[Federal Register Volume 89, Number 99 (Tuesday, May 21, 2024)]
[Proposed Rules]
[Pages 44597-44622]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-11137]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-1362; A.G. Order No. 5931-2024]


Schedules of Controlled Substances: Rescheduling of Marijuana

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: The Department of Justice (``DOJ'') proposes to transfer 
marijuana from schedule I of the Controlled Substances Act (``CSA'') to 
schedule III of the CSA, consistent with the view of the Department of 
Health and Human Services (``HHS'') that marijuana has a currently 
accepted medical use as well as HHS's views about marijuana's abuse 
potential and level of physical or psychological dependence. The CSA 
requires that such actions be made through formal rulemaking on the 
record after opportunity for a hearing. If the transfer to schedule III 
is finalized, the regulatory controls applicable to schedule III 
controlled substances would apply, as appropriate, along with existing 
marijuana-specific requirements and any additional controls that might 
be implemented, including those that might be implemented to meet U.S. 
treaty obligations. If marijuana is transferred into schedule III, the 
manufacture, distribution, dispensing, and possession of marijuana 
would remain subject to the applicable criminal prohibitions of the 
CSA. Any drugs containing a substance within the CSA's definition of 
``marijuana'' would also remain subject to the applicable prohibitions 
in the Federal Food, Drug, and Cosmetic Act (``FDCA''). DOJ is 
soliciting comments on this proposal.

DATES: Comments must be submitted electronically or postmarked on or 
before July 22, 2024. Interested persons may file a request for a 
hearing or waiver of an opportunity for a hearing or to participate in 
a hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR 
1316.47 or 1316.49, as applicable, which must be received or postmarked 
on or before June 20, 2024.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-1362'' on all correspondence, including any 
attachments.
     Electronic comments: DOJ encourages that all comments be 
submitted through the Federal eRulemaking Portal, which provides the 
ability to type short comments directly

[[Page 44598]]

into the comment field on the web page or to attach a file for 
lengthier comments. Please go to https://www.regulations.gov and follow 
the online instructions at that site for submitting comments. Upon 
completion of your submission, you will receive a Comment Tracking 
Number for your comment. Please be aware that submitted comments are 
not instantaneously available for public view on https://www.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 submitting a comment electronically, it 
should be sent via regular or express mail to: Drug Enforcement 
Administration, Attn: DEA Federal Register Representative/DPW, 8701 
Morrissette Drive, Springfield, Virginia 22152.
     Hearing requests: All requests for a hearing and waivers, 
together with a written statement of position on the matters of fact 
and law asserted in the hearing, must be filed with DEA. 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 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: Drug & Chemical Evaluation Section, 
Diversion Control Division, Drug Enforcement Administration; Telephone: 
(571) 362-3249; Email: [email protected].

SUPPLEMENTARY INFORMATION: To be considered 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 comment, hearing request, or other information was 
previously submitted to the Drug Enforcement Administration (``DEA'') 
in connection with any prior matter relating to the scheduling of 
marijuana.

I. Posting of Public Comments

    Please note that all comments received in response to this docket 
are considered part of the public record. DOJ will make comments 
available for public inspection online at https://www.regulations.gov. 
Such information includes personal or business identifiers (such as 
name, address, State or Federal identifiers, etc.) voluntarily 
submitted by the commenter. Generally, all information voluntarily 
submitted by the commenter, unless clearly marked as ``Confidential 
Information'' in the method described below, will be publicly posted. 
Comments may be submitted anonymously. The Freedom of Information Act, 
5 U.S.C. 552, applies to all comments received.
    Commenters submitting comments that include personal identifying 
information (``PII'') or confidential or proprietary business 
information that the commenter does not want made publicly available 
should submit two copies of the comment. One copy must be marked 
``CONTAINS CONFIDENTIAL INFORMATION'' and should clearly identify all 
PII or business information the commenter does not want to be made 
publicly available, including any supplemental materials. DOJ will 
review this copy, including the claimed PII and confidential business 
information, in its consideration of comments. The second copy should 
be marked ``TO BE PUBLICLY POSTED'' and must have all claimed 
confidential PII and business information already redacted. DOJ will 
post only the version of the comment with redactions on https://www.regulations.gov for public inspection.
    An electronic copy of this document and supplemental information to 
this proposed rule are available at https://www.regulations.gov for 
easy reference. DOJ specifically solicits written comments regarding 
the economic analysis of the impact of these proposed changes. DOJ 
requests that commenters provide detailed descriptions in their 
comments of any expected economic impacts, especially to small 
entities. Commenters should provide empirical data to illustrate the 
nature and scope of such impact.

II. Request for Hearing, Notice of Appearance at, or Waiver of 
Participation in Hearing

    Pursuant to 21 U.S.C. 811(a), this scheduling action is a formal 
rulemaking ``on the record after opportunity for a hearing.'' Such 
proceedings are conducted pursuant to the Administrative Procedure Act 
(``APA''), 5 U.S.C. 551-559. See 21 CFR 1308.41 through 1308.45; id 
part 1316, subpart D. Interested persons, as defined in 21 CFR 
1300.01(b), may file requests for a hearing in conformity with the 
requirements of 21 CFR 1308.44(a) and 1316.47(a), and such requests 
must:
    (1) state with particularity the interest of the person in the 
proceeding;
    (2) state with particularity the objections or issues concerning 
which the person desires to be heard; and
    (3) state briefly the position of the person regarding the 
objections or issues.
    All requests for a hearing and waivers of an opportunity for a 
hearing or 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 an in-person hearing will be needed to address 
such matters of fact and law in the rulemaking will be made by the 
Administrator of DEA. Upon the Administrator's determination to grant 
an in-person hearing, DEA will publish a notice of hearing on the 
proposed rulemaking in the Federal Register. See 21 CFR 1308.44(b), 
1316.53.
    If the Administrator determines to grant an in-person hearing to 
address such matters of fact and law in this rulemaking, the 
Administrator 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. The ALJ will have all 
powers necessary to conduct a fair hearing, to take all necessary 
action to avoid delay, and to maintain order. Id. The ALJ's authorities 
include the power to hold conferences to simplify or determine the 
issues in the hearing or to consider other matters that may aid in the 
expeditious disposition of the hearing; require parties to state their 
position in writing; sign and issue subpoenas to compel the production 
of documents and materials to the extent necessary to conduct the 
hearing; examine witnesses and direct witnesses to testify; receive, 
rule on, exclude, or limit evidence; rule on procedural items; and take 
any action permitted by the presiding officer under DEA's hearing 
procedures and the APA. Id.
    Comments on or objections to the proposed rule submitted under 21 
CFR 1308.43(g) will be offered as evidence at the hearing, but the 
presiding officer shall admit only evidence that is competent, 
relevant, material, and not unduly repetitive. 21 CFR 1316.59(a).

[[Page 44599]]

    Any interested person may file a waiver of 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. Such statement, if admissible, will be included in the record 
and considered as described in 21 CFR 1308.44(c).
    In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing 
would be to ``receiv[e] factual evidence and expert opinion regarding'' 
whether marijuana should be transferred to schedule III of the list of 
controlled substances. 21 CFR 1308.42. Concurrent with this rulemaking, 
DEA will consider the marijuana-specific controls that would be 
necessary to comply with relevant treaty obligations in the event that, 
after the hearing, a final order reschedules marijuana, and, to the 
extent such controls are needed if marijuana is rescheduled, will seek 
to finalize any such regulations as soon as possible.
    All requests for hearing and waivers of an opportunity for a 
hearing or participation must be sent to DEA using the address 
information above, on or before the date specified above.

III. Legal Authority

    Under the CSA, 21 U.S.C. 801 et seq., the Attorney General shall, 
before initiating proceedings to control, decontrol, or transfer 
between schedules a drug or other substance, request from the Secretary 
of HHS a scientific and medical evaluation, and the Secretary's 
recommendations, as to whether such drug or other substance should be 
so controlled or removed as a controlled substance. 21 U.S.C. 811(b). 
The recommendations of the Secretary shall include recommendations with 
respect to the appropriate schedule, if any, under which such drug or 
other substance should be listed. Id.
    HHS recommended in August 2023 that marijuana be rescheduled to 
schedule III. See Letter for Anne Milgram, Administrator, DEA, from 
Rachel L. Levine, M.D., Assistant Secretary for Health, HHS (Aug. 29, 
2023) (``August 2023 Letter''). The Attorney General then sought the 
legal advice of the Office of Legal Counsel (``OLC'') at DOJ on 
questions relevant to this rulemaking proceeding. Among other 
conclusions, OLC concluded that ``HHS's scientific and medical 
determinations must be binding until issuance of a notice of proposed 
rulemaking [(`NPRM')].'' Questions Related to the Potential 
Rescheduling of Marijuana, 45 Op. O.L.C. __, at *25 (Apr. 11, 2024) 
(``OLC Op.'').\1\ After the issuance of a notice of rulemaking 
proceedings, HHS's scientific and medical determinations are accorded 
``significant deference'' through the rest of the rulemaking 
process.\2\ OLC Op. at *26.
---------------------------------------------------------------------------

    \1\ OLC's opinion is available in its entirety under 
``Supporting and Related Material'' of the public docket for this 
proposed rule at https://www.regulations.gov under docket number 
DEA-1362.
    \2\ The CSA's reliance on formal rulemaking for scheduling 
decisions indicates that HHS's determinations do not bind DOJ for 
the entirety of the rulemaking process, because outside participants 
may submit additional scientific and medical evidence during the 
rulemaking that DOJ would need to consider. OLC Op. at *25. However, 
DOJ ``may not simply cast aside HHS's scientific and medical 
recommendations once it initiates rulemaking proceedings by issuing 
an NPRM,'' since ``[t]he categorical use of the word `binding' in 
section 811(b) suggests that Congress intended HHS's scientific and 
medical views to at least be a very significant input in the 
scheduling process,'' and the legislative history of the CSA 
bolsters that conclusion. Id. at 25-26 (citing H.R. Rep. No. 91-
1444, at 22-23 (1970)).
---------------------------------------------------------------------------

    Under the CSA, when recommending or determining that a drug should 
be controlled (and if so, under which schedule), the Secretary and the 
Attorney General must consider eight factors set forth in 21 U.S.C. 
811(c). The eight factors are:
    1. The drug's actual or relative potential for abuse;
    2. Scientific evidence of its pharmacological effect, if known;
    3. The state of current scientific knowledge regarding the drug or 
other substance;
    4. Its history and current pattern of abuse;
    5. The scope, duration, and significance of abuse;
    6. What, if any, risk there is to the public health;
    7. Its psychic or physiological dependence liability; and
    8. Whether the substance is an immediate precursor of a substance 
already controlled.
21 U.S.C. 811(c); see also id. 811(b) (specifying how HHS should 
consider each of the eight factors).
    The United States is a party to the 1961 United Nations Single 
Convention on Narcotic Drugs, March 30, 1961, 18 U.S.T. 1407, 520 
U.N.T.S. 151 (``Single Convention''), as amended by the 1972 Protocol, 
March 25, 1972, 26 U.S.T. 1439, 976 U.N.T.S. 3. Under 21 U.S.C. 
811(d)(1), if control of a substance is required ``by United States 
obligations under international treaties, conventions, or protocols in 
effect on October 27, 1970,'' the Attorney General must issue an order 
controlling such drug ``under the schedule he deems most appropriate to 
carry out such obligations, without regard to the findings'' required 
by 21 U.S.C. 811(a) or 812(b), ``and without regard to the procedures'' 
prescribed by 21 U.S.C. 811(a) and (b). Marijuana is a drug covered by 
the Single Convention. See Single Convention art. 1(1)(b); OLC Op. at 
*26 & n.7.
    OLC and the United States Court of Appeals for the D.C. Circuit 
have explained that section 811(d)(1) does not supersede the scheduling 
procedures set forth in sections 811(a) through (b) and 812(b), 
including the requirement to consider the eight factors set forth in 
section 811(c). Instead, section 811(d)(1) allows the Attorney General 
to ``identify which schedules would satisfy the United States' 
international obligations with respect to a particular drug, and then--
if more than one schedule would do so--select which schedule to use 
through the section 811(a) through (b) and 812(b) procedures.'' OLC Op. 
at *29 n.8; accord Nat'l Org. for Reform of Marijuana Laws (NORML II) 
v. DEA, 559 F.2d 735, 747 (D.C. Cir. 1977). HHS performed the eight-
factor analysis. See Memorandum for DEA, from HHS, Re: Basis for the 
Recommendation to Reschedule Marijuana to Schedule III of the 
Controlled Substances Act (``HHS Basis for Rec.''). As noted above, 
HHS's scientific and medical determinations are binding on DOJ until an 
NPRM is published, and, in addition, DOJ must accord ``significant 
deference'' to HHS's scientific and medical determinations throughout 
the rulemaking process. OLC Op. at *25-26.
    Once the determination is made that a particular drug or substance 
must be controlled under the CSA, the Attorney General must determine 
the level of control over the drug or substance under the CSA. See 21 
U.S.C. 811(a), (b). The CSA divides controlled substances into five 
levels of control, or ``schedules,'' based on (1) a drug's potential 
for abuse, (2) whether the drug has a currently accepted medical use in 
treatment in the United States (``CAMU''), and (3) whether there is a 
lack of accepted safety for use of the drug under medical supervision 
or the level of psychological or physical dependence that could result 
from abuse of the drug. See id. 812(b). Schedule I drugs have a high 
potential for abuse, no CAMU, and a lack of accepted safety for use 
under medical supervision. Id. 812(b)(1). Schedule II drugs also have a 
high potential for abuse but have a CAMU (or a CAMU with ``severe 
restrictions''), and abuse of the drug may lead to severe psychological 
or physical dependence. Id. 812(b)(2). Schedule III drugs, meanwhile, 
have a lower potential for

[[Page 44600]]

abuse when compared to drugs in schedules I and II, have a CAMU, and 
their abuse may lead to moderate or low physical dependence or high 
psychological dependence.\3\ 21 U.S.C. 812(b)(3). The initial schedules 
of controlled substances established by Congress are found at 21 U.S.C. 
812(c), and the current list of all scheduled substances is published 
at 21 CFR part 1308.
---------------------------------------------------------------------------

    \3\ Schedule IV includes drugs that have a low potential for 
abuse relative to those in schedule III, that have a CAMU, and for 
which abuse may lead to limited physical or psychological dependence 
relative to those in schedule III. 21 U.S.C. 812(b)(4). Schedule V 
includes drugs that have a low potential for abuse relative to those 
in schedule IV, that have a CAMU, and for which abuse may lead to 
limited physical or psychological dependence relative to those in 
schedule IV. Id. 812(b)(5).
---------------------------------------------------------------------------

    Pursuant to 21 U.S.C. 811(a)(1), the Attorney General may, by rule, 
add to such a schedule or transfer between such schedules any drug or 
other substance if he (A) finds that such drug or other substance has a 
potential for abuse, and (B) 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 is to be placed. 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, at the request of the Secretary, or on the petition of any 
interested party. Id.

IV. Background

    When Congress enacted the CSA in 1970, it placed marijuana in 
schedule I. Comprehensive Drug Abuse Prevention and Control Act of 
1970, Public Law 91-513, tit. II, sec. 202(c), 84 Stat. 1236, 1249 
(1970); 21 U.S.C. 812(c).\4\ The Attorney General is authorized to 
amend this initial placement. 21 U.S.C. 812(c); see also id. 811, 
812(b). Other schedule I substances include heroin, lysergic acid 
diethylamide (commonly known as LSD), and 3,4-
methylenedioxymethamphetamine (ecstasy). See 21 CFR 1308.11. Drugs 
controlled under schedule II include cocaine, methamphetamine, 
methadone, oxycodone, and fentanyl. Id. Sec.  1308.12. Drugs controlled 
under schedule III include products containing less than 90 milligrams 
of codeine per dosage unit, ketamine, and anabolic steroids. Id. Sec.  
1308.13. Petitioners have requested that marijuana be rescheduled 
several times over the years. See, e.g., Schedule of Controlled 
Substances: Petition To Remove Marihuana From Control or in the 
Alternative To Control Marihuana in Schedule V of the Controlled 
Substances Act, 37 FR 18097 (Sept. 7, 1972); Notice of Denial of 
Petition, 66 FR 20038 (Apr. 18, 2001); Denial of Petition To Initiate 
Proceedings To Reschedule Marijuana, 76 FR 40552 (July 8, 2011).
---------------------------------------------------------------------------

    \4\ The CSA refers to the drug as ``marijuana'' and 
``marihuana'' interchangeably. See, e.g., 21 U.S.C. 802(16)(A), 
812(c). As used in this NPRM, ``marijuana'' means the term defined 
at 21 U.S.C. 802(16).
---------------------------------------------------------------------------

    DEA and HHS last examined the issue of whether to reschedule 
marijuana eight years ago, in 2016, when DEA denied two petitions to 
reschedule marijuana.\5\ At the time, HHS concurred that marijuana 
should remain a schedule I drug because it met the three criteria for 
placement in schedule I. 81 FR 53706-07. In accordance with the 
requirements for placement in schedule I, HHS found that: (1) marijuana 
had a high potential for abuse; (2) it did not have a CAMU; and (3) 
there was a lack of accepted safety for use of marijuana under medical 
supervision. Id. As discussed in detail below, in 2023, HHS conducted a 
scientific and medical evaluation of marijuana based on a comprehensive 
review of available data at that time and recommended that marijuana be 
transferred to schedule III.
---------------------------------------------------------------------------

    \5\ Denial of Petition To Initiate Proceedings To Reschedule 
Marijuana, 81 FR 53688 (Aug. 12, 2016); Denial of Petition To 
Initiate Proceedings To Reschedule Marijuana, 81 FR 53767 (Aug. 12, 
2016).
---------------------------------------------------------------------------

    Since 1996, 38 States, the District of Columbia, and 4 Federal 
Territories have legalized the use of medical marijuana. HHS Basis for 
Rec. at 30; OLC Op at *9. These laws typically allow the cultivation, 
sale, and use of marijuana by patients (or their caregivers) whose 
health care practitioners have recommended that they use marijuana to 
treat certain health conditions. See, e.g., Ohio Rev. Code secs. 
3796.01(A)(6)(a)-(v), 3796.01(A); N.Y. Cannabis Law secs. 3(18), 30, 
31; N.M. Stat. secs. 26-2B-3(F)(1)-(23), 26-2B-3(N), 26-2B-4(A). 
Further, beginning in Fiscal Year 2015, Congress has adopted an 
appropriations rider every year that prohibits DOJ from using funds to 
prevent certain States, Territories, and the District of Columbia from 
implementing their own laws with respect to medical marijuana. E.g., 
Consolidated Appropriations Act, 2024, Public Law 118-42, sec. 531, 138 
Stat. 25; Consolidated Appropriations Act, 2023, Public Law 117-328, 
sec. 531, 136 Stat. 4459, 4561 (2022); see also Cong. Research Serv., 
R44782, The Evolution of Marijuana as a Controlled Substance and the 
Federal-State Policy Gap 26 & n.159 (updated Apr. 7, 2022) (collecting 
additional appropriations riders).
    Marijuana is generally defined by statute to mean ``the plant 
Cannabis sativa L., whether growing or not; the seeds thereof; the 
resin extracted from any part of such plant; and every compound, 
manufacture, salt, derivative, mixture, or preparation of such plant, 
its seeds or resin.'' 21 U.S.C. 802(16)(A). In 2018, Congress amended 
the CSA to remove ``(i) hemp, as defined in section [1639o of title 7 
of the U.S. Code]'' from the definition of marijuana.\6\ Agricultural 
Improvement Act of 2018, Public Law 115-334, sec. 12619, 132 Stat. 
4490, 5018. Section 1639o(1) of title 7 in turn defines hemp as ``the 
plant Cannabis sativa L. and any part of that plant, including the 
seeds thereof and all derivatives, extracts, cannabinoids, isomers, 
acids, salts, and salts of isomers, whether growing or not, with a 
delta-9-tetrahydrocannabinol concentration of not more than 0.3 percent 
on a dry weight basis.'' Delta-9-tetrahydrocannabinol (``[Delta]9-
THC'') is the major psychoactive intoxicating cannabinoid in marijuana. 
See HHS Basis for Rec. at 10. This exclusion of hemp from the 
definition of marijuana had the effect of removing many products 
containing predominantly cannabidiol (``CBD'') derived from hemp and 
containing no more than 0.3 percent [Delta]9-THC on a dry weight basis 
from control as marijuana.
---------------------------------------------------------------------------

    \6\ Marijuana under the CSA also does not include ``the mature 
stalks of [the cannabis] plant, fiber produced from such stalks, oil 
or cake made from the seeds of such plant, any other compound, 
manufacture, salt, derivative, mixture, or preparation of such 
mature stalks (except the resin extracted therefrom), fiber, oil, or 
cake, or the sterilized seed of [the cannabis] plant which is 
incapable of germination.'' 21 U.S.C. 802(16)(B)(ii).
---------------------------------------------------------------------------

    On October 6, 2022, President Biden requested that the Attorney 
General and the Secretary of HHS ``initiate the administrative process 
to review expeditiously how marijuana is scheduled under federal law.'' 
\7\ HHS thereafter undertook a scientific and medical evaluation of 
marijuana as defined under the CSA in accordance with the President's 
request.
---------------------------------------------------------------------------

    \7\ The White House, Statement from President Biden on Marijuana 
Reform (Oct. 6, 2022), https://www.whitehouse.gov/briefing-room/statements-releases/2022/10/06/statement-from-president-biden-on-marijuana-reform/.
---------------------------------------------------------------------------

    In a letter dated August 29, 2023, Admiral Rachel L. Levine, M.D., 
HHS's Assistant Secretary for Health, recommended to the Administrator 
of DEA that marijuana be controlled in schedule III of the CSA. August 
2023 Letter. HHS found that marijuana has a potential for abuse less 
than the drugs or other substances in schedules I and II; that 
marijuana has a CAMU; and that the abuse of marijuana may lead to 
moderate or low physical dependence or high psychological dependence. 
HHS

[[Page 44601]]

Basis for Rec. at 62-65. These findings correspond to the criteria for 
placement of a substance in schedule III. See 21 U.S.C. 812(b)(3). DEA 
has not yet made a determination as to its views of the appropriate 
schedule for marijuana.

V. Proposal To Reschedule Marijuana

    The CSA vests the Attorney General with the authority to schedule, 
reschedule, or decontrol drugs. 21 U.S.C. 811(a). The Attorney General 
has delegated that authority to the DEA Administrator, see 28 CFR 
0.100, but also retains the authority to schedule drugs under the CSA 
in the first instance, see 28 U.S.C. 509, 510. The HHS Assistant 
Secretary for Health has provided a recommendation for transferring 
marijuana to schedule III. In light of that recommendation, the 
Attorney General is exercising the Attorney General's authority under 
21 U.S.C. 811(a) to initiate a rulemaking that proposes the placement 
of marijuana in schedule III.
    DEA believes that additional information arising from this 
rulemaking will further inform the findings regarding the appropriate 
schedule for marijuana. DEA has maintained an active review of the 
scientific literature addressing marijuana with a focus on how it 
relates to the scientific and medical evaluation and informs any 
updates to the eight-factor analysis. In addition to HHS's scientific 
and medical determinations, which are binding until the issuance of 
this NPRM and which must be accorded significant deference throughout 
the rulemaking, DEA believes that factual evidence (including 
scientific data) and expert opinions, including additional data 
regarding different forms, formulations, and delivery methods for 
marijuana, as well as evidence regarding the effects of marijuana at 
various dosages or concentrations, may be relevant.
    The HHS Basis for Recommendation, DEA's analyses explaining its 
decisions to deny the petitions to reschedule marijuana in 2016, and 
the 2024 OLC opinion (cited throughout) are available in their entirety 
under ``Supporting and Related Material'' of the public docket for this 
proposed rule at https://www.regulations.gov under docket number DEA-
1362.

VI. Eight-Factor Analysis

    DOJ has reviewed the scientific and medical evaluation and 
scheduling recommendation provided by HHS and has conducted a separate 
review of the eight factors identified in 21 U.S.C. 811(c). At this 
point in the proceedings, DOJ must treat HHS's scientific and medical 
determinations as binding. See OLC Op. at *4, *25. HHS's scientific and 
medical determinations are included below, as well as certain 
information from DEA.

1. Marijuana's Actual or Relative Potential for Abuse

    The first factor that DOJ and HHS must consider under 21 U.S.C. 
811(c) is the actual or relative potential for abuse of marijuana. The 
term ``abuse'' is not defined in the CSA. However, consistent with the 
legislative history of the CSA, DEA and HHS have typically weighed the 
following factors in determining whether a particular drug or substance 
has a potential for abuse: \8\
---------------------------------------------------------------------------

    \8\ See, e.g., 81 FR 53740; see also HHS Basis for Rec. at 6 
(citing Comprehensive Drug Abuse Prevention and Control Act of 1970, 
H.R. Rep. No. 91-1444 (1970), reprinted in 1970 U.S.C.C.A.N. 4566, 
4603).
---------------------------------------------------------------------------

    A. Whether there is evidence that individuals are taking the drug 
or drugs containing such a substance in amounts sufficient to create a 
hazard to their health or to the safety of other individuals or to the 
community.
    As part of its analysis, HHS concluded that evidence shows that, 
although some individuals are taking marijuana in amounts sufficient to 
create a hazard to their health and to the safety of other individuals 
and the community, the vast majority of individuals who use marijuana 
are doing so in a manner that does not lead to dangerous outcomes to 
themselves or others. HHS Basis for Rec. at 6-7. The data supportive of 
this conclusion are discussed in detail in HHS's analysis of Factors 4, 
5, and 6. See HHS Basis for Rec. at 28-57.
    In particular, HHS emphasized that an evaluation of various 
epidemiological databases of adverse outcomes from 2015 to 2021 
involving marijuana or comparator drugs that are used nonmedically 
showed that the utilization-adjusted rate of adverse outcomes involving 
marijuana was consistently lower than the utilization-adjusted rates of 
adverse outcomes involving heroin, cocaine, and, for certain outcomes, 
other comparators, including alcohol. Also, alcohol or heroin typically 
ranked first or in immediately subsequent positions among the 
comparators in terms of incidence of adverse outcomes, with marijuana 
in a lower place in that ranking. This pattern also was observed for 
serious medical outcomes, including death, observed in Poison Center 
data, where marijuana was in the lowest ranking group. This suggests 
consistency across databases, across drugs, and over time. HHS thus 
concluded that although abuse of marijuana produces clear evidence of 
harmful consequences, these appear to be relatively less common and 
less severe than the consequences of some other comparator substances. 
HHS Basis for Rec. at 7-8.
    Importantly, these comparisons of the prevalence of adverse 
outcomes were from descriptive analyses only, following the established 
practice in previous eight-factor analyses. Thus, differences in 
outcome frequency and severity, and the ranked order across 
comparators, may be attributable in part to underlying differences in 
the populations being compared (e.g., age or pre-existing medical 
conditions), among other things. Despite these limitations, qualitative 
synthesis of descriptive analyses is the established practice in 
previous eight-factor analyses, and HHS determined that it is the most 
appropriate approach here. HHS Basis for Rec. at 7-8.
    HHS also concluded that the public-health risks posed by marijuana 
are lower compared to those posed by other drugs of abuse (e.g., 
heroin, oxycodone, cocaine), based on HHS's evaluation of various 
epidemiological databases for emergency department (``ED'') visits, 
hospitalizations, unintentional exposures, and most importantly, 
overdose deaths. The rank order of the comparators in terms of greatest 
adverse consequences typically ranked heroin, benzodiazepines, and 
cocaine first or in immediately subsequent positions, with marijuana in 
a lower place in the ranking, especially when HHS adjusted for 
utilization. For overdose deaths, marijuana is always in the lowest 
ranking among comparator drugs. These evaluations demonstrate that 
there is consistency across databases, across substances, and over 
time. HHS thus concluded that although abuse of marijuana produces 
clear evidence of a risk to public health, that risk is relatively 
lower than that posed by most other comparator drugs. HHS Basis for 
Rec. at 7-8.
    DEA notes that data provided by HHS in its recommendation included 
a 2023 national survey that tracks drug use trends among 8th-, 10th-, 
and 12th-grade students, and showed that by 12th grade, 20.2 percent of 
students reported using marijuana in the past month.\9\ DEA also notes 
that the same study showed that the prevalence of ingesting marijuana 
by vaping is evidenced by

[[Page 44602]]

students reporting vaping in the 30 days prior at the following rates: 
4.2 percent for 8th graders, 10.3 percent for 10th graders, and 14.8 
percent for 12th graders.\10\ In 2022, the Substance Abuse and Mental 
Health Services Administration's (``SAMHSA'') Drug Abuse Warning 
Network (``DAWN'') reported that 11.9 percent of drug-related ED visits 
nationwide involved cannabis.\11\ The rate of cannabis-related ED 
visits was highest in these demographic groups: 18 to 25 years old, 
male, Black or African American, and Not Hispanic or Latino.\12\
---------------------------------------------------------------------------

    \9\ See HHS Basis for Rec. at 35 (discussing Richard A. Miech et 
al., Univ. of Mich. Inst. for Soc. Rsch., Monitoring the Future: 
National Survey Results on Drug Use, 1975-2022: Secondary School 
Students 71 (2023), https://monitoringthefuture.org/wp-content/uploads/2022/12/mtf2022.pdf).
    \10\ Miech et al., supra note 9, at 75.
    \11\ Drug Abuse Warning Network, Substance Abuse & Mental Health 
Servs. Admin., Findings from Drug-Related Emergency Department 
Visits, 2022, at 1 (2023), https://store.samhsa.gov/sites/default/files/pep23-07-03-001.pdf.
    \12\ Id.at 27.
---------------------------------------------------------------------------

    In addition to the data considered by the HHS Basis for 
Recommendation, the data considered by HHS and DEA in their 2015 eight-
factor analysis, and the additional data discussed above, DEA 
anticipates that additional data on seizures of marijuana by law 
enforcement, cannabis-related ED visits, as well as updated 
epidemiological survey data since 2022, may be appropriate for 
consideration.
    B. Whether there is significant diversion of the drug or drugs 
containing such a substance from legitimate drug channels.
    HHS found that there is a lack of evidence of significant diversion 
of marijuana from legitimate drug channels. HHS Basis for Rec. at 8. It 
noted that marijuana is used by researchers for clinical research under 
investigational new drug (``IND'') applications, and that there are 
multiple DEA registrants that are approved to produce marijuana and 
derived formulations for use in DEA-authorized nonclinical and clinical 
research. HHS observed that these authorizations represent the only 
federally sanctioned drug channels in the United States, and there is a 
lack of data indicating diversion occurring from these entities or 
activities. However, there are significant additional sources of 
marijuana in the United States, including from illicit cultivation and 
production, illicit importation from other countries, and from State 
programs that permit dispensing of marijuana for medical use and, in 
some States, recreational adult use. HHS Basis for Rec. at 8.
    Given this unique landscape, DEA believes that the lack of data 
indicating diversion of marijuana from federally sanctioned drug 
channels to the illicit market is not indicative of a lack of potential 
for abuse of the drug. DEA anticipates that additional data on 
diversion from State programs and DEA-registered manufacturers may aid 
in a determination of whether diversion is taking place.
    C. Whether individuals are taking the drug or drugs containing such 
a substance on their own initiative rather than on the basis of medical 
advice from a practitioner licensed by law to administer such drugs in 
the course of their professional practice.
    As HHS notes, the Food and Drug Administration (``FDA'') has not 
approved a New Drug Application (``NDA'') for a drug product containing 
botanical marijuana for any therapeutic indication. Thus, the only way 
an individual can use marijuana on the basis of medical advice through 
legitimate channels under Federal law is by participating in research 
under an IND. However, 38 States and the District of Columbia have 
enacted laws allowing individuals to use marijuana under certain 
circumstances for medical purposes. Outside of the Federal- and State-
sanctioned medical use of marijuana, individuals are using marijuana on 
their own initiative for medical, as well as nonmedical, purposes. 
Epidemiological data related to nonmedical use of marijuana is detailed 
in HHS's analysis of Factor 4. HHS Basis for Rec. at 8.
    DEA notes that data is not available to determine the number of 
individuals using marijuana under State law. According to 2022 National 
Survey on Drug Use and Health (``NSDUH'') data on people who are 12 and 
older in the United States, 61.9 million people reported using 
marijuana in the past year, and marijuana was the illicit drug used 
with the greatest frequency.\13\ Specifically, 42.3 million people 
reported use in the past month, including 14.7 million people who vaped 
marijuana in that same period, representing 5.2 percent of the study's 
target population.\14\ Furthermore, as reported by NSDUH in 2022, 3.7 
million people initiated marijuana use in the past year, with more than 
half (53 percent or 2.0 million people) initiating marijuana use before 
the age of 21.\15\ DEA also notes that HHS concluded that, outside of 
the Federal- and State-sanctioned medical use of marijuana, individuals 
are using marijuana on their own initiative for medical as well as 
nonmedical purposes. HHS Basis for Rec. at 8. In 2016, DEA reached a 
similar conclusion.\16\ In addition to the data considered in the HHS 
Basis for Recommendation, and by HHS and DEA in their earlier eight-
factor analyses, DEA anticipates that updated epidemiological survey 
data since 2022 may be appropriate for consideration.
---------------------------------------------------------------------------

    \13\ Substance Abuse & Mental Health Servs. Admin., Key 
Substance Use and Mental Health Indicators in the United States: 
Results from the 2022 National Survey on Drug Use and Health 14 
(Nov. 2023), https://www.samhsa.gov/data/sites/default/files/reports/rpt42731/2022-nsduh-nnr.pdf.
    \14\ Id. at 13.
    \15\ Id. at 27.
    \16\ 81 FR 53691 (``Based on the large number of individuals 
reporting current use of marijuana and the lack of an FDA-approved 
drug product in the United States, one can assume that it is likely 
that the majority of individuals using marijuana do so on their own 
initiative rather than on the basis of medical advice from a 
licensed practitioner.'').
---------------------------------------------------------------------------

    D. Whether the drug or drugs containing such a substance are new 
drugs so related in their action to a drug or drugs already listed as 
having a potential for abuse to make it likely that it will have the 
same potentiality for abuse as such drugs, thus making it reasonable to 
assume that there may be significant diversions from legitimate 
channels, significant use contrary to or without medical advice, or 
that they have a substantial capability of creating hazards to the 
health of the user or to the safety of the community.
    Marijuana has been a schedule I substance since the CSA was enacted 
in 1970. See Public Law 91-513, tit. II, sec. 202(c), 84 Stat. 1236, 
1249 (1970); 21 U.S.C. 812(c); see also 21 CFR 1308.11(d)(23). The 
primary compound in marijuana that is responsible for its abuse 
potential is [Delta]9-THC (also known as dronabinol, when specifically 
referring to the (-)-trans-[Delta]9-THC stereoisomer), which has 
agonist activity at cannabinoid CB1 receptors. HHS found 
that there are extensive nonclinical and clinical studies establishing 
that marijuana, due to the CB1 agonist activity of its main 
cannabinoid constituent [Delta]9-THC, produces rewarding effects that 
would be consistent with observed long-term patterns of nonmedical use 
and abuse, both before and in the years since enactment of the CSA. HHS 
Basis for Rec. at 9. For further discussion of these effects, see HHS 
Basis for Rec. at 9-18 (Factor 2), 28-37 (Factor 4).
    Additionally, FDA has approved two drug products containing 
dronabinol: Marinol (in 1985; schedule III) and Syndros (in 2016; 
schedule II). HHS Basis for Rec. at 9. Marinol was approved by FDA in 
1985 for the treatment of nausea and vomiting associated with cancer 
chemotherapy in patients who did not respond to conventional anti-
emetic treatments. FDA approved Marinol in 1992 for the treatment of 
anorexia associated with weight loss in patients with acquired

[[Page 44603]]

immunodeficiency syndrome (``AIDS''). After the first FDA approval, 
Marinol was transferred from schedule I to schedule II and was later 
rescheduled to schedule III. Syndros, a drug product also containing 
dronabinol but formulated in an oral solution, was approved by FDA in 
2016 for the treatment of anorexia associated with weight loss in 
patients with AIDS, as well as nausea and vomiting associated with 
cancer chemotherapy in patients who failed to respond adequately to 
conventional anti-emetic treatments. In 2017, DEA rescheduled ``FDA-
approved products containing dronabinol in an oral solution'' from 
schedule I into schedule II. HHS Basis for Rec. at 4.
    When Marinol and Syndros were being developed, they underwent a 
systematic evaluation of their abuse potential based on animal and 
human behavioral studies, which showed that dronabinol has abuse 
potential. The abuse-related studies confirmed the abuse potential of 
[Delta]9-THC. HHS has concluded that these findings suggest that 
marijuana will continue to be used nonmedically, diverted from 
legitimate channels, and trafficked in illicit channels as a potential 
source for continued nonmedical use in the United States. HHS Basis for 
Rec. at 9; see also HHS Basis for Rec. at 37-45 (Factor 5).
HHS Conclusion With Respect to Factor 1
    HHS determined that epidemiological data indicate that marijuana 
has the potential for creating hazards to the health of the user and to 
the safety of the community. However, as a relative finding on abuse 
liability, when comparing marijuana to heroin, oxycodone, hydrocodone, 
fentanyl, cocaine, ketamine, benzodiazepines, zolpidem, tramadol, and 
alcohol in various epidemiological databases that allow for some or all 
of these comparisons, marijuana is not typically among the substances 
producing the most frequent incidence of adverse outcomes or severity 
of substance use disorder. HHS Basis for Rec. at 9; see also HHS Basis 
for Rec. at 28-57 (Factors 4, 5, and 6). But as noted above, there are 
limitations in comparing descriptive data on adverse outcomes across 
drugs, although descriptive analyses of epidemiologic data are an 
established practice in previous eight-factor analyses. HHS Basis for 
Rec. at 9.
    In 2016, DEA found that ``[m]arijuana has a high potential for 
abuse. Preclinical and clinical data show that it has reinforcing 
effects characteristic of drugs of abuse. . . . Data on marijuana 
seizures show widespread availability and trafficking.'' 81 FR 53739. 
DEA believes that additional data in this area may be appropriate for 
consideration in assessing marijuana's actual or relative potential for 
abuse.

2. Scientific Evidence of Marijuana's Pharmacological Effects, If Known

    The second factor that DOJ and HHS must consider under 21 U.S.C. 
811(c) is the scientific evidence of marijuana's pharmacological 
effects, if known. In making its recommendation, HHS considered the 
scientific evidence of the pharmacological effects of marijuana based 
on the effects of [Delta]9-THC. HHS conducted a scientific evaluation 
of the neurochemistry, receptor pharmacology, animal abuse-related 
behavioral effects, and human behavioral and physiological effects of 
marijuana. HHS Basis for Rec. at 9.
A. Neurochemistry and Receptor Pharmacology of Marijuana
    Cannabis is the genus of a plant that contains numerous natural 
constituents, including cannabinoids. See HHS Basis for Rec. at 18-21 
(discussing Factor 3). Because cultivated chemovars may vary in their 
composition and concentration of various chemical constituents, 
including with respect to whether they contain significant amounts of 
[Delta]9-THC or other cannabinoids, marijuana products from different 
strains will have differing biological and pharmacological profiles. 
HHS Basis for Rec. at 10.
    Marijuana contains at least 560 identified natural constituents, 
including 125 compounds classified as cannabinoids. Most major 
cannabinoid compounds occurring naturally in cannabis have been 
identified chemically, but new and minor compounds are continuously 
being characterized. HHS Basis for Rec. at 10.
    The two most abundant cannabinoids present in marijuana are 
[Delta]9-THC and CBD. [Delta]9-THC is the major psychoactive 
intoxicating cannabinoid in marijuana and is the component of marijuana 
that is primarily responsible for its abuse potential. In contrast, CBD 
has negligible abuse potential, as assessed by FDA during the NDA 
review for Epidiolex, an FDA-approved drug product containing plant 
derived, highly purified CBD. HHS Basis for Rec. at 10.
    There are two cannabinoid receptors: CB1 and 
CB2. CB1 and CB2 receptors belong to 
the family of G-protein-coupled receptors and present a typical seven 
transmembrane-spanning domain structure. Cannabinoid receptors 
primarily link to an inhibitory G protein (Gi/o), such that 
adenylate cyclase activity is inhibited when a cannabinoid ligand binds 
to the receptor. This, in turn, prevents the conversion of adenosine 
triphosphate to the second messenger, cyclic AMP (``cAMP''), which 
decreases cAMP levels. As HHS's analysis described, G proteins also 
contain beta/gamma G protein units that are also liberated following 
ligand binding, which then bind to and alter ion channel function, 
including inhibition of voltage-gated ion channels and activation of 
potassium channels. Ligand binding can also activate some subforms of 
phospholipase C as well as beta-arrestin protein. All of these second 
messenger routes amplify the neural signal following cannabinoid 
binding at the CB1 and CB2 receptors. HHS Basis 
for Rec. at 10.
    CB1 receptors are found primarily in the central nervous 
system (``CNS''), but are also present in peripheral tissues, such as 
the liver, heart, and lungs. In the brain, CB1 receptors are 
expressed with highest density in the cortical regions, hippocampus, 
basal ganglia, and cerebellum and with lowest density in brainstem and 
hypothalamic areas. The localization of these receptors may explain 
cannabinoid effects on movement coordination, memory, and cognition. 
Additionally, CB1 receptors are found in glial cells as well 
as in the immune system. However, the concentration of CB1 
receptors is considerably lower in peripheral tissues than in the CNS. 
CB2 receptors are found primarily in the immune system, 
including in numerous leukocyte cell types, as well as in activated CNS 
microglia. Additionally, there is some evidence that CB2 
receptors are localized in the brain, primarily in the cerebellum and 
hippocampus. The distribution of CB2 receptors throughout 
the body is less extensive than the distribution of CB1 
receptors. HHS Basis for Rec. at 10-11.
    There are two endogenous cannabinoid receptor agonists: anandamide 
and arachidonyl glycerol (``2-AG''). At CB1 receptors, 
anandamide is a partial agonist with low intrinsic efficacy while 2-AG 
is a full agonist with high intrinsic efficacy. These endogenous 
cannabinoid ligands are present in central as well as peripheral 
tissues. A combination of uptake and hydrolysis terminates the action 
of anandamide and 2-AG. The endogenous cannabinoid system is a locally 
active signaling system activated on demand in response to changes to 
the local conditions to help restore homeostasis. The endogenous 
cannabinoid system, including the endogenous cannabinoids and the 
cannabinoid receptors, demonstrates substantial plasticity in response 
to several physiological and pathological

[[Page 44604]]

stimuli. This plasticity is particularly evident in the CNS. HHS Basis 
for Rec. at 11.
    [Delta]9-THC and CBD have varying affinity and effects at the 
cannabinoid receptors. HHS determined that [Delta]9-THC is a partial 
agonist at both CB1 (Ki = 18-218 nM) and CB2 
receptors (Ki = 36-309 nM). However, CB1 receptors are the 
main pharmacological site of action for [Delta]9-THC, making 
CB1 receptors the site that is responsible for the abuse 
potential of marijuana. The other CNS site where [Delta]9-THC may have 
activity is the 5HT3 receptor, where it functions as an 
antagonist. In contrast, CBD has low affinity for both CB1 
and CB2 receptors and may act as a negative allosteric 
modulator or weak antagonist at these sites. CBD has additional CNS 
effects as a serotonin 5HT1A agonist and a serotonin 
5HT2A weak partial agonist, as well as a serotonin 
5HT3A antagonist. HHS Basis for Rec. at 11.
    In the past 30 years, the potency of marijuana with regard to 
[Delta]9-THC has increased dramatically. HHS described one study 
finding that the concentration of [Delta]9-THC in marijuana samples in 
the United States increased from 3 percent in 1991 to 17.1 percent in 
2017. These increases are likely due to an increase in the number of 
high potency samples (i.e., sinsemilla) in the overall samples tested. 
Based on an evaluation of marijuana seized by DEA, the majority of 
samples contained high concentrations of [Delta]9-THC and low 
concentrations of CBD. HHS Basis for Rec. at 11-12.
B. Animal Abuse-Related Behavioral Effects
Self-Administration
    Self-administration is a method that assesses the ability of a drug 
to produce rewarding effects. The presence of rewarding effects 
increases the likelihood that individuals will try to obtain additional 
quantities of a drug. Animal self-administration of a drug is often 
useful in suggesting whether humans will experience a particular 
substance as having rewarding effects, which is indicative of abuse 
potential. For example, the tendency of rhesus monkeys to self-
administer a drug is correlated with humans' propensity to abuse it. 
HHS Basis for Rec. at 12.
    Since self-administration is a methodology in which the test drug 
is typically administered intravenously to rats, it is not possible to 
evaluate botanical marijuana through self- administration. However, 
given that [Delta]9-THC is the primary substance that confers abuse 
potential to marijuana, its ability to induce self-administration can 
serve as an indicator of the abuse potential of marijuana. HHS Basis 
for Rec. at 12.
    HHS concluded, after weighing the relevant scientific evidence, 
that [Delta]9-THC produces rewarding effects that lead an animal to 
repeatedly seek out the substance. HHS Basis for Rec. at 12. 
Specifically, some studies have demonstrated successful animal self-
administration of [Delta]9-THC following intravenous administration, 
administration of inhaled vapor, oral administration, and 
intracerebroventricular administration. Other recent animal studies 
have not been able to produce [Delta]9-THC self-administration 
following intravenous administration and oral administration, but HHS 
concluded that these results were due to the specific methodology of 
those respective studies, rather than valid evidence of the rewarding 
effects of [Delta]9-THC, and thus do not negate HHS's reliance on 
studies in which [Delta]9-THC was actively self-administered by 
animals. HHS Basis for Rec. at 12-13.
    Furthermore, a comprehensive deconstruction of which animal 
methodology is optimal for producing preclinical self-administration of 
[Delta]9-THC is not necessary for an evaluation of the abuse potential 
of marijuana in humans because it is already clear that humans utilize 
marijuana for its rewarding properties. HHS Basis for Rec. at 13. 
Animal self-administration is used primarily to predict whether a novel 
substance is likely to be used by humans for its rewarding properties 
as an indication of its abuse potential. However, epidemiological data 
already amply demonstrates that humans self-administer substances that 
contain [Delta]9-THC, including botanical marijuana, for their ability 
to produce positive subjective responses, including euphoria. HHS Basis 
for Rec. at 13; see also sections VI.4-6 of this preamble (discussing 
Factors 4-6).
Conditioned Place Preference
    A conditioned place preference (``CPP'') study is another method 
for determining whether drugs have rewarding properties; a CPP study 
relies on an animal's decision to spend time in a location associated 
with receiving a drug. The studies in which [Delta]9-THC successfully 
produced CPP occurred under very specific experimental conditions, 
similar to the [Delta]9-THC self-administration studies in animals. 
Experimental manipulations in CPP studies with [Delta]9-THC have 
included varying the animal species, sex, dose, or route of 
administration; introducing flavors to obscure unpleasant taste; and 
varying the drug history of the animals tested. However, as with animal 
self-administration, the purpose of CPP studies is typically to 
determine if a new drug produces rewarding sensations, which would 
suggest that a drug has abuse potential in humans. Since it is clear 
that humans self-administer substances that contain [Delta]9-THC, 
including botanical marijuana, HHS determined that it was not necessary 
to determine which CPP methods are optimal for demonstrating that 
[Delta]9-THC has rewarding properties in animals. HHS Basis for Rec. at 
13.
Drug Discrimination Studies
    Drug discrimination is a method in which animals indicate whether a 
test drug produces sensations similar to those produced by a training 
drug with a known pharmacological mechanism of action. Drug 
discrimination is considered to be an abuse-related study only when the 
training drug is a known drug of abuse that is scheduled under the CSA 
and the test drug may have abusable effects similar to the training 
drug based on having a similar mechanism of action to the training 
drug. Because animal drug discrimination studies often use [Delta]9-THC 
as the standard for establishing if new drugs have classic marijuana-
like pharmacological activity, HHS did not examine whether this method 
should be applied when evaluating the abuse potential of [Delta]9-THC. 
HHS Basis for Rec. at 14.
C. Human Behavioral and Physiological Effects
Subjective Effects of [Delta]9-THC
    The psychological, behavioral, and subjective responses to 
marijuana in humans have been known and characterized since antiquity. 
In the modern period, data on the psychological, behavioral, and 
subjective responses to marijuana are available from the drug labels of 
FDA-approved drug products, from prospective human abuse potential 
(``HAP'') studies, from accounts published in the scientific and 
medical literature, and from an evaluation published in 2017 by the 
National Academies of Science, Engineering, and Medicine (``NASEM''). 
HHS Basis for Rec. at 14.
FDA-Approved Drug Products Containing [Delta]9-THC
    Clinical scientific studies investigated the effects of [Delta]9-
THC on humans during the development of the FDA-approved drug product 
Marinol, which contains 2.5, 5, and 10 mg dronabinol ((-)-trans-
[Delta]9-THC of synthetic origin in sesame seed oil). During controlled 
clinical

[[Page 44605]]

trials (as reported in section 6.1 of the drug labels for Marinol and 
Syndros (which relied on the safety data from Marinol during drug 
development)), various adverse events (``AEs'') were observed, 
including amnesia, anxiety/nervousness, ataxia, confusion, 
depersonalization, hallucination, asthenia, palpitations, tachycardia, 
vasodilation/facial flush, euphoria, paranoid reaction, somnolence, 
abnormal thinking, dizziness, abdominal pain, nausea, and vomiting. HHS 
Basis for Rec. at 14-15.
HAP Studies
    HAP studies evaluate whether a test drug produces positive 
subjective responses compared to a placebo and a known drug of abuse 
that is scheduled under the CSA and serves as the positive control. If 
the test drug produces rewarding effects that are statistically 
significantly greater than the placebo, and beyond the acceptable 
placebo range of response, it is an indication that the drug may have 
abuse potential. The relative abuse potential is suggested by the 
responses from the positive control on these measures in comparison to 
the test drug. HHS Basis for Rec. at 15.
    After analyzing a number of HAP studies of marijuana and [Delta]9-
THC, which varied in the in dose of [Delta]9-THC, the route of 
administration, or whether the [Delta]9-THC was provided in the form of 
marijuana or isolated compound, HHS identified a number of 
commonalities. First, following administration of the study drug (i.e., 
marijuana or [Delta]9-THC), there were increases in positive subjective 
responses. Second, the studies demonstrated increases on the Addiction 
Research Center Inventory scales for the morphine benzedrine group 
(euphoria), marijuana, and amphetamine. HHS concluded that these data 
consistently demonstrated that [Delta]9-THC, in the form of marijuana 
or as an isolated compound, produces rewarding effects that are 
indicative of abuse potential when it is administered under controlled 
experimental conditions. Third, and in contrast to the prior findings, 
the data also demonstrated that the administration of marijuana or 
[Delta]9-THC may result in negative subjective responses reflecting 
negative drug effects and sedation; these are often delayed in onset 
from when the positive subjective effects begin. HHS noted that the 
positive and negative subjective responses following administration of 
marijuana or [Delta]9-THC were often dose-dependent. It also noted that 
there were typically few differences between responses to marijuana and 
[Delta]9-THC, or between responses based on route of administration of 
the study drug. HHS Basis for Rec. at 15.
Common Responses to Marijuana in Humans Published in Scientific and 
Medical Literature
    HHS concluded that the responses to dronabinol reported during 
development of Marinol and the responses to marijuana and [Delta]9-THC 
reported in HAP studies paralleled the common responses to marijuana 
that have been described by other medical scientists. These responses 
include positive subjective responses (such as euphoria or happiness), 
sedative responses (such as drowsiness or changes in sleep), anxiety 
and negative responses (such as panic attacks, agitation, and 
paranoia), perceptual changes (such as hallucinations and changes in 
perception), psychiatric, social, and cognitive changes (such as drug 
abuse, delusions, memory and concentration impairment, and impaired 
judgment), and physiological responses (such as nausea, tachycardia, 
facial flushing, dry mouth, tremor, dizziness, ataxia, and 
hyperemesis). The literature reviewed by HHS also concluded that the 
positive changes that occur following use of marijuana are pleasurable 
to many humans and are associated with drug-seeking and drug-taking; 
and that these effects are typically dose-dependent, with higher doses 
and routes of administration that produce faster onset producing more 
intense responses and the likelihood of more negative subjective 
effects. HHS Basis for Rec. at 16-17.
National Academies of Science, Engineering, and Medicine (NASEM)
    HHS also reviewed a book-length evaluation of marijuana by NASEM 
entitled The Health Effects of Cannabis and Cannabinoids: The Current 
State of Evidence and Recommendations for Research.\17\ According to 
HHS, in this evaluation, NASEM provided a brief summary of the clinical 
features of marijuana intoxication and found that (1) during acute 
cannabis intoxication, the user's sociability and sensitivity to 
certain stimuli (e.g., colors, music) may be enhanced, the perception 
of time is altered, and the appetite for sweet and fatty foods is 
heightened; (2) some users report feeling relaxed or experiencing a 
pleasurable rush or buzz after smoking cannabis; (3) these subjective 
effects were often associated with decreased short-term memory, dry 
mouth, and impaired perception and motor skills; and (4) when very high 
blood levels of [Delta]9-THC were attained, persons might experience 
panic attacks, paranoid thoughts, and hallucinations. HHS Basis for 
Rec. at 17-18.
---------------------------------------------------------------------------

    \17\ National Academies of Science, Engineering, & Medicine, The 
Health Effects of Cannabis & Cannabinoids: The Current State of 
Evidence & Recommendations for Research (2017), https://nap.nationalacademies.org/read/24625/chapter/1.
---------------------------------------------------------------------------

HHS Conclusion With Respect to Factor 2
    Based on its analysis of the studies discussed above, HHS concluded 
that [Delta]9-THC, the substance largely responsible for the abuse 
potential of marijuana, is a partial agonist at the cannabinoid 
CB1 receptor. When [Delta]9-THC is administered to animals, 
it produces rewarding responses, as evidenced by its ability to induce 
self-administration and CPP. This is consistent with the data from 
human studies and from clinical observations, where administration of 
[Delta]9-THC or use of marijuana produces euphoria and other 
pleasurable responses, as well as sedation and anxiety responses. 
Psychiatric, social, and cognitive responses, which are often 
experienced as negative, are also reported, as are physiological 
responses such as dry mouth, ataxia, and increased hunger. As described 
in HHS's analysis of Factor 4, see HHS Basis for Rec. at 32-37, the 
rewarding responses observed in humans are consistent with the 
prevalence of nonmedical use of marijuana, which includes abuse of the 
substance. Abuse of marijuana by individuals can lead to other negative 
consequences, including addiction and the need to seek medical 
attention through calls to poison centers or visits to an ED, as 
described in Factor 5, see HHS Basis for Rec. at 38-39, 42. HHS Basis 
for Rec. at 18.
    DEA believes that additional data on marijuana's pharmacological 
effects may be appropriate for consideration in assessing this factor.

3. The State of Current Scientific Knowledge Regarding Marijuana

    The third factor that DOJ and HHS must consider under 21 U.S.C. 
811(c) is the state of current scientific knowledge regarding 
marijuana. In considering this factor and making its recommendation, 
HHS examined the chemistry of marijuana and the human pharmacokinetics 
of marijuana. HHS Basis for Rec. at 18-24.
Chemistry
    Cannabis is a genus of annual flowering plant with digitate leaves 
in the family Cannabaceae Martinov that likely originated in Central or 
Southeast Asia over 10,000 years ago and was first cultivated in China 
for fiber and seed production. Cultivation eventually

[[Page 44606]]

spread across Asia, Africa, and Europe and then to the Americas. A 
longstanding and significant historical debate by botanists and 
taxonomists continues today regarding the number of species in the 
Cannabis genus, but it is generally treated as a single, highly 
polymorphic species known as Cannabis sativa L., with the other two 
previously reported species listed as Cannabis indica Lam. and Cannabis 
ruderalis Janisch. Plants previously believed to be part of the latter 
two species are generally recognized as varieties (or subspecies) of 
Cannabis sativa L., which are commonly referred to as sativa var. 
indica and sativa var. ruderalis. Cannabis sativa and sativa var. 
indica plants are widely cultivated for their size, branching, and 
cannabinoid content, while sativa var. ruderalis is rarely cultivated 
alone because it is shorter, is often unbranched, and has very low 
cannabinoid content. Worldwide Cannabis varieties are separated into 
hundreds of different cultivars and strains. Plants selected for 
cultivation are known as cultivated varieties or cultivars, whereas 
plants reproduced asexually from a cultivar through clonal propagation 
are known as strains. These practices have resulted in significantly 
different chemical profiles for Cannabis cultivars, and the 
classification term to account for these chemical profile differences 
has evolved. The term ``chemovar'' accounts for the plant's chemical 
profile and is a more meaningful classification for clinical 
researchers studying the plant's potential drug effects. Marijuana 
products developed from diverse chemovars will have different safety, 
biological, pharmacological, and toxicological profiles. HHS Basis for 
Rec. at 18-19.
    Cannabis is a dioecious plant, meaning female and male flowers 
occur on separate plants, and rarely occurs as a monoecious plant 
(i.e., single plant containing male and female flowers). The glandular 
trichomes found on the female plant's unfertilized flower heads and 
bracts contain the highest concentrations of cannabinoids. For this 
reason, unfertilized female chemovars are favored to harvest large 
inflorescences (i.e., complete flower head) for their rich cannabinoid 
and terpene content. HHS Basis for Rec. at 19.
    The Cannabis sativa L. plant naturally contains many different 
compounds, and more than 550 have been identified, such as 
cannabinoids, terpenoids, flavonoids, stilbenoids, steroids, 
polysaccharides, benzoquinone, phenanthrenes, spiroindans, lignans, 
fatty acids, sugars, hydrocarbons, amino acids, and proteins. 
Cannabinoids are mainly found in living Cannabis sativa L. plants in 
their non-psychoactive carboxylated forms (i.e., acid form), which 
require drying, heating, combustion, or aging to decarboxylate to their 
neutral forms, and are primarily composed of C21 
terpenophenolic compounds. The most abundant neutral form cannabinoids 
are [Delta]9-THC and CBD, but nearly 200 have been identified in the 
plant and are divided into subclasses: cannabigerols, cannabichromenes, 
CBDs, [Delta]9-THCs, (-)-[Delta]8-trans-tetrahydrocannabinols 
(``[Delta]8-THCs''), cannabicyclols, cannabielsoins, cannabinols, 
cannabinodiols, cannabitriols, and the miscellaneous cannabinoids. HHS 
Basis for Rec. at 19.
    Like any other botanical substance, marijuana plants are 
heterogeneous in nature and contain a complex chemical profile. 
Moreover, variable organic plant material, as well as manufactured 
preparations, result in a variety of product forms that dictate 
different routes of administration, associated risks, and differences 
in quality of the product used, which may also influence risk for 
users. Among other things, these differences can result from 
differences in harvest location, growing conditions, the season in 
which the marijuana is harvested, and the manner in which the marijuana 
is processed, handled, transported, and tested. The potential for high 
variability of marijuana and marijuana-derived products, both in 
product composition and impurity profile, is a major consideration for 
the potential variability of drug effects and safety. HHS Basis for 
Rec. at 19-20.
    Processing of marijuana and its use in further manufacturing can 
lead to a range of forms that individuals may use or consume, including 
crude mixtures and highly purified substances of botanical origin, many 
of which may be cannabinoid compounds. Among known cannabinoids in the 
Cannabis plant, both [Delta]9-THC and [Delta]8-THC produce marijuana's 
psychoactive effects. Because [Delta]9-THC is significantly more 
abundant than [Delta]8-THC, marijuana's intoxicating effects are 
largely attributed to the former. Only small quantities of [Delta]8-THC 
acid and [Delta]8-THC have been identified in plants. HHS Basis for 
Rec. at 20.
    As noted above, the 2018 amendments to the CSA removed hemp from 
the definition of marijuana. However, the term ``cannabis'' is still 
often broadly used to refer to a wide variety of products manufactured 
from the Cannabis sativa L. plant, regardless of their control status. 
As a result of the 2018 amendments to the CSA, a large hemp marketplace 
exists, containing a wide variety of products. In addition, the public 
has access to cannabis products within the CSA definition of marijuana 
through State-authorized adult-use (i.e., nonmedical use) and medical-
use programs, as well as via the illicit marketplace. See HHS Basis for 
Rec. at 28-37 (Factor 4). Because of these diverse sources of 
marijuana, there is a lack of unified controls on cultivation and 
manufacturing, which raises concerns related to the safety, quality, 
and consistency of botanical substances (e.g., botanical raw materials, 
extracts, and intermediates) and final product formulations that are 
currently accessed for medical and nonmedical use. Products sourced 
from State-authorized adult-use and medical-use programs are subject to 
a patchwork of inconsistent product standards and safety requirements. 
Although some State programs have a set of standards (for example, on 
manufacturing, testing, labeling, and packaging), each program's 
controls are different, leading to a wide variation of products across 
State-authorized programs. And the illicit marketplace is not subject 
to any standards or oversight. As a result, the range of products 
within the CSA's definition of marijuana encompasses a large degree of 
variation in forms for consumption, composition of biologically 
relevant constituents, potency, and contaminants. HHS Basis for Rec. at 
21.
    In short, marijuana has hundreds of chemovars containing variable 
concentrations of [Delta]9-THC, cannabinoids, and other compounds. As a 
result, in evaluating whether to recommend that marijuana be 
rescheduled, HHS focused to the greatest extent possible on wide-
ranging substances derived from cannabis plants that are vehicles for 
the self-administration of [Delta]9-THC as the key biologically active 
substance on which the CSA's current definition of marijuana is based. 
HHS Basis for Rec. at 21.
Human Pharmacokinetics of [Delta]9-THC
    HHS reported that the pharmacokinetics of [Delta]9-THC in humans--
i.e., the study of how the body interacts with [Delta]9-THC--have been 
evaluated following inhaled administration of marijuana and oral 
administration of marijuana. These are the most frequently used routes 
of administration for marijuana or isolated [Delta]9-THC. HHS Basis for 
Rec. at 21.
    Marijuana is commonly administered by humans via inhalation through 
smoking and, more recently, through vaping (e.g., heating and 
inhalation of

[[Page 44607]]

botanical matter or other volatile substances containing [Delta]9-THC). 
Generally, inhalation of a drug is the route that produces the fastest 
rate of drug absorption. Once marijuana is inhaled, [Delta]9-THC is 
absorbed through the lungs in the form of an aerosol within seconds. 
Peak plasma levels of [Delta]9-THC following inhalation occur very 
quickly, within 6 to 10 minutes. Psychoactive effects begin immediately 
following absorption, although peak subjective effects do not coincide 
with peak plasma [Delta]9-THC levels and are often delayed. Following 
administration of marijuana through inhalation, the bioavailability of 
[Delta]9-THC is 10 percent to 35 percent. That bioavailability is 
relatively low and varies widely due to several factors. An 
individual's experience and technique with smoking marijuana also 
determines the dose absorbed. HHS Basis for Rec. at 22.
    When marijuana or [Delta]9-THC is administered orally (such as by 
eating marijuana-infused foods), the effects start within 30 to 90 
minutes, reach their peak at 1.5 to 3 hours, and remain measurable for 
4 to 12 hours. Oral bioavailability of [Delta]9-THC, following 
ingestion of an edible containing marijuana or isolated [Delta]9-THC, 
ranges from 5 to 20 percent. The low and variable bioavailability of 
[Delta]9-THC from oral ingestion is a consequence of its first-pass 
hepatic elimination from blood and erratic absorption from stomach and 
bowel. Ingestion of brownies containing marijuana also results in lower 
[Delta]9-THC plasma levels relative to inhalation of marijuana. HHS 
Basis for Rec. at 22-23.
    Although there are differences in absorption of [Delta]9-THC 
depending on route of administration, the distribution, metabolism, and 
excretion of [Delta]9-THC is similar regardless of how the drug is 
administered. Plasma concentrations of [Delta]9-THC decrease quickly 
after absorption through rapid distribution into tissues and through 
liver metabolism. Because [Delta]9-THC has high lipophilicity, the 
apparent volume of distribution of [Delta]9-THC is high (10 L/kg) as it 
is distributed initially into organs such as lung, heart, brain, and 
liver that are highly perfused. Over time with regular exposure to 
marijuana, [Delta]9-THC will concentrate and be retained in fat. HHS 
Basis for Rec. at 23.
    Metabolism of [Delta]9-THC occurs primarily via cytochrome P450 
isozymes (CYP2C9, CYP2C19, and CYP3A4) via microsomal hydroxylation to 
both active and inactive metabolites. The primary active metabolite of 
[Delta]9-THC is 11-hydroxy-[Delta]9-THC. [Delta]9-THC clears from the 
blood relatively rapidly, largely because it is redistributed to other 
tissues in the body. Metabolism of [Delta]9-THC in most tissues is 
relatively slow or absent. The majority of the absorbed [Delta]9-THC 
dose is eliminated in feces, and about 33 percent in urine. HHS Basis 
for Rec. at 23.
HHS Conclusion With Respect to Factor 3
    In conclusion, HHS found that the pharmacokinetic profile of 
marijuana varies greatly depending on route of administration. 
Inhalation of marijuana produces a rapid increase in plasma levels of 
[Delta]9-THC and an immediate onset of psychological effects. In 
comparison, oral administration of marijuana produces a much slower 
increase in plasma levels of [Delta]9-THC and onset of psychological 
effects. Once [Delta]9-THC has been absorbed, however, the metabolism 
and excretion of [Delta]9-THC follows a standard path. HHS Basis for 
Rec. at 24.
    DEA likewise notes that there is considerable variability in the 
cannabinoid concentrations and chemical constituency among marijuana 
samples and that the interpretation of clinical data related to 
marijuana is complicated. A primary issue is the lack of consistent 
concentrations of [Delta]9-THC and other substances in marijuana, which 
complicates the interpretation of the effects of different marijuana 
constituents. Additionally, the non-cannabinoid components in marijuana 
may potentially modify the overall pharmacological and toxicological 
properties of various marijuana strains and products. DEA anticipates 
that additional data on other marijuana constituents, routes of 
administration of marijuana, and the impact on [Delta]9-THC potency may 
be appropriate for consideration.

4. Marijuana's History and Current Pattern of Abuse

    The fourth factor that DOJ and HHS must consider under 21 U.S.C. 
811(c) is marijuana's history and current pattern of abuse, which can 
include its abuse relative to relevant comparator substances that are 
abused. See HHS Basis for Rec. at 28-37. HHS concluded that it is 
appropriate to consider the Federal- and State-level history of 
marijuana control, marijuana sources for nonmedical and medical use, 
marijuana use in the United States since passage of the CSA, and 
current patterns of use and abuse of marijuana. HHS Basis for Rec. at 
28.
Federal History of Marijuana Control
    According to HHS, marijuana was described in the United States 
Pharmacopoeia \18\ as early as 1850. Around the time that Congress 
passed the Pure Food and Drug Act of 1906, Public Law 59-384, 34 Stat. 
768, drugs such as marijuana, alcohol, heroin, morphine, and cocaine 
began to be characterized by the Federal Government as addictive and 
dangerous. These drugs were frequently included in patent medicines, 
often without the consumer's knowledge. The 1906 law required accurate 
drug labeling with respect to ingredients and dosage. But it did not 
prohibit the sale or possession of drugs characterized as addictive and 
dangerous drugs, including marijuana. As nonmedical use of marijuana 
and opioids became more popular in the United States, Congress provided 
funding in 1929 for two ``narcotic farms'' in Lexington, Kentucky, and 
Fort Worth, Texas, which were medical treatment centers run by the 
Public Health Service for federal prisoners who were ``habitual users 
of narcotics,'' including marijuana-derived products. HHS Basis for 
Rec. at 28-29.
---------------------------------------------------------------------------

    \18\ The United States Pharmacopoeia was formed as an 
``independent, scientific, non-profit organization dedicated to 
public health'' that published ``a national, uniform set of 
guidelines for the best understood medicinal substances and 
preparations of the day.'' Building Trust for Over 200 Years: A 
Timeline of USP, U.S. Pharmacopoeia, https://www.usp.org/200-anniversary/usp-timeline (last visited May 11, 2024).
---------------------------------------------------------------------------

    In the first half of the twentieth century, marijuana use was 
curbed by several Federal laws. In 1931, the importation of marijuana 
into the United States began to be restricted under regulations under 
the Pure Food and Drug Act, except for medicinal purposes. The 
Marihuana Tax Act of 1937, Public Law 75-238, 50 Stat. 551, imposed 
taxes that effectively prohibited marijuana use for medical, 
nonmedical, scientific, or industrial purposes. Five years later, in 
1942, marijuana was removed from the United States Pharmacopoeia. 
Through the imposition of mandatory minimums, the Boggs Act of 1951, 
Public Law 82-255, 65 Stat. 767, lengthened the average sentence for 
first time marijuana offenders to 2 to 5 years, similar to that for 
opioid offenses, regardless of whether the individual was a nonmedical 
user or a trafficker. The Narcotic Control Act of 1956, Public Law 84-
728, 70 Stat. 567, increased the minimum sentence for a first offender 
for marijuana to 2 to 10 years. HHS Basis for Rec. at 29.
    Despite the legal consequences, nonmedical marijuana use increased 
dramatically in the 1960s, especially among youth. Congress passed the 
CSA in 1970. The CSA effectively repealed

[[Page 44608]]

all previous Federal drug laws, including the Marihuana Tax Act, and 
provided a unified framework for control of drugs with abuse potential. 
When the CSA was enacted, marijuana was placed into schedule I, which 
prohibited use of marijuana for medicinal or nonmedical purposes other 
than legitimate scientific research and analysis. This placement was 
consistent with the criteria established by the CSA under 21 U.S.C. 
812. HHS Basis for Rec. at 29-30.
Marijuana Control at the State Level
    According to HHS, changes in State-level marijuana laws in the 
United States in the modern era began in 1996 with the approval of 
Proposition 215, the Compassionate Use Act, by voters in California. 
This law legalized the use, possession, and cultivation of marijuana 
for treatment of patients with cancer, anorexia, AIDS, chronic pain, 
spasticity, glaucoma, arthritis, migraine, or any other illness for 
which marijuana provides relief, when recommended by a physician. Under 
the law, marijuana could also be cultivated by patient caregivers. HHS 
Basis for Rec. at 30.
    As of August 2023, when HHS submitted its Basis for Recommendation 
to DEA, State-level laws allowing medicinal use of marijuana had been 
passed in a total of 38 States, plus the District of Columbia: Alabama, 
Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, 
District of Columbia, Florida, Hawaii, Illinois, Kentucky, Louisiana, 
Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, 
Missouri, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New 
York, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, 
South Dakota, Utah, Vermont, Virginia, Washington, and West Virginia. 
Medical use of marijuana was legalized through the action of 20 State 
legislatures and by 18 ballot measures.\19\ HHS Basis for Rec. at 30.
---------------------------------------------------------------------------

    \19\ Data on the number of patients who participate in State-
sanctioned medical cannabis use is available here: Medical Cannabis 
Patient Numbers, Marijuana Pol'y Project, https://www.mpp.org/issues/medical-marijuana/state-by-state-medical-marijuana-laws/medical-marijuana-patient-numbers (last visited May 13, 2024).
---------------------------------------------------------------------------

    In 2012, Colorado and Washington became the first States to 
legalize the nonmedical use of marijuana. As of August 2023, State-
level legalization of the nonmedical use of marijuana has occurred in a 
total of 23 States and the District of Columbia: Alaska, Arizona, 
California, Colorado, Connecticut, Delaware, District of Columbia, 
Illinois, Maine, Maryland, Massachusetts, Michigan, Minnesota, 
Missouri, Montana, Nevada, New Jersey, New Mexico, New York, Oregon, 
Rhode Island, Vermont, Virginia, and Washington. Nonmedical use of 
marijuana was legalized by ballot initiatives in 13 States and by State 
legislatures in 9 States. HHS Basis for Rec. at 30.
Marijuana Use in the United States Since Passage of the CSA
    Marijuana use has varied since the CSA was passed in 1970. Gallup 
Poll data from 1969 to 2013 show a steady increase over time in 
affirmative responses to whether the respondent had personally tried 
marijuana, with only 4 percent of people saying they had tried 
marijuana in 1969 compared to 38 percent in 2013. As HHS observed, the 
2017 NASEM report stated that the prevalence of marijuana use peaked in 
the late 1970s, declined through the 1980s, and then increased again in 
the mid-1990s. From 2007 to 2017, there were steady year-over-year 
increases in the share of the general population that used marijuana in 
the past month, although there is no clear explanation for the post-
2007 increase in use rates. HHS Basis for Rec. at 31-32.
Current Patterns of Use and Abuse of Marijuana
    In considering current patterns of use and abuse of marijuana and 
marijuana-derived products, HHS analyzed epidemiological databases from 
2015 to the most recent years of available data (which vary among data 
sources). A wide variety of epidemiological databases provide necessary 
data for HHS's analyses. These include the NSDUH; Behavioral Risk 
Factor Surveillance System (``BRFSS''); Research Abuse, Diversion and 
Addiction-Related Surveillance (``RADARS''); Nonmedical Use of 
Prescription Drugs (``NMURx''); Monitoring the Future (``MTF''); Youth 
Risk Behavioral Surveillance System (``YRBSS''); and International 
Cannabis Policy Study (``ICPS''). HHS Basis for Rec. at 32.
National Survey on Drug Use and Health
    Based on NSDUH data, HHS concluded that from 2015 to 2019 the past-
year use of marijuana for any reason (nonmedical and medical) among 
people ages 12 years and older increased from 14 percent to 18 percent. 
By contrast, past-year (nonmedical and medical) use of comparator drugs 
that have FDA-approved therapeutic indications declined or remained 
relatively stable over the same timeframe, including hydrocodone (22 
percent to 16 percent), benzodiazepines (12 percent to 11 percent, 2017 
to 2019 only), oxycodone (11 percent to 9 percent), tramadol (7 percent 
to 6 percent), zolpidem (4 percent to 3 percent), and ketamine (less 
than 1 percent). Although there were trend breaks for the years 2020 
and 2021,\20\ marijuana past-year use continued to increase during 
these two years. HHS Basis for Rec. at 32-33.
---------------------------------------------------------------------------

    \20\ HHS noted that NSDUH data collection was disrupted in 2020 
and 2021 due to the COVID-19 pandemic, leading to trend breaks in 
these years. HHS Basis for Rec. at 32.
---------------------------------------------------------------------------

    Based on NSDUH data, HHS concluded that from 2015 to 2019, the 
prevalence of past-year nonmedical use of marijuana (i.e., use without 
a health care provider (``HCP'') recommendation) among people ages 12 
years and older also increased. HHS's finding was based on an increase 
in the prevalence of overall nonmedical use of marijuana from 12 
percent to 15 percent and on an increase in nonmedical use of marijuana 
only, without nonmedical use of other drugs that are abused, from 8 
percent to 11 percent during this period. There was a slight decrease 
in both categories in 2020, but the prevalence of both kinds of uses 
increased again in 2021 (to 16 percent and 11 percent, respectively) to 
levels that were higher than those reported in 2019. In contrast, the 
prevalence of past-year nonmedical use of comparator drugs was less 
than 3 percent for heroin, cocaine, oxycodone, hydrocodone, tramadol, 
benzodiazepines, and zolpidem, which is much less than that for 
marijuana, either alone or with other drugs. Over the 2015 to 2021 
reporting period, the overall use of these comparator drugs declined 
slightly or remained fairly stable. Notably, the majority of 
individuals who reported nonmedical use of marijuana did not report 
nonmedical use of the comparator drugs. And over the same reporting 
period of 2015 to 2021, the prevalence of past-year use of alcohol 
ranged from 62 percent to 65 percent for individuals ages 12 years and 
older, far exceeding the prevalence for marijuana or other comparator 
drugs. These data demonstrate that alcohol has the highest prevalence 
of past-year-only use, followed by nonmedical use of marijuana. The 
prevalence of the other comparators is far below that of alcohol and 
marijuana. HHS Basis for Rec. at 33.
    HHS also concluded that the NSDUH data show that most individuals 
who used marijuana in the past year did not do so based on a 
recommendation from an HCP, but marijuana use was more frequent among 
users with an HCP

[[Page 44609]]

recommendation. The yearly percentage of individuals who used marijuana 
but did not have an HCP recommendation ranged between 84 and 89 percent 
between 2015 and 2021; by comparison, exclusive medical use of 
marijuana that was recommended by an HCP ranged between 7 and 10 
percent of marijuana users in the same period. According to HHS, 
approximately 50 percent of those individuals without an HCP 
recommendation used marijuana for 60 or fewer days in the year, while 
29 percent used marijuana for more than 241 days in the year. In 
contrast, for those individuals whose use of marijuana was sometimes or 
always recommended by an HCP, 51 percent and 55 percent (respectively) 
used marijuana at least 241 days in the year. HHS Basis for Rec. at 33-
34.
    The NSDUH data from 2021 showed that among individuals who used any 
marijuana in the past year, 69 percent used marijuana in the prior 
month. For comparator drugs, the percentage of individuals with past-
year use who used each substance nonmedically in the past month was 76 
percent for alcohol, 49 percent for heroin, 38 percent for cocaine, and 
28 percent for ketamine. HHS Basis for Rec. at 34.
Behavioral Risk Factor Surveillance System
    BRFSS is a national, State-based, cross-sectional telephone survey 
conducted by the Centers for Disease Control and Prevention (``CDC''). 
The participants in the 2021 BRFSS module for marijuana included 
approximately 68 million individuals 18 years and older, residing in 24 
States and Territories: Alaska, Connecticut, Delaware, Hawaii, Idaho, 
Illinois, Indiana, Kentucky, Maine, Maryland, Minnesota, Montana, 
Nebraska, Nevada, New Hampshire, New York, North Dakota, Ohio, 
Oklahoma, Rhode Island, Utah, Vermont, Wyoming, and Guam. HHS Basis for 
Rec. at 34.
    For the 2021 survey year, the estimated prevalence of past-month 
marijuana use for any reason in the BRFSS survey was 12 percent, with 
88 percent reporting no marijuana use. Among those with past-month 
marijuana use, the mean frequency of use was 17 days per month, with 
half of respondents reporting that they used marijuana 20 to 30 days 
per month. This pattern was consistent across all age and sex 
categories. HHS Basis for Rec. at 34.
    When the reason for use was evaluated, the percentage of 
individuals who reported use for both medical and nonmedical reasons 
was 39 percent, compared to 36 percent for those who reported use for 
nonmedical reasons only, and 25 percent for those who reported use for 
medical reasons only. Those individuals who reported past-month use of 
marijuana for medical reasons were more likely to be adults 55 years 
and older, while individuals who reported past-month marijuana use for 
nonmedical reasons only were more likely to be younger adults aged 18 
to 24 years. HHS Basis for Rec. at 34.
    Individuals who reported using marijuana in the past 30 days for 
both nonmedical and medical reasons were more likely (62 percent) to 
report marijuana use near daily (20 to 30 days per month) than 
individuals who reported marijuana use for nonmedical reasons only (34 
percent). Similarly, individuals who used marijuana for medical reasons 
only were also more likely (57 percent) to report near daily use than 
those who used it for nonmedical reasons only. HHS Basis for Rec. at 
34.
Researched Abuse, Diversion and Addiction-Related Surveillance System 
Survey of Nonmedical Use of Prescription Drugs
    The RADARS System conducts the NMURx Program, a serial, cross-
sectional, online survey of the general adult population (18 years and 
older) to elicit information on the nonmedical use of drugs 
(prescription, nonprescription, unapproved, and illicit). The NMURx 
Program estimates represent measures of past-year drug use in an 
enriched sample of United States adults with higher-than-average 
nonmedical use of prescription pain relievers and illicit drugs. NMURx 
program data demonstrated that past-year use of marijuana was reported 
by 21 percent of individuals, while past-year use of comparator 
substances was substantially lower: benzodiazepines (4 percent), 
hydrocodone, oxycodone, tramadol (2 percent), cocaine or crack (less 
than 2 percent), and illicit fentanyl, heroin, and ketamine (less than 
1 percent). This pattern of much greater marijuana use compared to 
other drugs is consistent with the patterns reported in NSDUH and 
BRFSS. HHS Basis for Rec. at 35.
Monitoring the Future
    MTF collects information on the use of selected prescription and 
illicit drugs and alcohol by conducting an annual, nationally 
representative, cross-sectional survey of 8th, 10th, and 12th graders 
in public and private schools.\21\ MTF data showed that during the 
years 2012 to 2022, the illicit drug most frequently used by 12th-grade 
students who reported past-year drug use was marijuana/hashish 
(approximately 35 percent per year from 2012 to 2020, with a reduction 
to 30 percent per year in 2021 and 2022). In contrast, in 2022, alcohol 
was used by 52 percent of 12th-grade students within the last 12 
months, similar to percentages in 2019 and 2020 (52 percent and 55 
percent, respectively), but higher than the 2021 level of 47 percent. 
All other comparator drugs (hydrocodone, heroin, tramadol, cocaine, 
ketamine, and zolpidem) were each used in the past year by fewer than 5 
percent of 12th graders from 2012 to 2022. HHS Basis for Rec. at 35.
---------------------------------------------------------------------------

    \21\ As a result of the COVID-19 pandemic, there is a potential 
trend break in the 2020 MTF data. HHS Basis for Rec. at 35.
---------------------------------------------------------------------------

    MTF data for past-month use showed a similar pattern. During the 
years 2012 to 2022, the illicit drug most frequently used by 12th-grade 
students who reported past-month drug use was marijuana/hashish 
(approximately 20 to 22 percent per year) compared to past-month use of 
cocaine (approximately 1 percent per year) or heroin (less than 0.5 
percent per year). However, past-month alcohol use by 12th-grade 
students (28 percent) exceeded that of marijuana in 2022. For those who 
used marijuana in the past month, 6 to 7 percent used it daily. By 
comparison, for those who used cocaine and heroin in the last month, 
less than one percent used it daily. MTF does not provide past-month 
use data for hydrocodone, heroin, tramadol, ketamine, or zolpidem. HHS 
Basis for Rec. at 35.
Youth Risk Behavior Surveillance System
    YRBSS was established by the CDC and conducts school-based surveys 
every 2 years, in partnership with State, local, Territorial, and 
Tribal governments, with a focus on youth health behavior in the United 
States. The YRBSS high school component, the Youth Risk Behavior 
Survey, includes a nationally representative survey of 9th- through 
12th-grade students. YRBSS data showed that from 2009 to 2019, 
approximately 20 percent of students in 9th through 12th grade reported 
using marijuana at least once in the past month during each year 
evaluated. When students 17 years and older were asked how old they 
were when they first used marijuana, 43 percent reported they initiated 
use between the ages of 15 to 16 years, 25 percent initiated use 
between the ages of 13 to 14 years, and 13 percent initiated use at 12 
years of age and younger. YRBSS data also showed, however, that past-
month alcohol use by high school students (29 percent) in 2019 was 
greater than that of marijuana use, while past month

[[Page 44610]]

prescription opioid misuse (including codeine, hydrocodone, or 
oxycodone) (7 percent) in 2019 was much lower than that of both alcohol 
and marijuana use. HHS Basis for Rec. at 36.
International Cannabis Policy Study
    ICPS conducted serial, cross-sectional surveys from 2019 to 2021 of 
individuals ages 16 to 65 years living in the United States to 
understand the public health impact of marijuana legalization. HHS's 
evaluation of that survey data focused on respondents who reported at 
least some past-year marijuana nonmedical use (by indicating that they 
were not a medical marijuana user, defined as someone who uses 
marijuana only to treat a medical condition). HHS Basis for Rec. at 36.
    According to HHS, ICPS data showed that the prevalence of past-year 
nonmedical use of marijuana ranged from 18 percent to 22 percent of 
individuals surveyed from 2019 to 2021, while the prevalence of past-
month nonmedical use was lower, ranging from 12 percent to 14 percent 
of individuals surveyed. Individuals aged 26 to 34 years had the 
highest relative prevalence of nonmedical marijuana use, with 26 
percent reporting past-year use and 18 percent reporting past-month 
use. When those individuals who reported past-year marijuana use in 
2021 were asked why they used the drug, 33 percent reported use for 
medical reasons, while 61 percent were classified as using marijuana 
for nonmedical reasons only. (The other 6 percent did not respond.) HHS 
Basis for Rec. at 36.
    When frequency of nonmedical use of marijuana was evaluated in ICPS 
for those individuals who used marijuana nonmedically at least once a 
year, individuals aged 16 to 17 years had the highest percentage of use 
less than once a month (approximately 40 percent, compared to 
approximately 25 to 31 percent for other age cohorts); while 
individuals aged 26 to 34 years had the highest percentage of daily use 
(approximately 43 percent, compared to approximately 34 to 37 percent 
for individuals in other adult cohorts and approximately 24 percent 
among individuals 16 and 17 years). Among individuals who used 
marijuana for nonmedical reasons in the past year, 49 percent reported 
never using alcohol and marijuana at the same time, while 35 percent 
sometimes used the two substances together, 9 percent often used them 
together, and 5 percent used alcohol every time they used marijuana. 
HHS Basis for Rec. at 36-37.
HHS Conclusion With Respect to Factor 4
    In light of the evidence cited above, HHS determined that certain 
conclusions could be drawn about marijuana's current pattern of abuse. 
HHS concluded that the use of marijuana for medical and nonmedical 
purposes is extensive in the United States. HHS also concluded that the 
prevalence of marijuana use is less than that of alcohol and 
significantly more than that of other drugs of abuse that are scheduled 
under the CSA. Specifically, HHS noted that NSDUH data from 2015 to 
2019 showed that the prevalence of past-year use of alcohol was five to 
six times greater than that of nonmedical use of marijuana. In 
contrast, the prevalence of past-year nonmedical use of heroin, 
cocaine, oxycodone, hydrocodone, tramadol, benzodiazepines, and 
zolpidem was four to five times less than that of marijuana nonmedical 
use. Similar past-year comparative drug use data were reported in 
RADARS-NMURx, MTF, and ICPS. HHS Basis for Rec. at 37. In 2016, DEA 
found that marijuana continues to be the most widely used illicit drug. 
It noted that in 2014, there were 22.2 million current users; that 
there were also 2.6 million new users, most of whom were less than 18 
years of age; and that marijuana was the most frequently identified 
drug identified in Federal, State, and local forensic laboratories. 81 
FR 53739. In addition to the data provided in the HHS Basis for 
Recommendation and the data considered by HHS and DEA in their 2015 
eight-factor analyses, DEA anticipates that additional information 
arising from this rulemaking will further inform the findings that must 
be made to reschedule marijuana, including with respect to this factor. 
DEA also notes that, according to the World Health Organization, 
cannabis is globally the most commonly used psychoactive substance 
under international control.\22\ Accounting for half of all drug 
seizures worldwide, the global annual prevalence of cannabis 
consumption is 2.5 percent or about 147 million people.\23\ In 2016, an 
estimated 28.6 million individuals age 12 or older were current (in the 
past month) illicit drug users.\24\ By 2020, approximately 59.3 million 
individuals age 12 or older reported using an illicit drug within the 
past year; 83.6 percent (49.6 million) of those past-year illicit drug 
users reported using marijuana.\25\ In 2022, the Domestic Cannabis 
Eradication and Suppression Program was responsible for the eradication 
of 4,435,859 illegally cultivated outdoor cannabis plants and 1,245,980 
illegally cultivated indoor plants for a total of 5,681,839 illegally 
cultivated marijuana plants.\26\ DEA believes that additional data on 
marijuana's pattern of abuse may be appropriate for consideration in 
assessing this factor.
---------------------------------------------------------------------------

    \22\ World Health Org., The Health and Social Effects of 
Nonmedical Cannabis Use, at v (2016), https://iris.who.int/bitstream/handle/10665/251056/9789241510240-eng.pdf.
    \23\ Alcohol, Drugs & Addictive Behaviours Unit, Cannabis, World 
Health Org., https://www.who.int/teams/mental-health-and-substance-use/alcohol-drugs-and-addictive-behaviours/drugs-psychoactive/cannabis (last visited May 13, 2024).
    \24\ Substance Abuse & Mental Health Servs. Admin., Key 
Substance Use and Mental Health Indicators in the United States: 
Results from the 2016 National Survey on Drug Use and Health 1 
(2017), https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2016/NSDUH-FFR1-2016.pdf.
    \25\ Substance Abuse & Mental Health Servs. Admin, Key Substance 
Use and Mental Health Indicators in the United States: Results from 
the 2020 National Survey on Drug Use and Health 2 (2021), https://www.samhsa.gov/data/sites/default/files/reports/rpt35325/NSDUHFFRPDFWHTMLFiles2020/2020NSDUHFFR1PDFW102121.pdf.
    \26\ Domestic Cannabis Suppression/Eradication Program, DEA, 
https://www.dea.gov/operations/eradication-program (last visited May 
13, 2024).
---------------------------------------------------------------------------

5. The Scope, Duration, and Significance of Abuse

    The fifth factor that DOJ and HHS must consider under 21 U.S.C. 
811(c) is the scope, duration, and significance of marijuana abuse. In 
conducting its analysis, HHS analyzed the consequences over time of 
marijuana abuse compared to the abuse of other substances based on data 
from the United States Poison Centers National Poison Data System 
(``NPDS''), NSDUH, the Treatment Episode Data Set (``TEDS''), the 
National Addictions Vigilance Intervention and Prevention Program 
(``NAVIPPRO''), the National Emergency Department Sample (``NEDS''), 
the National Inpatient Sample (``NIS''), and the National Forensic 
Laboratory Information System (``NFLIS''). HHS Basis for Rec. at 37-45.
Epidemiological Data on Consequences of Marijuana Abuse
National Poison Data System
    Data from NPDS provide information on the scope of contacts with a 
poison center (``PC'') following marijuana abuse relative to abuse of 
selected comparators. HHS Basis for Rec. at 38.
    The number of PC abuse cases for a substance (either alone or in 
combination with another substance) for the period of 2015 to 2021 
showed that the highest number of PC abuse cases was for alcohol, 
followed by heroin and

[[Page 44611]]

then benzodiazepines. The fourth highest number of PC abuse cases was 
for marijuana, with all other comparators showing fewer PC abuse cases. 
When the PC abuse cases for 2015 to 2021 were analyzed for cases 
involving a single substance only, the rank order of PC abuse cases by 
number was the same as the order from all PC abuse cases for substances 
used alone or in combination with another substance, meaning that 
marijuana accounted for the fourth highest number of PC abuse cases for 
a single substance. HHS Basis for Rec. at 38.
    HHS's analysis of the data from 2015 to 2021 showed cases resulting 
from abuse (as opposed to those resulting from other causes, such as 
accidental ingestion) made up the largest proportion of PC cases for 
illicit fentanyl (72 percent), heroin (65 percent), cocaine (41 
percent) and ketamine (40 percent). The fifth highest percentage was 
for cases involving marijuana (36 percent), followed by alcohol (15 
percent), oxycodone (13 percent), benzodiazepines (8 percent), 
hydrocodone (5 percent), tramadol (4 percent), and zolpidem (3 
percent). A similar analysis for single-substance-only abuse for the 
same period showed that the three substances most likely to lead to a 
PC call following abuse were heroin (65 percent), oxycodone (47 
percent), and tramadol (47 percent). The fourth highest percentage was 
for marijuana and ketamine (46 percent), followed by alcohol (43 
percent), zolpidem (40 percent), hydrocodone (37 percent), illicit 
fentanyl (34 percent), benzodiazepines (32 percent), and cocaine (28 
percent). HHS Basis for Rec. at 38.
    Annual utilization-adjusted abuse case rates were calculated by 
dividing the number of PC abuse case counts by the prevalence of past-
year use based on NSDUH estimates from people aged 12 years and older, 
for the period 2015 to 2019, for both (1) any past-year use of the 
substance and (2) past-year nonmedical use of the substance. These 
utilization-adjusted rates convey the likelihood that use of a drug 
will result in PC abuse cases when considering how many people use the 
drug for either (1) any reason or (2) nonmedical reasons. The 
utilization-adjusted abuse rates for any past-year use of a substance 
showed the highest rate for heroin (increasing from 4,038 to 7,201 
cases per one million people). The next highest rates were for 
ketamine, cocaine, and benzodiazepines; all these rates were 
considerably lower than the rate for heroin. The rates for marijuana 
(relatively stable at 75 to 70 cases per one million people) and 
oxycodone were similar, as were the rates for alcohol, zolpidem, 
tramadol, and hydrocodone; all these rates were considerably lower than 
the rates for ketamine, cocaine, and benzodiazepines. A similar pattern 
of utilization-adjusted abuse rates was seen among cases involving a 
single substance only during the same time period. HHS Basis for Rec. 
at 39.
    An analysis of medical outcomes related to exposure based on 
severity, timing, and assessment of clinical effects for all single-
substance PC abuse cases involving marijuana or comparator drugs showed 
that serious medical outcomes (moderate effect, major effect, or death) 
were greatest for illicit fentanyl (81 percent) and heroin (79 
percent), followed by oxycodone (70 percent), ketamine (64 percent), 
tramadol (62 percent), cocaine (59 percent), hydrocodone (44 percent), 
marijuana (41 percent), benzodiazepines (32 percent), alcohol (31 
percent), and zolpidem (27 percent). HHS noted that death rates are 
underreported in NPDS, but HHS observed that the highest death rate was 
for fentanyl (25 percent); cocaine, heroin, and alcohol had 
comparatively very low death rates (3 percent, 2 percent, and 2 
percent, respectively), with all other comparators reporting death 
rates of less than 1 percent. HHS Basis for Rec. at 39-40.
National Survey on Drug Use and Health
    Data from NSDUH provide nationally representative information on 
the prevalence of substance use disorder (``SUD'') in 2021 among 
individuals aged 12 years or older who reported nonmedical use of 
marijuana in past year in comparison to heroin, cocaine, or alcohol use 
in the past year. A diagnosis of SUD is made when an individual 
endorses at least 2 of the 11 criteria for SUD according to the 
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition 
(``DSM-V''). Individuals are classified with a mild SUD if they meet 
two to three of the criteria, a moderate SUD if they meet four to five 
of the criteria, and a severe SUD if they meet six or more of the 
criteria. HHS Basis for Rec. at 40.
    NSDUH data showed that, among individuals with past-year heroin use 
in 2021, there was an 81 percent prevalence of meeting the criteria for 
a heroin SUD. In comparison, there was a 30 percent prevalence of 
meeting the criteria for marijuana SUD among individuals who used 
marijuana for nonmedical reasons only (17 percent mild, 8 percent 
moderate, and 5 percent severe). For individuals who used marijuana for 
nonmedical purposes and did not use other drugs illicitly, there was a 
slightly lower prevalence (24 percent) of meeting the criteria for SUD 
(15 percent mild, 6 percent moderate, and 3 percent severe). For 
cocaine, 30 percent of individuals who used cocaine in the past year 
met criteria for cocaine SUD (13 percent mild, 5 percent moderate, and 
12 percent severe). For individuals who used alcohol in the past year, 
the prevalence of alcohol SUD was 17 percent (10 percent mild, 4 
percent moderate, and 3 percent severe). HHS Basis for Rec. at 40.
    Although the 2021 NSDUH data showed that the likelihood of meeting 
the criteria for a SUD was highest for heroin, followed by marijuana, 
cocaine, and alcohol, the absolute number of individuals who met the 
criteria had a different order. Alcohol had the highest number of such 
individuals (approximately 29,544,000), followed by marijuana 
(approximately 13,078,000 people with marijuana nonmedical-only use, 
and approximately 7,454,000 with nonmedical-only use and no nonmedical 
use of other drugs), cocaine (approximately 1,408,000), and heroin 
(approximately 894,000). HHS Basis for Rec. at 40.
Treatment Episode Data Set
    TEDS is a database run by SAMHSA within HHS that presents 
information on the demographic and substance use characteristics of 
annual admissions for treatment for alcohol and drug abuse in State-
approved facilities that are required by the States to provide TEDS 
client-level data. Because TEDS is based only on reports from these 
facilities, TEDS data do not represent the total national demand for 
substance abuse treatment or the prevalence of substance abuse in the 
general population. HHS Basis for Rec. at 40-41.
    Out of 1.4 million admissions documented in the 2020 TEDS dataset, 
the most frequently reported primary drug of admission was alcohol (31 
percent, or 442,014 admissions), followed by heroin (21 percent, or 
292,126 admissions), marijuana (10 percent, or 139,481 admissions), and 
cocaine (5 percent, or 71,725 admissions). Other comparator drugs were 
each reported as the primary drug in less than 2 percent of admissions. 
Over the reporting period of 2015 to 2020, the proportion of admissions 
each year ranged from 30 to 33 percent for alcohol; from 21 to 26 
percent for heroin; from 10 to 14 percent for marijuana; and from 5 to 
6 percent for cocaine. The proportion of admissions with marijuana as 
the primary drug declined each year from 14 percent in 2015 to a low of 
10 percent in 2020,

[[Page 44612]]

while the proportion of admissions with cocaine as the primary drug 
increased slightly during this time from 5 percent in 2015 to 6 percent 
in 2019. During this reporting period, other comparator drugs were each 
reported as the primary drug in less than 2 percent of admissions each 
year. HHS Basis for Rec. at 41.
    In 2020, marijuana and cocaine were most likely to be reported as 
the secondary drug at admission (25 percent and 24 percent, 
respectively), followed by alcohol (15 percent), heroin (8 percent), 
and benzodiazepines (6 percent), with all other comparators reported as 
less than 2 percent. For tertiary drugs at admission, marijuana (29 
percent) was reported most frequently, followed by cocaine (18 
percent), alcohol (16 percent), and heroin (5 percent), with all other 
comparators reported as less than 2 percent. HHS Basis for Rec. at 41.
National Addictions Vigilance Intervention and Prevention Program
    NAVIPPRO is a surveillance system for substance use and nonmedical 
use of prescription medication in a convenience sample of adults 
seeking treatment or being assessed for SUD treatment at participating 
facilities across the United States. NAVIPPRO Addiction Severity Index-
Multimedia Version (``ASI-MV'') is a clinical assessment tool that 
collects data on recent drug use behaviors for evaluation and treatment 
planning at intake. From 2020 through 2021, there were a total of 
76,249 NAVIPPRO ASI-MV assessments in individuals entering or being 
assessed for SUD treatment at a center participating in the NAVIPPRO 
network. The drug most frequently endorsed for past-month use was 
marijuana (20,458 individuals, or 27 percent), followed by alcohol (5 
or more alcoholic drinks per day, 16,388 individuals, or 22 percent), 
heroin (9,078 individuals, or 16 percent), fentanyl (6,186 individuals, 
or 8 percent), hydrocodone (3,448 individuals, or 5 percent), oxycodone 
(3,186 individuals, or 4 percent), cocaine or crack (5,417 individuals, 
or 7 percent), tramadol (543 individuals, or 1 percent), and ketamine 
(169 individuals, or less than 1 percent). HHS Basis for Rec. at 41.
Nationwide Emergency Department Sample
    NEDS is the largest all-payer ED database in the United States, as 
developed for HHS's Agency for Healthcare Research and Quality 
(``AHRQ''). NEDS is a sample of records from ED visits from the State 
Emergency Department Databases, which capture discharge information on 
all ED visits that do not result in hospital admission, and the State 
Inpatient Databases, which contain information on patients first seen 
in the ED and then admitted. The 2020 ED sample covered 995 hospital 
EDs and 41 States; the unweighted 2020 sample contained data from over 
28 million ED visits, which resulted in a weighted estimate of 123 
million ED visits. HHS compared ED visits that noted an alcohol, 
marijuana, or cocaine-related disorder; this comparison included ED 
visits not directly due to a specific substance-related disorder, but 
in which the patient was recorded as having had an alcohol, marijuana, 
or cocaine-related disorder in the administrative claim associated with 
the visit. HHS Basis for Rec. at 42.
    Based on NEDS data, from 2016 to 2020, the highest estimated number 
of annual ED visits was for an alcohol-related disorder, with between 4 
million and 4.1 million visits each year, 3.2 million of which involved 
alcohol as a single substance. Over the same timeframe, estimated 
annual ED visits involving a marijuana-related disorder ranged from 
approximately 1.3 million to over 1.7 million, with the estimated 
annual ED visits for single-substance marijuana disorder ranging from 
757,731 to 1.08 million. For cocaine, the estimated annual ED visits 
involving a related disorder were between 559,165 and 774,737, with 
annual visits for single-substance cocaine-related disorder ranging 
from 204,257 to 266,614. HHS Basis for Rec. at 42.
    HHS calculated a utilization-adjusted rate of estimated ED visits, 
and the highest rate was for cocaine-related disorder, which ranged 
from 11,765 to 14,014 visits per 100,000 individuals, of which 4,011 to 
4,952 were single-substance visits. Marijuana had the second-highest 
utilization-adjusted rate of estimated ED visits, ranging from 3,472 to 
3,940 per 100,000 individuals 2,017 to 2,413 of which were single-
substance visits. The utilization-adjusted rate of visits involving an 
alcohol disorder, the lowest of the three substances, ranged from 2,225 
to 2,327 per 100,000 individuals, of which 1,775 to 1,843 were single-
substance ED visits. HHS Basis for Rec. at 42-43.
National Inpatient Sample
    NIS is the largest publicly available all-payer inpatient 
administrative health care database in the United States, and it is 
sponsored by AHRQ. It is a sample of discharges from participating 
community hospitals from 46 to 48 States and the District of Columbia 
each year, with approximately 7 million unweighted inpatient stays 
annually, accounting for weighted annual estimates of 35 million 
hospitalizations. HHS used NIS data to compare alcohol, marijuana, and 
cocaine. HHS Basis for Rec. at 43.
    From 2016 to 2020, alcohol-related disorder had the highest 
estimated annual number of hospitalizations, at approximately 1.8 
million each year, of which approximately 1.2 to 1.25 million involved 
single-substance alcohol-related disorder. Marijuana-related disorder 
had the second-highest estimated annual number of hospitalizations, 
increasing from 795,140 in 2016 to 914,810 in 2020, of which 373,160 to 
452,985 were for single-substance marijuana-related disorder. Cocaine 
had the lowest estimated annual number of hospitalizations, ranging 
from 387,385 to 453,955, of which 94,695 to 112,725 were for single-
substance cocaine-related disorder. HHS Basis for Rec. at 43.
    HHS then calculated a utilization-adjusted rate of estimated 
hospitalizations, and the highest rate was for cocaine-related 
disorder, which ranged from 7,185 to 8,211 hospitalizations per 100,000 
individuals with any past-year use, of which 1,796 to 2,039 were 
single-substance hospitalizations. Marijuana-related disorder had the 
second-highest rate of estimated hospitalizations, ranging from 1,850 
to 2,117 per 100,000 individuals, of which 906 to 1,026 were single-
substance hospitalizations. Alcohol had the lowest rate, ranging from 
987 to 1,039 per 100,000 individuals, of which 675 to 715 were single-
substance hospitalizations. HHS Basis for Rec. at 43.
National Forensic Laboratory Information System
    NFLIS is a program of the Diversion Control Division of DEA. The 
NFLIS-Drug system is a component of the NFLIS that contains data that 
serve as a surveillance resource to monitor drug encounters by law 
enforcement across the United States, including data on drugs seized by 
law enforcement and submitted to Federal, State, and local forensic 
laboratories for analysis. In NFLIS, a law enforcement investigation 
(``case'') may result in one or more ``reports'' or ``exhibits'' of 
drug evidence, and each report or exhibit may contain one drug or 
multiple drugs. However, NFLIS-Drug data has limitations because not 
all drugs encountered by law enforcement are sent for analysis and not 
all drugs sent to reporting forensic laboratories are tested. To 
account for nonreporting

[[Page 44613]]

laboratories, among other things, DEA publishes NFLIS-Drug national 
report estimates annually and semiannually. Analyzing national 
estimates data allows for a comparison of the number of reports by year 
and reporting trends. In calculating national and regional estimates, 
DEA uses all NFLIS-Drug reporting laboratories. HHS Basis for Rec. at 
43-44.
    In 2021, there were 1,326,205 drug reports from State and local 
forensic laboratories in the United States, an increase of 3 percent 
from 2020. Nationally, 61 percent of all drug reports in NFLIS were 
identified as involving methamphetamine (406,200 reports or 31 
percent), cannabis/THC (167,669 reports or 13 percent), cocaine 
(165,162 reports or 12 percent), or heroin (72,315 reports or 5 
percent). HHS Basis for Rec. at 44-45.
    In 2021, there were 1,027,219 drug-specific cases submitted to and 
analyzed by State and local laboratories, a 2 percent increase from 
2020. Although the total NFLIS-Drug number of drug reports increased in 
2021 from 2020, the total number of cases and drugs reported continues 
to be noticeably lower than the numbers reported for the years before 
the COVID-19 pandemic. Nationally, in 2021, 45 percent of all drug 
cases contained one or more reports of methamphetamine, followed by 
cocaine (18 percent), cannabis/THC (17 percent), and heroin (8 
percent). Nationally, the number of cannabis/THC reports as well as the 
number of cases in which cannabis/THC was identified decreased from 
2015 through 2021, including a decrease from 188,735 to 167,669 from 
2020 to 2021. HHS noted that this could mean there was a decrease in 
the number of cannabis/THC encounters, but it could also mean that 
there was a decrease in the number of exhibits submitted by law 
enforcement for analysis or a decrease in the number of exhibits 
processed (analyzed) by forensic laboratories. HHS Basis for Rec. at 
45.
HHS Conclusion With Respect to Factor 5
    In HHS's view, the most notable conclusion from its evaluation of 
epidemiological databases related to the medical outcomes from drug 
abuse is that, for all evaluated measures from 2015 to 2020, the rank 
order of comparators in terms of greatest adverse consequences 
typically placed alcohol (unscheduled), heroin (schedule I), and 
cocaine (schedule II) in the first or immediately subsequent position, 
with marijuana in a lower position. This pattern also held for PC data 
for serious medical outcomes, including death, where marijuana was in 
the lowest ranking group. HHS determined that this demonstrated that 
there is consistency across databases, across substances, and over 
time, and that although abuse of marijuana produces clear evidence of 
harmful consequences, including SUD, the consequences are relatively 
less common and less harmful than some other comparator drugs. 
Additionally, HHS concluded, the number of law enforcement encounters 
with marijuana decreased from 2020 to 2021, at a time when law 
enforcement encounters were increasing for other scheduled drugs of 
abuse. However, as it noted with respect to Factor 1.A, HHS emphasized 
that there are limitations in comparing descriptive data on adverse 
outcomes across drugs, although descriptive analyses of epidemiologic 
data are an established practice in previous eight-factor analyses. HHS 
Basis for Rec. at 45.
    In 2016, DEA found that abuse of marijuana is widespread and 
significant. 81 FR 53739. In addition, DEA found in 2016 that a 
significant proportion of all admissions for substance abuse treatment 
are for marijuana/hashish as the primary drug of abuse. Id. DEA notes 
that national data demonstrate that marijuana is one of the most widely 
used federally illicit substances in the United States, consistent with 
findings from the HHS Basis for Recommendation. According to the NSDUH, 
in 2022, among people aged 12 or older in the United States, an 
estimated 61.9 million people (22 percent) had used marijuana in the 
past year, and 42.3 million (15.0 percent) had used it in the past 
month. DEA notes that, according to one National Institutes of Health-
supported study, the prevalence of daily marijuana use reached its 
highest level reported in 2021, at 11 percent of Americans aged 12 or 
older, a 3 percent increase from 2017 and a 5 percent increase from 
2012.\27\ It also notes that the average percentage of [Delta]9-THC in 
seized marijuana has increased over time.\28\ Also, TEDS data showed 
that, in 2020, marijuana was the primary drug of admission in 
approximately 10 percent of all admissions to substance abuse treatment 
among patients aged 12 and older. HHS Basis for Rec. at 41, 46. DEA 
also notes that TEDS data for 2021 reported that marijuana/hashish was 
the primary substance of abuse in 10.2 percent of all admissions to 
substance abuse treatment among patients aged 12 and older.\29\ The 
2021 TEDS data further reported that New York, California, Georgia, 
North Carolina, New Jersey, Texas, Minnesota, South Carolina, Florida, 
and Connecticut accounted for 55.9 percent of admissions to substance 
use treatments services where marijuana/hashish was listed as the 
primary substance.\30\ DEA also believes that additional information 
regarding the scope, duration, and significance of marijuana abuse may 
be appropriate for consideration in assessing this factor.
---------------------------------------------------------------------------

    \27\ Marijuana and hallucinogen use among young adults reached 
all time-high in 2021, Nat'l Inst. on Drug Abuse (Aug. 22, 2022), 
https://nida.nih.gov/news-events/news-releases/2022/08/marijuana-and-hallucinogen-use-among-young-adults-reached-all-time-high-in-2021.
    \28\ Cannabis Potency Data, Nat'l Inst. on Drug Abuse (Nov. 23, 
2022), https://nida.nih.gov/research/research-data-measures-resources/cannabis-potency-data.
    \29\ Substance Abuse & Mental Health Servs. Admin., Treatment 
Episode Data Set (TEDS) 2021: Admissions to and Discharges from 
Substance Use Treatment Services Reported by Single State Agencies 
10 (2023), https://www.samhsa.gov/data/sites/default/files/reports/rpt42794/2021-teds-annual-report.pdf (Figure 3.A.9).
    \30\ Id. at 29 (Figure 6.B.4).
---------------------------------------------------------------------------

6. What, if Any, Risk There Is to the Public Health

    The sixth factor that DOJ and HHS must consider under 21 U.S.C. 
811(c) is the risk posed to the public health by marijuana. In 
analyzing this factor, HHS examined NSDUH data related to the 
demographics of U.S. individuals meeting criteria for marijuana use 
disorder, TEDS data related to the demographics of admission to 
treatment centers for marijuana use disorder, NEDS and NIS data on 
admissions to EDs and hospitals related to marijuana poisoning, ToxIC 
Core Registry data on intentional and unintentional exposure, and NPDS 
data describing the risks to youth of unintentional exposure to 
marijuana. HHS also assessed the risks to the public health through 
NSDUH data on driving under the influence of marijuana in adults and 
high school students. Finally, HHS reported data regarding the risk of 
serious AEs and death associated with nonmedical use/use of uncertain 
intent of marijuana as reported to the FDA Adverse Event Reporting 
System, Center for Food Safety and Applied Nutrition Adverse Event 
Reporting System, National Vital Statistics System-Mortality (``NVSS-
M''), DAWN, FDA's Sentinel Distributed Database System, and Centers for 
Medicare and Medicaid Services, and as reflected in the Drug-Involved 
Mortality data linking NVSS-M to death certificates. HHS Basis for Rec. 
at 46.
HHS Conclusion With Respect to Factor 6
    HHS's detailed analysis of the risks posed by marijuana to the 
public health

[[Page 44614]]

can be found at pages 46-57 of the HHS Basis for Recommendation. In 
summary, HHS found that the risks to the public health posed by 
marijuana are low compared to other drugs of abuse (e.g., heroin 
(schedule I), cocaine (schedule II)), based on its evaluation of 
various epidemiological databases for ED visits, hospitalizations, 
unintentional exposures, and, most importantly, for overdose deaths. 
The rank order of comparator drugs in terms of greatest adverse 
consequences typically places heroin, benzodiazepines, or cocaine in 
the first or immediately subsequent positions, with marijuana in a 
lower place in the ranking, especially when comparing among individuals 
who reported using the respective drugs at least once in the prior 
year. For overdose deaths, marijuana is always ranked the lowest among 
comparator drugs. HHS interpreted these evaluations to demonstrate that 
there is consistent evidence across databases, across substances, and 
over time that, although the abuse of marijuana poses a risk to public 
health, the risk is relatively lower than that posed by most other 
comparator drugs. However, as HHS noted in its discussion of Factor 1, 
see HHS Basis for Rec. at 7-8, there are limitations in comparing 
descriptive data on adverse outcomes across drugs. HHS Basis for Rec. 
at 57.
    In 2016, DEA found that, ``[t]ogether with the health risks 
outlined in terms of pharmacological effects above, public health risks 
from acute use of marijuana include impaired psychomotor performance, 
impaired driving, and impaired performance on tests of learning and 
associative processes. Chronic use of marijuana poses a number of other 
risks to the public health including physical as well as psychological 
dependence.'' 81 FR 53739-40. In addition to the data provided in the 
HHS Basis for Recommendation and the data considered by HHS and DEA in 
their prior eight-factor analyses, DEA anticipates that additional data 
on public safety risks, risks from acute and chronic marijuana use via 
oral and inhaled administration routes, and the impact of [Delta]9-THC 
potency may be appropriate for consideration.
    As discussed in the HHS Basis for Recommendation, DEA notes that 
studies have examined the risk associated with marijuana use and 
driving. HHS Basis for Rec. at 50. The Rocky Mountain High Intensity 
Drug Trafficking Area reported in a publication that traffic deaths in 
Colorado in which drivers tested positive for marijuana more than 
doubled from 55 in 2013 to 131 in 2020, although other evidence in the 
same report suggests that driving under the influence citations 
involving marijuana have grown at a rate similar to the rate for 
citations involving other drugs.\31\ DEA also identified some evidence 
suggesting that, among drivers who test positive for at least one drug 
in a traffic stop, a growing share test positive for cannabis.\32\
---------------------------------------------------------------------------

    \31\ See 8 Rocky Mountain High Intensity Drug Trafficking Area, 
The Legalization of Marijuana in Colorado: The Impact 8, 13 (2021), 
https://www.rmhidta.org/_files/ugd/4a67c3_b391ac360f974a8bbf868d2e3e25df3d.pdf. Note that the 
publication did not address the timing of marijuana use associated 
with fatal traffic accidents.
    \32\ See Fernando A. Wilson et al., Fatal Crashes from Drivers 
Testing Positive for Drugs, 1993-2010, 129 Public Health Reports 
342, 347-348 (2014).
---------------------------------------------------------------------------

7. Marijuana's Psychic or Physiological Dependence Liability

    The seventh factor that DOJ and HHS are required to consider under 
21 U.S.C. 811(c) is the psychic or physiologic dependence liability of 
marijuana.
A. Psychic Dependence
    The term ``psychic or psychological dependence'' has been used to 
refer to a state similar to addiction. For diagnosis purposes, the DSM-
V has combined the diagnoses ``abuse'' and ``drug dependence'' (i.e., 
addiction), which the DSM's Fourth Edition specified separately, into a 
single ``substance use disorder,'' which may occur in a broad range of 
severity, from mild to severe. HHS Basis for Rec. at 57.
    The abuse potential of a drug can be assessed, in part, by 
evaluating the rewarding effects produced by that drug in humans and 
animals. As HHS described in its analysis of Factor 2, see HHS Basis 
for Rec. at 12-13, rodent behavioral studies show that [Delta]9-THC 
produces both self-administration and CPP. HHS determined that these 
results demonstrate that [Delta]9-THC has rewarding properties that are 
indicative of abuse potential. Further, as HHS described in its 
analysis of Factor 4, see HHS Basis for Rec. at 32-37, there is ample 
epidemiological evidence that marijuana is self-administered by humans, 
which may result from its ability to produce rewarding psychological 
effects, such as euphoria, see HHS Basis for Rec. at 15. HHS Basis for 
Rec. at 58.
    In some individuals, extensive use of marijuana can lead to SUD. 
HHS noted that, in general, SUDs listed in the DSM-V are defined by an 
inability to cease drug use despite harmful consequences; Cannabis Use 
Disorder (``CUD'') shares this and other diagnostic criteria common to 
SUDs for other drugs of abuse. Estimates of CUD in individuals who 
regularly use marijuana vary and range from about 10 to 20 percent. 
These estimates are similar to data from the United States National 
Comorbidity Study, which showed that 9 percent of lifetime cannabis 
users met the criteria for dependence outlined in the DSM's revised 
Third Edition at some time in their life, compared to 32 percent of 
tobacco users, 23 percent of opiate users, and 15 percent of alcohol 
users. The National Epidemiologic Survey on Alcohol and Related 
Conditions also reported a nine percent lifetime cumulative probability 
of transitioning from marijuana use to dependence, with a higher risk 
of dependence in individuals with a history of psychiatric or other 
substance dependence comorbidity. In the United States, data from the 
2020 NSDUH show that approximately 14 million individuals aged 12 or 
older who use marijuana or other cannabinoid preparations met criteria 
for CUD, representing 5.1 percent of all individuals aged 12 or older 
meeting the NSDUH survey inclusion criteria. HHS Basis for Rec. at 58.
    Individuals who develop a SUD, including CUD, may seek treatment. 
From 2015 to 2020, TEDS documented approximately 10.8 million treatment 
episode admissions reported by individuals treated at publicly funded 
substance use treatment programs. Out of 1.4 million treatment 
admissions documented by TEDS in 2020, marijuana was reported as the 
primary substance of abuse in approximately 10 percent of admissions, 
making it the third most frequently reported primary substance of 
abuse, after alcohol (31.2 percent) and heroin (20.6 percent). A 
similar pattern was seen from 2015 to 2019. HHS Basis for Rec. at 58.
    HHS concluded that the animal behavioral data show that [Delta]9-
THC produces rewarding properties that underlie the abuse potential of 
marijuana. Epidemiological data demonstrate that some individuals who 
use marijuana for its rewarding properties go on to develop CUD, which 
shows that marijuana can produce psychological dependence. Among those 
individuals who seek admission for treatment for SUD associated with a 
drug of abuse, marijuana was the third most frequently reported primary 
substance of abuse. Thus, marijuana can produce psychic dependence in 
some individuals who use the drug. HHS Basis for Rec. at 58-59.
B. Physical Dependence
    Physical dependence is a state of adaptation manifested by a drug-
class

[[Page 44615]]

specific withdrawal syndrome produced by abrupt cessation, rapid dose 
reduction, decreasing blood level of the drug, or administration of an 
antagonist. Although physical dependence is often associated with 
addiction, it can be produced by repeated administration of drugs both 
with and without abuse potential. HHS Basis for Rec. at 59.
    As HHS discussed in its analysis of Factor 2, see HHS Basis for 
Rec. at 11, [Delta]9-THC is a partial agonist at CB1 
receptors. When marijuana (or isolated [Delta]9-THC) is administered 
chronically, there is a down-regulation of CB1 receptors, 
which leads to behavioral tolerance. The underlying mechanism for 
marijuana withdrawal appears to be the uncoupling or desensitization of 
CB1 receptors that precedes receptor down-regulation. Abrupt 
discontinuation of marijuana after prolonged administration produces 
withdrawal symptoms in rats and in humans that are typically opposite 
to those that occur with activation of the CB1 receptor. 
Precipitated withdrawal can also be induced with administration of 
CB1 antagonists following chronic administration, while 
administration of CB1 agonists can attenuate some withdrawal 
symptoms associated with marijuana discontinuation. These data confirm 
the importance of the CB1 receptor in marijuana physical 
dependence. HHS Basis for Rec. at 59.
    HHS noted that research has not yet documented the occurrence of 
withdrawal symptoms in individuals who use marijuana only occasionally. 
However, in individuals who use marijuana heavily and chronically, drug 
discontinuation can lead to a withdrawal syndrome. Most marijuana 
withdrawal symptoms begin within 24 to 48 hours of drug 
discontinuation, peak within two to six days, and reduce over one to 
two weeks as [Delta]9-THC levels decline. HHS Basis for Rec. at 59.
    The most commonly reported withdrawal symptoms from clinical 
investigations are sleep difficulties, decreased appetite and weight 
loss, craving, irritability, anger, anxiety or nervousness, and 
restlessness. Less commonly reported withdrawal symptoms include 
depressed mood, sweating, shakiness, physical discomfort, and chills. 
HHS described the symptoms of ``cannabis withdrawal'' listed in the 
DSM-V as being similar to those reported in the experimental studies, 
including nervousness or anxiety, irritability or aggression, insomnia 
or unpleasant dreams, depressed mood, decreased appetite or weight 
loss, restlessness, abdominal pain, shakiness or tremors, sweating, 
fever, chills, and headache. HHS Basis for Rec. at 59-60.
    HHS reported that up to 40 to 50 percent of individuals who use 
marijuana on a regular basis may experience physical dependence. A 
meta-analysis of 23,518 individuals who frequently used marijuana 
showed that 47 percent of subjects reported symptoms of marijuana 
withdrawal. The prevalence of physical dependence was 54 percent in 
outpatient samples, 17 percent in community samples, and 87 percent 
among inpatients in drug abuse treatment centers. This is consistent 
with data showing that 90 percent of individuals who were diagnosed 
with CUD also reported physical dependence. Further, individuals 
diagnosed with CUD experience more severe and longer lasting withdrawal 
symptoms when discontinuing marijuana than individuals who do not have 
a diagnosis of CUD. This may be because individuals with CUD have 
greater exposure to marijuana. HHS Basis for Rec. at 60.
    Symptoms associated with marijuana withdrawal appear to be 
relatively mild compared to those associated with alcohol withdrawal, 
which can include agitation, paranoia, seizures, and even death. 
Multiple studies comparing the withdrawal symptoms associated with 
tobacco (not scheduled in the CSA) and marijuana demonstrate that the 
magnitude and time course of the two withdrawal syndromes are similar. 
Animal studies have shown that after short-term administration of 
equianalgesic doses of heroin and [Delta]9-THC to monkeys, withdrawal 
signs were observed after heroin administration but not after [Delta]9-
THC administration, further demonstrating that withdrawal from 
marijuana is associated with less severe symptoms than withdrawal from 
other drug classes. HHS Basis for Rec. at 60.
HHS Conclusion With Respect to Factor 7
    In conclusion, HHS found experimental and clinical evidence that 
chronic, but not acute, use of marijuana can produce both psychic and 
physical dependence in humans. Epidemiological data, discussed in 
greater detail in the sections describing Factors 4 and 5 in sections 
VI.4 and VI.5 of this preamble, provide additional evidence of psychic 
dependence. The symptoms associated with both kinds of dependence are 
relatively mild for most individuals, although their severity may be 
greater with increased exposure to marijuana. HHS Basis for Rec. at 61.
    In 2016, DEA found that ``[l]ong-term, heavy use of marijuana can 
lead to physical dependence and withdrawal following discontinuation, 
as well as psychic or psychological dependence.'' 81 FR 53740. DEA 
notes that some physicians have argued that CUD is underdiagnosed and 
undertreated in the medical setting,\33\ and that other medical 
professionals have noted that CUD needs to be better understood and 
characterized to better inform users and treatment professionals.\34\ 
DEA anticipates that additional psychic or physiological dependence 
liability may be appropriate for consideration.
---------------------------------------------------------------------------

    \33\ See, e.g., Theresa A. Matson et al., Association Between 
Cannabis Use Disorder Symptom Severity and Probability of 
Clinically-Documented Diagnosis and Treatment in a Primary Care 
Sample, 251 Drug & Alcohol Dependence, no. 110946, 2023.
    \34\ See, e.g., Gwen T. Lapham et al., Prevalence of Cannabis 
Use Disorder and Reasons for Use Among Adults in a U.S. State Where 
Recreational Cannabis Use is Legal, 6 JAMA Open no. e2328934, 2023, 
at 7.
---------------------------------------------------------------------------

8. Whether Marijuana Is an Immediate Precursor of a Substance Already 
Controlled Under the CSA

    The eighth factor that DOJ and HHS are required to consider under 
21 U.S.C. 811(c) is whether marijuana is an immediate precursor of a 
substance already controlled under the CSA. HHS concluded that 
marijuana is not an immediate precursor of another controlled 
substance. HHS Basis for Rec. at 61. This finding is consistent with 
DEA's finding in 2016. 81 FR 53740. DEA welcomes additional information 
on this factor.

VII. Determination of Appropriate Schedule for Marijuana

    After conducting the eight-factor analysis in 2023, HHS has 
recommended three findings regarding the appropriate schedule in which 
to place marijuana. The three findings relate to: (1) a substance's 
abuse potential; (2) whether the substance has a CAMU; and (3) the 
safety or dependence potential of the substance. 21 U.S.C. 812(b); HHS 
Basis for Rec. at 62-65.
1. Potential for Abuse
    In 2016, HHS found that many factors indicated marijuana's high 
abuse potential, ``including the large number of individuals regularly 
using marijuana, marijuana's widespread use, and the vast amount of 
marijuana available for illicit use.'' 81 FR 53688 at 53706. As a 
result of its most recent evaluation, which incorporates post-2016 data 
into its analysis, HHS has recommended a finding that marijuana has a 
potential for abuse less than the drugs or other substances in 
schedules I and II.

[[Page 44616]]

    Marijuana contains [Delta]9-THC (also known as dronabinol when 
specifically referring to (-)-trans-[Delta]9-THC stereoisomer), the 
substance responsible for the abuse potential of marijuana. [Delta]9-
THC has agonist properties at CB1 cannabinoid receptors and 
produces rewarding responses in animals, as evidenced by its ability to 
produce self-administration and CPP. When marijuana is administered to 
humans under experimental conditions, it produces a wide range of 
positive subjective responses in addition to certain negative 
subjective responses. Common responses to marijuana when it is used by 
individuals for nonmedical purposes include euphoria and other positive 
subjective responses, as well as perceptual changes, sedative 
responses, anxiety responses, psychiatric, social, and cognitive 
changes, and physiological changes. HHS Basis for Rec. at 62.
    HHS noted that epidemiological data from NSDUH show that marijuana 
is the most frequently used federally illicit drug in the United States 
on a past-year and past-month basis among the illicit comparator drugs 
considered. Although 50 percent of respondents in NSDUH reported using 
marijuana nonmedically fewer than 5 days per month, another 30 percent 
reported using it nonmedically for 20 days or more per month. HHS Basis 
for Rec. at 62.
    Despite the high prevalence of nonmedical use of marijuana, HHS 
observed that an overall evaluation of epidemiological indicators 
suggests that it does not produce serious outcomes compared to drugs in 
schedules I or II. HHS found this especially notable given the 
availability of marijuana and marijuana-derived products that contain 
extremely high levels of [Delta]9-THC. Due to such availability, the 
epidemiological data described in HHS's evaluation inherently include 
the outcomes from individuals who use marijuana and marijuana-derived 
products that have doses of [Delta]9-THC that range from low to very 
high, and yet the data demonstrate that these products overall are 
producing fewer negative outcomes than drugs in schedules I or II. HHS 
Basis for Rec. at 62.
    HHS compared the rank ordering of selected drugs that are abused 
for various epidemiological measures and observed that marijuana was 
among the drugs at the very lowest ranking for a number of measures, 
including PC abuse cases, likelihood that any use would lead to a PC 
call, accidental or unintentional poisoning, utilization-adjusted rates 
of unintentional exposure, utilization-adjusted and population-adjusted 
rates for ED visits and hospitalizations, likelihood of being diagnosed 
with a serious SUD, deaths reported to PCs, and overdose deaths when 
used with other drugs or as a single substance (as total numbers and 
when utilization-adjusted). In contrast, comparators such as heroin 
(schedule I), oxycodone (schedule II), and cocaine (schedule II) 
typically were in the highest rank ordering on these measures. HHS 
Basis for Rec. at 62.
    For the various epidemiological measures evaluated above, HHS noted 
that marijuana was also compared to controlled substances in schedule 
III (ketamine) and schedule IV (benzodiazepines, zolpidem, and 
tramadol), as well as to other schedule II substances (fentanyl and 
hydrocodone). The analyses were conducted in this manner to provide a 
comprehensive assessment of the relative abuse potential of marijuana. 
However, the rank order of these substances regarding harms does not 
consistently align with the relative scheduling placement of these 
drugs in the CSA due to the pharmacological differences between various 
classes of drugs. HHS Basis for Rec. at 63.
    There are a number of confounding factors that likely influence the 
adverse outcomes measured in various epidemiological databases and 
account for the rank ordering of the drugs evaluated on these measures. 
For example, a different population abuses each substance, and each 
substance has a different prevalence of abuse and a different profile 
of severe adverse outcomes in a setting of nonmedical use and abuse. 
Thus, it is challenging to reconcile the ranking of relative harms 
associated with the comparators used in this evaluation when the 
rankings differ across various epidemiological databases and when these 
rankings often do not align with the scheduling placement of these 
comparators under the CSA. HHS Basis for Rec. at 63.
    To address these challenges, HHS evaluated the totality of the 
available data and has concluded that it supports the placement of 
marijuana in schedule III. Overall, these data demonstrate that, 
although marijuana is associated with a high prevalence of abuse, the 
profile of and propensity for serious outcomes related to that abuse 
lead to a conclusion that marijuana is most appropriately controlled in 
schedule III under the CSA. HHS Basis for Rec. at 63.
    The Attorney General has considered HHS's recommendations and 
conclusions and accords HHS's scientific and medical determinations 
binding weight at this stage of the scheduling process. See OLC Op. at 
*22 n.6 (``HHS's recommendations with respect to `scientific and 
medical matters' are binding for all eight factors listed in section 
811(c).''). The Attorney General concurs with HHS's recommendation, for 
purposes of initiation of these rulemaking proceedings, that marijuana 
has a potential for abuse less than the drugs or other substances in 
schedules I and II.

2. Currently Accepted Medical Use in Treatment in the United States

    In 2016, HHS recommended a finding that marijuana had no CAMU due 
in part to a lack of adequate safety studies or evidence that qualified 
experts accepted marijuana for use in treating a specific, recognized 
disorder. 81 FR 53688 at 53707. As a result of its most recent 
evaluation, which incorporates post-2016 data into its analysis, HHS 
recommends a finding that marijuana has a CAMU.
    In making that recommendation, HHS analyzed whether there is (1) 
widespread current experience with medical use of the substance in the 
United States by licensed health care practitioners operating in 
accordance with implemented State-authorized programs, where the 
medical use is recognized by entities that regulate the practice of 
medicine; and (2) some credible scientific support for a least one of 
those medical uses. Applying this test, HHS recommended a finding that 
marijuana has a currently accepted medical use in the United States, 
specifically for the treatment of anorexia related to a medical 
condition, nausea and vomiting (e.g., chemotherapy-induced), and pain. 
According to HHS, its evaluation also supported a finding that there is 
accepted safety for the use of marijuana under medical supervision for 
the treatment of anorexia related to a medical condition, nausea and 
vomiting (e.g., chemotherapy-induced), and pain. HHS Basis for Rec. at 
63-64.
    In the past, DEA has concluded that a substance has a CAMU under 
the CSA only if one of two tests is satisfied. First, DEA has 
determined that a substance has a CAMU if the substance has been 
approved by FDA for marketing under the FDCA, either through the NDA 
process or by meeting the criteria to be recognized as a ``Generally 
Recognized As Safe and Effective'' (``GRASE'') drug. 57 FR 10499, 10503 
(March 26, 1992). Second, DEA has determined a substance has a CAMU if 
the substance satisfies a five-part test established by DEA in 1992 
that was based on the ``core FDCA standards for acceptance of drugs for 
medical use'':

[[Page 44617]]

    1. There must be adequate safety studies;
    2. The drug's chemistry must be known and reproducible;
    3. There must be adequate and well-controlled studies proving 
efficacy;
    4. The drug must be accepted by qualified experts; and
    5. The scientific evidence must be widely available.

57 FR 10499, 10503-06 (1992); see also All. for Cannabis Therapeutics 
v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).

    In its most recent evaluation, HHS informed DEA of its view that 
DEA's previous approach to determining whether a drug has a CAMU does 
not adequately account for certain indicia of medical use that, where 
present, are relevant to determining whether a substance has a CAMU for 
purposes of scheduling under the CSA. Specifically, HHS observed that 
DEA's tests left no room for an evaluation of (1) whether there is 
widespread medical use of a drug under the supervision of licensed 
health care practitioners under State-authorized programs and, (2) if 
so, whether there is credible scientific evidence supporting such 
medical use. HHS therefore developed an alternative test composed of 
those two inquiries as a third, independently sufficient approach for 
determining whether a substance has a CAMU under the CSA. HHS applied 
this two-part test to marijuana and recommended a finding that 
marijuana has a CAMU under the CSA. HHS Basis for Rec. at 24-28.
    Upon receiving HHS's recommendation, the Attorney General requested 
that OLC advise on whether HHS's test, if satisfied, established a CAMU 
``even if the drug has not been approved by FDA and even if the drug 
does not satisfy DEA's five-part test.'' OLC Op. at *3. OLC determined 
that DEA's current approach to determining whether a drug has a CAMU is 
impermissibly narrow, because it ``ignor[es] widespread clinical 
experience with a drug that is sanctioned by state medical licensing 
regulators.'' Id. at *13-14; see also id. at *12. OLC further opined 
that satisfying HHS's two-part inquiry is sufficient to establish that 
a drug has a CAMU. Id. at *4, *16-20. And OLC concluded that, while 
HHS's CAMU recommendation is not binding on DEA, the medical and 
scientific determinations that underlie its recommendation are binding 
until the initiation of formal rulemaking proceedings, and that DEA 
must accord those determinations ``significant deference'' throughout 
the rulemaking process. Id. at *4, *20-26.
    Under Part 1 of the HHS CAMU test, the Office of the Assistant 
Secretary for Health (``OASH'') considered whether there is widespread 
current experience with medical use of marijuana in the United States 
by licensed HCPs operating in accordance with implemented State-
authorized programs, where such medical use is recognized by entities 
that regulate the practice of medicine under these State jurisdictions. 
Part 2 of the CAMU test evaluated whether there exists some credible 
scientific support for at least one of the medical conditions for which 
the Part 1 test is satisfied. The evaluation in Part 2, undertaken by 
FDA, was not meant to be, nor is it, a determination of safety and 
efficacy under the Federal Food, Drug, and Cosmetic Act's drug approval 
standard for new human or animal drugs. Rather, HHS's two-part test is 
designed to evaluate whether a substance, in this case marijuana, has a 
CAMU for purposes of drug scheduling recommendations and placement in a 
drug schedule consistent with criteria set forth in 21 U.S.C. 812(b). 
HHS Basis for Rec. at 24.
    In the evaluation and assessment under Part 1 of the CAMU test, 
OASH found that more than 30,000 HCPs are authorized to recommend the 
use of marijuana for more than six million registered patients, 
constituting widespread clinical experience associated with various 
medical conditions recognized by a substantial number of jurisdictions 
across the United States. For several jurisdictions, these programs 
have been in place for several years, and include features that 
actively monitor medical use and product quality characteristics of 
marijuana dispensed. HHS Basis for Rec. at 24.
    Based on OASH's findings in Part 1 of the CAMU test, the Assistant 
Secretary for Health concluded that an FDA assessment under Part 2 of 
the CAMU test was warranted to determine if credible scientific support 
exists for the use of marijuana to treat at least one of the medical 
conditions identified by OASH under Part 1. HHS Basis for Rec. at 24.
    At this stage of initiating a rulemaking, the Attorney General 
agrees with OASH that there is widespread clinical experience with 
marijuana for at least one medical condition.
    FDA conducted Part 2 of the CAMU test for seven indications, based 
in part on OASH's findings under Part 1 of the CAMU test \35\ and in 
part on FDA's own analysis of the landscape in which marijuana is 
currently used medically, including information from State-authorized 
programs on how and to what extent marijuana is being utilized for 
medical purposes. The seven indications are: (1) anorexia; \36\ (2) 
anxiety; \37\ (3) epilepsy; (4) inflammatory bowel disease (``IBD''); 
(5) nausea and vomiting; (6) pain; and (7) post-traumatic stress 
disorder (``PTSD''). FDA's evaluation under Part 2 of the CAMU test was 
based on systematic reviews of studies investigating the safety and 
effectiveness of marijuana, relevant professional societies' position 
statements, data from State medical marijuana programs and United 
States national surveys, and the labeling of FDA-approved products 
relevant to the analysis. HHS Basis for Rec. at 25.
---------------------------------------------------------------------------

    \35\ In Part 1 of the CAMU test, OASH identified at least 15 
medical conditions for which there is widespread current experience 
with medical use of marijuana in the United States by licensed HCPs 
operating in accordance with implemented State-authorized programs, 
where the medical use is recognized by entities that regulate the 
practice of medicine. These conditions include amyotrophic lateral 
sclerosis (commonly known as ALSI), autism, cachexia, cancer, 
chronic pain, Crohn's disease, epilepsy or condition causing 
seizures, glaucoma, HIV/AIDS, multiple sclerosis, Parkinson's 
disease, persistent/severe muscle spasm, persistent/severe nausea, 
PTSD, and spasticity. FDA conducted Part 2 of the analysis for the 
medical conditions identified by OASH that were likely to have the 
most robust evidence available for review; because the analysis 
concluded that the Part 2 test has been met for at least one of the 
conditions identified in Part 1, there was no need to analyze all of 
them. HHS Basis for Rec. at 25 n.9.
    \36\ The anorexia indication reflects anorexia due to a medical 
condition (e.g., HIV/AIDS) and does not represent anorexia nervosa. 
HHS Basis for Rec. at 25 n.10.
    \37\ While anxiety was not one of the specific medical 
conditions identified by OASH, it is included herein because anxiety 
was identified by the FDA during the Part 2 review of State-level 
usage data. FDA considered the medical use of marijuana for the 
treatment of anxiety of importance to evaluate given the reported 
prevalence of marijuana use for the treatment of anxiety regardless 
of the legal status of such use in a given jurisdiction. HHS Basis 
for Rec. at 25 n.11.
---------------------------------------------------------------------------

    In evaluating whether there exists some credible scientific support 
under Part 2 of the CAMU test for a particular use, factors in favor of 
a positive finding included whether: (1) favorable clinical studies of 
the medical use of marijuana, although not necessarily adequate and 
well-controlled clinical studies that would support approval of an NDA, 
have been published in peer-reviewed journals or (2) qualified expert 
organizations (e.g., academic groups, professional societies, or 
government agencies) have opined in favor of the medical use or 
provided guidance to HCPs on the medical use. Factors that weigh 
against a finding that Part 2 of the CAMU test is met included whether: 
(1) data or information indicate that medical use of the substance is 
associated with unacceptably high

[[Page 44618]]

safety risks for the likely patient population, e.g., due to toxicity 
concerns; (2) clinical studies with negative efficacy findings for the 
medical use of marijuana have been published in peer reviewed journals; 
or (3) qualified expert organizations (e.g., academic or professional 
societies, government agencies) recommend against the medical use of 
marijuana based on the available data at the time of their position 
statement. HHS Basis for Rec. at 25.
    FDA's review of the available information identified mixed findings 
of effectiveness across indications, ranging from data showing 
inconclusive findings to considerable evidence in favor of 
effectiveness, depending on the source. The largest evidence base for 
effectiveness exists for marijuana use within the pain indication (in 
particular, neuropathic pain). Numerous systematic reviews concluded 
that there exists some level of evidence supporting the use of 
marijuana for chronic pain. The 2017 NASEM report concluded there was 
``substantial evidence'' \38\ supporting the use of cannabis products 
relevant to this review for pain, as have other reviews. The AHRQ 
living systematic review has concluded that there is some support for 
the use of marijuana-related products in the treatment of chronic pain, 
but overall concluded these effects were small and the increased risk 
of dizziness, nausea, and sedation may limit the benefit. A systematic 
review of scientific and medical literature was conducted in 2023 by 
the University of Florida (``UF'') under contract with FDA. UF 
epidemiologists identified some data supporting effectiveness of 
marijuana, including some within their own meta-analysis; however, they 
ultimately concluded the results are inconclusive or mixed. FDA also 
conducted a separate analysis of published scientific reviews, several 
of which drew conclusions similar to those of UF. HHS Basis for Rec. at 
25-26.
---------------------------------------------------------------------------

    \38\ The term ``substantial evidence'' refers to language used 
within the 2017 NASEM report and is not meant to represent 
``substantial evidence'' as defined in 21 U.S.C. 355(d). HHS Basis 
for Rec. at 26 n.12.
---------------------------------------------------------------------------

    UF evaluated other therapeutic conditions mentioned above, i.e., 
anorexia, anxiety, epilepsy, IBD, nausea, and PTSD, employing a similar 
systematic review of scientific and medical literature. UF found that 
there is low- to moderate-quality evidence supporting the use of 
marijuana as medical treatment for outcomes in anorexia, nausea and 
vomiting, and PTSD. FDA's review of systematic reviews showed mixed 
results for these indications. In particular, FDA found that the 
potential for psychiatric adverse events associated with treating PTSD 
with marijuana may be more substantial than any limited benefit in 
observational studies. Although UF did not conclude that there was 
evidence in support of the effectiveness of marijuana in IBD, both 
their review and other systematic reviews found some benefit with 
respect to subjective symptoms in this condition. With regard to 
epilepsy and anxiety, both UF's review and FDA's review of other 
systematic reviews did not find support for marijuana providing benefit 
in the treatment of these conditions. Where positive results on 
effectiveness outcome measures were found, the effects and the quality 
of evidence were generally in the low-to-moderate range. UF did not 
find high quality evidence supporting worsening of outcomes in any 
indication. HHS Basis for Rec. at 26.
    FDA concluded that none of the evidence from the systematic reviews 
included in the CAMU test Part 2 analysis identified any safety 
concerns that would preclude the use of marijuana in the indications 
for which there exists some credible scientific support for its 
therapeutic benefit. FDA assessed the clinical safety data identified 
in the literature from controlled trials as generally consistent 
between sources but limited in the rigor of safety reporting. FDA also 
explained that the vast majority of the observational studies evaluated 
in the context of medical use were excluded from the final synthesis of 
evidence due to concerns regarding their quality (e.g., only one 
observational study for the anxiety indication and one for the PTSD 
indication were included). According to FDA, data on safety from both 
clinical trials and observational studies were generally scarce, but 
the literature shows that marijuana has more AEs when compared to a 
placebo or active control group, however, typically in the mild to 
moderate severity range. HHS Basis for Rec. at 26.
    FDA also reviewed results from State reporting data from 37 States 
with medical marijuana programs and surveys of patients using marijuana 
in Maryland and Minnesota, which had data available for review. Surveys 
of patients using marijuana in these two States found most patients did 
not report any side effects and those that did report side effects 
mostly described them as mild. Neither State's databases included 
patients who chose to stop using marijuana, which FDA noted might 
result in an overestimation of positive experiences. HHS Basis for Rec. 
at 27.
    As of August 2023, FDA reported that the real-world data sources 
available to FDA, in general, lack the necessary elements to identify 
the exposure (i.e., to marijuana), to distinguish the reason for use 
(medical vs. recreational) and, if applicable, the condition that 
prompted its medical use, and to permit sound inferential analyses. 
Therefore, they were not included in HHS's review. HHS Basis for Rec. 
at 27.
    According to FDA, data from United States national surveys, in 
general, lacked details on patient characteristics and factors that 
prompted the use of marijuana for medical purposes, and data collection 
for these surveys was impacted by the COVID-19 pandemic. FDA observed 
that, despite these limitations, the data suggested that medical use of 
marijuana increases as age increases. Only data from one survey 
provided information on the intended indication for use, suggesting 
that individuals often use marijuana to improve or manage conditions 
such as depression, anxiety, PTSD, pain, headaches or migraines, sleep 
disorders, nausea and vomiting, lack of appetite, and muscle spasms, 
but only approximately half of them reportedly had ever asked a health 
care professional for a recommendation to use medical marijuana. HHS 
Basis for Rec. at 27.
    Additionally, although the safety data obtained from use in a 
medical context are considered to be the most relevant for the CAMU 
analysis, FDA evaluated the safety of marijuana in the nonmedical 
setting to inform the potential for more severe outcomes. Specifically, 
FDA evaluated safety outcomes related to marijuana use in the setting 
of nonmedical use, use of uncertain intent, and unintentional exposure 
through a variety of epidemiological data sources and in relation to 
several comparator substances controlled under the CSA, including drugs 
in schedule I: heroin (an illicit opioid drug); schedule II: 
hydrocodone and oxycodone (approved opioid prescription drug products), 
cocaine and fentanyl (largely illicitly produced drugs in the 
nonmedical use setting, although there are approved prescription 
drugs); schedule III: ketamine (an approved prescription drug); and 
schedule IV: zolpidem, benzodiazepines, and tramadol (approved 
prescription drugs). According to FDA, the comparative data demonstrate 
that, even in the context of nonmedical use, marijuana has a less 
concerning overall safety profile relative to the comparators for a 
number of important outcomes (e.g., single substance use overdose 
death,

[[Page 44619]]

hospitalizations). However, FDA observed that in young children, 
population-adjusted rates of ED visits and hospitalizations involving 
marijuana poisoning were higher than heroin, cocaine, and 
benzodiazepines for the periods studied. Of note, some of the 
comparator substances are approved for use in conditions similar to the 
indications for which marijuana was evaluated in the CAMU analysis 
(e.g., opioids for pain, benzodiazepines for anxiety-related 
conditions). HHS Basis for Rec. at 27.
    FDA also considered position statements from professional 
organizations relevant to the indications discussed. The vast majority 
of professional organizations did not recommend the use of marijuana in 
their respective specialties; however, none specifically recommended 
against it, with the exception of the American Psychiatric Association, 
which stated that marijuana is known to worsen certain psychiatric 
conditions. HHS Basis for Rec. at 27-28.
    On balance, FDA found the available data indicated that there is 
some credible scientific support for the use of marijuana in the 
treatment of chronic pain, anorexia related to a medical condition, and 
nausea and vomiting, with varying degrees of support and consistency of 
findings. Additionally, no safety concerns were identified in FDA's 
review that would indicate that medical use of marijuana poses 
unacceptably high safety risks for the indications where there is some 
credible scientific evidence supporting its therapeutic use. HHS Basis 
for Rec. at 28.
    Based on the totality of the available data, FDA concluded that 
there exists some credible scientific support for the medical use of 
marijuana in at least one of the indications for which there is 
widespread current experience in the United States, as identified by 
OASH under Part 1 of the CAMU test. The indications evaluated were 
anorexia related to a medical condition, anxiety, epilepsy, IBD, nausea 
and vomiting (e.g., chemotherapy-induced), pain, and PTSD. FDA 
clarified that the analysis and conclusions on the available data are 
not meant to imply that safety and effectiveness have been established 
for marijuana that would support FDA approval of a marijuana drug 
product for a particular indication. However, FDA determined that the 
available data do provide some level of support for the way marijuana 
is being recommended by health care practitioners in clinical practice. 
Thus, based on the widespread HCP experience and the extent of medical 
use evaluated by OASH under the Part 1 test, and FDA's evaluation of 
available credible scientific support described herein for at least 
some therapeutic uses identified in the Part 1 test, HHS recommended a 
finding that, for purposes of the drug scheduling criteria in 21 U.S.C. 
812(b), marijuana has a CAMU for: anorexia related to a medical 
condition; nausea and vomiting (e.g., chemotherapy-induced); and pain. 
HHS Basis for Rec. at 28.
    The Attorney General has considered HHS's recommendations and 
conclusions and accords HHS's scientific and medical determinations 
binding weight until the initiation of the formal rulemaking process. 
See OLC Op. at *24. Applying HHS's two-part test, and in light of OLC's 
legal opinion that the HHS's test is sufficient under the CSA, the 
Attorney General concurs with HHS's conclusion, for purposes of the 
initiation of these rulemaking proceedings, that there is a CAMU for 
marijuana.

3. Level of Physical or Psychological Dependence

    As a result of its most recent evaluation, which incorporates post-
2016 data into its analysis, HHS has recommended a finding that abuse 
of marijuana may lead to moderate or low physical dependence or high 
psychological dependence. HHS Basis for Rec. at 65.
    According to HHS, clinical studies have demonstrated that marijuana 
produces physical and psychological dependence. Regarding physical 
dependence, as evidenced by its associated withdrawal symptomology upon 
abrupt discontinuation of use, the most commonly reported marijuana 
withdrawal symptoms in clinical investigations are sleep difficulties, 
decreased appetite and weight loss, craving, irritability, anger, 
anxiety or nervousness, and restlessness. Marijuana withdrawal symptoms 
typically peak within two to six days and decline over one to two weeks 
as [Delta]9-THC is eliminated. Similarly, the drug labels for the FDA-
approved drug products Marinol and Syndros state that, following 
chronic administration of dronabinol, drug discontinuation leads to 
irritability, insomnia, and restlessness at 12 hours, and by 24 hours 
the withdrawal symptoms can include hot flashes, sweating, rhinorrhea, 
diarrhea, and anorexia. HHS Basis for Rec. at 64.
    HHS observes that marijuana withdrawal syndrome has been reported 
in individuals with heavy, chronic marijuana use, but its occurrence in 
occasional users of marijuana has not been established. The marijuana 
withdrawal syndrome appears to be relatively mild compared to the 
withdrawal syndrome associated with alcohol, which can include more 
serious symptoms such as agitation, paranoia, seizures and even death. 
Multiple studies comparing the withdrawal symptoms associated with 
marijuana and tobacco demonstrate that the magnitude and time course of 
the two withdrawal syndromes are similar. HHS Basis for Rec. at 64.
    HHS also notes that the ability of marijuana to produce psychic 
dependence is shown through its ability to produce rewarding effects 
that underlie its nonmedical use and epidemiological outcomes related 
to abuse, as detailed in the first finding on abuse potential. HHS 
Basis for Rec. at 64-65.
    Based on the evidence, HHS determined that the abuse of marijuana 
may lead to moderate or low physical dependence, depending on frequency 
and degree of marijuana exposure. HHS further concluded that marijuana 
can produce psychic dependence in some individuals, but that the 
likelihood of serious outcomes is low, suggesting that high 
psychological dependence does not occur in most individuals who use 
marijuana. HHS Basis for Rec. at 65.
    The Attorney General has considered HHS's recommendations and 
conclusions and accords HHS's scientific and medical determinations 
binding weight at this stage of the scheduling process. See OLC Op. at 
*22 n.6. For purposes of the initiation of these rulemaking 
proceedings, the Attorney General concurs with HHS's conclusion that 
the abuse of marijuana may lead to moderate or low physical dependence, 
depending on frequency and degree of marijuana exposure.
Determination To Propose Rescheduling Marijuana to Schedule III
    HHS has recommended a finding that marijuana has a CAMU. HHS Basis 
for Rec. at 63-64. After considering the foregoing facts and data and 
the recommendation of HHS, and after according binding weight to HHS's 
scientific and medical determinations, the Attorney General concludes 
that there is, at present, substantial evidence that marijuana does not 
warrant control under schedule I of the CSA. Accordingly, the Attorney 
General is issuing this notice of proposed rulemaking to initiate 
rulemaking proceedings to reschedule marijuana. 21 U.S.C. 811(b).
    HHS has recommended that marijuana be transferred from schedule I 
to schedule III rather than from schedule I to schedule II based on its

[[Page 44620]]

evaluation that the drug has a relatively lower level of abuse compared 
to drugs currently scheduled in schedules I and II and its evaluation 
that marijuana may lead to moderate or low physical dependence and has 
a low likelihood of psychic dependence. Consistent with HHS's analysis, 
the Attorney General has determined at this initial stage that 
marijuana does not appear to meet the elements of a schedule II drug, 
which include a high potential for abuse and a likelihood of severe 
physiological or physical dependence from such abuse. 21 U.S.C. 
812(b)(3). Rather, marijuana's profile as a drug with a lower degree of 
abuse potential than schedule I (e.g., heroin) and schedule II (e.g., 
fentanyl, cocaine) drugs and a moderate to low level of physical 
dependence militates in favor of rescheduling it in schedule III. 
Accordingly, in this notice of proposed rulemaking, the Attorney 
General is proposing to reschedule marijuana in schedule III and 
solicits comments on these preliminary findings.
Types of Marijuana To Be Rescheduled
    This rescheduling of marijuana would apply to marijuana as listed 
in 21 CFR 1308.11(d)(23). The rescheduling also would apply to 
marijuana extracts as defined in 21 CFR 1308.11(d)(58) because they 
meet the statutory definition of marijuana and, prior to 2017, were 
included in 21 CFR 1308.11(d)(23). See Establishment of a New Drug Code 
for Marihuana Extract, 81 FR 90194 (Dec. 14, 2016). In addition, this 
proposal would apply to [Delta]9-THC derived from the marijuana plant 
(other than the mature stalks and seeds) that falls outside the 
definition of hemp, because it meets the statutory definition of 
marijuana.
    This proposal would not apply to synthetically derived THC, which 
is outside the CSA's definition of marijuana. Those 
tetrahydrocannabinols that can be derived only through a process of 
artificial synthesis (e.g., delta-10-tetrahydrocannabinol) are 
excluded. HHS provided a recommendation only relating to ``marijuana'' 
as defined in the CSA. That definition is limited to the plant (other 
than the mature stalks and seeds) and derivatives of the plant. 
Therefore, synthetic THC will remain in schedule I. This rulemaking 
would not affect the status of hemp (as defined in 7 U.S.C. 1639o), 
because hemp is excluded from the definition of marijuana. This 
rulemaking is not proposing to reschedule any drug product containing 
marijuana or THC that previously has been rescheduled out of schedule I 
(e.g., Marinol and Syndros). Nor does it impact the status of any 
previously scheduled synthetic cannabinoids.

VIII. International Treaty Obligations

    In proposing an appropriate schedule for marijuana, the Attorney 
General must also consider compliance with the treaty obligations of 
the United States. As the CSA recognizes, the United States is a party 
to the Single Convention. 21 U.S.C. 801(7). Parties to the Single 
Convention are obligated to maintain various control provisions related 
to the drugs that are covered by the treaty. See, e.g., Single 
Convention arts. 2, 4. Congress enacted many of the CSA's provisions 
for the specific purpose of ensuring U.S. compliance with the treaty. 
See OLC Op. at *27. Among these is a scheduling provision, 21 U.S.C. 
811(d)(1). Section 811(d)(1) provides that, where a drug is subject to 
control under the Single Convention, the Attorney General must ``issue 
an order controlling such drug under the schedule he deems most 
appropriate to carry out such [treaty] obligations, without regard to 
the findings required by [21 U.S.C. 811(a) or 812(b)] and without 
regard to the procedures prescribed by [21 U.S.C. 811(a) and (b)].'' 
\39\
---------------------------------------------------------------------------

    \39\ As noted above, OLC and the D.C. Circuit do not understand 
the ``without regard'' clause in section 811(d)(1) as prohibiting 
the Attorney General from following the normal scheduling practices 
when international obligations are involved. Instead, they have 
interpreted it as requiring the Attorney General to identify which 
schedules would satisfy the international obligations of the United 
States with respect to a particular drug and, if more than one 
schedule would do so, to select among schedules using the procedures 
set forth in sections 811(a), 811(b), and 812(b). See OLC Op. at *29 
n.8; NORML II, 559 F.2d at 747.
---------------------------------------------------------------------------

    Marijuana is a drug covered in the Single Convention under the term 
``cannabis.'' \40\ OLC initially advised in 1972 that controls under 
Article 21 of the Single Convention would not be satisfied if marijuana 
were listed in schedule III, IV, or V of the CSA. Memorandum for John 
E. Ingersoll, Director, Bureau of Narcotics and Dangerous Drugs, from 
Mary C. Lawton, Deputy Assistant Attorney General, Office of Legal 
Counsel, Re: Petition to Decontrol Marihuana; Interpretation of Section 
201 of the Controlled Substances Act of 1970 at 12-13 (Aug. 21, 1972). 
However, OLC has reexamined the conclusion of its 1972 memorandum, 
taking into account statutory amendments since 1972 and a possibility 
it did not consider in 1972: placing marijuana into schedule III while 
issuing regulations that would enable the United States to comply with 
its international obligations. OLC Op. at *4, 26-35. OLC has concluded 
that both the Single Convention and the CSA allow the Attorney General 
to satisfy the treaty obligations of the United States with respect to 
marijuana by supplementing scheduling decisions with additional 
controls under the CSA. Id.
---------------------------------------------------------------------------

    \40\ Under the Single Convention, ```[c]annabis plant' means any 
plant of the genus Cannabis.'' Single Convention art. 1(1)(c). The 
Single Convention defines ``cannabis'' to mean ``the flowering or 
fruiting tops of the cannabis plant (excluding the seeds and leaves 
when not accompanied by the tops) from which the resin has not been 
extracted, by whatever name they may be designated.'' Id. art. 
1(1)(b). This definition of ``cannabis'' under the Single Convention 
is slightly less inclusive in certain respects than the CSA 
definition of ``marijuana,'' which includes all parts of the 
cannabis plant except for the mature stalks, sterilized seeds, oil 
from the seeds, and certain derivatives thereof. See 21 U.S.C. 
802(16). Cannabis and cannabis resin are included in the list of 
drugs in Schedule I of the Single Convention, and cannabis is 
subject to the same controls as Schedule I drugs as well as 
additional controls. See Single Convention art. 2(6); id. art. 28.
---------------------------------------------------------------------------

    If marijuana were listed in schedule III, most of the Single 
Convention's obligations would continue to be met by CSA statutory 
authorities and associated regulations. See OLC Op. at *33-34. One 
potential gap concerns the quota on manufacturing cannabis required by 
Article 21 of the Convention, but that gap can be filled using the 
CSA's regulatory authorities. See id. at *34; see also, e.g., 21 U.S.C. 
821 (authorizing the Attorney General to impose restrictions 
``relate[ed] to the . . . control of the manufacture'' of a drug); id. 
871(b) (authorizing the Attorney General to issue regulations 
``necessary and appropriate for the efficient execution of his 
functions under this subchapter''); id. 822(b) (allowing the Attorney 
General to regulate ``the extent'' of manufacture of a drug through 
registration); id. 823(e) (requiring the Attorney General to register 
an applicant to manufacture a schedule III drug ``unless he determines 
that the issuance of such registration is inconsistent with the public 
interest'').
    In addition, if marijuana is transferred into schedule III, DEA 
will continue to have authority to maintain its existing regulatory 
scheme, located at 21 CFR part 1318, governing the registration of 
manufacturers seeking to plant, grow, cultivate, or harvest marijuana, 
as required to comply with Articles 23 and 28 of the Single Convention. 
Authority for those regulations currently flows from 21 U.S.C. 823(a), 
which is applicable to drugs in schedules I and II. OLC has concluded, 
however, that 21 U.S.C. 823(e), which is applicable to drugs in 
schedules III, IV, and V, provides an alternative source of authority 
for complying with Articles 23 and 28 of the Single Convention. See

[[Page 44621]]

OLC Op. at *34 n.9. The CSA also recognizes that the United States is 
also a party to the Convention on Psychotropic Substances, Feb. 21, 
1971, 32 U.S.T. 543, 1019 U.N.T.S. 175 (``Convention on Psychotropic 
Substances''). See also 21 U.S.C. 801a(2). As with the Single 
Convention, parties to the Convention on Psychotropic Substances are 
obligated to take various control measures related to the drugs that 
are covered by the treaty. Id. Congress implemented the additional 
authority necessary to comply with the Convention on Psychotropic 
Substances through various amendments to the CSA. Id. 801a(2)-(3).
    [Delta]9-THC is a substance covered by schedule II of the 
Convention on Psychotropic Substances. In this rule, DOJ proposes to 
reschedule [Delta]9-THC that falls within the CSA's definition of 
marijuana into CSA schedule III. As is the case for marijuana under the 
Single Convention, the controls available under CSA schedule III are 
sufficient to comply with the requirements of the Convention on 
Psychotropic Substances with respect to [Delta]9-THC, although 
additional regulatory action may be necessary to implement certain 
Convention requirements, such as the export and import authorizations 
required by Article 12. See, e.g., Schedules of Controlled Substances: 
Rescheduling of the Food and Drug Administration Approved Product 
Containing Synthetic Dronabinol [(-)-D \9\ -(trans)-
Tetrahydrocannabinol] in Sesame Oil and Encapsulated in Soft Gelatin 
Capsules From Schedule II to Schedule III, 64 FR 35928, 35928 (July 2, 
1999). Compare, e.g., Convention on Psychotropic Substances art. 12(1) 
(requiring export and import authorizations for substances in 
Convention Schedule II), with 21 U.S.C. 952(b)(2) (authorizing import 
permits for CSA schedule III substances), and id. 953(e)(2) 
(authorizing export permits for CSA schedule III substances).
    Accordingly, concurrent with this rulemaking, DEA will consider the 
marijuana-specific controls that would be necessary to meet U.S. 
obligations under the Single Convention and the Convention on 
Psychotropic Substances in the event that marijuana is rescheduled to 
schedule III, and, to the extent they are needed if marijuana is 
rescheduled, will seek to finalize any such regulations as soon as 
possible.

IX. Requirements for Handling Marijuana and Other Applicable Controls

    If marijuana is transferred to schedule III, the regulatory 
controls applicable to schedule III controlled substances would apply, 
as appropriate, along with existing marijuana-specific requirements and 
any additional controls that might be implemented, including those that 
might be implemented to meet U.S. treaty obligations. The manufacture, 
distribution, dispensing, and possession of marijuana would also remain 
subject to applicable criminal prohibitions under the CSA. 21 U.S.C. 
841-844.
    In addition, marijuana would remain subject to applicable 
provisions of the FDCA. For example, under the FDCA, a drug containing 
a substance within the CSA's definition of ``marijuana'' would need FDA 
approval to be lawfully ``introduce[d] or deliver[ed] for introduction 
into interstate commerce,'' unless an IND is in effect for that drug. 
See 21 U.S.C. 355(a), 355(i), 331(d). To date, although there have been 
INDs for drugs containing a substance within the CSA's definition of 
``marijuana,'' no such drugs have been approved by FDA.
    DOJ is seeking comment on the practical consequences of 
rescheduling marijuana into schedule III under the relevant statutory 
frameworks.

Conclusion

    Based on the legal opinion of OLC and consideration of the 
scientific and medical evaluation and accompanying recommendation of 
HHS, the Attorney General is initiating a rulemaking that proposes the 
placement of marijuana in schedule III of the CSA. DOJ is soliciting 
comments on this proposal.

X. Regulatory Analyses

1. Executive Orders 12866 (Regulatory Planning and Review), 13563 
(Improving Regulation and Regulatory Review) and 14094 (Modernizing 
Regulatory Review)

    In accordance with 21 U.S.C. 811(a), this scheduling action is 
subject to formal rulemaking procedures done ``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 criteria for 
removing a drug or other substance from the list of controlled 
substances. Such actions are exempt from review by the Office of 
Management and Budget pursuant to section 3(d)(1) of Executive Order 
12866 and the principles reaffirmed in Executive Order 13563 and 14094.
    While this scheduling action is exempt from review under Executive 
Order 12866, DOJ recognizes this action may have unique economic 
impacts. As stated above, marijuana is subject to a number of State 
laws that have allowed a multibillion dollar industry to develop. DOJ 
acknowledges that there may be large impacts related to Federal taxes 
and research and development investment for the pharmaceutical 
industry, among other things. DOJ is specifically soliciting comments 
on the economic impact of this proposed rule. DOJ will revise this 
section at the final rule stage if warranted after consideration of any 
comments received.

2. Executive Order 12988 (Civil Justice Reform)

    This proposed regulation meets the applicable standards set forth 
in sections 3(a) and 3(b)(2) of Executive Order 12988 to eliminate 
drafting errors and ambiguity, minimize litigation, provide a clear 
legal standard for affected conduct, and promote simplification and 
burden reduction.

3. Executive Order 13132 (Federalism)

    This rulemaking does not have federalism implications warranting 
the application of Executive Order 13132. The rule does not have 
substantial direct effects on the States, on the relationship between 
the Federal Government and the States, or the distribution of power and 
responsibilities among the various levels of government.

4. Executive Order 13175 (Consultation and Coordination With Indian 
Tribal Governments)

    This proposed rule does not have Tribal implications warranting the 
application of Executive Order 13175. This rule 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.

5. Regulatory Flexibility Act

    DOJ has concluded that this action may have a significant economic 
impact on a substantial number of small entities under the Regulatory 
Flexibility Act, 5 U.S.C. 601 et seq. For example, section 280E of the 
Internal Revenue Code bars businesses from claiming tax deductions for 
otherwise allowable expenses where the business ``consists of 
trafficking in controlled substances (within the meaning of schedule I 
and II of the Controlled Substances Act).'' 26 U.S.C. 280E. If 
marijuana is ultimately transferred to schedule III, section 280E would 
no longer serve as a statutory bar to claiming deductions for those 
expenses. In addition, small entities engaged in research on marijuana 
may

[[Page 44622]]

be subject to different research protocols set by DEA if the research 
is conducted on a schedule III substance rather than a schedule I 
substance.\41\ However, DOJ is currently not in a position to estimate 
the number of small entities affected by these or other potential 
effects of this action. DOJ seeks comment and additional information to 
inform its analysis.
---------------------------------------------------------------------------

    \41\ See Drug Enforcement Admin., Researcher's Manual 18-21 
(2022), https://www.deadiversion.usdoj.gov/GDP/(DEA-DC-057)(E.O.-
DEA217)_Researchers_Manual_Final_signed.pdf.
---------------------------------------------------------------------------

6. Unfunded Mandates Reform Act of 1995

    In accordance with the Unfunded Mandates Reform Act of 1995 
(``UMRA''), 2 U.S.C. 1501 et seq., DOJ has determined that this 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.'' See 2 U.S.C. 1532(a). Therefore, 
neither a Small Government Agency Plan nor any other action is required 
under UMRA.

7. Paperwork Reduction Act of 1995

    This action does not impose any new or revised ``collection[s] of 
information'' as defined by the Paperwork Reduction Act of 1995, 44 
U.S.C. 3502(3).

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 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. Amend Sec.  1308.11 by:
0
a. Removing paragraphs (d)(23) and (58).
0
b. Redesignating paragraphs (d)(24) through (57) and (59) through (104) 
as paragraphs (d)(23) through (102), respectively.
0
c. Revising newly redesignated paragraph (d)(30).
    The revision reads as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (d) * * *
    (30) Tetrahydrocannabinols--7370
    (i) Meaning tetrahydrocannabinols, except as in paragraphs 
(d)(30)(ii) and (iii) of this section, naturally contained in a plant 
of the genus Cannabis (cannabis plant), as well as synthetic 
equivalents of the substances contained in the cannabis plant, or in 
the resinous extracts of such plant, or synthetic substances, 
derivatives, and their isomers with similar chemical structure and 
pharmacological activity to those substances contained in the plant.
    (ii) Tetrahydrocannabinols does not include any material, compound, 
mixture, or preparation that falls within the definition of hemp set 
forth in 7 U.S.C. 1639o.
    (iii) Tetrahydrocannabinols does not include any substance that 
falls within the definition of marijuana set forth in 21 U.S.C. 
802(16).
* * * * *
0
3. Amend Sec.  1308.13 by adding paragraphs (h) through (j) to read as 
follows:


Sec.  1308.13  Schedule III.

* * * * *
    (h) Marijuana. Marijuana, as defined in 21 U.S.C. 802(16).
    (i) Marijuana extract. Marijuana extract, meaning an extract 
containing one or more cannabinoids that has been derived from any 
plant of the genus Cannabis, containing greater than 0.3 percent delta-
9-tetrahydrocannabinol on a dry weight basis, other than the separated 
resin (whether crude or purified) obtained from the plant.
    (j) Naturally derived delta-9-tetrahydrocannabinols. (1) Meaning 
those delta-9-tetrahydrocannabinols, except as in paragraphs (j)(2) and 
(3) of this section, that are naturally contained in a plant of the 
genus Cannabis (cannabis plant).
    (2) Naturally derived delta-9-tetrahydrocannabinols do not include 
any material, compound, mixture, or preparation that falls within the 
definition of hemp set forth in 7 U.S.C. 1639o.
    (3) Naturally derived delta-9-tetrahydrocannabinols do not include 
any delta-9-tetrahydrocannabinols contained in substances excluded from 
the definition of marijuana as set forth in 21 U.S.C. 802(16)(B)(ii).

    Dated: May 16, 2024.
Merrick B. Garland,
Attorney General.
[FR Doc. 2024-11137 Filed 5-17-24; 11:15 am]
BILLING CODE 4410-09-P