Schedules of Controlled Substances: Temporary Placement of Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam in Schedule I, 48112-48118 [2023-15748]
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various projects. A tool manufacturer
sends the influencer an expensive fullsize lathe in the hope that the influencer
would post about it. The woodworker
uses the lathe for several products and
comments favorably about it in videos.
If a significant minority of viewers are
likely unaware that the influencer
received the lathe free of charge, the
woodworker should clearly and
conspicuously disclose receiving it for
free, a fact that could affect the
credibility that viewers attach to the
endorsements. The manufacturer should
advise the woodworker at the time it
provides the lathe that this connection
should be disclosed, and it should have
reasonable procedures in place to
monitor the influencer’s postings for
compliance and follow those
procedures. (See § 255.1(d).)
(8) Example 8. An online community
has a section dedicated to discussions of
robotic products. Community members
ask and answer questions and otherwise
exchange information and opinions
about robotic products and
developments. Unbeknownst to this
community, an employee of a leading
home robot manufacturer has been
posting messages on the discussion
board promoting the manufacturer’s
new product. Knowledge of this poster’s
employment likely would affect the
weight or credibility of the
endorsements. Therefore, the poster
should clearly and conspicuously
disclose their relationship to the
manufacturer. To limit its own liability
for such posts, the employer should
engage in appropriate training of
employees. To the extent that the
employer has directed such
endorsements or otherwise has reason to
know about them, it should also be
monitoring them and taking other steps
to ensure compliance. (See § 255.1(d).)
The disclosure requirements in this
example would apply equally to
employees posting their own reviews of
the product on retail websites or review
platforms.
(9) Example 9. A college student signs
up to be part of a program in which
points are awarded each time a
participant posts on social media about
a particular advertiser’s products.
Participants can then exchange their
points for prizes, such as concert tickets
or electronics. These incentives would
materially affect the weight or
credibility of the college student’s
endorsements. They should be clearly
and conspicuously disclosed, and the
advertiser should take steps to ensure
that these disclosures are being
provided.
(10) Example 10. Great Paper
Company sells photocopy paper with
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packaging that has a seal of approval
from the No Chlorine Products
Association, a non-profit third-party
association. Great Paper Company paid
the No Chlorine Products Association a
reasonable fee for the evaluation of its
product and its manufacturing process.
Consumers would reasonably expect
that marketers have to pay for this kind
of certification. Therefore, there is no
unexpected material connection
between the company and the
association, and the use of the seal
without disclosure of the fee paid to the
association would not be deceptive.
(11) Example 11. A coffee lover
creates a blog that reviews coffee
makers. The blogger writes the content
independently of the marketers of the
coffee makers but includes affiliate links
to websites on which consumers can
buy these products from their marketers.
Whenever a consumer clicks on such a
link and buys the product, the blogger
receives a portion of the sale. Because
knowledge of this compensation could
affect the weight or credibility site
visitors give to the blogger’s reviews, the
reviews should clearly and
conspicuously disclose the
compensation.
(12) Example 12. (i) Near the
beginning of a podcast, the host reads
what is obviously a commercial for a
product. Even without a statement
identifying the advertiser as a sponsor,
listeners would likely still expect that
the podcaster was compensated, so
there is no need for a disclosure of
payment for the commercial. Depending
upon the language of the commercial,
however, the audience may believe that
the host is expressing their own views
in the commercial, in which case the
host would need to hold the views
expressed. (See § 255.0(b).)
(ii) Assume that the host also
mentions the product in a social media
post. The fact that the host did not have
to make a disclosure in the podcast has
no bearing on whether there has to be
a disclosure in the social media post.
(13) Example 13. An app developer
gives a consumer a game app to review.
The consumer clearly and
conspicuously discloses in the review
that they were given the app, which
normally costs 99 cents, for free. That
disclosure suggests that the consumer
did not receive anything else for the
review. If the app developer also gave
the consumer $50 for the review, the
mere disclosure that the app was free
would be inadequate.
(14) Example 14. Speed Ways, an
internet Service Provider, advertises
that it has the ‘‘Fastest ISP Service’’ as
determined by the ‘‘Data Speed Testing
Company.’’ If Speed Ways
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commissioned and paid for the analysis
of its and competing services, it should
clearly and conspicuously disclose its
relationship to the testing company
because the relationship would likely be
material to consumers in evaluating the
claim. If the ‘‘Data Speed Testing
Company’’ is not a bona fide
independent testing organization with
expertise in judging ISP speeds or it did
not conduct valid tests that supported
the endorsement message, the
endorsement would also be deceptive.
(See § 255.3(c)(3))
§ 255.6
Endorsements directed to children.
Endorsements in advertisements
addressed to children may be of special
concern because of the character of the
audience. Practices that would not
ordinarily be questioned in
advertisements addressed to adults
might be questioned in such cases.
By direction of the Commission.
April J. Tabor,
Secretary.
[FR Doc. 2023–14795 Filed 7–25–23; 8:45 am]
BILLING CODE 6750–01–P
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA–989]
Schedules of Controlled Substances:
Temporary Placement of Etizolam,
Flualprazolam, Clonazolam,
Flubromazolam, and Diclazepam in
Schedule I
Drug Enforcement
Administration, Department of Justice.
ACTION: Temporary amendment;
temporary scheduling order.
AGENCY:
The Administrator of the Drug
Enforcement Administration is issuing
this temporary order to schedule five
synthetic benzodiazepine substances:
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam, in
schedule I of the Controlled Substances
Act. This action is based on a finding by
the Administrator that the placement of
these five substances in schedule I is
necessary to avoid imminent hazard to
the public safety. As a result of this
order, the regulatory controls and
administrative, civil, and criminal
sanctions applicable to schedule I
controlled substances will be imposed
on persons who handle (manufacture,
distribute, reverse distribute, import,
export, engage in research, conduct
instructional activities or chemical
SUMMARY:
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analysis with, or possess) or propose to
handle these five specified controlled
substances.
This temporary scheduling order
is effective July 26, 2023, until July 26,
2025. If this order is extended or made
permanent, DEA will publish a
document in the Federal Register.
FOR FURTHER INFORMATION CONTACT:
Terrence L. Boos, Ph.D., Drug and
Chemical Evaluation Section, Diversion
Control Division, Drug Enforcement
Administration; Mailing Address: 8701
Morrissette Drive, Springfield, Virginia
22152; Telephone: (571) 362–3249.
SUPPLEMENTARY INFORMATION: The Drug
Enforcement Administration (DEA)
issues a temporary scheduling order 1
(in the form of a temporary amendment)
to add the following five substances,
including their salts, isomers, and salts
of isomers, whenever the existence of
such salts, isomers, and salts of isomers
is possible, to schedule I under the
Controlled Substances Act (CSA):
• 4-(2-chlorophenyl)-2-ethyl-9methyl-6H-thieno[3,2f][1,2,4]triazolo[4,3-a][1,4]diazepine
(commonly known as etizolam),
• 8-chloro-6-(2-fluorophenyl)-1methyl-4H-benzo[f][1,2,4]triazolo[4,3a][1,4]diazepine (commonly known as
flualprazolam),
• 6-(2-chlorophenyl)-1-methyl-8nitro-4H-benzo[f][1,2,4]triazolo[4,3a][1,4]diazepine (commonly known as
clonazolam),
• 8-bromo-6-(2-fluorophenyl)-1methyl-4H-benzo[f][1,2,4]triazolo[4,3a][1,4]diazepine (alternate chemical
name: 8-bromo-6-(2-fluorophenyl)-1methyl-4H-[1,2,4]triazolo[4,3a][1,4]benzodiazepine and commonly
known as, flubromazolam), and
• 7-chloro-5-(2-chlorophenyl)-1methyl-1,3-dihydro-2Hbenzo[e][1,4]diazepin-2-one (commonly
known as diclazepam).
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DATES:
Legal Authority
The CSA provides the Attorney
General, as delegated to the
Administrator of DEA (Administrator)
pursuant to 28 CFR 0.100, with the
authority to temporarily place a
substance in schedule I of the CSA for
two years without regard to the
requirements of 21 U.S.C. 811(b), if the
Administrator finds that such action is
necessary to avoid an imminent hazard
to public safety. 21 U.S.C. 811(h)(1). In
addition, if proceedings to control a
1 Though DEA has used the term ‘‘final order’’
with respect to temporary scheduling orders in the
past, this order adheres to the statutory language of
21 U.S.C. 811(h), which refers to a ‘‘temporary
scheduling order.’’ No substantive change is
intended.
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substance are initiated under 21 U.S.C.
811(a)(1) while the substance is
temporarily controlled under section
811(h), the Administrator may extend
the temporary scheduling for up to one
year. 21 U.S.C. 811(h)(2).
Where the necessary findings are
made, a substance may be temporarily
scheduled if it is not listed in any other
schedule under 21 U.S.C. 812, and if
there is no exemption or approval in
effect for the substance under section
505 of the Federal Food, Drug, and
Cosmetic Act, 21 U.S.C. 355. 21 U.S.C.
811(h)(1); 21 CFR part 1308.
Background
The CSA requires the Administrator
to notify the Secretary of the
Department of Health and Human
Services (HHS) of an intent to place a
substance in schedule I of the CSA
temporarily (i.e., to issue a temporary
scheduling order). 21 U.S.C. 811(h)(4).
The Administrator transmitted the
required notice to the Assistant
Secretary for Health of HHS (Assistant
Secretary),2 by letter dated October 27,
2021, regarding etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam. The Assistant Secretary
responded to this notice by letter dated
January 3, 2022, and advised that, based
on a review by the Food and Drug
Administration (FDA), there are
currently no investigational new drug
applications (INDs) or approved new
drug applications (NDA) for etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam. The
Assistant Secretary also stated that HHS
had no objection to the temporary
placement of these substances in
schedule I.
DEA has taken into consideration the
Assistant Secretary’s comments as
required by subsection 811(h)(4). DEA
has found that the control of these five
benzodiazepines in schedule I on a
temporary basis is necessary to avoid an
imminent hazard to the public safety.
Etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam
currently are not listed in any schedule
under the CSA, and no exemptions or
approvals under 21 U.S.C. 355 are in
effect for these five benzodiazepine
substances.
As required by 21 U.S.C. 811(h)(1)(A),
DEA published a notice of intent (NOI)
to temporarily schedule etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam on
December 23, 2022. 87 FR 78887. That
2 The Secretary of HHS has delegated to the
Assistant Secretary for Health of HHS the authority
to make domestic drug scheduling
recommendations. 58 FR 35460, July 1, 1993.
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NOI discussed findings from DEA’s
three-factor analysis dated October
2022, which DEA made available on
www.regulations.gov.
To find that temporarily placing a
substance in schedule I of the CSA is
necessary to avoid an imminent hazard
to the public safety, the Administrator
must consider three of the eight factors
set forth in 21 U.S.C. 811(c): The
substance’s history and current pattern
of abuse; the scope, duration and
significance of abuse; and what, if any,
risk there is to the public health. 21
U.S.C. 811(h)(3). Consideration of these
factors includes any information
indicating actual abuse, diversion from
legitimate channels, and clandestine
importation, manufacture, or
distribution of these substances. 21
U.S.C. 811(h)(3).
Substances meeting the statutory
requirements for temporary scheduling
may only be placed in schedule I. 21
U.S.C. 811(h)(1). Substances in schedule
I are those that have high potential for
abuse, no currently accepted medical
use in treatment in the United States,
and a lack of accepted safety for use
under medical supervision. 21 U.S.C.
812(b)(1).
DEA’s October 2022 three-factor
analysis and the Assistant Secretary’s
January 3, 2022 letter are available in
their entirety under the tab ‘‘Supporting
Documents’’ of the public docket of this
action at www.regulations.gov.
Five Benzodiazepine Substances:
Etizolam, Flualprazolam, Clonazolam,
Flubromazolam, and Diclazepam
The dramatic increase in trafficking
and abuse associated with novel
psychoactive substances (NPS) of the
benzodiazepine class, also known as
designer benzodiazepines, in the United
States has become a national public
health concern in recent years. The
availability of NPS benzodiazepine
substances in the illicit drug market
continues to pose an imminent hazard
to the public safety. The Centers for
Disease Control and Prevention (CDC)
highlights this issue in their Morbidity
and Mortality Weekly Report (MMWR)
published on August 27, 2021.3 CDC
indicated that from April 2019 to June
2020 prescription and illicit
benzodiazepine-involved overdose
deaths increased by 21.8 percent and
519.6 percent respectively.
Additionally, benzodiazepines were
involved in nearly 7,000 overdose
3 Centers for Disease Control and Prevention
Morbidity and Mortality Weekly Report: Trends in
Nonfatal and Fatal Overdoses Involving
Benzodiazepines—38 States and the District of
Columbia, 2019–2020. Vol. 70, No. 34. August 27,
2021.
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deaths in 23 states from January 2019 to
June 2020, accounting for 17 percent of
all drug overdose deaths. Adverse
health effects associated with the abuse
of such substances, their continued
evolution, and increased popularity of
these substances have been a serious
concern in recent years.
The increase in the co-use of opioids
with designer benzodiazepines has
become a particular concern as the
United States continues to experience
an unprecedented epidemic of opioid
misuse and abuse.4 CDC’s 2021 MMWR
further states that between January and
June 2020, 92.7 percent of
benzodiazepine-involved deaths also
involved opioids and 66.7 percent
involved illicitly manufactured
fentanyl. The combination of
benzodiazepines with opioids
substantially enhances the potential for
lethality. Etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam are benzodiazepine
substances recently identified on the
illicit drug market in the United States.
The abuse of etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam has been associated with
fatalities in recent years in the United
States. The positive identification of
these five substances in post-mortem
cases is a serious concern to the public
safety. Additionally, law enforcement
data indicate that the substances at issue
here have significant presence in the
illicit drug market found in the United
States. In light of the law enforcement
encounters and fatalities associated with
the abuse of etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam, these substances pose an
imminent hazard to public safety.
Available data and information for
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam,
summarized below, indicate that these
substances have high potential for
abuse, no currently accepted medical
use in treatment in the United States,
and lack of accepted safety for use
under medical supervision. DEA’s threefactor analysis is available in its entirety
under ‘‘Supporting and Related
Material’’ of the public docket for this
action at www.regulations.gov under
Docket Number DEA–989.
Factor 4. History and Current Pattern of
Abuse
The chemical synthesis of etizolam,
flualprazolam, clonazolam,
4 Centers for Disease Control and Prevention
Morbidity and Mortality Weekly Report: Trends in
Nonfatal and Fatal Overdoses Involving
Benzodiazepines—38 States and the District of
Columbia, 2019–2020. Vol. 70, No. 34. August 27,
2021.
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flubromazolam, and diclazepam was
previously reported in the scientific
literature; however, the research did not
lead to any medically approved
products in the United States. Since
2012, synthetic drugs belonging to the
benzodiazepine class have begun to
emerge in the illicit drug market as
evidenced by the identification of these
drugs in forensic drug exhibits reported
to the National Forensic Laboratory
Information System (NFLIS-Drug) 5 and
toxicology samples. Beginning in 2012,
etizolam emerged on the illicit synthetic
drug market as evidenced by its
identification in drug seizures in the
United States.
In recent years, there has been a rise
in the recreational use of etizolam. As
evidenced by their identification in
NFLIS-Drug, diclazepam emerged in the
United States’ illicit drug market in
2014, flubromazolam and clonazolam in
2015, and flualprazolam in 2017. While
these substances are not approved for
medical use in the United States,
etizolam is approved for medical use in
Italy, India, and Japan.6 In a letter dated
January 3, 2022, the Assistant Secretary
informed DEA that there are no INDs or
FDA-approved NDAs for etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam in the
United States. Hence, there are no
legitimate channels for these substances
as marketed drug products in the United
States. These five benzodiazepine
substances are likely to be abused in the
same manner as other sedative
hypnotics. They have been identified in
tablet form, as white to beige powders,
5 NFLIS-Drug represents an important resource in
monitoring illicit drug trafficking, including the
diversion of legally manufactured pharmaceuticals
into illegal markets. NFLIS-Drug is a comprehensive
information system that includes data from forensic
laboratories that handle more than 96 percent of an
estimated 1.0 million distinct annual state and local
drug analysis cases. NFLIS-Drug includes drug
chemistry results from completed analyses only.
While NFLIS-Drug data is not direct evidence of
abuse, it can lead to an inference that a drug has
been diverted and abused. See 76 FR 77330, 77332,
Dec. 12, 2011.
6 Although there is no evidence suggesting that
etizolam, flualprazolam, clonazolam,
flubromazolam, or diclazepam has a currently
accepted medical use in treatment in the United
States, it bears noting that a drug cannot be found
to have such medical use unless DEA concludes
that it satisfies a five-part test. Specifically, with
respect to a drug that has not been approved by
FDA, to have a currently accepted medical use in
treatment in the United States, all of the following
must be demonstrated: i. The drug’s chemistry must
be known and reproducible; ii. there must be
adequate safety studies; iii. there must be adequate
and well-controlled studies proving efficacy; iv. the
drug must be accepted by qualified experts; and v.
the scientific evidence must be widely available. 57
FR 10499 (1992), pet. for rev. denied, Alliance for
Cannabis Therapeutics v. DEA, 15 F.3d 1131, 1135
(D.C. Cir. 1994).
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or in liquid forms, typically of unknown
purity or concentration.
Based on data from NFLIS-Drug, law
enforcement often encounters etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam in
counterfeit pills, liquid, or powder form.
Substances often found in combination
with some of these benzodiazepines
include substances of abuse such as
heroin (schedule I), fentanyl (schedule
II), substances structurally related to
fentanyl, other benzodiazepines (both
FDA-approved schedule IV
benzodiazepines and other novel noncontrolled benzodiazepines), and
tramadol (schedule IV). Evidence
suggests that individuals are using these
substances to obtain ‘‘legal highs’’ 7 or to
self-medicate. Information gathered
from case histories and autopsy findings
shows that deaths involving etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam were
predominantly associated with polydrug use.
Factor 5. Scope, Duration, and
Significance of Abuse
Etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam are
novel benzodiazepines and evidence
suggests they are abused for their
sedative effects (see Factor 6). In death
investigations involving polysubstance
use, the co-appearance of
benzodiazepines and opioids in
toxicological analysis was common.
Between August 2019 and January 2020,
flualprazolam and etizolam were
identified in seven and six postmortem
blood specimens, respectively, out of 18
deaths associated with the abuse of
isotonitazene, a schedule I opioid that
was recently controlled.8 These cases
corresponded to four states—Illinois (9),
Indiana (7), Minnesota (1), and
Wisconsin (1). Most (12) of the
decedents were male. The ages ranged
from 24 to 66 years old with an average
age of 41 years.9
In another recent publication, 20
forensic postmortem cases were
reviewed and analyzed for the presence
of metonitazine, NPS benzodiazepines,
and opioids. Clonazolam was positively
identified in four cases, etizolam in two
cases, flualprazolam in two cases, and
7 Substances used as ‘‘legal highs’’ are
psychoactive substances that are not controlled
under the CSA, but can be used to obtain a desired
psychoactive effect.
8 85 FR 51342 and 86 FR 60761.
9 Krotulski AJ, Papsun DM, Kacinko SL, and
Logan BK. Isotonitazene Quantitation and
Metabolite Discovery in Authentic Forensic
Casework. Journal of Analytical Toxicology, 2020,
44(6):521–530.
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pyrazolam in one case.10 Law
enforcement encounters of etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam as
reported to NFLIS-Drug include 34,781
drug reports since 2014 (queried 01/13/
2022). NFLIS-Drug registered three
encounters of etizolam in 2012 (first
year of encounter) and 3,022 reports in
2021. Flualprazolam was first
encountered in 2017 when one report
was identified in NFLIS-Drug, and then
in 2021, 1,305 encounters were
reported. A similar trend was seen with
clonazolam. During 2015 (its first year
of encounter), 57 cases were reported in
NFLIS-Drug, while 3,994 drug reports
were identified in 2021. NFLIS-Drug
registered five diclazepam encounters in
2014 (its first year of encounter) and 54
encounters in 2021. Flubromazolam
encounters totaled 14 in 2015 (its first
year of encounter) and 414 in 2021.
The population likely to abuse
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam appears
to be the same as those abusing
prescription benzodiazepines,
barbiturates, and other sedative
hypnotic substances. This is evidenced
by drug user reports associated with
these substances. Because abusers of
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam are
likely to obtain these substances
through unregulated sources, the
identity, purity, and quantity of these
substances are uncertain and
inconsistent, thus posing significant
adverse health risks to the end user.
The misuse and abuse of
benzodiazepines have been
demonstrated and are wellcharacterized.11 According to the most
recent data from the National Survey on
Drug Use and Health (NSDUH),12 as of
10 Krotulski AJ, Papsun DM, Walton SE, and
Logan BK. Metonitazene in the United StatesForensic toxicology assessment of a potent new
synthetic opioid using liquid chromatography mass
spectrometry. Drug Testing Analysis, 2021,
13(10):1697–1711.
11 Votaw VR, Geyer R, Rieselbach MM, and
McHugh RK. The epidemiology of benzodiazepine
misuse: A systematic review. Drug Alcohol
Dependence, 2019, 200:95–114.
12 The National Survey on Drug Use and Health
(NSDUH), formerly known as the National
Household Survey on Drug Abuse (NHSDA), is
conducted annually by the Department of Health
and Human Services Substance Abuse and Mental
Health Services Administration (SAMHSA). It is the
primary source of estimates of the prevalence and
incidence of nonmedical use of pharmaceutical
drugs, illicit drugs, alcohol, and tobacco use in the
United States. The survey is based on a nationally
representative sample of the civilian, noninstitutionalized population 12 years of age and
older. The survey excludes homeless people who
do not use shelters, active military personnel, and
residents of institutional group quarters such as
jails and hospitals. The NSDUH provides yearly
national and state level estimates of drug abuse, and
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2020, an estimated 4.8 million people
aged 12 years or older misused
prescription benzodiazepines in the past
year. This included 1.1 million young
adults aged 18 to 25, 3.5 million adults
aged 26 or older, and 157,000
adolescents aged 12 to 17. This
population abusing prescription
benzodiazepines is likely to be at risk of
abusing etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam. Individuals who initiate
use of these five substances (i.e., use a
drug for the first time) are likely to be
at risk of developing substance use
disorder, overdose, and death at rates
similar to that of other sedative
hypnotics (e.g., alprazolam, etc.). Law
enforcement or toxicology reports
demonstrate that the five substances at
issue are being distributed and abused.
Factor 6. What, if Any, Risk There Is to
the Public Health
The increase in benzodiazepinerelated overdose deaths in the United
States has been exacerbated recently by
the availability of NPS benzodiazepines
in the illicit drug market. Etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam have
been described as derivatives of other
known benzodiazepines, each
possessing various degrees of potency.
Evidence suggests these substances are
being abused for their sedative/hypnotic
effects (see DEA 3-Factor Analysis).
Public health risks associated with the
five substances at issue here relate to
their pharmacological similarities with
known benzodiazepines. Thus, risk to
the public health is associated with
adverse reactions in humans, which are
expected to include CNS depressant-like
effects, such as slurred speech, ataxia,
altered mental state, and respiratory
depression.
Etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam have
been increasingly identified in
toxicology reports, death investigations,
and driving under the influence of drugs
(DUID) cases since their first appearance
in law enforcement seizures. According
to the Center for Forensic Science
Research and Education (CFSRE), a nonprofit organization in collaboration with
the Department of Justice and CDC
between 2020 and 2021, etizolam was
the most identified NPS benzodiazepine
accounting for 697 total toxicology cases
in 2020, many of which were coidentified with fentanyl. In 2021,
etizolam was identified in 1,012
includes prevalence estimates by lifetime (i.e., ever
used), past year, and past month abuse or
dependence. The 2020 NSDUH annual report is
available at https://www.samhsa.gov/data/ (last
accessed February 8, 2022).
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toxicology cases, while flualprazolam,
clonazolam, flubromazolam, and
diclazepam were associated with 432,
331, 170, and four toxicology cases,
respectively (CSFRE Quarterly Trend
Reports: NPS Benzodiazepines in the
United States).
Death investigations associated with
four of the five NPS benzodiazepines at
issue here have increased in recent
years. In a 2021 publication by the
Orange County Crime Lab in Santa Ana,
California, flualprazolam was identified
as serving a contributory role in the
death of 13 of 24 cases analyzed in the
study.13 In another recently published
study, between August 2019 and
January 2020, flualprazolam and
etizolam were identified in seven and
six postmortem blood specimens
respectively, out of 18 deaths associated
with the abuse of isotonitazene, a
schedule I opioid.14 Then, a study
published in 2021 which compiled data
from 254 reports published between
2008 and 2021, identified: 33 deaths
associated with etizolam, 20
flualprazolam-related deaths, six
emergency department (ED) visits
associated with clonazolam, 14
flubromazolam-related ED visits, and
one death, 12 DUID cases, and four ED
visits associated with diclazepam.15
Additionally, in 2020, the European
Monitoring Centre for Drugs and Drug
Addiction reported 34 deaths associated
with diclazepam use, which were
determined through the analysis of
biological samples.16 Furthermore, the
National Poison Data System reported
that between January 2014 and
December 2017, clonazolam was the
second most common benzodiazepine
associated with poison control center
calls, accounting for 50 incidents.17
Impaired driving is another risk factor
associated with the use and abuse of
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam. In a
recent published report from the
13 Ha HH and Mata DC. Flualprazolam
distribution in postmortem samples. Journal of
Forensic Sciences, 2022, 67(1): 297–308.
14 Krotulski AJ, Papsun DM, Kacinko SL, and
Logan BK. Isotonitazene Quantitation and
Metabolite Discovery in Authentic Forensic
Casework. Journal of Analytical Toxicology, 2020,
44(6): 521–530.
15 Brunetti P, Giorgetti R, Tagliabracci A, Huestis
MA, Busardo` FP. Designer Benzodiazepines: A
Review of Toxicology and Public Health Risks.
Pharmaceuticals (Basel). 2021 Jun 11;14(6):560.
16 EMCDDA (2020). EMCDDA response to WHO
request for information on the new psychoactive
substances, eutylone, a-PHiP, 4F-furanylfentanyl, 2methyl-AP–237, and, diclazepam.
17 Carpenter JE, Murray BP, Dunkley C, Kazzi ZN,
Gittinger MH. Designer benzodiazepines: a report of
exposures recorded in the National Poison Data
System, 2014–2017. Clin Toxicol (Phila). 2019
Apr;57(4):282–286.
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Sedgwick County Regional Forensic
Science Center in Wichita, Kansas, 12
DUID case samples were analyzed.
Etizolam was positively identified in
three cases, while flubromazolam was
identified in nine of these cases.18 In a
2021 publication, similar involvement
of flubromazolam in drug-impaired
driving was reported in Canada where
flubromazolam was detected in 10
percent of 113 case samples.19
Diclazepam has also been implicated in
DUID cases domestically and
internationally. In a Norwegian study
conducted between July 2013 and May
2016, diclazepam was identified in 15 of
77 analyzed samples taken from
impaired drivers and individuals
involved in other criminal offenses.
Then, in 2019, a study of Norwegian
drivers was conducted using 575
samples taken predominantly from
intoxicated drivers and individuals who
committed other criminal offenses.20
Notably, 334 samples were found to
contain diclazepam. Additionally, in a
2021 publication from Orange County
Crime Laboratory in Santa Ana,
California, researchers identified 22
samples that tested positive for
flualprazolam in samples obtained from
DUID investigations between August
2018 and September 2020.21
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Finding of Necessity of Schedule I
Placement To Avoid Imminent Hazard
to Public Safety
In accordance with 21 U.S.C.
811(h)(3), based on the available data
and information summarized above, the
uncontrolled manufacture, distribution,
reverse distribution, importation,
exportation, conduct of research and
chemical analysis, possession, and/or
abuse of etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam pose imminent hazards to
public safety. DEA is not aware of any
currently accepted medical uses for
these substances in the United States. A
substance meeting the statutory
requirements for temporary scheduling,
21 U.S.C. 811(h)(1), may only be placed
in schedule I. Substances in schedule I
18 Rohrig TP, Osawa KA, Baird TR, Youso KB.
Driving Impairment Cases Involving Etizolam and
Flubromazolam. J Anal Toxicol. 2021 Feb
6;45(1):93–98.
19 Vaillancourt L, Viel E, Dombrowski C,
Desharnais B, Mireault P. Drugs and driving prior
to cannabis legalization: A 5-year review from DECP
(DRE) cases in the province of Quebec, Canada.
Accid Anal Prev. 2021 Jan;149:105832.
20 Heide G, H2014
17:11 Jul 25, 2023
Jkt 259001
are those that have a high potential for
abuse, no currently accepted medical
use in treatment in the United States,
and a lack of accepted safety for use
under medical supervision. Available
data and information for etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam
indicate that these five synthetic
benzodiazepine substances have a high
potential for abuse, no currently
accepted medical use in treatment in the
United States, and a lack of accepted
safety for use under medical
supervision.
As required by 21 U.S.C. 811(h)(4),
the Administrator transmitted to the
Assistant Secretary for Health, via a
letter dated October 27 2021, notice of
her intent to place etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam in
schedule I on a temporary basis. HHS
had no objection to the temporary
placement of these substances in
schedule I.
DEA subsequently published a NOI
on December 23, 2022. 87 FR 78887.
Conclusion
In accordance with 21 U.S.C.
811(h)(1) and (3), the Administrator
considered available data and
information, herein set forth the
grounds for her determination that it is
necessary to temporarily place etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam in
schedule I of the CSA and finds that
such placement is necessary to avoid an
imminent hazard to the public safety.
This temporary order scheduling
these substances will be effective on the
date the order is published in the
Federal Register and remain in effect for
two years, with a possible extension of
one year, pending completion of the
regular (permanent) scheduling process.
21 U.S.C. 811(h)(1) and (2).
The CSA sets forth specific criteria for
scheduling drugs or other substances.
Permanent scheduling actions in
accordance with 21 U.S.C. 811(a) are
subject to formal rulemaking procedures
done ‘‘on the record after opportunity
for a hearing’’ conducted pursuant to
the provisions of 5 U.S.C. 556 and 557.
21 U.S.C. 811. The permanent
scheduling process of formal
rulemaking affords interested parties
with an appropriate process and the
government any additional relevant
information needed to make
determinations. Final decisions that
conclude the permanent scheduling
process of formal rulemaking are subject
to judicial review. 21 U.S.C. 877.
Temporary scheduling orders are not
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subject to judicial review. 21 U.S.C.
811(h)(6).
Requirements for Handling
Upon the effective date of this
temporary order, etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam will be
subject to the regulatory controls and
administrative, civil, and criminal
sanctions applicable to the manufacture,
distribution, reverse distribution,
importation, exportation, possession of,
and engagement in research and
conduct of instructional activities or
chemical analysis with, schedule I
controlled substances, including the
following:
1. Registration. Any person who
handles (possesses, manufactures,
distributes, reverse distributes, imports,
exports, engages in research, or
conducts instructional activities or
chemical analysis with) or desires to
handle, etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam must be registered with
DEA to conduct such activities,
pursuant to 21 U.S.C. 822, 823, 957, and
958, and in accordance with 21 CFR
parts 1301 and 1312, as of July 26, 2023.
Any person who currently handles
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam and is
not registered with DEA must submit an
application for registration and may not
continue to handle etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam as of
July 26, 2023, unless DEA has approved
that application for registration
pursuant to 21 U.S.C. 822, 823, 957, and
958, and in accordance with 21 CFR
parts 1301 and 1312. Retail sales of
schedule I controlled substances to the
general public are not allowed under the
CSA. Possession of any quantity of these
substances in a manner not authorized
by the CSA on or after July 26, 2023 is
unlawful, and those in possession of
any quantity of these substances may be
subject to prosecution pursuant to the
CSA.
2. Disposal of stocks. Any person who
does not desire or is unable to obtain a
schedule I registration to handle
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam must
surrender all currently held quantities
of these five substances.
3. Security. Etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam are subject to schedule I
security requirements and must be
handled in accordance with 21 CFR
1301.71–1301.93, as of July 26, 2023.
4. Labeling and Packaging. All labels,
labeling, and packaging for commercial
containers of etizolam, flualprazolam,
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clonazolam, flubromazolam, and
diclazepam must comply with 21 U.S.C.
825 and 958(e) and 21 CFR part 1302.
Current DEA registrants will have 30
calendar days from July 26, 2023 to
comply with all labeling and packaging
requirements.
5. Inventory. Every DEA registrant
who possesses any quantity of etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam on the
effective date of this order must take an
inventory of all stocks of these
substances on hand pursuant to 21
U.S.C. 827 and 958, and in accordance
with 21 CFR 1304.03, 1304.04, and
1304.11. Current DEA registrants will
have 30 calendar days from the effective
date of this order to comply with all
inventory requirements. After the initial
inventory, every DEA registrant must
take an inventory of all controlled
substances (including etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam) on
hand on a biennial basis pursuant to 21
U.S.C. 827 and 958 and in accordance
with 21 CFR 1304.03, 1304.04, and
1304.11.
6. Records. All DEA registrants must
maintain records with respect to
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam
pursuant to 21 U.S.C. 827 and 958(e)
and in accordance with 21 CFR parts
1304, 1312, and 1317, and section
1307.11. Current DEA registrants
authorized to handle these five
substances shall have 30 calendar days
from the effective date of this order to
comply with all recordkeeping
requirements.
7. Reports. All DEA registrants must
submit reports with respect to etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam
pursuant to 21 U.S.C. 827 and in
accordance with 21 CFR parts 1304,
1312, and 1317, and sections 1301.74(c)
and 1301.76(b), as of July 26, 2023.
Manufacturers and distributors must
also submit reports regarding these five
substances to the Automation of Reports
and Consolidated Order System
pursuant to 21 U.S.C. 827 and in
accordance with 21 CFR parts 1304 and
1312.
8. Order Forms. All DEA registrants
who distribute etizolam, flualprazolam,
clonazolam, flubromazolam, and
diclazepam must comply with order
form requirements pursuant to 21 U.S.C.
828 and in accordance with 21 CFR part
1305 as of July 26, 2023.
9. Importation and Exportation. All
importation and exportation of etizolam,
flualprazolam, clonazolam,
flubromazolam, and diclazepam must be
in compliance with 21 U.S.C. 952, 953,
VerDate Sep<11>2014
17:11 Jul 25, 2023
Jkt 259001
957, and 958, and in accordance with 21
CFR part 1312 as of July 26, 2023.
10. Quota. Only DEA-registered
manufacturers may manufacture
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam in
accordance with a quota assigned
pursuant to 21 U.S.C. 826 and in
accordance with 21 CFR part 1303, as of
July 26, 2023.
11. Liability. Any activity involving
etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam not
authorized by or in violation of the CSA,
occurring as of July 26, 2023, is
unlawful and may subject the person to
administrative, civil, and/or criminal
sanctions.
Regulatory Matters
The CSA provides for expedited
temporary scheduling actions where
necessary to avoid imminent hazards to
the public safety. Under 21 U.S.C.
811(h), the Administrator, as delegated
by the Attorney General, may, by order,
temporarily schedule substances in
schedule I. Such orders may not be
issued before the expiration of 30 days
from: (1) The publication of a notice in
the Federal Register of the intent to
issue such order and the grounds upon
which such order is to be issued, and (2)
the date that notice of the proposed
temporary scheduling order is
transmitted to the Assistant Secretary
for Health of HHS, as delegated by the
Secretary of HHS. 21 U.S.C. 811(h)(1).
Inasmuch as section 811(h) directs
that temporary scheduling actions be
issued by order (as distinct from a rule)
and sets forth the procedures by which
such orders are to be issued, including
the requirement to publish in the
Federal Register a notice of intent, the
notice-and-comment requirements of
section 553 of the Administrative
Procedure Act (APA), 5 U.S.C. 553,
which are applicable to rulemaking, do
not apply to this temporary scheduling
order. The APA expressly differentiates
between orders and rules, as it defines
an ‘‘order’’ to mean a ‘‘final disposition,
whether affirmative, negative,
injunctive, or declaratory in form, of an
agency in a matter other than rule
making.’’ 5 U.S.C. 551(6) (emphasis
added). The specific language chosen by
Congress indicates its intent that DEA
issue orders instead of proceeding by
rulemaking when temporarily
scheduling substances. Given that
Congress specifically requires the
Administrator (as delegated by the
Attorney General) to follow rulemaking
procedures for other kinds of scheduling
actions, see 21 U.S.C. 811(a), it is
noteworthy that, in section 811(h),
Congress authorized the issuance of
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48117
temporary scheduling actions by order
rather than by rule.
Alternatively, even if this action was
subject to section 553 of the APA, the
Administrator finds that there is good
cause to forgo its notice-and-comment
requirements, as any further delays in
the process for issuing temporary
scheduling orders would be
impracticable and contrary to the public
interest given the manifest urgency to
avoid imminent hazards to public
safety.
Although DEA believes this
temporary scheduling order is not
subject to the notice-and-comment
requirements of section 553 of the APA,
DEA notes that in accordance with 21
U.S.C. 811(h)(4), the Administrator took
into consideration comments submitted
by the Assistant Secretary in response to
the notice that DEA transmitted to the
Assistant Secretary pursuant to such
subsection.
Further, DEA believes that this
temporary scheduling action is not a
‘‘rule’’ as defined by 5 U.S.C. 601(2),
and, accordingly, is not subject to the
requirements of the Regulatory
Flexibility Act. The requirements for the
preparation of an initial regulatory
flexibility analysis in 5 U.S.C. 603(a) are
not applicable where, as here, DEA is
not required by section 553 of the APA
or any other law to publish a general
notice of proposed rulemaking.
In accordance with the principles of
Executive Orders (E.O.) 12866 and
13563, this action is not a significant
regulatory action. E.O. 12866 directs
agencies to assess all costs and benefits
of available regulatory alternatives and,
if regulation is necessary, to select
regulatory approaches that maximize
net benefits (including potential
economic, environmental, public health,
and safety effects; distributive impacts;
and equity). E.O. 13563 is supplemental
to and reaffirms the principles,
structures, and definitions governing
regulatory review as established in E.O.
12866. E.O. 12866 classifies a
‘‘significant regulatory action,’’
requiring review by the Office of
Management and Budget, as any
regulatory action that is likely to result
in a rule that may: (1) Have an annual
effect on the economy of $100 million
or more or adversely affect in a material
way the economy; a sector of the
economy; productivity; competition;
jobs; the environment; public health or
safety; or State, local, or tribal
governments or communities; (2) create
a serious inconsistency or otherwise
interfere with an action taken or
planned by another agency; (3)
materially alter the budgetary impact of
entitlements, grants, user fees, or loan
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programs, or the rights and obligations
of recipients thereof; or (4) raise novel
legal or policy issues arising out of legal
mandates, the President’s priorities, or
the principles set forth in the E.O.
Because this is not a rulemaking action,
this is not a significant regulatory action
as defined in section 3(f) of E.O. 12866.
This action will not have substantial
direct effects on the States, on the
relationship between the national
government and the States, or on the
distribution of power and
responsibilities among the various
levels of government. Therefore, in
accordance with E.O. 13132
(Federalism), it is determined that this
action does not have sufficient
federalism implications to warrant the
preparation of a Federalism Assessment.
Signing Authority
This document of the Drug
Enforcement Administration was signed
on July 18, 2023, by Administrator Anne
Milgram. That document with the
original signature and date is
maintained by DEA. For administrative
purposes only, and in compliance with
requirements of the Office of the Federal
Register, the undersigned DEA Federal
Register Liaison Officer has been
authorized to sign and submit the
document in electronic format for
publication, as an official document of
DEA. This administrative process in no
way alters the legal effect of this
document upon publication in the
Federal Register.
List of Subjects in 21 CFR Part 1308
Administrative practice and
procedure, Drug traffic control,
Reporting and recordkeeping
requirements.
For the reasons set out above, DEA
amends 21 CFR part 1308 as follows:
1. The authority citation for part 1308
continues to read as follows:
■
Authority: 21 U.S.C. 811, 812, 871(b),
956(b), unless otherwise noted.
2. In § 1308.11, add paragraphs (h)(57)
through (h)(61) to read as follows:
■
Schedule I.
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*
*
*
*
*
(h) * * *
(57) 4-(2-chlorophenyl)-2-ethyl-9methyl-6H-thieno[3,2f][1,2,4]triazolo[4,3-a][1,4]diazepine, its
salts, isomers, and salts of isomers
(Other name: etizolam) 2780
(58) 8-chloro-6-(2-fluorophenyl)-1methyl-4H-benzo[f][1,2,4]triazolo[4,3a][1,4]diazepine, its salts, isomers, and
VerDate Sep<11>2014
17:11 Jul 25, 2023
Jkt 259001
Scott Brinks,
Federal Register Liaison Officer, Drug
Enforcement Administration.
[FR Doc. 2023–15748 Filed 7–25–23; 8:45 am]
BILLING CODE 4410–09–P
DEPARTMENT OF THE TREASURY
Internal Revenue Service
26 CFR Part 31
[TD 9978]
RIN 1545–BQ08
Recapture of Certain Excess
Employment Tax Credits Under
COVID–19 Legislation
Internal Revenue Service (IRS),
Treasury.
ACTION: Final regulations and removal of
temporary regulations.
AGENCY:
This document sets forth the
final regulations under sections 3111,
3131, 3132, 3134, and 3221 of the
Internal Revenue Code (Code) issued
under the authority granted by the
Families First Coronavirus Response
Act, the Coronavirus Aid, Relief, and
Economic Security Act, and the
American Rescue Plan Act of 2021.
These final regulations authorize the
assessment of any erroneous refund of
the tax credits paid under sections 7001
and 7003 of the Families First
Coronavirus Response Act (including
any increases in those credits under
section 7005 thereof), and section 2301
of the Coronavirus Aid, Relief, and
Economic Security Act, as well as under
sections 3131, 3132 (including any
increases in those credits under section
3133), and 3134 of the Code.
DATES:
Effective date: These final regulations
are effective on July 24, 2023.
Applicability date: For date of
applicability, see §§ 31.3111–6(e),
SUMMARY:
PART 1308—SCHEDULES OF
CONTROLLED SUBSTANCES
§ 1308.11
salts of isomers (Other name:
flualprazolam) 2785
(59) 6-(2-chlorophenyl)-1-methyl-8nitro-4H-benzo[f][1,2,4]triazolo[4,3a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name:
clonazolam) 2786
(60) 8-bromo-6-(2-fluorophenyl)-1methyl-4H-benzo[f][1,2,4]triazolo[4,3a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name:
flubromazolam) 2788
(61) 7-chloro-5-(2-chlorophenyl)-1methyl-1,3-dihydro-2Hbenzo[e][1,4]diazepin-2-one, its salts,
isomers, and salts of isomers (Other
name: diclazepam) 2789
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31.3131–1(d), 31.3132–1(d), 31.3134–
1(d), and 31.3221–5(e).
FOR FURTHER INFORMATION CONTACT:
NaLee Park at 202–317–6798 (not a tollfree number).
SUPPLEMENTARY INFORMATION:
Background
This document sets forth amendments
to the Employment Tax Regulations (26
CFR part 31) under sections 3111, 3131,
3132, 3133, 3134, and 3221.
The Families First Coronavirus
Response Act (Families First Act),
Public Law 116–127, 134 Stat. 178
(March 18, 2020), as amended and
extended by the COVID-related Tax
Relief Act of 2020 (Tax Relief Act),
enacted as Subtitle B of Title II of
Division N of the Consolidated
Appropriations Act, 2021, Public Law
116–260, 134 Stat.1182 (December 27,
2020), and the Coronavirus Aid, Relief,
and Economic Security Act (CARES
Act), Public Law 116–136, 134 Stat. 281
(March 27, 2020), as amended and
extended by the Taxpayer Certainty and
Disaster Tax Relief Act of 2020 (Relief
Act), enacted as Division EE of the
Consolidated Appropriations Act, 2021,
provided relief to taxpayers from
economic hardships resulting from the
Coronavirus Disease 2019 (COVID–19),
including paid sick and family leave
credits to eligible employers with
respect to qualified leave wages paid for
a period of leave taken beginning April
1, 2020, and ending March 31, 2021,
and an employee retention credit (ERC)
with respect to qualified wages paid
after March 12, 2020, and before July 1,
2021, respectively. The American
Rescue Plan Act of 2021 (ARP), Public
Law 117–2, 135 Stat. 4 (March 11,
2021), provided additional COVID–19
relief with similar paid leave credits
under sections 3131 through 3133 of the
Code, enacted by section 9641 of the
ARP, with respect to qualified leave
wages paid for a period of leave taken
beginning April 1, 2021, and ending
September 30, 2021, and a substantially
similar ERC under section 3134 of the
Code, enacted by section 9651 of the
ARP, with respect to qualified wages
paid after June 30, 2021, and before
January 1, 2022.1
1 Section 80604 of the Infrastructure Investment
and Jobs Act (Infrastructure Act), Public Law 117–
68, 135 Stat. 429 (November 15, 2021) amended
section 3134(n) of the Code to provide that the ERC
under section 3134 applies only to wages paid after
June 30, 2021, and before October 1, 2021 (or, in
the case of wages paid by an eligible employer
which is a recovery startup business, January 1,
2022). Therefore, the only type of employer eligible
for the ERC for wages paid after September 30,
2021, and before January 1, 2022, is an employer
that meets the definition of a recovery startup
business under section 3134(c)(5). See Notice 2021–
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Agencies
[Federal Register Volume 88, Number 142 (Wednesday, July 26, 2023)]
[Rules and Regulations]
[Pages 48112-48118]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-15748]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-989]
Schedules of Controlled Substances: Temporary Placement of
Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam in
Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Temporary amendment; temporary scheduling order.
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SUMMARY: The Administrator of the Drug Enforcement Administration is
issuing this temporary order to schedule five synthetic benzodiazepine
substances: etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam, in schedule I of the Controlled Substances Act. This action
is based on a finding by the Administrator that the placement of these
five substances in schedule I is necessary to avoid imminent hazard to
the public safety. As a result of this order, the regulatory controls
and administrative, civil, and criminal sanctions applicable to
schedule I controlled substances will be imposed on persons who handle
(manufacture, distribute, reverse distribute, import, export, engage in
research, conduct instructional activities or chemical
[[Page 48113]]
analysis with, or possess) or propose to handle these five specified
controlled substances.
DATES: This temporary scheduling order is effective July 26, 2023,
until July 26, 2025. If this order is extended or made permanent, DEA
will publish a document in the Federal Register.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Ph.D., Drug and
Chemical Evaluation Section, Diversion Control Division, Drug
Enforcement Administration; Mailing Address: 8701 Morrissette Drive,
Springfield, Virginia 22152; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION: The Drug Enforcement Administration (DEA)
issues a temporary scheduling order \1\ (in the form of a temporary
amendment) to add the following five substances, including their salts,
isomers, and salts of isomers, whenever the existence of such salts,
isomers, and salts of isomers is possible, to schedule I under the
Controlled Substances Act (CSA):
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\1\ Though DEA has used the term ``final order'' with respect to
temporary scheduling orders in the past, this order adheres to the
statutory language of 21 U.S.C. 811(h), which refers to a
``temporary scheduling order.'' No substantive change is intended.
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4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-
f][1,2,4]triazolo[4,3-a][1,4]diazepine (commonly known as etizolam),
8-chloro-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (commonly known as
flualprazolam),
6-(2-chlorophenyl)-1-methyl-8-nitro-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (commonly known as
clonazolam),
8-bromo-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (alternate chemical name:
8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-
a][1,4]benzodiazepine and commonly known as, flubromazolam), and
7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-
benzo[e][1,4]diazepin-2-one (commonly known as diclazepam).
Legal Authority
The CSA provides the Attorney General, as delegated to the
Administrator of DEA (Administrator) pursuant to 28 CFR 0.100, with the
authority to temporarily place a substance in schedule I of the CSA for
two years without regard to the requirements of 21 U.S.C. 811(b), if
the Administrator finds that such action is necessary to avoid an
imminent hazard to public safety. 21 U.S.C. 811(h)(1). In addition, if
proceedings to control a substance are initiated under 21 U.S.C.
811(a)(1) while the substance is temporarily controlled under section
811(h), the Administrator may extend the temporary scheduling for up to
one year. 21 U.S.C. 811(h)(2).
Where the necessary findings are made, a substance may be
temporarily scheduled if it is not listed in any other schedule under
21 U.S.C. 812, and if there is no exemption or approval in effect for
the substance under section 505 of the Federal Food, Drug, and Cosmetic
Act, 21 U.S.C. 355. 21 U.S.C. 811(h)(1); 21 CFR part 1308.
Background
The CSA requires the Administrator to notify the Secretary of the
Department of Health and Human Services (HHS) of an intent to place a
substance in schedule I of the CSA temporarily (i.e., to issue a
temporary scheduling order). 21 U.S.C. 811(h)(4). The Administrator
transmitted the required notice to the Assistant Secretary for Health
of HHS (Assistant Secretary),\2\ by letter dated October 27, 2021,
regarding etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam. The Assistant Secretary responded to this notice by letter
dated January 3, 2022, and advised that, based on a review by the Food
and Drug Administration (FDA), there are currently no investigational
new drug applications (INDs) or approved new drug applications (NDA)
for etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam.
The Assistant Secretary also stated that HHS had no objection to the
temporary placement of these substances in schedule I.
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\2\ The Secretary of HHS has delegated to the Assistant
Secretary for Health of HHS the authority to make domestic drug
scheduling recommendations. 58 FR 35460, July 1, 1993.
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DEA has taken into consideration the Assistant Secretary's comments
as required by subsection 811(h)(4). DEA has found that the control of
these five benzodiazepines in schedule I on a temporary basis is
necessary to avoid an imminent hazard to the public safety. Etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam currently are
not listed in any schedule under the CSA, and no exemptions or
approvals under 21 U.S.C. 355 are in effect for these five
benzodiazepine substances.
As required by 21 U.S.C. 811(h)(1)(A), DEA published a notice of
intent (NOI) to temporarily schedule etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam on December 23, 2022. 87 FR
78887. That NOI discussed findings from DEA's three-factor analysis
dated October 2022, which DEA made available on www.regulations.gov.
To find that temporarily placing a substance in schedule I of the
CSA is necessary to avoid an imminent hazard to the public safety, the
Administrator must consider three of the eight factors set forth in 21
U.S.C. 811(c): The substance's history and current pattern of abuse;
the scope, duration and significance of abuse; and what, if any, risk
there is to the public health. 21 U.S.C. 811(h)(3). Consideration of
these factors includes any information indicating actual abuse,
diversion from legitimate channels, and clandestine importation,
manufacture, or distribution of these substances. 21 U.S.C. 811(h)(3).
Substances meeting the statutory requirements for temporary
scheduling may only be placed in schedule I. 21 U.S.C. 811(h)(1).
Substances in schedule I are those that have high potential for abuse,
no currently accepted medical use in treatment in the United States,
and a lack of accepted safety for use under medical supervision. 21
U.S.C. 812(b)(1).
DEA's October 2022 three-factor analysis and the Assistant
Secretary's January 3, 2022 letter are available in their entirety
under the tab ``Supporting Documents'' of the public docket of this
action at www.regulations.gov.
Five Benzodiazepine Substances: Etizolam, Flualprazolam, Clonazolam,
Flubromazolam, and Diclazepam
The dramatic increase in trafficking and abuse associated with
novel psychoactive substances (NPS) of the benzodiazepine class, also
known as designer benzodiazepines, in the United States has become a
national public health concern in recent years. The availability of NPS
benzodiazepine substances in the illicit drug market continues to pose
an imminent hazard to the public safety. The Centers for Disease
Control and Prevention (CDC) highlights this issue in their Morbidity
and Mortality Weekly Report (MMWR) published on August 27, 2021.\3\ CDC
indicated that from April 2019 to June 2020 prescription and illicit
benzodiazepine-involved overdose deaths increased by 21.8 percent and
519.6 percent respectively. Additionally, benzodiazepines were involved
in nearly 7,000 overdose
[[Page 48114]]
deaths in 23 states from January 2019 to June 2020, accounting for 17
percent of all drug overdose deaths. Adverse health effects associated
with the abuse of such substances, their continued evolution, and
increased popularity of these substances have been a serious concern in
recent years.
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\3\ Centers for Disease Control and Prevention Morbidity and
Mortality Weekly Report: Trends in Nonfatal and Fatal Overdoses
Involving Benzodiazepines--38 States and the District of Columbia,
2019-2020. Vol. 70, No. 34. August 27, 2021.
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The increase in the co-use of opioids with designer benzodiazepines
has become a particular concern as the United States continues to
experience an unprecedented epidemic of opioid misuse and abuse.\4\
CDC's 2021 MMWR further states that between January and June 2020, 92.7
percent of benzodiazepine-involved deaths also involved opioids and
66.7 percent involved illicitly manufactured fentanyl. The combination
of benzodiazepines with opioids substantially enhances the potential
for lethality. Etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam are benzodiazepine substances recently identified on the
illicit drug market in the United States.
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\4\ Centers for Disease Control and Prevention Morbidity and
Mortality Weekly Report: Trends in Nonfatal and Fatal Overdoses
Involving Benzodiazepines--38 States and the District of Columbia,
2019-2020. Vol. 70, No. 34. August 27, 2021.
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The abuse of etizolam, flualprazolam, clonazolam, flubromazolam,
and diclazepam has been associated with fatalities in recent years in
the United States. The positive identification of these five substances
in post-mortem cases is a serious concern to the public safety.
Additionally, law enforcement data indicate that the substances at
issue here have significant presence in the illicit drug market found
in the United States. In light of the law enforcement encounters and
fatalities associated with the abuse of etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam, these substances pose an
imminent hazard to public safety.
Available data and information for etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam, summarized below, indicate
that these substances have high potential for abuse, no currently
accepted medical use in treatment in the United States, and lack of
accepted safety for use under medical supervision. DEA's three-factor
analysis is available in its entirety under ``Supporting and Related
Material'' of the public docket for this action at www.regulations.gov
under Docket Number DEA-989.
Factor 4. History and Current Pattern of Abuse
The chemical synthesis of etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam was previously reported in the scientific
literature; however, the research did not lead to any medically
approved products in the United States. Since 2012, synthetic drugs
belonging to the benzodiazepine class have begun to emerge in the
illicit drug market as evidenced by the identification of these drugs
in forensic drug exhibits reported to the National Forensic Laboratory
Information System (NFLIS-Drug) \5\ and toxicology samples. Beginning
in 2012, etizolam emerged on the illicit synthetic drug market as
evidenced by its identification in drug seizures in the United States.
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\5\ NFLIS-Drug represents an important resource in monitoring
illicit drug trafficking, including the diversion of legally
manufactured pharmaceuticals into illegal markets. NFLIS-Drug is a
comprehensive information system that includes data from forensic
laboratories that handle more than 96 percent of an estimated 1.0
million distinct annual state and local drug analysis cases. NFLIS-
Drug includes drug chemistry results from completed analyses only.
While NFLIS-Drug data is not direct evidence of abuse, it can lead
to an inference that a drug has been diverted and abused. See 76 FR
77330, 77332, Dec. 12, 2011.
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In recent years, there has been a rise in the recreational use of
etizolam. As evidenced by their identification in NFLIS-Drug,
diclazepam emerged in the United States' illicit drug market in 2014,
flubromazolam and clonazolam in 2015, and flualprazolam in 2017. While
these substances are not approved for medical use in the United States,
etizolam is approved for medical use in Italy, India, and Japan.\6\ In
a letter dated January 3, 2022, the Assistant Secretary informed DEA
that there are no INDs or FDA-approved NDAs for etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam in the United
States. Hence, there are no legitimate channels for these substances as
marketed drug products in the United States. These five benzodiazepine
substances are likely to be abused in the same manner as other sedative
hypnotics. They have been identified in tablet form, as white to beige
powders, or in liquid forms, typically of unknown purity or
concentration.
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\6\ Although there is no evidence suggesting that etizolam,
flualprazolam, clonazolam, flubromazolam, or diclazepam has a
currently accepted medical use in treatment in the United States, it
bears noting that a drug cannot be found to have such medical use
unless DEA concludes that it satisfies a five-part test.
Specifically, with respect to a drug that has not been approved by
FDA, to have a currently accepted medical use in treatment in the
United States, all of the following must be demonstrated: i. The
drug's chemistry must be known and reproducible; ii. there must be
adequate safety studies; iii. there must be adequate and well-
controlled studies proving efficacy; iv. the drug must be accepted
by qualified experts; and v. the scientific evidence must be widely
available. 57 FR 10499 (1992), pet. for rev. denied, Alliance for
Cannabis Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).
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Based on data from NFLIS-Drug, law enforcement often encounters
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam in
counterfeit pills, liquid, or powder form. Substances often found in
combination with some of these benzodiazepines include substances of
abuse such as heroin (schedule I), fentanyl (schedule II), substances
structurally related to fentanyl, other benzodiazepines (both FDA-
approved schedule IV benzodiazepines and other novel non-controlled
benzodiazepines), and tramadol (schedule IV). Evidence suggests that
individuals are using these substances to obtain ``legal highs'' \7\ or
to self-medicate. Information gathered from case histories and autopsy
findings shows that deaths involving etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam were predominantly associated
with poly-drug use.
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\7\ Substances used as ``legal highs'' are psychoactive
substances that are not controlled under the CSA, but can be used to
obtain a desired psychoactive effect.
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Factor 5. Scope, Duration, and Significance of Abuse
Etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
are novel benzodiazepines and evidence suggests they are abused for
their sedative effects (see Factor 6). In death investigations
involving polysubstance use, the co-appearance of benzodiazepines and
opioids in toxicological analysis was common. Between August 2019 and
January 2020, flualprazolam and etizolam were identified in seven and
six postmortem blood specimens, respectively, out of 18 deaths
associated with the abuse of isotonitazene, a schedule I opioid that
was recently controlled.\8\ These cases corresponded to four states--
Illinois (9), Indiana (7), Minnesota (1), and Wisconsin (1). Most (12)
of the decedents were male. The ages ranged from 24 to 66 years old
with an average age of 41 years.\9\
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\8\ 85 FR 51342 and 86 FR 60761.
\9\ Krotulski AJ, Papsun DM, Kacinko SL, and Logan BK.
Isotonitazene Quantitation and Metabolite Discovery in Authentic
Forensic Casework. Journal of Analytical Toxicology, 2020,
44(6):521-530.
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In another recent publication, 20 forensic postmortem cases were
reviewed and analyzed for the presence of metonitazine, NPS
benzodiazepines, and opioids. Clonazolam was positively identified in
four cases, etizolam in two cases, flualprazolam in two cases, and
[[Page 48115]]
pyrazolam in one case.\10\ Law enforcement encounters of etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam as reported to
NFLIS-Drug include 34,781 drug reports since 2014 (queried 01/13/2022).
NFLIS-Drug registered three encounters of etizolam in 2012 (first year
of encounter) and 3,022 reports in 2021. Flualprazolam was first
encountered in 2017 when one report was identified in NFLIS-Drug, and
then in 2021, 1,305 encounters were reported. A similar trend was seen
with clonazolam. During 2015 (its first year of encounter), 57 cases
were reported in NFLIS-Drug, while 3,994 drug reports were identified
in 2021. NFLIS-Drug registered five diclazepam encounters in 2014 (its
first year of encounter) and 54 encounters in 2021. Flubromazolam
encounters totaled 14 in 2015 (its first year of encounter) and 414 in
2021.
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\10\ Krotulski AJ, Papsun DM, Walton SE, and Logan BK.
Metonitazene in the United States-Forensic toxicology assessment of
a potent new synthetic opioid using liquid chromatography mass
spectrometry. Drug Testing Analysis, 2021, 13(10):1697-1711.
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The population likely to abuse etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam appears to be the same as those abusing
prescription benzodiazepines, barbiturates, and other sedative hypnotic
substances. This is evidenced by drug user reports associated with
these substances. Because abusers of etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam are likely to obtain these
substances through unregulated sources, the identity, purity, and
quantity of these substances are uncertain and inconsistent, thus
posing significant adverse health risks to the end user.
The misuse and abuse of benzodiazepines have been demonstrated and
are well-characterized.\11\ According to the most recent data from the
National Survey on Drug Use and Health (NSDUH),\12\ as of 2020, an
estimated 4.8 million people aged 12 years or older misused
prescription benzodiazepines in the past year. This included 1.1
million young adults aged 18 to 25, 3.5 million adults aged 26 or
older, and 157,000 adolescents aged 12 to 17. This population abusing
prescription benzodiazepines is likely to be at risk of abusing
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam.
Individuals who initiate use of these five substances (i.e., use a drug
for the first time) are likely to be at risk of developing substance
use disorder, overdose, and death at rates similar to that of other
sedative hypnotics (e.g., alprazolam, etc.). Law enforcement or
toxicology reports demonstrate that the five substances at issue are
being distributed and abused.
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\11\ Votaw VR, Geyer R, Rieselbach MM, and McHugh RK. The
epidemiology of benzodiazepine misuse: A systematic review. Drug
Alcohol Dependence, 2019, 200:95-114.
\12\ The National Survey on Drug Use and Health (NSDUH),
formerly known as the National Household Survey on Drug Abuse
(NHSDA), is conducted annually by the Department of Health and Human
Services Substance Abuse and Mental Health Services Administration
(SAMHSA). It is the primary source of estimates of the prevalence
and incidence of nonmedical use of pharmaceutical drugs, illicit
drugs, alcohol, and tobacco use in the United States. The survey is
based on a nationally representative sample of the civilian, non-
institutionalized population 12 years of age and older. The survey
excludes homeless people who do not use shelters, active military
personnel, and residents of institutional group quarters such as
jails and hospitals. The NSDUH provides yearly national and state
level estimates of drug abuse, and includes prevalence estimates by
lifetime (i.e., ever used), past year, and past month abuse or
dependence. The 2020 NSDUH annual report is available at https://www.samhsa.gov/data/ (last accessed February 8, 2022).
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Factor 6. What, if Any, Risk There Is to the Public Health
The increase in benzodiazepine-related overdose deaths in the
United States has been exacerbated recently by the availability of NPS
benzodiazepines in the illicit drug market. Etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam have been described as
derivatives of other known benzodiazepines, each possessing various
degrees of potency. Evidence suggests these substances are being abused
for their sedative/hypnotic effects (see DEA 3-Factor Analysis). Public
health risks associated with the five substances at issue here relate
to their pharmacological similarities with known benzodiazepines. Thus,
risk to the public health is associated with adverse reactions in
humans, which are expected to include CNS depressant-like effects, such
as slurred speech, ataxia, altered mental state, and respiratory
depression.
Etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
have been increasingly identified in toxicology reports, death
investigations, and driving under the influence of drugs (DUID) cases
since their first appearance in law enforcement seizures. According to
the Center for Forensic Science Research and Education (CFSRE), a non-
profit organization in collaboration with the Department of Justice and
CDC between 2020 and 2021, etizolam was the most identified NPS
benzodiazepine accounting for 697 total toxicology cases in 2020, many
of which were co-identified with fentanyl. In 2021, etizolam was
identified in 1,012 toxicology cases, while flualprazolam, clonazolam,
flubromazolam, and diclazepam were associated with 432, 331, 170, and
four toxicology cases, respectively (CSFRE Quarterly Trend Reports: NPS
Benzodiazepines in the United States).
Death investigations associated with four of the five NPS
benzodiazepines at issue here have increased in recent years. In a 2021
publication by the Orange County Crime Lab in Santa Ana, California,
flualprazolam was identified as serving a contributory role in the
death of 13 of 24 cases analyzed in the study.\13\ In another recently
published study, between August 2019 and January 2020, flualprazolam
and etizolam were identified in seven and six postmortem blood
specimens respectively, out of 18 deaths associated with the abuse of
isotonitazene, a schedule I opioid.\14\ Then, a study published in 2021
which compiled data from 254 reports published between 2008 and 2021,
identified: 33 deaths associated with etizolam, 20 flualprazolam-
related deaths, six emergency department (ED) visits associated with
clonazolam, 14 flubromazolam-related ED visits, and one death, 12 DUID
cases, and four ED visits associated with diclazepam.\15\ Additionally,
in 2020, the European Monitoring Centre for Drugs and Drug Addiction
reported 34 deaths associated with diclazepam use, which were
determined through the analysis of biological samples.\16\ Furthermore,
the National Poison Data System reported that between January 2014 and
December 2017, clonazolam was the second most common benzodiazepine
associated with poison control center calls, accounting for 50
incidents.\17\
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\13\ Ha HH and Mata DC. Flualprazolam distribution in postmortem
samples. Journal of Forensic Sciences, 2022, 67(1): 297-308.
\14\ Krotulski AJ, Papsun DM, Kacinko SL, and Logan BK.
Isotonitazene Quantitation and Metabolite Discovery in Authentic
Forensic Casework. Journal of Analytical Toxicology, 2020, 44(6):
521-530.
\15\ Brunetti P, Giorgetti R, Tagliabracci A, Huestis MA,
Busard[ograve] FP. Designer Benzodiazepines: A Review of Toxicology
and Public Health Risks. Pharmaceuticals (Basel). 2021 Jun
11;14(6):560.
\16\ EMCDDA (2020). EMCDDA response to WHO request for
information on the new psychoactive substances, eutylone, [alpha]-
PHiP, 4F-furanylfentanyl, 2-methyl-AP-237, and, diclazepam.
\17\ Carpenter JE, Murray BP, Dunkley C, Kazzi ZN, Gittinger MH.
Designer benzodiazepines: a report of exposures recorded in the
National Poison Data System, 2014-2017. Clin Toxicol (Phila). 2019
Apr;57(4):282-286.
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Impaired driving is another risk factor associated with the use and
abuse of etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam. In a recent published report from the
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Sedgwick County Regional Forensic Science Center in Wichita, Kansas, 12
DUID case samples were analyzed. Etizolam was positively identified in
three cases, while flubromazolam was identified in nine of these
cases.\18\ In a 2021 publication, similar involvement of flubromazolam
in drug-impaired driving was reported in Canada where flubromazolam was
detected in 10 percent of 113 case samples.\19\ Diclazepam has also
been implicated in DUID cases domestically and internationally. In a
Norwegian study conducted between July 2013 and May 2016, diclazepam
was identified in 15 of 77 analyzed samples taken from impaired drivers
and individuals involved in other criminal offenses. Then, in 2019, a
study of Norwegian drivers was conducted using 575 samples taken
predominantly from intoxicated drivers and individuals who committed
other criminal offenses.\20\ Notably, 334 samples were found to contain
diclazepam. Additionally, in a 2021 publication from Orange County
Crime Laboratory in Santa Ana, California, researchers identified 22
samples that tested positive for flualprazolam in samples obtained from
DUID investigations between August 2018 and September 2020.\21\
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\18\ Rohrig TP, Osawa KA, Baird TR, Youso KB. Driving Impairment
Cases Involving Etizolam and Flubromazolam. J Anal Toxicol. 2021 Feb
6;45(1):93-98.
\19\ Vaillancourt L, Viel E, Dombrowski C, Desharnais B,
Mireault P. Drugs and driving prior to cannabis legalization: A 5-
year review from DECP (DRE) cases in the province of Quebec, Canada.
Accid Anal Prev. 2021 Jan;149:105832.
\20\ Heide G, H[oslash]iseth G, Middelkoop G, and [Oslash]iestad
[Aring]ML. Blood concentrations of designer benzodiazepines:
Relation to impairment and findings in forensic cases. Journal of
Analytical Toxicology, 2020, 44(8): 905-914.
\21\ Ha HH and Mata DC. Flualprazolam distribution in postmortem
samples. Journal of Forensic Sciences, 2022, 67(1): 297-308.
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Finding of Necessity of Schedule I Placement To Avoid Imminent Hazard
to Public Safety
In accordance with 21 U.S.C. 811(h)(3), based on the available data
and information summarized above, the uncontrolled manufacture,
distribution, reverse distribution, importation, exportation, conduct
of research and chemical analysis, possession, and/or abuse of
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam pose
imminent hazards to public safety. DEA is not aware of any currently
accepted medical uses for these substances in the United States. A
substance meeting the statutory requirements for temporary scheduling,
21 U.S.C. 811(h)(1), may only be placed in schedule I. Substances in
schedule I are those that have a high potential for abuse, no currently
accepted medical use in treatment in the United States, and a lack of
accepted safety for use under medical supervision. Available data and
information for etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam indicate that these five synthetic benzodiazepine substances
have a high potential for abuse, no currently accepted medical use in
treatment in the United States, and a lack of accepted safety for use
under medical supervision.
As required by 21 U.S.C. 811(h)(4), the Administrator transmitted
to the Assistant Secretary for Health, via a letter dated October 27
2021, notice of her intent to place etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam in schedule I on a temporary
basis. HHS had no objection to the temporary placement of these
substances in schedule I.
DEA subsequently published a NOI on December 23, 2022. 87 FR 78887.
Conclusion
In accordance with 21 U.S.C. 811(h)(1) and (3), the Administrator
considered available data and information, herein set forth the grounds
for her determination that it is necessary to temporarily place
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam in
schedule I of the CSA and finds that such placement is necessary to
avoid an imminent hazard to the public safety.
This temporary order scheduling these substances will be effective
on the date the order is published in the Federal Register and remain
in effect for two years, with a possible extension of one year, pending
completion of the regular (permanent) scheduling process. 21 U.S.C.
811(h)(1) and (2).
The CSA sets forth specific criteria for scheduling drugs or other
substances. Permanent scheduling actions in accordance with 21 U.S.C.
811(a) are subject to formal rulemaking procedures done ``on the record
after opportunity for a hearing'' conducted pursuant to the provisions
of 5 U.S.C. 556 and 557. 21 U.S.C. 811. The permanent scheduling
process of formal rulemaking affords interested parties with an
appropriate process and the government any additional relevant
information needed to make determinations. Final decisions that
conclude the permanent scheduling process of formal rulemaking are
subject to judicial review. 21 U.S.C. 877. Temporary scheduling orders
are not subject to judicial review. 21 U.S.C. 811(h)(6).
Requirements for Handling
Upon the effective date of this temporary order, etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam will be
subject to the regulatory controls and administrative, civil, and
criminal sanctions applicable to the manufacture, distribution, reverse
distribution, importation, exportation, possession of, and engagement
in research and conduct of instructional activities or chemical
analysis with, schedule I controlled substances, including the
following:
1. Registration. Any person who handles (possesses, manufactures,
distributes, reverse distributes, imports, exports, engages in
research, or conducts instructional activities or chemical analysis
with) or desires to handle, etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam must be registered with DEA to conduct
such activities, pursuant to 21 U.S.C. 822, 823, 957, and 958, and in
accordance with 21 CFR parts 1301 and 1312, as of July 26, 2023. Any
person who currently handles etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam and is not registered with DEA must
submit an application for registration and may not continue to handle
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam as
of July 26, 2023, unless DEA has approved that application for
registration pursuant to 21 U.S.C. 822, 823, 957, and 958, and in
accordance with 21 CFR parts 1301 and 1312. Retail sales of schedule I
controlled substances to the general public are not allowed under the
CSA. Possession of any quantity of these substances in a manner not
authorized by the CSA on or after July 26, 2023 is unlawful, and those
in possession of any quantity of these substances may be subject to
prosecution pursuant to the CSA.
2. Disposal of stocks. Any person who does not desire or is unable
to obtain a schedule I registration to handle etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam must surrender all currently
held quantities of these five substances.
3. Security. Etizolam, flualprazolam, clonazolam, flubromazolam,
and diclazepam are subject to schedule I security requirements and must
be handled in accordance with 21 CFR 1301.71-1301.93, as of July 26,
2023.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of etizolam, flualprazolam,
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clonazolam, flubromazolam, and diclazepam must comply with 21 U.S.C.
825 and 958(e) and 21 CFR part 1302. Current DEA registrants will have
30 calendar days from July 26, 2023 to comply with all labeling and
packaging requirements.
5. Inventory. Every DEA registrant who possesses any quantity of
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam on
the effective date of this order must take an inventory of all stocks
of these substances on hand pursuant to 21 U.S.C. 827 and 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11. Current DEA
registrants will have 30 calendar days from the effective date of this
order to comply with all inventory requirements. After the initial
inventory, every DEA registrant must take an inventory of all
controlled substances (including etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam) on hand on a biennial basis pursuant to
21 U.S.C. 827 and 958 and in accordance with 21 CFR 1304.03, 1304.04,
and 1304.11.
6. Records. All DEA registrants must maintain records with respect
to etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
pursuant to 21 U.S.C. 827 and 958(e) and in accordance with 21 CFR
parts 1304, 1312, and 1317, and section 1307.11. Current DEA
registrants authorized to handle these five substances shall have 30
calendar days from the effective date of this order to comply with all
recordkeeping requirements.
7. Reports. All DEA registrants must submit reports with respect to
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
pursuant to 21 U.S.C. 827 and in accordance with 21 CFR parts 1304,
1312, and 1317, and sections 1301.74(c) and 1301.76(b), as of July 26,
2023. Manufacturers and distributors must also submit reports regarding
these five substances to the Automation of Reports and Consolidated
Order System pursuant to 21 U.S.C. 827 and in accordance with 21 CFR
parts 1304 and 1312.
8. Order Forms. All DEA registrants who distribute etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam must comply
with order form requirements pursuant to 21 U.S.C. 828 and in
accordance with 21 CFR part 1305 as of July 26, 2023.
9. Importation and Exportation. All importation and exportation of
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam must
be in compliance with 21 U.S.C. 952, 953, 957, and 958, and in
accordance with 21 CFR part 1312 as of July 26, 2023.
10. Quota. Only DEA-registered manufacturers may manufacture
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam in
accordance with a quota assigned pursuant to 21 U.S.C. 826 and in
accordance with 21 CFR part 1303, as of July 26, 2023.
11. Liability. Any activity involving etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam not authorized by or in
violation of the CSA, occurring as of July 26, 2023, is unlawful and
may subject the person to administrative, civil, and/or criminal
sanctions.
Regulatory Matters
The CSA provides for expedited temporary scheduling actions where
necessary to avoid imminent hazards to the public safety. Under 21
U.S.C. 811(h), the Administrator, as delegated by the Attorney General,
may, by order, temporarily schedule substances in schedule I. Such
orders may not be issued before the expiration of 30 days from: (1) The
publication of a notice in the Federal Register of the intent to issue
such order and the grounds upon which such order is to be issued, and
(2) the date that notice of the proposed temporary scheduling order is
transmitted to the Assistant Secretary for Health of HHS, as delegated
by the Secretary of HHS. 21 U.S.C. 811(h)(1).
Inasmuch as section 811(h) directs that temporary scheduling
actions be issued by order (as distinct from a rule) and sets forth the
procedures by which such orders are to be issued, including the
requirement to publish in the Federal Register a notice of intent, the
notice-and-comment requirements of section 553 of the Administrative
Procedure Act (APA), 5 U.S.C. 553, which are applicable to rulemaking,
do not apply to this temporary scheduling order. The APA expressly
differentiates between orders and rules, as it defines an ``order'' to
mean a ``final disposition, whether affirmative, negative, injunctive,
or declaratory in form, of an agency in a matter other than rule
making.'' 5 U.S.C. 551(6) (emphasis added). The specific language
chosen by Congress indicates its intent that DEA issue orders instead
of proceeding by rulemaking when temporarily scheduling substances.
Given that Congress specifically requires the Administrator (as
delegated by the Attorney General) to follow rulemaking procedures for
other kinds of scheduling actions, see 21 U.S.C. 811(a), it is
noteworthy that, in section 811(h), Congress authorized the issuance of
temporary scheduling actions by order rather than by rule.
Alternatively, even if this action was subject to section 553 of
the APA, the Administrator finds that there is good cause to forgo its
notice-and-comment requirements, as any further delays in the process
for issuing temporary scheduling orders would be impracticable and
contrary to the public interest given the manifest urgency to avoid
imminent hazards to public safety.
Although DEA believes this temporary scheduling order is not
subject to the notice-and-comment requirements of section 553 of the
APA, DEA notes that in accordance with 21 U.S.C. 811(h)(4), the
Administrator took into consideration comments submitted by the
Assistant Secretary in response to the notice that DEA transmitted to
the Assistant Secretary pursuant to such subsection.
Further, DEA believes that this temporary scheduling action is not
a ``rule'' as defined by 5 U.S.C. 601(2), and, accordingly, is not
subject to the requirements of the Regulatory Flexibility Act. The
requirements for the preparation of an initial regulatory flexibility
analysis in 5 U.S.C. 603(a) are not applicable where, as here, DEA is
not required by section 553 of the APA or any other law to publish a
general notice of proposed rulemaking.
In accordance with the principles of Executive Orders (E.O.) 12866
and 13563, this action is not a significant regulatory action. E.O.
12866 directs agencies to assess all costs and benefits of available
regulatory alternatives and, if regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, public health, and safety effects;
distributive impacts; and equity). E.O. 13563 is supplemental to and
reaffirms the principles, structures, and definitions governing
regulatory review as established in E.O. 12866. E.O. 12866 classifies a
``significant regulatory action,'' requiring review by the Office of
Management and Budget, as any regulatory action that is likely to
result in a rule that may: (1) Have an annual effect on the economy of
$100 million or more or adversely affect in a material way the economy;
a sector of the economy; productivity; competition; jobs; the
environment; public health or safety; or State, local, or tribal
governments or communities; (2) create a serious inconsistency or
otherwise interfere with an action taken or planned by another agency;
(3) materially alter the budgetary impact of entitlements, grants, user
fees, or loan
[[Page 48118]]
programs, or the rights and obligations of recipients thereof; or (4)
raise novel legal or policy issues arising out of legal mandates, the
President's priorities, or the principles set forth in the E.O. Because
this is not a rulemaking action, this is not a significant regulatory
action as defined in section 3(f) of E.O. 12866.
This action will not have substantial direct effects on the States,
on the relationship between the national government and the States, or
on the distribution of power and responsibilities among the various
levels of government. Therefore, in accordance with E.O. 13132
(Federalism), it is determined that this action does not have
sufficient federalism implications to warrant the preparation of a
Federalism Assessment.
Signing Authority
This document of the Drug Enforcement Administration was signed on
July 18, 2023, by Administrator Anne Milgram. That document with the
original signature and date is maintained by DEA. For administrative
purposes only, and in compliance with requirements of the Office of the
Federal Register, the undersigned DEA Federal Register Liaison Officer
has been authorized to sign and submit the document in electronic
format for publication, as an official document of DEA. This
administrative process in no way alters the legal effect of this
document upon publication in the Federal Register.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, DEA amends 21 CFR part 1308 as
follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for part 1308 continues to read as follows:
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. In Sec. 1308.11, add paragraphs (h)(57) through (h)(61) to read as
follows:
Sec. 1308.11 Schedule I.
* * * * *
(h) * * *
(57) 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-
f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and salts
of isomers (Other name: etizolam) 2780
(58) 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name: flualprazolam) 2785
(59) 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name: clonazolam) 2786
(60) 8-bromo-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name: flubromazolam) 2788
(61) 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-
benzo[e][1,4]diazepin-2-one, its salts, isomers, and salts of isomers
(Other name: diclazepam) 2789
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2023-15748 Filed 7-25-23; 8:45 am]
BILLING CODE 4410-09-P