83 FR 3741 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization; Scheduling Recommendations; Carfentanil;4-fluoroamphetamine (4-FA) and Ten Other Substances; Request for Comments

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 18 (January 26, 2018)

Page Range		3741-3748
FR Document		2018-01471
The Food and Drug Administration (FDA) is providing interested persons with the opportunity to submit written comments 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 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 2018. This notice is issued under the Controlled Substances Act (CSA).
Federal Register, Volume 83 Issue 18 (Friday, January 26, 2018)
[Federal Register Volume 83, Number 18 (Friday, January 26, 2018)]
[Notices]
[Pages 3741-3748]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2018-01471]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-0181]


International Drug Scheduling; Convention on Psychotropic 
Substances; Single Convention on Narcotic Drugs; World Health 
Organization; Scheduling Recommendations; Carfentanil; 4-
fluoroamphetamine (4-FA) and Ten Other Substances; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is providing interested 
persons with the opportunity to submit written comments 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 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 
2018. This notice is issued under the Controlled Substances Act (CSA).

DATES: Submit either electronic or written comments by February 26, 
2018.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before February 26, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of February 26, 2018. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery

[[Page 3742]]

service acceptance receipt is on or before that date.

Electronic Submissions

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

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-N-0181 for ``International Drug Scheduling; Convention on 
Psychotropic Substances; Single Convention on Narcotic Drugs; World 
Health Organization; Scheduling Recommendations; Carfentanil; 4-
fluoroamphetamine (4-FA) and Ten Other Substances; Request for 
Comments.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

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 six substances to be considered for 
control under the Psychotropic Convention. This notification reflects 
the recommendation from the 39th WHO Expert Committee for Drug 
Dependence (ECDD), which met in November 2017. In the Federal Register 
of August 14, 2017 (82 FR 37866), 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 six 
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, 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

[[Page 3743]]

the proposal regarding control of substances under the 1961 Single 
Convention.
    The short 30-day time period for the submission of comments is 
needed to ensure that Health and Human Services may, in a timely 
fashion, carry out the required action and be responsive to the United 
Nations.

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.4/2017
WHO/ECDD39; 1961C-Art.3; 1971C-Art.2
CU 2017/437/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 Schedules I and IV of the 
Single Convention on Narcotic Drugs (1961), as amended by the 1972 
Protocol:

Carfentanil
    Chemical name: Methyl 1-(2-phenylethyl)- 4-[phenyl(propanoyl) 
amino]piperidine- 4-carboxylate

    Substances recommended to be placed in Schedule I of the Single 
Convention on Narcotic Drugs (1961), as amended by the 1972 
Protocol:

Ocfentanil
    Chemical name: N-(2-Fluorophenyl)-2-methoxy-N-[1-(2-
phenylethyl)piperidin-4-yl]acetamide
Furanyl fentanyl
    Chemical name: N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-
yl]furan-2-carboxamide
Acryloylfentanyl (Acryl fentanyl)
    Chemical name: N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]prop-
2-enamide
4-Fluoroisobutyryl fentanyl (4-FIBF, pFIBF)
    Chemical name: N-(4-Fluorophenyl)-2-methyl-N-[1-(2-
phenylethyl)piperidin-4-yl]propanamide
Tetrahydrofuranylfentanyl (THF-F)
    Chemical name: N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-
yl]oxolane-2-carboxamide

    Substances recommended to be placed in Schedule II of the 
Convention on Psychotropic Substances (1971):

AB-CHMINACA
    Chemical name: N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-
(cyclohexylmethyl)-1H-indazole-3-carboxamide
5F-ADB (5F-MDMB-PINACA)
    Chemical name: Methyl (2S)-2-{[1-(5-fluoropentyl)-1H-indazole-3-
carbonyl]amino{time} -3,3-dimethylbutanoate
AB-PINACA
    Chemical name: N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-
pentyl-1H-indazole-3-carboxamide
UR-144
    Chemical name: (1-Pentyl-1H-indol-3-yl)(2,2,3,3-
tetramethylcyclopropyl)methanone
5F-PB-22
    Chemical name: Quinolin-8-yl 1-(5-fluoropentyl)-1H-indole-3-
carboxylate
4-Fluoroamphetamine (4-FA)
    Chemical name: 1-(4-Fluorophenyl)propan-2-amine

    In addition, in the letter from the Director-General of the 
World Health Organization to the Secretary-General, reference is 
also made to the recommendations by the thirty-ninth meeting of the 
WHO Expert Committee on Drug Dependence (ECDD) for carrying out a 
critical review of preparations containing almost exclusively 
cannabidiol (CBD), Pregabalin, and Tramadol at a subsequent Expert 
Committee meeting, as well as for Etizolam to remain 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. Also in accordance with the same 
provisions, the notification from WHO will be brought to the 
attention of the sixty-first session of the Commission on Narcotic 
Drugs (12-16 March 2018).
    In connection with the notification, WHO has also submitted the 
relevant extract from the report of the thirty-ninth 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: 
Carfentanil, Ocfentanil, Furanyl fentanyl, Acryloylfentanyl (Acryl 
fentanyl), 4-Fluoroisobutyryl fentanyl (4-FIBF, pFIBF), and 
Tetrahydrofuranylfentanyl (THF-F)) and the 1971 Convention (namely: 
AB CHMINACA, 5F-ADB (5F-MDMB-PINACA), AB-PINACA, UR-144, 5F-PB-22 
and 4-Fluoroamphetamine (4-FA)).
    Communications are to be sent at the latest by 2 February 2018 
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, e-mail: [email protected].

28 December 2017
His Excellency
Mr. Rex Tillerson
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-Ninth meeting of the WHO Expert Committee on Drug 
Dependence convened from 6 to 10 November 2017, 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 Schedules I and IV of the Single Convention on 
Narcotic Drugs (1961):

--Carfentanil
    chemical name: Methyl 1-(2-phenylethyl)-4- [phenyl(propionoyl) 
amino]piperidine-4-carboxylate

    To be placed in Schedule I of the Single Convention on Narcotic 
Drugs (1961):

--Ocfentanil
    chemical name: N-(2-Fluorophenyl)-2-methoxy-N-[1-(2-
phenylethyl)piperidin-4-yl]acetamide
--Furanyl fentanyl
    chemical name: N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-
yl]furan-2-carboxamide
--Acryloylfentanyl (Acryl fentanyl)
    chemical name: N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]prop-
2-enamide
--4-Fluoroisobutyryl fentanyl (4-FIBF, pFIBF)
    chemical name: N-(4-Fluorophenyl)-2-methyl-N-[1-(2-
phenylethyl)piperidin-4-yl]propanamide
--Tetrahydrofuranylfentanyl (THF-F)
    chemical name: N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-
yl]oxolane-2-carboxamide

    To be placed in Schedule II of the Convention on Psychotropic 
Substances (1971):

--AB-CHMINACA
    chemical name: N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-
(cyclohexylmethyl)-lH-indazole-3-carboxamide
--5F-ADB (5F-MDMB-PINACA)
    chemical name: Methyl (2S)-2-{[l-(5-fluoropentyl)-1H-indazole-3-
carbonyl] amino{time} -3,3-dimethylbutanoate
--AB-PINACA
    chemical name: N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-
pentyl-1H-indazole-3-carboxamide
--UR-144
    chemical name: (1-Pentyl-1H-indol-3-yl)(2,2,3,3-
tetramethylcyclopropyl)methanone
--5F-PB-22

[[Page 3744]]

    chemical name: Quinolin-8-yl 1-(5-fluoropentyl)-l H-indole-3-
carboxylate
--4-Fluoroamphetamine (4-FA)
    chemical name: 1-(4-Fluorophenyl)propan-2-amine
    In addition, the Expert Committee recommended to carry out a 
critical review at a subsequent Expert Committee meeting for:

--Preparations containing almost exclusively cannabidiol (CBD)
    chemical name: (1'R,2'R)-5'-Methyl-4-pentyl-2'-(prop-1-en-2-yl)-
1',2',3',4'-tetrahydro-[1,l'biphenyl]-2,6-diol
--Pregabalin
    chemical name: (3S)-3-(Aminomethyl)-5-methylhexanoic acid
--Tramadol
    chemical name: rac-(1R,2R)-2-[(Dimethylamino)methyl]-1-(3-
methoxyphenyl)cyclohexan-1-ol
    It also recommended that the following substance remain under 
surveillance:

--Etizolam (INN)
    chemical name: 4-(2-Chlorophenyl)-2-ethyl-9-methyl-6H-
thieno[3,2:/] [1,2,4]triazolo[4,3-a][1,4]diazepine

    The recommendations and the assessments and findings on which 
they are based are set out in detail in the Report of the 39th 
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.
    I would like to take this opportunity to inform you that the 
40th Expert Committee on Drug Dependence will take place in May 2018 
and will be specifically dedicated to the pre review of cannabis and 
its major components substances.''

Annex II

Extract From the Report of the 39th 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:

Carfentanil

    Chemically, carfentanil is Methyl 1-(2-phenylethyl)-4-
[phenyl(propionoyl)amino]piperidine-4-carboxylate. Carfentanil has 
no stereoisomers.
    Carfentanil has not been previously pre-reviewed or critically 
reviewed. A notification was received from a Party to the 
Conventions thus initiating a critical review.
    Carfentanil is convertible into sufentanil and alfentanil, two 
very potent opioid analgesics controlled as Schedule I drugs under 
the Single Convention on Narcotic Drugs of 1961. It is a [micro]-
opioid receptor agonist, and its pharmacodynamic and clinical 
effects are similar to fentanyl but it is about 100 times more 
potent. It binds to opioid receptors, and produces respiratory 
depression, decreased consciousness, antinociception, and miosis. 
The substance has been associated with hundreds of deaths and 
nonfatal intoxications globally, and it has created significant 
concerns in a number of countries. Due to the extremely small doses 
that induce lethal effects, it poses a particularly serious threat 
to public health.
    Carfentanil is a compound liable to similar abuse and with 
similar ill effects to controlled opioids such as fentanyl that are 
included in Schedule I of the Single Convention on Narcotic Drugs of 
1961. 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 carfentanil (Methyl 1-(2-phenylethyl)-4-
[phenyl(propionoyl)amino]piperidine-4-carboxylate) be placed in 
Schedule I of the Single Convention on Narcotic Drugs of 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 to drugs in Schedule I.
    The Committee considered and recognized the impact that 
international scheduling could have on veterinary access to 
carfentanil in relation to its therapeutic use in large animals. 
However, the Committee was particularly concerned regarding the 
extreme potency of the substance and serious risk to public health. 
The Committee felt that the therapeutic advantages did not offset 
the severe threat to human health. As such, and with consideration 
that substances in Schedule IV afford Parties the opportunity to 
adopt special measures for drugs with particularly dangerous 
properties, the Committee recommended that carfentanil (Methyl 1-(2-
phenylethyl)-4-[phenyl(propionoyl)amino]piperidine-4-carboxylate) be 
also placed in Schedule IV of the Single Convention on Narcotic 
Drugs of 1961.
    Substances recommended to be placed in Schedule I of the Single 
Convention on Narcotic Drugs (1961), as amended by the 1972 
Protocol:

Ocfentanil

    Chemically, ocfentanil is N-(2-Fluorophenyl)-2-methoxy-N-[1-(2-
phenylethyl)piperidin-4-yl]acetamide. It has no stereoisomers.
    Ocfentanil has not been previously pre-reviewed or critically 
reviewed. A direct critical review was proposed based on information 
brought to the attention of WHO that ocfentanil is clandestinely 
manufactured, poses a risk to public health and society, and has no 
recognized therapeutic use by any party.
    Ocfentanil is an opioid that is structurally related to fentanyl 
that is regulated under Schedule I of the Single Convention on 
Narcotic Drugs of 1961, and produces opioid effects including 
analgesia, euphoria, sedation, and potentially serious respiratory 
depression. Ocfentanil-related deaths have been reported, and it has 
come under national control in several countries in different 
regions of the world.
    Ocfentanil is a compound liable to similar abuse and with 
similar ill effects to controlled opioids such as fentanyl that are 
included in Schedule I of the Single Convention on Narcotic Drugs of 
1961. It has no recorded therapeutic use, and its use has been 
associated with 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 ocfentanil (N-(2-
Fluorophenyl)-2-methoxy-N-[1-(2-phenylethyl)piperidin-4-
yl]acetamide) be placed in Schedule I of the Single Convention on 
Narcotic Drugs of 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 to drugs in Schedule I.

Furanyl fentanyl

    Chemically, furanyl fentanyl is N-Phenyl-N-[1-(2-
phenylethyl)piperidin-4-yl]furan-2-carboxamide. Furanyl fentanyl has 
no stereoisomers.
    Furanyl fentanyl has not been previously pre-reviewed or 
critically reviewed. A direct critical review was proposed based on 
information brought to WHO's attention that furanyl fentanyl is 
clandestinely manufactured, of especially serious risk to public 
health and society, and of no recognized therapeutic use by any 
party.
    Furanyl fentanyl is a compound liable to similar abuse and with 
similar ill effects to controlled opioids such as fentanyl that are 
included in Schedule I of the Single Convention on Narcotic Drugs of 
1961. It has no recorded therapeutic use and its use has been 
associated with 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 furanyl fentanyl (N-Phenyl-N-
[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide) be placed in 
Schedule I of the Single Convention on Narcotic Drugs of 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 to drugs in Schedule I.

Acryloylfentanyl (Acryl fentanyl)

    Chemically, acryloylfentanyl is N-Phenyl-N-[1-(2-
phenylethyl)piperidin-4-yl]prop-2-enamide. It has no stereoisomers.
    Acryloylfentanyl has not been previously pre-reviewed or 
critically reviewed. A direct critical review was proposed based on 
information brought to WHO's attention that acryloylfentanyl is 
clandestinely manufactured, of especially serious risk to public 
health and society, and of no recognized therapeutic use by any 
party.
    Acryloylfentanyl is a compound liable to similar abuse and with 
similar ill effects to

[[Page 3745]]

controlled opioids such as fentanyl that are included in Schedule I 
of the Single Convention on Narcotic Drugs of 1961. It has no 
recorded therapeutic use, and its use has been associated with 
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 acryloylfentanyl (N-Phenyl-N-[1-
(2-phenylethyl)piperidin-4-yl]prop-2-enamide) be placed in Schedule 
I of the Single Convention on Narcotic Drugs of 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 to drugs in Schedule I.

4-Fluoroisobutyryl fentanyl (4-FIBF, pFIBF)

    Chemically, 4-fluoroisobutyryl fentanyl (4-FIBF, pFIBF) is N-(4-
Fluorophenyl)-2-methyl-N-[1-(2-phenylethyl)piperidin-4-
yl]propanamide.
    4-Fluoroisobutyryl fentanyl has not been previously pre-reviewed 
or critically reviewed. A direct critical review was proposed based 
on information brought to WHO's attention that it is clandestinely 
manufactured, of especially serious risk to public health and 
society, and of no recognized therapeutic use by any party.
    4-Fluoroisobutyryl fentanyl is a compound liable to similar 
abuse and with similar ill effects to controlled opioids such as 
fentanyl that are included in Schedule I of the Single Convention on 
Narcotic Drugs of 1961. It has no recorded therapeutic use, and its 
use has been associated with 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 4-
fluoroisobutyryl fentanyl (N-(4-Fluorophenyl)-2-methyl-N-[l-(2-
phenylethyl)piperidin-4-yl]propanamide) be placed in Schedule I of 
the Single Convention on Narcotic Drugs of 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 to drugs in Schedule I.

Tetrahydrofuranylfentanyl (THF-F)

    Chemically, tetrahydrofuranylfentanyl is N-Phenyl-N-[1-(2-
phenylethyl)piperidin-4-yl]oxolane-2-carboxamide. 
Tetrahydrofuranylfentanyl contains a stereogenic centre allowing for 
the existence of a pair of enantiomers, (S)-
tetrahydrofuranylfentanyl and (R)-tetrahydrofuranylfentanyl. There 
is no information on the actual enantiomers found on the illicit 
drug market at the time of the report.
    Tetrahydrofuranylfentanyl has not been previously pre-reviewed 
or critically reviewed. A direct critical review was proposed based 
on information brought to WHO's attention that 
tetrahydrofuranylfentanyl is clandestinely manufactured, of 
especially serious risk to public health and society, and of no 
recognized therapeutic use by any party.
    Tetrahydrofuranylfentanyl is a compound liable to similar abuse 
and with similar ill effects to controlled opioids such as fentanyl 
that are included in Schedule I of the Single Convention on Narcotic 
Drugs of 1961. It has no recorded therapeutic use, and its use has 
been associated with 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 
tetrahydrofuranylfentanyl (N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-
yl]oxolane-2-carboxamide) be placed in Schedule I of the Single 
Convention on Narcotic Drugs of 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 to drugs in 
Schedule I.
    Substances recommended to be scheduled in Schedule II of the 
Convention on Psychotropic Substances (1971):

AB-CHMINACA

    Chemically, AB-CHMINACA is N-[(2S)-l-Amino-3-methyl-1-oxobutan-
2-yl]-1-(cyclohexylmethyl)-lHindazole-3-carboxamide. AB-CHMINACA 
contains a chiral centre, so that two enantiomers exist: (R)-
ABCHMINACA and (S)-AB-CHMINACA. Based on the literature and the most 
likely precursors to be used in manufacture, an (S)-configuration of 
the stereocenter should be expected.
    AB-CHMINACA has not been previously pre-reviewed or critically 
reviewed. A direct critical review was proposed based on information 
brought to WHO's attention that AB-CHMINACA is clandestinely 
manufactured, of especially serious risk to public health and 
society, and of no recognized therapeutic use by any party.
    AB-CHMINACA is a synthetic cannabinoid receptor agonist. It is 
clandestinely manufactured and sold under a variety of brand names. 
Its mode of action suggests also the potential for dependence and 
likelihood of misuse. Effects of AB-CHMINACA are consistent with 
those of synthetic cannabinoid receptor agonists and include 
relaxation, euphoria, depersonalization, distorted perception of 
time, impaired motor performance, hallucinations, paranoia, 
confusion, fear, anxiety, tachycardia, and nausea and vomiting. Its 
cannabimimetic effects are more potent than those of THC, which is 
listed in Schedule II in the Convention on Psychotropic Substances 
of 1971. There is evidence of an increase in number of persons using 
AB-CHMINACA in many countries that have included fatal and non-fatal 
cases. This substance causes substantial harm and has no therapeutic 
usefulness. AB-CHMINACA has similar abuse and similar ill effects as 
other synthetic cannabinoids receptor agonists already scheduled in 
Schedule II of the Convention on Psychotropic Substances of 1971. 
The Committee recommended that AB-CHMINACA (N-[(2S)-l-Amino-3-
methyl-1-oxobutan-2-yl]-1-(cyclohexylmethyl)-1H-indazole-3-
carboxamide) be placed in Schedule II under the Convention on 
Psychotropic Substances of 1971.

5F-ADB/5F-MDMB-PINACA

    Chemically, 5F-ADB (also known as 5F-MDMB-PINACA) is Methyl 
(2S)-2-{[l-(5-fluoropentyl)-1Hindazole-3-carbonyl]amino{time} -3,3-
dimethylbutanoate. 5F-ADB contains a chiral centre, so that two 
enantiomers exist: (R)-5F-ADB and (S)-5F-ADB.
    5F-ADB has not been previously pre-reviewed or critically 
reviewed. A direct critical review was proposed based on information 
brought to WHO's attention that 5F-ADB is clandestinely 
manufactured, of especially serious risk to public health and 
society, and of no recognized therapeutic use by any party.
    5F-ADB is a synthetic cannabinoid receptor agonist. It has 
cannabimimetic effects that are more potent than those of THC and 
MDMB-CHMICA, substances which are listed in Schedule II of the 
Convention on Psychotropic Substances of 1971. Its mode of action 
suggests the potential for dependence and likelihood of abuse. There 
is evidence of an increase in number of persons using 5F-ADB in many 
countries that have included fatal and non-fatal cases. This 
substance causes substantial harm and has no therapeutic usefulness. 
The Committee recommended that 5F-ADB, also known as 5F-MDMB-PINACA, 
(Methyl (2S)-2-{[l-(5-fluoropentyl)-1H-indazole-3-
carbonyl]amino{time} -3,3-dimethylbutanoate) be placed in Schedule 
II under the Convention on Psychotropic Substances of 1971.

AB-PINACA

    Chemically, AB-PINACA is N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-
yl]-1-pentyl-1H-indazole-3-carboxamide. AB-PINACA has stereoisomers.
    AB-PINACA has not been previously pre-reviewed or critically 
reviewed. A direct critical review was proposed based on information 
brought to WHO's attention that AB-PINACA is clandestinely 
manufactured, of especially serious risk to public health and 
society, and of 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 AB-PINACA is 
substantial. Therapeutic usefulness has not been recorded. It 
recognized that AB-PINACA has similar abuse and similar ill-effects 
to other synthetic cannabinoids receptor agonists in Schedule II of 
the Convention on Psychotropic Substances of 1971. The Committee 
considered that there is sufficient evidence that AB-PINACA 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. The Committee recommended that ABPINACA (N-
[(2S)-l-Amino-3-methyl-1-oxobutan-2-yl]-1-pentyl-1H -indazole-3-
carboxamide) be placed in Schedule II under the Convention on 
Psychotropic Substances of 1971.

UR-144

    Chemically, UR-144 is (1-Pentyl-1H-indol-3-yl)(2,2,3,3-
tetramethylcyclopropyl)methanone. It has no stereoisomers.
    UR-144 was previously critically reviewed by the 36th ECDD in 
2014. The Committee

[[Page 3746]]

recommended that UR-144 not be placed under international control at 
that time but be kept under surveillance.
    Of particular significance to the Committee was the lack of 
analytically confirmed cases of non-fatal and fatal intoxications at 
the time involving solely UR-144. Subsequent data collected from the 
literature and from different countries indicating that this 
substance may cause substantial harm and that it has no medical use, 
warranted an updated critical review.
    The Committee considered that the degree of risk to public 
health and society associated with the abuse of UR-144 is 
substantial. Therapeutic usefulness has not been recorded. It 
recognized that UR-144 has similar abuse and similar ill-effects to 
other synthetic cannabinoids receptor agonists in Schedule II of the 
Convention on Psychotropic Substances of 1971. The Committee 
considered that there is sufficient evidence that UR-144 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. The Committee recommended that UR-144 ((1-
Pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone) be 
placed in Schedule II under the Convention on Psychotropic 
Substances of 1971.

5F-PB-22

    Chemically, 5F-PB-22 is Quinolin-8-yl 1-(5-fluoropentyl)-lH-
indole-3-carboxylate. It has no stereoisomers.
    5F-PB-22 has not been previously pre-reviewed or critically 
reviewed. A direct critical review was proposed based on information 
brought to WHO's attention that 5F-PB-22 is clandestinely 
manufactured, of especially serious risk to public health and 
society, and of 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-PB-22 is 
substantial. Therapeutic usefulness has not been recorded. It 
recognized that 5F-PB-22 has similar abuse and similar ill-effects 
to other synthetic cannabinoids receptor agonists in Schedule II of 
the Convention on Psychotropic Substances of 1971. The Committee 
considered that there is sufficient evidence that 5F-PB-22 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. The Committee recommended that 5F-PB-22 
(Quinolin-8-yl 1-(5-fluoropentyl)-l H-indole-3-carboxylate) be 
placed in Schedule II under the Convention on Psychotropic 
Substances of 1971.

4-Fluoroamphetamine (4-FA)

    The chemical name of 4-FA is 1-(4-Fluorophenyl)propan-2-amine. 
The presence of a chiral centre gives rise to the enantiomeric pair 
of (S)-4-FA and (R)-4-FA, respectively. 4-FA is most likely to be 
available as the racemic mixture.
    4-FA underwent a critical review in 2015. At that time, the 
committee recommended that 4-FA not be placed under international 
control due to insufficient evidence regarding dependence, abuse, 
and risks to public health. However, it was kept under surveillance. 
Preliminary information collected from various sources indicated 
that this substance may cause substantial harm and that it has no 
medical use, thereby warranting an updated critical review.
    4-FA is a ring-substituted derivative of amfetamine that is 
listed in Schedule II of the Convention on Psychotropic Substances 
of 1971. The clinical features associated with 4-FA intoxications 
include agitation, tachycardia, hypertension, hyperthermia, 
cardiovascular toxicity and cerebrovascular complications such as 
severe headaches and cerebral hemorrhage. Some severe adverse 
reactions required hospitalizations and others resulted in death.
    The Committee considered that the degree of risk to public 
health and society associated with the abuse of 4-FA is substantial. 
Therapeutic usefulness has not been recorded. It recognized that 4-
FA has similar abuse and similar ill-effects to substances in 
Schedule II of the Convention on Psychotropic Substances of 1971.
    The Committee considered that there is sufficient evidence that 
4-FA 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. The Committee recommended that 4-FA (1-
(4-Fluorophenyl)propan-2-amine) be placed in Schedule II under the 
Convention on Psychotropic Substances of 1971.
    Substances recommended for critical review:

Preparations Containing Almost Exclusively Cannabidiol (CBD)

    Chemically, cannabidiol is (l'R,2'R)-5'-Methyl-4-pentyl-2'-
(prop-1-en-2-yl)-l',2',3',4'-tetrahydro-[1,1'-biphenyl]-2,6-diol. 
Cannabidiol (CBD) is normally taken to refer to the naturally 
occurring (-)- enantiomer.
    Cannabidiol has not been previously pre-reviewed or critically 
reviewed by the Expert Committee on Drug Dependence (ECDD). The 
current review was based on the recommendation from the 38th ECDD 
that pre-review documentation on cannabis-related substances, 
including cannabidiol, be prepared and evaluated at a subsequent 
committee meeting.
    CBD is not specifically listed in the schedules of the 1961, 
1971 or 1988 International Drug Control Conventions. There is no 
evidence that CBD as a substance is liable to similar abuse and 
similar ill-effects as substances in the 1961 or 1971 Conventions 
(including cannabis and dronabinol (THC), respectively). The purpose 
of the pre-review was to determine whether current information 
justifies an Expert Committee critical review whereby the Committee 
finds that information may justify the scheduling or a change in the 
scheduling of the substance in the 1961 or 1971 Conventions. As CBD 
is not currently a scheduled substance in its own right (only as a 
component of cannabis extracts), current information does not 
justify a change in this scheduling position and does not justify 
scheduling of the substance.
    However, CBD is produced for pharmaceutical purposes as an 
extract of cannabis, and cannabis extracts and tinctures are 
included in the Single Convention on Narcotic Drugs of 1961. The 
pre-review of Cannabis Extracts and Tinctures will be held at the 
40th ECDD meeting in May 2018. Therefore it is also recommended that 
extracts or preparations containing almost exclusively CBD 
(cannabidiol; (l'R,2'R)-5' Methyl-4-pentyl-2'-(prop-1-en-2-yl)-
1',2',3',4'-tetrahydro-[1,l'-biphenyl]-2,6-diol) be subject to 
critical review at that meeting.

Pregabalin

    Chemically, pregabalin is (3S)-3-(Aminomethyl)-5-methylhexanoic 
acid. Pregabalin is the (S)-(+)-isomer of 3-isobutyl-GABA.
    Pregabalin has not been previously pre-reviewed or critically 
reviewed. A pre-review at the 39th ECDD was proposed based on 
information received by the WHO Secretariat regarding the misuse of 
pregabalin.
    Pregabalin, a gabapentinoid, is an analogue of gamma amino 
butyric acid (GABA), but does not act at GABA receptors or synapses 
or bind to benzodiazepine receptors. While pregabalin has 
therapeutic uses, the increasing evidence of its misuse and abuse in 
many countries is becoming a growing cause for concern.
    Pregabalin has been shown to have the capacity to produce a 
state of dependence. On this basis, the Committee recommended that 
pregabalin ((3S)-3-(Aminomethyl)-5-methylhexanoic acid) proceed to a 
future critical review. The Committee requested that the Secretariat 
collect further data to support the critical review.

Tramadol

    Chemically, tramadol is rac-(1R,2R)-2-[(Dimethylamino)methyl]-1-
(3-methoxyphenyl)cyclohexan-1-ol. Tramadol has two chiral centres 
and consequently, four different stereoisomers exist: (1R,2R), 
(1S,2S), (1R,2S), and (1S,2R).
    Pre-reviews of Tramadol have been carried out by the ECDD in 
1992, 2000, 2006, and 2014 and a critical review in 2002. The 
Committee most recently at its 36th meeting in 2014, and based on 
the evidence available regarding dependence, abuse and risks to 
public health, recommended that a critical review of tramadol was 
not warranted at that time. On the basis of information received by 
the WHO Secretariat regarding the misuse of tramadol, it was 
recommended that a pre-review of tramadol be carried out at the 39th 
ECDD in November 2017.
    Tramadol is used as a medication for controlling moderate acute 
and chronic painful conditions, and it is listed in several national 
essential medicines lists. It produces opioid-like effects 
predominately through the conversion of tramadol into its active 
metabolite. There is growing evidence of abuse of tramadol in many 
countries, accompanied by adverse reactions, and tramadol-associated 
deaths. The Committee recommended that tramadol ((rac-(1R,2R)-2-
[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol) proceed 
to a critical review at a subsequent meeting. The Committee 
requested the Secretariat to collect additional data for the 
critical review, including engagement with Member States to

[[Page 3747]]

obtain information on the extent of problems associated with 
tramadol misuse. Also, the Committee asked for information on the 
medical use of tramadol including the extent that low income 
countries, countries facing conflicts and aid and relief agencies 
use and possibly rely on tramadol for provision of analgesia.
    Substance recommended to remain under surveillance:

Etizolam (INN)

    Chemically, etizolam is 4-(2-Chlorophenyl)-2-ethyl-9-methyl-6H-
thieno[3,2-f][1,2,4]triazolo[4,3-a][l,4]diazepine. It does not have 
stereoisomers.
    The ECDD reviewed etizolam at the 26th meeting (1989) and the 
27th meeting (1990). At the 37th ECDD in 2015, the committee pre-
reviewed etizolam and recommended that a critical review of etizolam 
was warranted for a future meeting. The Committee noted deficiencies 
in information and suggested several potential sources that could be 
helpful in the preparation of the critical review, including those 
from traffic accident reports, seizure data, user forums, and 
pharmacovigilance data.
    Owing to the lack of significantly more information since the 
pre-review conducted by the 37th ECDD in 2015, and considering the 
current insufficiency of data regarding dependence, abuse and risks 
to public health, the Committee recommended that etizolam (4-(2-
Chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f] [1,2,4]triazolo[4,3-
a][l,4]diazepine) be kept under surveillance. The Committee asked 
the Secretariat to request more data from Member States that may be 
affected by the misuse of etizolam, and which could facilitate a 
future review.

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.
    Carfentanil, also known as 4-carbomethoxyfentanyl, is an extremely 
potent synthetic opioid that is similar in structure to and 
approximately 100 times more potent than fentanyl as an analgesic. At 
one time legitimately produced, carfentanil is no longer manufactured, 
marketed, or used in the United States; it is approved by FDA for use 
under restricted conditions by veterinarians as an immobilizing agent 
for certain large animals. Illicitly produced carfentanil is a 
particularly harmful fentanyl analogue that is also being laced into 
heroin or sold by itself and trafficked in the United States. It is not 
approved for human use. Drug seizure data indicate that carfentanil is 
typically used in small doses to cut heroin and other illicitly abused 
drugs. The significant risk to public health associated with 
carfentanil use stems from its respiratory depressive effects with very 
small amounts. Several fatalities have been reported as the result of 
carfentanil overdoses. On October 28, 1988, the Drug Enforcement 
Administration (DEA) published a Final Rule that placed carfentanil in 
Schedule II of the CSA (53 FR 43684). As such, no additional controls 
will be necessary to fulfill U.S. obligations if carfentanil is placed 
in Schedules I and IV of the Single Convention on Narcotic Drugs 
(1961).
    Ocfentanil is a synthetically produced opioid that is structurally 
related to fentanyl and approximately equipotent in effect. Reported 
risks associated with use of ocfentanil include development of opioid 
use disorder, overdose, and fatal overdose. It has no approved medical 
use in the United States. The DEA initiated the temporary placement of 
this substance under Schedule I by publishing a notification of intent 
in the Federal Register on December 13, 2017 (82 FR 58575). As such, 
additional controls will be necessary to fulfill U.S. obligations if 
ocfentanil is placed in Schedules I of the Single Convention on 
Narcotic Drugs (1961).
    Furanyl fentanyl (Fu-F) is a potent clandestinely produced 
synthetic opioid that is an analog of fentanyl. Evidence suggests that 
the pattern of abuse of fentanyl analogues, including furanyl fentanyl, 
parallels that of heroin and prescription opioid analgesics. Fu-F 
produces typical opioid effects that include respiratory depression and 
loss of consciousness. Seizures of Fu-F have been encountered in powder 
form. Fu-F has been connected to fatal overdoses, in which intravenous 
routes of administration are documented. It has no approved medical use 
in the United States. On November 29, 2016, the DEA issued a final 
order to temporarily schedule Fu-F and its isomers, esters, ethers, 
salts and salts of isomers, esters and ethers into Schedule I pursuant 
to the temporary scheduling provisions of the CSA (81 FR 85873). As 
such, additional permanent controls will be necessary to fulfill U.S. 
obligations if Fu-F is controlled under Schedule I of the 1961 Single 
Convention.
    Acryloylfentanyl (Acryl fentanyl) belongs to the 4-
anilidopiperidine class of synthetic opioids and is similar in 
structure to fentanyl. Acryloylfentanyl is a clandestinely produced 
analog of fentanyl and sold illegally as a research chemical on several 
websites. Acryloylfentanyl has also been associated with adverse events 
typically associated with opioid use such as respiratory depression, 
anxiety, constipation, tiredness, hallucinations, and withdrawal. The 
use of acryloylfentanyl has also been linked to the development of 
opioid use disorder, overdose, and fatal overdose.
    Acryloylfentanyl has no commercial or medical uses. On July 14, 
2017, the DEA issued a temporary order to temporarily schedule 
acryloylfentanyl, its isomers, esters, ethers, salts and salts of 
isomers, esters and ethers into Schedule I pursuant to the temporary 
scheduling provisions of the CSA (82 FR 32453). As such, additional 
permanent controls will be necessary to fulfill U.S. obligations if Fu-
F is controlled under Schedule I of the 1961 Single Convention.
    4-fluoroisobutyryl fentanyl (4-FIBF) is a clandestinely produced 
synthetic opioid that is an analog of fentanyl. It has m-receptor 
agonist activity similar to that of fentanyl. This would result in 
effects associated with opioid agonists such as analgesia, respiratory 
depression, anxiety, constipation, tiredness, hallucinations, 
withdrawal, development of opioid use disorder, overdose, and fatal 
overdose. The use of 4-FIBF has been implicated in several cases of 
overdose and fatal overdoses. 4-FIBF has not been approved for medical 
use in the United States. On May 3, 2017, the DEA issued a temporary 
order to temporarily schedule 4-FIBF, its isomers, esters, ethers, 
salts and salts of isomers, esters and ethers into Schedule I pursuant 
to the temporary scheduling provisions of the CSA (82 FR 20544). As 
such, additional permanent controls will be necessary to fulfill U.S. 
obligations if 4-FIBF is controlled under Schedule I of the 1961 Single 
Convention.
    AB-CHMINACA is a clandestinely produced synthetic cannabinoid 
agonist that is approximately 16 times more potent than delta-9-
tetrahydrocannabinol. Adverse effects produced by cannabinoid agonists 
include tachycardia, agitation, hallucination, chest pain, seizure, 
organ failure, anxiety, acute psychosis, and death. AB-CHMINACA has 
been detected in illicit synthetic cannabinoid substances and found in 
cases of overdose and hospitalizations. On October 16, 2017, the DEA 
published a Final Rule to permanently control AB-CHMINACA as a Schedule 
I substance under the CSA (82 FR 47971). As such, additional permanent 
controls will be not necessary to fulfill U.S. obligations if AB-
CHMINACA is controlled under

[[Page 3748]]

Schedule I of the 1961 Single Convention.
    5F-ADB is a clandestinely produced synthetic cannabinoid agonist. 
In general, adverse effects produced by cannabinoid agonists include 
tachycardia, agitation, hallucination, chest pain, seizure, anxiety, 
and acute psychosis. 5F-ADB has been identified in overdose and/or 
cases involving death attributed to their abuse. Adverse health effects 
reported from incidents involving 5F-ADB and other synthetic 
cannabinoids have included: nausea, persistent vomiting, agitation, 
altered mental status, seizures, convulsions, loss of consciousness, 
and/or cardio toxicity. On April 10, 2017, the DEA issued a temporary 
scheduling order to temporarily schedule 5F-ADB, its isomers, esters, 
ethers, salts and salts of isomers, esters, and ethers into Schedule I 
pursuant to the temporary scheduling provisions of the CSA (82 FR 
17119). As such, additional permanent controls will be necessary to 
fulfill U.S. obligations if 5F-ADB is controlled under Schedule II of 
the 1971 Convention on Psychotropic Substances.
    AB-PINACA is a clandestinely produced synthetic cannabinoid agonist 
approximately 1.5 times as potent as delta-9-tetrahydrocannabinol. 
Adverse effects produced by cannabinoid agonists include tachycardia, 
agitation, hallucination, chest pain, seizure, anxiety, acute 
psychosis, and death. AB-PINACA has been detected in illicit synthetic 
cannabinoid substances, and reported in cases of overdose and 
hospitalizations. It has not been approved for medical use in the 
United States. On October 16, 2017, the DEA published a Final Rule to 
permanently control AB-PINACA as a Schedule I substance under the CSA 
(82 FR 47971). As such, additional permanent controls will not be 
necessary to fulfill U.S. obligations if AB-PINACA is controlled under 
Schedule II of the 1971 Convention on Psychotropic Substances.
    UR-144 is a clandestinely produced synthetic cannabinoid agonist. 
In general, adverse effects produced by cannabinoid agonists include 
tachycardia, agitation, hallucination, chest pain, seizure, anxiety, 
acute psychosis, and death. UR-144 has been detected in herbal smoking 
blends that are sold as herbal incense. On May 11, 2016, the DEA issued 
a Final Rule to permanently schedule UR-144 into Schedule I of the CSA 
(81 FR 29142). As such, additional permanent controls will not be 
necessary to fulfill U.S. obligations if UR-144 is controlled under 
Schedule II of the 1971 Convention on Psychotropic Substances.
    5F-PB-22 is a synthetic cannabinoid agonist with similar effects to 
delta-9-tetrahydrocannabinol, one of the main psychoactive components 
of cannabis. Adverse effects produced by cannabinoid agonists include 
tachycardia, agitation, hallucination, chest pain, seizure, anxiety, 
acute psychosis, and death. 5F-PB-22 is clandestinely produced. It has 
been found laced on plant material and marketed as herbal products, and 
is smoked for its psychoactive effects. According to the WHO, 5F-PB-22 
has been associated with fatal intoxications. On September 6, 2016, the 
DEA issued a Final Rule to permanently place 5F-PB-22 into Schedule I 
of the CSA (81 FR 61130). As such, additional permanent controls will 
not be necessary to fulfill U.S. obligations if 5F-PB-22 is controlled 
under Schedule II of the 1971 Convention on Psychotropic Substances.
    4-Fluoroamphetamine (4-FA) is a psychoactive substance of the 
phenethylamine and substituted amphetamine chemical classes and 
produces stimulant effects. WHO reports that 4-FA is clandestinely 
produced, and its use is associated with fatal and non-fatal 
intoxications. 4-FA is not approved for medical use in the United 
States and it is not controlled under the CSA. As such, additional 
permanent controls will be necessary to fulfill U.S. obligations if 4-
FA 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 2018.
    Comments regarding the WHO recommendations for control of 
carfentanil, ocfentanil, furanyl fentanyl (Fu-F), acryloylfentanyl 
(acryl fentanyl), 4-fluoroisobutyryl fentanyl (4-FIBF), and 
tetrahydrofuranylfentanyl (THF-F), 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.

    Dated: January 23, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-01471 Filed 1-25-18; 8:45 am]
 BILLING CODE 4164-01-P
Federal Register / Vol. 83, No. 18 / Friday, January 26, 2018 / Notices 3747

obtain information on the extent of problems and trafficked in the United States. It is chemical on several websites.
associated with tramadol misuse. Also, the not approved for human use. Drug Acryloylfentanyl has also been
Committee asked for information on the seizure data indicate that carfentanil is associated with adverse events typically
medical use of tramadol including the extent typically used in small doses to cut associated with opioid use such as
that low income countries, countries facing
conflicts and aid and relief agencies use and heroin and other illicitly abused drugs. respiratory depression, anxiety,
possibly rely on tramadol for provision of The significant risk to public health constipation, tiredness, hallucinations,
analgesia. associated with carfentanil use stems and withdrawal. The use of
Substance recommended to remain under from its respiratory depressive effects acryloylfentanyl has also been linked to
surveillance: with very small amounts. Several the development of opioid use disorder,
Etizolam (INN) fatalities have been reported as the overdose, and fatal overdose.
result of carfentanil overdoses. On Acryloylfentanyl has no commercial
Chemically, etizolam is 4-(2- or medical uses. On July 14, 2017, the
October 28, 1988, the Drug Enforcement
Chlorophenyl)-2-ethyl-9-methyl-6H-
Administration (DEA) published a Final DEA issued a temporary order to
thieno[3,2-f][1,2,4]triazolo[4,3-
a][l,4]diazepine. It does not have Rule that placed carfentanil in Schedule temporarily schedule acryloylfentanyl,
stereoisomers. II of the CSA (53 FR 43684). As such, its isomers, esters, ethers, salts and salts
The ECDD reviewed etizolam at the 26th no additional controls will be necessary of isomers, esters and ethers into
meeting (1989) and the 27th meeting (1990). to fulfill U.S. obligations if carfentanil is Schedule I pursuant to the temporary
At the 37th ECDD in 2015, the committee placed in Schedules I and IV of the scheduling provisions of the CSA (82 FR
pre-reviewed etizolam and recommended Single Convention on Narcotic Drugs 32453). As such, additional permanent
that a critical review of etizolam was (1961). controls will be necessary to fulfill U.S.
warranted for a future meeting. The Ocfentanil is a synthetically produced obligations if Fu-F is controlled under
Committee noted deficiencies in information
and suggested several potential sources that
opioid that is structurally related to Schedule I of the 1961 Single
could be helpful in the preparation of the fentanyl and approximately equipotent Convention.
critical review, including those from traffic in effect. Reported risks associated with 4-fluoroisobutyryl fentanyl (4–FIBF)
accident reports, seizure data, user forums, use of ocfentanil include development is a clandestinely produced synthetic
and pharmacovigilance data. of opioid use disorder, overdose, and opioid that is an analog of fentanyl. It
Owing to the lack of significantly more fatal overdose. It has no approved has m-receptor agonist activity similar
information since the pre-review conducted medical use in the United States. The to that of fentanyl. This would result in
by the 37th ECDD in 2015, and considering DEA initiated the temporary placement effects associated with opioid agonists
the current insufficiency of data regarding of this substance under Schedule I by such as analgesia, respiratory
dependence, abuse and risks to public health, publishing a notification of intent in the depression, anxiety, constipation,
the Committee recommended that etizolam tiredness, hallucinations, withdrawal,
(4-(2-Chlorophenyl)-2-ethyl-9-methyl-6H-
Federal Register on December 13, 2017
thieno[3,2-f] [1,2,4]triazolo[4,3- (82 FR 58575). As such, additional development of opioid use disorder,
a][l,4]diazepine) be kept under surveillance. controls will be necessary to fulfill U.S. overdose, and fatal overdose. The use of
The Committee asked the Secretariat to obligations if ocfentanil is placed in 4–FIBF has been implicated in several
request more data from Member States that Schedules I of the Single Convention on cases of overdose and fatal overdoses.
may be affected by the misuse of etizolam, Narcotic Drugs (1961). 4–FIBF has not been approved for
and which could facilitate a future review. Furanyl fentanyl (Fu-F) is a potent medical use in the United States. On
clandestinely produced synthetic opioid May 3, 2017, the DEA issued a
III. Discussion
that is an analog of fentanyl. Evidence temporary order to temporarily schedule
Although WHO has made specific suggests that the pattern of abuse of 4–FIBF, its isomers, esters, ethers, salts
scheduling recommendations for each of fentanyl analogues, including furanyl and salts of isomers, esters and ethers
the drug substances, the CND is not fentanyl, parallels that of heroin and into Schedule I pursuant to the
obliged to follow the WHO prescription opioid analgesics. Fu-F temporary scheduling provisions of the
recommendations. Options available to produces typical opioid effects that CSA (82 FR 20544). As such, additional
the CND for substances considered for include respiratory depression and loss permanent controls will be necessary to
control under the Psychotropic of consciousness. Seizures of Fu-F have fulfill U.S. obligations if 4–FIBF is
Convention include the following: (1) been encountered in powder form. Fu- controlled under Schedule I of the 1961
Accept the WHO recommendations; (2) F has been connected to fatal overdoses, Single Convention.
accept the recommendations to control, in which intravenous routes of AB–CHMINACA is a clandestinely
but control the drug substance in a administration are documented. It has produced synthetic cannabinoid agonist
schedule other than that recommended; no approved medical use in the United that is approximately 16 times more
or (3) reject the recommendations States. On November 29, 2016, the DEA potent than delta-9-
entirely. issued a final order to temporarily tetrahydrocannabinol. Adverse effects
Carfentanil, also known as 4- schedule Fu-F and its isomers, esters, produced by cannabinoid agonists
carbomethoxyfentanyl, is an extremely ethers, salts and salts of isomers, esters include tachycardia, agitation,
potent synthetic opioid that is similar in and ethers into Schedule I pursuant to hallucination, chest pain, seizure, organ
structure to and approximately 100 the temporary scheduling provisions of failure, anxiety, acute psychosis, and
times more potent than fentanyl as an the CSA (81 FR 85873). As such, death. AB–CHMINACA has been
analgesic. At one time legitimately additional permanent controls will be detected in illicit synthetic cannabinoid
produced, carfentanil is no longer necessary to fulfill U.S. obligations if substances and found in cases of
manufactured, marketed, or used in the Fu-F is controlled under Schedule I of overdose and hospitalizations. On
daltland on DSKBBV9HB2PROD with NOTICES

United States; it is approved by FDA for the 1961 Single Convention. October 16, 2017, the DEA published a
use under restricted conditions by Acryloylfentanyl (Acryl fentanyl) Final Rule to permanently control AB–
veterinarians as an immobilizing agent belongs to the 4-anilidopiperidine class CHMINACA as a Schedule I substance
for certain large animals. Illicitly of synthetic opioids and is similar in under the CSA (82 FR 47971). As such,
produced carfentanil is a particularly structure to fentanyl. Acryloylfentanyl additional permanent controls will be
harmful fentanyl analogue that is also is a clandestinely produced analog of not necessary to fulfill U.S. obligations
being laced into heroin or sold by itself fentanyl and sold illegally as a research if AB–CHMINACA is controlled under

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Document Created: 2018-10-26 10:05:18
Document Modified: 2018-10-26 10:05:18
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; request for comments.
Dates		Submit either electronic or written comments by February 26, 2018.
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		83 FR 3741
83 FR 3741 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization; Scheduling Recommendations; Carfentanil;4-fluoroamphetamine (4-FA) and Ten Other Substances; Request for Comments

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 83, Issue 18 (January 26, 2018)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
