Proposed Rule2025-19348
Schedules of Controlled Substances: Placement of MDMB-4en-PINACA in Schedule I
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
October 2, 2025
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration proposes placing methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido)butanoate (other name: MDMB-4en-PINACA), including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible, in schedule I of the Controlled Substances Act. This action is being taken, in part, to enable the United States to meet its obligations under the 1971 Convention on Psychotropic Substances. If finalized, this action would make permanent the existing 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, conduct instructional activities or chemical analysis with, or possess) or propose to handle MDMB-4en-PINACA.
Full Text
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<title>Federal Register, Volume 90 Issue 189 (Thursday, October 2, 2025)</title>
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[Federal Register Volume 90, Number 189 (Thursday, October 2, 2025)]
[Proposed Rules]
[Pages 47663-47669]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-19348]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-1356]
Schedules of Controlled Substances: Placement of MDMB-4en-PINACA
in Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: The Drug Enforcement Administration proposes placing methyl
3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido)butanoate
(other name: MDMB-4en-PINACA), including its salts, isomers, and salts
of isomers whenever the existence of such salts, isomers, and salts of
isomers is possible, in schedule I of the Controlled Substances Act.
This action is being taken, in part, to enable the United States to
meet its obligations under the 1971 Convention on Psychotropic
Substances. If finalized, this action would make permanent the existing
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, conduct
instructional activities or chemical analysis with, or possess) or
propose to handle MDMB-4en-PINACA.
DATES: Comments must be submitted electronically or postmarked on or
before November 3, 2025.
Interested persons may file a request for a hearing or waiver of an
opportunity for a hearing or to participate in a hearing pursuant to 21
CFR 1308.44 and in accordance with 21 CFR 1316.47 and 1316.49, as
applicable, which must be received or postmarked on or before November
3, 2025.
ADDRESSES: Interested persons may file written comments on this
proposal in accordance with 21 CFR 1308.43(g). The electronic Federal
Docket Management System will not accept comments after 11:59 p.m.
Eastern Time on the last day of the comment period. To ensure proper
handling of comments, please reference ``Docket No. DEA-1356'' on all
electronic and written correspondence, including any attachments.
<bullet> Electronic comments: The Drug Enforcement Administration
(DEA) encourages commenters to submit comments electronically through
the Federal eRulemaking Portal, which provides the ability to type
short comments directly into the comment field on the web page or
attach a file for lengthier comments. Please go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and follow the online instructions at that site for
submitting comments. Upon completion of your comment submission, you
will receive a Comment Tracking Number for your comment. If you have
received a Comment Tracking Number, your comment has been successfully
submitted, and there is no need to resubmit the same comment.
Commenters should be aware that the electronic Federal Docket
Management System will not accept comments after 11:59 p.m. Eastern
Time on the last day of the comment period.
<bullet> Paper comments: Paper comments that duplicate electronic
submissions are not necessary. Should you wish to mail a paper comment
in lieu of an electronic comment, it should be sent via regular or
express mail to: Drug Enforcement Administration, Attn: DEA Federal
Register Representative/DPW, 8701 Morrissette Drive, Springfield,
Virginia 22152.
<bullet> Hearing requests: All requests for a hearing and waivers
of participation, together with a written statement of position on the
matters of fact and law asserted in the hearing, must be filed with the
DEA Administrator, who will make the determination of whether a hearing
will be needed to address such matters of fact and law in the
rulemaking. Such requests must be sent to: Drug Enforcement
Administration, Attn: Administrator, 8701 Morrissette Drive,
Springfield, Virginia 22152. For informational purposes, a courtesy
copy of requests for hearing and waivers of participation should also
be sent to: (1) Drug Enforcement Administration, Attn: Hearing Clerk/
OALJ, 8701 Morrissette Drive, Springfield, Virginia 22152; and (2) Drug
Enforcement Administration, Attn: DEA Federal Register Representative/
DPW, 8701 Morrissette Drive, Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: Dr. Terrence L. Boos, Drug and
Chemical Evaluation Section, Diversion Control Division, Drug
Enforcement Administration; Telephone: (571) 362-3249.
As required by 5 U.S.C. 553(b)(4), a summary of this proposed rule
may be
[[Page 47664]]
found in the docket for this rulemaking at <a href="http://www.regulations.gov">www.regulations.gov</a>.
SUPPLEMENTARY INFORMATION: The Drug Enforcement Administration (DEA)
intends to place methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-
3-carboxamido)butanoate (other name: MDMB-4en-PINACA), including its
salts, isomers, and salts of isomers whenever the existence of such
salts, isomers, and salts of isomers is possible, in schedule I of the
Controlled Substances Act (CSA).
Posting of Public Comments
All comments received in response to this docket are considered
part of the public record. DEA will make comments available for public
inspection online at <a href="http://www.regulations.gov">http://www.regulations.gov</a>, unless reasonable
cause is given. Such information includes personal or business
identifiers (such as name, address, state of federal identifiers, etc.)
voluntarily submitted by the commenter.
Commenters submitting comments which include personal identifying
information (PII), confidential, or proprietary business information
that the commenter does not want made publicly available should submit
two copies of the comment. One copy must be marked ``CONTAINS
CONFIDENTIAL INFORMATION'' and should clearly identify all PII or
business information the commenter does not want to be made publicly
available, including any supplemental materials. DEA will review this
copy, including the claimed PII and confidential business information,
in its consideration of comments. The second copy should be marked ``TO
BE PUBLICLY POSTED'' and must have all claimed confidential PII and
business information already redacted. DEA will post only the redacted
comment on <a href="https://www.regulations.gov">https://www.regulations.gov</a> for public inspection. DEA
generally will not redact additional information contained in the
comment marked ``TO BE PUBLICLY POSTED.'' The Freedom of Information
Act applies to all comments received.
For easy reference, an electronic copy of this document and
supplemental information to this proposed scheduling action are
available at <a href="http://www.regulations.gov">http://www.regulations.gov</a>.
Request for Hearing or Waiver of Participation in a Hearing
Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking
``on the record after opportunity for a hearing.'' Such proceedings are
conducted pursuant to the provisions of the Administrative Procedure
Act (APA), 5 U.S.C. 551-559.\1\ Interested persons, as defined in 21
CFR 1300.01(b), may file requests for a hearing in conformity with the
requirements of 21 CFR 1308.44(a) and 1316.47(a), and such requests
must:
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\1\ 21 CFR 1308.41-1308.45; 21 CFR part 1316, subpart D.
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(1) state with particularity the interest of the person in the
proceeding;
(2) state with particularity the objections or issues concerning
which the person desires to be heard; and
(3) state briefly the position of the person regarding the
objections or issues.
Any interested person may file a waiver of an opportunity for a
hearing or to participate in a hearing in conformity with the
requirements of 21 CFR 1308.44(c), together with a written statement of
position on the matters of fact and law involved in any hearing.\2\
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\2\ 21 CFR 1316.49.
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All requests for a hearing and waivers of participation, together
with a written statement of position on the matters of fact and law
involved in such hearing, must be sent to DEA using the address
information provided above. The decision whether a hearing will be
needed to address such matters of fact and law in the rulemaking will
be made by the Administrator. If a hearing is needed, DEA will publish
a notice of hearing on the proposed rulemaking in the Federal
Register.\3\ Further, once the Administrator determines a hearing is
needed to address such matters of fact and law in rulemaking, he will
then designate an Administrative Law Judge (ALJ) to preside over the
hearing. The ALJ's functions shall commence upon designation, as
provided in 21 CFR 1316.52.
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\3\ 21 CFR 1308.44(b), 1316.53.
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In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing
would be to determine whether MDMB-4en-PINACA meets the statutory
criteria for placement in schedule I, as proposed in this proposed
rule.
Legal Authority
The CSA provides that proceedings for the issuance, amendment, or
repeal of the scheduling of any drug or other substance may be
initiated by the Attorney General (delegated to the Administrator of
DEA pursuant to 28 CFR 0.100) on her own motion, at the request of the
Secretary of Health and Human Services (HHS), or on the petition of an
interested party.\4\ This proposed action is initiated on the
Administrator's own motion and supported by, inter alia, a
recommendation from the then-Assistant Secretary for Health of HHS.
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\4\ 21 U.S.C. 811(a).
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In addition, the United States is a party to the 1971 United
Nations Convention on Psychotropic Substances (1971 Convention), Feb.
21, 1971, 32 U.S.T. 543, 1019 U.N.T.S. 175, as amended. Procedures
respecting changes in drug schedules under the 1971 Convention are
governed domestically by 21 U.S.C. 811(d)(2)-(4). When the United
States receives notification of a scheduling decision pursuant to
Article 2 of the 1971 Convention indicating that a drug or other
substance has been added to a schedule specified in the notification,
the Secretary of HHS (Secretary),\5\ after consultation with the
Attorney General, shall first determine whether existing legal controls
under subchapter I of the CSA and the Federal Food, Drug, and Cosmetic
Act meet the requirements of the schedule specified in the notification
with respect to the specific drug or substance.\6\
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\5\ As discussed in a memorandum of understanding entered into
by the FDA and the National Institute on Drug Abuse (NIDA), FDA acts
as the lead agency within HHS in carrying out the Secretary's
scheduling responsibilities under the CSA, with the concurrence of
NIDA. 50 FR 9518 (Mar. 8, 1985). The Secretary has delegated to the
Assistant Secretary for Health of HHS the authority to make domestic
drug scheduling recommendations. 58 FR 35460 (July 1, 1993).
\6\ 21 U.S.C. 811(d)(3).
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In the event that the Secretary did not consult with the Attorney
General, and the Attorney General did not issue a temporary order, as
provided under 21 U.S.C. 811(d)(4), the procedures for permanent
scheduling are set forth in 21 U.S.C. 811(a) and (b) control. Pursuant
to 21 U.S.C. 811(a)(1) and (2), the Attorney General (as delegated to
the Administrator of DEA) may, by rule, and upon the recommendation of
the Secretary, add to such a schedule or transfer between such
schedules any drug or other substance, if she finds that such drug or
other substance has a potential for abuse, and makes with respect to
such drug or other substance the findings prescribed by 21 U.S.C.
812(b) for the schedule in which such drug or other substance is to be
placed.
Background
On June 10, 2021, the Secretary-General of the United Nations
advised the Secretary of State of the United States that the Commission
on Narcotic Drugs (CND) voted to place MDMB-4en-PINACA in Schedule II
of the 1971 Convention during its 64th Session held on April 14, 2021.
As a signatory to this international treaty, the United States is
required, by scheduling under the CSA, to place
[[Page 47665]]
appropriate controls on MDMB-4en-PINACA to meet the minimum
requirements of the treaty. Because the procedures in 21 U.S.C.
811(d)(3) and (4) for consultation and issuance of a temporary order,
discussed in the above legal authority section, were not followed for
MDMB-4en-PINACA, DEA is utilizing the procedures for permanent
scheduling set forth in 21 U.S.C. 811(a) and (b) to control MDMB-4en-
PINACA. Such scheduling would satisfy the United States' international
obligations.
Article 2, paragraph 7(b), of the 1971 Convention sets forth the
minimum requirements that the United States must meet when a substance
has been added to Schedule II of the 1971 Convention. Pursuant to the
1971 Convention, the United States must require licenses for the
manufacture, export and import, and distribution of MDMB-4en-PINACA.
This license requirement is accomplished by the CSA's registration
requirement as set forth in 21 U.S.C. 822, 823, 957, and 958, and in
accordance with 21 CFR parts 1301 and 1312.
In addition, the United States must adhere to specific export and
import provisions set forth in the 1971 Convention. This requirement is
accomplished by the CSA with the export and import provisions
established in 21 U.S.C. 952, 953, 957, and 958, and in accordance with
21 CFR part 1312. Likewise, under Article 13, paragraphs 1 and 2, of
the 1971 Convention, a party to the 1971 Convention may notify through
the UN Secretary-General another party that it prohibits the
importation of a substance in Schedule II, III, or IV of the 1971
Convention. If such notice is presented to the United States, the
United States shall take measures to ensure that the named substance is
not exported to the notifying country. This requirement is also
accomplished by the CSA's export provisions mentioned above.
Under Article 16, paragraph 4, of the 1971 Convention, the United
States is required to provide annual statistical reports to the
International Narcotics Control Board (INCB). Using INCB Form P, the
United States shall provide the following information: (1) In regard to
each substance in Schedule I and II of the 1971 Convention, quantities
manufactured, exported to, and imported from each country or region as
well as stocks held by manufacturers; (2) in regard to each substance
in Schedule III and IV of the 1971 Convention, quantities manufactured,
as well as quantities exported and imported; (3) in regard to each
substance in Schedule II and III of the 1971 Convention, quantities
used in the manufacture of exempt preparations; and (4) in regard to
each substance in Schedule II-IV of the 1971 Convention, quantities
used for the manufacture of non-psychotropic substances or products.
Lastly, under Article 2 of the 1971 Convention, the United States
must adopt measures in accordance with Article 22 to address violations
of any statutes or regulations that are adopted pursuant to its
obligations under the 1971 Convention. Persons acting outside the legal
framework established by the CSA are subject to administrative, civil,
and/or criminal action; therefore, the United States complies with this
provision.
DEA notes that there are differences between the schedules of
substances in the 1971 Convention and the CSA. The CSA has five
schedules (schedules I-V) with specific criteria set forth for each
schedule. Schedule I is the only possible schedule in which a drug or
other substance may be placed if it has high potential for abuse and no
currently accepted medical use in treatment in the United States.\7\ In
contrast, the 1971 Convention has four schedules (Schedules I-IV) but
does not have specific criteria for each schedule. The 1971 Convention
simply defines its four schedules, in Article 1, to mean the
correspondingly numbered lists of psychotropic substances annexed to
the Convention and altered in accordance with Article 2.
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\7\ See 21 U.S.C. 812(b).
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Proposed Determination to Schedule MDMB-4en-PINACA
Pursuant to 21 U.S.C. 811(b), DEA gathered the necessary data on
MDMB-4en-PINACA and, on November 29, 2021, submitted it to the then-
Assistant Secretary of Health of HHS with a request for a scientific
and medical evaluation and scheduling recommendation for this
substance. On September 29, 2023, HHS \8\ provided DEA with a
scientific and medical evaluation entitled ``Basis for the
Recommendation to Control MDMB-4en-PINACA and Its Salts in Schedule I
of the Controlled Substances Act'' and a scheduling recommendation.
Pursuant to 21 U.S.C. 811(b), following consideration of the eight-
factors and findings related to the substance's abuse potential,
legitimate medical use, and safety or dependence liability, HHS
recommended that MDMB-4en-PINACA, its salts, isomers, and salts of
isomers be controlled in schedule I of the CSA.\9\ HHS noted that MDMB-
4en-PINACA is a full agonist at the cannabinoid type 1 (CB1) receptor,
has no known medical use in the United States, has no approved new drug
applications, and is not known to be marketed anywhere in the world as
an approved drug product. HHS also noted that health care practitioners
and medical examiners have reported cases of severe clinical adverse
events and even death when MDMB-4en-PINACA was used.
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\8\ Administrative responsibilities for evaluating a substance
for control under the CSA are performed for HHS by FDA, with the
concurrence of the National Institute on Drug Abuse (NIDA),
according to a Memorandum of Understanding. 50 FR 9518 (Mar. 8,
1985).
\9\ NIDA concurred with HHS's recommendation.
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On December 12, 2023, the previous Administrator published a
temporary scheduling order in the Federal Register \10\ temporarily
placing six synthetic cannabinoids (SCs) in schedule I of the CSA upon
finding that these substances pose an imminent threat to public safety.
The six SCs temporarily controlled under the CSA were (1) MDMB-4en-
PINACA; (2) methyl 2-[[1-(4-fluorobutyl)indole-3-carbonyl]amino]-3,3-
dimethyl-butanoate (other name: 4F-MDMB-BUTICA); (3) 4F-MDMB-BICA); N-
(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(pent-4-en-1-yl)-1H-indazole-
3-carboxamide (other name: ADB-4en-PINACA); (4) 5-pentyl-2-(2-
phenylpropan-2-yl)pyrido[4,3-b]indol-1-one (other names: CUMYL-
PEGACLONE; SGT-151); (5) ethyl 2-[[1-(5-fluoropentyl)indole-3-
carbonyl]amino]-3,3-dimethyl-butanoate (other names: 5F-EDMB-PICA; 5F-
EDMB-2201); and (6) methyl 2-(1-(4-fluorobenzyl)-1H-indole-3-
carboxamido)-3-methyl butanoate (other name: MMB-FUBICA). These six SCs
have not been investigated for medical use nor are they intended for
human use.
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\10\ 88 FR 86040.
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As noted above, the Administrator, on his own motion, is now
initiating proceedings under 21 U.S.C. 811(a)(1) to permanently
schedule MDMB-4en-PINACA in schedule I of the CSA. Upon receipt of the
scientific and medical evaluation and scheduling recommendation from
HHS, DEA reviewed the documents and all other relevant data and
conducted its own eight-factor analysis in accordance with 21 U.S.C.
811(c). Included below is a brief summary of each factor as analyzed by
HHS and DEA, and as considered by DEA in its proposed scheduling
action. Readers should refer to the full eight-factor analyses prepared
by HHS and by DEA in support of this proposal, which are available in
their entirety under the tab ``Supporting
[[Page 47666]]
Documents'' of the public docket of this rulemaking action at <a href="https://www.regulations.gov">https://www.regulations.gov</a>, under docket number ``DEA-1356.''
1. The Drug's Actual or Relative Potential for Abuse
In addition to considering the information HHS provided in its
scientific and medical evaluation document for MDMB-4en-PINACA, DEA
also considered all other relevant data regarding actual or relative
potential for abuse of MDMB-4en-PINACA. The term ``abuse'' is not
defined in the CSA; however, the legislative history of the CSA
suggests that DEA consider the following criteria in determining
whether a particular drug or substance has a potential for abuse: \11\
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\11\ Comprehensive Drug Abuse Prevention and Control Act of
1970, H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); reprinted
in 1970 U.S.C.C.A.N. 4566, 4603.
(a) There is evidence that individuals are taking the drug or
drugs containing such a substance in amounts sufficient to create a
hazard to their health or to the safety of other individuals or to
the community; or
(b) There is significant diversion of the drug or drugs
containing such a substance from legitimate drug channels; or
(c) Individuals are taking the drug or drugs containing such a
substance on their own initiative rather than on the basis of
medical advice from a practitioner licensed by law to administer
such drugs in the course of his professional practice; or
(d) The drug or drugs containing such a substance are new drugs
so related in their action to a drug or drugs already listed as
having a potential for abuse to make it likely that the drug will
have the same potentiality for abuse as such drugs, thus making it
reasonable to assume that there may be significant diversions from
legitimate channels, significant use contrary to or without medical
advice, or that it has a substantial capability of creating hazards
to the health of the user or to the safety of the community.
In its recommendation, HHS noted that the abuse of MDMB-4en-PINACA
is creating a hazard to the health and safety of both the individual
users and others within the community. According to HHS, MDMB-4en-
PINACA has been associated with numerous reports of emergency
department admission, severe intoxication, and death. HHS also noted
that MDMB-4en-PINACA is not an FDA-approved drug product, MDMB-4en-
PINACA is not approved as a drug in any country, and there is no
legitimate source for MDMB-4en-PINACA as a marketed drug. Since 2019,
the National Forensic Laboratory Information System (NFLIS)-Drug \12\
registered 14,801 reports pertaining to MDMB-4en-PINACA. These
encounters of MDMB-4en-PINACA by law enforcement indicate that this
substance is being trafficked in the United States.\13\
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\12\ NFLIS-Drug is a national forensic laboratory reporting
system that systematically collects results from drug chemistry
analyses conducted by state and local forensic laboratories in the
United States. NFLIS-Drug data were queried February 1, 2024.
\13\ While law enforcement data is 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).
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According to HHS, because MDMB-4en-PINACA is not approved for
medical use, reports of human self-administration indicate that
individuals are taking this substance of their own accord as opposed to
under the direction of a medical professional. HHS also stated that the
pharmacological action of MDMB-4en-PINACA is similar to other schedule
I cannabinoids, such as [Delta]9-tetrahydrocannabinol ([Delta]9-THC),
which all have high abuse potential. HHS concluded that MDMB-4en-PINACA
has a substantial capability to be a hazard to the health of the user
and to the safety of the community.
2. Scientific Evidence of the Drug's Pharmacological Effects, if Known
In its recommendation, HHS stated that the neurochemical effects of
MDMB-4en-PINACA occur primarily through cannabinoid receptor systems in
the brain. HHS noted that MDMB-4en-PINACA binds to CB1 receptors and
functions as a full agonist, and that the binding affinity and
functional activity profile is similar to that of other schedule I
cannabinoids, including [Delta]9-THC. Studies were conducted to
evaluate in vitro cannabinoid receptor binding and functional effects
of MDMB-4en-PINACA. These results indicate that MDMB-4en-PINACA,
similar to other schedule I SCs, binds to CB1 receptors and acts as an
agonist at CB1 receptors. Drug discrimination studies were conducted in
animals to evaluate whether MDMB-4en-PINACA has discriminative stimulus
effects similar to those of other substances in schedule I of the CSA.
MDMB-4en-PINACA was shown to fully substitute for the discriminative
stimulus effects produced by [Delta]9-THC.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance
MDMB-4en-PINACA is a potent cannabinoid that is reported to be
smoked for recreational purposes. MDMB-4en-PINACA is a CB1 receptor
agonist that is pharmacologically similar to [Delta]9-THC. Neither HHS
nor DEA is aware of any currently accepted medical use for MDMB-4en-
PINACA in treatment in the United States.\14\
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\14\ To place a drug or other substance in schedule I under the
CSA, DEA must consider whether the substance has a currently
accepted medical use in treatment in the United States. 21 U.S.C.
812(b)(1)(B). There is no evidence suggesting that MDMB-4en-PINACA
has 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 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 proposal, there is no evidence that health care
providers have widespread experience with medical use of MDMB-4en-
PINACA or that the use of MDMB-4en-PINACA is recognized by entities
that regulate the practice of medicine under either the traditional
five-part test or the two-part test.
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4. Its History and Current Pattern of Abuse
HHS reviewed the current literature and law enforcement data
supplied by DEA within HHS's recommendation for control of MDMB-4en-
PINACA. HHS stated that, although law enforcement data are not direct
evidence of abuse, it can be inferred that MDMB-4en-PINACA, like other
SCs, has been consumed for the substance's psychoactive and
intoxicating effects. HHS also noted that in terms of the propensity of
new SCs to emerge as new drugs of abuse, MDMB-4en-PINACA fits an
established pattern. MDMB-4en-PINACA was reported in Slovenia in 2018
but didn't appear in the United States until January 2019.
Presentations at emergency departments that were directly linked to the
abuse of MDMB-4en-PINACA have included violent seizures, body spams,
agitation,
[[Page 47667]]
vomiting, tachycardia, and elevated blood pressure.
5. The Scope, Duration, and Significance of Abuse
According to HHS, SCs continue to be encountered in the illicit
market despite scheduling actions that attempt to safeguard the public
from the adverse effects and safety issues associated with these
substances. Novel SCs continue to be encountered that differ only by
small chemical structural modifications, intended to avoid prosecution
while maintaining the pharmacological effects. Law enforcement and
health care professionals continue to report the abuse of these
substances and their associated products. Since 2019, NFLIS registered
20,620 reports pertaining to MDMB-4en-PINACA.
6. What, If Any, Risk There is to the Public Health
HHS and DEA documented multiple cases where MDMB-4en-PINCA was
identified in overdoses and/or cases involving death attributed to its
abuse in the United States and abroad. Full details of the overdose
cases can be found under the tab ``Supporting Documents'' of the public
docket of this action at <a href="https://www.regulations.gov">https://www.regulations.gov</a>, under Docket
Number ``DEA-1356.'' Emergency medical intervention has been required,
alongside reports of serious adverse health effects, from these
incidents involving MDMB-4en-PINACA.
7. Its Psychic or Physiological Dependence Liability
There are no clinical studies evaluating dependence liabilities
specific to MDMB-4en-PINACA. However, scientific data indicate that
MDMB-4en-PINACA has a pharmacological profile that is similar to other
schedule I SCs. HHS stated that based upon this similar pharmacological
profile, it is reasonable to assume that MDMB-4en-PINACA would retain a
physiological and psychological dependence liability that is similar to
that of [Delta]9-THC (a schedule I drug) and other schedule I SCs, such
as 1-pentyl-3-(1-naphthoyl)indole (JWH-018), [1-(5-fluoropentyl)-1H-
indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (XLR11), and N-(1-
adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48).
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA
As noted by HHS, MDMB-4en-PINACA is not an immediate precursor of
any substance controlled under the CSA, as defined by 21 U.S.C.
802(23).
Conclusion
After considering the scientific and medical evaluation conducted
by HHS, HHS's scheduling recommendation, and DEA's own eight-factor
analysis, DEA finds that the facts and all relevant data constitute
substantial evidence of the potential for abuse of MDMB-4en-PINACA. As
such, DEA hereby proposes to permanently schedule MDMB-4en-PINACA as a
schedule I controlled substance under the CSA. This action would enable
the United States to meet its obligations under the 1971 Convention on
Psychotropic Substances.
Proposed Determination of Appropriate Schedule
The CSA establishes five schedules of controlled substances known
as schedules I, II, III, IV, and V. The CSA also outlines the findings
required to place a drug or other substance in any particular
schedule.\15\ After consideration of the analysis and recommendation of
the Assistant Secretary for Health of HHS and review of all other
available data, the Administrator of DEA, pursuant to 21 U.S.C. 811(a)
and 812(b)(1), finds that:
---------------------------------------------------------------------------
\15\ 21 U.S.C. 812(b).
---------------------------------------------------------------------------
1. MDMB-4en-PINACA has a high potential for abuse that is
comparable to other schedule I substances such as [Delta]9-THC and JWH-
018;
2. MDMB-4en-PINACA has no currently accepted medical use in
treatment in the United States; and
3. There is a lack of accepted safety for use of MDMB-4en-PINACA
under medical supervision.
Based on these findings, the Administrator concludes that MDMB-4en-
PINACA, including its salts, isomers, and salts of isomers, whenever
the existence of such salts, isomers, and salts of isomers is possible,
warrant control in schedule I of the CSA.
Requirements for Handling MDMB-4en-PINACA
If this proposed rule is finalized as proposed, MDMB-4en-PINACA
would continue \16\ to be subject to the CSA's schedule I regulatory
controls and administrative, civil, and criminal sanctions applicable
to the manufacture, distribution, reverse distribution, import, export,
engagement in research, conduct of instructional activities or chemical
analysis with, and possession of schedule I controlled substances,
including the following:
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\16\ MDMB-4en-PINACA is currently subject to schedule I controls
on a temporary basis, pursuant to 21 U.S.C. 811(h). See 88 FR 86040
(Dec. 12, 2023).
---------------------------------------------------------------------------
1. Registration. Any person who handles (manufactures, distributes,
dispenses, imports, exports, engages in research, or conducts
instructional activities or chemical analysis with, or possesses) MDMB-
4en-PINACA 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.
2. Security. MDMB-4en-PINACA is subject to schedule I security
requirements and must be handled and stored pursuant to 21 U.S.C. 821,
823, and in accordance with 21 CFR 1301.71 through 1301.76. Non-
practitioners handling these three substances also must comply with the
screening requirements of 21 CFR 1301.90 through 1301.93.
3. Labeling and Packaging. All labels and labeling for commercial
containers of MDMB-4en-PINACA must comply with 21 U.S.C. 825 and 958(e)
and be in accordance with 21 CFR part 1302.
4. Quota. Only registered manufacturers would be permitted to
manufacture MDMB-4en-PINACA in accordance with a quota assigned,
pursuant to 21 U.S.C. 826 and in accordance with 21 CFR part 1303.
5. Inventory. Any person registered with DEA to handle MDMB-4en-
PINACA 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 MDMB-4en-
PINACA) on hand every two years pursuant to 21 U.S.C. 827 and 958(e)
and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
6. Records and Reports. Every DEA registrant must maintain records
and submit reports with respect to MDMB-4en-PINACA, pursuant to 21
U.S.C. 827, 832(a), and 958(e), and in accordance with 21 CFR
1301.74(b) and (c) and 1301.76(b) and parts 1304, 1312, and 1317.
Manufacturers and distributors would be required to submit reports
regarding MDMB-4en-PINACA to the Automation of Reports and Consolidated
Order System pursuant 21 U.S.C. 827, and in accordance with 21 CFR
parts 1304 and 1312.
7. Order Forms. Every DEA registrant who distributes MDMB-4en-
PINACA must comply with the order form
[[Page 47668]]
requirements, pursuant to 21 U.S.C. 828 and 21 CFR part 1305.
8. Importation and Exportation. All importation and exportation of
MDMB-4en-PINACA must be in compliance with 21 U.S.C. 952, 953, 957, and
958, and in accordance with 21 CFR part 1312.
9. Liability. Any activity involving MDMB-4en-PINACA not authorized
by, or in violation of, the CSA or its implementing regulations would
be unlawful, and may subject the person to administrative, civil, and/
or criminal sanctions.
Regulatory Analyses
Executive Orders 12866, 13563, 14192 and 14294 (Regulatory Review)
In accordance with 21 U.S.C. 811(a), this proposed scheduling
action is subject to formal rulemaking procedures done ``on the record
after opportunity for a hearing,'' which are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the criteria for
scheduling a drug or other substance. Such actions are exempt from
review by the Office of Management and Budget (OMB) pursuant to section
3(d)(1) of Executive Order (E.O.) 12866 and the principles reaffirmed
in E.O. 13563. DEA scheduling actions are not subject to either E.O.
14192, Unleashing Prosperity Through Deregulation, or E.O. 14294,
Fighting Overcriminalization in Federal Regulations.
Executive Order 12988, Civil Justice Reform
This proposed regulation 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 proposed rulemaking does not have federalism implications
warranting the application of E.O. 13132. The proposed rule does not
have substantial direct effects on the States, on the relationship
between the national government and the States, or the distribution of
power and responsibilities among the various levels of government.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
This proposed rule does not have tribal implications warranting the
application of E.O. 13175. It does not have substantial direct effects
on one or more Indian tribes, on the relationship between the Federal
government and Indian tribes, or on the distribution of power and
responsibilities between the Federal government and Indian tribes.
Regulatory Flexibility Act
The Administrator, in accordance with the Regulatory Flexibility
Act, 5 U.S.C. 601-612, has reviewed this proposed rule and by approving
it, certifies that it will not have a significant economic impact on a
substantial number of small entities. DEA proposes placing the
substance methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-
carboxamido)butanoate (Other name: MDMB-4en-PINACA), including its
salts, isomers, and salts of isomers, in schedule I of the CSA. This
action is being taken to enable the United States to meet its
obligations under the 1971 Convention on Psychotropic Substances. If
finalized, this action would 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 with, or possess), or
propose to handle, MDMB-4en-PINACA.
The entities affected by this proposed rule include the
manufacturers, distributors, importers, exporters, and researchers of
MDMB-4en-PINACA. DEA determines the North American Industry
Classification System (NAICS) industries that best represent these
business activities. Table 1 lists the business activities and
corresponding NAICS industries.\17\
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\17\ Executive Office of the President Office of Management and
Budget, North American Industry Classification System, United
States, 2022, <a href="https://www.census.gov/naics/reference_files_tools/2022_NAICS_Manual.pdf">https://www.census.gov/naics/reference_files_tools/2022_NAICS_Manual.pdf</a>. (Accessed 4/2/2024.)
Table 1--Business Activity and Corresponding NAICS Industries
----------------------------------------------------------------------------------------------------------------
Business activity NAICS code NAICS industry description
----------------------------------------------------------------------------------------------------------------
Manufacturer.................................. 325412 Pharmaceutical Preparation Manufacturing.
Distributor, Importer, Exporter............... 424210 Drugs and Druggists' Sundries Merchant
424690 Wholesalers.
Other Chemical and Allied Products Merchant
Wholesalers.
Researcher.................................... 541715 Research and Development in the Physical,
Engineering, and Life Sciences (except
Nanotechnology and Biotechnology).
611310 Colleges, Universities and Professional Schools.
----------------------------------------------------------------------------------------------------------------
From Statistics of U.S. Businesses (SUSB) data, DEA determined the
number of firms and small firms for each of the affected industries,
and by comparing the number of affected small entities to the number of
small entities for each industry, DEA determined whether a substantial
number of small entities are affected in any of the industries. Table 2
lists the number of firms, small firms, and percent small firms in each
affected industry.
Table 2--Percent Affected Small Entities by Industry
----------------------------------------------------------------------------------------------------------------
Small firms Percent small
NAICS industry Firms \18\ SBA size standard \19\ \20\ entities (%)
----------------------------------------------------------------------------------------------------------------
325412--Pharmaceutical Preparation 1,179 1,300 employees.................. 1,099 93.2
Manufacturing.
424210--Drugs and Druggists' 7,012 250 employees.................... 6,760 96.4
Sundries Merchant Wholesalers.
424690--Other Chemical and Allied 5,487 175 employees.................... 5,197 94.7
Products Merchant Wholesalers.
[[Page 47669]]
541715--Research and Development in 10,042 1,000 employees.................. 9,599 95.6
the Physical, Engineering, and
Life Sciences (except
Nanotechnology and Biotechnology).
611310--Colleges, Universities and 2,494 $34.5 million.................... 1,515 60.8
Professional Schools.
----------------------------------------------------------------------------------------------------------------
Based on the American Chemical Society's SciFinder database,\21\
DEA identified one entity supplying MDMB-4en-PINACA across the
industries 325412, 424210, and 424690. This entity has already
registered with DEA to handle controlled substances. Hence, DEA expects
none of the entities in the 325412, 424210, and 424690 industries will
be affected by this rule. Additionally, DEA expects that the number of
researchers working with MDMB-4en-PINACA is small, because MDMB-4en-
PINACA is not approved for medical use and has a substantial capability
to be a hazard to the health of the user and to the safety of the
community. Also, DEA believes that the researchers working with MDMB-
4en-PINACA may also work with other controlled substances; hence, these
researchers are likely already registered with DEA and are qualified to
handle controlled substances. For these reasons, DEA believes the
number of affected researchers that are small entities is not a
substantial number of small entities in 541715 and 611310 industries.
---------------------------------------------------------------------------
\18\ Statistics of U.S. Businesses, 2022 SUSB Annual Data Tables
by Establishment Industry, <a href="https://www.census.gov/data/tables/2021/econ/susb/2021-susb-annual.html">https://www.census.gov/data/tables/2021/econ/susb/2021-susb-annual.html</a> (Accessed June 24, 2025).
\19\ U.S. Small Business Administration, Table of size
standards, Version March 2023, Effective: March 17, 2023, <a href="https://www.sba.gov/sites/default/files/2023-06/Table%20of%20Size%20Standards_Effective%20March%2017%2C%202023%20%282%29.pdf">https://www.sba.gov/sites/default/files/2023-06/Table%20of%20Size%20Standards_Effective%20March%2017%2C%202023%20%282%29.pdf</a> (Accessed 6/24/2025) Size standards are based on the number
of employees or annual receipts depending on industry.
\20\ Based on the estimated number of firms below the SBA size
standard for each industry.
\21\ SciFinder; Chemical Abstracts Service: Columbus, OH; CAS
2504100-70-1; <a href="https://scifinder.cas.org">https://scifinder.cas.org</a> (accessed May 14, 2024).
---------------------------------------------------------------------------
In summary, an insubstantial number of small entities will be
affected by this proposed rule. As such, the proposed rule, if
finalized, is not expected to result in a significant economic impact
on a substantial number of small entities.
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 the UMRA
of 1995.
Paperwork Reduction Act of 1995
This proposed rule would not impose a new collection or modify an
existing collection of information under the Paperwork Reduction Act of
1995.\22\ Also, this proposed rule would not impose new or modify
existing recordkeeping or reporting requirements on state or local
governments, individuals, businesses, or organizations. However, this
proposed rule would require compliance with the following existing OMB
collections: 1117-0003, 1117-0004, 1117-0006, 1117-0008, 1117-0009,
1117-0010, 1117-0012, 1117-0014, 1117-0021, 1117-0023, 1117-0029, and
1117-0056. An agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays
a currently valid OMB control number.
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\22\ 44 U.S.C. 3501-3521.
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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 21 CFR part 1308 continues to read as
follows:
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. In Sec. 1308.11,
0
a. Add new paragraph (d)(106); and
0
b. Remove and reserve paragraph (h)(62).
The addition to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(d) * * *
------------------------------------------------------------------------
------------------------------------------------------------------------
* * * * * * *
(106) MDMB-4en-PINACA (other name: methyl 3,3-dimethyl-2- 7090
(1-(pent-4-en-1-yl)-1H-indazole-3-
carboxamido)butanoate).................................
------------------------------------------------------------------------
* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
September 30, 2025, by Administrator Terrance Cole. That document with
the original signature and date is maintained by DEA. For
administrative purposes only, and in compliance with requirements of
the Office of the Federal Register, the undersigned DEA Federal
Register Liaison Officer has been authorized to sign and submit the
document in electronic format for publication, as an official document
of DEA. This administrative process in no way alters the legal effect
of this document upon publication in the Federal Register.
Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2025-19348 Filed 10-1-25; 8:45 am]
BILLING CODE 4410-09-P
</pre></body>
</html>Indexed from Federal Register on October 2, 2025.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.