International Drug Scheduling; Single Convention on Narcotic Drugs; Convention on Psychotropic Substances; Clobromazolam (Phenazolam); Cychlorphine (N-Propionitrile Chlorphine); Desalkylgidazepam (Bromonordiazepam); Ethylbromazolam; Etomethazene (5-Methyl Etodesnitazene); Spirochlorphine (R6980); Etomidate; Medetomidine; Request for Comments

Issuing agencies

Abstract

The Food and Drug Administration (FDA or Agency) is providing interested persons with the opportunity to submit comments concerning abuse potential, actual abuse, medical usefulness, trafficking, and impact of scheduling changes on availability for medical use of eight drug substances. These comments will be considered in preparing a response from the United States to the Expert Committee on Drug Dependence (ECDD) regarding the abuse liability and diversion of these drugs. The ECDD will use this information to consider whether to recommend that certain international restrictions be placed on these drug substances. This notice requesting comments is required by the Controlled Substances Act (CSA).

Full Text

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<title>Federal Register, Volume 91 Issue 164 (Wednesday, August 26, 2026)</title>
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[Federal Register Volume 91, Number 164 (Wednesday, August 26, 2026)]
[Notices]
[Pages 55098-55101]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-17380]



[[Page 55098]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2026-N-9208]


International Drug Scheduling; Single Convention on Narcotic 
Drugs; Convention on Psychotropic Substances; Clobromazolam 
(Phenazolam); Cychlorphine (N-Propionitrile Chlorphine); 
Desalkylgidazepam (Bromonordiazepam); Ethylbromazolam; Etomethazene (5-
Methyl Etodesnitazene); Spirochlorphine (R6980); Etomidate; 
Medetomidine; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is providing 
interested persons with the opportunity to submit comments concerning 
abuse potential, actual abuse, medical usefulness, trafficking, and 
impact of scheduling changes on availability for medical use of eight 
drug substances. These comments will be considered in preparing a 
response from the United States to the Expert Committee on Drug 
Dependence (ECDD) regarding the abuse liability and diversion of these 
drugs. The ECDD will use this information to consider whether to 
recommend that certain international restrictions be placed on these 
drug substances. This notice requesting comments is required by the 
Controlled Substances Act (CSA).

DATES: Either electronic or written comments must be submitted by 
September 3, 2026.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before September 3, 2026. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of September 3, 2026. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are received on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
    <bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
    <bullet> If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
    <bullet> Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    <bullet> For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2026-N-9208 for ``International Drug Scheduling; Single Convention 
on Narcotic Drugs; Convention on Psychotropic Substances; clobromazolam 
(phenazolam); cychlorphine (N-propionitrile chlorphine); 
desalkylgidazepam (bromonordiazepam); ethylbromazolam; etomethazene (5-
methyl etodesnitazene); spirochlorphine (R6980); etomidate; 
medetomidine; Request for Comments''. Received comments, those filed in 
a timely manner (see ADDRESSES), will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management 
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
    <bullet> Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: Edward (Greg) Hawkins, Center for Drug 
Evaluation and Research, Controlled Substance Staff, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5148, Silver 
Spring, MD 20993-0002, 301-796-0727, <a href="/cdn-cgi/l/email-protection#2b4e4f5c4a594f05434a5c404245586b4d4f4a05434358054c445d"><span class="__cf_email__" data-cfemail="d7b2b3a0b6a5b3f9bfb6a0bcbeb9a497b1b3b6f9bfbfa4f9b0b8a1">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Background

    The United States is a party to the 1971 Convention on Psychotropic 
Substances (Psychotropic Convention). Article 2 of the Psychotropic 
Convention provides that if a party to the convention has information 
about a substance, which, in its opinion, may require international 
control or change in such control, it shall so notify the Secretary-
General of the United Nations (U.N. Secretary-General) and provide the 
U.N. Secretary-General with information in support of its opinion.
    Paragraph (d)(2)(A) of the CSA (21 U.S.C. 811(d)(2)(A)) (Title II 
of the Comprehensive Drug Abuse Prevention and Control Act of 1970) 
provides that

[[Page 55099]]

when the United States is notified under Article 2 of the Psychotropic 
Convention that there is information that may justify adding a drug or 
other substances to one of the schedules of the Psychotropic 
Convention, transferring a drug or substance from one schedule to 
another, or deleting it from the schedules, the Secretary of State must 
transmit the notice to the Secretary of Health and Human Services 
(Secretary of HHS). The Secretary of HHS must then publish the notice 
in the Federal Register and provide opportunity for interested persons 
to submit comments that will be considered by HHS in its preparation of 
the scientific and medical evaluations of the drug or substance.

II. Notification to the HHS Secretary

    The Secretary of HHS received the following notification 
(nonrelevant text removed):

    [T]he 49th Expert Committee on Drug Dependence (ECDD) will meet 
from 19 to 22 October 2026 in Geneva, Switzerland. Given that . . . 
Expert Committee meetings are of a closed nature, this letter serves 
to notify Member States of the Agenda of the 49th ECDD, which is in 
the Annex I file, attached for reference.
    [T]he 1961 and 1971 International Drug Control Conventions 
[mandates recommendations be made] to the UN Secretary-General on 
the need for and level of international control of psychoactive 
substances based on the advice of its independent scientific 
advisory body, the ECDD. To assess whether or not a psychoactive 
substance should be placed under international control, the ECDD 
convenes annually to review the potential of that substance to cause 
dependence, abuse and harm to health, as well as any therapeutic 
applications. In order to perform this review and make evidence-
based decisions, the ECDD conducts medical, scientific, and public 
health evaluations of the selected psychoactive substances using the 
best available information.
    Although the meetings are of a closed nature, Member States and 
Associate Members are invited to contribute to the ECDD review 
process by joining the 49th ECDD Information Session on 19 October 
2026. The Information Session will be held virtually and allow 
interested parties to learn about present and future activities of 
the ECDD Secretariat, and to present information concerning 
substances under review to the 49th Expert Committee for 
consideration in its deliberations.
    As in the past and in line with the [Annex 6 of EB126/2010/
REC1], Member States and Associate Members can also contribute to 
the ECDD review process by providing up to date and accurate 
information concerning the substances under review in advance of the 
meeting. For this purpose, and as per previous practice, a 
questionnaire will be sent to Member States and Associate Members to 
gather country information on the legitimate use, harmful use, 
status of national control and potential impact of international 
control for each substance under evaluation.
    All recommendations made by the 48th ECDD, held in October 2025, 
were accepted by the 69th UN Commission on Narcotic Drugs and all 
technical reports and recommendations made by the ECDD will be 
available online through the recently launched ECDD Information 
Repository (<a href="https://ecddrepository.org/en">https://ecddrepository.org/en</a>).

Geneva, 9 July 2026

49th Expert Committee on Drug Dependence (ECDD) Substances for Review 
19-22 October 2026

    Critical reviews: The substances listed below have been proposed 
. . . for critical review and are not currently under international 
control. Information was brought to [ECDD's] attention that these 
substances are clandestinely manufactured, of especially serious 
risk to public health and society, and of no recognized therapeutic 
use by any Party. The Expert Committee will consider whether 
information presented during a critical review may justify the 
scheduling or a change in the scheduling of the substance in the 
1961 or 1971 Conventions.

Opioids

1. Cychlorphine (N-propionitrile chlorphine)
2. Etomethazene (5-methyl etodesnitazene)
3. Spirochlorphine

Benzodiazepines

1. Desalkylgidazepam
2. Ethylbromazolam
3. Clobromazolam (phenazolam)

    Pre-reviews: The substances listed below have been proposed . . 
. for pre-review and are not currently under international control. 
Information [has been received] that these substances are 
clandestinely manufactured, of especially serious risk to public 
health and society, and of no recognized therapeutic use by any 
Party. The Expert Committee will consider whether information 
presented during a pre-review may justify further action on these 
substances.

1. Etomidate (anesthetic)
2. Medetomidine (anesthetic)

III. Substances Under Review

A. Critical Reviews

    Clobromazolam (phenazolam) is a synthetic triazolobenzodiazepine 
first synthesized in the 1980s and emerged as a novel psychoactive 
substance (NPS), distributed through online markets and detected in 
forensic casework. It is commonly encountered in powders, capsules, and 
counterfeit pressed tablets and misrepresented as alprazolam or other 
licit benzodiazepines. Clobromazolam functions as a positive allosteric 
modulator of the gamma-aminobutyric acid type A (GABA-A) receptor 
producing sedative, anxiolytic, muscle-relaxant, and hypnotic effects. 
Available evidence suggests clobromazolam may possess a higher binding 
affinity at the GABA-A receptor relative to other designer 
benzodiazepines, potentially indicating greater potency; however, 
controlled human pharmacokinetic and pharmacodynamic data remain 
limited. The substance carries potential for abuse, physical 
dependence, and addiction consistent with the benzodiazepine class, and 
abrupt discontinuation following regular use may precipitate life-
threatening withdrawal, including seizures and delirium. Overdose risk 
is substantially elevated when clobromazolam is combined with other 
central nervous system (CNS) depressants, including opioids, alcohol, 
xylazine, or nitazenes, with which it can synergistically amplify 
respiratory depression. The substance has been detected in complex 
illicit drug mixtures alongside fentanyl and other high-potency 
depressants, raising significant public health concerns. There are no 
approved commercial or medical uses for clobromazolam in the United 
States, and it is not currently controlled under the CSA.
    Cychlorphine (N-propionitrile chlorphine) is a novel synthetic 
opioid of the benzimidazolone (``orphine'') class, structurally related 
to brorphine and chlorphine. In vitro receptor binding and activity 
data indicate that cychlorphine is a potent mu-opioid receptor agonist, 
with laboratory studies suggesting it is approximately ten times more 
potent than fentanyl. As a result, cychlorphine is expected to produce 
adverse effects consistent with other potent opioid agonists, including 
nausea, vomiting, constipation, pruritus, dizziness, sedation, and 
respiratory depression, which can lead to death. The substance was 
first identified by the Center for Forensic Science Research and 
Education (CFSRE) in mid-2024 and has since been detected in illicit 
drug supplies across multiple U.S. states and at least ten countries 
internationally. According to available forensic data, cychlorphine has 
been confirmed in 225 law enforcement seizures across 19 domestic 
jurisdictions. As of early 2026, cychlorphine has been associated with 
at least 55 fatalities in the United States, with the substance 
identified as the sole opioid in a number of those cases. There are no 
approved commercial or medical uses for cychlorphine in the United 
States. On July 1, 2026, the Drug Enforcement Administration (DEA) 
published a notice of intent to temporarily control cychlorphine (N-
propionitrile chlorphine) in Schedule I under the CSA.
    Desalkylgidazepam is a designer benzodiazepine and the primary 
active

[[Page 55100]]

metabolite of gidazepam, a benzodiazepine with limited historical 
clinical use in Russia and Ukraine. Desalkylgidazepam functions as a 
positive allosteric modulator of the gamma-aminobutyric acid type A 
(GABA-A) receptor, producing sedative, anxiolytic, muscle-relaxant, and 
hypnotic effects. A notable pharmacokinetic feature is its long 
elimination half-life, averaging approximately 86 hours, which prolongs 
its central nervous system depressant effects and increases the risk of 
protracted withdrawal, including seizures upon abrupt discontinuation. 
Desalkylgidazepam first appeared on illicit drug markets in 2022 and 
had become the second most prevalent designer benzodiazepine detected 
in the United States by 2024. It has been detected in 227 polydrug 
intoxication and fatality cases, frequently alongside opioids and other 
central nervous system depressants. Like other benzodiazepines, 
desalkylgidazepam can synergistically amplify respiratory depression 
when combined with opioids or alcohol. There are no approved commercial 
or medical uses for desalkylgidazepam in the United States, and it is 
not currently controlled under the CSA.
    Ethylbromazolam is a designer benzodiazepine that is structurally 
related to bromazolam. It acts as a positive allosteric modulator at 
the GABA-A receptor, producing sedative, anxiolytic, and muscle-
relaxant effects. The CFSRE first identified ethylbromazolam in the 
United States in July 2025; by October 2025, the compound had been 
detected in 13 toxicology cases and 93 drug material cases originating 
from multiple U.S. states. The substance has frequently been found in 
counterfeit pharmaceutical tablets misrepresented as diazepam, 
alprazolam, or clonazepam. Bromazolam-like effects have been described 
anecdotally by users as producing euphoria, increased confidence, 
empathy, hypnosis, sedation, muscle relaxation and amnesia consistent 
with the effects of other benzodiazepine-related compounds. There are 
no approved commercial or medical uses for ethylbromazolam in the 
United States, and it is not currently controlled under the CSA.
    Etomethazene (5-Methyl etodesnitazene) is a synthetic opioid of the 
benzimidazole class and is structurally related to etonitazene, with a 
methyl group in place of the nitro substituent. In vitro binding and 
activity data indicate that etomethazene is a mu-opioid receptor 
agonist with a potency twice that of fentanyl. It produces subjective 
effects in animal behavior studies consistent with other opioid 
agonists, including morphine. As a result, etomethazene is expected to 
have an abuse potential similar to other potent opioid agonists and to 
produce adverse events including nausea, vomiting, constipation, 
pruritus, dizziness, sedation, and respiratory depression which can 
lead to death. Etomethazene was first identified in Sweden in January 
2023 and has since been sold as a designer drug via online markets. The 
CFSRE first detected etomethazene in the United States in January 2024. 
Since 2023, the National Forensic Laboratory Information System (NFLIS) 
has reported 184 instances related to its trafficking, distribution, 
and use. As of 2024, it has been identified in at least six forensic 
toxicology cases. It is frequently detected alongside fentanyl, 
designer benzodiazepines such as bromazolam, and other nitazene and 
benzimidazole analogues. As of October 15, 2025, etomethazene is 
temporarily controlled in Schedule I under the CSA.
    Spirochlorphine is a novel synthetic opioid of the benzimidazolone 
(``orphine'') class, also known by the research designation R-6890. It 
was first investigated in the 1970s as a narcotic analgesic and has re-
emerged in illicit drug markets across North America and Europe. In 
vitro binding and activity data indicate that spirochlorphine acts as a 
potent mu-opioid receptor agonist with high binding affinity and 
analgesic potency in animal models. As a result, it is expected to have 
an abuse potential similar to that of other potent opioid agonists and 
to produce adverse events including nausea, vomiting, constipation, 
pruritus, dizziness, sedation, and respiratory depression, which can 
lead to death. The CFSRE first identified spirochlorphine in the United 
States in May 2025. As of early 2026, spirochlorphine has been detected 
in approximately 36 cases in the United States, with samples 
originating from Illinois, New England, and other regions. It has been 
detected both alone and in combination with other synthetic opioids 
such as fentanyl. The United Nations Office of Drugs and Crime (UNODC) 
Early Warning Advisory (EWA) on new psychoactive substances has 
reported spirochlorphine among orphine analogues of concern, noting its 
presence in both Europe and North America. There are no approved 
commercial or medical uses for spirochlorphine in the United States. On 
July 1, 2026, the DEA published a notice of intent to temporarily 
control spirochlorphine in Schedule I under the CSA.

B. Pre-Reviews

    Etomidate is a short-acting imidazole-based intravenous anesthetic 
agent approved in the United States for the induction of general or 
supplemental anesthesia. Etomidate has an established medical use 
profile and is used in clinical settings including emergency medicine 
and procedural sedation. Despite its recognized medical utility, 
increasing concerns have emerged regarding its non-medical use, 
particularly across East and Southeast Asia and Oceania. The UNODC 
issued an alert in March 2025 regarding the growing detection of 
etomidate and its analogues in illicit drug markets, including its 
presence in e-liquids. Several countries have adopted national control 
measures: the United Kingdom classified etomidate as a Class C drug 
under the Misuse of Drugs Act (July 2025); South Korea upgraded it to a 
narcotic drug (February 2025); Taiwan escalated its classification to a 
Category II narcotic (November 2024); and Hong Kong (China) listed 
etomidate and three analogues as dangerous drugs (February 2025). A 
pre-review will allow the ECDD to evaluate whether available evidence 
is sufficient to justify a full critical review. Etomidate is currently 
approved for marketing in the United States and is not controlled under 
the CSA.
    Medetomidine is a potent alpha-2 adrenergic agonist approved for 
veterinary use as a sedative and analgesic, primarily in companion 
animals. It has no approved human medical use in the United States. 
Medetomidine has increasingly been detected as an adulterant in illicit 
drug supplies, particularly in conjunction with fentanyl and xylazine, 
across multiple U.S. states since 2022. Its potency is estimated to be 
100 to 200 times greater than that of xylazine, another veterinary 
tranquilizer of emerging public health concern. When administered to 
humans, medetomidine produces sedation, bradycardia, hypotension, and 
respiratory depression, especially when combined with other central 
nervous system depressants such as opioids, complicating overdose 
management and increasing the risk of fatality. Withdrawal from 
medetomidine after chronic or high-dose exposure may be severe, often 
requiring intensive care. Medetomidine has been detected in illicit 
drug samples and associated with overdose events and hospitalizations 
across multiple jurisdictions. In response to these public health

[[Page 55101]]

concerns, Pennsylvania classified medetomidine as a Schedule III 
controlled substance in 2026. Medetomidine is not currently controlled 
under the CSA at the federal level. A pre-review would allow the ECDD 
to assess whether the pattern of non-medical use and associated harms 
justifies formal international review.

IV. Opportunity To Submit Domestic Information

    As required by paragraph (d)(2)(A) of the CSA, FDA, on behalf of 
HHS, invites interested persons to submit comments regarding the eight 
drug substances identified in this document. Any comments received by 
the deadline will be considered by HHS when it prepares a scientific 
and medical evaluation for drug substances in response to the 
scientific questionnaire for these drug substances. HHS will forward 
such evaluation of these drug substances to the ECDD, for their 
consideration in deciding whether to recommend international control/
decontrol of any of these drug substances. Such control could limit, 
among other things, the manufacture and distribution (import/export) of 
these drug substances and could impose certain recordkeeping 
requirements on them.
    Although FDA is, through this notice, requesting comments from 
interested persons, which will be considered by HHS when it prepares an 
evaluation of these drug substances, HHS will not now make any 
recommendations regarding whether any of these drugs should be 
subjected to international controls. Instead, HHS will defer such 
consideration until official recommendations have been sent to the 
Commission on Narcotic Drugs, which are expected to be made in late 
2026. Any HHS position regarding international control of these drug 
substances will be preceded by another Federal Register notice 
soliciting public comments, as required by paragraph (d)(2)(B) of the 
CSA (21 U.S.C. 811).

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-17380 Filed 8-25-26; 8:45 am]
BILLING CODE 4164-01-P


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