[Federal Register Volume 87, Number 69 (Monday, April 11, 2022)]
[Proposed Rules]
[Pages 21069-21075]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-07648]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA824]


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. 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 June 10, 2022.
    Interested persons may file a request for hearing or waiver of 
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR 
1316.45 and/or 1316.47, as applicable. Requests for hearing and waivers 
of an opportunity for a hearing or to participate in a hearing, 
together with a written statement of position on the matters of fact 
and law asserted in the hearing, must be received on or before May 11, 
2022.

ADDRESSES: Interested persons may file written comments on this 
proposal in

[[Page 21070]]

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. DEA-824'' on all electronic 
and written correspondence, including any attachments.
     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.
     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.
     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 sent to: Drug 
Enforcement Administration, Attn: Administrator, 8701 Morrissette 
Drive, Springfield, Virginia 22152. All 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 FR 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:

 2,5-dimethoxy-4-iodoamphetamine (DOI) and
 2,5-dimethoxy-4-chloroamphetamine (DOC)

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, 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 or 
notices of intent to participate in a hearing in conformity with the 
requirements of 21 CFR 1308.44(a) or (b), and such requests must 
include a statement of interest in the proceeding and the objections or 
issues, if any, concerning which the person desires to be heard. 21 CFR 
1316.47(a). Any interested person may file a waiver of an opportunity 
for a hearing or to participate in a hearing together with a written 
statement regarding the interested person's position on the matters of 
fact and law involved in any hearing as set forth in 21 CFR 1308.44(c).
    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.

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, 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

[[Page 21071]]

consultation with the Attorney General, shall first determine whether 
existing legal controls under subchapter I of the Controlled Substances 
Act (CSA) and the Federal Food, Drug, and Cosmetic Act meet the 
requirements of the schedule specified in the notification with respect 
to the specific drug or substance. 21 U.S.C. 811(d)(3). In the event 
that the Secretary did not so consult with the Attorney General, and 
the Attorney General did not issue a temporary order, as provided under 
21 U.S.C. 811(d)(4), the procedures for permanent scheduling set forth 
in 21 U.S.C. 811(a) and (b) control. Pursuant to 21 U.S.C. 811(a)(1), 
the Attorney General (as delegated to the Administrator of DEA) may, by 
rule, add to such a schedule or transfer between such schedules any 
drug or other substance, if he finds that such drug or other substance 
has a potential for abuse, and makes with respect to such drug or other 
substance the findings prescribed by 21 U.S.C. 812(b) for the schedule 
in which such drug or other substance is to be placed.
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    \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).
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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, 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). 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 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 ``DEA-824.''

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: \2\
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    \2\ 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

[[Page 21072]]

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-HT2A) receptors. In rats, DOI 
administration induced an increase in wet dog shakes and back muscle 
contractions. These effects were attributed to 5-HT2A 
receptor activation, since pretreatment with a 5-HT2A 
receptor inverse agonist blocked the effect. Agonism of the 5-
HT2A 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.
    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 \3\ 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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    \3\ 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 
C11H16INO2 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 
C11H16ClNO2 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).\4\ 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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    \4\ NFLIS 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 data were queried on February 23, 2021.
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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.
    A July 2019 report from the European Monitoring Centre for Drugs 
and Drug Addiction included data from their

[[Page 21073]]

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 indicate that DOI and DOC were found in samples 
starting in 2005, in the United States. Specifically, there were 40 
NFLIS reports for DOI from 2005 through February 2021, and 785 NFLIS 
reports for DOC during the same period. DOI has been encountered in 14 
states, whereas DOC has been encountered in 38 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. 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 
judgement, 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 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 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) FDA has not approved a marketing application for a drug product 
containing DOI or DOC for any therapeutic indication. In addition, DEA 
and HHS know of no clinical studies or petitioners claiming an accepted 
medical use in the United States. Therefore, DOI and DOC have no 
currently accepted medical use in treatment in the United States.\5\
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    \5\ 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. 
Therefore, there is a lack of accepted safety for use of DOI and DOC 
under medical supervision.
    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

[[Page 21074]]

sanctions applicable to the manufacture, distribution, reverse 
distribution, import, export, engagement in research, conduct of 
instructional activities or chemical analysis with, and possession of 
schedule I controlled substances, including the following:
    1. Registration. Any person who handles (manufactures, distributes, 
reverse distributes, imports, exports, engages in research, or conducts 
instructional activities or chemical analysis with, or possesses) or 
desires to handle DOI or DOC would be required to register 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, as of the effective 
date of a final scheduling action. Any person who currently handles DOI 
or DOC and is not registered with DEA would need to submit an 
application for registration and may not continue to handle DOI and DOC 
as of the effective date of a final scheduling action unless DEA has 
approved that application for registration pursuant to 21 U.S.C. 822, 
823, 957, 958, and in accordance with 21 CFR parts 1301 and 1312.
    2. Disposal of Stocks. Any person unwilling or unable to obtain a 
schedule I registration would be required to surrender or transfer all 
quantities of currently held DOI and DOC to a person registered with 
DEA before the effective date of a final scheduling action, in 
accordance with all applicable Federal, State, local, and tribal laws. 
As of the effective date of a final scheduling action, DOI and DOC 
would be required to be disposed of in accordance with 21 CFR part 
1317, in addition to all other applicable Federal, State, local, and 
tribal laws.
    3. Security. 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. 823 and in accordance with 21 CFR 1301.71-1301.76, as of the 
effective date of a final scheduling action. Non-practitioners handling 
DOI and DOC would also need to comply with the employee screening 
requirements of 21 CFR 1301.90-1301.93.
    4. Labeling and Packaging. All labels and packaging for commercial 
containers of DOI and DOC would need to be in compliance with 21 U.S.C. 
825, and be in accordance with 21 CFR part 1302, as of the effective 
date of a final scheduling action.
    5. Quota. Only registered manufacturers would be permitted to 
manufacture DOI and DOC in accordance with quotas assigned pursuant to 
21 U.S.C. 826, and in accordance with 21 CFR part 1303, as of the 
effective date of a final scheduling action.
    6. Inventory. Every DEA registrant who possesses any quantity of 
DOI and DOC on the effective date of the final scheduling action would 
be required to take an inventory of DOI and DOC on hand at that time, 
pursuant to 21 U.S.C. 827, and in accordance with 21 CFR 1304.03, 
1304.04, and 1304.11(a) and (d).
    Any person who registers with DEA on or after the effective date of 
the final scheduling action would be required to take an initial 
inventory of all stocks of controlled substances (including 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(a) and (b).
    After the initial inventory, every DEA registrant would be required 
to take a new 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.
    7. Records and Reports. Every DEA registrant would be required to 
maintain records and submit reports for DOI and DOC, or products 
containing DOI and DOC, pursuant to 21 U.S.C. 827, and in accordance 
with 21 CFR 1301.74(b) and (c) and parts 1304, 1312, and 1317, as of 
the effective date of a final scheduling action. Manufacturers and 
distributors would need to submit reports regarding DOI and DOC to the 
Automation of Reports and Consolidated Order System pursuant to 21 
U.S.C. 827 and in accordance with 21 CFR parts 1304 and 1312, as of the 
effective date of a final scheduling action.
    8. Order Forms. Every DEA registrant who distributes DOI and DOC 
would be required to comply with the order form requirements, pursuant 
to 21 U.S.C. 828, and 21 CFR part 1305, as of the effective date of a 
final scheduling action.
    9. 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, as of the 
effective date of a final scheduling action.
    10. 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.

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

[[Page 21075]]

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 will not, if promulgated, result in a significant effect 
on a substantial number of small entities.

Unfunded Mandates Reform Act of 1995

    On the basis of information contained in the ``Regulatory 
Flexibility Act'' section above, DEA has determined pursuant to the 
Unfunded Mandates Reform Act (UMRA) of 1995 (2 U.S.C. 1501 et seq.) 
that this proposed action would not result in any Federal mandate that 
may result ``in the expenditure by State, local, and tribal 
governments, in the aggregate, or by the private sector, of 
$100,000,000 or more (adjusted annually for inflation) in any 1 year . 
. . .'' Therefore, neither a Small Government Agency Plan nor any other 
action is required under UMRA of 1995.

List of Subjects in 21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.

    For the reasons set out above, 21 CFR part 1308 is proposed to be 
amended to read as follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for 21 CFR part 1308 continues to read as 
follows:

    Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise 
noted.

0
2. In Sec.  1308.11, as proposed to be amended at 86 FR 16553 (March 
30, 2021), 86 FR 37719 (July 16, 2021), 86 FR 69187 (December 7, 2021), 
and 87 FR 2383 (January 14, 2022), add paragraphs (d)(106) and (107) to 
read as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (d) * * *

(106) 2,5-dimethoxy-4-iodoamphetamine (Other name: DOI)..........   7447
(107) 2,5-dimethoxy-4-chloroamphetamine (Other name: DOC)........   7448
 

* * * * *

Anne Milgram,
Administrator.
[FR Doc. 2022-07648 Filed 4-8-22; 8:45 am]
BILLING CODE 4410-09-P