International Drug Scheduling: Single Convention on Narcotic Drugs, Convention on Psychotropic Substances; Clobromazolam (phenazolam), Cychlorphine (N-propionitrile[...]

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

DATES:

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

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov 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 https://www.regulations.gov.

• 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:

• 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.

• 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 https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• 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 https://www.regulations.gov. 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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov 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.

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 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 ( https://ecddrepository.org/en ).

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 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 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).