Proposed Rule2026-10380
Schedules of Controlled Substances: Placement of Diphenidine in Schedule I
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
May 26, 2026
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration proposes placing diphenidine (1-(1,2-diphenylethyl)piperidine), 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, in part, 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 diphenidine.
Full Text
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<title>Federal Register, Volume 91 Issue 100 (Tuesday, May 26, 2026)</title>
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[Federal Register Volume 91, Number 100 (Tuesday, May 26, 2026)]
[Proposed Rules]
[Pages 30519-30526]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-10380]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA1155]
Schedules of Controlled Substances: Placement of Diphenidine 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
diphenidine (1-(1,2-diphenylethyl)piperidine), 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, in part, 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 diphenidine.
DATES: Comments must be submitted electronically or postmarked on or
before June 25, 2026. The electronic Federal Docket Management System
will not accept comments after 11:59 p.m. Eastern Time on the last day
of the comment period.
Interested persons may file a request for a hearing or waiver of
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR
1316.47 and/or 1316.49, as applicable. 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 June 25,
2026.
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. DEA1155'' on all
correspondence, including any attachments.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 <a href="http://Regulations.gov">Regulations.gov</a>.
If you have received a Comment Tracking Number, your comment has been
successfully submitted and there is no need to resubmit the same
comment. 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.
<bullet> Paper comments: Paper comments that duplicate electronic
submissions are not necessary and are discouraged. Should you wish to
mail a paper comment in lieu of an electronic comment, it should be
sent via regular or express mail to: Drug Enforcement Administration,
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive,
Springfield, Virginia 22152.
<bullet> 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, 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 <a href="http://www.regulations.gov">www.regulations.gov</a>.
SUPPLEMENTARY INFORMATION: The Drug Enforcement Administration (DEA)
[[Page 30520]]
proposes to schedule diphenidine (1-(1,2-diphenylethyl)piperidine) 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
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>, unless reasonable
cause is given. Such information includes personal or business
identifiers (such as name, address, state or federal identifiers, etc.)
voluntarily submitted by the commenter.
Commenters submitting comments which include personal identifying
information (PII), confidential, or proprietary business information
that the commenter does not want to be 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> for public inspection. DEA
generally will not redact additional information contained in the
comment marked ``TO BE PUBLICLY POSTED.'' The Freedom of Information
Act applies to all comments received.
For easy reference, an electronic copy of this document and
supplemental information to this proposed rule are available at <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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 regarding 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 diphenidine meets the statutory criteria
for placement in schedule I, as proposed in this rulemaking.
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 her own motion, at the request of the
Secretary of Health and Human Services (HHS), or on the petition of an
interested party.\4\ This proposed action is initiated on the
Administrator's own motion and supported by, inter alia, a
recommendation from the then-Assistant Secretary for Health of the
Department of HHS (Assistant Secretary) and an evaluation of all other
relevant data by DEA. 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 diphenidine.
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\4\ 21 U.S.C. 811(a).
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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 set forth in 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),\5\ after consultation with the
Attorney General, shall first determine whether existing legal controls
under subchapter I of the 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.\6\ In the event that
the Secretary did not 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.
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\5\ 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. Memorandum of Understanding with
the National Institute on Drug Abuse, 50 FR 9518 (Mar. 8, 1985). The
Secretary has delegated to the Assistant Secretary for Health of HHS
the authority to make domestic drug scheduling recommendations.
Comprehensive Drug Abuse Prevention and Control Act of 1970, Public
Law 91-513, As Amended; Delegation of Authority, 58 FR 35460 (July
1, 1993).
\6\ 21 U.S.C. 811(d)(3).
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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.
Background
Diphenidine (1-(1,2-diphenylethyl)piperidine) is a dissociative
hallucinogen of the 1,2-diarylethylamine class that has been identified
in the United States' illicit
[[Page 30521]]
drug market. It was first synthesized in 1924 but not encountered for
recreational use until 2014. Diphenidine 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 diphenidine in Schedule II of the 1971 Convention (CND
Decision 64/5). As a signatory to the 1971 Convention, the United
States is required, by scheduling under the CSA, to place appropriate
controls on diphenidine 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
diphenidine. 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 through the U.N.
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.\7\ 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.
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\7\ See 21 U.S.C. 812(b).
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Proposed Determination To Schedule Diphenidine
Pursuant to 21 U.S.C. 811(b), DEA gathered the necessary data on
diphenidine and, on January 24, 2022, 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 diphenidine.
On November 26, 2022, HHS provided DEA a scientific and medical
evaluation entitled, ``Basis for the Recommendation to Control 1-(1,2-
Diphenylethyl)piperidine (Diphenidine) and its Salts in Schedule I of
the Controlled Substances Act,'' and a scheduling recommendation.
Pursuant to 21 U.S.C. 811(b), following consideration of the eight
factors and findings related to this substance's abuse potential,
legitimate medical use, and safety or dependence liability, HHS
recommended that diphenidine 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 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 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 the tab
``Supporting Documents'' of the public docket for this proposed rule at
<a href="https://www.regulations.gov">https://www.regulations.gov</a> under docket number ``DEA1155.''
1. Its Actual or Relative Potential for Abuse
In addition to considering the information HHS provided in its
scientific and medical evaluation document for diphenidine, DEA also
considered all other relevant data regarding actual or relative
potential for abuse of diphenidine. 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: \8\
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\8\ 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. 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 of the community;
or
b. There is significant diversion of the drug or other 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
[[Page 30522]]
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.
DEA reviewed the scientific and medical evaluation provided by HHS
and all other data relevant to the abuse potential of diphenidine.
These data as presented below demonstrate that diphenidine 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 diphenidine has been encountered by law enforcement
in the United States (see Factor 5 below, discussing evidence of abuse
in the United States), indicating diphenidine is available for abuse.
Case reports of overdoses and fatalities where diphenidine had been
positively confirmed in biological fluids have been published. Adverse
effects appear similar to those induced by dissociative drugs such as
methoxetamine (MXE, schedule I controlled substance), phencyclidine
(PCP) (schedule II controlled substance), and ketamine (schedule III
controlled substance) and include agitation, disorientation, altered
conscious state, tachycardia, an increased respiratory rate, miotic
pupils, muscular rigidity, metabolic acidosis, and rhabdomyolysis.
Additionally, reports of driving under the influence with diphenidine
have been reported in the United States, Japan, Belgium, Italy, Sweden,
France, and the United Kingdom. According to HHS, individuals are using
diphenidine and taking amounts sufficient to create a hazard to the
individual or to the safety of other individuals or to the community.
b. There is significant diversion of the drug or substance from
legitimate drug channels.
Diphenidine is not a Food and Drug Administration (FDA)-approved
drug for treatment or legally marketed as a drug in the United States,
nor marketed in any country in which its use is legal. Legitimate drug
channels are limited to research conducted with the drug and
manufacturing facilities and to the supply chain that produces the drug
for legitimate research. However, HHS noted that FDA is not aware of
any diversion from research or legitimate manufacturing activities for
diphenidine. Therefore, HHS concluded this characteristic of abuse is
not applicable.
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.
Diphenidine is not approved for medical use and is not formulated
or available for clinical use. Diphenidine has been sold on the
internet. Case reports of overdoses and fatalities with biological
confirmation of diphenidine with toxicological analysis have been
reported. Therefore, it is assumed that individuals are taking
diphenidine on their own initiative, rather than based on medical
advice from a practitioner licensed by law to administer drugs.
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.
Diphenidine has high-binding affinity and functions as an
antagonist at the N-methyl-D-aspartate (NMDA) receptor similar to known
drugs of abuse MXE, PCP, and ketamine. HHS notes that in rats,
diphenidine disrupts pre-pulse inhibition (PPI) of acoustic startle, an
effect indicative of NMDA receptor antagonism. Since diphenidine shares
the same NMDA receptor binding and antagonism effects with already
listed substances known to have potential for abuse, HHS stated it's
reasonable to assume that diphenidine will be subject to significant
use contrary to or without medical advice. Based on this assessment DEA
expects diphenidine to have a high abuse potential and pose a high risk
to public health.
2. Scientific Evidence of Its Pharmacological Effects, If Known
Diphenidine is structurally related to and shares pharmacological
properties with PCP and ketamine. Based on non-clinical in vitro
studies, diphenidine binds to the glutamatergic NMDA receptor and acts
as an antagonist at this receptor with high affinity. Diphenidine also
interacts with monoamine transmission through binding at the
norepinephrine and dopamine transporters and increasing
neurotransmitter transmission. Non-clinical in vivo studies indicate
diphenidine produces a similar pharmacological profile to that of other
NMDA receptor antagonists assessed via pre-pulse inhibition, locomotor
activity, and conditioned place preference assays. Although no clinical
studies have been performed for diphenidine, case reports of human
exposure show that the effects of diphenidine are similar to abuse of,
or intoxication with, ketamine or MXE.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance
Diphenidine is a substance belonging to the 1,2-diarylethylamine
class and shares structural similarities with schedule II and III
dissociative hallucinogens, such as PCP and ketamine. Diphenidine
(Chemical Abstracts Service Registry Number 36794-52-2) has a molecular
formula of C<INF>19</INF>H<INF>23</INF>N and a molecular weight of
265.4 g/mol. Diphenidine is highly lipophilic and high concentrations
of diphenidine have been detected in fat tissue in postmortem samples.
Diphenidine is metabolized by at least two distinct pathways,
glucuronidation and a multi-step process starting with hydroxylation
(mono- and bis-hydroxylation), which is followed by methylation of one
of the hydroxy groups (N,N-bis-dealkylation). Cytochrome (CYP) enzymes
such as CYP1A2, CYP2B6, CYP2C9, and CYP3A4 are thought to play a role
in the metabolism of diphenidine.
As HHS states in its review, there is no currently accepted medical
use for diphenidine in treatment in the United States, and a World
Health Organization (WHO) critical review states there are no known
therapeutic applications. A PubMed search conducted by HHS and DEA did
not identify any established therapeutic uses. Thus, DEA concludes that
diphenidine has no currently accepted medical use according to
established DEA procedures and case law.
4. Its History and Current Pattern of Abuse
Diphenidine was first encountered in the United States by law
enforcement in 2014. A limited number of encounters of diphenidine have
been reported in the years since (see Factor 5). The WHO reports that
diphenidine was first observed in the illicit drug market in 2013.
Based on the WHO Critical Review and available scientific and medical
literature, HHS noted that diphenidine has been sold on the internet as
``herbal blends'' and ``research chemicals,'' and at times promoted as
producing a ``legal high.'' Diphenidine is generally sold in powder
form. Anecdotal reports suggest that
[[Page 30523]]
diphenidine may induce dissociative effects with various routes of
administration (e.g., oral, sublingual, insufflation [snorting],
smoking, and intravenous injection). HHS noted that online user reports
suggest the onset of action is 10-30 minutes and the duration of action
is generally between 2.5 to 6 hours.
5. The Scope, Duration, and Significance of Abuse
Internationally, evidence of abuse of diphenidine initially
appeared in 2013, one year earlier than was reported in the United
States. Based on the WHO 2020 review of diphenidine, there were 61
total international reports of drug seizures between 2018 to 2020.
Additionally, eight countries (including six from the European region,
one from the Americas, and one from the Western pacific region)
reported that diphenidine was being used by individuals for its
psychoactive properties. Data from DEA's National Forensic Laboratory
Information System (NFLIS-Drug) \9\ indicate that, starting in 2014,
diphenidine was found in 22 samples in Indiana and Alabama. Diphenidine
has been encountered in 11 states (Alabama, California, Colorado,
Florida, Illinois, Indiana, Iowa, Louisiana, New Hampshire, South
Dakota, and Texas). These reports show evidence of trafficking,
distribution, and abuse of diphenidine in the United States.
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\9\ NFLIS-Drug 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 more than 96 percent of an estimated 1
million distinct annual federal, state, and local drug analysis
cases. NFLIS-Drug includes drug chemistry results from completed
analyses only. While NFLIS-Drug data are not direct evidence of
abuse, these can lead to an inference that a drug has been diverted
and abused. See Schedules of Controlled Substances: Placement of
Carisoprodol Into Schedule IV, 76 FR 77330, 77332 (Dec. 12, 2011).
NFLIS-Drug data were queried on May 7, 2026.
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Diphenidine was reported in several published toxicology-related
cases in several countries outside of the United States, including
Japan, Belgium, Italy, Sweden, France, and the United Kingdom. Based on
available abuse data, public health risk, and drug trafficking data,
the WHO recommended to the United Nations that diphenidine be
controlled internationally. In April 2021, the CND voted to place
diphenidine into Schedule II of the 1971 Convention.
6. What, if Any, Risk There Is to the Public Health
Diphenidine 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, diphenidine 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
diphenidine in medical literature; however, all have been reported as
poly-substance use. Adverse events associated with diphenidine included
agitation or agitated delirium, anxiety, dilated pupils,
disorientation, dissociation, frothing from the mouth, hypertension,
tachycardia, and urinary retention. At least five fatalities have been
associated with diphenidine use. 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 there are no clinical studies evaluating the
dependence potential of diphenidine. However, diphenidine has similar
pharmacological properties of MXE, PCP, and ketamine, which do have
well-demonstrated dependence potential. Thus, the HHS and DEA reviews
both concluded that it is probable that diphenidine 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
Diphenidine 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 the facts and all relevant data constitute
substantial evidence of potential for abuse of diphenidine. As such,
DEA proposes to schedule diphenidine as a schedule I controlled
substance under the CSA. This proposed action would also enable the
United States to meet its obligations under the 1971 Convention.
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.\10\ After consideration of the analysis and recommendation of
the Assistant Secretary for Health of HHS and review of all other
available data, the Administrator of DEA, pursuant to 21 U.S.C. 811(a)
and 21 U.S.C. 812(b)(1), finds that:
---------------------------------------------------------------------------
\10\ 21 U.S.C. 812(b).
---------------------------------------------------------------------------
1. Diphenidine Has a High Potential for Abuse
Diphenidine's pharmacological profile, including its high binding
affinity and function as an antagonist at the NMDA receptor, is
indicative that it has a high potential for abuse. Binding and
antagonism to the NMDA receptor are also characteristic of and believed
to be important in the subjective and mind-altering effects of other
dissociative drugs, such as MXE, PCP, and ketamine, all known drugs
that are abused. Published case reports support that the subjective
effects and use patterns are similar to other NMDA receptor antagonists
that have known high abuse.
2. Diphenidine Has No Currently Accepted Medical Use in Treatment in
the United States
Diphenidine is not legally marketed in the United States. As noted
in the HHS's review, diphenidine 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 are no
known medically approved uses worldwide at this time. There is no
evidence that diphenidine has a currently accepted medical use in
treatment in the United States.\11\
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\11\ Pursuant to 21 U.S.C. 812(b)(1)(B), when placing a drug or
other substance in schedule I, DEA must consider whether the
substance has a currently accepted medical use in treatment in the
United States. First, DEA looks to whether the drug or substance has
FDA approval. When no FDA approval exists, DEA has traditionally
applied a five-part test to determine whether a drug or substance
has a currently accepted medical use: (1) the drug's chemistry must
be known and reproducible; (2) there must be adequate safety
studies; (3) there must be adequate and well-controlled studies
proving efficacy; (4) the drug must be accepted by qualified
experts; and (5) the scientific evidence must be widely available.
See 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 and concluded the test
was not satisfied. 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 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'
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
diphenidine or that the use of diphenidine is recognized by entities
that regulate the practice of medicine, so the two-part test also is
not satisfied.
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[[Page 30524]]
3. There Is a Lack of Accepted Safety for Use of Diphenidine Under
Medical Supervision
Because diphenidine 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 Administrator concludes that
diphenidine (1-(1,2-diphenylethyl)piperidine) warrants control in
schedule I of the CSA. More precisely, because of its dissociative
hallucinogenic effects, and because it may produce hallucinogenic-like
dependence in humans, DEA proposes to place diphenidine, 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 hallucinogens category
of schedule I).
Requirements for Handling Diphenidine
If this rule is finalized as proposed, diphenidine would be subject
to the CSA's schedule I regulatory controls and administrative, civil,
and criminal sanctions applicable to the manufacture, distribution,
reverse distribution, dispensing, 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, dispenses, imports, exports, engages in research,
or conducts instructional activities or chemical analysis with, or
possesses), or who desires to handle diphenidine 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.
Any person who currently handles diphenidine and is not registered
with DEA to conduct research with a schedule I controlled substance
must submit an application for registration and may not continue to
handle diphenidine, 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.
Notwithstanding the foregoing, pursuant to 21 U.S.C. 822(h), if, on
the date the final rule is effectuated, a person is conducting research
on diphenidine and is already registered to conduct research with
another controlled substance in schedule I, the person may continue to
conduct research on diphenidine if they submit a completed application
for registration or modification of existing registration, as
applicable, to conduct research with diphenidine not later than 90
calendar days after the date of effectuation of the final rule. The
person may continue to conduct such research until the person withdraws
the application or the Administrator serves on the person an order to
show cause proposing denial of the application pursuant to 21 U.S.C.
824(c) and in accordance with 21 CFR 1301.37. If the Administrator
serves an order to show cause proposing denial of the application or
modification, the person may not continue to conduct research with
diphenidine and may not receive or otherwise obtain additional
diphenidine. If an order to show cause is served and the person
requests a hearing in accordance with 21 CFR 1301.37(d), the hearing
shall be held in accordance with 21 CFR 1301.41-1301.46 on an expedited
basis and not later than 45 calendar days after the request is made,
except that the hearing may be held at a later time if so requested by
the person. If the person sends a copy of the application to a
manufacturer or distributor of diphenidine, receipt of the copy by the
manufacturer or distributor constitutes sufficient evidence that the
person is authorized to receive diphenidine pursuant to 21 U.S.C.
822(h)(4). Continuation of research under 21 U.S.C. 822(h) does not
authorize any other handling (e.g., distribution) of diphenidine.
Retail sales of schedule I controlled substances to the general
public are not allowed under the CSA. Possession of any quantity of a
schedule I controlled substance in a manner not authorized by the CSA
is unlawful and those in possession of any quantity may be subject to
prosecution pursuant to the CSA.
2. Disposal of Stocks. Any person unwilling or unable to obtain a
schedule I registration must surrender or transfer all quantities of
currently held diphenidine to a person registered with DEA before the
effective date of the final scheduling action in accordance with all
applicable Federal, State, local, and Tribal laws. Diphenidine must be
disposed of in accordance with 21 CFR part 1317, in addition to all
other applicable Federal, State, local, and Tribal laws.
3. Security. Diphenidine would be subject to schedule I security
requirements and must be handled and stored pursuant to 21 U.S.C. 821
and 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.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of diphenidine would need to comply with 21
U.S.C. 825 and 958(e) and be in accordance with 21 CFR part 1302.
5. Quota. Generally, only registered manufacturers would be
permitted to manufacture diphenidine in accordance with a quota
assigned pursuant to 21 U.S.C. 826, and in accordance with 21 CFR part
1303.
6. Inventory. Every DEA registrant who would handle diphenidine
must have an initial inventory of all stocks of controlled substances
including diphenidine 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.
After the initial inventory, every DEA registrant would need to
take an inventory of all controlled substances (including diphenidine)
on hand every two years, pursuant to 21 U.S.C. 827 and 958(e), and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
[[Page 30525]]
7. Records and Reports. Every DEA registrant would need to maintain
records and submit reports with respect to diphenidine, pursuant to 21
U.S.C. 827, 832(a), and 958(e), and in accordance with 21 CFR 1301.74
and 1301.76, and parts 1304, 1312, and 1317. Manufacturers and
distributors would need to submit reports regarding diphenidine to the
Automated Reports and Consolidated Ordering System pursuant to 21
U.S.C. 827, and in accordance with 21 CFR parts 1304 and 1312.
8. Order Forms. Every DEA registrant who distributes diphenidine
would need to comply with the order form requirements, pursuant to 21
U.S.C. 828 and 21 CFR part 1305.
9. Importation and Exportation. All importation and exportation of
diphenidine would need to comply with 21 U.S.C. 952, 953, 957, and 958,
and in accordance with 21 CFR part 1312.
10. Liability. Any activity involving diphenidine 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, 14192, and 14294
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 either E.O. 14192, Unleashing Prosperity Through
Deregulation, or E.O. 14294, Fighting Overcriminalization in Federal
Regulations.
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 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, 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 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 diphenidine (chemical name: 1-
(1,2-diphenylethyl)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
diphenidine.
The entities affected by this rule include the manufacturers,
distributors, importers, exporters, and researchers of diphenidine. 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.\12\
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\12\ Executive Office of the President Office of Management and
Budget, North American Industry Classification System, United
States, 2022, <a href="https://www.census.gov/naics/reference_files_tools/2022_NAICS_Manual.pdf">https://www.census.gov/naics/reference_files_tools/2022_NAICS_Manual.pdf</a>. (Accessed 2/5/2026).
Table 1--Business Activity and Corresponding NAICS Industries
------------------------------------------------------------------------
NAICS industry
Business activity NAICS code description
------------------------------------------------------------------------
Manufacturer.................. 325412........... Pharmaceutical
Preparation
Manufacturing.
Distributor, Importer, 424210, 424690... Drugs and Druggists'
Exporter. Sundries Merchant
Wholesalers Other
Chemical and Allied
Products Merchant
Wholesalers.
Researcher.................... 541715, 611310... Research and
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 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.
[[Page 30526]]
Table 2--Percent Small Entities by Industry
----------------------------------------------------------------------------------------------------------------
Small firms Percent small
NAICS industry Firms \13\ SBA size standard \14\ \15\ entities (%)
----------------------------------------------------------------------------------------------------------------
325412--Pharmaceutical Preparation 1,179 1,300 employees......... 1,099 93.2
Manufacturing.
424210--Drugs and Druggists' Sundries 7,012 250 employees........... 6,703 95.6
Merchant Wholesalers.
424690--Other Chemical and Allied 5,487 175 employees........... 5,197 94.7
Products Merchant Wholesalers.
541715--Research and Development in 10,042 1,000 employees......... 9,599 95.6
the Physical, Engineering, and Life
Sciences (except Nanotechnology and
Biotechnology).
611310--Colleges, Universities and 2,494 $34.5 million........... 1,515 60.8
Professional Schools.
----------------------------------------------------------------------------------------------------------------
Based on the American Chemical Society's SciFinder database,\16\
DEA identified three domestic entities supplying diphenidine across
these industries. Suppliers include 325412, 424210, and 424690
industries. Even if all affected suppliers were small entities, they
would account for only 0.02 percent of the small entities in those
industries, not a substantial number.\17\ Additionally, DEA expects the
number of researchers working with diphenidine is small because
diphenidine 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 diphenidine 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 611310 industries.
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\13\ Statistics of U.S. Businesses, 2022 SUSB Annual Data Tables
by Establishment Industry, <a href="https://www.census.gov/data/tables/2022/econ/susb/2022-susb-annual.html">https://www.census.gov/data/tables/2022/econ/susb/2022-susb-annual.html</a> (Accessed 2/5/2026).
\14\ U.S. Small Business Administration, Table of size
standards, Version March 2023, Effective: March 17, 2023, <a href="https://www.sba.gov/document/support-table-size-standards">https://www.sba.gov/document/support-table-size-standards</a>. (Accessed 2/5/
2026) Size standards are based on the number of employees or annual
receipts depending on industry.
\15\ Based on the estimated number of firms below the SBA size
standard for each industry.
\16\ SciFinder; Chemical Abstracts Service: Columbus, OH;
<a href="https://scifinder.cas.org">https://scifinder.cas.org</a> (accessed 2/6/2026).
\17\ 3/(1,179 + 7,012 + 5,487) = 0.02%.
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In summary, an insubstantial number of small entities will be
affected by this proposed rule. As such, the proposed rule, if
finalized, is not expected to result in a significant economic impact
on a substantial number of small entities.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995,
2 U.S.C. 1532, DEA has determined and certifies that this proposed
action would not result in any Federal mandate that may result ``in the
expenditure by State, local, and Tribal governments, in the aggregate,
or by the private sector, of $100,000,000 or more (adjusted annually
for inflation) in any 1 year . . . .'' Therefore, neither a Small
Government Agency Plan nor any other action is required under UMRA of
1995.
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:
0
a. Add paragraph (d)(117) to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(d) * * *
------------------------------------------------------------------------
------------------------------------------------------------------------
* * * * * * *
(117) Diphenidine (Other names: 1-(1,2- 7292
diphenylethyl)piperidine).............................
* * * * * * *
------------------------------------------------------------------------
* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
May 14, 2026, by DEA Administrator Terrance C. Cole. That document with
the original signature and date is maintained by DEA. For
administrative purposes only, and in 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. 2026-10380 Filed 5-22-26; 8:45 am]
BILLING CODE 4410-09-P
</pre></body>
</html>Indexed from Federal Register on May 26, 2026.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.