Federal Register, Volume 80 Issue 93 (Thursday, May 14, 2015)

[Federal Register Volume 80, Number 93 (Thursday, May 14, 2015)]
[Proposed Rules]
[Pages 27611-27616]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-11762]

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-417N]

Schedules of Controlled Substances: Placement of UR-144, XLR11,
and AKB48 Into Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration (DEA) proposes placing (1-
pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (UR-
144), [1-(5-fluoro-pentyl)-1H-indol-3-yl](2,2,3,3-
tetramethylcyclopropyl)methanone (5-fluoro-UR-144, XLR11), and N-(1-
adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA, AKB48)
including their salts, isomers, and salts of isomers whenever the
existence of such salts, isomers, and salts of isomers is possible,
into schedule I of the Controlled Substances Act. This proposed
scheduling action is pursuant to the Controlled Substance Act which
requires that such actions be made on the record after opportunity for
a hearing through formal rulemaking. If finalized, this action would
impose the regulatory controls and administrative, civil, and criminal
sanctions applicable to schedule I controlled substances on persons who
handle (manufacture, distribute, import, export, engage in research,
conduct instructional activities, or possess), or propose to handle UR-
144, XLR11, or AKB48.

DATES: Interested persons may file written comments on this proposal in
accordance with 21 CFR 1308.43(g). Electronic comments must be
submitted, and written comments must be postmarked, on or before June
15, 2015. Commenters should be aware that the electronic Federal Docket
Management System will not accept comments after 11:59 p.m. Eastern
Time on the last day of the comment period.
Interested persons, defined at 21 CFR 1300.01 as those ``adversely
affected or aggrieved by any rule or proposed rule issuable pursuant to
section 201 of the Act (21 U.S.C. 811),'' may file a request for
hearing, notice of appearance, or waiver of hearing pursuant to 21 CFR
1308.44 and in accordance with 21 CFR 1316.45, 1316.47, 1316.48, or
1316.49, as applicable. Requests for hearing, notices of appearance,
and waivers of an opportunity for a hearing or to participate in a
hearing must be received on or before June 15, 2015.

ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-417N'' on all correspondence, including any
attachments.
Electronic comments: The Drug Enforcement Administration
encourages that all comments be submitted electronically through the
Federal eRulemaking Portal, which provides the ability to type short
comments directly into the comment field on the Web page or to attach a
file for lengthier comments. Please go to http://www.regulations.gov
and follow the online instructions at that site for submitting
comments. Upon completion of your submission you will receive a Comment
Tracking Number for your comment. Please be aware that submitted
comments are not instantaneously available for public view on
Regulations.gov. If you have received a Comment Tracking Number, your
comment has been successfully submitted and there is no need to
resubmit the same comment.
Paper comments: Paper comments that duplicate the
electronic submission are not necessary and are discouraged. Should you
wish to mail a paper comment in lieu of an electronic comment, it
should be sent via regular or express mail to: Drug Enforcement
Administration, Attn: DEA Federal Register Representative/ODXL, 8701
Morrissette Drive, Springfield, Virginia 22152.
Hearing requests: All requests for hearing and waivers of
participation must be sent to: Drug Enforcement Administration, Attn:
Federal Register Representative/ODL, 8701 Morrissette Drive,
Springfield, Virginia 22152. All requests for hearing and waivers of
participation should also be sent to: Drug Enforcement Administration,
Attn: Hearing Clerk/LJ, 8701 Morrissette Drive, Springfield, Virginia
22152.

FOR FURTHER INFORMATION CONTACT: John R. Scherbenske, Office of
Diversion Control, Drug Enforcement Administration; Mailing Address:
8701 Morrissette Drive, Springfield, Virginia 22152; Telephone: (202)
598-6812.

SUPPLEMENTARY INFORMATION:

Posting of Public Comments

Please note that all comments received are considered part of the
public record. They will, unless reasonable cause is given, be made
available by the Drug Enforcement Administration (DEA) for public
inspection online at http://www.regulations.gov. Such information
includes personal identifying information (such as your name, address,
etc.) voluntarily submitted by the commenter. The Freedom of
Information Act (FOIA) applies to all comments received. If you want to
submit personal identifying information (such as your name, address,
etc.) as part of your comment, but do not want it to be made publicly
available, you must include the phrase ``PERSONAL IDENTIFYING
INFORMATION'' in the first paragraph of your comment. You must also
place all of the personal identifying information you do not want made
publicly available in the first paragraph of your comment and identify
what information you want redacted.
If you want to submit confidential business information as part of
your comment, but do not want it to be made publicly available, you
must include the phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the
first paragraph of your comment. You must also prominently identify
confidential business information to be redacted within the comment.
Comments containing personal identifying information and
confidential business information identified as directed above will
generally be made publicly available in redacted form. If a comment has
so much confidential business information or personal identifying
information that it cannot be effectively redacted, all or part of that
comment may not be made publicly available. Comments posted to http://www.regulations.gov may include any personal identifying information
(such as name, address, and phone number) included in the text of your
electronic submission that is not identified as directed above as
confidential.
An electronic copy of this document and supplemental information to
this proposed rule are available at http://www.regulations.gov for easy
reference.

[[Page 27612]]

Request for Hearing, Notice of Appearance at Hearing, Waiver of an
Opportunity for a Hearing or To Participate in a Hearing

Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking
``on the record after opportunity for a hearing.'' Such proceedings are
conducted pursuant to the provisions of the Administrative Procedure
Act (APA), 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316,
subpart D. In accordance with 21 CFR 1308.44 (a)-(c), requests for
hearing, notices of appearance, and waivers of an opportunity for a
hearing or to participate in a hearing may be submitted only by
interested persons, defined as those ``adversely affected or aggrieved
by any rule or proposed rule issuable pursuant to section 201 of the
Act (21 U.S.C. 811).'' 21 CFR 1300.01. Such requests or notices must
conform to the requirements of 21 CFR 1308.44 (a) or (b), and 1316.47
or 1316.48, as applicable, and include a statement of interest of the
person in the proceeding and the objections or issues, if any,
concerning which the person desires to be heard. Any waiver must
conform to the requirements of 21 CFR 1308.44(c) and 1316.49, including
a written statement regarding the interested person's position on the
matters of fact and law involved in any hearing.
Please note that pursuant to 21 U.S.C. 811(a), the purpose and
subject matter of a hearing is restricted to: ``find[ing] that such
drug or other substance has a potential for abuse, and . . . mak[ing]
with respect to such drug or other substance the findings prescribed by
subsection (b) of section 812 of this title for the schedule in which
such drug is to be placed . . .'' All requests for hearing and waivers
of participation must be sent to the DEA using the address information
provided above.

Legal Authority

The DEA implements and enforces Titles II and III of the
Comprehensive Drug Abuse Prevention and Control Act of 1970, as
amended. 21 U.S.C. 801-971. Titles II and III are referred to as the
``Controlled Substances Act'' and the ``Controlled Substances Import
and Export Act,'' respectively, and are collectively referred to as the
``Controlled Substances Act'' or the ``CSA'' for the purposes of this
action. 21 U.S.C. 801-971. The DEA publishes the implementing
regulations for these statutes in title 21 of the Code of Federal
Regulations (CFR), chapter II. The CSA and its implementing regulations
are designed to prevent, detect, and eliminate the diversion of
controlled substances and listed chemicals into the illicit market
while providing for the legitimate medical, scientific, research, and
industrial needs of the United States. Controlled substances have the
potential for abuse and dependence and are controlled to protect the
public health and safety.
Under the CSA, each controlled substance is classified into one of
five schedules based upon its potential for abuse, its currently
accepted medical use in treatment in the United States, and the degree
of dependence the substance may cause. 21 U.S.C. 812. The initial
schedules of controlled substances established by Congress are found at
21 U.S.C. 812(c) and the current list of scheduled substances is
published at 21 CFR part 1308. 21 U.S.C. 812(a).
Pursuant to 21 U.S.C. 811(a)(1), the Attorney General may, by rule,
``add to such a schedule or transfer between such schedules any drug or
other substance if he . . . finds that such drug or other substance has
a potential for abuse, and . . . makes with respect to such drug or
other substance the findings prescribed by subsection (b) of section
812 of this title for the schedule in which such drug is to be placed .
. . .'' The Attorney General has delegated scheduling authority under
21 U.S.C. 811 to the Administrator of the DEA. 28 CFR 0.100.
The CSA provides that proceedings for the issuance, amendment, or
repeal of the scheduling of any drug or other substance may be
initiated by the Attorney General (1) on her own motion; (2) at the
request of the Secretary of the Department of Health and Human Services
(HHS),\1\ or (3) on the petition of any interested party. 21 U.S.C.
811(a). This proposed action is supported by a recommendation from the
Assistant Secretary of the HHS and an evaluation of all other relevant
data by the DEA. If finalized, this action would impose the regulatory
controls and administrative, civil, and criminal sanctions of schedule
I controlled substances on any person who handles, or proposes to
handle, UR-144, XLR11, or AKB48.
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\1\ As discussed in a memorandum of understanding entered into
by the Food and Drug Administration (FDA) and the National Institute
on Drug Abuse (NIDA), the FDA acts as the lead agency within the HHS
in carrying out the Secretary's scheduling responsibilities under
the CSA, with the concurrence of NIDA. 50 FR 9518, Mar. 8, 1985. The
Secretary of the HHS has delegated to the Assistant Secretary for
Health of the HHS the authority to make domestic drug scheduling
recommendations. 58 FR 35460, July 1, 1993.
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Background

On April 12, 2013, the Deputy Administrator of the DEA published a
Notice of Intent to temporarily place (1-pentyl-1H-indol-3-yl)(2,2,3,3-
tetramethylcyclopropyl)methanone (UR-144), [1-(5-fluoro-pentyl)-1H-
indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (5-fluoro-UR-144,
XLR11), and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide
(APINACA, AKB48) into schedule I pursuant to the temporary scheduling
provisions of the CSA (78 FR 21858). On May 16, 2013, the Deputy
Administrator of the DEA published a Final Order in the Federal
Register (78 FR 28735) amending 21 CFR 1308.11(h) to temporarily place
these three synthetic cannabinoids into schedule I of the CSA pursuant
to the temporary scheduling provisions of 21 U.S.C. 811(h). That Final
Order, which became effective on the date of publication, was based on
findings by the Deputy Administrator of the DEA that the temporary
scheduling of these three synthetic cannabinoids was necessary to avoid
an imminent hazard to the public safety pursuant to 21 U.S.C.
811(h)(1). At the time the Final Order took effect, Section 201(h)(2)
of the CSA (21 U.S.C. 811(h)(2)) required that the temporary scheduling
of a substance expire at the end of two years from the date of issuance
of the scheduling order, and it provided that, during the pendency of
proceedings under 21 U.S.C. 811(a)(1) with respect to the substance,
temporary scheduling of that substance could be extended for up to 1
year. Pursuant to 21 U.S.C. 811(h)(2), the temporary scheduling of UR-
144, XLR11, and AKB48 expires on May 15, 2015, unless extended. An
extension of the temporary order is being ordered by the DEA
Administrator in a separate action.
As described in the Final Order published on May 16, 2013, UR-144,
XLR11, and AKB48 are synthetic cannabinoids that are pharmacologically
similar to delta 9-tetrahydrocannabinol ([Delta] \9\-THC) and JWH-018.
While UR-144, XLR11, and AKB48 have been used as research chemicals
and/or studied due to their misuse and abuse, based on the review of
the scientific literature, there are no known medical uses for UR-144,
XLR11, and AKB48. The Assistant Secretary of Health for the HHS has
advised that there are no exemptions or approvals in effect for UR-144,
XLR11, and AKB48 under section 505 (21 U.S.C. 355) of the Federal Food,
Drug and Cosmetic Act (FD&C Act). As stated by the HHS, UR-144, XLR11,
and AKB48 have no known accepted medical use. They are not the

[[Page 27613]]

subject of any approved new drug applications (NDA) or investigational
new drug applications (IND), and are not currently marketed as approved
drug products.

Proposed Determination to Schedule UR-144, XLR11, and AKB48

Pursuant to 21 U.S.C. 811(a)(1), proceedings to add a drug or
substance to those controlled under the CSA may be initiated by the
Attorney General, or her delegate, the DEA Administrator. On August 31,
2013, the DEA requested a scientific and medical evaluation and
scheduling recommendation from the Assistant Secretary of Health for
the HHS for UR-144, XLR11, and AKB48 pursuant to 21 U.S.C. 811(b). Upon
receipt of the scientific and medical evaluation and scheduling
recommendations from the HHS, the DEA reviewed the documents and all
other relevant data, and conducted its own eight-factor analysis of the
abuse potential of UR-144, XLR11, and AKB48 pursuant to 21 U.S.C.
811(c).
Included below is a brief summary of each of the eight factors as
analyzed by the HHS and the DEA, and as considered by the DEA in this
proposed action. Please note that both the DEA and the HHS analyses are
available under ``Supporting and Related Material'' of the public
docket for this proposed rule at http://www.regulations.gov under
docket number DEA-417N.
1. The Drug's Actual or Relative Potential for Abuse: As described
by the HHS, the abuse potential of UR-144, XLR11, and AKB48 is
associated with their ability to evoke pharmacological effects similar
to those evoked by other schedule I substances that have a high
potential for abuse such as [Delta] \9\-THC and JWH-018.
The legislative history of the CSA suggests the DEA consider the
following factors when determining whether a particular drug or
substance has a potential for abuse: \2\
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\2\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); 1970 U.S.C.C.A.N.
4566, 4601.

(1) There is evidence that individuals are taking the drug or
drugs containing such a substance in amounts sufficient to create a
hazard to their health or to the safety of other individuals or to
the community;
(2) There is significant diversion of the drug or drugs
containing such a substance from legitimate drug channels;
(3) Individuals are taking the drug or drugs containing such a
substance on their own initiative rather than on the basis of
medical advice from a practitioner licensed by law to administer
such drugs in the course of his professional practice; or
(4) The drug or drugs containing such a substance are new drugs
so related in their action to a drug or drugs already listed as
having a potential for abuse to make it likely that the drug will
have the same potentiality for abuse as such drugs, thus making it
reasonable to assume that there may be significant diversions from
legitimate channels, significant use contrary to or without medical
advice, or that it has a substantial capability of creating hazards
to the health of the user or to the safety of the community.

The substances UR-144, XLR11, and AKB48 share pharmacological
properties with schedule I substances, including [Delta] \9\-THC and
JWH-018. Evaluations in animal models, specifically in drug
discrimination studies, have demonstrated that cyclopropoylindoles
(such as UR-144 and XLR11) and indazole-3-carboximides (such as AKB48)
produce [Delta] \9\-THC-like discriminative stimulus effects. There
have also been numerous anecdotal self-reports substantiating that
these substances and their products are abused by humans for their
hallucinogenic effects, as well as published reports indicating an
increase in the abuse of these substances. State public health
departments and poison control centers have issued warnings in response
to adverse health effects associated with herbal incense products
containing synthetic cannabinoids which include: tachycardia, elevated
blood pressure, unconsciousness, tremors, seizures, vomiting,
hallucinations, agitation, anxiety, pallor, numbness, and tingling.
Numerous public health and poison control centers have issued warnings
regarding the abuse of synthetic cannabinoids and their associated
products. Law enforcement has also encountered incidents of exposure,
primarily in response to the smoking of products purported to be laced
with these substances.
2. Scientific Evidence of the Drug's Pharmacological Effects, If
Known: As described by the HHS, UR-144, XLR11, and AKB48 have all been
shown to bind to the cannabinoid 1 (CB1) receptor, act as agonists at
the CB1 receptor, and substitute fully for the discriminative stimulus
effects of [Delta] \9\-THC in the drug discrimination assay. To date,
no human pharmacological studies involving UR-144, XLR11, or AKB48 have
been reported.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: Synthetic cannabinoids emerged in the early 1980s.
They were originally designed to investigate structure activity
relationships (SAR) based on the potent substance, 9-nor-9[beta]-
hydroxyhexahydrocannabinol (HHC). Interest in the various structural
classes was generated by the mouse vas deferens (MVD) and prostaglandin
synthetase activity of pravadoline and subsequent findings of affinity
to the cannabinoid receptor.
The emergence of synthetic cannabinoids in the designer drug market
can be traced back to the initial forensic laboratory confirmation in
December 2008 at a forensic laboratory in Frankfurt, Germany that
announced the identification of JWH-018 in samples of herbal incense,
and others shortly thereafter. UR-144 and XLR11 are classified as
cyclopropoylindoles whereas AKB48 is classified as an indazole-3-
carboximide. While UR-144 was first developed as a research tool by
Abbott Laboratories, XLR11 and AKB48 were not designed for use in the
laboratory and began showing up in drug seizures in 2011.
The DEA is not aware of any currently accepted medical use or NDAs
for UR-144, XLR11, or AKB48. A letter dated February 14, 2013, was sent
from the DEA Deputy Administrator to the Assistant Secretary for the
HHS as notification of intent to temporarily place these three
substances into schedule I and solicit comments, including whether
there was an exemption or if an approval was in effect for the
substances in question under the FD&C Act. The Assistant Secretary of
HHS responded that there were no current INDs or NDAs for these
synthetic cannabinoids in a letter addressed to the DEA Deputy
Administrator dated March 14, 2013. In their recent scheduling
recommendation, the HHS reiterated that UR-144, XLR11, and AKB48 have
no known accepted medical use, are not the subject of any approved NDAs
or INDs, and are not currently marketed as any approved drug products.
4. Its History and Current Pattern of Abuse: Synthetic cannabinoids
were first reported in the United States in a December 2008 encounter,
where a shipment of ``Spice'' was seized and analyzed by U.S. Customs
and Border Protection in Dayton, Ohio. Additionally, around the same
time, in December 2008, JWH-018 and cannabicyclohexanol were being
identified by German forensic laboratories. Though these substances
were identified in 2008, these substances likely existed and were
abused some time prior to their identification.
Since the initial identification of JWH-018 in December 2008, many
additional synthetic cannabinoids have been found laced on designer
drug products abused for their psychoactive

[[Page 27614]]

effects. The popularity of synthetic cannabinoids has increased
tremendously since January 2010 in the United States based on seizure
exhibits and media reports. This trend is similar and consistent with
the increased popularity of synthetic cannabinoids in Europe since
2008. Synthetic cannabinoids are being encountered in most regions of
the United States with the substances found as adulterants on plant
material or being abused alone as self-reported on internet discussion
boards.
Data gathered from published studies, supplemented by internet
discussion Web sites, and personal communications demonstrate that
these products are being abused mainly by smoking for their
psychoactive properties and are marketed as ``legal'' alternatives to
marijuana. This characterization and their reputation as potent herbal
intoxicants increased their popularity. These substances alone or laced
on plant material have the potential to be extremely harmful due to
their method of manufacture and the potency of the substances. Smoking
mixtures of these substances for the purpose of achieving intoxication
has resulted in numerous emergency room visits and calls to poison
control centers. Numerous states, local jurisdictions, and the
international community have also controlled these substances.
Youth appear to be the primary abusers of synthetic cannabinoids
and synthetic cannabinoid-containing products, as supported by law
enforcement encounters and reports from emergency rooms; however, all
age groups have been discussed in media reports as abusing these
substances and related products. More recently, clandestinely produced
synthetic cannabinoid products have been encountered in liquid forms,
and law enforcement has communicated that these designer drug products
are intended for use in electronic cigarettes and vaporizers.
5. The Scope, Duration, and Significance of Abuse: As stated by the
HHS, based on their pharmacological properties, it is reasonable to
assume that, if uncontrolled, the scope, duration, and significance of
UR-144, XLR11, and AKB48 abuse could be similar to marijuana. National
Forensic Laboratory Information Systems (NFLIS),\3\ a national database
capturing data from forensic laboratories, has reported 46,324 reports
(January 2010 to December 2014) related to UR-144, XLR11, and AKB48
from 44 states (query date: April 30, 2015). From January 1, 2010,
through December 31, 2014, according to the System to Retrieve
Information on Drug Evidence (STRIDE) and STARLiMS data,\4\ there were
2,049 reports involving 245 cases for UR-144, 4,041 reports involving
487 cases for XLR11, and 201 reports involving 63 cases for AKB48
(query date: April 30, 2015). Recently, numerous exposure incidents
have been documented by poison control centers in the United States as
the abuse of synthetic cannabinoids has become associated with both
acute and long-term public health and safety concerns. The American
Association of Poison Control Centers (AAPCC) has reported exposure
calls corresponding to products purportedly laced with synthetic
cannabinoids since 2011, although the data provided do not generally
include biological sample testing that would confirm the specific
cannabinoid. AAPCC reported 6,968 exposure calls in 2011 and 5,230
calls in 2012. While exposure calls decreased in 2013 to 2,668, calls
involving exposure to a synthetic cannabinoid rebounded in 2014
reaching 3,680. In addition, 623 calls have been reported from January
1 through February 28, 2015. A majority of exposure incidents resulted
in seeking medical attention at health care facilities. In 2010, the
Substance Abuse and Mental Health Services Administration (SAMHSA)
reported 11,406 emergency department visits involving a synthetic
cannabinoid product. In 2011, SAMHSA reported the number of emergency
department visits involving a synthetic cannabinoid product had
increased 2.5 times to 28,531.
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\3\ NFLIS is a program of the DEA that collects drug
identification results from drug cases analyzed by other Federal,
State, and local forensic laboratories.
\4\ STRIDE collected the results of drug evidence analyzed at
DEA laboratories and reflects evidence submitted by the DEA, other
Federal law enforcement agencies, and some local law enforcement
agencies. On October 1, 2014, STARLiMS replaced STRIDE as the DEA
laboratory drug evidence data system of record.
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6. What, if Any, Risk There is to the Public Health: Law
enforcement, military, and public health officials have reported
exposure incidents that demonstrate the dangers associated with abuse
of synthetic cannabinoids to both the individual abusers and those
connected to the misuse and abuse of these substances not intended for
human use. Warnings regarding the dangers associated with abuse of
synthetic cannabinoids and their products have been issued by numerous
state public health departments, poison control centers, and private
organizations. Detailed product analyses describe large variations in
the amount of synthetic cannabinoid laced on the plant material even
within samplings of the same product. These unknowns present a
significant risk of danger to the abusing individuals. Some of the
common clinical effects reported in emergency rooms in response to the
abuse of synthetic cannabinoids include: vomiting, anxiety, agitation,
irritability, seizures, hallucinations, tachycardia, elevated blood
pressure, and loss of consciousness.
At least one death has been reported in Minnesota following
ingestion of UR-144 and XLR11. In 2013, in California, a 27-year-old
female developed hypertension, tachycardia, and rhabdomyolisis prior to
being intubated and admitted to the ICU for protection of the airway
following ingestion of a synthetic cannabinoid product containing
XLR11. A 33-year-old-man developed acute cerebral ischemia and
infarction shortly following the use of XLR11. In addition, reports
have detailed various driving under the influence cases where users
operated a motor vehicle while intoxicated with synthetic cannabinoids,
including UR-144, XLR11, and/or AKB48.
In February 2013, the Centers for Disease Control (CDC) reported on
an association between XLR11 exposure and acute kidney injury. The CDC
examined 16 patients with acute kidney injury who reported recent
smoking of synthetic cannabinoids. Seven of the 16 patients smoked
substances that were positive for XLR11 or its metabolite. In addition,
one of these seven cases also tested positive for UR-144.
Additional cases reported adverse health effects including nausea,
vomiting, agitation, panic attacks, involuntary muscle twitching and
confusion following ingestion of UR-144 and/or XLR11.
7. Its Psychic or Physiological Dependence Liability: Chronic abuse
of synthetic cannabinoids has been linked to signs of addiction and
withdrawal. According to the HHS, the pharmacologic profiles of UR-144,
XLR11, and AKB48 strongly suggest that they possess physiological and
psychological dependence liability that is similar to that of delta-9-
tetrahydrocannabinol ([Delta] \9\-THC) (schedule I) and JWH-018
(schedule I). Additionally, tolerance to these drugs may develop fairly
rapidly with larger doses being required to achieve the desired effect.
However, there are no studies or case reports that document the psychic
or physiological dependence potential of UR-144, XLR11, or AKB48.

[[Page 27615]]

8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA: UR-144, XLR11, and AKB48 are not
considered immediate precursors of any controlled substance of the CSA
as defined by 21 U.S.C 802(23).
Conclusion: Based on consideration of the scientific and medical
evaluations and accompanying recommendation of the HHS, and based on
the DEA's considerations of its own eight-factor analysis, the DEA
finds that these facts and all other relevant data constitute
substantial evidence of the potential for abuse of UR-144, XLR11, and
AKB48. As such, the DEA hereby proposes to schedule UR-144, XLR11, and
AKB48 as controlled substances under the CSA.

Proposed Determination of Appropriate Schedule

The CSA establishes five schedules of controlled substances known
as schedules I, II, III, IV, and V. The CSA also outlines the findings
required to place a drug or other substance in any particular schedule.
21 U.S.C. 812(b). After consideration of the analysis and
recommendation of the Assistant Secretary for HHS and review of all
other available data, the Administrator of the DEA, pursuant to 21
U.S.C. 811(a) and 21 U.S.C. 812(b)(1), finds that:
(1) (1-pentyl-1H-indol-3-yl)(2,2,3,3-
tetramethylcyclopropyl)methanone (UR-144), [1-(5-fluoro-pentyl)-1H-
indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (5-fluoro-UR-144,
XLR11), and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide
(APINACA, AKB48) have a high potential for abuse that is comparable to
other schedule I substances such as delta-9-tetrahydrocannabinol
([Delta] \9\-THC) and JWH-018;
(2) (1-pentyl-1H-indol-3-yl)(2,2,3,3-
tetramethylcyclopropyl)methanone (UR-144), [1-(5-fluoro-pentyl)-1H-
indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (5-fluoro-UR-144,
XLR11), and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide
(APINACA, AKB48) have no currently accepted medical use in treatment in
the United States; and
(3) There is a lack of accepted safety for use of (1-pentyl-1H-
indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144), [1-(5-
fluoro-pentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone
(5-fluoro-UR-144, XLR11) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-
carboxamide (APINACA, AKB48) under medical supervision.
Based on these findings, the Administrator of the DEA concludes
that (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone
(UR-144), [1-(5-fluoro-pentyl)-1H-indol-3-yl](2,2,3,3-
tetramethylcyclopropyl)methanone (5-fluoro-UR-144, XLR11), and N-(1-
adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA, AKB48)
including their salts, isomers and salts of isomers, whenever the
existence of such salts, isomers, and salts of isomers is possible,
warrant control in schedule I of the CSA. 21 U.S.C. 812(b)(1).

Requirements for Handling UR-144, XLR11 and AKB48

If this rule is finalized as proposed, persons who handle UR-144,
XLR11, or AKB48 would continue \5\ to be subject to the regulatory
controls and administrative, civil, and criminal sanctions applicable
to the manufacture, distribution, possession, importing, and exporting
of schedule I controlled substances, including those listed below:
---------------------------------------------------------------------------

\5\ UR-144, XLR11, and AKB48 are currently subject to schedule I
controls on a temporary basis, pursuant to 21 U.S.C. 811(h).
---------------------------------------------------------------------------

1. Registration. Any person who handles (manufactures, distributes,
imports, exports, engages in research, or conducts instructional
activities or chemical analysis with, or possesses) UR-144, XLR11, or
AKB48, or who desires to handle UR-144, XLR11, or AKB48 would be
required to be registered with the DEA to conduct such activities
pursuant to 21 U.S.C. 822, 823, 957, and 958, and in accordance with 21
CFR parts 1301 and 1312.
2. Security. UR-144, XLR11, and AKB48 would be subject to schedule
I security requirements and would need to be handled and stored
pursuant to 21 U.S.C. 821, 823, and 871(b), and in accordance with 21
CFR 1301.71-1301.93.
3. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of UR-144, XLR11, and AKB48 would need to be in
compliance with 21 U.S.C. 825 and 958(e), and be in accordance with 21
CFR part 1302.
4. Quota. Only registered manufacturers would be permitted to
manufacture UR-144, XLR11, or AKB48 in accordance with a quota assigned
pursuant to 21 U.S.C. 826 and in accordance with 21 CFR part 1303.
5. Inventory. Every DEA registrant who possesses any quantity of
UR-144, XLR11, and/or AKB48 on the effective date of the final rule
would be required to continue to maintain an inventory of all stocks of
UR-144, XLR11, and/or AKB48 on hand, pursuant to 21 U.S.C. 827, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
6. Records and Reports. Every DEA registrant would be required to
maintain records and submit reports with respect to UR-144, XLR11, and/
or AKB48 pursuant to 21 U.S.C. 827 and 958, and in accordance with 21
CFR parts 1304 and 1312.
7. Order Forms. Every DEA registrant who distributes UR-144, XLR11,
and/or AKB48 would be required to comply with the order form
requirements, pursuant to 21 U.S.C. 828, and 21 CFR part 1305.
8. Importation and Exportation. All importation and exportation of
UR-144, XLR11, and AKB48 would need to be in compliance with 21 U.S.C.
952, 953, 957, and 958, and in accordance with 21 CFR part 1312.
9. Liability. Any activity involving UR-144, XLR11, or AKB48 not
authorized by, or in violation of the CSA or its implementing
regulations would be unlawful, and could subject the person to
administrative, civil, and/or criminal sanctions.

Regulatory Analyses

Executive Orders 12866 and 13563

In accordance with 21 U.S.C. 811(a), this proposed scheduling
action is subject to formal rulemaking procedures done ``on the record
after opportunity for a hearing,'' which are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the criteria for
scheduling a drug or other substance. Such actions are exempt from
review by the Office of Management and Budget (OMB) pursuant to Section
3(d)(1) of Executive Order 12866 and the principles reaffirmed in
Executive Order 13563.

Executive Order 12988

This proposed regulation meets the applicable standards set forth
in sections 3(a) and 3(b)(2) of Executive Order 12988 to eliminate
drafting errors and ambiguity, minimize litigation, provide a clear
legal standard for affected conduct, and promote simplification and
burden reduction.

Executive Order 13132

This proposed rulemaking does not have federalism implications
warranting the application of Executive Order 13132. The proposed rule
does not have substantial direct effects on the States, on the
relationship between the national government and the States, or the
distribution of power and responsibilities among the various levels of
government.

[[Page 27616]]

Executive Order 13175

This proposed rule does not have tribal implications warranting the
application of Executive Order 13175. It does not have substantial
direct effects on one or more Indian tribes, on the relationship
between the Federal Government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
Government and Indian tribes.

Regulatory Flexibility Act

The Administrator, in accordance with the Regulatory Flexibility
Act (RFA), 5 U.S.C. 601-602, has reviewed this proposed rule and by
approving it certifies that it will not have a significant economic
impact on a substantial number of small entities. On May 16, 2013, the
Deputy Administrator published a Final Order in the Federal Register
(78 FR 28735) amending 21 CFR 1308.11(h) to temporarily place these
three synthetic cannabinoids into schedule I of the CSA pursuant to the
temporary scheduling provisions of 21 U.S.C. 811(h). All entities that
currently handle or plan to handle these synthetic cannabinoids are
estimated to have already established and implemented the systems and
processes required to handle UR-144, XLR11, and AKB48. Therefore, the
DEA anticipates that this proposed rule will impose minimal or no
economic impact on businesses that currently handle UR-144, XLR11, or
AKB48 for lawful purposes. This estimate applies to entities large and
small. Therefore, DEA has concluded that this proposed rule will not
have a significant effect on a substantial number of small entities.

Unfunded Mandates Reform Act of 1995

On the basis of information contained in the ``Regulatory
Flexibility Act'' section above, the DEA has determined and certifies
pursuant to the Unfunded Mandates Reform Act (UMRA) of 1995 (2 U.S.C.
1501 et seq.), that this action would not result in any Federal mandate
that may result in the expenditure by State, local, and tribal
governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted for inflation) in any one year.
Therefore, neither a Small Government Agency Plan nor any other action
is required under provisions of the UMRA of 1995.

Paperwork Reduction Act of 1995

This action does not impose a new collection of information under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). This action
would not impose recordkeeping or reporting requirements on State or
local governments, individuals, businesses, or organizations. An agency
may not conduct or sponsor, and a person is not required to respond to,
a collection of information unless it displays a currently valid OMB
control number.

List of Subjects in 21 CFR Part 1308

Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.

For the reasons set out above, 21 CFR part 1308 is proposed to be
amended to read as follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for 21 CFR part 1308 continues to read as
follows:

Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted.

0
2. Amend Sec. 1308.11 by:
0
a. Adding paragraphs (g)(16) through (18); and
0
b. Removing paragraphs (h)(1) through (3) and redesignating paragraphs
(h)(4) through (23) as paragraphs (h)(1) through (20), respectively.
The additions read as follows:

Sec. 1308.11 Schedule I.

* * * * *
(g) * * *

(16) (1-pentyl-1H-indol-3-yl)(2,2,3,3- (7144)
tetramethylcyclopropyl)methanone (UR-144).................
(17) [1-(5-fluoro-pentyl)-1H-indol-3-yl](2,2,3,3- (7011)
tetramethylcyclopropyl)methanone (5-fluoro-UR-144, XLR11).
(18) N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (7048)
(APINACA, AKB48)..........................................

* * * * *

Dated: May 12, 2015.
Michele M. Leonhart,
Administrator.
[FR Doc. 2015-11762 Filed 5-13-15; 8:45 am]
BILLING CODE 4410-09-P