[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]


=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

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\
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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