Proposed Rule2025-14022
Schedules of Controlled Substances: Placement of Clonazolam, Diclazepam, Etizolam, Flualprazolam, and Flubromazolam in Schedule I of the Controlled Substances Act
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
July 25, 2025
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration proposes placing clonazolam, diclazepam, etizolam, flualprazolam, and flubromazolam and their salts, isomers, and salts of isomers, whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation, as identified in this proposed rule, in schedule I of the Controlled Substances Act. These five substances were temporarily scheduled in an order dated July 26, 2023, and subsequently extended until July 26, 2026, pursuant to an extension published elsewhere in this issue of the Federal Register. This action will also 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, or possess), or propose to handle these five specific controlled substances.
Full Text
<html>
<head>
<title>Federal Register, Volume 90 Issue 141 (Friday, July 25, 2025)</title>
</head>
<body><pre>
[Federal Register Volume 90, Number 141 (Friday, July 25, 2025)]
[Proposed Rules]
[Pages 35253-35261]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-14022]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-989]
Schedules of Controlled Substances: Placement of Clonazolam,
Diclazepam, Etizolam, Flualprazolam, and Flubromazolam in Schedule I of
the Controlled Substances Act
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
-----------------------------------------------------------------------
SUMMARY: The Drug Enforcement Administration proposes placing
clonazolam, diclazepam, etizolam, flualprazolam, and flubromazolam and
their salts, isomers, and salts of isomers, whenever the existence of
such salts, isomers, and salts of isomers is possible within the
specific chemical designation, as identified in this proposed rule, in
schedule I of the Controlled Substances Act. These five substances were
temporarily scheduled in an order dated July 26, 2023, and subsequently
extended until July 26, 2026, pursuant to an extension published
elsewhere in this issue of the Federal Register. This action will also
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, or possess), or propose to handle these five
specific controlled substances.
DATES: Comments must be submitted electronically or postmarked on or
before August 25, 2025.
Interested persons may file a request for a hearing or waiver of
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR
1316.47 and/or 1316.49, as applicable. Requests for a hearing and
waivers of an opportunity for a hearing or to participate in a hearing,
together with a written statement of position on the matters of fact
and law asserted in the hearing, must be received on or before August
25, 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-989'' on all
electronic and written correspondence, including any attachments.
<bullet<ls-thn-eq> Electronic comments: The Drug Enforcement
Administration (DEA) encourages commenters to submit all 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 to attach a file for lengthier comments. Please go to
<a href="http://www.regulations.gov">http://www.regulations.gov</a> and follow the online instructions at that
site for submitting comments. Upon completion of your submission, you
will receive a Comment Tracking Number. 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<ls-thn-eq> Paper comments: Paper comments that duplicate
electronic submissions are not necessary and are discouraged. 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<ls-thn-eq> 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 found in the docket for this rulemaking at <a href="http://www.regulations.gov">http://www.regulations.gov</a>.
SUPPLEMENTARY INFORMATION: The Drug Enforcement Administration (DEA)
proposes to permanently schedule the following five controlled
substances in schedule I of the Controlled Substances Act (CSA),
including their salts, isomers, and salts of isomers, whenever the
existence of such salts, isomers, and salts of isomers is possible
within the specific chemical designation:
<bullet> clonazolam (6-(2-chlorophenyl)-1-methyl-8-nitro-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine),
<bullet> diclazepam (7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-
dihydro-2H-benzo[e][1,4]diazepin-2-one),
<bullet> etizolam (4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-
thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine),
<bullet> flualprazolam (8-chloro-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine), and
<bullet> flubromazolam (8-bromo-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine).
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
[[Page 35254]]
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="http://www.regulations.gov">http://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 Appearance; Waiver
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:
---------------------------------------------------------------------------
\1\ 21 CFR 1308.41-1308.45; 21 CFR part 1316, subpart D.
---------------------------------------------------------------------------
(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 with regard to 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\
---------------------------------------------------------------------------
\2\ 21 CFR 1316.49.
---------------------------------------------------------------------------
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 only commence upon designation, as
provided in 21 CFR 1316.52.
---------------------------------------------------------------------------
\3\ 21 CFR 1308.44(b), 1316.53.
---------------------------------------------------------------------------
In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing
would be to determine whether clonazolam, diclazepam, etizolam,
flualprazolam, and flubromazolam meet the statutory criteria for
placement in schedule I, as proposed in this rulemaking.
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 the Department of Health and Human Services (HHS), or on
the petition of an interested party.\4\ This proposed action was
initiated on the Acting Administrator's own motion and is supported by,
inter alia, a recommendation from the Acting Assistant Secretary for
Health of HHS (Assistant Secretary) and an evaluation of all other
relevant data by DEA. If finalized, this action would make permanent
the existing temporary regulatory controls and administrative, civil,
and criminal sanctions of schedule I controlled substances on any
person who handles or proposes to handle these five substances.
---------------------------------------------------------------------------
\4\ 21 U.S.C. 811(a).
---------------------------------------------------------------------------
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 set
forth in 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,\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 (FD&C Act) \6\ meet the
requirements of the schedule specified in the notification with respect
to the specific drug or substance.\7\ 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 set forth in 21 U.S.C. 811(a) and
(b) control.
---------------------------------------------------------------------------
\5\ As discussed in a memorandum of understanding entered into
by the U.S. Food and Drug Administration (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. Memorandum of
Understanding with the National Institute on Drug Abuse, 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. Comprehensive Drug Abuse Prevention and
Control Act of 1970, Public Law 91-513, As Amended; Delegation of
Authority, 58 FR 35460 (July 1, 1993).
\6\ 21 U.S.C. 355.
\7\ 21 U.S.C. 811(d)(3).
---------------------------------------------------------------------------
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 May 7, 2020, the Secretariat of the United Nations advised the
Secretary of State of the Unites States that the Commission on Narcotic
Drugs (CND), during its 63rd Session on March 4, 2020, voted to place
etizolam and flualprazolam in Schedule IV of the 1971 Convention (CND
Decisions 63/12, 63/13). On June 10, 2021, the Secretariat advised the
Secretary of State that the CND, during its 64th Session, voted to
place clonazolam, diclazepam, and flubromazolam in Schedule IV of the
1971 Convention (CND Decisions 64/6, 64/7, 64/8). As a signatory party
to this international treaty, the United States is required, by
scheduling under the CSA, to place appropriate controls on the five
designer benzodiazepines to meet the requirements of this treaty.
To meet the minimum requirements of this treaty and to confront
these emerging substances, DEA published an order in the Federal
Register on July 26, 2023, temporarily placing clonazolam, diclazepam,
etizolam, flualprazolam, and flubromazolam in schedule I of the CSA
based upon a finding that these substances pose an imminent hazard to
the public safety under 21 U.S.C. 811(h)(1).\8\ That temporary order
was effective upon the date of publication.
---------------------------------------------------------------------------
\8\ Schedules of Controlled Substances: Temporary Placement of
Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam
in Schedule I, 88 FR 48112 (July 26, 2023).
---------------------------------------------------------------------------
[[Page 35255]]
Pursuant to 21 U.S.C. 811(h)(2), the temporary scheduling of a
substance expires at the end of two years from the date of issuance of
the scheduling order, except that DEA may extend temporary scheduling
of that substance for up to one year during the pendency of proceedings
under 21 U.S.C. 811(a)(1) with the respect to the temporarily
controlled substance. The temporary control of these five substances is
set to expire on July 26, 2025. DEA is publishing a temporary
scheduling order to extend the temporary schedule I status of these
five substances elsewhere in this issue of the Federal Register, which
will extend the temporary scheduling of these substances for one year,
or until the permanent scheduling action for these substances is
completed, whichever occurs first.
The Acting Administrator, on his own motion pursuant to 21 U.S.C.
811(a), is initiating proceedings to permanently schedule clonazolam,
diclazepam, etizolam, flualprazolam, and flubromazolam, including their
salts, isomers, and salts of isomers, whenever the existence of such
salts, isomers, and salts of isomers is possible within the specific
chemical designation. DEA gathered and reviewed the available
information regarding the pharmacology, chemistry, trafficking, actual
abuse, pattern of abuse, and the relative potential for abuse for these
substances. On March 17 and 24, 2022, in accordance with 21 U.S.C.
811(b), the former Administrator submitted a request to the former
Assistant Secretary to provide DEA with a scientific and medical
evaluation of available information and a scheduling recommendation for
these five substances.
On June 18, 2025, the Acting Assistant Secretary submitted HHS's
scientific and medical evaluation, entitled ``Basis for the
Recommendation to Control Clonazolam, Diclazepam, Etizolam,
Flualprazolam, and Flubromazolam, and Their Salts, in Schedule I of the
Controlled Substances Act,'' and scheduling recommendation to the
Acting Administrator. Following consideration of the eight factors and
findings related to these substances' abuse potential, legitimate
medical use, and dependence liability, HHS recommended that clonazolam,
diclazepam, etizolam, flualprazolam, and flubromazolam and their salts
be controlled in schedule I of the CSA under 21 U.S.C. 812(b).
Proposed Determination to Permanently Schedule Clonazolam, Diclazepam,
Etizolam, Flualprazolam, and Flubromazolam
As discussed in the background section, the Acting Administrator is
initiating proceedings, pursuant to 21 U.S.C. 811(a), to permanently
add clonazolam, diclazepam, etizolam, flualprazolam, and flubromazolam,
including their salts, isomers, and salts of isomers, whenever the
existence of such salts, isomers, and salts of isomers is possible
within the specific chemical designation, to schedule I. In accordance
with 21 U.S.C. 811(c), 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 of the abuse potential of these five substances.
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. Please
note that both DEA and HHS analyses are available in their entirety
under ``Supporting Documents'' of the public docket for this proposed
rule at <a href="http://www.regulations.gov">http://www.regulations.gov</a> under ``Docket Number DEA-989.''
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 clonazolam, diclazepam,
etizolam, flualprazolam, and flubromazolam, DEA also considered all
other relevant data regarding actual or relative potential for abuse of
these five substances. The term ``abuse'' is not defined in the CSA;
however, the legislative history of the CSA suggests that DEA consider
the following criteria when determining whether a particular drug or
substance has a potential for abuse: \9\
---------------------------------------------------------------------------
\9\ 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.
Toxicological and epidemiological data, as well as numerous case
reports and U.S. poison center data, indicate that individuals are
taking the five designer benzodiazepines in amounts sufficient to
create a hazard to their health, the safety of other individuals, or
the community. The U.S. Food and Drug Administration (FDA) has not
approved clonazolam, diclazepam, etizolam, flualprazolam, and
flubromazolam under the FD&C Act, and thus, these five substances not
legally marketed as drugs in the United States. Therefore, HHS has not
identified significant diversion of these substances from legitimate
drug channels in the United States and is not aware of any research or
legitimate manufacturing activities in the United States from which
these substances can be diverted. These substances are thus presumed to
be obtained from clandestine manufacturing or diverted from
international countries for nonmedical use, on an individual's own
initiative, rather than on the basis of medical advice from a licensed
practitioner.
In addition, law enforcement data indicate that clonazolam,
diclazepam, etizolam, flualprazolam, and flubromazolam have been
encountered in the U.S. illicit drug market. DEA's National Forensic
Laboratory Information System (NFLIS) registered a collective total of
50,015 reports, from all 50 states and Washington, DC, pertaining to
the trafficking, distribution, and abuse of the five designer
benzodiazepines.\10\ As such,
[[Page 35256]]
these data suggest that clonazolam, diclazepam, etizolam,
flualprazolam, and flubromazolam are being abused and thus pose safety
hazards to the health of users or the community.
---------------------------------------------------------------------------
\10\ The National Forensic Laboratory Information System (NFLIS)
represents an important resource in monitoring illicit drug
trafficking, including the diversion of legally manufactured
pharmaceuticals into illegal markets. NFLIS is a comprehensive
information system that includes data from forensic laboratories
that handle more than 96% of an estimated 1.0 million distinct
annual federal, state, and local drug analysis cases. 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 (Dec. 12, 2011). NFLIS data were queried on May
29, 2025.
---------------------------------------------------------------------------
Lastly, based on available data, these five designer
benzodiazepines are structurally and pharmacologically related to
classical benzodiazepines (e.g., alprazolam), which are positive
allosteric modulators of [gamma]-aminobutyric acid type A
(GABA<INF>A</INF>) receptors. This allosteric modulation is thought to
be responsible for the sedative-hypnotic, subjective effects commonly
reported on drug user forums. According to HHS, in vitro binding data,
animal behavioral data, and anecdotal reports involving human use
indicate that the five designer benzodiazepines bind to
GABA<INF>A</INF> receptors and produce similar drug effects, as well as
adverse effects, associated with the benzodiazepine class, which have a
potential for abuse. Thus, the five designer benzodiazepines have a
similar potential for abuse and present a hazard to the health and
safety of individuals and the community.
2. Scientific Evidence of the Drug's Pharmacological Effects, if Known
Published scientific data on the functional activity of the five
designer benzodiazepines is limited; however, in vitro binding and
animal behavioral studies demonstrate that the pharmacological
mechanisms of action of these five substances are similar to those of
the benzodiazepine drug class. These substances bind to the
GABA<INF>A</INF> receptors with high affinity; this affinity increases
in the presence of GABA and is blocked by the GABA<INF>A</INF> receptor
antagonist, flumazenil.\11\ In addition, in drug discrimination
experiments,\12\ the data demonstrate that these substances fully
substitute for the discriminative stimulus effects of midazolam, a
schedule IV benzodiazepine.\13\
---------------------------------------------------------------------------
\11\ In vitro pharmacology data was collected through the DEA-
Veterans Affairs interagency agreement, ``In Vitro Receptor and
Transporter Assays for Abuse Liability Testing for the DEA by the
VA.''
\12\ Drug discrimination is widely used to determine whether a
new test drug or substance is pharmacologically similar to a known
drug of abuse. The discriminative stimulus effects of a given drug
in animals and its subjective effects in humans are strongly
correlated. See Balster, R. L., & Bigelow, G. E. (2003). Guidelines
and methodological reviews concerning drug abuse liability
assessment. Drug and alcohol dependence, 70(3 Suppl), S13-S40.
<a href="https://doi.org/10.1016/s0376-8716">https://doi.org/10.1016/s0376-8716</a>(03)00097-8. See also Schuster, C.
R., & Johanson, C. E. (1988). Relationship between the
discriminative stimulus properties and subjective effects of drugs.
Psychopharmacology series, 4, 161-175. <a href="https://doi.org/10.1007/978-3-642-73223-2_13">https://doi.org/10.1007/978-3-642-73223-2_13</a>. See also Solinas, M., Panlilio, L. V., Justinova,
Z., Yasar, S., & Goldberg, S. R. (2006). Using drug-discrimination
techniques to study the abuse-related effects of psychoactive drugs
in rats. Nature protocols, 1(3), 1194-1206. <a href="https://doi.org/10.1038/nprot.2006.167">https://doi.org/10.1038/nprot.2006.167</a>.
\13\ Drug Enforcement Administration Contract 15DDHQ21P00000835,
``Evaluation of synthetic opioid substances using analgesia and drug
discrimination assays.'' Annual report for 2022, unpublished.
---------------------------------------------------------------------------
Clinical studies have not been conducted to evaluate the
pharmacological effects of clonazolam, diclazepam, flualprazolam, or
flubromazolam. However, a few clinical studies exist for etizolam,
which select countries have approved for limited use. According to HHS,
these studies compared the therapeutic effects of etizolam to known
benzodiazepines, such as alprazolam, but did not address the abuse
potential of the drug. In addition, trip reports on user forums
indicate that these five substances produce CNS depression and
sedative-hypnotic effects, similar to other benzodiazepines. These
data, collectively with the extensive clinical studies on classical
benzodiazepines, strongly suggest that these five designer
benzodiazepines have pharmacological effects similar to those of other
known benzodiazepines.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance
The five designer benzodiazepines share structural similarities
with other substances of the benzodiazepine class. Benzodiazepines are
named after their parent structure, which is formed from the fusion of
two ring systems--the benzene ring and diazepine ring. Diclazepam
contains this parent structure and is further modified with the
addition of a methyl and keto group. Clonazolam, flualprazolam, and
flubromazolam are considered to be part of the class of benzodiazepines
known as triazolobenzodiazepines because they contain the parent
structure and the addition of a triazole ring fused to the diazepine
ring. Etizolam is considered to be a thienotriazolodiazepine because it
contains the triazolo-diazepine fused rings, but with a thiophene ring
replacing the benzene ring. Although etizolam is structurally different
from a classical benzodiazepine, etizolam has similar pharmacological
and chemical properties and thus considered to be an analog of
benzodiazepines.\14\ In addition, all five designer benzodiazepines
have a pendant phenyl group that is further substituted with a halogen
in the ortho position.
---------------------------------------------------------------------------
\14\ See Sanna, E., Pau, D., Tuveri, F., Massa, F., Maciocco,
E., Acquas, C., Floris, C., Fontana, S.N., Maira, G., & Biggio, G.
(1999). Molecular and neurochemical evaluation of the effects of
etizolam on GABAA receptors under normal and stress conditions.
Arzneimittel-Forschung, 49(2), 88-95. <a href="https://doi.org/10.1055/s-0031-1300366">https://doi.org/10.1055/s-0031-1300366</a>.
---------------------------------------------------------------------------
4. Its History and Current Pattern of Abuse
Classical benzodiazepines have been extensively prescribed in the
United States; however, these medications have also been used non-
therapeutically and recreationally, with initial reports of abuse soon
after pharmaceutical development (Loveridge, 1981; Woody et al., 1975).
Unlike these classical benzodiazepines that have FDA approval,
clonazolam, diclazepam, etizolam, flualprazolam, and flubromazolam have
no legitimate channel as marketed drug products in the United States.
Despite this, available data from user reports, toxicological cases,
scientific literature, and law enforcement seizures indicate that each
of these substances appear on the illicit drug market and are
trafficked for their psychoactive effects. Based on these available
data, the five designer benzodiazepines are often used alone or in
combination with other substances, such as fentanyl, traditional and
NPS benzodiazepines, NPS opioids, and stimulants. The five designer
benzodiazepines substances have been encountered in various forms
(e.g., powder, tablet, liquid), are primarily reported as orally
consumed (at doses less than 4 mg), and lead to toxicity and other
adverse health consequences, including death.
The misuse and abuse of benzodiazepines have been demonstrated and
are well-characterized.\15\ According to the Substance Abuse and Mental
Health Services Administration's National Survey on Drug Use and Health
2023 annual report,\16\ 4.7 million people reported misusing
prescription tranquilizers or sedatives (e.g., benzodiazepines) in the
past year. Of the 4.7 million people who reported misusing prescription
tranquilizers or sedatives in the past year in 2023, 4.0 million
individuals were aged 26 years
[[Page 35257]]
or older and included both males and females. Drug user reports
indicate that the population likely to abuse the five designer
benzodiazepines appears to be the same as those abusing prescription
benzodiazepines, barbiturates, and other sedative-hypnotic substances.
This is reflected in available reports for toxicological cases
involving flualprazolam; in these cases, users had an average age of 32
years and included both males and females.\17\ In addition, available
reports for toxicological cases involving etizolam and flubromazolam
indicate that users had an average age of 39 years and included both
males and females.\18\ These users are likely to obtain the substances
through unregulated sources and, therefore, with uncertain and
inconsistent identity, purity, and quantity of these substances.
Consequently, this poses significant, adverse health risks to the end
user.
---------------------------------------------------------------------------
\15\ See Votaw, V.R., Geyer, R., Rieselbach, M.M., & McHugh,
R.K. (2019). The epidemiology of benzodiazepine misuse: A systematic
review. Drug and alcohol dependence, 200, 95-114. <a href="https://doi.org/10.1016/j.drugalcdep.2019.02.033">https://doi.org/10.1016/j.drugalcdep.2019.02.033</a>.
\16\ Key substance use and mental health indicators in the
United States: Results from the 2023 National Survey on Drug Use and
Health (HHS Publication No. PEP24-07-021, NSDUH Series H-59). Center
for Behavioral Health Statistics and Quality, Substance Abuse and
Mental Health Services Administration. <a href="https://www.samhsa.gov/data/report/2023-nsduh-annual-national-report">https://www.samhsa.gov/data/report/2023-nsduh-annual-national-report</a>.
\17\ See Krotulski, A.J., Papsun, D.M., Homan, J.W., Nelson, L.,
& Logan, B.K. (2019). Flualprazolam: Potent benzodiazepine
identified among death and impaired driving cases in the U.S.
(December 2019 Report). Center for Forensic Science Research and
Education. <a href="https://www.cfsre.org/images/content/reports/public_alerts/2019.12.05.Public-Alert_Flualprazolam_NPS-Discovery_120519.pdf">https://www.cfsre.org/images/content/reports/public_alerts/2019.12.05.Public-Alert_Flualprazolam_NPS-Discovery_120519.pdf</a>.
\18\ See Aldy, K., Mustaquim, D., Campleman, S., Meyn, A.,
Abston, S., Krotulski, A., Logan, B., Gladden, M.R., Hughes, A.,
Amaducci, A., Shulman, J., Schwarz, E., Wax, P., Brent, J., Manini,
A., & Toxicology Investigators Consortium Fentalog Study Group
(2021). Notes from the field: Illicit benzodiazepines detected in
patients evaluated in emergency departments for suspected opioid
overdose--Four States, October 6, 2020-March 9, 2021. MMWR.
Morbidity and mortality weekly report, 70(34), 1177-1179. <a href="https://doi.org/10.15585/mmwr.mm7034a4">https://doi.org/10.15585/mmwr.mm7034a4</a>.
---------------------------------------------------------------------------
5. The Scope, Duration, and Significance of Abuse
Law enforcement data, including data from DEA's NFLIS, indicate
that the abuse of the five designer benzodiazepines have become
increasingly widespread across the United States. NFLIS-Drug \19\
registered a collective total of 50,015 reports, from all 50 states and
Washington, DC, pertaining to the trafficking, distribution, and abuse
of the five designer benzodiazepines. Through May 2025, NFLIS-Drug
reported 16,326 total encounters of clonazolam since 2015; 706 of
diclazepam since 2014; 19,650 of etizolam since 2002; 10,468 of
flualprazolam since 2004; and 2,865 of flubromazolam since 2015.
---------------------------------------------------------------------------
\19\ DEA's National Forensic Laboratory Information System
(NFLIS) is a comprehensive information system that collects
scientifically verified data on drug items and cases submitted to
and analyzed by participating federal, state, and local forensic
drug laboratories within the United States. NFLIS-Drug, a component
of NFLIS, includes drug chemistry results from completed analyses
only. While NFLIS data are not direct evidence of abuse, it can lead
to an inference that a drug has been diverted and abused. See
Schedules of Controlled Substances: Placement of Carisoprodol Into
Schedule IV, 76 FR 77330, 77332 (Dec. 12, 2011). NFLIS-Drug data
were queried on May 29, 2025. NFLIS-Drug reports are still pending
for 2024 and 2025 due to normal lag time.
---------------------------------------------------------------------------
In addition, HHS evaluated reports of human exposure to
benzodiazepines to U.S. poison centers and included data over a 10-year
period (2012-2021). According to HHS, among the five designer
benzodiazepines, etizolam had the highest number of total exposure
cases (n = 878) and total abuse cases (n = 377), followed by clonazolam
(n = 343 and n = 162, respectively), flubromazolam (n = 96; n = 47),
diclazepam (n = 78; n = 32), and flualprazolam (n = 67; n = 30).\20\
Moreover, many toxicological cases have involved these five substances,
including cases submitted to and analyzed by DEA's Toxicology Testing
Program (DEA TOX).\21\ Through May 2025, DEA TOX detected clonazolam in
11 cases since 2019, metabolite 8-amino clonazolam \22\ in 57 cases
since 2021, etizolam in 16 cases since 2019, flualprazolam in 24 cases
since 2019, and flubromazolam in 6 cases since 2020. Similarly,
according to HHS, the National Medical Service Labs detected clonazolam
(n = 14), diclazepam (n = 40), etizolam (n = 772), and flubromazolam (n
= 151) among 131,883 postmortem blood samples from January 1, 2018,
through June 30, 2020.\23\ The Center for Forensic Science Research and
Education also reported steady increases in postmortem cases and
toxicology reports associated with clonazolam, etizolam, flualprazolam,
and flubromazolam through June 2022.\24\ Collectively, these data
strongly suggest that the clonazolam, diclazepam, etizolam,
flualprazolam, and flubromazolam are increasingly abused in the United
States.
---------------------------------------------------------------------------
\20\ See HHS's scientific and medical evaluation, entitled
``Basis for the Recommendation to Control Clonazolam, Diclazepam,
Etizolam, Flualprazolam, and Flubromazolam, and Their Salts, in
Schedule I of the Controlled Substances Act.''
\21\ DEA's Toxicology Testing Program (DEA TOX) is a
surveillance program that aims to detect novel psychoactive
substances (NPS) in fatal and nonfatal overdose cases within the
United States. From these cases, biological samples, as well as drug
paraphernalia (on limited occasions), are submitted for analysis by
hospitals, medical examiners, poison centers, and law enforcement
nationwide. DEA TOX data include confirmed detections of NPS through
the data query date, May 27, 2025.
\22\ The amino metabolite of clonazolam has been noted in
literature as both 7-aminoclonazolam and 8-aminoclonazolam; however,
the proper nomenclature is 8-aminoclonazolam, based on the
International Union of Pure and Applied Chemistry (IUPAC) rules for
a triazolobenzodiazepine. See Maskell, P.D., Parks, C., Button, J.,
Liu, H., & McKeown, D.A. (2021). Clarification of the correct
nomenclature of the amino metabolite of clonazolam: 8-
Aminoclonazolam. Journal of analytical toxicology, 45(2), e1-e2.
<a href="https://doi.org/10.1093/jat/bkaa169">https://doi.org/10.1093/jat/bkaa169</a>.
\23\ The National Medical Service (NMS) Labs is a reference
laboratory that provides clinical and postmortem toxicological
testing. NMS Labs data does not include cause-of-death data.
According to HHS, FDA contracted NMS Labs (U.S. Food and Drug
Administration Solicitation 75F40119R00070) to receive a study
report (Loperamide Postmortem Toxicology, November 6, 2020) that
tabulated the number of blood specimens in which a specific
substance was detected, using liquid chromatography-time-of-flight
mass spectrometry, from January 1, 2018 through June 30, 2020.
\24\ The Center for Forensic Science Research and Education's
quarterly trend reports are available online at <a href="https://www.cfsre.org/nps-discovery/trend-reports/nps-benzodiazepines/report/49?trend_type_id=1">https://www.cfsre.org/nps-discovery/trend-reports/nps-benzodiazepines/report/49?trend_type_id=1</a> (last accessed June 3, 2025).
---------------------------------------------------------------------------
6. What, if Any, Risk There is to the Public Health
The increase in benzodiazepine-related overdoses in the United
States has been exacerbated by the availability of NPS benzodiazepines
on the illicit drug market. Public health risks associated with
clonazolam, diclazepam, etizolam, flualprazolam, and flubromazolam
abuse relate to their pharmacological similarities with known
benzodiazepines. These similarities result in similar adverse reactions
in humans and expectedly include CNS depressant-like effects, such as
slurred speech, ataxia, altered mental state, and respiratory
depression. Abuse of clonazolam, diclazepam, etizolam, flualprazolam,
and flubromazolam--both alone and in combination with other
substances--have resulted in adverse effects, including impaired
driving, unintentional overdose, emergency department visits, and
fatalities, within the United States and in other countries. Thus,
these data collectively indicate that the abuse of clonazolam,
diclazepam, etizolam, flualprazolam, and flubromazolam pose increased
risks to public health.
7. Its Psychic or Physiological Dependence Liability
Published scientific data on the dependence liability of the five
designer benzodiazepines is limited; however, collective data from
preclinical studies, trip reports on user forums, and case studies
strongly suggest that the five designer benzodiazepines produce both
psychic and physiological dependence that are consistent with the known
dependence produced by classical benzodiazepines. According to HHS,
every benzodiazepine that has been studied in a nonclinical or clinical
model of dependence has been shown to produce physical dependence--a
conclusion that the scientific and medical community generally accepts.
Data from preclinical studies demonstrate that the pharmacological
[[Page 35258]]
mechanisms of action of the five designer benzodiazepines is similar to
those of the benzodiazepine drug class; thus, clonazolam, diclazepam,
etizolam, flualprazolam, and flubromazolam are expected to produce
psychic and physiological dependence. In addition, trip reports on user
forums indicate that clonazolam, diclazepam, etizolam, flualprazolam,
and flubromazolam produce benzodiazepine-like effects and can have
significantly higher potencies in comparison to other classical
benzodiazepine drugs; thus, the five designer benzodiazepines are
expected to produce psychic and physiological dependence. Lastly,
available case studies for etizolam exemplify the dependence potential
of this designer benzodiazepine in young adults. Overall, based on the
pharmacological similarities of clonazolam, diclazepam, etizolam,
flualprazolam, and flubromazolam to classical benzodiazepines that have
demonstrated psychic and physiological dependence liability, these five
designer benzodiazepines are expected to also produce both psychic and
physiological dependence.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA
The five designer benzodiazepines--clonazolam, diclazepam,
etizolam, flualprazolam, and flubromazolam--are not known to be
immediate precursors of any controlled substance of the CSA, as defined
by 21 U.S.C. 802(23).
Conclusion
After considering the scientific and medical evaluation and
accompanying recommendation of HHS, and DEA's own eight-factor
analysis, DEA finds that these facts and all relevant data constitute
substantial evidence of potential for abuse of clonazolam, diclazepam,
etizolam, flualprazolam, and flubromazolam. As such, DEA proposes to
permanently schedule these five designer benzodiazepines as controlled
substances under the CSA.
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.\25\ After consideration of the analysis and recommendation of
the Assistant Secretary of HHS and review of all other available data,
the Acting Administrator of DEA, pursuant to 21 U.S.C. 811(a) and
812(b)(1), finds that:
---------------------------------------------------------------------------
\25\ 21 U.S.C. 812(b).
---------------------------------------------------------------------------
(1) Clonazolam, diclazepam, etizolam, flualprazolam, and
flubromazolam have a high potential for abuse. These five designer
benzodiazepines are pharmacologically similar to classical
benzodiazepines (e.g., diazepam), which have been shown to produce
dependence and are abused by millions of individuals in the United
States. In vitro binding affinity and functional activity studies, as
well as in vivo drug discrimination studies, demonstrate that these
substances are highly potent positive allosteric modulators of
GABA<INF>A</INF> receptors--a mechanism of action that accounts for the
inhibitory effects of GABA, decreased neuronal activity, and result in
the pharmacological properties of the benzodiazepine class. These
pharmacological properties include CNS depressant effects, such as
anxiolytic, amnesic, anticonvulsant, sedative-hypnotic, respiratory
depressant, and muscle relaxant effects. This finding is consistent
with drug abuse patterns and adverse outcomes from epidemiological data
sources. Thus, these five substances have a high potential for abuse.
(2) Clonazolam, diclazepam, etizolam, flualprazolam, and
flubromazolam have no currently accepted medical use in treatment in
the United States. According to HHS, FDA has not approved a marketing
application for clonazolam, diclazepam, etizolam, flualprazolam, or
flubromazolam. In addition, there are no adequate and well-controlled
clinical studies for any of these substances, and there are no well-
defined finished dosage forms for any of these substances. Furthermore,
these five substances have no known therapeutic applications in the
United States. Thus, these five substances have no currently accepted
medical use in treatment in the United States.\26\
---------------------------------------------------------------------------
\26\ Pursuant to 21 U.S.C. 812(b)(1)(B), when placing a drug or
other substance in schedule I of the CSA, DEA must consider whether
the substance has a currently accepted medical use in treatment in
the United States. First, DEA looks to whether the drug or substance
has FDA approval. When no FDA approval exists, DEA has traditionally
applied a five-part test to determine whether a drug or substances
has a currently accepted medical use: (1) the drug's chemistry must
be known and reproducible; (2) there must be adequate safety
studies; (3) there must be adequate and well-controlled studies
proving efficacy; (4) the drug must be accepted by qualified
experts; and (5) the scientific evidence must be widely available.
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 the 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
(Apr. 11, 2024). In its eight-factor assessment, HHS determined that
clonazolam, diclazepam, etizolam, flualprazolam, and flubromazolam
do not satisfy this two-part test. Therefore, since both DEA and HHS
have determined that these substances do not satisfy the five-part
test, and HHS has determined that the substances do not satisfy the
additional two-part test, DEA concludes that clonazolam, diclazepam,
etizolam, flualprazolam, and flubromazolam do not have a currently
accepted medical use.
---------------------------------------------------------------------------
(3) There is a lack of accepted safety for use of clonazolam,
diclazepam, etizolam, flualprazolam, and flubromazolam under medical
supervision. As stated by HHS, because these five substances have no
approved medical use and have not been investigated as new drugs, their
safety for use under medical supervision has not been determined.
Therefore, there is a lack of accepted safety for use of these five
substances under medical supervision.
Based on these findings, the Acting Administrator of DEA concludes
that clonazolam, diclazepam, etizolam, flualprazolam, and
flubromazolam, including their salts, isomers, and salts of isomers
whenever the existence of such salts, isomers, and salts of isomers is
possible within the specific chemical designation, warrant continued
control in schedule I of the CSA.\27\
Requirements for Handling Clonazolam, Diclazepam, Etizolam,
Flualprazolam, and Flubromazolam
As discussed above, these five designer benzodiazepines are
currently subject to a temporary scheduling order adding them to
schedule I under the CSA. If this rule is finalized as proposed,
clonazolam, diclazepam, etizolam, flualprazolam, and flubromazolam
would be subject, on a permanent basis, to the CSA's schedule I
regulatory controls and administrative, civil, and criminal sanctions
applicable to the manufacture, distribution, dispensing, importing,
exporting, research, and conduct of instructional activities, including
the following:
1. Registration. Any person who handles (manufactures, distributes,
[[Page 35259]]
dispenses, imports, exports, engages in research, or conducts
instructional activities or chemical analysis with, or possesses)
clonazolam, diclazepam, etizolam, flualprazolam, or flubromazolam 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. Clonazolam, diclazepam, etizolam, flualprazolam, and
flubromazolam are subject to schedule I security requirements and must
be handled and stored pursuant to 21 U.S.C. 821 and 823 and in
accordance with 21 CFR 1301.71 through 1301.76. Non-practitioners
handling these five 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 clonazolam, diclazepam, etizolam, flualprazolam, or
flubromazolam must comply with 21 U.S.C. 825 and be in accordance with
21 CFR part 1302.
4. Quota. Only registered manufacturers are permitted to
manufacture clonazolam, diclazepam, etizolam, flualprazolam, and
flubromazolam 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 clonazolam,
diclazepam, etizolam, flualprazolam, or flubromazolam must have an
initial inventory of all stocks of controlled substances (including
these substances) on hand on the date the registrant first engages in
the handling of controlled substances pursuant to 21 U.S.C. 827 and
958, 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 clonazolam,
diclazepam, etizolam, flualprazolam, and flubromazolam) on hand every
two years pursuant to 21 U.S.C. 827 and 958 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 clonazolam, diclazepam, etizolam,
flualprazolam, and flubromazolam pursuant to 21 U.S.C. 827, 832(a), and
958(e) and in accordance with 21 CFR 1301.74(b), 1301.74(c),
1301.76(b), and parts 1304, 1312, and 1317. Manufacturers and
distributors would be required to submit reports regarding clonazolam,
diclazepam, etizolam, flualprazolam, and flubromazolam 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 clonazolam,
diclazepam, etizolam, flualprazolam, or flubromazolam must comply with
the order form requirements pursuant to 21 U.S.C. 828 and 21 CFR part
1305.
8. Importation and Exportation. All importation and exportation of
clonazolam, diclazepam, etizolam, flualprazolam, or flubromazolam 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 clonazolam, diclazepam,
etizolam, flualprazolam, or flubromazolam not authorized by, or in
violation of, the CSA or its implementing regulations is unlawful, and
may subject the person to administrative, civil, and/or criminal
sanctions.
Regulatory Analyses
Executive Orders 12866, 13563, 14192, and 14294 (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 Acting 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.
On July 26, 2023, DEA published an order to temporarily place five
designer benzodiazepines, as defined in the order, in schedule I of the
CSA pursuant to the temporary scheduling provisions of 21 U.S.C.
811(h). DEA estimates that all entities handling or planning to handle
clonazolam, diclazepam, etizolam, flualprazolam, or flubromazolam have
already established and implemented systems and processes required to
handle these substances. DEA proposes placing clonazolam, diclazepam,
etizolam, flualprazolam, and flubromazolam, including its salts,
isomers, and salts of isomers, in schedule I on a permanent basis.
According to HHS, these five designer benzodiazepines have a high
potential for abuse, have no currently accepted medical use in
treatment in the United States, and lack accepted safety for use under
medical supervision. There appear to be no legitimate sources for
clonazolam, diclazepam, etizolam, flualprazolam, or flubromazolam as a
marketed drug in the United States, but DEA notes that these substances
are available for purchase from legitimate suppliers for scientific
research. There is no evidence of significant diversion of these five
substances from legitimate suppliers. Therefore, DEA has concluded that
this proposed rule, if finalized, will not have a significant economic
impact on a substantial number of small entities.
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
[[Page 35260]]
research, conduct instructional activities or chemical analysis with,
or possess), or propose to handle clonazolam, diclazepam, etizolam,
flualprazolam, or flubromazolam, including its salts, isomers, and
salts of isomers, or any combination thereof. DEA determines the
industries that best represent these business activities using the
North American Industry Classification System (NAICS).\28\ 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. The following
table lists the number of firms, small firms, and percent small firms
in each affected industry.
---------------------------------------------------------------------------
\28\ 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> (last accessed 4/2/2024).
Table 1--Business Activity and Corresponding NAICS Industries
----------------------------------------------------------------------------------------------------------------
SBA size Percent
Business activity NAICS NAICS industry Firms \29\ standard Small small
code description \30\ firms \31\ entities
----------------------------------------------------------------------------------------------------------------
Manufacturer.................. 325412 Pharmaceutical 1,179 1,300 1,099 93.2
Preparation
Manufacturing.
Distributor, Importer, 424210 Drugs and Druggists' 7,012 250 6,760 96.4
Exporter. Sundries Merchant
Wholesalers.
424690 Other Chemical and 5,487 175 5,197 94.7
Allied Products
Merchant Wholesalers.
Researcher.................... 541715 Research and 10,042 1,000 9,599 95.6
Development in the
Physical,
Engineering, and
Life Sciences
(except
Nanotechnology and
Biotechnology).
611310 Colleges, 2,494 $34.5 1,515 60.8
Universities, and
Professional Schools.
----------------------------------------------------------------------------------------------------------------
Based on the American Chemical Society's SciFinder database, DEA
identified ten entities supplying clonazolam, diclazepam, etizolam,
flualprazolam, or flubromazolam across the industries 325412, 424210,
and 424690. Two of these entities have already registered with DEA to
handle controlled substances. Hence, DEA expects only eight entities
will be impacted by this rule. Assuming that all affected suppliers
were small entities and concentrated in the smallest NAICS industry,
325412, they would account for only 0.73 percent of the small entities
in those industries, not a substantial number.\32\
---------------------------------------------------------------------------
\29\ 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> (last accessed 6/24/2025).
\30\ U.S. Small Business Administration (SBA), 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> (last accessed 6/24/2025).
\31\ Based on the estimated number of firms below the SBA size
standard for each industry.
\32\ 8/1,099 = 0.73%.
---------------------------------------------------------------------------
Additionally, DEA expects that the number of researchers working
with clonazolam, diclazepam, etizolam, flualprazolam, or flubromazolam
is small, because each of these substances 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 clonazolam, diclazepam, etizolam,
flualprazolam, or flubromazolam 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 the 541715
and 622310 industries.
In summary, the small entities affected by this proposed rule are
those in 325412--Pharmaceutical Preparation Manufacturing, 424210--
Drugs and Druggists' Sundries Merchant Wholesalers, and 424690--Other
Chemical and Allied Products Merchant Wholesalers. The affected small
entities account for less than 0.73 percent of the small businesses and
are not likely to manufacture or carry inventory of clonazolam,
diclazepam, etizolam, flualprazolam, or flubromazolam, including its
salts, isomers, and salts of isomers. 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 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.\33\ 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.
---------------------------------------------------------------------------
\33\ 44 U.S.C. 3501-3521.
---------------------------------------------------------------------------
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:
[[Page 35261]]
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. In Sec. 1308.11:
0
a. Redesignate paragraphs (e)(1) through (3) as paragraphs (e)(6)
through (8);
0
b. Add new paragraphs (e)(1) through (5); and
0
c. Remove and reserve paragraphs (h)(57) through (61).
The addition reads as follows:
Sec. 1308.11 Schedule I.
* * * * *
(e) * * *
* * * * * * *
(1) Clonazolam (Other name: 6-(2-chlorophenyl)-1-methyl-8-nitro- 2786
4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine)..............
* * * * * * *
(2) Diclazepam (Other name: 7-chloro-5-(2-chlorophenyl)-1- 2789
methyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one)............
* * * * * * *
(3) Etizolam (Other name: 4-(2-chlorophenyl)-2-ethyl-9-methyl- 2780
6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine).........
* * * * * * *
(4) Flualprazolam (Other name: 8-chloro-6-(2-fluorophenyl)-1- 2785
methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine).......
* * * * * * *
(5) Flubromazolam (Other name: 8-bromo-6-(2-fluorophenyl)-1- 2788
methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine).......
* * * * * * *
------------------------------------------------------------------------
* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
July 22, 2025, by Acting Administrator Robert J. Murphy. That document
with the original signature and date is maintained by DEA. For
administrative purposes only, and in compliance with requirements of
the Office of the Federal Register, the undersigned DEA Federal
Register Liaison Officer has been authorized to sign and submit the
document in electronic format for publication, as an official document
of DEA. This administrative process in no way alters the legal effect
of this document upon publication in the Federal Register.
Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2025-14022 Filed 7-24-25; 8:45 am]
BILLING CODE 4410-09-P
</pre></body>
</html>Indexed from Federal Register on July 25, 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.