Schedules of Controlled Substances: Placement of N-Ethylhexedrone, alpha-Pyrrolidinohexanophenone, 4-Methyl-alpha-ethylaminopentiophenone, 4′-Methyl-alpha-pyrrolidinohexiophenone, alpha-Pyrrolidinoheptaphenone, and 4′-Chloro-alpha-pyrrolidinovalerophenone in Schedule I
| Published date | 16 July 2021 |
| Citation | 86 FR 37719 |
| Record Number | 2021-15114 |
| Section | Proposed rules |
| Court | Drug Enforcement Administration |
Federal Register, Volume 86 Issue 134 (Friday, July 16, 2021)
[Federal Register Volume 86, Number 134 (Friday, July 16, 2021)]
[Proposed Rules]
[Pages 37719-37725]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-15114]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-495]
Schedules of Controlled Substances: Placement of N-
Ethylhexedrone, alpha-Pyrrolidinohexanophenone, 4-Methyl-alpha-
ethylaminopentiophenone, 4'-Methyl-alpha-pyrrolidinohexiophenone,
alpha-Pyrrolidinoheptaphenone, and 4'-Chloro-alpha-
pyrrolidinovalerophenone in Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: The Drug Enforcement Administration proposes placing six
synthetic cathinones, as identified in this proposed rule, in schedule
I of the Controlled Substances Act. If finalized, this action would
make permanent the existing regulatory controls and administrative,
civil, and criminal sanctions applicable to schedule I controlled
substances on persons who handle (manufacture, distribute, reverse
distribute, import, export, engage in research, conduct instructional
activities or chemical analysis, or possess), or propose to handle
these six specified controlled substances.
DATES: Comments must be submitted electronically or postmarked on or
before August 16, 2021.
Requests for hearing and waivers of an opportunity for a hearing or
to participate in a hearing must be received on or before August 16,
2021.
ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-495'' on all electronic and written correspondence,
including any attachments.
Electronic comments: The Drug Enforcement Administration
(DEA) 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 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. 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/DPW, 8701 Morrissette Drive,
Springfield, Virginia 22152.
Hearing requests: All requests for a hearing and waivers
of participation, together with a written statement of position on the
matters of fact and law asserted in the hearing, must be sent to: Drug
Enforcement Administration, Attn: Administrator, 8701 Morrissette
Drive, Springfield, Virginia 22152. All requests for hearing and
waivers of participation should also be sent to: (1) Drug Enforcement
Administration, Attn: Hearing Clerk/OALJ, 8701 Morrissette Drive,
Springfield, Virginia 22152; and (2) Drug Enforcement Administration,
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive,
Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Ph.D., Drug and
Chemical Evaluation Section, Drug Enforcement Administration;
Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION:
In this proposed rule, the Drug Enforcement Administration (DEA)
proposes to permanently schedule the following six controlled
substances in schedule I of the Controlled Substances Act (CSA),
including their salts, isomers, and salts of isomers whenever the
existence of such salts, isomers, and salts of isomers is possible
within the specific chemical designation:
N-ethylhexedrone (other names: [alpha]-
ethylaminohexanophenone, ethyl hexedrone, HEXEN, 2-(ethylamino)-1-
phenylhexan-1-one),
alpha-pyrrolidinohexanophenone (other names: [alpha]-
pyrrolidino-hexanophenone, alpha-PHP, [alpha]-PHP, PV7, 1-phenyl-2-
(pyrrolidin-1-yl)hexan-1-one),
4-methyl-alpha-ethylaminopentiophenone (other names: N-
ethyl-4-methylnorpentedrone, 4-methyl-[alpha]-ethylaminopentiophenone,
4-MEAP, 2-(ethylamino)-1-(4-methylphenyl)pentan-1-one),
4'-methyl-alpha-pyrrolidinohexiophenone (other names: 4'-
methyl-[alpha]-PHP, 4'-methyl PHP, PV4, 4-MPHP, MPHP, 4-methyl-alpha-
pyrrolidino hexanophenone, 1-(4-methylphenyl)-2-(pyrrolidin-1-yl)hexan-
1-one),
alpha-pyrrolidinoheptaphenone (other names: alpha-
pyrrolidinoheptiophenone, alpha-PHpP, PV8, 1-phenyl-2-(pyrrolidin-1-
yl)heptan-1-one), and
4'-chloro-alpha-pyrrolidinovalerophenone (other names: 4-
chloro-[alpha]-pyrrolidinopentiophenone, 4-chloro-[alpha]-PVP, 4-Cl-
[alpha]-PVP, 4-chloro-2-(1-pyrrolidinyl)-valerophenone, 1-(4-
chlorophenyl)-2-(pyrrolidin-1-yl)pentan-1-one).
Posting of Public Comments
Please note that all comments received in response to this docket
are considered part of the public record. They will, unless reasonable
cause is given, be made available by 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 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 the
confidential business information to be redacted within the comment.
Comments containing personal identifying information or
confidential business information identified as directed above will be
made publicly available in redacted form. If a comment has so much
confidential business 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
[[Page 37720]]
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.
Request for Hearing or Waiver of Particpation in 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, 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316,
subpart D. Interested persons may file requests for hearing or notices
of intent to participate in a hearing in conformity with the
requirements of 21 CFR 1308.44(a) or (b), and include a statement of
interest in the proceeding and the objections or issues, if any,
concerning which the person desires to be heard. Any interested person
may file a waiver of an opportunity for a hearing or to participate in
a hearing together with a written statement regarding the interested
person's position on the matters of fact and law involved in any
hearing as set forth in 21 CFR 1308.44(c).
All requests for a hearing and waivers of participation, together
with a written statement of position on the matters of fact and law
involved in such hearing, must be sent to DEA using the address
information provided above.
Legal Authority
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 on his own motion. 21 U.S.C. 811(a).
This proposed action is supported by a recommendation from the
Assistant Secretary for Health of the Department of Health and Human
Services (HHS) and an evaluation of all other relevant data by DEA. If
finalized, this action would make permanent the existing temporary
regulatory controls and administrative, civil, and criminal sanctions
for schedule I controlled substances on any person who handles
(manufactures, distributes, imports, exports, engages in research,
conducts instructional activities or chemical analysis, or possesses)
or proposes to handle N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8,
or 4-chloro-[alpha]-PVP.
Background
On July 18, 2019, pursuant to 21 U.S.C. 811(h)(1), DEA published an
order in the Federal Register (84 FR 34291) temporarily placing N-
ethylhexedrone, alpha-pyrrolidinohexanophenone ([alpha]-PHP), 4-methyl-
alpha-ethylaminopentiophenone (4-MEAP), 4'-methyl-alpha-
pyrrolidinohexiophenone (MPHP), alpha-pyrrolidinoheptaphenone (PV8),
and 4'-chloro-alpha-pyrrolidinovalerophenone (4-chloro-[alpha]-PVP) in
schedule I of the CSA upon finding that these synthetic cathinones pose
an imminent hazard to the public safety. That temporary order was
effective on the date of publication. Pursuant to 21 U.S.C. 811(h)(2),
the temporary control of these substances is set to expire on July 18,
2021. However, this same subsection also provides that, during the
pendency of proceedings under 21 U.S.C. 811(a)(1) with respect to a
substance, the temporary scheduling of that substance may be extended
for up to one year. Proceedings for the scheduling of a substance under
21 U.S.C. 811(a) may be initiated by the Attorney General (delegated to
the Administrator of DEA (Administrator) pursuant to 28 CFR 0.100) on
his own motion, at the request of the Secretary of HHS,\1\ or on the
petition of any interested party. An extension of the existing
temporary order is being ordered by the Administrator in a separate
action, and is being simultaneously published elsewhere in this issue
of the Federal Register.
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\1\ Because the Secretary of HHS has delegated to the Assistant
Secretary for Health (Assistant Secretary) the authority to make
domestic drug scheduling recommendations, for purposes of this
proposed rulemaking, all subsequent references to ``Secretary'' have
been replaced with ``Assistant Secretary.''
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The Administrator, on her own motion, is initiating proceedings
under 21 U.S.C. 811(a)(1) to permanently schedule N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP. DEA has
gathered and reviewed the available information regarding the
pharmacology, chemistry, trafficking, actual abuse, pattern of abuse,
and the relative potential for abuse for these synthetic cathinones. On
October 22, 2020, the Acting Administrator of DEA submitted a request
to the Assistant Secretary for Health of HHS (Assistant Secretary) to
provide DEA with a scientific and medical evaluation of available
information and a scheduling recommendation for N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP, in accordance
with 21 U.S.C. 811(b) and (c). Upon evaluating the scientific and
medical evidence, on July 8, 2021, the Assistant Secretary submitted to
the Acting Administrator HHS's scientific and medical evaluation and
scheduling recommendation for these substances. Upon receipt of the
scientific and medical evaluation and scheduling recommendation from
HHS, DEA reviewed the document and all other relevant data, and
conducted its own eight-factor analysis of the abuse potential of N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP in accordance with 21 U.S.C. 811(c).
Proposed Determination of Schedule N-Ethylhexedrone, [alpha]-PHP, 4-
MEAP, MPHP, PV8, and 4-Chloro-[alpha]-PVP
As discussed in the background section, the Administrator is
initiating proceedings, pursuant to 21 U.S.C. 811(a)(1), to add N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP permanently to schedule I. DEA has reviewed the scientific and
medical evaluation and scheduling recommendation, received from HHS,
and all other relevant data and conducted its own eight-factor analysis
of the abuse potential of N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP,
PV8, and 4-chloro-[alpha]-PVP pursuant to 21 U.S.C. 811(c). Included
below is a brief summary of each factor as analyzed by HHS and DEA, and
as considered by DEA in its proposed scheduling action. Please note
that both the DEA and the HHS 8-Factor analyses and the Assistant
Secretary's July 8, 2021 letter are available in their entirety under
the tab ``Supporting Documents'' of the public docket of this
rulemaking action at http://www.regulations.gov, under Docket Number
``DEA-495.''
1. The Drug's Actual or Relative Potential for Abuse: Both the DEA
and the HHS 8-factor analyses found that N-ethylhexedrone, [alpha]-PHP,
4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP have abuse potential
associated with its abilities to produce psychoactive effects that are
similar to those produced by schedule I synthetic cathinones such as
methcathinone, mephedrone, methylone, pentylone, and 3,4-
methylenedioxypyrovalerone (MDPV) and schedule II stimulants such as
methamphetamine and cocaine that have a high potential for abuse. In
particular, the responses in humans to N-ethylhexedrone, [alpha]-PHP,
4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP are stimulant-like and
include paranoia, agitation, palpitations, tachycardia, hypertension,
and hyperthermia.
N-Ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-
[alpha]-PVP have no approved medical uses in the United
[[Page 37721]]
States but there have been reports of individuals experiencing adverse
outcomes after taking these substances. Because these substances are
not approved drug products, a practitioner may not legally prescribe
them, and they cannot be dispensed to an individual. The use of these
substances without medical advice leads to the conclusion that these
synthetic cathinones are being abused for their psychoactive
properties.
Reports from public health and law enforcement state that these
substances are being abused and taken in amounts sufficient to create a
hazard to an individual's health. This hazard is evidenced by emergency
department admissions or deaths, representing a significant safety
issue for those in the community. Further, from January 2012 through
December 2020 (query date: May 3, 2021), the National Forensic
Laboratory Information System (NFLIS) databases registered a total of
2,289 reports by participating DEA, State, local, and other forensic
laboratories, as applicable, pertaining to N-ethylhexedrone, [alpha]-
PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP.\2\ NFLIS registered
these reports identifying these substances in drug-related exhibits
from more than 40 States. MPHP was first identified in June 2012 in
seized drug evidence (although MPHP was identified in blood samples
from a 27-year-old decedent in 2011), followed by 4-MEAP and PV8
(August and December 2013, respectively), alpha-PHP (May 2014), 4-
chloro-[alpha]-PVP (December 2015) and most recently N-ethylhexedrone
(August 2016). Consequently, the data indicate that N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP are being
abused, and they present safety hazards to the health of individuals
who consume them due to their stimulant properties.
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\2\ NFLIS is a national drug forensic laboratory reporting
system that systematically collects results from drug chemistry
analyses conducted by state and local forensic laboratories across
the country. The NFLIS participation rate, defined as the percentage
of the national drug caseload represented by laboratories that have
joined NFLIS, is over 97 percent. NFLIS includes drug chemistry
results from completed analyses only.
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2. Scientific Evidence of the Drug's Pharmacological Effects, if
Known: As described by HHS, studies show that N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP produce
pharmacological effects that are similar to those produced by schedule
I and II substances such as methamphetamine (II), cocaine (II),
mephedrone (I), MDPV (I), and methylone (I). Similar to these schedule
I and II substances, N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8,
and 4-chloro-[alpha]-PVP bind to monoamine transporters for dopamine
and norepinephrine, and block the uptake of these neurotransmitters at
their transporters. N-Ethylhexedrone, [alpha]-PHP, and MPHP (4-MEAP,
PV8, and 4-chloro-[alpha]-PVP were not tested in this assay) do not
promote the release of these monoamines. Additionally, behavioral
studies in animals demonstrate that N-ethylhexedrone, [alpha]-PHP, 4-
MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP produce locomotor behavior
and discriminative stimulus effects that are similar to those of
methamphetamine and cocaine. Overall, these data indicate that N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP produce pharmacological effects and stimulant-like behaviors that
are similar to those of other schedule I synthetic cathinones such as
methcathinone, mephedrone, MDPV, and methylone, as well as schedule II
stimulants methamphetamine and cocaine.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: N-Ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and
4-chloro-[alpha]-PVP are designer drugs of the phenethylamine class and
they are structurally similar to permanently controlled schedule I
synthetic cathinones and schedule II stimulants like methamphetamine.
Pharmacokinetic studies show that humans, in general, metabolize
synthetic cathinones to their corresponding amphetamines followed by
reduction of the beta-keto group to the corresponding alcohol which can
involve hydrogenation, deethylation, demethylation, or hydroxylation.
Given that N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-
chloro-[alpha]-PVP are synthetic cathinones, it is likely that these
six synthetic cathinones are also metabolized to their corresponding
amphetamines and alcohols.
Neither DEA nor HHS is aware of any currently accepted medical use
for N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-
[alpha]-PVP. According to HHS's 2021 scientific and medical evaluation
and scheduling recommendation, the Food and Drug Administration (FDA)
has not approved marketing applications for drug products containing N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP for any therapeutic indication, nor is HHS aware of any reports of
clinical studies or claims of accepted medical use for N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP in the United States.
A drug has a ``currently accepted medical use'' if DEA concludes
that it satisfies a five-part test. Specifically, with respect to a
drug that has not been approved by FDA, all of the following must be
demonstrated: The drug's chemistry is known and reproducible; there are
adequate safety studies; there are adequate and well-controlled studies
proving efficacy; the drug is accepted by qualified experts; and the
scientific evidence is widely available.\3\ Based on this analysis, N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP have no currently accepted medical use in the United States.
Furthermore, DEA has not found any references regarding clinical
testing of these substances in the scientific and medical literature.
Although the chemistry of synthetic cathinones, in general, is known
and has been reproduced, as mentioned above there are no clinical
studies involving N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and
4-chloro-[alpha]-PVP. Taken together with HHS's conclusion, DEA finds
that there is no legitimate medical use for N-ethylhexedrone, [alpha]-
PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP in the United States.
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\3\ 57 FR 10499 (1992), pet. for rev. denied, Alliance for
Cannabis Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).
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4. History and Current Pattern of Abuse: Available evidence
suggests that the history and pattern of abuse of N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP parallel that
of permanently controlled schedule I cathinone stimulants. N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP are synthetic cathinones of the phenethylamine class and they are
structurally and pharmacologically similar to schedule I and II
substances such as methcathinone (I) and methamphetamine (II). Like
these schedule I and II substances, N-ethylhexedrone, [alpha]-PHP, 4-
MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP are most likely ingested by
swallowing capsules or tablets or snorted by nasal insufflation of the
powder tablets. As reported by DEA and HHS, products containing N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-
PVP, similar to schedule I synthetic cathinones, are likely to be
falsely marketed as ``research chemicals,'' ``jewelry cleaner,''
``stain remover,'' ``plant food or fertilizer,'' ``insect repellants,''
or ``bath salts;'' sold at smoke shops, head shops, convenience stores,
adult book stores, or gas stations; and purchased on the internet. Like
those seen with commercial products
[[Page 37722]]
that contain synthetic cathinones, the packages of products that
contain N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-
[alpha]-PVP also probably contain the warning ``not for human
consumption,'' most likely in an effort to circumvent statutory
restrictions for these substances. Law enforcement data indicate that
N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP are available for illicit use and are being abused. Demographic
data collected from published reports and mortality records suggest
that the main users of N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP,
PV8, and 4-chloro-[alpha]-PVP, similar to other schedule I synthetic
cathinones permanently placed in schedule I, are young adults.
Toxicology reports also revealed that N-ethylhexedrone, [alpha]-PHP, 4-
MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP are being ingested with other
substances including other synthetic cathinones, common cutting agents,
or other recreational substances. Consequently, products containing
synthetic cathinones, including N-ethylhexedrone, [alpha]-PHP, 4-MEAP,
MPHP, PV8, or 4-chloro-[alpha]-PVP, are distributed to users, often
with unpredictable outcomes. Thus, the recreational abuse of N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP is a significant concern. These data indicate that N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP have a history and current pattern of abuse.
5. Scope, Duration and Significance of Abuse: N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP are
recreational drugs that emerged on the United States' illicit drug
market after the scheduling of other synthetic cathinones (e.g., N-
ethylpentylone, ethylone, mephedrone, methylone, pentylone, and MDPV)
(see DEA's Eight Factor Analysis for a full discussion). Forensic
laboratories have confirmed the presence of N-ethylhexedrone, [alpha]-
PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP in drug exhibits
received from Federal, State, and local law enforcement agencies. MPHP
was first identified in June 2012 in seized drug evidence (although
MPHP was identified in blood samples from a 27-year-old decedent in
2011--see Factor 6 for details), followed by 4-MEAP and PV8 (August and
December 2013, respectively), alpha-PHP (May 2014), 4-chloro-[alpha]-
PVP (December 2015) and most recently N-ethylhexedrone (August 2016).
From January 2012 through December 2020 (query date: May 3, 2021),
NFLIS database registered a total of 2,289 reports from forensic
laboratories pertaining to the 6 synthetic cathinones (N-
ethylhexedrone, 613 reports; [alpha]-PHP--984 reports; 4-MEAP--131
reports; MPHP--92 reports; PV8--174 reports; and 4-chloro-[alpha]-PVP--
295 reports). HHS reported that there were 13,238 calls to United
States poison control centers (PCCs) \4\ involving synthetic cathinones
from 2010 to 2019 and 39 mentions of cathinones of which 23 were for
[alpha]-PHP on the Dashboard \5\ from July 2018 to July 2020.
Accordingly, concerns over the continuing abuse of synthetic cathinones
have led to the control of many synthetic cathinones. A full
presentation of the NFLIS reports by substance and year, PCC, and
Dashboard data are available in both DEA's and HHS's eight-factor
analyses within the Supporting Documents section of the public docket
available at http://www.regulations.gov.
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\4\ PCC data are derived from the National Poison Data System, a
database managed by the American Association of Poison Control
Centers (AAPCC). AAPCC is a nationwide network of PCCs that receive
calls from individuals, healthcare professionals, and other
interested persons in the general U.S. population regarding
exposures to prescription drugs and other substances.
\5\ The Dashboard is an online, interactive tool that reports on
the identification of certain novel psychoactive substances in de-
identified sample extracts from forensic investigations, including
medicolegal death investigations and toxicology testing. The
Dashboard was accessed on February 26, 2021.
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6. What, if Any, Risk There Is to the Public Health: HHS reported
that the public health risks of N-ethylhexedrone, [alpha]-PHP, 4-MEAP,
MPHP, PV8, and 4-chloro-[alpha]-PVP result from their ability to induce
stimulant-like responses, which may lead to impaired judgement and
dangerous behavior. Adverse health effects associated with the abuse of
N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP include a number of stimulant-like adverse health effects such as
diaphoresis, insomnia, mydriasis, hyperthermia, vomiting, agitation,
disorientation, paranoia, and abdominal pain. Serious adverse events
such as acute kidney failure, cardiac arrest, rhabdomyolysis, and coma
have been associated with the use of N-ethylhexedrone, [alpha]-PHP, 4-
MEAP, and PV8. In addition, N-ethylhexedrone, [alpha]-PHP, MPHP, and
PV8 have been involved in the deaths of individuals. The identification
of N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-
[alpha]-PVP in toxicological samples associated with fatal and non-
fatal overdoses as reported in the medical and scientific literature,
forensic laboratory reports, and public health documents confirms these
adverse effects of N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or
4-chloro-[alpha]-PVP. Like schedule I synthetic cathinones, N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP have caused acute health problems leading to emergency department
(ED) admissions, violent behaviors causing harm to self or others, and/
or death. Specifically, evidence demonstrate that all six synthetic
cathinones have resulted in ED visits that required medical attention,
but only N-ethylhexedrone, [alpha]-PHP, MPHP, and PV8 abuse have been
associated with the deaths of individuals. It remains highly likely
that additional cases of adverse health effects involving N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP in the United States have occurred and will continue to be under-
reported as these substances are not part of standard panels for
toxicological analyses of biological specimens. Thus, the abuse of N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP, like that of the abuse of schedule I synthetic cathinones and
stimulant drugs, poses significant adverse health risks including
death.
Furthermore, because abusers of synthetic cathinones obtain these
substances through unregulated sources, the identity, purity, and
quantity are uncertain and inconsistent. These unknown factors pose an
additional risk for significant adverse health effects to the end user.
Based on information received by DEA, the abuse of N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP has led to, at least, the same qualitative public health risks as
other schedule I synthetic cathinones and the schedule II stimulant
methamphetamine. The public health risks attendant to the abuse of
synthetic cathinones, including N-ethylhexedrone, [alpha]-PHP, 4-MEAP,
MPHP, PV8, or 4-chloro-[alpha]-PVP, are well established and have
resulted in large numbers of ED visits and fatal overdoses.
7. Its Psychic or Physiological Dependence Liability: According to
HHS, the psychic or physiological dependence liability of N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP is demonstrated by their positive abuse-related studies in animals
and reported stimulant effects in humans. The results from two
behavioral studies (drug discrimination and locomotor studies)
demonstrate that N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or
4-chloro-[alpha]-PVP produced behavioral effects that are similar to
those of substances with
[[Page 37723]]
stimulant effects such as the schedule II stimulants cocaine and
methamphetamine. Thus, based on the structural and pharmacological
similarities of N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and
4-chloro-[alpha]-PVP to schedule II stimulant substances that have
demonstrated psychic or physiological dependence liability, it is
anticipated that the stimulant properties of N-ethylhexedrone, [alpha]-
PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP produce psychic
dependence liability.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA: N-Ethylhexedrone, [alpha]-PHP, 4-
MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP are not immediate precursors
of any controlled substance under the CSA as defined by 21 U.S.C.
802(23).
Conclusion: After considering the scientific and medical evaluation
conducted by HHS, HHS's scheduling recommendation, and DEA's own eight-
factor analysis, DEA finds that the facts and all relevant data
constitute substantial evidence of the potential for abuse of N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP. As such, DEA hereby proposes to permanently schedule N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP as controlled substances under the CSA.
Proposed Determination of Appropriate SSchedule
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 Health of HHS and review
of all other available data, the Administrator of DEA, pursuant to 21
U.S.C. 811(a) and 812(b)(1), finds that:
1. N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-
[alpha]-PVP have a high potential for abuse;
2. N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-
[alpha]-PVP have no currently accepted medical use in treatment in the
United States; and
3. There is a lack of accepted safety for use of N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP under medical
supervision.
Based on these findings, the Administrator concludes that N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP, including their salts, isomers, and salts of isomers, whenever the
existence of such salts, isomers, and salts of isomers is possible
within the specific chemical designation, warrant control in schedule I
of the CSA. 21 U.S.C. 812(b)(1).
Requirements for Handling N-Ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP,
PV8, and 4-Chloro-[alpha]-PVP
If this rule is finalized as proposed, N-ethylhexedrone, [alpha]-
PHP, 4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-PVP would continue \6\ to
be subject to the CSA's schedule I regulatory controls and
administrative, civil, and criminal sanctions applicable to the
manufacture, distribution, reverse distribution, importation,
exportation, research, and conduct of instructional activities
involving the handling of schedule I controlled substances including
the following:
---------------------------------------------------------------------------
\6\ N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-
chloro-[alpha]-PVP are currently subject to schedule I controls on a
temporary basis, pursuant to 21 U.S.C. 811(h). 84 FR 34291, July 18,
2019. An order extending the temporary scheduling of N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-
[alpha]-PVP for one year is published elsewhere in this issue of the
Federal Register, on the same day as this notice of proposed
rulemaking.
---------------------------------------------------------------------------
1. Registration. Any person who handles (manufactures, distributes,
reverse distributes, imports, exports, engages in research, or conducts
instructional activities or chemical analysis with, or possesses) or
who desires to handle N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8,
or 4-chloro-[alpha]-PVP is required to be registered with 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. N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and
4-chloro-[alpha]-PVP are subject to schedule I security requirements
and must be handled and stored pursuant to 21 U.S.C. 823 and in
accordance with 21 CFR 1301.71-1301.76. Non-practitioners handling N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-PVP
must also comply with the employee screening requirements of 21 CFR
1301.90-1301.93.
3. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP,
PV8, and 4-chloro-[alpha]-PVP must be in compliance with 21 U.S.C. 825,
and be in accordance with 21 CFR part 1302.
4. Quota. Only registered manufacturers are permitted to
manufacture N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-
chloro-[alpha]-PVP in accordance with a quota assigned pursuant to 21
U.S.C. 826 and in accordance with 21 CFR part 1303.
5. Inventory. Any person registered with DEA to handle N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-PVP
must have an initial inventory of all stocks of controlled substances
(including N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-
chloro-[alpha]-PVP) on hand on the date the registrant first engages in
the handling of controlled substances pursuant to 21 U.S.C. 827 and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
After the initial inventory, every DEA registrant must take an
inventory of all controlled substances (including N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-PVP) on hand every
two years, 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 is required to
maintain records and submit reports with respect to N-ethylhexedrone,
[alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-PVP pursuant to 21
U.S.C. 827, and in accordance with 21 CFR 1301.74(b) and (c) and parts
1304, 1312, and 1317. Manufacturers and distributors must submit
reports regarding these substances to the Automation of Reports and
Consolidated Order System pursuant to 21 U.S.C. 827 and in accordance
with 21 CFR parts 1304 and 1312.
7. Order Forms. Every DEA registrant who distributes N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-PVP
is 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
N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-
PVP must 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 N-ethylhexedrone, [alpha]-PHP,
4-MEAP, MPHP, PV8, or 4-chloro-[alpha]-PVP not authorized by, or in
violation of the CSA or its implementing regulations, is unlawful, and
could subject the person to administrative, civil, and/or criminal
sanctions.
Regulatory Analyses
Executive Orders 12866 (Regulatory Planning and Review) and 13563
(Improving Regulation and Regulatory Review)
In accordance with 21 U.S.C. 811(a), this proposed scheduling
action is subject to formal rulemaking procedures performed ``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
[[Page 37724]]
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 (E.O.) 12866 and
the principles reaffirmed in E.O. 13563.
Executive Order 12988, Civil Justice Reform
This proposed regulation meets the applicable standards set forth
in sections 3(a) and 3(b)(2) of E.O. 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, Federalism
This proposed rulemaking does not have federalism implications
warranting the application of E.O. 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.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
This proposed rule does not have tribal implications warranting the
application of E.O. 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, 5 U.S.C. 601-612, 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 July 18, 2019, DEA published
an order to temporarily place N-ethylhexedrone, [alpha]-PHP, 4-MEAP,
MPHP, PV8, and 4-chloro-[alpha]-PVP in schedule I of the CSA pursuant
to the temporary scheduling provisions of 21 U.S.C. 811(h). DEA
estimates that all entities handling or planning to handle these
substances have already established and implemented the systems and
processes required to handle N-ethylhexedrone, [alpha]-PHP, 4-MEAP,
MPHP, PV8, or 4-chloro-[alpha]-PVP. There are currently 34 unique
registrations authorized to handle N-ethylhexedrone, [alpha]-PHP, 4-
MEAP, MPHP, PV8, or 4-chloro-[alpha]-PVP specifically, as well as a
number of registered analytical labs that are authorized to handle
schedule I controlled substances generally. From review of entity
names, DEA estimates these 34 registrations represent 29 entities. Some
of these entities are likely to be large entities. However, since DEA
does not have information of registrant size and the majority of DEA
registrants are small entities or are employed by small entities, DEA
estimates a maximum of 29 entities are small entities. Therefore, DEA
conservatively estimates as many as 29 small entities are affected by
this proposed rule.
A review of the 34 registrations indicates that all entities that
currently handle N-ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, or
4-chloro-[alpha]-PVP also handle other schedule I controlled
substances, and thus they have established and implemented (or
maintain) the systems and processes required to handle N-
ethylhexedrone, [alpha]-PHP, 4-MEAP, MPHP, PV8, and 4-chloro-[alpha]-
PVP as a schedule I substance. Therefore, DEA anticipates that this
proposed rule will impose minimal or no economic impact on any affected
entities, and, thus, will not have a significant economic impact on any
of the 29 affected small entities. Therefore, DEA has concluded that
this proposed rule will not have a significant economic impact on a
substantial number of small entities.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995,
2 U.S.C. 1501 et seq., DEA has determined and certifies that this
proposed 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
annually for inflation) in any 1 year * * * .'' Therefore, neither a
Small Government Agency Plan nor any other action is required under
UMRA of 1995.
Paperwork Reduction Act of 1995
This proposed action does not impose a new collection of
information under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-
3521. This proposed 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, DEA proposes to amend 21 CFR part
1308 as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for part 1308 continues to read as follows:
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. Amend Sec. 1308.11 by:
0
a. Adding paragraphs (d)(94) through (99); and
0
b. Removing and reserving paragraphs (h)(42) through (h)(47).
The additions to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(d) * * *
(94) N-Ethylhexedrone (Other name: [alpha]- 7246
ethylaminohexanophenone)...............................
(95) alpha-Pyrrolidinohexanophenone (Other names: 7544
[alpha]-PHP, [alpha]-pyrrolidino-hexanophenone, 1-
phenyl-2-(pyrrolidin-1-yl)hexan-1-one).................
(96) 4-Methyl-alpha-Ethylaminopentiophenone (Other 7245
names: 4-MEAP, 2-(ethylamino)-1-(4-methylphenyl)pentan-
1-one).................................................
(97) 4'-Methyl-alpha-pyrrolidinohexiophenone (Other 7446
names: MPHP, 4'-methyl-alpha- pyrrolidino
hexanophenone; 1-(4-methylphenyl)-2-(pyrrolidin-1-
yl)hexan-1-one)........................................
(98) alpha-Pyrrolidinoheptaphenone (Other names: PV8, 1- 7548
phenyl-2-(pyrrolidin-1-yl)heptan-1-one)................
(99) 4'-Chloro-alpha-Pyrrolidinovalerophenone (Other 7443
names: 4-chloro-[alpha]-PVP, 4-chloro-[alpha]-
pyrrolidinopentiophenone, 1-(4-chlorophenyl)-2-
(pyrrolidin-1-yl)pentan-1-one).........................
[[Page 37725]]
* * * * *
Anne Milgram,
Administrator.
[FR Doc. 2021-15114 Filed 7-15-21; 8:45 am]
BILLING CODE 4410-09-P
