometric isomers, esters,
ethers, salts, and salts of isomers, esters, and ethers whenever the
existence of such isomers, esters, ethers, and salts is possible within
the specific chemical designation, in schedule I of the Controlled
Substances Act. This scheduling action discharges the United States'
obligations under the Single Convention on Narcotic Drugs (1961). This
action imposes the 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
propose to handle 2-methyl AP-237.
DATES: Effective April 15, 2024.
FOR FURTHER INFORMATION CONTACT: Dr. Terrence L. Boos, Drug and
Chemical Evaluation Section, Diversion Control Division, Drug
Enforcement Administration; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION:
Legal Authority
The United States is a party to the 1961 United Nations Single
Convention on Narcotic Drugs, March 30, 1961, 18 U.S.T. 1407, 570
U.N.T.S. 151 (Single Convention), as amended by the 1972 Protocol.
Article 3, paragraph 7 of the Single Convention requires that if the
Commission on Narcotic Drugs (Commission) adds a substance to one of
the schedules of such Convention, and the United States receives
notification of such scheduling decision from the Secretary-General of
the United Nations (Secretary-General), the United States, as a
signatory Member State, is obligated to control the substance under its
national drug control legislation. Under 21 U.S.C. 811(d)(1) of the
Controlled Substances Act (CSA), if control of a substance is required
``by United States obligations under international treaties,
conventions, or protocols in effect on October 27, 1970,'' the Attorney
General must issue an order controlling such drug under the schedule he
deems most appropriate to carry out such obligations, without regard to
the findings required by 21 U.S.C. 811(a) or 812(b), and without regard
to the procedures prescribed by 21 U.S.C. 811(a) and (b). The Attorney
General has delegated scheduling authority under 21 U.S.C. 811 to the
Administrator of the Drug Enforcement Administration (Administrator of
DEA or Administrator). 28 CFR 0.100.
Background
In a letter dated November 24, 2022, the Director-General of the
World Health Organization recommended to the Secretary-General of the
United Nations that 2-methyl AP-237 be placed in Schedule I of the
Single Convention, as this substance has an opioid mechanism of action
and similarity to drugs that are controlled in Schedule I of the Single
Convention (i.e., 2-methyl AP-237 is similar to drugs such as
isotonitazene) and has dependence and abuse potential. On May 17, 2023,
the United States Government was informed by the Secretariat of the
United Nations, by letter, that during its 66th session in March 2023,
the Commission voted to place 2-methyl AP-237 in Schedule I of the
Single Convention (CND Mar/66/1).
2-Methyl AP-237
2-Methyl AP-237 has a pharmacological profile similar to other
classical opioids such as fentanyl (schedule II), morphine (schedule
II) and heroin (schedule I), which act as mu-opioid receptor agonists.
Because of the pharmacological similarities of 2-methyl AP-237 to the
aforementioned opioids, 2-methyl AP-237 presents a high risk of abuse
and has negatively affected users and communities. According to the DEA
Toxicology Testing Program (DEA TOX) \1\ and a recent publication,\2\
the abuse of 2-methyl AP-237 has been associated with at least seven
fatalities in the United States between February 2020 and July 2023.
The identification of this substance in post-mortem cases is a serious
concern to public safety.
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\1\ The DEA Toxicology Testing Program (DEA TOX) was initiated
in response to the ongoing novel synthetic drug abuse epidemic. This
program provides toxicology data on synthetic drugs from biological
samples that may not be routinely identified, which are generated
from drug overdose victims. Data queried on 8/7/2023.
\2\ Fogarty, MF, Vandeputte, MM, Krotulski, AJ, Walton, SE,
Stove, CP, and Logan, BK (2022). Toxicological and pharmacological
characterization of novel cinnamylpiperazine synthetic opioids in
humans and in vitro including 2-methyl AP-237 and AP-238. Archives
of Toxicology 96:1701-1710.
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In June 2019, 2-methyl AP-237 emerged on the United States illicit
drug market as evidenced by its identification in drug seizures.\3\ Law
enforcement
[[Page 18794]]
reports demonstrate that 2-methyl AP-237 is being illicitly distributed
and abused. The illicit use and distribution of this substance is
similar to that of heroin (schedule I) and prescription opioid
analgesics. According to the National Forensic Laboratory Information
System (NFLIS-Drug) database, which collects drug identification
results from drug cases submitted to and analyzed by Federal, State,
and local forensic laboratories, there have been 92 reports of 2-methyl
AP-237 in the United States since 2019 (data queried July 17, 2023).
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\3\ NFLIS 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, is
currently 98.5 percent. NFLIS includes drug chemistry results from
completed analyses only. While NFLIS 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, December 12,
2011. NFLIS data was queried on July 17, 2023. Reports to NFLIS-Drug
are still pending for 2023.
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DEA is not aware of any claims or any medical or scientific
literature suggesting that 2-methyl AP-237 has a currently accepted
medical use in treatment in the United States. In addition, the
Assistant Secretary for Health of the U.S. Department of Health and
Human Services, by a letter to DEA dated December 22, 2022, stated that
there are no investigational new drug applications or approved new drug
applications for 2-methyl AP-237 in the United States; hence, there are
no legitimate channels for this substance as a marketed drug product in
the United States. Because 2-methyl AP-237 is not formulated or
available for clinical use as an approved medicinal product, all
current use of this substance 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 a drug.
Therefore, consistent with 21 U.S.C. 811(d)(1), DEA concludes that
2-methyl AP-237 has no currently accepted medical use in treatment in
the United States \4\ and is most appropriately placed in schedule I of
the CSA. Because control is required under the Single Convention, DEA
will not be initiating regular rulemaking proceedings to permanently
schedule 2-methyl AP-237 pursuant to 21 U.S.C. 811(a).
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\4\ Although, as discussed above, there is no evidence
suggesting that 2-methyl AP-237 has a currently accepted medical use
in treatment in the United States, it bears noting that a drug
cannot be found to have such medical use unless DEA concludes that
it satisfies a five-part test. Specifically, with respect to a drug
that has not been approved by the Food and Drug Administration, to
have a currently accepted medical use in treatment in the United
States, all of the following must be demonstrated: i. the drug's
chemistry must be known and reproducible; ii. there must be adequate
safety studies; iii. there must be adequate and well-controlled
studies proving efficacy; iv. the drug must be accepted by qualified
experts; and v. the scientific evidence must be widely available. 57
FR 10499 (Mar 26,1992), pet. for rev. denied, Alliance for Cannabis
Therapeutics v. Drug Enforcement Admin., 15 F.3d 1131, 1135 (D.C.
Cir. 1994).
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Conclusion
In order to meet the United States' obligations under the Single
Convention and because 2-methyl AP-237 has no currently accepted
medical use in treatment in the United States, the Administrator has
determined that 2-methyl AP-237, including its optical and geometric
isomers, esters, ethers, salts, and salts of isomers, esters, and
ethers, whenever the existence of such isomers, esters, ethers, and
salts is possible within the specific chemical designation, should be
placed in schedule I of the CSA.
Requirements for Handling
Upon the effective date of the final order contained in this
document, 2-methyl AP-237 will be permanently subject to the CSA's
schedule I regulatory controls and administrative, civil, and criminal
sanctions applicable to the manufacture of, distribution of,
importation of, exportation of, engagement in research or conduct of
instructional activities with, and possession of, schedule I controlled
substances, including the following:
1. Registration. Any person who handles (manufactures, distributes,
imports, exports, engages in research or conducts instructional
activities with, or possesses), or who desires to handle, 2-methyl AP-
237 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 this substance in a manner not authorized by the CSA is
unlawful and those in possession of any quantity of this substance may
be subject to prosecution pursuant to the CSA.
2. Disposal of stocks. 2-Methyl AP-237 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. 2-Methyl AP-237 is subject to schedule I security
requirements and must be handled and stored pursuant to 21 U.S.C. 823,
and in accordance with 21 CFR 1301.71-1301.76. Non-practitioners
handling 2-methyl AP-237 must comply with the employee screening
requirements of 21 CFR 1301.90-1301.93.
4. Labeling and packaging. All labels, labeling, and packaging for
commercial containers of 2-methyl AP-237 must comply with 21 U.S.C.
825, and be in accordance with 21 CFR part 1302.
5. Quota. Only registered manufacturers are permitted to
manufacture 2-methyl AP-237 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 2-methyl AP-
237 must have an initial inventory of all stocks of controlled
substances (including this substance) on hand on the date the
registrant first engages in the handling of controlled substances
pursuant to 21 U.S.C. 827 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 2-methyl
AP-237) on hand every two years pursuant to 21 U.S.C. 827 and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
7. Records and Reports. DEA registrants must maintain records and
submit reports with respect to 2-methyl AP-237 pursuant to 21 U.S.C.
827, and in accordance with 21 CFR 1301.74(b) and (c), 1301.76(b), and
1307.11 and parts 1304, 1312, and 1317. Manufacturers and distributors
must submit reports regarding 2-methyl AP-237 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 2-methyl AP-237
must comply with the 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
2-methyl AP-237 must comply with 21 U.S.C. 952, 953, 957, and 958, and
in accordance with 21 CFR part 1312.
10. Liability. Any activity involving 2-methyl AP-237 not
authorized by, or in violation of the CSA, is unlawful, and may subject
the person to administrative, civil, and/or criminal sanctions.
[[Page 18795]]
Regulatory Analyses
Executive Orders 12866 (Regulatory Planning and Review) and 13563
(Improving Regulation and Regulatory Review) and 14094 (Modernizing
Regulatory Review)
This action is not a significant regulatory action as defined by
Executive Order (E.O.) 12866 (Regulatory Planning and Review), section
3(f), as amended by E.O. 14094, section 1(b), and the principles
reaffirmed in E.O. 13563 (Improving Regulation and Regulatory Review);
and, accordingly, this action has not been reviewed by the Office of
Management and Budget (OMB).
Executive Order 12988, Civil Justice Reform
This action meets the applicable standards set forth in sections
3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors and
ambiguity, minimize litigation, provide a clear legal standard for
affected conduct, and promote simplification and burden reduction.
Executive Order 13132, Federalism
This action does not have federalism implications warranting the
application of E.O. 13132. This action does not have substantial direct
effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
This action does not have tribal implications warranting the
application of E.O. 13175. The action does not have substantial direct
effects on one or more Indian tribes, on the relationship between the
Federal Government and Indian tribes, or on the distribution of power
and responsibilities between the Federal Government and Indian tribes.
Administrative Procedure Act
The CSA provides for an expedited scheduling action where control
is required by the United States' obligations under international
treaties, conventions, or protocols. 21 U.S.C. 811(d)(1). If control is
required pursuant to such international treaty, convention, or
protocol, the Attorney General, as delegated to the Administrator, must
issue an order controlling such drug under the schedule he deems most
appropriate to carry out such obligations, and ``without regard to''
the findings and rulemaking procedures otherwise required for
scheduling actions in 21 U.S.C. 811(a) and (b). Id.
In accordance with 21 U.S.C. 811(d)(1), scheduling actions for
drugs that are required to be controlled by the United States'
obligations under international treaties, conventions, or protocols in
effect on October 27, 1970, shall be issued by order (as opposed to
scheduling by rule pursuant to 21 U.S.C. 811(a)). Therefore, DEA
believes that the notice and comment requirements of section 553 of the
Administrative Procedure Act (APA), 5 U.S.C. 553, do not apply to this
scheduling action.
Regulatory Flexibility Act
The Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612) applies to
rules that are subject to notice and comment under section 553(b) of
the APA or any other law. As explained above, the CSA exempts this
final order from notice and comment. Consequently, the RFA does not
apply to this action.
Paperwork Reduction Act of 1995
This order would modify an existing collection of information
requirement under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501-
3521. Pursuant to section 3507(d) of the PRA of 1995 (44 U.S.C.
3507(d)), DEA is adding new reporting and recordkeeping requirements
for 1117-0003. This order also involves existing collection 1117-0004,
but would not modify the existing collection of information requirement
under the PRA. An agency may not conduct or sponsor, and a person is
not required to respond to a collection of information, unless it
displays a valid OMB control number. Copies of existing information
collections approved by OMB may be obtained at http://www.reginfo.gov/public/do/PRAMain.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995,
2 U.S.C. 1501 et seq., DEA has determined and certifies that this
action would not result in any Federal mandate that may result ``in the
expenditure by State, local, and tribal governments, in the aggregate,
or by the private sector, of $100,000,000 or more (adjusted annually
for inflation) in any 1 year * * *.'' Therefore, neither a Small
Government Agency Plan nor any other action is required under UMRA of
1995.
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 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)(59) through (b)(103) as follows:
------------------------------------------------------------------------
Old paragraph New paragraph
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(b)(59) through (103)..................... (b)(60) through (104).
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0
b. Add new paragraph (b)(59).
The addition reads as follows:
Sec. 1308.11 Schedule I.
* * * * *
(b) * * *
* * * * * * *
(59) 2-Methyl AP-237 (1-(2-methyl-4-(3-phenylprop-2-en-1- 9664
yl)piperazin-1-yl)butan-1-one)..............................
* * * * * * *
* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
March 8, 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
[[Page 18796]]
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.
Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2024-05543 Filed 3-14-24; 8:45 am]
BILLING CODE 4410-09-P
