[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\
---------------------------------------------------------------------------

    \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