[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 [www.gpo.gov]
[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 https://www.regulations.gov 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 
regulations.gov. If you have received a Comment Tracking Number, your 
comment has been successfully submitted and there is no need to 
resubmit the same comment. 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 https://www.regulations.gov. Such information includes personal identifying 
information (such as your name, address, etc.) voluntarily submitted by 
the commenter. The Freedom of Information Act applies to all comments 
received. If you want to submit personal identifying information (such 
as your name, address, etc.) as part of your comment, but do not want 
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 https://www.regulations.gov may include any 
personal identifying information (such as name, address, and phone 
number) included in the text of your electronic submission that is not 
identified as confidential as directed above.
    An electronic copy of this document and supplemental information to 
this proposed rule are available at https://www.regulations.gov 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 https://www.regulations.gov 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 www.erowid.org, 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).
---------------------------------------------------------------------------

    (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