International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization; Scheduling Recommendations; 4-Methylethcathinone and Nine Other Substances; Request for Comments, 3326-3332 [2017-00373]
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Federal Register / Vol. 82, No. 7 / Wednesday, January 11, 2017 / Notices
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Dated: January 5, 2017.
William N. Parham, III,
Director, Paperwork Reduction Staff, Office
of Strategic Operations and Regulatory
Affairs.
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third party may not wish to be posted,
[FR Doc. 2017–00298 Filed 1–10–17; 8:45 am]
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Food and Drug Administration
[Docket No. FDA–2016–N–4619]
International Drug Scheduling;
Convention on Psychotropic
Substances; Single Convention on
Narcotic Drugs; World Health
Organization; Scheduling
Recommendations; 4Methylethcathinone and Nine Other
Substances; Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is providing
interested persons with the opportunity
to submit written comments, and to
request an informal public meeting
concerning recommendations by the
World Health Organization (WHO) to
impose international manufacturing and
distributing restrictions, under
international treaties, on certain drug
substances. The comments received in
response to this notice and/or public
meeting will be considered in preparing
the United States’ position on these
proposals for a meeting of the United
Nations Commission on Narcotic Drugs
(CND) in Vienna, Austria, in March
2017. This notice is issued under the
Controlled Substances Act (CSA).
DATES: Submit either electronic or
written comments by February 10, 2017.
Submit requests for a public meeting on
or before January 23, 2017. The short
time period for the submission of
comments and requests for a public
meeting is needed to ensure that HHS
may, in a timely fashion, carry out the
required action and be responsive to the
United Nations. For additional
information, see section IV of this
document.
SUMMARY:
ADDRESSES:
You may submit comments
as follows:
Electronic Submissions
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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): Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Division of Dockets
Management, 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–
2016–N–4619 for ‘‘International Drug
Scheduling; Convention on
Psychotropic Substances; Single
Convention on Narcotic Drugs; World
Health Organization; Scheduling
Recommendations; 4Methylethcathinone and Nine Other
Substances; Request for Comments.’’
Received comments will be placed in
the docket and, except for those
submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday.
• 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
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Federal Register / Vol. 82, No. 7 / Wednesday, January 11, 2017 / Notices
https://www.regulations.gov. Submit
both copies to the Division of Dockets
Management. 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.fda.gov/
regulatoryinformation/dockets/
default.htm.
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 Division of Dockets
Management, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
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,
james.hunter@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
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I. Background
The United States is a party to the
1971 Convention on Psychotropic
Substances (Psychotropic Convention).
Section 201(d)(2)(B) of the CSA (21
U.S.C. 811(d)(2)(B)) provides that when
the United States is notified under
Article 2 of the Psychotropic
Convention that the CND proposes to
decide whether to add a drug or other
substance to one of the schedules of the
Psychotropic Convention, transfer a
drug or substance from one schedule to
another, or delete it from the schedules,
the Secretary of State must transmit
notice of such information to the
Secretary of Health and Human Services
(Secretary of HHS). The Secretary of
HHS must then publish a summary of
such information in the Federal
Register and provide opportunity for
interested persons to submit comments.
The Secretary of HHS must then
evaluate the proposal and furnish a
recommendation to the Secretary of
State that shall be binding on the
representative of the United States in
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discussions and negotiations relating to
the proposal.
As detailed in the following
paragraphs, the Secretary of State has
received notification from the SecretaryGeneral of the United Nations (the
Secretary-General) regarding eight
substances to be considered for control
under the Psychotropic Convention.
This notification reflects the
recommendation from the 38th WHO
Expert Committee for Drug Dependence
(ECDD), which met in November 2016.
In the Federal Register of September 19,
2016 (81 FR 64162), FDA announced the
WHO ECDD review and invited
interested persons to submit
information for WHO’s consideration.
The full text of the notification from
the Secretary-General is provided in
section II of this document. Section
201(d)(2)(B) of the CSA requires the
Secretary of HHS, after receiving a
notification proposing scheduling, to
publish a notice in the Federal Register
to provide the opportunity for interested
persons to submit information and
comments on the proposed scheduling
action.
The United States is also a party to
the 1961 Single Convention on Narcotic
Drugs (1961 Single Convention). The
Secretary of State has received a
notification from the Secretary-General
regarding two substances to be
considered for control under this
convention. The CSA does not require
HHS to publish a summary of such
information in the Federal Register.
Nevertheless, in an effort to provide
interested and affected persons an
opportunity to submit comments
regarding the WHO recommendations
for narcotic drugs, the notification
regarding these substances is also
included in this Federal Register notice.
The comments will be shared with other
relevant Agencies to assist the Secretary
of State in formulating the position of
the United States on the control of these
substances. The HHS recommendations
are not binding on the representative of
the United States in discussions and
negotiations relating to the proposal
regarding control of substances under
the 1961 Single Convention.
II. United Nations Notification
The formal notification from the
United Nations that identifies the drug
substances and explains the basis for the
recommendations is reproduced as
follows (non-relevant text removed):
Reference:
NAR/CL.8/2016
WHO/ECDD38; 1961C–Art.3; 1971C–Art.2
CU 2016/495/DTA/SGB
The Secretary-General of the United
Nations presents his compliments to the
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Secretary of State of the United States of
America and has the honour to inform the
Government that the Director-General of the
World Health Organization (WHO), pursuant
to article 3, paragraphs 1 and 3 of the Single
Convention on Narcotic Drugs of 1961 as
amended by the 1972 Protocol (1961
Convention) and article 2, paragraphs 1 and
4 of the Convention on Psychotropic
Substances of 1971 (1971 Convention)
notified the Secretary-General of the
following recommendations:
Substances recommended to be placed in
Schedule I of the Single Convention on
Narcotic Drugs (1961), as amended by the
1972 Protocol:
—U–4770
chemical name: 3,4-dichloro-N-(2dimethylamino-cyclohexyl)-N-methylbenzamide
—butyrfentanyl
chemical name: N-phenyl-N-[1-(2phenylethyl)-4-piperidinyl]butanamide
Substances recommended to be placed in
Schedule II of the 1971 Convention:
—4–MEC (4-methylethcathinone)
chemical name: 2-(ethylamino)-1-(4methylphenyl)propan-1-one
—ethylone
chemical name: 1-(2H–1,3-benzodioxol-5yl)-2-(ethylamino)propan-1-one
—pentedrone
chemical name: 2-(methylamino)-1phenylpentan-1-one
—ethylphenidate
chemical name: ethyl phenyl(piperidin-2yl)acetate
—MPA (methiopropamine)
chemical name: N-methyl-1-(thiophen-2yl)propan-2-amine
—MDMB–CHMICA
chemical name: methyl N-{[1(cyclohexylmethyl)-1H-indol-3yl]carbonyl}-3-methyl-L-valinate
—5F–APINACA (5F–AKB–48)
chemical name: N-(adamantan-1-yl)-1-(5fluoropentyl)-1H-indazole-3carboxamide
—XLR–11
chemical name: [1-(5-fluoropentyl)-1Hindol-3-yl](2,2,3,3tetramethylcyclopropyl)methanone
In addition, in the letter from the DirectorGeneral of the World Health Orgazniation to
the Secretary-General, reference is also made
to the recommendations by the thirty-eighth
meeting of the WHO Expert Committee on
Drug Dependence (ECDD) for carrying out a
critical review of one substance at a
subsequent Expert Committee meeting, as
well as for one substance to continue to be
kept under surveillance. Furthermore, the
letter also makes reference to the
recommendation by the Expert Committee
with regard to cannabis and its component
substances.
In accordance with the provisions of article
3, paragraph 2 of the 1961 Convention and
article 2, paragraph 2 of the 1971 Convention,
the Secretary-General hereby transmits the
notification as annex I to the present note. In
accordance with the provisions of article 3,
paragraph 2 of the 1961 Convention and
article 2, paragraph 2 of the 1971 Convention,
the notification from WHO will be brought to
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the attention of the sixtieth session of the
Commission on Narcotic Drugs (13–17 March
2017).
In connection with the notification, WHO
has also submitted the relevant extract from
the report of the thirty-eighth meeting of the
WHO Expert Committee on Drug Dependence
which is hereby transmitted as annex II.
In order to assist the Commission in
reaching a decision, it would be appreciated
if the Government could communicate any
economic, social, legal, administrative or
other factors that it considers relevant to the
possible scheduling of the afore-mentioned
substances that are recommended by WHO to
be placed under international control under
the 1961 Convention (namely: U–4770 and
butyrfentanyl) and the 1971 Convention
(namely: 4–MEC, ethylone, pentedrone,
ethylphenidate, MPA, MDMB–CHMICA, 5FAPINACA, and XLR–11).
Communications are to be sent at the latest
by 20 January 2017 to the Executive Director
of the United Nations Office on Drugs and
Crime, c/o Secretary, Commission on
Narcotic Drugs, P.O. Box 500, 1400 Vienna,
Austria, fax: +43–1–26060–5885, email: sgb@
unodc.org.
21 December 2016
His Excellency
Mr. John Kerry
Secretary of State of the United States of
America
Annex I
Letter Addressed to the Secretary-General of
the United Nations From the DirectorGeneral of the World Health Organization
‘‘The Thirty-eighth meeting of the WHO
Expert Committee on Drug Dependence
convened from 14 to 18 November 2016, at
WHO headquarters in Geneva. The objective
of this meeting was to carry out an in-depth
evaluation of psychoactive substances in
order to determine whether or not WHO
should recommend these substances to be
placed under international control.
With reference to Article 2, paragraphs 1
and 4 of the Convention on Psychotropic
Substances (1971) and Article 3, paragraphs
1 and 3 of the Single Convention on Narcotic
Drugs (1961), as amended by the 1972
Protocol, I am pleased to submit
recommendations of the World Health
Organization as follows:
to be placed in Schedule I of the Single
Convention on Narcotic Drugs (1961), as
amended by the 1972 Protocol:
—U–47700
chemical name: 3,4-dichloro-N-(2dimethylamino-cyclohexyl)-N-methylbenzamide
—butyrfentanyl
chemical name: N-phenyl-N-[1-(2phenylethyl)-4-piperidinyl]butanamide
to be placed in Schedule II of the Convention
on Psychotropic Substances (1971):
—4–MEC (4-methylethcathinone)
chemical name: 2-(ethylamino)-1-(4methylphenyl)propan-1-one
—ethylone
chemical name: 1-(2H–1,3-benzodioxol-5yl)-2-(ethylamino)propan-1-one
—pentedrone
chemical name: 2-(methylamino)-1phenylpentan-1-one
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—ethylphenidate
chemical name: ethyl phenyl(piperidin-2yl)acetate
—MPA (methiopropamine)
chemical name: N-methyl-1-(thiophen-2yl)propan-2-amine
—MDMB–CHMICA
chemical name: methyl N-{[1(cyclohexylmethyl)-1H-indol-3yl]carbonyl}-3-methyl-L-valinate
—5F–APINACA (5F–AKB–48)
chemical name: N-(adamantan-1-yl)-1-(5fluoropentyl)-1H-indazole-3carboxamide
—XLR–11
chemical name: [1-(5-fluoropentyl)-1Hindol-3-yl](2,2,3,3tetramethylcyclopropyl)methanone.
In addition, the Expert Committee
recommended to carry out a critical review
at a subsequent Expert Committee meeting
for:
—3–MMC (3-Methylmethcathinone)
chemical name: 2-(methylamino)-1-(3methylphenyl)propan-1-one
It also recommended to continue to keep
the following substance under surveillance:
—JWH–073
chemical name: (1-butyl-1H-indol-3-yl)(1naphthyl)methanone
The Committee recommended that a
specific ECDD meeting dedicated to cannabis
and its component substances should be held
within the next eighteen months from the
38th meeting, and will carry out pre-reviews
for the following substances:
—Cannabis plant and cannabis resin;
—Extracts and tinctures of cannabis;
—Delta-9-tetrahydrocannabinol (THC);
—Cannabidiol (CBD);
—Stereoisomers of THC.
The recommendations and the assessments
and findings on which they are based are set
out in detail in the Report of the 38th Expert
Committee on Drug Dependence, which is
the Committee that advises me on these
issues. An extract of the Committee’s Report
is attached in Annex 1 to this letter.
I am very pleased with the ongoing
collaboration among the United Nations
Office on Drugs and Crime (UNODC),
International Narcotics Control Board (INCB)
and WHO, in particular, how this
collaboration has supported the work of the
WHO Expert Committee on Drug
Dependence, and more generally, the
implementation of operational
recommendations from the United Nations
General Assembly Special Session (UNGASS)
2016.’’
NAR/CL.8/2016
Annex II
Extract From the Report of the 38th Expert
Committee on Drug Dependence
Substances recommended to be scheduled
in Schedule I and Schedule IV of the Single
Convention on Narcotic Drugs (1961), as
amended by the 1972 Protocol:
U–47700
Chemically, U–47700 is 3,4-dichloro-N-(2dimethylamino-cyclohexyl)-N-methylbenzamide. U47700 has two chiral centres
resulting in four isomers; cis and trans
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conformations each have two enantiomers
[cis: are (1R,2R), and (1S,2S); trans are
(1R,2S) and (1S,2R)].
U–47700 was not previously pre-reviewed
or critically reviewed by the Committee. A
direct critical review is proposed based on
information brought to the attention of the
WHO that U–47700 is clandestinely
manufactured, poses risk to public health
and society, and has no recognized
therapeutic use by any Party.
U–47700 (3,4-dichloro-N-(2dimethylamino-cyclohexyl)-N-methylbenzamide) is a compound liable to similar
abuse and with similar ill-effects to
controlled opioids such as morphine and
AH–7921 that are included in Schedule I of
the 1961 Single Convention on Narcotic
Drugs. It has no recorded therapeutic use,
and its use has resulted in fatalities. There is
sufficient evidence that it is being or is likely
to be abused so as to constitute a public
health and social problem warranting the
placing of the substance under international
control. Thus, because it meets the required
condition of similarity, it is recommended
that U–47700 be placed in Schedule I of the
Single Convention on Narcotic Drugs, 1961,
as consistent with Article 3, paragraph 3 (iii)
of that Convention in that the substance is
liable to similar abuse and productive of
similar ill effects as drugs in Schedule I.
Butyrfentanyl
Chemically, butyrfentanyl is N-phenyl-N[1-(2-phenylethyl)-4-piperidinyl]butanamide.
Butyrfentanyl has not been previously prereviewed or critically reviewed by the
Committee. A direct critical review is
proposed based on information brought to
the attention of the WHO that butyrfentanyl
is clandestinely manufactured, poses risk to
public health and society, and has no
recognized therapeutic use by any Party.
Butyrfentanyl (N-phenyl-N-[1-(2phenylethyl)-4-piperidinyl]butanamide) is a
compound liable to similar abuse and with
similar ill-effects to controlled opioids such
as morphine and fentanyl that are included
in Schedule I of the 1961 Single Convention
on Narcotic Drugs. It can be converted into
fentanyl as well. It has no recorded
therapeutic use and its use has resulted in
fatalities. There is sufficient evidence that it
is being or is likely to be abused so as to
constitute a public health and social problem
warranting the placing of the substance
under international control. Thus, because it
meets either of the required conditions of
similarity or convertibility, it is
recommended that butyrfentanyl be placed in
Schedule I of the Single Convention on
Narcotic Drugs, 1961, as consistent with
Article 3, paragraph 3 (iii) of that Convention
in that the substance is liable to similar abuse
and productive of similar ill effects as drugs
in Schedule I.
Substances recommended to be scheduled
in Schedule II of the Convention on
Psychotropic Substances (1971):
4–MEC (4-Methylethcathinone)
Chemically, 4-methylethcathinone (4–
MEC) is 2-(ethylamino)-1-(4methylphenyl)propan-1-one. 4–MEC has a
chiral centre giving rise to an enantiomeric
pair of (S)-4–MEC and (R)-4–MEC isomers.
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A critical review report on 4–MEC was
discussed in June 2014 at the 36th meeting
of the WHO Expert Committee on Drug
Dependence. The Committee recommended
that 4–MEC not be placed under
international control at that time due to
insufficiency of data regarding dependence,
abuse and risks to public health, but be kept
under surveillance. 4–MEC continues to
appear as a psychostimulant with
monoamine transporter activity with
indications of abuse liability. New data have
emerged from in vitro and in vivo studies
since the 36th ECCD meeting that has
prompted the current critical review.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of 4–MEC (2-(ethylamino)-1(4-methylphenyl)propan-1-one) is
substantial. Therapeutic usefulness has not
been recorded. It recognized that it has
similar abuse and similar ill-effects as
substances in Schedule II of the UN 1971
Convention on Psychotropic Substances. The
Committee considered that there is sufficient
evidence that 4–MEC is being or is likely to
be abused so as to constitute a public health
and social problem warranting the placing of
the substance under international control. As
per the Guidance on the WHO review of
psychoactive substances for international
control, higher regard was accorded to the
substantial public health risk than to the lack
of therapeutic usefulness. The Committee
recommended that 4–MEC be placed in
Schedule II under the UN 1971 Convention
on Psychotropic Substances.
Ethylone
Chemically, ethylone is 1-(2H-1,3benzodioxol-5-yl)-2-(ethylamino)propan-1one. It is a chiral compound with isomers,
and its hydrochloride salt can exist in two
conformations (polymorphs) at the C–C bond
linking the side chain to the aromatic ring.
Ethylone was not previously pre-reviewed
or critically reviewed. A direct critical review
is proposed based on information brought to
the attention of the WHO that ethylone is
clandestinely manufactured, poses serious
risk to public health and society, and has no
recognized therapeutic use by any Party.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of ethylone (1-(2H-1,3benzodioxol-5-yl)-2-(ethylamino)propan-1one) is substantial. Therapeutic usefulness
has not been recorded. It recognized that it
has similar abuse and similar ill-effects as
substances in Schedule II of the UN 1971
Convention on Psychotropic Substances. The
Committee considered that there is sufficient
evidence that ethylone is being or is likely to
be abused so as to constitute a public health
and social problem warranting the placing of
the substance under international control. As
per the Guidance on the WHO review of
psychoactive substances for international
control, higher regard was accorded to the
substantial public health risk than to the lack
of therapeutic usefulness. The Committee
recommended that ethylone be placed in
Schedule II under the UN 1971 Convention
on Psychotropic Substances.
Pentedrone (a-Methylaminovalerophenone)
Chemically, pentedrone is 2(methylamino)-1-phenylpentan-1-one. It has
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a chiral centre giving rise to two
stereoisomers, (S)- and (R)- pentedrone.
Pentedrone has not been previously
reviewed or critically reviewed by the Expert
Committee on Drug Dependence of the WHO.
A direct critical review is proposed based on
information brought to WHO’s attention that
pentedrone is clandestinely manufactured,
poses serious risk to public health and
society, and has no recognized therapeutic
use by any Party.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of pentedrone (2(methylamino)-1-phenylpentan-1-one) is
substantial. Therapeutic usefulness has not
been recorded. It recognized that it has
similar abuse and similar ill-effects as
substances in Schedule II of the UN 1971
Convention on Psychotropic Substances. The
Committee considered that there is sufficient
evidence that pentedrone is being or is likely
to be abused so as to constitute a public
health and social problem warranting the
placing of the substance under international
control. As per the Guidance on the WHO
review of psychoactive substances for
international control, higher regard was
accorded to the substantial public health risk
than to the lack of therapeutic usefulness.
The Committee recommended that
pentedrone be placed in Schedule II under
the UN 1971 Convention on Psychotropic
Substances.
Ethylphenidate (EPH)
Chemically, ethylphenidate is ethyl
phenyl(piperidin-2-yl)acetate.
Ethylphenidate was not previously prereviewed or critically reviewed. A direct
critical review is proposed based on
information brought to the attention of the
WHO that ethylphenidate is clandestinely
manufactured, poses serious risk to public
health and society, and has no recognized
therapeutic use by any Party.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of ethylphenidate (ethyl
phenyl(piperidin-2-yl)acetate) is substantial.
Therapeutic usefulness has not been
recorded. It recognized that it has similar
abuse and similar ill-effects as substances in
Schedule II of the UN 1971 Convention on
Psychotropic Substances. The Committee
considered that there is sufficient evidence
that ethylphenidate is being or is likely to be
abused so as to constitute a public health and
social problem warranting the placing of the
substance under international control. As per
the Guidance on the WHO review of
psychoactive substances for international
control, higher regard was accorded to the
substantial public health risk than to the lack
of therapeutic usefulness. The Committee
recommended that ethylphenidate be placed
in Schedule II under the UN 1971
Convention on Psychotropic Substances.
MPA (Methiopropamine)
Chemically, methiopropamine is N-methyl1-(thiophen-2-yl)propan-2-amine. It has a
chiral centre with two enantiomers.
Methiopropamine was previously critically
reviewed by the Committee at its 36th
meeting. Owing to the insufficiency of data
regarding dependence, abuse and risks to
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public health, the Committee recommended
that methiopropamine not be placed under
international control but be kept under
surveillance. Subsequent data collected from
the literature and from different countries
indicated that this substance may cause
substantial harm and that it has no medical
use warranting an updated critical review.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of methiopropamine (Nmethyl-1-(thiophen-2-yl)propan-2-amine) is
substantial. Therapeutic usefulness has not
been recorded. It recognized that it has
similar abuse and similar ill-effects as
substances in Schedule II of the UN 1971
Convention on Psychotropic Substances. The
Committee considered that there is sufficient
evidence that methiopropamine is being or is
likely to be abused so as to constitute a
public health and social problem warranting
the placing of the substance under
international control. As per the Guidance on
the WHO review of psychoactive substances
for international control, higher regard was
accorded to the substantial public health risk
than to the lack of therapeutic usefulness.
The Committee recommended that
methiopropamine be placed in Schedule II
under the UN 1971 Convention on
Psychotropic Substances.
MDMB–CHMICA
Chemically, MDMB–CHMICA is methyl N{[1-(cyclohexylmethyl)-1H-indol-3yl]carbonyl}-3-methyl-L-valinate. MDMB–
CHMICA has a chiral carbon in the butanoic
chain. Therefore, two stereoisomers exist: (S)MDMB–CHMICA and (R)-MDMB–CHMICA.
MDMB–CHMICA has not been previously
pre-reviewed or critically reviewed. A direct
critical review is proposed based on
information brought to the attention of the
WHO that MDMB–CHMICA is clandestinely
manufactured, poses serious risk to public
health and society, and has no recognized
therapeutic use by any Party.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of MDMB–CHMICA (methyl
N-{[1-(cyclohexylmethyl)-1H-indol-3yl]carbonyl}-3-methyl-L-valinate) is
substantial. Therapeutic usefulness has not
been recorded. It recognized that it has
similar abuse and similar ill-effects as
substances in Schedule II of the UN 1971
Convention on Psychotropic Substances. The
Committee considered that there is sufficient
evidence that MDMB–CHMICA is being or is
likely to be abused so as to constitute a
public health and social problem warranting
the placing of the substance under
international control. As per the Guidance on
the WHO review of psychoactive substances
for international control, higher regard was
accorded to the substantial public health risk
than to the lack of therapeutic usefulness.
The Committee recommended that MDMB–
CHMICA be placed in Schedule II under the
UN 1971 Convention on Psychotropic
Substances.
5F–APINACA (5F–AKB–48)
Chemically, 5F–APINACA is N(adamantan-1-yl)-1-(5-fluoropentyl)-1Hindazole-3-carboxamide.
5F–APINACA has not been previously prereviewed or critically reviewed by the Expert
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Committee on Drug Dependence of the WHO.
A direct critical review is proposed based on
information brought to the attention of the
WHO that 5F–APINACA is clandestinely
manufactured, poses serious risk to public
health and society, and has no recognized
therapeutic use by any Party.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of 5F–APINACA (N(adamantan-1-yl)-1-(5-fluoropentyl)-1Hindazole-3-carboxamide) is substantial.
Therapeutic usefulness has not been
recorded. It recognized that it has similar
abuse and similar ill-effects as substances in
Schedule II of the UN 1971 Convention on
Psychotropic Substances. The Committee
considered that there is sufficient evidence
that 5F–APINACA is being or is likely to be
abused so as to constitute a public health and
social problem warranting the placing of the
substance under international control. As per
the Guidance on the WHO review of
psychoactive substances for international
control, higher regard was accorded to the
substantial public health risk than to the lack
of therapeutic usefulness. The Committee
recommended that 5F–APINACA be placed
in Schedule II under the UN 1971
Convention on Psychotropic Substances.
XLR–11
Chemically, XLR–11 is [1-(5-fluoropentyl)1H-indol-3-yl](2,2,3,3tetramethylcyclopropyl)methanone.
XLR–11 has not been previously prereviewed or critically reviewed. A direct
critical review is proposed based on
information brought to WHO’s attention that
XLR–11 is clandestinely manufactured, poses
serious risk to public health and society, and
has no recognized therapeutic use by any
Party.
The Committee considered that the degree
of risk to public health and society associated
with the abuse of XLR–11 ([1-(5fluoropentyl)-1H-indol-3-yl](2,2,3,3tetramethylcyclopropyl)methanone) is
substantial. Therapeutic usefulness has not
been recorded. It recognized that it has
similar abuse and similar ill-effects as
substances in Schedule II of the UN 1971
Convention on Psychotropic Substances such
as JWH–018 and AM–2201. The Committee
considered that there is sufficient evidence
that XLR–11 is being or is likely to be abused
so as to constitute a public health and social
problem warranting the placing of the
substance under international control. As per
the Guidance on the WHO review of
psychoactive substances for international
control, higher regard was accorded to the
substantial public health risk than to the lack
of therapeutic usefulness. The Committee
recommended that XLR–11 be placed in
Schedule II under the UN 1971 Convention
on Psychotropic Substances.
Substance recommended for critical
review:
3-Methylmethcathinone (3-methyl-Nmethylcathinone; 3–MMC)
Chemically, 3–MMC is 2-(methylamino)-1(3-methylphenyl)propan-1-one. 3–MMC
contains a chiral centre at the C–2 carbon of
the propane sidechain, so two enantiomers
exist: (R)-3–MMC and (S)-3–MMC.
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3–MMC was not previously pre-reviewed
or critically reviewed. A direct critical review
is proposed based on information brought to
the attention of the WHO that 3–MMC is
clandestinely manufactured, poses serious
risk to public health and society, and has no
recognized therapeutic use by any Party.
The Committee deliberated at length
regarding the information available pertinent
to the degree of risk to public health and
society associated with the abuse of 3–MMC
(2-(methylamino)-1-(3-methylphenyl)propan1-one). The Committee decided that the
information as currently provided, and the
ensuing discussions that had occurred, were
inadequate to form a consensus and
confident recommendation regarding the
scheduling of 3–MMC. As per paragraph 59
of the Guidance on the WHO review of
psychoactive substances for international
control, and as supported by its procedural
reference to the Thirty-fourth report of the
WHO Expert Committee on Drug
Dependence, ‘‘. . . in cases where additional
information concerning the substance under
review is required, the Committee may
decide that it will reach a final opinion at a
subsequent meeting.’’ ‘‘. . . then it should
request another critical review in order to
refer the matter to a subsequent Expert
Committee.’’ As directed by these guidelines,
the Committee requested that the Secretariat
arrange another critical review of 3–MMC at
a subsequent Expert Committee.
Substance recommended for surveillance:
JWH–073
Chemically, JWH–073 is (1-butyl-1H-indol3-yl)(1-naphthyl)methanone.
During its 36th meeting, the WHO Expert
Committee on Drug Dependence discussed
the critical review report on JWH–073 and
concluded that owing to the current
insufficiency of data regarding dependence,
abuse and risks to public health, JWH–073
should not be placed under international
control at that time but be kept under
surveillance. New information on its
pharmacology and abuse potential warranted
an update of the critical review report for
discussion at the 38th ECDD.
The available pharmacodynamic data
related to JWH–073 (1-butyl-1H-indol-3-yl)(1naphthyl)methanone) demonstrates that this
substance has the capacity to produce some
effects similar to its homologue, JWH–018,
that is included in Schedule II of the UN
1971 Convention on Psychotropic
Substances. However, the data currently
available does not make it possible to
establish a direct link between JWH–073
abuse and appearance of public health and
social problems that would be a requirement
for placing this substance under international
control. It is therefore recommended not to
place JWH–073 under international control
but to continue to keep it under surveillance.
Update on Cannabis and Cannabis resin:
At the 37th ECDD meeting the Committee
requested that Secretariat begin collecting
data towards a pre-review of cannabis,
cannabis resin, extracts and tinctures of
cannabis at a future meeting. Consistent with
this request, two updates on the scientific
literature on cannabis were prepared and
subsequently presented to the Expert
Committee. Following its deliberations the
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Committee noted that the current Schedule I
of the 1961 Convention groups together
cannabis and cannabis resin, extracts and
tinctures of cannabis. Cannabis plant and
cannabis resin are also in Schedule IV of the
1961 Convention. The Committee further
noted that there are natural and synthetic
cannabinoids in Schedule I and Schedule II
of the 1971 Convention. The Committee
recognized:
—An increase in the use of cannabis and its
components for medical purposes;
—The emergence of new cannabis-related
pharmaceutical preparations for
therapeutic use;
—Cannabis has never been subject to a
formal pre-review or critical review by the
ECDD.
The Committee requested that the
Secretariat prepare relevant documentation
in accordance with the Guidance on the
WHO review of psychoactive substances for
international control in order to conduct prereviews for the following substances:
—Cannabis plant and cannabis resin;
—Extracts and tinctures of cannabis;
—Delta-9-tetrahydrocannabinol (THC);
—Cannabidiol (CBD);
—Stereoisomers of THC.
The Committee recommended that these
pre-reviews be evaluated at a specific ECDD
meeting dedicated to cannabis and its
component substances to be held within the
next eighteen months from the 38th meeting.
The purpose of the pre-review is to
determine whether current information
justifies an Expert Committee critical review.
The categories of information for evaluating
substances in pre-reviews are identical to
those used in critical reviews. The pre-review
is a preliminary analysis, and findings at this
stage should not determine whether the
control status of a substance should be
changed.
III. Discussion
Although WHO has made specific
scheduling recommendations for each of
the drug substances, the CND is not
obliged to follow the WHO
recommendations. Options available to
the CND for substances considered for
control under the Psychotropic
Convention include the following: (1)
Accept the WHO recommendations; (2)
accept the recommendations to control,
but control the drug substance in a
schedule other than that recommended;
or (3) reject the recommendations
entirely.
U–47700 is a synthetic opioid drug
developed in the 1970s. U–47700 is
structurally related to the opioid AH–
7921. U–47700 is selective for the mopioid receptor. U–47700 has never
been studied on humans, but would be
expected to produce effects similar to
those of other potent opioid agonists,
including strong analgesia, sedation,
euphoria, constipation, itching, and
respiratory depression which could be
harmful or fatal. Overdoses and
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overdose fatalities have been directly
attributed to U–47700 misuse. There
have been reports of U–47700 being
encountered in counterfeit pills. On
November 14, 2016, the U.S. Drug
Enforcement Administration (DEA)
temporarily scheduled U–47700 into
schedule I pursuant to the temporary
scheduling provisions of the Controlled
Substances Act. As such, additional
permanent controls will be necessary to
fulfill U.S. obligations if U–47700 is
controlled under Schedule I of the 1961
Single Convention.
Butyrfentanyl (butyrylfentanyl) is a
synthetic opioid and analog of fentanyl.
Fentanyl is controlled in Schedule II of
the CSA, and an active ingredient in
drug products approved for medical use
and marketed in the United States.
Butyrylfentanyl has a pharmacological
profile similar to that of fentanyl and
other m-opioid receptor agonists. Risks
associated with abuse of butyrylfentanyl
include development of substance use
disorder, overdose, and death similar to
that of other m-opioid agonists. The DEA
is aware of at least 40 confirmed
fatalities associated with
butyrylfentanyl. It has no approved
medical use in the United States. On
May 12, 2016, butyrylfentanyl was
temporarily placed into Schedule I of
the CSA for 2 years upon finding that
it posed an imminent hazard to the
public safety. The Attorney General,
though, may extend this temporary
scheduling for up to 1 year. As such,
additional permanent controls will be
necessary to fulfill U.S. obligations if
butyrylfentanyl is controlled under
Schedule I of the 1961 Single
Convention.
4-Methylethcathinone (4–MEC), 3Methylmethcathinone (3-methyl-Nmethylcathinone; 3–MMC): 3-methylmethcathinone (3–MMC), pentedrone,
and ethylone (3,4-methylenedioxy-Nethylcathinone; bk-MDEA; MDEC) are
synthetic cathinones that are
structurally and pharmacologically
similar to amphetamine, 3–4
methylenedioxymethamphetamine
(MDMA), cathinone, and other related
substances. These substances are central
nervous system stimulants with
psychoactive properties similar to
Schedule I and II amphetamine type
substances. Public health risks
associated with the use of synthetic
cathinones suggest that these substances
are associated with cardiac, psychiatric,
and neurological symptoms that may
lead to emergency department
admissions, violent behaviors causing
harm to self or others, or death. 4–MEC
and pentedrone have no known medical
use in the United States. On March 7,
2014, the DEA published a final order
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in the Federal Register amending 21
CFR 1308.11(h) to temporarily place 4–
MEC and pentedrone into Schedule I of
the CSA pursuant to the temporary
scheduling provisions of 21 U.S.C.
811(h). On March 4, 2016, the
temporary Schedule I status of 4–MEC
and pentedrone was extended for 1 year,
or until permanent scheduling is
completed. Permanent scheduling for 4–
MEC and pentedrone was initiated on
March 4, 2016, upon publication of the
notice of proposed rulemaking. As such,
additional permanent controls will be
necessary to fulfill U.S. obligations if 4–
MEC and pentedrone is controlled
under Schedule II of the 1971
Convention on Psychotropic
Substances.
In the United States, ethylone has
been sold as the street drug ‘‘Molly’’ and
encountered as a replacement for
methylone. Ethylone has no known
medical use in the United States. As a
positional isomer of the controlled drug
butylone, ethylone is considered a
Schedule I controlled substance under
the CSA. As such, no additional
controls will be necessary to fulfill U.S.
obligations if ethylone is controlled
under Schedule II of the 1971
Convention on Psychotropic
Substances.
Ethylphenidate is structurally related
to methylphenidate. Methylphenidate is
controlled in Schedule IV of the CSA,
and an active ingredient in drug
products approved for medical use and
marketed in the United States.
Ethylphenidate is not approved for
medical use in the United States.
Ethylphenidate is structurally related to
methylphenidate are being marketed as
novel psychoactive substances with
psychoactive effects similar to
methylphenidate, therefore posing
similar health risks to the users.
Ethylphenidate is a controlled substance
in several European countries, and is
not a controlled substance in the United
States under the CSA. As such,
additional permanent controls will be
necessary to fulfill U.S. obligations if
ethylphenidate is controlled under
Schedule II of the 1971 Convention on
Psychotropic Substances.
Methiopropamine (MPA) is a
structural analogue of the Schedule II
controlled substance methamphetamine.
Pharmacologically, it functions as a
norepinephrine-dopamine reuptake
inhibitor and, secondarily, as a
serotonin reuptake inhibitor. MPA is a
thiophene based analog of
methamphetamine. It has stimulant
properties as an inhibitor of dopamine,
norepinephrine transporters in the
central nervous system. MPA is not
approved for medical use or controlled
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3331
in the United States under the CSA. As
such, additional permanent controls
will be necessary to fulfill U.S.
obligations if MPA is controlled under
Schedule II of the 1971 Convention on
Psychotropic Substances.
MDMB–CHMICA is an indole-based
synthetic cannabinoid that is a potent
full agonist at cannabinoid type 1 (CB1)
receptors and mimics functionally
(biologically) the effects of the
structurally unrelated delta-9tetrahydrocannabinol, a Schedule I
substance, and the main active
ingredient of marijuana. Synthetic
cannabinoids are marketed under the
guise of ‘‘herbal incense,’’ and promoted
by drug traffickers as legal alternatives
to marijuana. MDMB–CHMICA use is
associated with serious adverse events
including death in several European
countries. There are no commercial or
approved medical uses for MDMB–
CHMICA. MDMB–CHMICA is not
controlled under the CSA, but may be
treated as a ‘‘controlled substance
analogue’’ under the CSA pursuant to 21
U.S.C. 802(32)(A) and 813, and is a
controlled substance in the State of
Louisiana. As such, additional
permanent controls will be necessary to
fulfill U.S. obligations if MDMB–
CHMICA is controlled under Schedule
II of the 1971 Convention on
Psychotropic Substances.
5F–APINACA (5F–AKB48) is a
synthetic cannabinoid belonging to a
chemical structural class with an
indazole core. In vitro studies show that
it binds to the CB1 receptors and
displays agonist properties in functional
assays, suggesting that it would share in
vivo effects with delta-9–THC and
various synthetic cannabinoids. There
are no commercial or medical uses for
5F–APINACA. Synthetic cannabinoids
are marketed under the guise of ‘‘herbal
incense,’’ and promoted by drug
traffickers as legal alternatives to
marijuana. SF–APINACA is not a
controlled substance under the CSA, but
may be treated as a ‘‘controlled
substance analogue’’ under the CSA
pursuant to 21 U.S.C. 802(32)(A) and
813. As such, additional permanent
controls will be necessary to fulfill U.S.
obligations if SF–APINACA is
controlled under Schedule II of the 1971
Convention on Psychotropic
Substances.
XLR–11 (5-Fluoro-UR–144, 5F–UR–
144) is an indole-based synthetic
cannabinoid and acts as an agonist at
CB1 receptors. Animal studies indicate
that it mimics functionally (biologically)
the effects of the structurally unrelated
delta-9–THC, a Schedule I substance,
and the main active ingredient of
marijuana and numerous other
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Schedule I synthetic cannabinoids.
Synthetic cannabinoids are marketed
under the guise of ‘‘herbal incense,’’ and
promoted by drug traffickers as legal
alternatives to marijuana. On May 11,
2016, XLR11 was permanently
controlled as a Schedule I substance
under the CSA. As such, additional
permanent controls will not be
necessary to fulfill U.S. obligations if
XLR–11 is controlled under Schedule II
of the 1971 Convention on Psychotropic
Substances.
FDA, on behalf of the Secretary of
HHS, invites interested persons to
submit comments on the notifications
from the United Nations concerning
these drug substances. FDA, in
cooperation with the National Institute
on Drug Abuse, will consider the
comments on behalf of HHS in
evaluating the WHO scheduling
recommendations. Then, under section
201(d)(2)(B) of the CSA, HHS will
recommend to the Secretary of State
what position the United States should
take when voting on the
recommendations for control of
substances under the Psychotropic
Convention at the CND meeting in
March 2017.
Comments regarding the WHO
recommendations for control of U–
47700 and Butyrylfentanyl under the
1961 Single Convention will also be
forwarded to the relevant Agencies for
consideration in developing the U.S.
position regarding narcotic substances
at the CND meeting.
IV. Opportunity for Public Meeting
FDA does not presently plan to hold
a public meeting. If any person believes
that, in addition to written comments, a
public meeting would contribute to the
development of the U.S. position on the
substances to be considered for control
under the Psychotropic Convention, a
request for a public meeting and the
reasons for such a request should be
sent to James R. Hunter (see FOR
FURTHER INFORMATION CONTACT) on or
before January 23, 2017.
sradovich on DSK3GMQ082PROD with NOTICES
Dated: January 5, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017–00373 Filed 1–10–17; 8:45 am]
BILLING CODE 4164–01–P
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2014–D–1862]
Recommended Warning for Over-theCounter Acetaminophen-Containing
Drug Products and Labeling
Statements Regarding Serious Skin
Reactions; Guidance for Industry;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA) is announcing the
availability of a guidance for industry
entitled ‘‘Recommended Warning for
Over-the-Counter AcetaminophenContaining Drug Products and Labeling
Statements Regarding Serious Skin
Reactions.’’ This guidance is intended to
inform manufacturers, members of the
medical and scientific community, and
other interested persons that at this time
FDA does not intend to take action
against the marketing of single- and
combination-ingredient,
acetaminophen-containing,
nonprescription (commonly referred to
as over-the-counter (OTC)) drug
products bearing a warning as described
in the guidance alerting consumers that
the use of acetaminophen may cause
severe skin reactions.
DATES: Submit either electronic or
written comments on Agency guidances
at any time.
ADDRESSES: You may submit comments
as follows:
SUMMARY:
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.
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• 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): Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Division of Dockets
Management, 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–
2014–D–1862 for ‘‘Recommended
Warning for Over-the-Counter
Acetaminophen-Containing Drug
Products and Labeling Statements
Regarding Serious Skin Reactions;
Guidance for Industry.’’ Received
comments will be placed in the docket
and, except for those submitted as
‘‘Confidential Submissions,’’ publicly
viewable at https://www.regulations.gov
or at the Division of Dockets
Management between 9 a.m. and 4 p.m.,
Monday through Friday.
• 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 Division of Dockets
Management. 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
E:\FR\FM\11JAN1.SGM
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]]>Agencies
[Federal Register Volume 82, Number 7 (Wednesday, January 11, 2017)]
[Notices]
[Pages 3326-3332]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-00373]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-N-4619]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; World Health
Organization; Scheduling Recommendations; 4-Methylethcathinone and Nine
Other Substances; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is providing interested
persons with the opportunity to submit written comments, and to request
an informal public meeting concerning recommendations by the World
Health Organization (WHO) to impose international manufacturing and
distributing restrictions, under international treaties, on certain
drug substances. The comments received in response to this notice and/
or public meeting will be considered in preparing the United States'
position on these proposals for a meeting of the United Nations
Commission on Narcotic Drugs (CND) in Vienna, Austria, in March 2017.
This notice is issued under the Controlled Substances Act (CSA).
DATES: Submit either electronic or written comments by February 10,
2017. Submit requests for a public meeting on or before January 23,
2017. The short time period for the submission of comments and requests
for a public meeting is needed to ensure that HHS may, in a timely
fashion, carry out the required action and be responsive to the United
Nations. For additional information, see section IV of this document.
ADDRESSES: You may submit comments as follows:
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): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Division of
Dockets Management, 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-2016-N-4619 for ``International Drug Scheduling; Convention on
Psychotropic Substances; Single Convention on Narcotic Drugs; World
Health Organization; Scheduling Recommendations; 4-Methylethcathinone
and Nine Other Substances; Request for Comments.'' Received comments
will be placed in the docket and, except for those submitted as
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
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
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``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
[[Page 3327]]
https://www.regulations.gov. Submit both copies to the Division of
Dockets Management. 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.fda.gov/regulatoryinformation/dockets/default.htm.
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 Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
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, james.hunter@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
The United States is a party to the 1971 Convention on Psychotropic
Substances (Psychotropic Convention). Section 201(d)(2)(B) of the CSA
(21 U.S.C. 811(d)(2)(B)) provides that when the United States is
notified under Article 2 of the Psychotropic Convention that the CND
proposes to decide whether to add a drug or other substance to one of
the schedules of the Psychotropic Convention, transfer a drug or
substance from one schedule to another, or delete it from the
schedules, the Secretary of State must transmit notice of such
information to the Secretary of Health and Human Services (Secretary of
HHS). The Secretary of HHS must then publish a summary of such
information in the Federal Register and provide opportunity for
interested persons to submit comments. The Secretary of HHS must then
evaluate the proposal and furnish a recommendation to the Secretary of
State that shall be binding on the representative of the United States
in discussions and negotiations relating to the proposal.
As detailed in the following paragraphs, the Secretary of State has
received notification from the Secretary-General of the United Nations
(the Secretary-General) regarding eight substances to be considered for
control under the Psychotropic Convention. This notification reflects
the recommendation from the 38th WHO Expert Committee for Drug
Dependence (ECDD), which met in November 2016. In the Federal Register
of September 19, 2016 (81 FR 64162), FDA announced the WHO ECDD review
and invited interested persons to submit information for WHO's
consideration.
The full text of the notification from the Secretary-General is
provided in section II of this document. Section 201(d)(2)(B) of the
CSA requires the Secretary of HHS, after receiving a notification
proposing scheduling, to publish a notice in the Federal Register to
provide the opportunity for interested persons to submit information
and comments on the proposed scheduling action.
The United States is also a party to the 1961 Single Convention on
Narcotic Drugs (1961 Single Convention). The Secretary of State has
received a notification from the Secretary-General regarding two
substances to be considered for control under this convention. The CSA
does not require HHS to publish a summary of such information in the
Federal Register. Nevertheless, in an effort to provide interested and
affected persons an opportunity to submit comments regarding the WHO
recommendations for narcotic drugs, the notification regarding these
substances is also included in this Federal Register notice. The
comments will be shared with other relevant Agencies to assist the
Secretary of State in formulating the position of the United States on
the control of these substances. The HHS recommendations are not
binding on the representative of the United States in discussions and
negotiations relating to the proposal regarding control of substances
under the 1961 Single Convention.
II. United Nations Notification
The formal notification from the United Nations that identifies the
drug substances and explains the basis for the recommendations is
reproduced as follows (non-relevant text removed):
Reference:
NAR/CL.8/2016
WHO/ECDD38; 1961C-Art.3; 1971C-Art.2
CU 2016/495/DTA/SGB
The Secretary-General of the United Nations presents his
compliments to the Secretary of State of the United States of
America and has the honour to inform the Government that the
Director-General of the World Health Organization (WHO), pursuant to
article 3, paragraphs 1 and 3 of the Single Convention on Narcotic
Drugs of 1961 as amended by the 1972 Protocol (1961 Convention) and
article 2, paragraphs 1 and 4 of the Convention on Psychotropic
Substances of 1971 (1971 Convention) notified the Secretary-General
of the following recommendations:
Substances recommended to be placed in Schedule I of the Single
Convention on Narcotic Drugs (1961), as amended by the 1972
Protocol:
--U-4770
chemical name: 3,4-dichloro-N-(2-dimethylamino-cyclohexyl)-N-
methyl-benzamide
--butyrfentanyl
chemical name: N-phenyl-N-[1-(2-phenylethyl)-4-
piperidinyl]butanamide
Substances recommended to be placed in Schedule II of the 1971
Convention:
--4-MEC (4-methylethcathinone)
chemical name: 2-(ethylamino)-1-(4-methylphenyl)propan-1-one
--ethylone
chemical name: 1-(2H-1,3-benzodioxol-5-yl)-2-(ethylamino)propan-
1-one
--pentedrone
chemical name: 2-(methylamino)-1-phenylpentan-1-one
--ethylphenidate
chemical name: ethyl phenyl(piperidin-2-yl)acetate
--MPA (methiopropamine)
chemical name: N-methyl-1-(thiophen-2-yl)propan-2-amine
--MDMB-CHMICA
chemical name: methyl N-{[1-(cyclohexylmethyl)-1H-indol-3-
yl]carbonyl{time} -3-methyl-L-valinate
--5F-APINACA (5F-AKB-48)
chemical name: N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-
indazole-3-carboxamide
--XLR-11
chemical name: [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-
tetramethylcyclopropyl)methanone
In addition, in the letter from the Director-General of the
World Health Orgazniation to the Secretary-General, reference is
also made to the recommendations by the thirty-eighth meeting of the
WHO Expert Committee on Drug Dependence (ECDD) for carrying out a
critical review of one substance at a subsequent Expert Committee
meeting, as well as for one substance to continue to be kept under
surveillance. Furthermore, the letter also makes reference to the
recommendation by the Expert Committee with regard to cannabis and
its component substances.
In accordance with the provisions of article 3, paragraph 2 of
the 1961 Convention and article 2, paragraph 2 of the 1971
Convention, the Secretary-General hereby transmits the notification
as annex I to the present note. In accordance with the provisions of
article 3, paragraph 2 of the 1961 Convention and article 2,
paragraph 2 of the 1971 Convention, the notification from WHO will
be brought to
[[Page 3328]]
the attention of the sixtieth session of the Commission on Narcotic
Drugs (13-17 March 2017).
In connection with the notification, WHO has also submitted the
relevant extract from the report of the thirty-eighth meeting of the
WHO Expert Committee on Drug Dependence which is hereby transmitted
as annex II.
In order to assist the Commission in reaching a decision, it
would be appreciated if the Government could communicate any
economic, social, legal, administrative or other factors that it
considers relevant to the possible scheduling of the afore-mentioned
substances that are recommended by WHO to be placed under
international control under the 1961 Convention (namely: U-4770 and
butyrfentanyl) and the 1971 Convention (namely: 4-MEC, ethylone,
pentedrone, ethylphenidate, MPA, MDMB-CHMICA, 5F- APINACA, and XLR-
11).
Communications are to be sent at the latest by 20 January 2017
to the Executive Director of the United Nations Office on Drugs and
Crime, c/o Secretary, Commission on Narcotic Drugs, P.O. Box 500,
1400 Vienna, Austria, fax: +43-1-26060-5885, email: sgb@unodc.org.
21 December 2016
His Excellency
Mr. John Kerry
Secretary of State of the United States of America
Annex I
Letter Addressed to the Secretary-General of the United Nations From
the Director-General of the World Health Organization
``The Thirty-eighth meeting of the WHO Expert Committee on Drug
Dependence convened from 14 to 18 November 2016, at WHO headquarters
in Geneva. The objective of this meeting was to carry out an in-
depth evaluation of psychoactive substances in order to determine
whether or not WHO should recommend these substances to be placed
under international control.
With reference to Article 2, paragraphs 1 and 4 of the
Convention on Psychotropic Substances (1971) and Article 3,
paragraphs 1 and 3 of the Single Convention on Narcotic Drugs
(1961), as amended by the 1972 Protocol, I am pleased to submit
recommendations of the World Health Organization as follows:
to be placed in Schedule I of the Single Convention on Narcotic
Drugs (1961), as amended by the 1972 Protocol:
--U-47700
chemical name: 3,4-dichloro-N-(2-dimethylamino-cyclohexyl)-N-
methyl-benzamide
--butyrfentanyl
chemical name: N-phenyl-N-[1-(2-phenylethyl)-4-
piperidinyl]butanamide
to be placed in Schedule II of the Convention on Psychotropic
Substances (1971):
--4-MEC (4-methylethcathinone)
chemical name: 2-(ethylamino)-1-(4-methylphenyl)propan-1-one
--ethylone
chemical name: 1-(2H-1,3-benzodioxol-5-yl)-2-(ethylamino)propan-
1-one
--pentedrone
chemical name: 2-(methylamino)-1-phenylpentan-1-one
--ethylphenidate
chemical name: ethyl phenyl(piperidin-2-yl)acetate
--MPA (methiopropamine)
chemical name: N-methyl-1-(thiophen-2-yl)propan-2-amine
--MDMB-CHMICA
chemical name: methyl N-{[1-(cyclohexylmethyl)-1H-indol-3-
yl]carbonyl{time} -3-methyl-L-valinate
--5F-APINACA (5F-AKB-48)
chemical name: N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-
indazole-3-carboxamide
--XLR-11
chemical name: [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-
tetramethylcyclopropyl)methanone.
In addition, the Expert Committee recommended to carry out a
critical review at a subsequent Expert Committee meeting for:
--3-MMC (3-Methylmethcathinone)
chemical name: 2-(methylamino)-1-(3-methylphenyl)propan-1-one
It also recommended to continue to keep the following substance
under surveillance:
--JWH-073
chemical name: (1-butyl-1H-indol-3-yl)(1-naphthyl)methanone
The Committee recommended that a specific ECDD meeting dedicated
to cannabis and its component substances should be held within the
next eighteen months from the 38th meeting, and will carry out pre-
reviews for the following substances:
--Cannabis plant and cannabis resin;
--Extracts and tinctures of cannabis;
--Delta-9-tetrahydrocannabinol (THC);
--Cannabidiol (CBD);
--Stereoisomers of THC.
The recommendations and the assessments and findings on which
they are based are set out in detail in the Report of the 38th
Expert Committee on Drug Dependence, which is the Committee that
advises me on these issues. An extract of the Committee's Report is
attached in Annex 1 to this letter.
I am very pleased with the ongoing collaboration among the
United Nations Office on Drugs and Crime (UNODC), International
Narcotics Control Board (INCB) and WHO, in particular, how this
collaboration has supported the work of the WHO Expert Committee on
Drug Dependence, and more generally, the implementation of
operational recommendations from the United Nations General Assembly
Special Session (UNGASS) 2016.''
NAR/CL.8/2016
Annex II
Extract From the Report of the 38th Expert Committee on Drug Dependence
Substances recommended to be scheduled in Schedule I and
Schedule IV of the Single Convention on Narcotic Drugs (1961), as
amended by the 1972 Protocol:
U-47700
Chemically, U-47700 is 3,4-dichloro-N-(2-dimethylamino-
cyclohexyl)-N-methyl-benzamide. U47700 has two chiral centres
resulting in four isomers; cis and trans conformations each have two
enantiomers [cis: are (1R,2R), and (1S,2S); trans are (1R,2S) and
(1S,2R)].
U-47700 was not previously pre-reviewed or critically reviewed
by the Committee. A direct critical review is proposed based on
information brought to the attention of the WHO that U-47700 is
clandestinely manufactured, poses risk to public health and society,
and has no recognized therapeutic use by any Party.
U-47700 (3,4-dichloro-N-(2-dimethylamino-cyclohexyl)-N-methyl-
benzamide) is a compound liable to similar abuse and with similar
ill-effects to controlled opioids such as morphine and AH-7921 that
are included in Schedule I of the 1961 Single Convention on Narcotic
Drugs. It has no recorded therapeutic use, and its use has resulted
in fatalities. There is sufficient evidence that it is being or is
likely to be abused so as to constitute a public health and social
problem warranting the placing of the substance under international
control. Thus, because it meets the required condition of
similarity, it is recommended that U-47700 be placed in Schedule I
of the Single Convention on Narcotic Drugs, 1961, as consistent with
Article 3, paragraph 3 (iii) of that Convention in that the
substance is liable to similar abuse and productive of similar ill
effects as drugs in Schedule I.
Butyrfentanyl
Chemically, butyrfentanyl is N-phenyl-N-[1-(2-phenylethyl)-4-
piperidinyl]butanamide.
Butyrfentanyl has not been previously pre-reviewed or critically
reviewed by the Committee. A direct critical review is proposed
based on information brought to the attention of the WHO that
butyrfentanyl is clandestinely manufactured, poses risk to public
health and society, and has no recognized therapeutic use by any
Party.
Butyrfentanyl (N-phenyl-N-[1-(2-phenylethyl)-4-
piperidinyl]butanamide) is a compound liable to similar abuse and
with similar ill-effects to controlled opioids such as morphine and
fentanyl that are included in Schedule I of the 1961 Single
Convention on Narcotic Drugs. It can be converted into fentanyl as
well. It has no recorded therapeutic use and its use has resulted in
fatalities. There is sufficient evidence that it is being or is
likely to be abused so as to constitute a public health and social
problem warranting the placing of the substance under international
control. Thus, because it meets either of the required conditions of
similarity or convertibility, it is recommended that butyrfentanyl
be placed in Schedule I of the Single Convention on Narcotic Drugs,
1961, as consistent with Article 3, paragraph 3 (iii) of that
Convention in that the substance is liable to similar abuse and
productive of similar ill effects as drugs in Schedule I.
Substances recommended to be scheduled in Schedule II of the
Convention on Psychotropic Substances (1971):
4-MEC (4-Methylethcathinone)
Chemically, 4-methylethcathinone (4-MEC) is 2-(ethylamino)-1-(4-
methylphenyl)propan-1-one. 4-MEC has a chiral centre giving rise to
an enantiomeric pair of (S)-4-MEC and (R)-4-MEC isomers.
[[Page 3329]]
A critical review report on 4-MEC was discussed in June 2014 at
the 36th meeting of the WHO Expert Committee on Drug Dependence. The
Committee recommended that 4-MEC not be placed under international
control at that time due to insufficiency of data regarding
dependence, abuse and risks to public health, but be kept under
surveillance. 4-MEC continues to appear as a psychostimulant with
monoamine transporter activity with indications of abuse liability.
New data have emerged from in vitro and in vivo studies since the
36th ECCD meeting that has prompted the current critical review.
The Committee considered that the degree of risk to public
health and society associated with the abuse of 4-MEC (2-
(ethylamino)-1-(4-methylphenyl)propan-1-one) is substantial.
Therapeutic usefulness has not been recorded. It recognized that it
has similar abuse and similar ill-effects as substances in Schedule
II of the UN 1971 Convention on Psychotropic Substances. The
Committee considered that there is sufficient evidence that 4-MEC is
being or is likely to be abused so as to constitute a public health
and social problem warranting the placing of the substance under
international control. As per the Guidance on the WHO review of
psychoactive substances for international control, higher regard was
accorded to the substantial public health risk than to the lack of
therapeutic usefulness. The Committee recommended that 4-MEC be
placed in Schedule II under the UN 1971 Convention on Psychotropic
Substances.
Ethylone
Chemically, ethylone is 1-(2H-1,3-benzodioxol-5-yl)-2-
(ethylamino)propan-1-one. It is a chiral compound with isomers, and
its hydrochloride salt can exist in two conformations (polymorphs)
at the C-C bond linking the side chain to the aromatic ring.
Ethylone was not previously pre-reviewed or critically reviewed.
A direct critical review is proposed based on information brought to
the attention of the WHO that ethylone is clandestinely
manufactured, poses serious risk to public health and society, and
has no recognized therapeutic use by any Party.
The Committee considered that the degree of risk to public
health and society associated with the abuse of ethylone (1-(2H-1,3-
benzodioxol-5-yl)-2-(ethylamino)propan-1-one) is substantial.
Therapeutic usefulness has not been recorded. It recognized that it
has similar abuse and similar ill-effects as substances in Schedule
II of the UN 1971 Convention on Psychotropic Substances. The
Committee considered that there is sufficient evidence that ethylone
is being or is likely to be abused so as to constitute a public
health and social problem warranting the placing of the substance
under international control. As per the Guidance on the WHO review
of psychoactive substances for international control, higher regard
was accorded to the substantial public health risk than to the lack
of therapeutic usefulness. The Committee recommended that ethylone
be placed in Schedule II under the UN 1971 Convention on
Psychotropic Substances.
Pentedrone ([alpha]-Methylaminovalerophenone)
Chemically, pentedrone is 2-(methylamino)-1-phenylpentan-1-one.
It has a chiral centre giving rise to two stereoisomers, (S)- and
(R)- pentedrone.
Pentedrone has not been previously reviewed or critically
reviewed by the Expert Committee on Drug Dependence of the WHO. A
direct critical review is proposed based on information brought to
WHO's attention that pentedrone is clandestinely manufactured, poses
serious risk to public health and society, and has no recognized
therapeutic use by any Party.
The Committee considered that the degree of risk to public
health and society associated with the abuse of pentedrone (2-
(methylamino)-1-phenylpentan-1-one) is substantial. Therapeutic
usefulness has not been recorded. It recognized that it has similar
abuse and similar ill-effects as substances in Schedule II of the UN
1971 Convention on Psychotropic Substances. The Committee considered
that there is sufficient evidence that pentedrone is being or is
likely to be abused so as to constitute a public health and social
problem warranting the placing of the substance under international
control. As per the Guidance on the WHO review of psychoactive
substances for international control, higher regard was accorded to
the substantial public health risk than to the lack of therapeutic
usefulness. The Committee recommended that pentedrone be placed in
Schedule II under the UN 1971 Convention on Psychotropic Substances.
Ethylphenidate (EPH)
Chemically, ethylphenidate is ethyl phenyl(piperidin-2-
yl)acetate.
Ethylphenidate was not previously pre-reviewed or critically
reviewed. A direct critical review is proposed based on information
brought to the attention of the WHO that ethylphenidate is
clandestinely manufactured, poses serious risk to public health and
society, and has no recognized therapeutic use by any Party.
The Committee considered that the degree of risk to public
health and society associated with the abuse of ethylphenidate
(ethyl phenyl(piperidin-2-yl)acetate) is substantial. Therapeutic
usefulness has not been recorded. It recognized that it has similar
abuse and similar ill-effects as substances in Schedule II of the UN
1971 Convention on Psychotropic Substances. The Committee considered
that there is sufficient evidence that ethylphenidate is being or is
likely to be abused so as to constitute a public health and social
problem warranting the placing of the substance under international
control. As per the Guidance on the WHO review of psychoactive
substances for international control, higher regard was accorded to
the substantial public health risk than to the lack of therapeutic
usefulness. The Committee recommended that ethylphenidate be placed
in Schedule II under the UN 1971 Convention on Psychotropic
Substances.
MPA (Methiopropamine)
Chemically, methiopropamine is N-methyl-1-(thiophen-2-yl)propan-
2-amine. It has a chiral centre with two enantiomers.
Methiopropamine was previously critically reviewed by the
Committee at its 36th meeting. Owing to the insufficiency of data
regarding dependence, abuse and risks to public health, the
Committee recommended that methiopropamine not be placed under
international control but be kept under surveillance. Subsequent
data collected from the literature and from different countries
indicated that this substance may cause substantial harm and that it
has no medical use warranting an updated critical review.
The Committee considered that the degree of risk to public
health and society associated with the abuse of methiopropamine (N-
methyl-1-(thiophen-2-yl)propan-2-amine) is substantial. Therapeutic
usefulness has not been recorded. It recognized that it has similar
abuse and similar ill-effects as substances in Schedule II of the UN
1971 Convention on Psychotropic Substances. The Committee considered
that there is sufficient evidence that methiopropamine is being or
is likely to be abused so as to constitute a public health and
social problem warranting the placing of the substance under
international control. As per the Guidance on the WHO review of
psychoactive substances for international control, higher regard was
accorded to the substantial public health risk than to the lack of
therapeutic usefulness. The Committee recommended that
methiopropamine be placed in Schedule II under the UN 1971
Convention on Psychotropic Substances.
MDMB-CHMICA
Chemically, MDMB-CHMICA is methyl N-{[1-(cyclohexylmethyl)-1H-
indol-3-yl]carbonyl{time} -3-methyl-L-valinate. MDMB-CHMICA has a
chiral carbon in the butanoic chain. Therefore, two stereoisomers
exist: (S)-MDMB-CHMICA and (R)-MDMB-CHMICA.
MDMB-CHMICA has not been previously pre-reviewed or critically
reviewed. A direct critical review is proposed based on information
brought to the attention of the WHO that MDMB-CHMICA is
clandestinely manufactured, poses serious risk to public health and
society, and has no recognized therapeutic use by any Party.
The Committee considered that the degree of risk to public
health and society associated with the abuse of MDMB-CHMICA (methyl
N-{[1-(cyclohexylmethyl)-1H-indol-3-yl]carbonyl{time} -3-methyl-L-
valinate) is substantial. Therapeutic usefulness has not been
recorded. It recognized that it has similar abuse and similar ill-
effects as substances in Schedule II of the UN 1971 Convention on
Psychotropic Substances. The Committee considered that there is
sufficient evidence that MDMB-CHMICA is being or is likely to be
abused so as to constitute a public health and social problem
warranting the placing of the substance under international control.
As per the Guidance on the WHO review of psychoactive substances for
international control, higher regard was accorded to the substantial
public health risk than to the lack of therapeutic usefulness. The
Committee recommended that MDMB-CHMICA be placed in Schedule II
under the UN 1971 Convention on Psychotropic Substances.
5F-APINACA (5F-AKB-48)
Chemically, 5F-APINACA is N-(adamantan-1-yl)-1-(5-fluoropentyl)-
1H-indazole-3-carboxamide.
5F-APINACA has not been previously pre-reviewed or critically
reviewed by the Expert
[[Page 3330]]
Committee on Drug Dependence of the WHO. A direct critical review is
proposed based on information brought to the attention of the WHO
that 5F-APINACA is clandestinely manufactured, poses serious risk to
public health and society, and has no recognized therapeutic use by
any Party.
The Committee considered that the degree of risk to public
health and society associated with the abuse of 5F-APINACA (N-
(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide) is
substantial. Therapeutic usefulness has not been recorded. It
recognized that it has similar abuse and similar ill-effects as
substances in Schedule II of the UN 1971 Convention on Psychotropic
Substances. The Committee considered that there is sufficient
evidence that 5F-APINACA is being or is likely to be abused so as to
constitute a public health and social problem warranting the placing
of the substance under international control. As per the Guidance on
the WHO review of psychoactive substances for international control,
higher regard was accorded to the substantial public health risk
than to the lack of therapeutic usefulness. The Committee
recommended that 5F-APINACA be placed in Schedule II under the UN
1971 Convention on Psychotropic Substances.
XLR-11
Chemically, XLR-11 is [1-(5-fluoropentyl)-1H-indol-3-
yl](2,2,3,3-tetramethylcyclopropyl)methanone.
XLR-11 has not been previously pre-reviewed or critically
reviewed. A direct critical review is proposed based on information
brought to WHO's attention that XLR-11 is clandestinely
manufactured, poses serious risk to public health and society, and
has no recognized therapeutic use by any Party.
The Committee considered that the degree of risk to public
health and society associated with the abuse of XLR-11 ([1-(5-
fluoropentyl)-1H-indol-3-yl](2,2,3,3-
tetramethylcyclopropyl)methanone) is substantial. Therapeutic
usefulness has not been recorded. It recognized that it has similar
abuse and similar ill-effects as substances in Schedule II of the UN
1971 Convention on Psychotropic Substances such as JWH-018 and AM-
2201. The Committee considered that there is sufficient evidence
that XLR-11 is being or is likely to be abused so as to constitute a
public health and social problem warranting the placing of the
substance under international control. As per the Guidance on the
WHO review of psychoactive substances for international control,
higher regard was accorded to the substantial public health risk
than to the lack of therapeutic usefulness. The Committee
recommended that XLR-11 be placed in Schedule II under the UN 1971
Convention on Psychotropic Substances.
Substance recommended for critical review:
3-Methylmethcathinone (3-methyl-N-methylcathinone; 3-MMC)
Chemically, 3-MMC is 2-(methylamino)-1-(3-methylphenyl)propan-1-
one. 3-MMC contains a chiral centre at the C-2 carbon of the propane
sidechain, so two enantiomers exist: (R)-3-MMC and (S)-3-MMC.
3-MMC was not previously pre-reviewed or critically reviewed. A
direct critical review is proposed based on information brought to
the attention of the WHO that 3-MMC is clandestinely manufactured,
poses serious risk to public health and society, and has no
recognized therapeutic use by any Party.
The Committee deliberated at length regarding the information
available pertinent to the degree of risk to public health and
society associated with the abuse of 3-MMC (2-(methylamino)-1-(3-
methylphenyl)propan-1-one). The Committee decided that the
information as currently provided, and the ensuing discussions that
had occurred, were inadequate to form a consensus and confident
recommendation regarding the scheduling of 3-MMC. As per paragraph
59 of the Guidance on the WHO review of psychoactive substances for
international control, and as supported by its procedural reference
to the Thirty-fourth report of the WHO Expert Committee on Drug
Dependence, ``. . . in cases where additional information concerning
the substance under review is required, the Committee may decide
that it will reach a final opinion at a subsequent meeting.'' ``. .
. then it should request another critical review in order to refer
the matter to a subsequent Expert Committee.'' As directed by these
guidelines, the Committee requested that the Secretariat arrange
another critical review of 3-MMC at a subsequent Expert Committee.
Substance recommended for surveillance:
JWH-073
Chemically, JWH-073 is (1-butyl-1H-indol-3-yl)(1-
naphthyl)methanone.
During its 36th meeting, the WHO Expert Committee on Drug
Dependence discussed the critical review report on JWH-073 and
concluded that owing to the current insufficiency of data regarding
dependence, abuse and risks to public health, JWH-073 should not be
placed under international control at that time but be kept under
surveillance. New information on its pharmacology and abuse
potential warranted an update of the critical review report for
discussion at the 38th ECDD.
The available pharmacodynamic data related to JWH-073 (1-butyl-
1H-indol-3-yl)(1-naphthyl)methanone) demonstrates that this
substance has the capacity to produce some effects similar to its
homologue, JWH-018, that is included in Schedule II of the UN 1971
Convention on Psychotropic Substances. However, the data currently
available does not make it possible to establish a direct link
between JWH-073 abuse and appearance of public health and social
problems that would be a requirement for placing this substance
under international control. It is therefore recommended not to
place JWH-073 under international control but to continue to keep it
under surveillance.
Update on Cannabis and Cannabis resin:
At the 37th ECDD meeting the Committee requested that
Secretariat begin collecting data towards a pre-review of cannabis,
cannabis resin, extracts and tinctures of cannabis at a future
meeting. Consistent with this request, two updates on the scientific
literature on cannabis were prepared and subsequently presented to
the Expert Committee. Following its deliberations the Committee
noted that the current Schedule I of the 1961 Convention groups
together cannabis and cannabis resin, extracts and tinctures of
cannabis. Cannabis plant and cannabis resin are also in Schedule IV
of the 1961 Convention. The Committee further noted that there are
natural and synthetic cannabinoids in Schedule I and Schedule II of
the 1971 Convention. The Committee recognized:
--An increase in the use of cannabis and its components for medical
purposes;
--The emergence of new cannabis-related pharmaceutical preparations
for therapeutic use;
--Cannabis has never been subject to a formal pre-review or critical
review by the ECDD.
The Committee requested that the Secretariat prepare relevant
documentation in accordance with the Guidance on the WHO review of
psychoactive substances for international control in order to
conduct pre-reviews for the following substances:
--Cannabis plant and cannabis resin;
--Extracts and tinctures of cannabis;
--Delta-9-tetrahydrocannabinol (THC);
--Cannabidiol (CBD);
--Stereoisomers of THC.
The Committee recommended that these pre-reviews be evaluated at
a specific ECDD meeting dedicated to cannabis and its component
substances to be held within the next eighteen months from the 38th
meeting.
The purpose of the pre-review is to determine whether current
information justifies an Expert Committee critical review. The
categories of information for evaluating substances in pre-reviews
are identical to those used in critical reviews. The pre-review is a
preliminary analysis, and findings at this stage should not
determine whether the control status of a substance should be
changed.
III. Discussion
Although WHO has made specific scheduling recommendations for each
of the drug substances, the CND is not obliged to follow the WHO
recommendations. Options available to the CND for substances considered
for control under the Psychotropic Convention include the following:
(1) Accept the WHO recommendations; (2) accept the recommendations to
control, but control the drug substance in a schedule other than that
recommended; or (3) reject the recommendations entirely.
U-47700 is a synthetic opioid drug developed in the 1970s. U-47700
is structurally related to the opioid AH-7921. U-47700 is selective for
the [micro]-opioid receptor. U-47700 has never been studied on humans,
but would be expected to produce effects similar to those of other
potent opioid agonists, including strong analgesia, sedation, euphoria,
constipation, itching, and respiratory depression which could be
harmful or fatal. Overdoses and
[[Page 3331]]
overdose fatalities have been directly attributed to U-47700 misuse.
There have been reports of U-47700 being encountered in counterfeit
pills. On November 14, 2016, the U.S. Drug Enforcement Administration
(DEA) temporarily scheduled U-47700 into schedule I pursuant to the
temporary scheduling provisions of the Controlled Substances Act. As
such, additional permanent controls will be necessary to fulfill U.S.
obligations if U-47700 is controlled under Schedule I of the 1961
Single Convention.
Butyrfentanyl (butyrylfentanyl) is a synthetic opioid and analog of
fentanyl. Fentanyl is controlled in Schedule II of the CSA, and an
active ingredient in drug products approved for medical use and
marketed in the United States. Butyrylfentanyl has a pharmacological
profile similar to that of fentanyl and other [micro]-opioid receptor
agonists. Risks associated with abuse of butyrylfentanyl include
development of substance use disorder, overdose, and death similar to
that of other [micro]-opioid agonists. The DEA is aware of at least 40
confirmed fatalities associated with butyrylfentanyl. It has no
approved medical use in the United States. On May 12, 2016,
butyrylfentanyl was temporarily placed into Schedule I of the CSA for 2
years upon finding that it posed an imminent hazard to the public
safety. The Attorney General, though, may extend this temporary
scheduling for up to 1 year. As such, additional permanent controls
will be necessary to fulfill U.S. obligations if butyrylfentanyl is
controlled under Schedule I of the 1961 Single Convention.
4-Methylethcathinone (4-MEC), 3-Methylmethcathinone (3-methyl-N-
methylcathinone; 3-MMC): 3-methyl-methcathinone (3-MMC), pentedrone,
and ethylone (3,4-methylenedioxy-N-ethylcathinone; bk-MDEA; MDEC) are
synthetic cathinones that are structurally and pharmacologically
similar to amphetamine, 3-4 methylenedioxymethamphetamine (MDMA),
cathinone, and other related substances. These substances are central
nervous system stimulants with psychoactive properties similar to
Schedule I and II amphetamine type substances. Public health risks
associated with the use of synthetic cathinones suggest that these
substances are associated with cardiac, psychiatric, and neurological
symptoms that may lead to emergency department admissions, violent
behaviors causing harm to self or others, or death. 4-MEC and
pentedrone have no known medical use in the United States. On March 7,
2014, the DEA published a final order in the Federal Register amending
21 CFR 1308.11(h) to temporarily place 4-MEC and pentedrone into
Schedule I of the CSA pursuant to the temporary scheduling provisions
of 21 U.S.C. 811(h). On March 4, 2016, the temporary Schedule I status
of 4-MEC and pentedrone was extended for 1 year, or until permanent
scheduling is completed. Permanent scheduling for 4-MEC and pentedrone
was initiated on March 4, 2016, upon publication of the notice of
proposed rulemaking. As such, additional permanent controls will be
necessary to fulfill U.S. obligations if 4-MEC and pentedrone is
controlled under Schedule II of the 1971 Convention on Psychotropic
Substances.
In the United States, ethylone has been sold as the street drug
``Molly'' and encountered as a replacement for methylone. Ethylone has
no known medical use in the United States. As a positional isomer of
the controlled drug butylone, ethylone is considered a Schedule I
controlled substance under the CSA. As such, no additional controls
will be necessary to fulfill U.S. obligations if ethylone is controlled
under Schedule II of the 1971 Convention on Psychotropic Substances.
Ethylphenidate is structurally related to methylphenidate.
Methylphenidate is controlled in Schedule IV of the CSA, and an active
ingredient in drug products approved for medical use and marketed in
the United States. Ethylphenidate is not approved for medical use in
the United States. Ethylphenidate is structurally related to
methylphenidate are being marketed as novel psychoactive substances
with psychoactive effects similar to methylphenidate, therefore posing
similar health risks to the users. Ethylphenidate is a controlled
substance in several European countries, and is not a controlled
substance in the United States under the CSA. As such, additional
permanent controls will be necessary to fulfill U.S. obligations if
ethylphenidate is controlled under Schedule II of the 1971 Convention
on Psychotropic Substances.
Methiopropamine (MPA) is a structural analogue of the Schedule II
controlled substance methamphetamine. Pharmacologically, it functions
as a norepinephrine-dopamine reuptake inhibitor and, secondarily, as a
serotonin reuptake inhibitor. MPA is a thiophene based analog of
methamphetamine. It has stimulant properties as an inhibitor of
dopamine, norepinephrine transporters in the central nervous system.
MPA is not approved for medical use or controlled in the United States
under the CSA. As such, additional permanent controls will be necessary
to fulfill U.S. obligations if MPA is controlled under Schedule II of
the 1971 Convention on Psychotropic Substances.
MDMB-CHMICA is an indole-based synthetic cannabinoid that is a
potent full agonist at cannabinoid type 1 (CB1) receptors and mimics
functionally (biologically) the effects of the structurally unrelated
delta-9-tetrahydrocannabinol, a Schedule I substance, and the main
active ingredient of marijuana. Synthetic cannabinoids are marketed
under the guise of ``herbal incense,'' and promoted by drug traffickers
as legal alternatives to marijuana. MDMB-CHMICA use is associated with
serious adverse events including death in several European countries.
There are no commercial or approved medical uses for MDMB-CHMICA. MDMB-
CHMICA is not controlled under the CSA, but may be treated as a
``controlled substance analogue'' under the CSA pursuant to 21 U.S.C.
802(32)(A) and 813, and is a controlled substance in the State of
Louisiana. As such, additional permanent controls will be necessary to
fulfill U.S. obligations if MDMB-CHMICA is controlled under Schedule II
of the 1971 Convention on Psychotropic Substances.
5F-APINACA (5F-AKB48) is a synthetic cannabinoid belonging to a
chemical structural class with an indazole core. In vitro studies show
that it binds to the CB1 receptors and displays agonist properties in
functional assays, suggesting that it would share in vivo effects with
delta-9-THC and various synthetic cannabinoids. There are no commercial
or medical uses for 5F-APINACA. Synthetic cannabinoids are marketed
under the guise of ``herbal incense,'' and promoted by drug traffickers
as legal alternatives to marijuana. SF-APINACA is not a controlled
substance under the CSA, but may be treated as a ``controlled substance
analogue'' under the CSA pursuant to 21 U.S.C. 802(32)(A) and 813. As
such, additional permanent controls will be necessary to fulfill U.S.
obligations if SF-APINACA is controlled under Schedule II of the 1971
Convention on Psychotropic Substances.
XLR-11 (5-Fluoro-UR-144, 5F-UR-144) is an indole-based synthetic
cannabinoid and acts as an agonist at CB1 receptors. Animal studies
indicate that it mimics functionally (biologically) the effects of the
structurally unrelated delta-9-THC, a Schedule I substance, and the
main active ingredient of marijuana and numerous other
[[Page 3332]]
Schedule I synthetic cannabinoids. Synthetic cannabinoids are marketed
under the guise of ``herbal incense,'' and promoted by drug traffickers
as legal alternatives to marijuana. On May 11, 2016, XLR11 was
permanently controlled as a Schedule I substance under the CSA. As
such, additional permanent controls will not be necessary to fulfill
U.S. obligations if XLR-11 is controlled under Schedule II of the 1971
Convention on Psychotropic Substances.
FDA, on behalf of the Secretary of HHS, invites interested persons
to submit comments on the notifications from the United Nations
concerning these drug substances. FDA, in cooperation with the National
Institute on Drug Abuse, will consider the comments on behalf of HHS in
evaluating the WHO scheduling recommendations. Then, under section
201(d)(2)(B) of the CSA, HHS will recommend to the Secretary of State
what position the United States should take when voting on the
recommendations for control of substances under the Psychotropic
Convention at the CND meeting in March 2017.
Comments regarding the WHO recommendations for control of U-47700
and Butyrylfentanyl under the 1961 Single Convention will also be
forwarded to the relevant Agencies for consideration in developing the
U.S. position regarding narcotic substances at the CND meeting.
IV. Opportunity for Public Meeting
FDA does not presently plan to hold a public meeting. If any person
believes that, in addition to written comments, a public meeting would
contribute to the development of the U.S. position on the substances to
be considered for control under the Psychotropic Convention, a request
for a public meeting and the reasons for such a request should be sent
to James R. Hunter (see FOR FURTHER INFORMATION CONTACT) on or before
January 23, 2017.
Dated: January 5, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-00373 Filed 1-10-17; 8:45 am]
BILLING CODE 4164-01-P
