[Federal Register Volume 90, Number 110 (Tuesday, June 10, 2025)]
[Proposed Rules]
[Pages 24370-24378]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-10503]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA1146]
Schedules of Controlled Substances: Placement of 3-
Methoxyphencyclidine (1-[1-(3-methoxyphenyl) cyclohexyl]piperidine) 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 3-
methoxyphencyclidine, including its salts, isomers, and salts of
isomers, an arylcyclohexylamine hallucinogen, in schedule I of the
Controlled Substances Act. This action is proposed 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 3-methoxyphencyclidine.
DATES: Comments must be submitted electronically or postmarked on or
before July 10, 2025. Interested persons may file written comments on
this proposal in accordance with 21 CFR 1308.43(g). 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.
Requests for a hearing and waivers of an opportunity for a hearing
or to participate in a hearing, together with a written statement of
position on the matters of fact and law involved in the hearing, must
be received on or before July 10, 2025.
ADDRESSES: Interested persons may file written comments on this
rulemaking in accordance with 21 CFR 1308.43(g). To ensure proper
handling of comments, please reference ``Docket No. DEA1146'' on all
correspondence, including any attachments.
Electronic comments: The Drug Enforcement Administration
(DEA) encourages commenters to submit all comments 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 https://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. 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 electronic
submissions 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 filed with the
DEA Administrator, who will make the determination of whether a hearing
will be needed to address such matters of fact and law in the
rulemaking. Such requests must be sent to: Drug Enforcement
Administration, Attn: Administrator, 8701 Morrissette Drive,
Springfield, Virginia 22152. For informational purposes, a courtesy
copy of 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,
[[Page 24371]]
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive,
Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug and Chemical
Evaluation Section, Diversion Control Division, Drug Enforcement
Administration; Telephone: (571) 362-3249. As required by 5 U.S.C.
553(b)(4), a summary of this rule may be found in the docket for this
rulemaking at www.regulations.gov.
SUPPLEMENTARY INFORMATION: In this proposed rule, the Drug Enforcement
Administration (DEA) proposes to schedule 3-methoxyphencyclidine (1-[1-
(3-methoxyphenyl)cyclohexyl] piperidine; 3-MeO-PCP) in schedule I of
the Controlled Substances Act (CSA), including its salts, isomers, and
salts of isomers whenever the existence of such salts, isomers, and
salts of isomers is possible within the specific chemical designation.
Posting of Public Comments
Please note that all comments received in response to this docket
are considered part of the public record. DEA will make comments
available for public inspection online at https://www.regulations.gov.
Such information includes personal identifying information (such as
your name, address, State or Federal identifiers, etc.) voluntarily
submitted by the commenter. In general, all information voluntarily
submitted by the commenter, unless clearly marked as Confidential
Information in the method described below, will be publicly posted.
Comments may be submitted anonymously. The Freedom of Information Act
applies to all comments received.
Commenters submitting comments which include personal identifying
information (PII), confidential, or proprietary business information
that the commenter does not want made publicly available should submit
two copies of the comment. One copy must be marked ``CONTAINS
CONFIDENTIAL INFORMATION'' and should clearly identify all PII or
business information the commenter does not want to be made publicly
available, including any supplemental materials. DEA will review this
copy, including the claimed PII and confidential business information,
in its consideration of comments. The second copy should be marked ``TO
BE PUBLICLY POSTED'' and must have all claimed confidential PII and
business information already redacted. DEA will post only the redacted
comment on https://www.regulations.gov for public inspection.
For easy reference, an electronic copy of this document and
supplemental information to this proposed rule are available at https://www.regulations.gov.
Request for Hearing or Appearance; Waiver
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).\1\ Interested persons, as defined in 21 CFR 1300.01(b), may
file requests for a hearing in conformity with the requirements of 21
CFR 1308.44(a) and 1316.47(a), and such requests must:
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\1\ 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316,
subpart D.
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(1) state with particularity the interest of the person in the
proceeding;
(2) state with particularity the objections or issues concerning
which the person desires to be heard; and
(3) state briefly the position of the person with regard to the
objections or issues.
Any interested person may file a waiver of an opportunity for a
hearing or to participate in a hearing in conformity with the
requirements of 21 CFR 1308.44(c), together with a written statement of
position on the matters of fact and law involved in any hearing.\2\
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\2\ 21 CFR 1316.49.
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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. The decision whether a hearing will be
needed to address such matters of fact and law in the rulemaking will
be made by the Administrator. If a hearing is needed, DEA will publish
a notice of hearing on the proposed rulemaking in the Federal
Register.\3\ Further, once the Administrator determines a hearing is
needed to address such matters of fact and law in rulemaking, he will
then designate an Administrative Law Judge (ALJ) to preside over the
hearing. The ALJ's functions shall commence upon designation, as
provided in 21 CFR 1316.52.
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\3\ 21 CFR 1308.44(b), 1316.53.
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In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing
would be to determine whether 3-MeO-PCP meets the statutory criteria
for placement in schedule I.
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 (delegated to the Administrator of
DEA pursuant to 28 CFR 0.100) on his own motion. 21 U.S.C. 811(a). This
proposed action is supported by a recommendation from the then
Assistant Secretary for Health of the Department of Health and Human
Services (HHS).
In addition, 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, 1019 U.N.T.S. 175, 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 indicating that a drug or
other substance has been added to a schedule specified in the
notification, the Secretary of HHS (Secretary),\4\ after 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.\5\ In the event that the Secretary did not so
consult with the Attorney General, 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 (as
delegated to the Administrator of DEA) 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.
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\4\ 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 has delegated to the Assistant Secretary for Health of HHS
the authority to make domestic drug scheduling recommendations. 58
FR 35460 (July 1, 1993).
\5\ 21 U.S.C. 811(d)(3).
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[[Page 24372]]
Background
3-Methoxyphencyclidine (1-[1-(3-
methoxyphenyl)cyclohexyl]piperidine; 3-MeO-PCP) is an
arylcyclohexylamine that has been identified in the United States'
illicit drug market. It is a 3-methoxy derivative of phencyclidine
(PCP; schedule II substance) and produces similar hallucinogenic
effects as PCP. 3-MeO-PCP has no approved medical use in the United
States.
On June 10, 2021, the Secretary-General of the United Nations
advised the Secretary of State of the United States that the Commission
on Narcotic Drugs (CND), during its 64th Session in April 2021, voted
to place 3-MeO-PCP in Schedule II of the 1971 Convention (CND Decision
64/4). As a signatory to this international treaty, the United States
is required, by scheduling under the CSA, to place appropriate controls
on 3-MeO-PCP to meet the minimum requirements of the treaty. The
relevant treaty provisions and domestic statutes executing those
provisions are below.
To begin, Article 2, paragraph 7(b), of the 1971 Convention sets
forth the minimum requirements that the United States must meet when a
substance has been added to Schedule II of the 1971 Convention.
Pursuant to the 1971 Convention, the United States must require
licenses for the manufacture, export and import, and distribution of 3-
MeO-PCP. The CSA's registration requirement as set forth in 21 U.S.C.
822, 823, 957, and 958, as well as implementing regulations in 21 CFR
parts 1301 and 1312, set forth this licensing requirement.
In addition, the United States must adhere to specific export and
import provisions that are provided in the 1971 Convention. The CSA's
export and import provisions established in 21 U.S.C. 952, 953, 957,
and 958, and implemented in 21 CFR part 1312, execute these
requirements.
Likewise, under Article 13, paragraphs 1 and 2, of the 1971
Convention, a party to the 1971 Convention may notify another party,
through the UN Secretary-General, that it prohibits the importation of
a substance in Schedule II, III, or IV of the 1971 Convention. If such
notice is presented to the United States, the United States shall take
measures to ensure that the named substance is not exported to the
country of the notifying party. The CSA's above-mentioned export
provisions set forth these procedures.
Further, under Article 16, paragraph 4, of the 1971 Convention, the
United States is required to provide annual statistical reports to the
International Narcotics Control Board (INCB). Using INCB Form P, the
United States shall provide the following information: (1) In regard to
each substance in Schedule I and II of the 1971 Convention, quantities
manufactured, exported to and imported from each country or region as
well as stocks held by manufacturers; (2) in regard to each substance
in Schedule III and IV of the 1971 Convention, quantities manufactured,
as well as quantities exported and imported; (3) in regard to each
substance in Schedule II and III of the 1971 Convention, quantities
used in the manufacture of exempt preparations; and (4) in regard to
each substance in Schedule II-IV of the 1971 Convention, quantities
used for the manufacture of non-psychotropic substances or products.
Lastly, under Article 2, paragraph 7(b)(vi) of the 1971 Convention,
the United States must adopt measures in accordance with Article 22 to
address violations of any statutes or regulations that are adopted
pursuant to its obligations under the 1971 Convention. The United
States complies with this provision, as persons acting outside the
legal framework established by the CSA are subject to administrative,
civil, and/or criminal action.
DEA notes that there are differences between the schedules of
substances in the 1971 Convention and the CSA. The CSA has five
schedules (schedules I-V) with specific criteria set forth for each
schedule. Schedule I is the only possible schedule in which a drug or
other substance may be placed if it has high potential for abuse and no
currently accepted medical use in treatment in the United States. See
21 U.S.C. 812(b). In contrast, the 1971 Convention has four schedules
(Schedules I-IV) but does not have specific criteria for each schedule.
The 1971 Convention simply defines its four schedules, in Article 1, to
mean the correspondingly numbered lists of psychotropic substances
annexed to the Convention, and altered in accordance with Article 2.
Proposed Determination to Schedule 3-MeO-PCP
Pursuant to 21 U.S.C. 811(b), DEA gathered the necessary data on 3-
MeO-PCP and on October 25, 2021, submitted it to the then Assistant
Secretary for Health of HHS with a request for a scientific and medical
evaluation of available information and a scheduling recommendation for
3-MeO-PCP. On November 15, 2022, HHS provided to DEA a scientific and
medical evaluation entitled ``Basis for the Recommendation to Control
1-[1-(3-Methoxyphenyl)cyclohexyl]piperidine and its Salts in Schedule I
of the Controlled Substances Act'' and a scheduling recommendation.
Following consideration of the eight factors and findings related to
these substances' abuse potential, legitimate medical use, and
dependence liability, HHS recommended that 3-MeO-PCP and its salts be
controlled in schedule I of the CSA under 21 U.S.C. 812(b).
In response, DEA reviewed the scientific and medical evaluation and
scheduling recommendation provided by HHS and all other relevant data,
and completed its own eight-factor review pursuant to 21 U.S.C. 811(c).
Included below is a brief summary of each factor as analyzed by HHS and
DEA in their respective eight-factor analyses, and as considered by DEA
in this proposed scheduling determination. Please note that both the
DEA and HHS analyses, including the evaluation of the eight factors
determinative of control along with their supporting data and
citations, are available in their entirety under ``Supporting
Documents'' of the public docket for this proposed rule at https://www.regulations.gov under docket number ``DEA-1146.''
1. The Drug's Actual or Relative Potential for Abuse
In addition to considering the information HHS provided in its
scientific and medical evaluation document for 3-MeO-PCP, DEA also
considered all other relevant data regarding actual or relative
potential for abuse of 3-MeO-PCP. The term ``abuse'' is not defined in
the CSA; however, the legislative history of the CSA suggests the
consideration of the following four criteria in determining whether a
particular drug or substance has a potential for abuse: \6\
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\6\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., 2nd Sess. (1970) reprinted in
1970 U.S.C.C.A.N. 4566, 4603.
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a. Individuals are taking the drug or other 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 a significant diversion of the drug or other substance
from legitimate drug channels; or
c. Individuals are taking the drug or other substance on their own
initiative rather than on the basis of medical advice from a
practitioner licensed by law to administer such substance; or
d. The drug or substance is so related in its action to a drug or
other substance already listed as having a potential for abuse to make
it likely that it will have
[[Page 24373]]
the same potential for abuse as such substance, 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.
DEA reviewed the scientific and medical evaluation provided by HHS
and all other data relevant to the abuse potential of 3-MeO-PCP. These
data as presented below demonstrate that 3-MeO-PCP has a high potential
for abuse.
a. There is evidence that individuals are taking the drug or other
substance in amounts sufficient to create a hazard to their health or
to the safety of other individuals or to the community.
Data show that 3-MeO-PCP has been encountered by law enforcement in
the United States (see Factor 5 below, discussing evidence of abuse in
the United States), indicating 3-MeO-PCP is available for abuse. Non-
fatal and fatal intoxications have been reported in the United States
and Europe. The 2020 European Monitoring Centre for Drugs and Drug
Addiction (EMCDDA) \7\ report on 3-MeO-PCP mentioned 19 cases of severe
intoxication that resulted in hospitalization and 21 confirmed deaths
(by analysis of postmortem biological samples). 3-MeO-PCP was
determined to be the cause of death in at least seven of those cases
(WHO, 2020). According to HHS, individuals are using 3-MeO-PCP for its
hallucinogenic effects and taking it in amounts sufficient to create a
hazard to their health.
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\7\ The European Monitoring Centre for Drugs and Drug Addiction
(EMCDDA) is an agency of the European Union tasked with gathering
and analyzing data of drug trends.
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b. There is significant diversion of the drug or substance from
legitimate drug channels.
HHS states that 3-MeO-PCP is not a Food and Drug Administration
(FDA)-approved drug for treatment in the United States and is unaware
of any country in which its use is legal. 3-MeO-PCP is available for
purchase from legitimate chemical synthesis companies because it is
used in scientific research.
EMCDDA reported drug seizures of 3-MeO-PCP from 12 countries,
including several European countries (Lithuania, Romania, Italy, Spain,
Latvia, Austria, Slovenia, and France) and noted that 24 countries had
the capability to detect 3-MeO-PCP in drug samples (WHO, 2020).
NFLIS-Drug \8\ data reflects that 3-MeO-PCP is present in the U.S.
drug market. DEA interprets this to mean that 3-MeO-PCP is being abused
domestically as a recreational drug. From January 2011 to August 2024,
NFLIS-Drug registered 399 reports from several states pertaining to the
trafficking, distribution, and abuse of 3-MeO-PCP. These encounters of
3-MeO-PCP by law enforcement indicate that this substance is being
trafficked in the United States.
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\8\ NFLIS-Drug represents an important resource in monitoring
illicit drug trafficking, including the diversion of legally
manufactured pharmaceuticals into illegal markets. NFLIS is a
comprehensive information system that includes data from forensic
laboratories that handle more than 96% of an estimated 1 million
distinct annual state and local drug analysis cases. NFLIS includes
drug chemistry results only from completed analyses. Although NFLIS-
Drug data are not direct evidence of abuse, they can lead to an
inference that a drug has been diverted and abused. See 76 FR 77330,
77332 (Dec. 12, 2011). NFLIS-Drug data was queried on September 6,
2024.
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c. Individuals are taking the substance on their own initiative
rather than on the basis of medical advice from a practitioner licensed
by law to administer such substance.
3-MeO-PCP is not an FDA-approved drug product and practitioners may
neither legally prescribe nor dispense these substances. Therefore, it
is inferred that individuals are taking 3-MeO-PCP on their own
initiative, rather than based on medical advice from practitioners
licensed by law to administer drugs. This is consistent with the data
from law enforcement seizures and case reports, discussed in greater
detail in Factor 5.
d. The drug or substance is so related in its action to a drug or
other substance already listed as having a potential for abuse to make
it likely that the drug or substance will have the same potential for
abuse as such drugs, thus making it reasonable to assume that there may
be significant diversion 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.
3-MeO-PCP is a synthetic arylcyclohexylamine and is a 3-methoxy
analogue of the abused drug phencyclidine (PCP; schedule II) and has
pharmacological properties similar to other arylcyclohexylamines such
as PCP and ketamine (schedule III). Both the DEA and the HHS analyses
concluded that 3-MeO-PCP is being abused for its hallucinogenic
effects.
PCP is a hallucinogen with a long history of abuse with clinical
effects that include dissociation and euphoria. 3-MeO-PCP has a similar
pharmacological profile to PCP, where the primary mechanism of action
is thought to be on glutamatergic neurotransmission. Glutamate is the
major excitatory neurotransmitter system in the brain. In vitro binding
studies show that 3-MeO-PCP binds to the glutamatergic N-methyl-D-
aspartate (NMDA) receptor and acts as an antagonist with higher potency
compared to PCP (schedule II) and ketamine (schedule III). As a result,
3-MeO-PCP is expected to have a high abuse potential and pose a high
risk to public health (HHS, 2022).
Due to the psychological and cognitive disturbances associated with
3-MeO-PCP, as with other similar schedule II and III hallucinogens
noted above, it is reasonable to conclude that 3-MeO-PCP has
substantial capability to be a hazard to the health of the user and to
the safety of the community.
2. Scientific Evidence of the Drug's Pharmacological Effects, If Known
3-MeO-PCP is a novel psychoactive substance with a mechanism of
action similar to PCP that produces psychopharmacological effects
similar to other dissociative amnestic drugs such as PCP and ketamine.
Based on non-clinical in vitro studies, 3-MeO-PCP has higher affinity
for the NMDA receptor and acts as an antagonist, suggesting it may have
greater potency than PCP or ketamine. 3-MeO-PCP also interacts with
monoamine transmission through binding at the serotonin transporter and
increasing serotonin transmission. Non-clinical in vivo studies show 3-
MeO-PCP acts as a NMDA receptor antagonist through the Maximal
Electroshock Seizure (MES) test and substitutes for PCP in drug
discrimination. Although no clinical studies have been performed for 3-
MeO-PCP, case reports show that the effects of 3-MeO-PCP are similar to
abuse of or intoxication with PCP.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance
3-MeO-PCP is a centrally-acting hallucinogen that is part of the
arylcyclohexylamine hallucinogen family and shares structural
similarities with schedule II and III phenethylamine hallucinogens such
as PCP and ketamine. 3-MeO-PCP (Chemical Abstracts Service Registry
Number 72242-03-6) has a molecular formula of
C18H27NO and a molecular weight of 273.41 g/mol.
The half-life of 3-MeO-PCP is estimated to be 10-11 hours. 3-MeO-PCP
undergoes extensive metabolism, such that at least 30 phase I and II
metabolites can be generated. Globally, there have been at least 19
cases of severe intoxication that required hospitalization and 21
deaths, where 3-MeO-PCP was identified in the blood of the decedent. In
at least seven
[[Page 24374]]
of those deaths, 3-MeO-PCP was listed as the cause of death. HHS notes
that in many of the cases reported by the WHO, other drugs of abuse
were also identified clouding the direct toxicity of 3-MeO-PCP, and
there is not sufficient information otherwise available to provide
specific toxicity information regarding 3-MeO-PCP since its usage was
primarily with other substances or lacking poly substance use
information.
4. Its History and Current Pattern of Abuse
3-MeO-PCP is a relatively new drug in the drug abuse and drug
trafficking setting, and thus, there is relatively little information
related to its history and pattern of abuse. The World Health
Organization (WHO) reports that 3-MeO-PCP has been available in Europe
since 2010. Distribution and trafficking of 3-MeO-PCP began increasing
in 2011 (WHO, 2020). The history and current pattern of abuse of 3-MeO-
PCP is described in law enforcement reports and anecdotal reports by
drug abusers. In the United States, law enforcement entities initially
encountered 3-MeO-PCP in 2011, according to the National Forensic
Laboratory Information System (NFLIS)-Drug \9\ database. See Factor 5
for additional information.
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\9\ NFLIS-Drug is a national forensic laboratory reporting
system that systematically collects results from drug chemistry
analyses conducted by state and local forensic laboratories in the
United States. NFLIS-Drug data were queried on September 6, 2024.
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HHS noted that since 3-MeO-PCP is an analogue of PCP with similar
mechanisms of action, the extensive history and pattern of PCP abuse
may be appropriate to inform on the potential pattern of abuse of 3-
MeO-PCP. The 2011 Substance Abuse and Mental Health Services
Administration reported 75,538 emergency department visits related to
PCP use. The 2011 National Survey on Drug Use and Health data showed
that 6.1 million Americans, 12 years or older, reported using PCP in
their lifetime. A case series study conducted at a tertiary care center
reported patients with PCP intoxication tended to be young males who
presented with signs and symptoms of retrograde amnesia, nystagmus,
hypertension, and agitation. Coadministration with other substances was
common (e.g., benzodiazepines, alcohol, marijuana, cocaine).
5. The Scope, Duration, and Significance of Abuse
3-MeO-PCP has pharmacological effects similar to the schedule II
hallucinogen PCP (with higher potency) and has no currently accepted
medical use in the United States or anywhere in the world. HHS states
(2022) it is not associated with an investigational new drug
application or an approved new drug application.
In the United States, evidence of abuse of 3-MeO-PCP initially
appeared in 2011, one year later than was reported by the EMCDDA. Since
then, reports of worldwide abuse have increased substantially.
According to the WHO Critical Review Report published in 2020, 15
countries reported that 3-MeO-PCP was being used by individuals for its
psychoactive properties. The WHO document also reported a total of 314
drug seizures from 2018-2020. Within the United States, from January
2011 to August 2024, there were 399 exhibits reported to the NFLIS-Drug
database, which show evidence of trafficking, distribution, and abuse
of 3-MeO-PCP in 33 states.
Case reports and case series of abuse and deaths associated with 3-
MeO-PCP have been published globally. 3-MeO-PCP is typically abused
orally and by insufflation (sniffing or snorting), but has also been
reported to be smoked, inhaled, or vaporized. It is often used with
other substances (e.g., benzodiazepines, cannabinoids). Clinical
effects from 3-MeO-PCP are similar to other abused arylcyclohexylamines
hallucinogens (e.g., PCP) and include confusion, dissociation,
hallucinations, sedation through agitation, disinhibition, euphoria,
cognitive changes, sensory changes, motor changes, and cardiovascular
effects (e.g., hypertension and tachycardia).
Abuse of 3-MeO-PCP has been characterized as causing acute public
health and safety issues worldwide. The WHO reported that 3-MeO-PCP has
been available in Europe since 2010. Based on available abuse data,
public health risk, and drug trafficking data, the WHO recommended to
the United Nations (UN) that 3-MeO-PCP be controlled internationally.
In April 2021, the UN Commission on Narcotic Drugs voted to place 3-
MeO-PCP into Schedule II of the 1971 Convention.
6. What, if Any, Risk There Is to the Public Health
3-MeO-PCP shares similar mechanisms of action with and produces
similar physiological and subjective effects (see Factor 2 for more
information) as other schedule II and III hallucinogens, such as PCP
and ketamine. Thus, 3-MeO-PCP poses the same risks to public health as
similar hallucinogens. Predominantly, the risks to public health are
borne by users (i.e., hallucinogenic effects, sensory distortion,
impaired judgement, strange or dangerous behaviors), but they can
affect the general public, as with driving under the influence. There
have been reports of distressing responses and death associated with 3-
MeO-PCP in medical literature, many of which, but not all, report poly-
substance use. Adverse events associated with 3-MeO-PCP have been
reported and include, but not limited to, hypertension, confusion,
dissociation, hallucinations, tachycardia, nystagmus, respiratory
acidosis, hypothermia, coma, and death. The 2020 review published by
the WHO noted at least 19 cases of severe intoxications occurred after
use of 3-MeO-PCP that required hospitalization and 21 deaths were
reported where 3-MeO-PCP was confirmed in blood samples. At least seven
of those deaths were attributed to 3-MeO-PCP as the cause of death.
Thus, based on the review of both HHS and DEA, serious adverse events
that may include death represent a risk to the individual drug users
and to public health.
7. Its Psychic or Physiological Dependence Liability
HHS noted that a study with 4-MeO-PCP (a structural isomer) does
produce rewarding (conditioned place preference) and reinforcing
effects (self-administration) through activation of the mesolimbic
dopamine reward pathway in rats. Therefore, HHS concluded that it is
likely that 3-MeO-PCP produces similar effects in rats. The only
literature available on human exposure to 3-MeO-PCP is based on case
study reports, two of which indicate long-term use of 3-MeO-PCP.
[[Page 24375]]
HHS noted that no studies have evaluated the dependence potential
of 3-MeO-PCP. However, 3-MeO-PCP has similar pharmacological properties
of PCP (schedule II) and ketamine (schedule III), which do have well-
demonstrated dependence potential. Thus, the HHS and DEA reviews both
concluded that it is probable that 3-MeO-PCP has a dependence profile
similar to these known substances.
8. Whether the Substance Is an Immediate Precursor of a Substance
Already Controlled Under the CSA
3-MeO-PCP is not an immediate precursor of any controlled substance
of the CSA as defined by 21 U.S.C. 802(23).
Conclusion
Based on consideration of the scientific and medical evaluation and
accompanying recommendation of HHS, and on DEA's own eight-factor
analysis, DEA finds that these facts and all relevant data constitute
substantial evidence of potential for abuse of 3-MeO-PCP. As such, DEA
proposes to schedule 3-MeO-PCP as a 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,
per 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 Acting Administrator of DEA, pursuant
to 21 U.S.C. 812(b)(1), finds that:
(1) 3-MeO-PCP has a high potential for abuse.
3-MeO-PCP is a synthetic arylcyclohexylamine, chemically related
and pharmacologically similar to the ethylamine analog of phencyclidine
(PCE; schedule I), the thiophene analog of phencyclidine (TCP; schedule
I), phencyclidine (PCP, schedule II), and ketamine (schedule III). 3-
MeO-PCP, similar to PCP and ketamine, produces dissociative anesthetic
and hallucinogenic effects.
3-MeO-PCP has a pharmacological profile similar to other
arylcyclohexylamines, such as PCP (schedule II) and ketamine (schedule
III). Binding studies demonstrate a similar mechanism of action (i.e.,
NMDA receptor antagonism) and case reports indicate that 3-MeO-PCP
clinically resembles PCP intoxication (i.e., hallucinogenic effects).
Little evidence exists regarding 3-MeO-PCP direct psychic or
physiologic dependence liability; 3-MeO-PCP fully substituted for PCP
in drug discrimination studies. However, it can be assumed from the
above evidence (Factor 7) that 3-MeO-PCP has a physical dependence
liability similar to these controlled substances, with evidence of
dependence potential.
(2) 3-MeO-PCP has no currently accepted medical use in treatment in
the United States.
3-MeO-PCP is not legally marketed in the United States, as the FDA
has not approved a marketing application for a drug product containing
3-MeO-PCP for any indication. As noted in the HHS review, 3-MeO-PCP
lacks current marketing approval under a new drug application or an
abbreviated new drug application, and is not subject to an
investigational new drug application. There is no evidence that 3-MeO-
PCP has a currently accepted medical use in treatment in the United
States.\10\
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\10\ To place a drug or other substance in schedule I under the
CSA, DEA must consider whether the substance has a currently
accepted medical use in treatment in the United States. 21 U.S.C.
812(b)(1)(B). There is no evidence suggesting that 3-MeO-PCP has a
currently accepted medical use in treatment in the United States. To
determine whether a drug or other substance has a currently accepted
medical use, DEA has traditionally applied a five-part test to a
drug that has not been approved by FDA: 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.
Marijuana Scheduling Petition; Denial of Petition; Remand, 57 FR
10499 (Mar. 26, 1992), pet. for rev. denied, Alliance for Cannabis
Therapeutics v. Drug Enforcement Admin., 15 F.3d 1131, 1135 (D.C.
Cir. 1994). DEA and HHS applied the traditional five-part test for
currently accepted medical use in this matter. In a recent published
letter in a different context, HHS applied an additional two-part
test to determine currently accepted medical use for substances that
do not satisfy the five-part test: (1) whether there exists
widespread, current experience with medical use of the substance by
licensed health care practitioners operating in accordance with
implemented jurisdiction-authorized programs, where medical use is
recognized by entities that regulate the practice of medicine, and,
if so, (2) whether there exists some credible scientific support for
at least one of the medical conditions for which the part 1 is
satisfied. On April 11, 2024, the Department of Justice's Office of
Legal Counsel (OLC) issued an opinion, which, among other things,
concluded that HHS's two-part test would be sufficient to establish
that a drug has a currently accepted medical use. Office of Legal
Counsel, Memorandum for Merrick B. Garland Attorney General Re:
Questions Related to the Potential Rescheduling of Marijuana at 3
(April 11, 2024). For purposes of this proposed rule, there is no
evidence that health care providers have widespread experience with
medical use of 3-MeO-PCP, or that the use of 3-MeO-PCP is recognized
by entities that regulate the practice of medicine under either the
traditional five-part test or the two-part test.
---------------------------------------------------------------------------
(3) There is a lack of accepted safety for use of 3-MeO-PCP under
medical supervision.
Because 3-MeO-PCP has no approved medical use and has not been
thoroughly investigated as a new drug, its safety for use under medical
supervision is not determined. Thus, there is a lack of accepted safety
for use of this substance under medical supervision.
Based on these findings, the Acting Administrator of DEA concludes
that 3-MeO-PCP warrants control in schedule I of the CSA. More
precisely, because of its hallucinogenic effects, and because it may
produce hallucinogenic-like dependence in humans, DEA proposes to place
3-MeO-PCP, including its salts, isomers, and salts of isomers whenever
the existence of such salts, isomers, and salts of isomers is possible
within the specific chemical description, in 21 CFR 1308.11(d) (the
hallucinogenic substances category of schedule I).
Requirements for Handling 3-MeO-PCP
If this rule is finalized as proposed, 3-MeO-PCP would be subject
to the CSA's schedule I regulatory controls and administrative, civil,
and criminal sanctions applicable to the manufacture, distribution,
dispensing, importing, exporting, research, and conduct of
instructional activities, including the following:
1. Registration. Any person who handles (manufactures, distributes,
dispenses, imports, exports, engages in research, or conducts
instructional activities or chemical analysis with, or possesses) 3-
MeO-PCP would need 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. 3-MeO-PCP would be subject to schedule I security
requirements, and handled and stored pursuant to 21 U.S.C. 821, 823,
and in accordance with 21 CFR 1301.71-1301.76. Non-practitioners
handling this substance also would need to comply with the screening
requirements of 21 CFR 1301.90-1301.93.
3. Labeling and Packaging. All labels and packaging for commercial
containers of 3-MeO-PCP would need to comply with 21 U.S.C. 825, and be
in accordance with 21 CFR part 1302.
4. Quota. Only registered manufacturers would be permitted to
manufacture 3-MeO-PCP 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 3-MeO-PCP
would need to have an initial inventory of all
[[Page 24376]]
stocks of controlled substances (including this substance) on hand on
the effective date of a final scheduling action 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 would need to
take a new inventory of all stocks of controlled substances (including
3-MeO-PCP) 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 would need to maintain
records and submit reports with respect to 3-MeO-PCP, pursuant to 21
U.S.C. 827 and 832(a), and in accordance with 21 CFR 1301.74 and
1301.76, and parts 1304, 1312, and 1317.
7. Order Forms. Every DEA registrant who distributes 3-MeO-PCP
would need 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
3-MeO-PCP would need to be in compliance with 21 U.S.C. 952, 953, 957,
and 958, and in accordance with 21 CFR part 1312.
9. Liability. Any activity involving 3-MeO-PCP 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 and 13563, and 14192 (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 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
pursuant to section 3(d)(1) of Executive Order (E.O.) 12866 and the
principles reaffirmed in E.O. 13563. DEA scheduling actions are not
subject to E.O. 14192, Unleashing Prosperity Through Deregulation.
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 on 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.
Paperwork Reduction Act
This proposed rule would not impose a new collection or modify an
existing collection of information under the Paperwork Reduction Act of
1995. Also, this proposed rule would not impose new or modify existing
recordkeeping or reporting requirements on state or local governments,
individuals, businesses, or organizations. However, this proposed rule
would require compliance with the following existing OMB collections:
1117-0003, 1117-0004, 1117-0006, 1117-0008, 1117-0009, 1117-0010, 1117-
0012, 1117-0014, 1117-0021, 1117-0023, 1117-0029, and 1117-0056. 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.
Regulatory Flexibility Act
The Acting 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.
DEA proposes placing the substance 3-MeO-PCP (chemical name: 1-[1-
(3-methoxyphenyl)cyclohexyl]piperidine), including its salts, isomers,
and salts of isomers whenever the existence of such salts, isomers, and
salts of isomers is possible within the specific chemical designation,
in schedule I of the CSA. This action is being taken, in part, to
enable the United States to meet its obligations under the 1971
Convention. 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 or propose to
handle 3-MeO-PCP.
The entities affected by this rule include the manufacturers,
distributors, importers, exporters, and researchers of 3-MeO-PCP. DEA
determined the North American Industry Classification System (NAICS)
industries that best represent these business activities. Table 1 lists
the business activities and corresponding NAICS industries.\11\
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\11\ Executive Office of the President Office of Management and
Budget, North American Industry Classification System, United
States, 2022, https://www.census.gov/naics/reference_files_tools/2022_NAICS_Manual.pdf. (Accessed 4/2/2024).
Table 1--Business Activity and Corresponding NAICS Industries
------------------------------------------------------------------------
NAICS industry
Business activity NAICS code description
------------------------------------------------------------------------
Manufacturer................... 325412 Pharmaceutical
Preparation
Manufacturing.
Distributor, Importer, Exporter 424210 Drugs and Druggists'
424690 Sundries Merchant
Wholesalers.
Other Chemical and
Allied Products
Merchant Wholesalers.
Researcher..................... 541715 Research and
611310 Development in the
Physical, Engineering,
and Life Sciences
(except Nanotechnology
and Biotechnology).
Colleges, Universities
and Professional
Schools.
------------------------------------------------------------------------
From Statistics of U.S. Businesses (SUSB) data, DEA determined the
number of firms and small firms for each of the affected industries,
and by comparing the number of affected small entities to the number of
small entities
[[Page 24377]]
for each industry, DEA determined whether a substantial number of small
entities are affected in any of the industries. Table 2 lists the
number of firms, small firms, and percent small firms in each affected
industry.
Table 2--Percent Small Entities by Industry
----------------------------------------------------------------------------------------------------------------
SBA size Small firms Percent small
NAICS industry Firms \12\ standard \13\ \14\ entities (%)
----------------------------------------------------------------------------------------------------------------
325412--Pharmaceutical Preparation Manufacturing 1,007 1,300 931 92.4
424210--Drugs and Druggists' Sundries Merchant 6,958 250 6,663 95.8
Wholesalers....................................
424690--Other Chemical and Allied Products 6,069 175 5,781 95.3
Merchant Wholesalers...........................
541715--Research and Development in the 8,019 1,000 7,571 94.4
Physical, Engineering, and Life Sciences
(except Nanotechnology and Biotechnology)......
611310--Colleges, Universities and Professional 2,433 $34.5 1,515 62.3
Schools........................................
----------------------------------------------------------------------------------------------------------------
Based on the American Chemical Society's SciFinder database, DEA
identified 13 entities supplying 3-MeO-PCP across these industries.
Suppliers include 325412, 424210, and 424690 industries. Even if all
affected suppliers were small entities, they would account for only
0.10 percent of the small entities in those industries, not a
substantial number.\15\ Additionally, DEA expects the number of
researchers working with 3-MeO-PCP is small because 3-MeO-PCP lacks
current marketing approval under a new drug application or an
abbreviated new drug application, and is not subject to an
investigational new drug application as noted in the HHS review. Also,
DEA believes the researchers working with 3-MeO-PCP may also work with
other controlled substances; hence, they have probably already
registered with DEA and are qualified to handle controlled substances.
For these reasons DEA believes the number of affected researchers that
are small entities is not a substantial number of small entities in
541715 and 622310 industries.
---------------------------------------------------------------------------
\12\ Statistics of U.S. Businesses, 2021 SUSB Annual Data Tables
by Establishment Industry, https://www.census.gov/data/tables/2021/econ/susb/2021-susb-annual.html (Accessed 4/2/2024).
\13\ U.S. Small Business Administration, Table of size
standards, Version March 2023, Effective: March 17, 2023, https://www.sba.gov/sites/sbagov/files/2023-06/Table%20of%20Size%20Standards_Effective%20March%2017%2C%202023_.xlsx.
(Accessed 4/2/2024).
\14\ Note 12.
\15\ 13/(931 + 6,664 + 5,781) = 0.10%.
---------------------------------------------------------------------------
The primary costs associated with this proposed rule would be the
annual registration fee for Schedule I controlled substances ($3,699
for manufacturers, $1,850 for distributors, and $296 for researchers).
As mentioned above, DEA has identified 13 domestic suppliers of 3-MeO-
PCP from the SciFinder database and none of these suppliers has
registered with DEA to handle Schedule I controlled substances.
However, it is common for suppliers to have items in their catalog
while not actually having any material level of sales because FDA has
not approved a marketing application for a drug product containing 3-
MeO-PCP. Therefore, some suppliers may simply remove 3-MeO-PCP from
their catalog without any impact. Additionally, as discussed above, the
researchers who work with 3-MeO-PCP are likely to work with other
controlled substances and hence, must already register with DEA.
In summary, the small entities impacted by this rule are those in
325412-Pharmaceutical Preparation Manufacturing, 424210-Drugs and
Druggists' Sundries Merchant Wholesalers, and 424690-Other Chemical and
Allied Products Merchant Wholesalers. The affected small entities
account for only 0.1 percent of the small businesses and are not likely
to manufacture or carry 3-MeO-PCP inventory. As such, the proposed rule
will not, if promulgated, result in a significant effect on a
substantial number of small entities.
Unfunded Mandates Reform Act of 1995
On the basis of information contained in the ``Regulatory
Flexibility Act'' section above, DEA has determined pursuant to the
Unfunded Mandates Reform Act (UMRA) of 1995 (2 U.S.C. 1501 et seq.)
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.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, 21 CFR part 1308 is proposed to be
amended to read as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for 21 CFR part 1308 continues to read as
follows:
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. In Sec. 1308.11, add paragraph (d)(105) to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(d) * * *
------------------------------------------------------------------------
------------------------------------------------------------------------
* * * * * * *
(105) 3-methoxyphencyclidine (Other names: 1-[1-(3- 7457
methoxyphenyl)cyclohexyl] piperidine; 3-MeO-PCP)..............
* * * * * * *
------------------------------------------------------------------------
* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
June 3, 2025, by Acting Administrator Robert J. Murphy. That document
with the original signature and date is maintained by DEA. For
administrative purposes only, and in
[[Page 24378]]
compliance with requirements of the Office of the Federal Register, the
undersigned DEA Federal Register Liaison Officer has been authorized to
sign and submit the document in electronic format for publication, as
an official document of DEA. This administrative process in no way
alters the legal effect of this document upon publication in the
Federal Register.
Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2025-10503 Filed 6-9-25; 8:45 am]
BILLING CODE 4410-09-P