Proposed Rule2023-27289
Schedules of Controlled Substances: Placement of 2,5-dimethoxy-4-iodoamphetamine (DOI) and 2,5-dimethoxy-4-chloroamphetamine (DOC) in Schedule I
Primary source
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Published
December 13, 2023
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration proposes placing two phenethylamine hallucinogens, as identified in this proposed rule, 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 for one of these substances 2,5-dimethoxy-4-chloroamphetamine. 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 these two specific controlled substances.
Full Text
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<title>Federal Register, Volume 88 Issue 238 (Wednesday, December 13, 2023)</title>
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[Federal Register Volume 88, Number 238 (Wednesday, December 13, 2023)]
[Proposed Rules]
[Pages 86278-86284]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-27289]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA1156]
Schedules of Controlled Substances: Placement of 2,5-dimethoxy-4-
iodoamphetamine (DOI) and 2,5-dimethoxy-4-chloroamphetamine (DOC) 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 two
phenethylamine hallucinogens, as identified in this proposed rule, 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 for one of these
substances 2,5-dimethoxy-4-chloroamphetamine. 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 these two
specific controlled substances.
DATES: Comments must be submitted electronically or postmarked on or
before January 12, 2024.
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
[[Page 86279]]
hearing, and waivers of an opportunity for a hearing or to participate
in a hearing, must be received or postmarked on or before January 12,
2024.
To be considered by DEA as part of this rulemaking, comments and
requests for a hearing must be submitted in response to this proposed
rule within the timeframe specified above, regardless of whether the
person previously submitted a comment or hearing request in response to
the notice of proposed rulemaking that DEA published in the Federal
Register on April 11, 2022 (87 FR 21069), and subsequently withdrew on
August 29, 2022 (87 FR 52712), under docket number DEA824.
ADDRESSES: 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. To ensure proper
handling of comments, please reference ``Docket No. DEA1156'' on all
electronic and written correspondence, including any attachments.
<bullet> Electronic comments: 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 on-line
instructions at that site for submitting comments. Upon completion of
your submission you will receive a Comment Tracking Number. 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 FR 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.
SUPPLEMENTARY INFORMATION: In this proposed rule, the Drug Enforcement
Administration (DEA) proposes to schedule the following two controlled
substances in schedule I of the Controlled Substances Act (CSA),
including their salts, isomers, and salts of isomers whenever the
existence of such salts, isomers, and salts of isomers is possible
within the specific chemical designation:
<bullet> 2,5-dimethoxy-4-iodoamphetamine (DOI) and
<bullet> 2,5-dimethoxy-4-chloroamphetamine (DOC).
This proposed rule supersedes the April 11, 2022 notice of proposed
rulemaking (NPRM) that DEA published in the Federal Register (87 FR
21069), to place DOI and DOC in schedule I of the CSA, which DEA
withdrew on August 29, 2022 (87 FR 52712) in order to provide
additional clarity on the process for submitting hearing requests. The
scientific, medical, and other bases for the proposed placement of DOI
and DOC in schedule I remain the same in this proposed rule as they
were described in the April 2022 proposed rule, except for minor
updates to certain data.
Posting of Public Comments
All comments received in response to this docket are considered
part of the public record. DEA will make comments available, unless
reasonable cause is given, for public inspection online at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. Such information includes personal identifying
information (such as your name, address, etc.) voluntarily submitted by
the commenter. The Freedom of Information Act applies to all comments
received. If you want to submit personal identifying information (such
as your name, address, etc.) as part of your comment, but do not want
DEA to make it publicly available, you must include the phrase
``PERSONAL IDENTIFYING INFORMATION'' in the first paragraph of your
comment. You must also place all of the personal identifying
information you do not want made publicly available in the first
paragraph of your comment and identify what information you want
redacted.
If you want to submit confidential business information as part of
your comment, but do not want it to be made publicly available, you
must include the phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the
first paragraph of your comment. You must also prominently identify the
confidential business information to be redacted within the comment.
DEA will generally make available in publicly redacted form
comments containing personal identifying information and confidential
business information identified, as directed above. If a comment has so
much confidential business information that DEA cannot effectively
redact it, DEA may not make available publicly all or part of that
comment. Comments posted to <a href="https://www.regulations.gov">https://www.regulations.gov</a> may include any
personal identifying information (such as name, address, and phone
number) included in the text of your electronic submission that is not
identified as confidential as directed above.
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> for
easy reference.
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), 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316,
subpart D. Interested persons 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:
(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 regarding to the
objections or issues.
[[Page 86280]]
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. 21 CFR
1316.49.
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.
21 CFR 1308.44(b), 1316.53. Further, once the Administrator determines
a hearing is needed to address such matters of fact and law in
rulemaking, she 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.
In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing
would be to determine whether DOI and/or DOC meet the statutory
criteria for placement in schedule I, as proposed in this rule.
Legal Authority
The CSA provides that proceedings for the issuance, amendment, or
repeal of the scheduling of any drug or other substance may be
initiated by the Attorney General on his own motion. 21 U.S.C. 811(a).
This proposed action is supported by a recommendation from the then-
Assistant Secretary for Health of the Department of Health and Human
Services (HHS).
In addition, regarding the placement of DOC in the Controlled
Substances Act (CSA), 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),\1\ 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.\2\ 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. Pursuant to 21 U.S.C. 811(a)(1)
and (2), the Attorney General (as delegated to the Administrator of
DEA), by rule, and upon the recommendation of the Secretary, may 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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\1\ As discussed in a memorandum of understanding entered into
by the Food and Drug Administration (FDA) and the National Institute
on Drug Abuse (NIDA), FDA acts as the lead agency within HHS in
carrying out the Secretary's scheduling responsibilities under the
CSA, with the concurrence of NIDA. 50 FR 9518 (March 8, 1985). The
Secretary has delegated to the Assistant Secretary for Health of HHS
the authority to make domestic drug scheduling recommendations. 58
FR 35460 (July 1, 1993).
\2\ 21 U.S.C. 811(d)(3).
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Background
DOI and DOC belong to the phenethylamine class of drugs with
hallucinogenic properties, similar to 2,5-dimethoxy-4-methamphetamine
(DOM), a schedule I hallucinogen. DOI and DOC have no approved medical
use in the United States.
On September 26, 2018, DEA, in accordance with the provisions of 21
U.S.C. 811(b), requested HHS provide a scientific and medical
evaluation as well as a scheduling recommendation for DOI and DOC.
Additionally, on May 7, 2020, 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 63rd Session in March
2020, voted to place DOC in Schedule I of the 1971 Convention (CND Dec/
63/4). As a signatory to this international treaty, the United States
is required, by scheduling under the CSA, to place appropriate controls
on DOC to meet the minimum requirements of the treaty.
Article 2, paragraph 7(a), of the 1971 Convention sets forth the
minimum requirements that the United States must meet when a substance
has been added to Schedule I of the 1971 Convention. The United States
must adhere to specific export and import provisions that are provided
in the 1971 Convention. This requirement is accomplished by the CSA
with the export and import provisions established in 21 U.S.C. 952,
953, 957, and 958, and in accordance with 21 CFR part 1312. 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(a)(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.
Proposed Determination To Schedule DOI and DOC
Pursuant to 21 U.S.C. 811(b), DEA gathered the necessary data on
DOI and DOC and on September 26, 2018, 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 DOI and DOC. On September 28, 2020, HHS provided to
DEA a scientific and medical evaluation entitled ``Basis for the
Recommendation to Control 2,5-dimethoxy-4-iodoamphetamine (DOI) and
2,5-dimethoxy-4-chloroamphetamine (DOC) and their Salts in Schedule I
of the Controlled Substances Act (CSA)'' and a scheduling
recommendation. Following consideration of the eight factors and
findings related to these substances' abuse potential, legitimate
medical use,
[[Page 86281]]
and dependence liability, HHS recommended that DOI and DOC and their
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).
After a review of the available data, including the scientific and
medical evaluation and scheduling recommendation provided by HHS, the
Administrator published an NPRM in the Federal Register on April 11,
2022 (87 FR 21069), to place DOI and DOC in schedule I of the CSA. DEA
withdrew that proposed rule on August 29, 2022 (87 FR 52712). This
proposed rule supersedes the April 2022 proposed rule, to provide
additional clarity on the process for submitting hearing requests. The
bases for the proposed placement of DOI and DOC in schedule I remain
the same in this proposed rule as they were described in the April 2022
proposed rule.
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 the April 2022 proposed rule and in this proposed scheduling
determination. Please note that both DEA and HHS analyses are available
in their entirety under ``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 ``DEA1156.''
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 DOI and DOC, DEA also
considered all other relevant data regarding actual or relative
potential for abuse of DOI and DOC. The term ``abuse'' is not defined
in the CSA; however, the legislative history of the CSA suggests the
following four prongs in determining whether a particular drug or
substance has a potential for abuse: \3\
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\3\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., 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 drugs; or
d. The drug 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 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 DOI and DOC.
These data as presented below demonstrate that DOI and DOC have 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 DOI and DOC have been encountered by law enforcement
in the United States (see Factor 5), indicating DOI and DOC
availability for abuse. According to HHS, individuals are using DOI and
DOC for their hallucinogenic effects and taking them in amounts
sufficient to create a hazard to their health.
b. There is significant diversion of the drug or substance from
legitimate drug channels.
HHS states that DOI and DOC are not Food and Drug Administration
(FDA)-approved drugs for treatment in the United States and is unaware
of any country in which their use is legal. DOI and DOC are available
for purchase from legitimate chemical synthesis companies because they
are used in scientific research. There is no evidence of diversion from
these companies.
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.
DOI and DOC are not found in FDA-approved drug products and
practitioners may neither legally prescribe nor dispense these
substances. Therefore, individuals are taking DOI and DOC 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 indicating that
individuals are taking DOI and DOC on their own initiative rather than
on the medical advice of licensed practitioners.
d. The drug is a new drug 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 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.
Chemically, DOI and DOC are analogs of the schedule I hallucinogen
DOM. The effects and pharmacological action of DOI and DOC are similar
to those of other schedule I hallucinogens, such as DOM and lysergic
acid diethylamide (LSD), which have no accepted medical use and a high
abuse potential.
In drug discrimination studies (an in vivo test to assess drug
abuse liability of test drugs in comparison to known drugs of abuse),
DOI and DOC produce full substitution for the discriminative stimulus
effects of DOM, LSD, and N,N-dimethyltryptamine (DMT, schedule I). In
humans, anecdotal reports suggest that DOI and DOC produce classic
hallucinogenic effects that are similar to DOM, including visual and
auditory hallucinations, fatigue, headache, gastrointestinal distress,
insomnia and anxiety. HHS notes that use of DOC in combination with
other drugs is associated with emergency department admissions and one
death.
Due to the psychological and cognitive disturbances associated with
DOI and DOC, as with other schedule I hallucinogens, it is reasonable
to assume that DOI and DOC have 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
In vitro testing shows that DOI and DOC bind to and act as agonists
at serotonin (5-HT) 2A (5-HT<INF>2A</INF>) receptors. In rats, DOI
administration induced an increase in wet dog shakes and back muscle
contractions. These effects were attributed to 5-HT<INF>2A</INF>
receptor activation, since pretreatment with a 5-HT<INF>2A</INF>
receptor inverse agonist blocked the effect. Agonism of the 5-
HT<INF>2A</INF> receptor is the primary mechanism of action of typical
hallucinogenic responses, suggesting that DOI and DOC have
hallucinogenic effects. Additionally, animal testing data in rats show
that DOI and DOC fully substitute for DOM, LSD, and DMT discriminative
stimulus effects in drug discrimination tests.
[[Page 86282]]
In humans, HHS reported that anecdotal reports of hallucinogenic
experiences with DOI and DOC are available on online drug forums such
as <a href="http://www.erowid.org">www.erowid.org</a>, in which recreational drug users report on their
experiences with all classes of substances. In these reports, DOI and
DOC are reported to induce hallucinogenic effects, including prominent
visual effects.
Additionally, a World Health Organization (WHO) critical review of
DOC \4\ mentions its hallucinogenic effects reported by those that
self-experimented with DOC and notes the duration of action may last 12
to 24 hours. WHO notes that the long duration of effects is shared by
other structurally related schedule I hallucinogens including DOI, 2,5-
dimethoxy-4-bromoamphetamine (DOB), and DOM. DOI and DOC are commonly
administered orally and/or sublingually when encountered in the form of
blotters.
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\4\ World Health Organization (WHO). 2019a. Critical Review
Report: DOC (4-Chloro-2,5-dimethoxyamfetamine) Expert Committee on
Drug Dependence, Forty-second Meeting. Geneva.
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3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance
DOI and DOC are centrally-acting hallucinogens and part of the
phenethylamine hallucinogen family and share structural similarities
with schedule I phenethylamine hallucinogens such as DOM. DOI (CAS
42203-78-1) has a molecular formula of
C<INF>11</INF>H<INF>16</INF>INO<INF>2</INF> and a molecular weight of
321.16 g/mol. The hydrochloride salt of DOI has a melting point of 201
[deg]C. DOC (CAS 123431-31-2) has a molecular formula of
C<INF>11</INF>H<INF>16</INF>ClNO<INF>2</INF> and a molecular weight of
229.70 g/mol. The hydrochloride salt of DOC has a melting point of 193-
194.5 [deg]C. DOI and DOC are white, odorless, and crystalline solids.
4. Its History and Current Pattern of Abuse
The history and current pattern of abuse of DOI and DOC are
described in law enforcement reports and anecdotal reports by drug
abusers. In the United States, law enforcement entities initially
encountered DOI and DOC in 2005, according to the National Forensic
Laboratory Information System (NFLIS)-Drug \5\ database. See Factor 5
for additional information. DOI and DOC are encountered in various
forms (e.g., powder, tablets, capsules, liquid, or on blotter paper).
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\5\ 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 October 27, 2023.
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Anecdotal reports on the internet indicate that individuals are
using substances they identified as DOI and DOC for their
hallucinogenic effects. Importantly, it is impossible to know if the
street drugs sold to an individual as DOI or DOC are actually the
substances they are marketed as in the absence of chemical analysis or
evaluation of biological fluids following ingestion. However, in animal
drug discrimination studies, DOI and DOC produced effects that are
similar to the effects elicited by schedule I hallucinogens such as
DOM, LSD, and DMT.
Regarding DOC, a July 2019 report from the European Monitoring
Centre for Drugs and Drug Addiction included data from their toxicology
portal, and indicated that 16 non-fatal intoxications associated with
DOC had been reported internationally between 2008 and 2017. In 2019,
the United Nations Office on Drugs and Crime reported three deaths
associated with DOC (one each in 2015 and 2018; information about the
third is unknown).
5. The Scope, Duration, and Significance of Abuse
Data from NFLIS-Drug indicate that DOI and DOC were found in
samples starting in 2005, in the United States. Specifically, there
were 40 NFLIS-Drug reports for DOI from 2005 through December 2022, and
790 NFLIS-Drug reports for DOC during the same period. DOI has been
encountered in 15 states, whereas DOC has been encountered in 39
states. In response to abuse and safety concerns, DOI has been
controlled in Florida.
Abuse of DOI and DOC has been characterized as causing acute public
health and safety issues worldwide. In particular, WHO reports that DOC
has been available in Europe since 2001. Based on available abuse data,
public health risk, and drug trafficking data, the WHO recommended to
the United Nations (UN) that DOC be controlled internationally. In
March 2020, the UN Commission on Narcotic Drugs voted to place DOC into
Schedule I of the 1971 Convention.
6. What, if Any, Risk There Is to the Public Health
DOI and DOC share similar mechanisms of action with and produce
similar physiological and subjective effects (see Factor 2 for more
information) as other schedule I hallucinogens, such as DOM, DMT, and
LSD. Thus, DOI and DOC pose 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
judgment, strange or dangerous behaviors), but they can affect the
general public, as with driving under the influence. To date, there are
no reports of distressing responses or death associated with DOI in
medical literature. There have been three published reports, in 2008,
2014, and 2015, of adverse events associated with DOC including, but
not limited to, seizures, agitation, tachycardia, hypertension, and
death of one individual. Since DOI is structurally similar to DOC and
produces similar effects to DOC, it is likely to produce serious
adverse effects similar to DOC. Thus, 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
According to HHS, the physiological dependence liability of DOI and
DOC in animals and humans is not reported in scientific and medical
literature. Thus, it is not possible to determine whether DOI and DOC
produce physiological dependence following acute or chronic
administration.
According to HHS, DOI, DOC, and other related phenethylamine
hallucinogens (such as the schedule I substance DOM) are highly
abusable substances. Drug discrimination studies in animals indicate
that DOI and DOC fully substitute to the discriminative stimulus
effects of schedule I hallucinogens DOM, LSD, and DMT. HHS notes that
hallucinogens are not usually associated with physical dependence,
likely due to the rapid development of tolerance precluding daily
administration. Hallucinogen abusers may develop psychological
dependence as evidenced by the continued use of these substances
despite knowledge of their potential toxic and adverse effects.
8. Whether the Substance Is an Immediate Precursor of a Substance
Already Controlled Under the CSA
DOI and DOC are not immediate precursors 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 DOI
[[Page 86283]]
and DOC. As such, DEA proposes to schedule DOI and DOC as controlled
substances 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 then-Assistant Secretary for Health of HHS to
place DOI and DOC in schedule I and review of all other available data,
the Administrator of DEA, pursuant to 21 U.S.C. 812(b)(1), finds that:
(1) DOI and DOC have a high potential for abuse that is comparable
to other schedule I substances, such as the phenethylamine hallucinogen
DOM;
(2) DOI and DOC have no currently accepted medical use in treatment
in the United States. FDA has not approved a marketing application for
a drug product containing DOI or DOC for any therapeutic indication,
and DEA and HHS know of no clinical studies or petitioners claiming an
accepted medical use in the United States.\6\
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\6\ Although there is no evidence suggesting that DOI and DOC
have a currently accepted medical use in treatment in the United
States, it bears noting that a drug cannot be found to have such
medical use unless DEA concludes that it satisfies a five-part test.
Specifically, with respect to a drug that has not been approved by
FDA, to have a currently accepted medical use in treatment in the
United States, all of the following must be demonstrated: i. the
drug's chemistry must be known and reproducible; ii. there must be
adequate safety studies; iii. there must be adequate and well-
controlled studies proving efficacy; iv. the drug must be accepted
by qualified experts; and v. the scientific evidence must be widely
available. 57 FR 10499 (1992), pet. for rev. denied, Alliance for
Cannabis Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).
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(3) There is a lack of accepted safety for use of DOI and DOC under
medical supervision. The use of DOC is associated with serious adverse
consequences including deaths. Since DOI is structurally similar to DOC
and produces effects similar to DOC, it is likely that DOI may produce
serious adverse events similar to DOC. Because DOI and DOC have no
approved medical use and have not been investigated as new drugs, their
safety for use under medical supervision has not been determined.
Based on these findings, the Administrator of DEA concludes that
DOI and DOC warrant control in schedule I of the CSA. More precisely,
because of their hallucinogenic effects, and because they may produce
hallucinogenic-like tolerance and dependence in humans, DEA proposes to
place DOI and DOC, including their salts, isomers, and salts of isomers
whenever the existence of such salts, isomers, and salts of isomers is
possible within the specific chemical description, in 21 CFR 1308.11(d)
(the hallucinogenic substances category of schedule I).
Requirements for Handling DOI and DOC
If this rule is finalized as proposed, DOI and DOC would be subject
to the CSA's schedule I regulatory controls and administrative, civil,
and criminal sanctions applicable to the manufacture, distributing,
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) 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. DOI and DOC would be subject to schedule I security
requirements and would need to be handled and stored pursuant to 21
U.S.C. 821, 823, and in accordance with 21 CFR 1301.71-1301.76. Non-
practitioners handling DOI and DOC 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 DOI and DOC 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 DOI and DOC in accordance with quota assigned pursuant to
21 U.S.C. 826 and in accordance with 21 CFR part 1303.
5. Inventory. Every DEA registrant who possesses any quantity of
DOI and DOC would need to have an initial inventory of all stocks of
controlled substances (including DOI and DOC) on hand on the date the
registrant first engages in the handling of controlled substances,
pursuant to 21 U.S.C. 827 and in accordance with 21 CFR 1304.03,
1304.04, and 1304.11.
After the initial inventory, every DEA registrant would need to
take inventory of all controlled substances (including DOI and DOC) 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 for DOI and DOC, pursuant to 21 U.S.C. 827
and 832(a), and in accordance with 21 CFR 1301.74(b) and (c) and parts
1304, 1312, and 1317
7. Order Forms. Every DEA registrant who distributes DOI and DOC
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
DOI and DOC 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 DOI and DOC 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, Regulatory Planning and Review, and
Improving Regulation and Regulatory Review
In accordance with 21 U.S.C. 811(a), this proposed scheduling
action is subject to formal rulemaking procedures performed ``on the
record after opportunity for a hearing,'' which are conducted pursuant
to the provisions of 5 U.S.C. 556 and 557. The CSA sets 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.
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.
[[Page 86284]]
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 action does not impose a new collection of
information requirement under the Paperwork Reduction Act, 44 U.S.C.
3501-3521.
Regulatory Flexibility Act
The Administrator of DEA, 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 substances DOI and DOC (chemical names:
2,5-dimethoxy-4-iodoamphetamine [DOI] and 2,5-dimethoxy-4-
chloroamphetamine [DOC]), including their salts, isomers, and salts of
isomers whenever the existence of such salts, isomers, and salts of
isomers is possible within the specific chemical designation, 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 for
DOC. 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 DOI and DOC.
According to HHS, and also by DEA's findings in this proposed rule,
DOI and DOC have a high potential for abuse, have no currently accepted
medical use in treatment in the United States, and lack accepted safety
for use under medical supervision. There appear to be no legitimate
sources for DOI and DOC as marketed drugs in the United States, but DEA
notes that these substances are available for purchase from legitimate
suppliers for scientific research. There is no evidence of significant
diversion of DOI and DOC from legitimate suppliers. 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
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.
Signing Authority
This document of the Drug Enforcement Administration was signed on
December 7, 2023, by Administrator Anne Milgram. 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.
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
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, as proposed to be amended at 88 FR 22388 (April
13, 2023), add paragraphs (d)(104) and (d)(105) to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(d) * * *
* * * * * * *
(104) 2,5-dimethoxy-4-iodoamphetamine (Other name: DOI).......... 7447
(105) 2,5-dimethoxy-4-chloroamphetamine (Other name: DOC)........ 7448
* * * * * * *
* * * * *
[FR Doc. 2023-27289 Filed 12-12-23; 8:45 am]
BILLING CODE 4410-09-P
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</html>Indexed from Federal Register on December 13, 2023.
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.