[Federal Register Volume 85, Number 95 (Friday, May 15, 2020)]
[Proposed Rules]
[Pages 29359-29366]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-09599]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-509]
Schedules of Controlled Substances: Placement of para-
Methoxymethamphetamine (PMMA) 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 1-(4-
methoxyphenyl)-N-methylpropan-2-amine (para-
[[Page 29360]]
methoxymethamphetamine, PMMA), including its salts, isomers, and salts
of isomers whenever the existence of such salts, isomers, and salts of
isomers is possible, in schedule I of the Controlled Substances Act.
This action is being taken to enable the United States to meet its
obligations under the 1971 Convention on Psychotropic Substances. 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
chemical analysis, or possess), or propose to handle PMMA.
DATES: Comments must be submitted electronically or postmarked on or
before June 15, 2020.
Interested persons may file a request for hearing or waiver of
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR
1316.45 and/or 1316.47, as applicable. Requests for hearing and waivers
of an opportunity for a hearing or to participate in a hearing must be
received on or before June 15, 2020.
ADDRESSES: Interested persons may file written comments on this
proposal in accordance with 21 CFR 1308.43(g). 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. To ensure proper handling of comments, please reference
``Docket No. DEA-509'' on all electronic and written correspondence,
including any attachments.
Electronic comments: 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 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. 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/DRW, 8701 Morrissette Drive,
Springfield, Virginia 22152.
Hearing requests: All requests for hearing and waivers of
participation must be sent to: Drug Enforcement Administration, Attn:
Administrator, 8701 Morrissette Drive, Springfield, Virginia 22152. All
requests for hearing and waivers of participation should be sent to:
Drug Enforcement Administration, Attn: Hearing Clerk/LJ, 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: Scott A. Brinks, Regulatory Drafting
and Policy Support Section, Diversion Control Division, Drug
Enforcement Administration; Mailing Address: 8701 Morrissette Drive,
Springfield, Virginia 22152; Telephone: (571) 362-8209.
SUPPLEMENTARY INFORMATION:
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 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 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 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.
Request for Hearing or Waiver of Participation 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. 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 the person's interests 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 may include a written statement regarding the interested person's
position on the matters of fact and law involved in any hearing.
All requests for hearing and waivers of participation must be sent
to DEA using the address information provided above.
Legal Authority
The United States is a party to the 1971 United Nations Convention
on Psychotropic Substances (1971 Convention), February 21, 1971, 32
U.S.T. 543 as amended. Procedures respecting changes in drug schedules
under the 1971 Convention are governed domestically by 21 U.S.C.
811(d)(2-4). When the United States receives notification of a
scheduling decision pursuant to Article 2 of the 1971 Convention adding
a drug or other substance to a specific schedule, the Secretary of the
Department of Health and Human Services (HHS),\1\ after
[[Page 29361]]
consultation with the Attorney General, shall first determine whether
existing legal controls under subchapter I of the Controlled Substances
Act (CSA) and the Federal Food, Drug, and Cosmetic Act meet the
requirements of the schedule specified in the notification with respect
to the specific drug or substance. 21 U.S.C. 811(d)(3). If such
requirements are not met by existing controls and the Secretary of HHS
concurs in the scheduling decision, the Secretary shall recommend to
the Attorney General that he initiate proceedings for scheduling the
drug or substance under the appropriate schedule pursuant to 21 U.S.C.
811(a) and (b). 21 U.S.C. 811(d)(3)(B).
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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), FDA acts as the lead agency within HHS in
carrying out the Secretary's scheduling responsibilities under the
CSA, with the concurrence of NIDA. 50 FR 9518, March 8, 1985. The
Secretary of HHS has delegated to the Assistant Secretary for Health
of HHS the authority to make domestic drug scheduling
recommendations. 58 FR 35460, July 1, 1993.
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In the event that the Secretary of HHS did not consult with the
Attorney General, as provided under 21 U.S.C. 811(d)(3), and the
Attorney General did not issue a temporary order, as provided under 21
U.S.C. 811(d)(4), the procedures for permanent scheduling set forth in
21 U.S.C. 811(a) and (b) control. 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 21
U.S.C. 812(b) for the schedule in which such drug or other substance is
to be placed. The Attorney General has delegated this scheduling
authority to the Administrator of DEA (Administrator). 28 CFR 0.100.
Background
para-Methoxymethamphetamine (PMMA) is a substituted phenethylamine
and shares structural similarity to methamphetamine (schedule II) and
para-methoxyamphetamine (PMA), schedule I. PMMA shares a similar
pharmacological profile with 3,4-methylenedioxymethamphetamine (MDMA or
ecstasy), a schedule I substance with high potential for abuse. Similar
to MDMA, data obtained from preclinical studies show that PMMA's
effects are mediated by monoaminergic (dopamine, norepinephrine, and
serotonin) transmission, mostly via activation of the serotonergic
system. In animals, PMMA mimics MDMA in producing discriminative
stimulus effect, indicative of similar subjective effects. Law
enforcement has encountered PMMA on the recreational drug market. In
this market, PMMA is available and sold as ``ecstasy'' either alone or
in combination with MDMA or PMA for oral consumption. For many years,
there has been worldwide (mostly in Europe) reporting of non-fatal and
fatal cases of overdoses involving PMMA. PMMA has no accepted medical
use in treatment in the United States.
Proposed Determination To Schedule PMMA
On March 18, 2016, the Commission on Narcotic Drugs (CND) voted to
place PMMA in Schedule I of the 1971 Convention (CND Dec/59/3) during
its 59th Session due to its dependence and abuse potential. The United
States is a member of the 1971 Convention, and in accordance with 21
U.S.C. 811(b), on April 7, 2017, DEA, after gathering the necessary
data, requested from HHS \2\ a scientific and medical evaluation and a
scheduling recommendation for PMMA. On December 18, 2018, pursuant to
21 U.S.C. 811(b), HHS provided DEA with a scheduling recommendation
entitled ``Basis for the Recommendation to Place 1-(4-methoxyphenyl)-N-
methylpropan-2-amine (para-methoxymethamphetamine, PMMA) in Schedule I
of the Controlled Substances Act.''
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\2\ Administrative responsibilities for evaluating a substance
for control under the CSA are performed for HHS by FDA, with the
concurrence of NIDA, according to a Memorandum of Understanding. 50
FR 9518, March 8, 1985.
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Upon receipt of the scientific and medical evaluation and
scheduling recommendation from HHS, DEA reviewed the documents and all
other relevant data, and conducted its own 8-Factor analysis in
accordance with 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 the
scheduling decision. Please note that both DEA and HHS 8-Factor
analyses are available in their entirety under the tab ``Supporting
Documents'' of the public docket for this action at http://www.regulations.gov under Docket Number ``DEA-509.''
1. The Drug's Actual or Relative Potential for Abuse: The term
``abuse'' is not defined in the CSA. However, the legislative history
of the CSA suggests that DEA consider the following criteria when
determining whether a particular drug or substance has a potential for
abuse: \3\
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\3\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); reprinted in 1970
U.S.C.C.A.N. 4566, 4603.
(a) 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; or
(b) There is significant diversion of the drug or drugs
containing such a substance from legitimate drug channels; or
(c) 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
(d) 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.
According to HHS, there is currently no approved medical use in
treatment for PMMA anywhere in the world, and there is no Food and Drug
Administration (FDA)-approved drug product containing PMMA used in
treatment in the United States. Evidence demonstrates that PMMA,
similar to MDMA, is abused for its stimulant, psychedelic, and
empathogenic effects. Over a period of approximately 30 years starting
in the 1990s, PMMA has been associated with numerous cases of non-fatal
intoxications (n = 31) and fatal intoxications (n = 131) in three
continents. PMMA and its metabolites have been positively identified in
blood, urine, and hair samples of individuals with a substance use
disorder. Evidence posits that PMMA is abused knowingly and/or
unknowingly as an MDMA (ecstasy) substitute.
Law enforcement seizure \4\ data indicate that individuals have
abused and are continuing to abuse PMMA. According to the National
Forensic Laboratory Information System (NFLIS) \5\ database, which
collects drug identification results from drug cases
[[Page 29362]]
submitted to and analyzed by some Federal, State, and local forensic
laboratories, there have been 39 reports for PMMA between January 2002
and October 2019, and no reports for PMMA from January 2003 to December
2010, January 2013 to December 2013, and January 2017 to December 2017
(query date: October 23, 2019).\6\ The identification of this substance
on the illicit drug market is an indication that individuals are taking
PMMA in amounts sufficient to create a hazard to public health. In the
United States, PMMA is not an approved drug product, and there appears
to be no legitimate source for this substance as a marketed drug
product.
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\4\ While law enforcement data is not direct evidence of abuse,
it can lead to an inference that a drug has been diverted and
abused. See 76 FR 77330, 77332, December 12, 2011.
\5\ NFLIS represents an important resource in monitoring illicit
drug trafficking, including the diversion of legally manufactured
pharmaceuticals into illegal markets. NFLIS-Drug is a comprehensive
information system that includes data from forensic laboratories
that handle the Nation's drug analysis cases. NFLIS-Drug
participation rate, defined as the percentage of the national drug
caseload represented by laboratories that have joined NFLIS, is
currently 98.5%. NFLIS includes drug chemistry results from
completed analyses only. While NFLIS data is not direct evidence of
abuse, it can lead to an inference that a drug has been diverted and
abused. See 76 FR 77330, 77332, December 12, 2011. NFLIS data were
queried October 23, 2019.
\6\ NFLIS is still reporting data for October-December 2018, due
to normal lag time in reporting.
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Based on available data, PMMA is related in its effects to the
actions of other substances such as PMA (schedule I) and MDMA (schedule
I) that are already listed as having potential for abuse. According to
HHS, PMMA has similar pharmacological effects to MDMA, and thus is
expected to have a high potential for abuse and high risk to public
health.
2. Scientific Evidence of the Drug's Pharmacological Effects, if
Known: According to HHS, PMMA is an empathogenic drug that produces
mild stimulant and psychedelic effects. Data obtained from in vitro
studies show that similar to MDMA, PMMA significantly increased
dopamine (DA) and serotonin (5-HT) levels in brain regions associated
with abuse liability. Data obtained from an enzymatic assay demonstrate
that PMMA inhibited monoamine oxidase A and B. According to HHS,
results from the enzymatic study may partially explain the higher
levels of monoamines seen with PMMA administration in brain
microdialysis studies. High levels of monoamines, especially 5-HT, can
lead to a serious medical condition referred to as serotonin syndrome.
High doses of PMMA have been associated with symptoms of serotonin
syndrome, including increased body temperature (hyperthermia), tremor,
and agitation, which can lead to death.
In preclinical studies, high doses of PMMA transiently increased
locomotor activity. HHS stated that PMMA's locomotor stimulatory
effects are not as robust as that of amphetamine or methamphetamine. In
drug discrimination studies, using a test to determine physical or
behavioral effects (an interoceptive response) of an unknown drug, the
effects of PMMA are different from structural analogs, amphetamine or
2,5-dimethoxy-4-methylamphetamine (DOM). However, in rats trained to
discriminate between MDMA or PMMA, MDMA and PMMA cross-substitute for
one another. Based on these and additional data, HHS stated that PMMA
likely has similar psychoactive effects as MDMA.
There are no clinical studies conducted with PMMA. However,
according to HHS, an article described that a self-administered 110
milligram (mg) dose of PMMA resulted in compulsive yawning and
increased pulse one hour post-administration. The described effects
returned ``back to baseline'' four hours post-administration. A study
examined the psychoactive effects of individuals who had taken
``ecstasy.'' The study followed 5,786 individuals who provided the
tablets for a chemical analysis and reported on their subjective
effects. Out of this sample set, 70 (1.2 percent) ``ecstasy'' tablets
were identified as containing PMMA and MDMA together, with PMMA
concentrations in a range of 5.0 to 128.0 mg/tablet. It was noted that
abusers of the PMMA and MDMA combination experienced hyperthermic
seizures, palpitations, agitation, hallucinations, abdominal cramps,
nausea, dizziness, and headache.
In summary, PMMA is a psychoactive substance with a mechanism of
action similar to that of MDMA. Data from in vitro studies show that
PMMA increases serotonin levels more than dopamine levels in the brain
reward circuitry. In addition, PMMA has an inhibitory effect on
monoamine oxidase-A enzyme that further increases monoamine levels and
can lead to serotonin syndrome, a dangerous medical condition. Data
from animal studies demonstrate that PMMA produced locomotor stimulant
effects at high doses with potency of about six times less than that of
(+)-amphetamine. In drug discrimination studies, PMMA produces stimulus
effect similar to MDMA in rats. Both PMMA and MDMA cross-substitute for
one another. There are currently no controlled clinical studies that
have evaluated the effects of PMMA in humans. However, anecdotal
reports show that similar to MDMA, PMMA produces adverse health
effects, such as hyperthermia, seizures, hallucinations, and nausea.
Taken together, these data demonstrate that PMMA shares a mechanism of
action and discriminative stimulus effects similar to the schedule I
substance, MDMA.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: PMMA is a substituted phenethylamine and is a methoxy-
derivative of methamphetamine. PMMA is also related to PMA and MDMA,
which are schedule I substances.
As stated by HHS, there are several sources describing the
synthesis of PMMA either directly or through alternate route by
conversion of PMA to PMMA. The precursor substances that can be used
for the synthesis of PMMA include methylamine, 4-methoxyphenyacetone,
and cyanoborohydride. Additional chemicals and solvents required for
PMMA synthesis include methanol, dichloromethane, isopropanol,
hydrochloric acid, ethyl chloroformate, trimethylamine, carbamate,
formamide, and lithium aluminum hydride.
Pharmacokinetic studies of PMMA in rats showed that after
subcutaneous administration, peak PMMA concentration was detected in
the plasma within 30 minutes. Brain levels of PMMA were delayed behind
the plasma levels for several hours. HHS states that this delay
supports user comments that PMMA has a longer onset of effect than
MDMA. Most of PMMA and its metabolites were excreted within the first
24-hours post-administration. Metabolites detected were products of O-
demethylation or N-demethylation of PMMA to 4-methoxyamphetamine (PMA),
4-hydroxymethamphetamine (OH-MAM), 4-hydroxyamphetamine (OH-AM), 4-
hydroxy-3'-methoxymethamphetamine (HM-MAM), and 4'-hydroxy-3'-
methoxyamphetamine (HM-AM). The cytochrome P450 enzyme CYP2D6 was
identified as being the only enzyme capable of demethylating PMMA.
PMMA toxicity data in animals demonstrate that toxicity occurs at
early stages of administration. In PMMA-dosed animals, prior to
lethality, hyperactivity, increased respiration, salivation, and tremor
were observed.
4. Its History and Current Pattern of Abuse: Abuse of PMMA was
first documented in the late 1980s and associated with ``ecstasy''
tablets as this drug was often substituted for MDMA. Abuse of PMMA has
been documented worldwide with usage particularly extensive in Europe,
Asia, and Canada. PMMA was originally used as a powder with doses
ranging around 100 mg or less. PMMA is now most commonly encountered in
a tablet form, and PMMA tablets have been seized in Europe, Asia, and
the United States.
PMMA tablets are primarily sold as ``ecstasy'' and are sometimes
encountered along with amphetamine, methamphetamine, or ephedrine. PMMA
tablets may be marked with different logos, including ``E,''
``Mitsubishi,'' ``Jumbo,'' or ``Superman.'' Street names for PMMA
tablets include ``Dr. Death,'' ``Death,'' or ``Killer.'' According to a
review of PMMA by the
[[Page 29363]]
European Monitoring Centre for Drugs and Drug Addition (EMCDDA) in
2003, tablets were reported to contain between 20 and 97 mg of PMMA.
PMMA is primarily administered orally in a tablet form. Data indicate
that MDMA is often mixed with other substances, one of which is PMMA.
It was observed that MDMA mixed with PMMA led to a higher number of
adverse events than other MDMA combinations. According to HHS, there is
little anecdotal information on the use of PMMA most likely because
individuals ingesting this substance in the context of abuse believe
they are taking MDMA rather than a mixture of drugs that may include
PMMA thus attributing its effects to MDMA.
DEA conducted a search of NFLIS and the System to Retrieve
Information from Drug Evidence (STRIDE)/STARLiMS for law enforcement
encounters of PMMA. Prior to October 1, 2014, STRIDE collected the
analytical results of drug evidence submitted by DEA, other Federal law
enforcement agencies, and some local law enforcement agencies to DEA
forensic laboratories. Since October 1, 2014, STARLiMS (a web-based,
commercial laboratory information management system) has replaced
STRIDE as DEA laboratory drug evidence data system of record. DEA
laboratory data submitted after September 30, 2014, are reposited in
STARLiMS. According to data from STRIDE \7\ and STARLiMS \8\ between
January 2000 and December 2018, DEA laboratories analyzed 41 drug
exhibits containing PMMA. NFLIS is a DEA program that collects drug
identification results from drug cases analyzed by other Federal,
State, and local forensic laboratories. Within the NFLIS database,
there have been 39 reports \9\ for PMMA between January 2002 and
October 2019, and no reports from January 2003 to December 2010,
January 2013 to December 2013, and January 2017 to December 2017 from
state and local laboratories. The NFLIS database shows there were two
reports in 2002 from one state; three reports from two states in 2011;
three reports from three states in 2012; 21 reports from one state in
2014; three reports from two states in 2015; two reports from one state
in 2016; four reports from two states in 2018; and one report from one
state in 2019.
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\7\ STRIDE data were queried through September 30, 2014, by the
date of collection for DEA forensic laboratories.
\8\ STRIDE/STARLIMS was queried October 23, 2019, by the date of
collection.
\9\ NFLIS is still reporting data for October-December 2018, due
to normal lag time in reporting.
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5. The Scope, Duration, and Significance of Abuse: PMMA abuse has
been associated with ``ecstasy'' tablets and is used as a substitute
for MDMA. As a result, most users think they are taking ``ecstasy''
with MDMA and are not intentionally purchasing PMMA on the illicit
market. One study reported that tablets containing a combination of
MDMA and PMMA resulted in adverse effects, such as hyperthermic
seizures, palpitations, agitation, nausea, and hallucinations. Most
abusers of PMMA take the drug in combination with other drugs as noted
in the PMMA-associated deaths (see Factor 6). Furthermore, there is
evidence of PMMA drug seizures or confiscation in the United States, as
reported by DEA's STRIDE/STARLiMS or NFLIS databases.
Numerous deaths and overdoses associated with PMMA usage
demonstrate that there is a considerable population abusing PMMA, and
its abuse is a significant public health concern. Prior to death,
individuals exhibit high temperatures, seizures, coma, and respiratory
distress. The PMMA-related public health risks, such as deaths and
overdoses, led the European Union Member States to control PMMA in
2002.
6. What, if Any, Risk There is to the Public Health: According to
HHS, there are several risk factors associated with the use of PMMA.
The first risk is that individuals inadvertently use PMMA because it is
sold as MDMA and such products may contain other drugs. This risk can
lead to poly-drug use, which is inherently more dangerous to the
individuals who consume such products. The second risk described by HHS
is the slow onset of action of PMMA compared to MDMA. The delay in
onset of effect for PMMA can make individuals consume more PMMA, and
such action can lead to overdose or death. Thirdly, HHS described that
the pharmacological actions of PMMA, such as increase in monoamine
levels (DA and 5-HT) combined with inhibition of monoamine oxidase-A,
an enzyme responsible for degradation of these monoamines, can lead to
a serious medical condition known as serotonin syndrome. The symptoms
of serotonin syndrome are similar to those seen when high doses of PMMA
are used. These include hyperthermia, tremor, agitation, and can result
in death.
Over a period of approximately 30 years starting in the 1990s, a
total of 131 analytically confirmed PMMA (detected in either blood and/
or urine)-associated deaths in Europe (69 deaths), Israel (27 deaths),
Canada (27 deaths), and Taiwan (8 deaths) has been reported. Published
case reports on PMMA-related deaths occurred mostly in males and ages
ranged from 14-59 years with the majority of them under the age of 30.
Common symptoms that were observed prior to death were hyperthermia,
decreased respiratory rate, seizures, and cardiac arrest. In most of
the PMMA-related fatalities, other drugs were detected in the blood or
urine.
7. Its Psychic or Physiological Dependence Liability: According to
HHS, abuse liability of PMMA has only been characterized through drug
discrimination studies. The drug discrimination studies do not provide
information that can be used to assess the psychic or physiological
dependence liability of PMMA, although they provide information on the
subjective effects of the drug. Data from drug discrimination studies
showed that both PMMA and MDMA share discriminative stimulus effects.
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition,
indicated that there is evidence of a withdrawal syndrome from MDMA
with observations of both psychological and physical dependence.
Similarities in the drug discriminative stimulus properties of PMMA and
MDMA indicate that the subjective effects of PMMA are similar to that
of the schedule I substance, MDMA. As stated by HHS, both PMMA and MDMA
also largely share a common mechanism of action. Thus, it is plausible
to extrapolate that PMMA has a dependence liability similar to that of
MDMA. HHS states some individuals have become tolerant to MDMA
resulting in taking high doses of the drug, and these individuals have
reported undergoing a withdrawal syndrome, although it is unclear
whether they were undergoing withdrawal or adverse effects from high
doses of MDMA. Thus, evidence suggests that MDMA causes psychological
dependence and may be associated with physical dependence, although not
to the same extent as that of cocaine.
HHS concludes that PMMA most likely has a psychic dependence
liability similar to that of MDMA, though not as strong as that of
cocaine. The use of PMMA may be associated with physical dependence.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA: PMMA is not an immediate precursor to
any substance already controlled in 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 8-
Factor analysis, DEA finds that the facts and all relevant data
constitute substantial evidence of the potential for
[[Page 29364]]
abuse of PMMA. As such, DEA hereby proposes to schedule PMMA as a
schedule I controlled substance 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 Health of HHS and review
of all available data, the Acting Administrator of DEA, pursuant to 21
U.S.C. 811(c) and 812(b)(1), finds the following:
(1) The Drug or Substance Has a High Potential for Abuse
PMMA has a mechanism of action similar to that of the schedule I
substance MDMA. Similar to MDMA, PMMA increases levels of monoamines,
specifically DA and 5-HT, in the brain reward circuitry. Data from
animal studies demonstrate that PMMA fully substitutes for the
discriminative stimulus effect of MDMA, indicative of similar
subjective effects. Although there is currently no data that has
directly assessed the psychological or physiological dependence
liability of PMMA, its pharmacological similarities to MDMA suggest it
likely has low physical dependence liability similar to that of MDMA.
Evidence demonstrates that users of PMMA seem to be seeking MDMA, which
may be mixed with PMMA. Because PMMA shares a pharmacological mechanism
of action and psychoactive effects similar to the schedule 1 substance
MDMA, PMMA has a high potential for abuse.
(2) The Drug or Substance Has No Currently Accepted Medical Use in
Treatment in the United States
According to HHS, FDA has not approved any marketing application
for a drug product containing PMMA for any indication. In addition,
there are no clinical studies or petitioners that have claimed an
accepted medical use of PMMA in the United States. Thus, PMMA has no
currently accepted medical use in treatment in the United States.\10\
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\10\ Although there is no evidence suggesting that PMMA has a
currently accepted medical use in treatment in the United States, it
bears noting that a drug cannot be found to have such medical use
unless DEA concludes that it satisfies a five-part test.
Specifically, with respect to a drug that has not been approved by
FDA, to have a currently accepted medical use in treatment in the
United States, all of the following must be demonstrated:
i. The drug's chemistry must be known and reproducible;
ii. there must be adequate safety studies;
iii. there must be adequate and well-controlled studies proving
efficacy;
iv. the drug must be accepted by qualified experts; and
v. the scientific evidence must be widely available.
57 FR 10499 (1992).
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(3) There Is a Lack of Accepted Safety for Use of the Drug or Substance
Under Medical Supervision
Because PMMA has no approved medical use in treatment in the United
States and has not been investigated as a new drug, its safety for use
under medical supervision has not been determined. Therefore, there is
a lack of accepted safety for use of PMMA under medical supervision.
Based on these findings, the Acting Administrator of DEA concludes
that PMMA warrants control in schedule I of the CSA. 21 U.S.C.
812(b)(1). More precisely, because PMMA shares a pharmacological
mechanism of action and psychoactive effects similar to the schedule 1
substance MDMA, DEA is proposing to place PMMA in 21 CFR 1308.11(d)
(the hallucinogenic category of schedule I). As such, the proposed
control of PMMA includes the substance, as well as its salts, isomers,
and salts of isomers whenever the existence of such isomers and salts
is possible, within the specific chemical designation.
Requirements for Handling PMMA
If this rule is finalized as proposed, PMMA would be subject to the
CSA's schedule I regulatory controls and administrative, civil, and
criminal sanctions applicable to the manufacture, distribution, reverse
distribution, import, export, engagement in research, conduct of
instructional activities or chemical analysis with, and possession of
schedule I controlled substances, including the following:
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) PMMA,
or who desires to handle PMMA, would need to be registered with DEA to
conduct such activities pursuant to 21 U.S.C. 822, 823, 957, 958, and
in accordance with 21 CFR parts 1301 and 1312, as of the effective date
of a final scheduling action. Any person who currently handles PMMA,
and is not registered with DEA, would need to submit an application for
registration and may not continue to handle PMMA after the effective
date of a final scheduling action unless DEA has approved that
application for registration pursuant to 21 U.S.C. 822, 823, 957, 958,
and in accordance with 21 CFR parts 1301 and 1312.
2. Disposal of stocks. Any person who does not desire or is not
able to obtain a schedule I registration would be required to surrender
all quantities of currently held PMMA or transfer all quantities of
currently held PMMA to a person registered with DEA before the
effective date of a final scheduling action, in accordance with all
applicable Federal, State, local, and tribal laws. As of the effective
date of a final scheduling action, PMMA would be required to be
disposed of in accordance with 21 CFR part 1317, in addition to all
other applicable Federal, State, local, and tribal laws.
3. Security. PMMA would be subject to schedule I security
requirements and would need to be handled and stored in accordance with
21 CFR 1301.71-1301.93 as of the effective date of a final scheduling
action.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of PMMA would need to be in compliance with 21
U.S.C. 825 and 958(e), and be in accordance with 21 CFR part 1302, as
of the effective date of a final scheduling action.
5. Quota. Only registered manufacturers would be permitted to
manufacture PMMA in accordance with a quota assigned, pursuant to 21
U.S.C. 826 and in accordance with 21 CFR part 1303, as of the effective
date of a final scheduling action.
6. Inventory. Every DEA registrant who possesses any quantity of
PMMA on the effective date of a final scheduling action would be
required to take an inventory of PMMA on hand at that time, pursuant to
21 U.S.C. 827 and 958, and in accordance with 21 CFR 1304.03, 1304.04,
and 1304.11(a) and (d).
Any person who becomes registered with DEA on or after the
effective date of the final scheduling action would be required to take
an initial inventory of all stocks of controlled substances (including
PMMA) on hand on the date the registrant first engages in the handling
of controlled substances, pursuant to 21 U.S.C. 827 and 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11(a) and (b).
After the initial inventory, every DEA registrant would be required
to take an inventory of all controlled substances (including PMMA) on
hand every two years, pursuant to 21 U.S.C. 827 and 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
[[Page 29365]]
7. Records and Reports. Every DEA registrant would be required to
maintain records and submit reports for PMMA, or products containing
PMMA, pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR
parts 1304, 1312, and 1317, as of the effective date of a final
scheduling action. Manufacturers and distributors would be required to
submit reports regarding PMMA 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, as of the effective date of a final
scheduling action.
8. Order Forms. Every DEA registrant who distributes PMMA would be
required to comply with order form requirements, pursuant to 21 U.S.C.
828, and in accordance with 21 CFR part 1305, as of the effective date
of a final scheduling action.
9. Importation and Exportation. All importation and exportation of
PMMA would need to be in compliance with 21 U.S.C. 952, 953, 957, and
958, and in accordance with 21 CFR part 1312, as of the effective date
of a final scheduling action.
10. Liability. Any activity involving PMMA not authorized by, or in
violation of, the CSA or its implementing regulations, would be
unlawful, and may subject the person to administrative, civil, and/or
criminal sanctions.
Regulatory Analyses
Executive Orders 12866, 13563, and 13771, Regulatory Planning and
Review, Improving Regulation and Regulatory Review, and Reducing
Regulation and Controlling Regulatory Costs
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 forth the
procedures and 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.
This rulemaking is not an Executive Order 13771 regulatory action
because this rule is not significant under Executive Order 12866.
Executive Order 12988, Civil Justice Reform
This proposed regulation meets the applicable standards set forth
in sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice
Reform, 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 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.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
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 Acting Administrator, in accordance with the Regulatory
Flexibility Act, 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.
DEA proposes placing the substance PMMA (chemical name: 1-(4-
methoxyphenyl)-N-methylpropan-2-amine), including its salts, isomers,
and salts of isomers whenever the existence of such salts, isomers, and
salts of isomers is possible, in schedule I of the CSA. This action is
being taken to enable the United States to meet its obligations under
the 1971 Convention on Psychotropic Substances. 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, reverse distribute,
import, export, engage in research, conduct instructional activities or
chemical analysis with, or possess), or propose to handle PMMA.
According to HHS, PMMA has a high potential for abuse, has no
currently accepted medical use in treatment in the United States, and
lacks accepted safety for use under medical supervision. DEA's research
confirms that there is no legitimate commercial market for PMMA in the
United States. Therefore, DEA estimates that no United States entity
currently handles PMMA and does not expect any United States entity to
handle PMMA in the foreseeable future. DEA concludes that no legitimate
United States entity would be affected by this rule if finalized. As
such, the proposed rule will not have a significant effect on a
substantial number of small entities.
Unfunded Mandates Reform Act of 1995
In accordance with Unfunded Mandates Reform Act (UMRA) of 1995, 2
U.S.C. 1501 et seq., DEA has determined and certifies 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 million 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 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 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), 956(b), unless otherwise
noted.
0
2. In Sec. 1308.11, add paragraph (d)(80) to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(d) * * *
[[Page 29366]]
(79) 1-(4-methoxyphenyl)-N-methylpropan-2-amine (other names: (1245)
para-methoxymethamphetamine, PMMA),.........................
* * * * *
Uttam Dhillon,
Acting Administrator.
[FR Doc. 2020-09599 Filed 5-14-20; 8:45 am]
BILLING CODE 4410-09-P