Notice2021-15685
International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; 4F-MDMB-BICA (4F-MDMB-BUTICA); Brorphine; Metonitazene; Eutylone (bk-EBDB); BMDP (3,4-Methylenedioxy-N-benzylcathinone); Kratom (mitragynine, 7-hydroxymitragynine); Phenibut; Request for Comments
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Published
July 23, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is inviting interested persons to submit comments concerning abuse potential, actual abuse, medical usefulness, trafficking, and impact of scheduling changes on availability for medical use of seven drug substances. These comments will be considered in preparing a response from the United States to the World Health Organization (WHO) regarding the abuse liability and diversion of these drugs. WHO 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 86 Issue 139 (Friday, July 23, 2021)</title>
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[Federal Register Volume 86, Number 139 (Friday, July 23, 2021)]
[Notices]
[Pages 39038-39040]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-15685]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2021-N-0739]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; 4F-MDMB-BICA (4F-MDMB-
BUTICA); Brorphine; Metonitazene; Eutylone (bk-EBDB); BMDP (3,4-
Methylenedioxy-N-benzylcathinone); Kratom (mitragynine, 7-
hydroxymitragynine); Phenibut; 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 inviting
interested persons to submit comments concerning abuse potential,
actual abuse, medical usefulness, trafficking, and impact of scheduling
changes on availability for medical use of seven drug substances. These
comments will be considered in preparing a response from the United
States to the World Health Organization (WHO) regarding the abuse
liability and diversion of these drugs. WHO 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: Submit either electronic or written comments by August 9, 2021.
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 August 9, 2021. 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 August 9, 2021. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are postmarked or the delivery service
acceptance receipt is 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-2021-N-0739 for ``International Drug Scheduling; Convention on
Psychotropic Substances; Single Convention on Narcotic Drugs; 4F-MDMB-
BICA (4F-MDMB-BUTICA); Brorphine; Metonitazene; Eutylone (bk-EBDB);
BMDP (3,4-Methylenedioxy-N-benzylcathinone); Kratom (mitragynine, 7-
hydroxymitragynine); Phenibut; 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: James R. Hunter, Center for Drug
Evaluation and Research, Controlled Substance Staff, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5150, Silver
Spring, MD 20993-0002, 301-796-3156, <a href="/cdn-cgi/l/email-protection#254f444840560b4d504b514057654341440b4d4d560b424a53"><span class="__cf_email__" data-cfemail="771d161a1204591f021903120537111316591f1f0459101801">[email 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 or WHO has
information about a substance, which in its opinion
[[Page 39039]]
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) (Title II of the
Comprehensive Drug Abuse Prevention and Control Act of 1970) provides
that when WHO notifies the United States under Article 2 of the
Psychotropic Convention that it has 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. WHO Notification
The Secretary of HHS received the following notice from WHO
(nonrelevant text removed):
Ref.: C.L.20.2021
The World Health Organization (WHO) presents its compliments to
Member States and Associate Members and has the pleasure of
announcing that the 44th Expert Committee on Drug Dependence (ECDD)
will meet from 11 to 15 October 2021, coordinated from Geneva,
Switzerland. Given that WHO Expert Committee meetings are of a
closed nature, this letter serves to notify Member States of the
substances under review at the 44th ECDD, which are in the Annex I,
attached for reference.
WHO is mandated by the 1961 and 1971 International Drug Control
Conventions to make recommendations 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 the appropriate control of a
psychoactive substance, the ECDD convenes annually to review the
potential of this substance to cause dependence, abuse and harm to
health, as well as any therapeutic applications. In order to perform
this review and make scientific and 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 are
invited to contribute to the ECDD review process by joining the 44th
ECDD Open Session on 11 October 2021. The Open Session will allow
interested parties to learn about present and future activities of
the ECDD Secretariat, and to present information concerning
substances under review to the Expert Committee Registration
information will be made available on the ECDD website: <a href="https://www.who.int/medicines/access/controlled-substances/en/">https://www.who.int/medicines/access/controlled-substances/en/</a>.
As in the past and in line with the publication ``Guidance on
the WHO review of psychoactive substances for international
control'' (EB126/2010/REC1, Annex 6),\1\ Member States can also
contribute to the ECDD review process by providing accurate
information concerning the substances under review in advance of the
meeting. For this purpose, a questionnaire will be sent to Member
States 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.
In addition to the questionnaire, Member States are also
encouraged to provide any additional relevant information
(unpublished or published) on substances to be reviewed by the 44th
ECDD by emailing <a href="/cdn-cgi/l/email-protection#6d080e09091e080e1f08190c1f040c192d1a050243040319"><span class="__cf_email__" data-cfemail="c5a0a6a1a1b6a0a6b7a0b1a4b7aca4b185b2adaaebacabb1">[email protected]</span></a> with the subject ``Ref:
C.L.20.2021''.
The World Health Organization takes this opportunity to renew to
Member States and Associate Members the assurance of its highest
consideration.
GENEVA, 10 June 2021
<SUP>1</SUP> <a href="https://apps.who.int/gb/ebwha/pdf_files/EB126-REC1/B126_REC1-en.pdf#page=58">https://apps.who.int/gb/ebwha/pdf_files/EB126-REC1/B126_REC1-en.pdf#page=58</a>.
Annex I
44th Expert Committee on Drug Dependence (ECDD) 11-15 October 2021,
Substances For Review
Critical reviews: The substances listed below have never been
formally reviewed by WHO and are not currently under international
control. Information was brought to WHO'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.
Synthetic cannabinoid receptor agonists
1. 4F-MDMB-BICA (4F-MDMB-BUTICA)
Novel synthetic opioids
2. Brorphine
3. Metonitazene
Cathinones/stimulants
4. Eutylone (bk-EBDB)
5. BMDP (3,4-Methylenedioxy-N-benzylcathinone), benzylone
Pre-reviews: The substances listed below have been proposed for
a pre-review. The purpose of a pre-review is to determine whether
current information justifies an Expert Committee critical review. A
pre-review is a preliminary analysis and findings at this stage
should not determine whether the control status of a substance
should be changed.
Herbal drugs
6. Kratom, mitragynine, 7-hydroxymitragynine
Medicines
7. Phenibut
FDA has verified the website addresses contained in the WHO notice,
as of the date this document publishes in the Federal Register, but
websites are subject to change over time. Access to view the WHO
questionnaire can be found at <a href="https://www.who.int/groups/who-expert-committee-on-drug-dependence/forty-fourth-ecdd-documents">https://www.who.int/groups/who-expert-committee-on-drug-dependence/forty-fourth-ecdd-documents</a>.
III. Substances Under WHO Review
4F-MDMB-BICA (4F-MDMB-BUTICA) is a synthetic cannabinoid that has
been sold online and used to mimic the biological effects of
tetrahydrocannabinol, the main psychoactive constituent in marijuana.
Research and clinical reports have demonstrated that synthetic
cannabinoids are applied onto plant material so that the material may
be smoked as users attempt to obtain a euphoric and psychoactive
``high.'' Synthetic cannabinoids have been marketed under the guise of
``herbal incense,'' and promoted by drug traffickers as legal
alternatives to marijuana. According to the National Forensic
Laboratory Information System database, 4F-MDMB-BICA emerged in the
United States in May 2020 through identification in drug seizures. Per
NPS Discovery,\1\ 4F-MDMB-BICA has been identified in at least 26
toxicology cases associated with postmortem and driving under the
influence of drugs investigations in the United States. There are no
commercial or approved medical uses for 4F-MDMB-BICA, and it is not a
controlled substance under the CSA but may be considered an analogue of
other Schedule I substances.
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\1\ <a href="https://www.npsdiscovery.org/positivity-of-new-synthetic-cannabinoid-4f-mdmb-bica-increasing-in-u-s-as-prevalence-of-5f-mdmb-pica-wanes/">https://www.npsdiscovery.org/positivity-of-new-synthetic-cannabinoid-4f-mdmb-bica-increasing-in-u-s-as-prevalence-of-5f-mdmb-pica-wanes/</a>.
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Brorphine (chemical name: 1-(1-(1-(4-bromophenyl)ethyl)piperidin-4-
yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one) is a potent synthetic opioid
encountered as both a single substance of abuse and in combination with
other opioid substances, such as heroin and fentanyl. The appearance of
brorphine on the illicit drug market is similar to other designer drugs
trafficked for their psychoactive effects. Beginning in June 2019,
brorphine emerged in the United States illicit, synthetic drug market
as evidenced by its identification in drug seizures. The use of
brorphine has been associated with at least seven fatalities between
June and July 2020 in the United States. Brorphine is not approved for
medical use in the United States. On March 1, 2021, the U.S. Drug
Enforcement Administration issued a
[[Page 39040]]
temporary order to control brorphine as a Schedule I substance under
the CSA.
Eutylone (bk-EBDB) (chemical name: 1-(1,3-benzodioxol-5-yl)-2-
(ethylamino)butan-1-one) is a designer drug of the phenethylamine
class. Eutylone is a synthetic cathinone with chemical structural and
pharmacological similarities to Schedule I and II amphetamines and
cathinones, such as to 3,4-Methylenedioxymethamphetamine, methylone,
and pentylone. Eutylone emerged in the United States illicit, synthetic
drug market in 2014 as evidenced by its identification in drug
seizures. Other evidence indicates that eutylone, like other Schedule I
synthetic cathinones, is abused for its psychoactive effects. Adverse
effects associated with synthetic cathinones abuse include agitation,
hypertension, tachycardia, and death. Eutylone is not approved for
medical use in the United States. As a positional isomer of pentylone,
eutylone is controlled in Schedule I of the CSA.
BMDP (chemical name: 3,4-Methylenedioxy-N-benzylcathinone) is a
designer drug of the phenethylamine class. BMDP is a synthetic
cathinone with chemical structural and pharmacological similarities to
Schedule I and II amphetamines (e.g., methamphetamine and 3,4-
methylenedioxymethamphetamine) and cathinones (e.g., methylone). Law
enforcement has seen an increase in the encounters of BMDP in 2019 in
the United States illicit, synthetic drug market as evidenced by its
identification in drug seizures. BMDP has no commercial or approved
medical uses, and it is not controlled under the CSA. However, if BMDP
is found to meet the criteria outlined in Title 21 of the United States
Code, section 802(32) (21 U.S.C. 802(32)), and it is intended for human
consumption, it may be treated as a Schedule I controlled substance
analogue for the purpose of Federal law pursuant to 21 U.S.C. 813.
Mitragynine and 7-hydroxymitragynine are the main active
constituents of the plant Mitragyna speciosa, commonly known as kratom,
an indigenous plant of Southeast Asia. Kratom is abused for its ability
to produce opioid-like effects. Kratom is available in several
different forms to include dried/crushed leaves, powder, capsules,
tablets, liquids, and gum/resin. Kratom is an increasingly popular drug
of abuse and readily available on the recreational drug market in the
United States. Evidence suggests that kratom is abused individually and
with other psychoactive substances. Kratom does not have an approved
medical use in the United States and has not been studied as a
treatment agent in the United States. Kratom has a history of being
used as an opium substitute in Southeast Asia. In the United States,
kratom is misused to self-treat chronic pain and opioid withdrawal
symptoms. Consumption of kratom can lead to a number of health impacts,
including, among others, respiratory depression, vomiting, nervousness,
weight loss, and constipation. Kratom has been reported to have both
narcotic and stimulant-like effects, and withdrawal symptoms may
include hostility, aggression, excessive tearing, aching of muscles and
bones, and jerky limb movements. Kratom is not a controlled substance
under the CSA.
Phenibut (chemical name: Beta-phenyl-gamma-aminobutyric acid HCl)
is a neuropsychotropic drug that is used in Russia to treat alcohol
withdrawal, anxiety, insomnia, and vestibular disorders. It has
anxiolytic and nootropic (cognition enhancing) effects. Phenibut acts
as a gamma-aminobutyric acid (GABA)-mimetic, primarily at GABA(B) and,
to some extent, at GABA(A) receptors. Phenibut is sold online as a
supplement to improve cognitive function, memory, creativity in healthy
persons, and used to self-medicate anxiety, insomnia, and alcohol
cravings. There are reports of people taking phenibut arriving to
emergency departments with agitation, intoxication, altered mental
status, and withdrawal, and also reports of phenibut in toxicology
urinalysis reports from a prison facility, where inmates were abusing
multiple drugs, including phenibut. There is no approved medical use
for phenibut in the United States, and phenibut is not a controlled
substance under the CSA.
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 11
drug substances. Any comments received will be considered by HHS when
it prepares a scientific and medical evaluation for drug substances
that is responsive to the WHO Questionnaire for these drug substances.
HHS will forward such evaluation of these drug substances to WHO, for
WHO's 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 to WHO regarding whether any of these drugs should be
subjected to international controls. Instead, HHS will defer such
consideration until WHO has made official recommendations to the
Commission on Narcotic Drugs, which are expected to be made in late
2021. 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.
Dated: July 19, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-15685 Filed 7-22-21; 8:45 am]
BILLING CODE 4164-01-P
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This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.