82 FR 3326 - 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

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 7 (January 11, 2017)

Page Range		3326-3332
FR Document		2017-00373
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).
Federal Register, Volume 82 Issue 7 (Wednesday, January 11, 2017)
[Federal Register Volume 82, Number 7 (Wednesday, January 11, 2017)]
[Notices]
[Pages 3326-3332]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-00373]


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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 
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

[[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: http://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, [email protected].

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: [email protected].

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
Document Created: 2018-02-01 14:59:44
Document Modified: 2018-02-01 14:59:44
Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
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.
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, [email protected]
FR Citation		82 FR 3326
82 FR 3326 - 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

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 82, Issue 7 (January 11, 2017)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
