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Proposed Rule2026-20943

Schedules of Controlled Substances: Temporary Placement of 7- Hydroxymitragynine and Mitragynine Pseudoindoxyl Above a Specified Threshold in Schedule I

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Published

October 14, 2026

Issuing agencies

Justice DepartmentDrug Enforcement Administration

Abstract

The Administrator of the Drug Enforcement Administration (DEA) is issuing this notice of intent to publish a temporary order to schedule 7-hydroxymitragynine and mitragynine pseudoindoxyl (including their isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, whenever the existence of such isomers, esters, ethers, and salts is possible) when either substance alone, or their combined amount if both are present, is above a specified threshold, in schedule I of the Controlled Substances Act (CSA). Based on a different threshold provided by the Department of Health and Human Services (HHS) in July of 2025, DEA published a notice of intent to temporarily schedule 7-hydroxymitragynine above that lower threshold on July 7, 2026. Additionally, DEA published a temporary order placing mitragynine pseudoindoxyl without a threshold in schedule I of the CSA on August 26, 2026. On October 8, 2026, HHS sent a letter recommending that DEA place of the CSA 7-hydroxymitragynine and mitragynine pseudoindoxyl in schedule I when either substance alone, or their combined amount if both are present, is above a new specified threshold. Based on the October 8, 2026 letter, DEA is issuing this notice of intent. While the new threshold recommended by HHS would permit certain products to remain in the marketplace without being subject to schedule I controls, neither HHS nor DEA has made a finding that these substances are safe to use at below-threshold levels. When a temporary order is issued, it will impose the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis with, or possess) or propose to handle 7- hydroxymitragynine and/or mitragynine pseudoindoxyl above the specified threshold. In a separate document contained in this issue of the Federal Register, DEA is withdrawing the July 7, 2026 notice of intent related to 7-hydroxymitragynine. The August 26, 2026 temporary order placing mitragynine pseudoindoxyl in schedule I of the CSA without a threshold remains in effect until either it expires or the new temporary order is published and the previous order is withdrawn, whichever occurs first.

Full Text

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<title>Federal Register, Volume 91 Issue 197 (Wednesday, October 14, 2026)</title>
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[Federal Register Volume 91, Number 197 (Wednesday, October 14, 2026)]
[Proposed Rules]
[Pages 65370-65381]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-20943]

[[Page 65369]]

Vol. 91

Wednesday,

No. 197

October 14, 2026

Part III

Department of Justice

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Drug Enforcement Administration

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21 CFR Part 1308

Schedules of Controlled Substances: Temporary Placement of 7-
Hydroxymitragynine and Mitragynine Pseudoindoxyl Above a Specified
Threshold in Schedule I and Temporary Placement of MGM-15 and MGM-16 in
Schedule I; Proposed Rules

Federal Register / Vol. 91 , No. 197 / Wednesday, October 14, 2026 /
Proposed Rules

[[Page 65370]]

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-1570]

Schedules of Controlled Substances: Temporary Placement of 7-
Hydroxymitragynine and Mitragynine Pseudoindoxyl Above a Specified
Threshold in Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Proposed amendment; notice of intent.

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SUMMARY: The Administrator of the Drug Enforcement Administration (DEA)
is issuing this notice of intent to publish a temporary order to
schedule 7-hydroxymitragynine and mitragynine pseudoindoxyl (including
their isomers, esters, ethers, salts, and salts of isomers, esters, and
ethers, whenever the existence of such isomers, esters, ethers, and
salts is possible) when either substance alone, or their combined
amount if both are present, is above a specified threshold, in schedule
I of the Controlled Substances Act (CSA). Based on a different
threshold provided by the Department of Health and Human Services (HHS)
in July of 2025, DEA published a notice of intent to temporarily
schedule 7-hydroxymitragynine above that lower threshold on July 7,
2026. Additionally, DEA published a temporary order placing mitragynine
pseudoindoxyl without a threshold in schedule I of the CSA on August
26, 2026. On October 8, 2026, HHS sent a letter recommending that DEA
place of the CSA 7-hydroxymitragynine and mitragynine pseudoindoxyl in
schedule I when either substance alone, or their combined amount if
both are present, is above a new specified threshold. Based on the
October 8, 2026 letter, DEA is issuing this notice of intent. While the
new threshold recommended by HHS would permit certain products to
remain in the marketplace without being subject to schedule I controls,
neither HHS nor DEA has made a finding that these substances are safe
to use at below-threshold levels. When a temporary order is issued, it
will impose the regulatory controls and administrative, civil, and
criminal sanctions applicable to schedule I controlled substances on
persons who handle (manufacture, distribute, reverse distribute,
import, export, engage in research, conduct instructional activities or
chemical analysis with, or possess) or propose to handle 7-
hydroxymitragynine and/or mitragynine pseudoindoxyl above the specified
threshold. In a separate document contained in this issue of the
Federal Register, DEA is withdrawing the July 7, 2026 notice of intent
related to 7-hydroxymitragynine. The August 26, 2026 temporary order
placing mitragynine pseudoindoxyl in schedule I of the CSA without a
threshold remains in effect until either it expires or the new
temporary order is published and the previous order is withdrawn,
whichever occurs first.

DATES: October 14, 2026.

ADDRESSES: 8701 Morrissette Drive, Springfield, Virginia 22152.

FOR FURTHER INFORMATION CONTACT: Drug and Chemical Evaluation Section,
Diversion Control Division, Drug Enforcement Administration; Telephone:
(571) 362-3249.

SUPPLEMENTARY INFORMATION: The notice of intent contained in this
document is issued pursuant to the temporary scheduling provisions of
21 U.S.C. 811(h). The Drug Enforcement Administration (DEA) intends to
issue a temporary scheduling order \1\ (in the form of a temporary
amendment) to add 7-hydroxymitragynine \2\ and mitragynine pseudindoxyl
\3\ above a specified threshold described herein, including their
isomers, esters, ethers, salts, and salts of isomers, esters, and
ethers, whenever the existence of such isomers, esters, ethers, and
salts is possible, to schedule I under the Controlled Substances Act
(CSA).\4\ The specified threshold for reflects the recommendation made
by the Assistant Secretary for Health (Assistant Secretary) of the
Department of Health and Human Services (HHS) in a letter to the
Administrator of DEA dated October 8, 2026, which described the
threshold as follows:
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\1\ Though DEA has used the term ``final order'' with respect to
temporary scheduling orders in the past, this notice of intent
adheres to the statutory language of 21 U.S.C. 811(h), which refers
to a ``temporary scheduling order.'' No substantive change is
intended.
\2\ Chemical name: Methyl (E)-2-((2S,3S,7aS)-3-ethyl-7a-hydroxy-
8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-
3-methoxyacrylate (also known as: ([alpha]E,2S,3S,7aS,12bS)-3-ethyl-
l,2,3,4,6,7,7a,12b-octahydro-7a-hydroxy-8-methoxy-a-
(methoxymethylene)-indolo[2,3-a]quinolizine-2-acetic acid, methyl
ester).
\3\ Chemical name: Methyl (E)-2-((1'S,6'S,7'S)-6'-ethyl-4-
methoxy-3-oxo-3',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-2,1'-
indolizine]-7'-yl)-3-methoxyacrylate (commonly known as mitragynine
pseudoindoxyl).
\4\ On July 6, 2026, DEA published a notice of intent to place
7-hydroxymitragynine above a specified threshold in schedule I of
the CSA. See Schedules of Controlled Substance: Temporary Placement
of 7-Hydroxymitragynine Above a Specified Threshold in Schedule I,
91 FR 40917 (July 6, 2026). DEA is withdrawing that notice of intent
elsewhere in this issue of the Federal Register. On August 26, 2026,
DEA published a temporary order that placed mitragynine
pseudoindoxyl, along with two other 7-hydroxymitragynine-related
substances, in schedule I of the CSA. See Schedules of Controlled
Substances: Temporary Placement of Mitragynine Pseudoindoxyl, MGM-
15, and MGM-16 in Schedule I, 91 FR 54948 (Aug. 26, 2026). That
temporary order is effective until August 26, 2028, or until a new
temporary order placing mitragynine pseudindoxyl above a specified
threshold is published and the previous order withdrawn, whichever
occurs first.
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The substances [7-hydroxymitragynine] and [mitragynine
pseudoindoxyl] be controlled in schedule I [pursuant to 21 U.S.C.
811(h)] when either substance alone, or their combined amount if both
present, is:
(A) Above a specified threshold concentration, that is, greater
than 1 mg per gram (for solid powders, encapsulated material, or other
solid forms) or greater than 1 mg per milliliter (for liquid
preparations), OR
(B) The mass of mitragynine present divided by the mass of [7-
hydroxymitragynine], or [mitragynine pseudoindoxyl], or the combined
amount of [7-hydroxymitragynine] and [mitragynine pseudoindoxyl] if
both present, is less than 100.\5\
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\5\ Letter from Assistant Secretary for Health of HHS Admiral
Brian Christine, M.D., to DEA, at page 8 (Oct. 8, 2026).
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The temporary scheduling order will be published in the Federal
Register on or after November 13, 2026.

Legal Authority

The CSA provides the Attorney General with the authority to
temporarily place a substance in schedule I of the CSA for two years
without regard to the requirements of 21 U.S.C. 811(b), if he finds
that such action is necessary to avoid an imminent hazard to public
safety.\6\ In addition, if proceedings to control a substance are
initiated under 21 U.S.C. 811(a)(1) while the substance is temporarily
controlled under section 811(h), the Attorney General may extend the
temporary scheduling for up to one year.\7\
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\6\ 21 U.S.C. 811(h)(1).
\7\ 21 U.S.C. 811(h)(2).
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Where the necessary findings are made, a substance may be
temporarily scheduled if it is not listed in any other schedule under
21 U.S.C. 812, or if there is no exemption or approval in effect for
the substance under section 505 of the Federal Food, Drug, and Cosmetic
Act, 21 U.S.C. 355.\8\ The Attorney General has delegated scheduling
authority

[[Page 65371]]

under 21 U.S.C. 811 to the Administrator of DEA (Administrator).\9\
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\8\ 21 U.S.C. 811(h)(1); 21 CFR part 1308.
\9\ 28 CFR 0.100.
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Background

The CSA requires the Administrator to notify the Secretary of the
Department of Health and Human Services (HHS) of this intent to issue a
temporary scheduling order.\10\ By letter dated October 8, 2026,
Assistant Secretary for Health sent a letter to DEA that, among other
things, recommended controlling 7-hydroxymitragynine and mitragynine
pseudoindoxyl when either substance alone, or their combined amount if
both are present, is above a specified threshold in schedule I. By
letter dated October 8, 2026, the Administrator transmitted the
required notice to place 7-hydroxymitragynine and mitragynine
pseudoindoxyl above the specified threshold recommended by HHS in
schedule I on a temporary basis to the Assistant Secretary.\11\ By
letter dated March 6, 2026, the Assistant Secretary advised that based
on a review by the Food and Drug Administration (FDA), there were
currently no investigational new drug applications (IND) or approved
new drug applications (NDA) for 7-hydroxymitragynine above a specified
threshold. In a separate letter dated January 20, 2026, the Assistant
Secretary advised that based on a review by the Food and Drug
Administration (FDA), there were currently no investigational new drug
applications (IND) or approved new drug applications (NDA) for
mitragynine pseudoindoxyl as of that date. The Assistant Secretary
provided no contrary information in its October 8, 2026, letter.
Neither 7-hydroxymitragynine nor mitragynine pseudoindoxyl is currently
listed in any other schedule than schedule I under the CSA.
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\10\ 21 U.S.C. 811(h)(4).
\11\ The Secretary of HHS has delegated to the Assistant
Secretary for Health of HHS the authority to make domestic drug
scheduling recommendations. Comprehensive Drug Abuse Prevention and
Control Act of 1970, Public Law 91-513, As Amended; Delegation of
Authority, 58 FR 35460 (July 1, 1993).
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To find that placing a substance temporarily in schedule I of the
CSA is necessary to avoid an imminent hazard to public safety, the
Administrator must consider three of the eight factors set forth in 21
U.S.C. 811(c): the substance's history and current pattern of abuse;
the scope, duration and significance of abuse; and what, if any, risk
there is to public health.\12\ This consideration includes any
information indicating actual abuse, diversion from legitimate
channels, and clandestine importation, manufacture, or distribution of
either 7-hydroxymitragynine and mitragynine pseudoindoxyl.\13\
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\12\ 21 U.S.C. 811(c)(4)-(6), (h)(3).
\13\ 21 U.S.C. 811(h)(3).
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Substances meeting the statutory requirements for temporary
scheduling may only be placed in schedule I.\14\ Substances in schedule
I have high potential for abuse, no currently accepted medical use in
treatment in the United States,\15\ and a lack of accepted safety for
use under medical supervision.\16\
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\14\ 21 U.S.C. 811(h)(1).
\15\ When finding schedule I placement on a temporary basis is
necessary to avoid imminent hazard to the public, 21 U.S.C 811(h)
does not require DEA to consider whether the substance has a
currently accepted medical use in treatment in the United States.
Nonetheless, there is no evidence suggesting that 7-
hydroxymitragynine or mitragynine pseudoindoxyl has a currently
accepted medical use in treatment in the United States. First, DEA
looks to whether the drug or substance has FDA approval. When no FDA
approval exists, DEA has traditionally applied a five-part test to
determine whether a drug or substances has a currently accepted
medical use: (1) the drug's chemistry must be known and
reproducible; (2) there must be adequate safety studies; (3) there
must be adequate and well-controlled studies proving efficacy; (4)
the drug must be accepted by qualified experts; and (5) the
scientific evidence must be widely available. Marijuana Scheduling
Petition; Denial of Petition; Remand, 57 FR 10499 (Mar. 26, 1992),
pet. for rev. denied, Alliance for Cannabis Therapeutics v. Drug
Enforcement Admin., 15 F.3d 1131, 1135 (D.C. Cir. 1994). DEA applied
the traditional five-part test and concluded the test was not
satisfied. In a recent published letter in a different context, HHS
applied an additional two-part test to determine currently accepted
medical use for substances that do not satisfy the five-part test:
(1) whether there exists widespread, current experience with medical
use of the substance by licensed health care providers operating in
accordance with implemented jurisdiction-authorized programs, where
medical use is recognized by entities that regulate the practice of
medicine, and, if so, (2) whether there exists some credible
scientific support for at least one of the medical conditions for
which part (1) is satisfied. On April 11, 2024, the Department of
Justice's Office of Legal Counsel (OLC) issued an opinion, which,
among other things, concluded that HHS's two-part test would be
sufficient to establish that a drug has a currently accepted medical
use. Office of Legal Counsel, Memorandum for Merrick B. Garland
Attorney General Re: Questions Related to the Potential Rescheduling
of Marijuana at 3 (April 11, 2024). For purposes of this notice of
intent, there is no evidence that health care providers have
widespread experience with medical use of 7-hydroxymitragynine or
mitragynine pseudoindoxyl is recognized by entities that regulate
the practice of medicine, so the two-part test also is not
satisfied. In HHS's letter dated January 20, 2026, HHS advised DEA
that there were currently no approved new drug applications or
investigational new drug applications for mitragynine pseudoindoxyl.
By letter dated March 6, 2026, the Assistant Secretary responded to
this notice and advised that based on a review by the Food and Drug
Administration (FDA), there were currently no investigational new
drug applications (IND) or approved new drug applications (NDA) for
7-hydroxymitragynine. The Assistant Secretary provided no contrary
information in its October 8, 2026 letter.
\16\ 21 U.S.C. 812(b)(1).
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7-Hydroxymitragynine Above a Specified Threshold

7-Hydroxymitragynine is a psychoactive alkaloid found in Mitragyna
speciosa (M. speciosa) plant, a tropical evergreen tree indigenous to
Southeast Asia. While the use of the plant was once geographically
limited, the use of M. speciosa has since extended to the United States
and other global markets. Among the numerous alkaloids identified in M.
speciosa, the indole alkaloids mitragynine (major) and 7-
hydroxymitragynine (minor) are primarily responsible for the plant's
psychoactive effects. In its natural botanical form, 7-
hydoxymitragynine makes up less than two percent of the total alkaloid
content or occurs in trace amount in M. speciosa. However, 7-
hydroxymitragynine can be synthesized from mitragynine through a one-
step chemical reaction, and it also exists as an active oxidized
metabolite of mitragynine in vivo. Despite the different origins of 7-
hydroxymitragynine, the chemical structures of synthetic and naturally
occurring 7-hydroxymitragynine are identical.
Recently, the United States has seen a proliferation of 7-
hydroxymitragynine products. Evidence suggests that commercially
available products, including extracts and synthetic formulations,
contain a significantly higher concentration of 7-hydroxymitragynine
than what is found in botanical M. speciosa. These products are
commonly sold on the internet and in retail outlets, such as gas
stations and smoke shops, in various forms, including powders, tablets,
gummies, and sublingual films designed for rapid absorption. To date,
the safety profile of these concentrated products in humans remains
unknown because no controlled clinical trials have been conducted to
establish safe consumption limits or standardized dosing.
7-Hydroxymitragynine has opioidergic activity, sharing a similar
pharmacological profile to schedule II opioids like morphine.
Preclinical data indicates that 7-hydroxymitragynine carries a high
abuse potential with safety risks, including tolerance, dependence, and
respiratory depression, which are comparable to those of classic opioid
analgesics. The United States has recently seen an emergence of
products containing 7-hydroxymitragynine, which are often characterized
by

[[Page 65372]]

ambiguous dosages and misleading marketing, frequently being labeled as
``natural M. speciosa extracts.'' While sellers promote these products
for their euphoric and opioidergic effects, evidence demonstrates they
may also contain other opioid alkaloids, such as mitragynine
pseudoindoxyl. These combinations, coupled with a lack of regulatory
oversight, pose significant safety risk to unsuspecting consumers by
exposing them to high doses of opioids. The absence of clinical
evidence to support vendor health claims is deeply concerning.
Consequently, 7-hydroxymitragynine products sold as unregulated dietary
supplements pose significant health risks, as essential information
regarding their purity, identity, quantity and long-term safety remain
unknown.
7-Hydroxymitragynine does not meet the United States Food and Drug
Administration (FDA) definitions for drugs, dietary supplements, or
dietary ingredients. FDA has issued warning letters to companies
clarifying that 7-hydroxymitragyine is not an FDA-approved drug product
and no food additive regulation has authorized the use of 7-
hydroxymitragynine in food supply. Furthermore, FDA has warned
consumers against using products labeled as 7-hydroxymitragynine, as
they have not been proven safe or effective for any use.\17\ Fatal
overdoses involving 7-hydroxymitragynine have been reported, making its
wide availability and unknown safety profile a significant threat to
public health, which is particularly concerning in the midst of an
opioid crisis. The availability of 7 hydroxymitragynine-containing
substances in the United States' M. speciosa consumer market poses an
imminent hazard to the public safety.
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\17\ FDA Issues Warning Letters to Firms Marketing Products
Containing 7-Hydroxymitragynine [verbar] FDA, available at https://
www.fda.gov/news-events/press-announcements/fda-issues-warning-
letters-firms-marketing-products-containing-
7hydroxymitragynine#:~:text=FDA%20Issues%20Warning%20Letters%20to%20F
irms%20Marketing%20Products%20Containing%207%2DHydroxymitragynine,-
Alkaloid%20known%20as&text=The%20U.S.%20Food%20and%20Drug,also%20know
n%20as%207%2DOH, Accessed July 31, 2025.
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Mitragynine Pseudoindoxyl

The prevalence and misuse of Mitragyna speciosa (commonly known as
kratom) and its psychoactive alkaloids, including mitragynine and 7-
hydroxymitragynine, have led to the proliferation of commercial
products containing opioids chemically synthesized from mitragynine or
7-hydroxymitragynine. In recent years, mitragynine pseudoindoxyl, which
is a chemical rearrangement product of 7-hydroxymitragynine has
recently emerged on the Mitragyna speciosa consumer markets. The
chemical scaffolds of mitragynine or 7-hydroxymitragynine were used in
scientific research to develop mitragynine pseudoindoxyl via chemical
modifications of purified isolates. Evidence from the Mitragyna
speciosa retail markets demonstrates that mitragynine pseudoindoxyl
transitioned from experimental substances studied in research to widely
available commercial products. These products are commonly sold in
different forms such as powders, tablets, and liquid shots. This is a
significant evolution from the traditional administration of Mitragyna
speciosa, which was once restricted to either chewing raw leaves or
steeping the leaves into water decoctions and teas.
These products are sold under numerous brand names like Kama,
Hydroxie, Fruity Perks, and Happie Tabs,\18\ and they are easily
purchased on the internet, as well as in gas stations, corner shops,
and vape shops. These products are available in consumer-friendly forms
to include flavored chewable tablets, which increases their appeal to a
broader demographic. Also, the aggressive marketing of mitragynine
pseudoindoxyl, which is a semi-synthetic opioid, as ``precision-
formulated products,'' ``botanical extracts,'' or as ``mood boosters''
for the treatment of health conditions is deeply concerning. The
branding creates a false sense of safety for unknowing consumers who
may equate the term ``botanical'' with lower risk. Furthermore, there
is paucity of data on quality control or standardized dosage available
for these products, making their use especially dangerous.
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\18\ The list of brand names is illustrative, non-exhaustive,
and provided solely as market context.
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Mitragynine pseudoindoxyl is a potent opioid that shares a similar
pharmacological profile with 7-hydroxymitragynine. Available
pharmacology data demonstrate that mitragynine pseudoindoxyl exhibit
strong affinity for the mu-opioid receptor (MOR) and function as MOR
agonists.<SUP>19 20</SUP> Data from preclinical studies show that this
substance produce analgesic effect that is more potent than
morphine.\21\ Because mitragynine pseudoindoxyl is a potent MOR
agonist, it poses similar health risks as other mu-opioid agonists
(i.e., morphine and fentanyl), including physical and psychological
dependence, and respiratory depression.
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\19\ Matsumoto, K., Narita, M., Muramatsu, N., Nakayama, T.,
Misawa, K., Kitajima, M., Tashima, K., Devi, L. A., Suzuki, T.,
Takayama, H., & Horie, S. (2014). Orally active opioid [mu]/[delta]
dual agonist MGM-16, a derivative of the indole alkaloid
mitragynine, exhibits potent antiallodynic effect on neuropathic
pain in mice. The Journal of Pharmacology and Experimental
Therapeutics, 348(3):383-392.
\20\ Yamamoto, L. T., Horie, S., Takayama, H., Aimi, N., Sakai,
S., Yano, S., Shan, J., Pang, P. K., Ponglux, D., & Watanabe, K.
(1999). Opioid receptor agonistic characteristics of mitragynine
pseudoindoxyl in comparison with mitragynine derived from Thai
medicinal plant Mitragyna speciosa. General Pharmacology, 33(1):73-
81.
\21\ V[aacute]radi, A., Marrone, G. F., Palmer, T. C., Narayan,
A., Szab[oacute], M. R., Le Rouzic, V., Grinnell, S. G., Subrath, J.
J., Warner, E., Kalra, S., Hunkele, A., Pagirsky, J., Eans, S. O.,
Medina, J. M., Xu, J., Pan, Y. X., Borics, A., Pasternak, G. W.,
McLaughlin, J. P., & Majumdar, S. (2016). Mitragynine/
Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism
and Delta Antagonism, Which Do Not Recruit [beta]-Arrestin-2.
Journal of Medicinal Chemistry, 59(18):8381-8397.
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A scan of retail data on the internet shows that vendors explicitly
market mitragynine pseudoindoxyl products for their ``clean and
powerful'' opioid-receptor activation, utilizing deceptive terminology
to target individuals seeking alternatives to pharmaceutical opioids.
These combinations and marketing strategies pose significant safety
risks to unsuspecting consumers who use these products by exposing them
to high doses of opioids. Recently, reports have confirmed the positive
identification of mitragynine pseudoindoxyl in toxicology cases in the
United States, and evidence demonstrates that these substances are
being misused. The lack of clinical data regarding its safety and
efficacy, coupled with the risk of life-threatening respiratory
depression and addiction, underscores the danger of marketing this
unapproved, highly potent opioid under the guise of therapeutic or
wellness products.
Available data and information for 7-hydroxymitragynine and
mitragynine pseudoindoxyl summarized below, indicate that these
substances have a high potential for abuse, no currently accepted
medical use in treatment in the United States, and a lack of accepted
safety for use under medical supervision. DEA's three-factor analysis
and HHS's October 8, 2026 letter are available in their entirety under
``Supporting and Related Material'' of the public docket for this
action at <a href="http://www.regulations.gov">www.regulations.gov</a> under Docket Number DEA-1570.

Factor 4. History and Current Pattern of Abuse

7-Hydroxymitragynine

7-Hydroxymitragynine is most commonly used in isolated form or as

[[Page 65373]]

component of M. speciosa. Historically, M. speciosa has been used for a
variety of purposes, including as an opium substitute and a treatment
of various opioid withdrawal symptoms, such as pain, cough, anxiety,
diarrhea, and intestinal difficulty.\22\ While its use was once
geographically limited, the marketing in the United States of 7-
hydroxymitragynine products has been aggressive and often
indistinguishable from the sale of M. speciosa.\23\ In recent years, 7-
hydroxymitragynine has been falsely marketed as a dietary supplement
\24\ or natural extract despite failing to meet FDA's definitions for
drugs, dietary supplements, or dietary ingredients. Anecdotal
information from users who post on social media indicates that many
users are self-treating chronic pain with unregulated 7-
hydroxymitragynine products.\25\
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\22\ Grundmann, O., Green, M., Berthold, E., Yoon, S.L., & Ray,
D. (2025). Prevalence and Use Patterns of Kratom (Mitragyna speciosa
Korth.) in a US Nationally Representative Sample. Journal of
psychoactive drugs, 1-9.
\23\ Smith, K.E., Boyer, E.W., Grundmann, O., McCurdy, C.R., &
Sharma, A. (2025). The rise of novel, semi-synthetic 7-
hydroxymitragnine products. Addiction (Abingdon, England), 120(2),
387-388.
\24\ FDA issued warning letters to firms marketing products
containing 7-hydroxymitragynine stating it is not a lawful dietary
supplement, food additive, or ingredient in any approved drug''. FDA
Issues Warning Letters to Firms Marketing Products Containing 7-
Hydroxymitragynine [verbar] FDA, available at https://www.fda.gov/
news-events/press-announcements/fda-issues-warning-letters-firms-
marketing-products-containing-7-
hydroxymitragynine#:~:text=FDA%20Issues%20Warning%20Letters%20to%20Fi
rms%20Marketing%20Products%20Containing%207%2DHydroxymitragynine,-
Alkaloid%20known%20as&text=The%20U.S.%20Food%20and%20Drug,also%20know
n%20as%207%2DOH, accessed on July 15, 2025.
\25\ National Drug Early Warning System (NDEWS). (2025). Alert
from the NDEWS Web Monitoring Team: Online mentions of Kratom and
Derivatives (May 30, 2025). Retrieved from <a href="http://ndews.org">ndews.org</a>.
---------------------------------------------------------------------------

Product Formulation and Marketing Claims of 7-Hydroxymitragynine

7-Hydroxymitragynine products are readily obtained from smoke
shops, gas stations, and online vendors in various forms, including
tablets, shots, capsules, powder, syrup, vapes, sublingual pouch/
strips, nasal spray, chewable, and liquid extracts. These products are
commonly sold with names such as ``7 Ohmz,'' ``7-hydroxy,'', and ``7-
OH,'' and they are presented in colorful packages. One investigation
identified 250 products sold between September 2024 through February
2025, noting that chewable/sublingual tablets were the most common
formulation.\26\ These products were sold for general wellbeing and
claims of increased focus. The investigation further highlighted the
concerns regarding standardized dosing and cost. The concentration of
7-hydroxymitragynine products varied significantly, ranging from 1 mg
to 700 mg in a single dose or serving. The average cost per dose across
most products containing 7-hydroxymitragynine was about $3.97.
---------------------------------------------------------------------------

\26\ Hill, K., Boyer, E.W., Grundmann, O., & Smith, K.E. (2025).
De facto opioids: Characterization of novel 7-hydroxymitragynine and
mitragynine pseudoindoxyl product marketing. Drug and Alcohol
Dependence, 272, 112701.
---------------------------------------------------------------------------

Anecdotal information synthesized from user-contributed reports and
subsequently analyzed by clinical educators \27\ between 2024 and early
2025 provide additional information on abuse patterns. Users
consistently report transition from traditional kratom leaf to 7-
hydroxymitragynine tablets (e.g., 7OHMZ, Press'd, Hydroxie). 7-
Hydroxymitragynine was described as ``the cleanest and most euphoric
high'' that lacks ``ceiling effect of nausea'' of the plain leaf. A
dominant theme is the short-lived nature of the 7-hydroxymitragynine
high. Users report the urge to redose frequently.
---------------------------------------------------------------------------

\27\ University of Connecticut School of Pharmacy and
Pharmaceutical Sciences. (2025), Kratom and Knock Offs, Should You
Leaf Them Alone: You Asked for It!. available at <a href="https://pharmacy.uconn.edu/course/kratom/">https://pharmacy.uconn.edu/course/kratom/</a>.
---------------------------------------------------------------------------

The National Drug Early Warning System (NDEWS) conducted web
monitoring on reddit mentions of kratom and its derivates. In the
report, information provided by reddit discussants surrounding kratom
and 7-hydroxymitragynine shows that users often compare 7-
hydroxymitragynine effects to prescription opioids, like oxycodone and
hydrocodone, with users expressing worry on how such potent products
are legally available at smoke shops. Commenters mentioned the ease and
convenience of buying products at gas stations and noted how this can
be a concern for impulse use due to ease of accessibility. Further,
discussions on prices ranged from $15-40 for a single dose product.\28\
---------------------------------------------------------------------------

\28\ Alert from the NDEWS Web Monitoring Team: Online mentions
of Kratom and Derivatives (May 30, 2025). Retrieved from <a href="http://ndews.org">ndews.org</a>.
---------------------------------------------------------------------------

In summary, 7-hydroxymitragynine products are available in
different forms and can be purchased easily via several avenues,
predominantly via the internet. This is a shift from traditional
botanical use to aggressive marketing of highly concentrated opioid
products in the United States.

Mitragynine Pseudoindoxyl

Mitragynine pseudoindoxyl is a synthetic derivatives of the indole
alkaloids, mitragynine or 7-hydroxymitragynine, of the Mitragyna
speciosa plant. Unlike the indole alkaloids mitragynine and 7-
hydroxymitragynine, which are naturally occurring in the plant,
mitragynine pseudoindoxyl is produced through synthetic modifications
of purified mitragynine isolates or 7-hydroxymitragynine.\29\ The
chemical scaffolds of mitragynine or 7-hydroxymitragynine were used in
scientific research to develop novel mitragynine pseudoindoxyl. The
first mention of mitragynine pseudoindoxyl in scientific literature
dates to 1974 when mitragynine pseudoindoxyl was isolated as a
metabolite from bio transformed mitragynine.
---------------------------------------------------------------------------

\29\ Id, 13;14; Takayama, H., Ishikawa, H., Kurihara, M.,
Kitajima, M., Aimi, N., Ponglux, D., Koyama, F., Matsumoto, K.,
Moriyama, T., Yamamoto, L.T., Watanabe, K., Murayama, T., & Horie,
S. (2002). Studies on the synthesis and opioid agonistic activities
of mitragynine-related indole alkaloids: discovery of opioid
agonists structurally different from other opioid ligands. Journal
of Medicinal Chemistry, 45(9):1949-1956.
---------------------------------------------------------------------------

Market Emergence and Designer-Drug Patterns of Mitragynine
Pseudoindoxyl

The first confirmed appearance of mitragynine pseudoindoxyl in
consumer products was reported in 2024.\30\ The introduction of
mitragynine pseudoindoxyl into the Mitragyna speciosa consumer market
follows a classic pattern of new designer drugs, where packaging
appears like those of designer novel psychoactive substances and are
often advertised as ``sold strictly for laboratory, botanical, and
research purposes only'' and ``not intended for human consumption.''
\31\ A study on products sold online containing mitragynine
pseudoindoxyl showed that of the 51 total products sold online, 35 had
an appealing flavor (e.g., various berry, mint, watermelon, pink
lemonade, candy apple, grape, citrus, mango, pistachio, and vanilla
bean), and 32 of the products had packaging that was formulated using
bright colors. Seventy-six percent (39 of 51) of these products were
chewable tablets, 18 percent were liquids (9 of 51), and the remaining
three were either dried ice cream cones with ice cream (two

[[Page 65374]]

products) or a chocolate bar (one product).\32\ Many of the products
typically feature serving sizes that require consumers to split tablets
or doses.
---------------------------------------------------------------------------

\30\ Hill, K., Boyer, E.W., Grundmann, O., & Smith, K.E. (2025).
De facto opioids: Characterization of novel 7-hydroxymitragynine and
mitragynine pseudoindoxyl product marketing. Drug and Alcohol
Dependence, 272: 112701; Krotulski, A.J.; Denn, M.T., Brower, J.O.,
Papsun, D.M., & Logan, B.K. (2025). Evaluation of Commercially
Available Smoke Shop Products Marketed as ``7-Hydroxy Mitragynine''
& Related Alkaloids, Center for Forensic Science Research and
Education, United States; Vadiei, N., Evoy, K.E., & Grundmann, O.
(2025). The Impact of Diverse Kratom Products on Use Patterns,
Dependence, and Toxicity. Current Psychiatry Reports, 27(10):584-
592.
\31\ Id, 24.
\32\ White, C.M., Belcourt, J., & Sedensky, A. (2025). A
Descriptive Assessment of Products Containing the Opioid Receptor
Stimulator Mitragynine Pseudoindoxyl. Substance Use & Misuse,
60(12):1950-1954.
---------------------------------------------------------------------------

Current Patterns of Use Mitragynine Pseudoindoxyl

Users seek mitragynine pseudoindoxyl for its psychoactive effects
and products are often advertised as mood enhancers or alternative to
prescription opioid analgesics (see Factor 5). These products are
commonly sold in different product forms, such as powders, tablets, or
liquid shots, which is a sharp contrast from the traditional mode of
administration of Mitragyna speciosa, which was confined to either
water decoctions or brewed into tea or chewing of fresh leaves. A
review of vendor websites \33\ show that these products are explicitly
marketed as ``potent'' and ``fast-acting'' substances and sold at low
prices. For example, mitragynine pseudoindoxyl tablets are sold in
varying fruit flavors and in bright colors, and prices vary from about
$2-4 per tablet or $34.99 per pack (single pack and 10-pack bulk). Of
great concern to DEA is that the price of these products may facilitate
high-frequency and rapid escalation of use (see Table 1).
---------------------------------------------------------------------------

\33\ Market Audit of Online Retailers, Jan. 2026.

Table 1--Retail Distribution of Mitragynine Pseudoindoxyl Products
----------------------------------------------------------------------------------------------------------------
Stated
Brand Product form concentration Marketing narrative
----------------------------------------------------------------------------------------------------------------
Kama Pseudoindoxyl............... Extract tablet...... 500 mg Kama 7- ``Stop settling for weak kratom
Hydroxy + Pseudo products.... Enjoy great flavor
extracts. and precise dosing without the
guesswork.''
Kream............................ Liquid Shot......... 90 mg 7-Hydroxy + ``Tired of slow supplements that
Pseudo. give you a crash? delivering fast-
acting effects and calm mental
clarity in a discreet little
bottle. This clean, lab-tested
liquid shot features 7-hydroxy
and pseudo in a citrus formula
for consistent potency, making it
easy to find focus and wellness
without waiting long.''
----------------------------------------------------------------------------------------------------------------

The shift from natural leaf decoctions of Mitragyna speciosa to
flavored, standardized, and high-potency semi-synthetic substances
suggests an intentional market strategy to maximize consumer appeal and
sale of products with rapid onset of effects. The use of ``research
chemical'' labeling, a common tactic to bypass regulatory oversight,
for flavored chewable products further demonstrates a pattern to reach
a broader consumer demographics.

Factor 5. Scope, Duration, and Significance of Abuse

7-Hydroxymitragynine

The abuse of 7-hydroxymitragynine is increasing and widespread.
Given its pharmacological profile as an opioid agonist and high abuse
potential,\34\ the marketing of 7-hydroxymitragynine products to
consumers as botanical supplements constitute a significant public
health risk. 7-Hydroxymitragynine, a potent opioid, presents overdose
risk and toxicity to users because its chemical manufacturing process
is inconsistent and does not adhere to good manufacturing practices.
This lack of oversight may lead to variation in doses and composition
in final products. Further, 7-hydroxymitragynine is sold as sublingual
pouch/tablet, a formulation known to deliver drugs rapidly into the
systemic circulation. This rapid delivery, coupled with 7-
hydroxymitragynine's known pharmacokinetic profile, presents a
significance of abuse.\35\
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\34\ Hemby, S.E., McIntosh, S., Leon, F., Cutler, S.J., &
McCurdy, C.R. (2019). Abuse liability and therapeutic potential of
the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-
hydroxymitragynine. Addiction Biology, 24(5), 874-885.
\35\ Hill, K., Boyer, E.W., Grundmann, O., & Smith, K.E. (2025).
De facto opioids: Characterization of novel 7-hydroxymitragynine and
mitragynine pseudoindoxyl product marketing. Drug and Alcohol
Dependence, 272, 112701; Sharma, A., Smith, K.E., Kuntz, M.A.,
Berthold, E.C., Elashkar, O.I., Guadagnoli, N., Kanumuri, S.R.R.,
Mukhopadhyay, S., Panlilio, L.V., Epstein, D.H., & McCurdy, C.R.
(2025). Chemical Analysis and Alkaloid Intake for Kratom Products
Available in the United States. Drug Testing and Analysis, 17(10),
1974-1984.
---------------------------------------------------------------------------

7-Hydroxymitragynine sellers make claims of its opioidergic
effects. Evidence demonstrates that 7-hydroxymitragynine products have
been identified to contain other opioid alkaloids, such as mitragynine
pseudoindoxyl.\36\ These combinations and practice pose significant
safety risks to unsuspecting consumers by exposing them to high doses
of opioids. The lack of evidence to support health claims made by
vendors selling 7-hydroxymitragynine products is worrisome. Hence, 7-
hydroxymitragynine products sold as unregulated dietary supplements
pose significant health risks to users because information on their
purity, identity, quantity and safety is unknown.
---------------------------------------------------------------------------

\36\ 7-Hydroxy Mitragynine NPS Discovery, available at <a href="https://www.cfsre.org/images/content/reports/public_alerts/7-Hydroxy_Mitragynine_NPS_Discovery_033125.pdf">https://www.cfsre.org/images/content/reports/public_alerts/7-Hydroxy_Mitragynine_NPS_Discovery_033125.pdf</a>, accessed March 10,
2026.
---------------------------------------------------------------------------

Law Enforcement Encounters

The number of seizures for 7-hydroxymitragynine as reported in law
enforcement systems is currently limited, primarily because forensic
chemists often prioritize the identification of mitragynine, the major
alkaloid in M. speciosa, rather than extending analysis to the
identification minor alkaloids, such as 7-hydroxymitragynine.
Furthermore, because 7-hydroxymitragynine is not federally controlled
under the CSA, specific forensic identification may be limited.
Consequently, some forensic laboratories may not place emphasis on
analyzing or tracking the encounters of non-controlled substances,
making it unlikely to be fully reported to forensic laboratories
databases. Nonetheless, available data from the National Forensic
Laboratory Information System (NFLIS) database \37\ shows that, in
2025, there were 42 reports of 7-hydroxymitagynine from 12 states. This
law enforcement data illustrates the widespread and increasing
availability of products containing 7-

[[Page 65375]]

hydroxymitragynine within the domestic kratom drug market.
---------------------------------------------------------------------------

\37\ NFLIS represents an important resource in monitoring
illicit drug trafficking, including the diversion of legally
manufactured pharmaceuticals into illegal markets. NFLIS is a
comprehensive information system that includes data from forensic
laboratories that handle more than 96 percent of an estimated 1.0
million distinct annual State and local drug analysis cases. NFLIS
includes drug chemistry results from completed analyses only. While
NFLIS data is not direct evidence of abuse, it can lead to an
inference that a drug has been diverted and abused. See Schedules of
Controlled Substances: Placement of Carisoprodol Into Schedule IV,
76 FR 77330, 77332 (Dec. 12, 2011). NFLIS data were queried on
February 26, 2026.
---------------------------------------------------------------------------

FDA Warning Letters

Between June and July 2025, FDA issued seven warning letters \38\
to marketers and distributors in response to the unauthorized claim of
7-hydroxymitragynine as a drug, dietary supplement, or dietary
ingredient. The warning letters explicitly stated that 7-
hydroxymitragyine is not an FDA-approved drug product and that no food
additive regulation has authorized the use of 7-hydroxymitragynine in
food. FDA further classified 7-hydroxymitragynine as a ``new dietary
ingredient'' under section 413(d) of the FD&C Act, 21 U.S.C. 350b(d),
because there is no evidence demonstrating it was marketed as a dietary
ingredient in the United States before October 15, 1994. Additionally,
some letters noted that, as a dietary supplement, 7-hydroxymitraghynine
is considered adulterated under section 402(f)(l)(B) of the FD&C Act,
21 U.S.C. 342(f)(l)(B). This is because there is inadequate information
providing reasonable assurance that the ingredient does not present a
significant or unreasonable risk of illness or injury. Of note was
FDA's warning letter issued on June 25, 2025, to a company selling
``7OHMZ 7-Hydroxymitragynine Gummies,'' \39\ in which FDA cautioned
that such products may be appealing to children due to their packaging.
Other warning letters targeted the illegal sale of unapproved 7-
hydroxymitragynine products marketed for the treatment of pain,
relaxation, mood enhancement, and other medical conditions.\40\ Vendors
utilized websites and social media pages to make unproven medical
claims for 7-hydroxymitragynine, such as describing tablets as
``expertly formulated to provide a potent dose'' or promising ``intense
relaxation and a feeling of pure bliss.''
---------------------------------------------------------------------------

\38\ FDA Issues Warning Letters to Firms Marketing Products
Containing 7-Hydroxymitragynine [verbar] FDA, available at <a href="https://www.fda.gov/news-events/press-announcements/fda-issues-warning-letters-firms-marketing-products-containing-7-hydroxymitragynine">https://www.fda.gov/news-events/press-announcements/fda-issues-warning-letters-firms-marketing-products-containing-7-hydroxymitragynine</a>;
7Tabz Retail, LLC--709546--06/25/2025 [verbar] FDA, available at
<a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/7tabz-retail-llc-709546-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/7tabz-retail-llc-709546-06252025</a>;
<a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/hydroxie-llc-709661-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/hydroxie-llc-709661-06252025</a>; <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/shaman-botanicals-llc-709622-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/shaman-botanicals-llc-709622-06252025</a>; <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/royal-diamond-imports-inc-709540-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/royal-diamond-imports-inc-709540-06252025</a>; <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/thang-botanicals-inc-dba-7ohmz-7-ohmz-or-7ohmz-710190-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/thang-botanicals-inc-dba-7ohmz-7-ohmz-or-7ohmz-710190-06252025</a>; <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/relax-relief-rejuvenate-trading-llc-dba-rrr-trading-or-edp-kratom-709475-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/relax-relief-rejuvenate-trading-llc-dba-rrr-trading-or-edp-kratom-709475-06252025</a>; <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/relax-relief-rejuvenate-trading-llc-dba-rrr-trading-or-edp-kratom-709475-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/relax-relief-rejuvenate-trading-llc-dba-rrr-trading-or-edp-kratom-709475-06252025</a>.
\39\ Thang Botanicals, Inc. d/b/a 7[ohm]HMZ, 7-OHMZ, or 7OHMZ--
710190--06/25/2025 [verbar] FDA, available at <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/thang-botanicals-inc-dba-7ohmz-7-ohmz-or-7ohmz-710190-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/thang-botanicals-inc-dba-7ohmz-7-ohmz-or-7ohmz-710190-06252025</a>.
\40\ FDA Warning Letter, Royal Diamond Imports, Inc. (June 25,
2025), available at <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/royal-diamond-imports-inc-709540-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/royal-diamond-imports-inc-709540-06252025</a>; FDA Warning Letter, Hydroxie,
LLC (June 25, 2025), available at <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/hydroxie-llc-709661-06252025">https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/hydroxie-llc-709661-06252025</a>.
---------------------------------------------------------------------------

State Regulations and Controls

Due to concerns over its abuse, several states have regulated or
banned the consumption of 7-hydroxymitragynine or M. speciosa.\41\
Currently, ten states (Alabama, Arkansas, Connecticut Indiana, Kansas,
Louisiana, Massachusetts, Tennessee, Vermont, and Wisconsin) have
prohibited 7-hydroxymitragynine consumption. Additionally, some states,
such as Arizona, Colorado, South Carolina, and Texas, have set
restrictions on the limits of 7-hydroxymitragynine (not to exceed a
specified percent of total alkaloid content).
---------------------------------------------------------------------------

\41\ Legislative Analysis and Public Policy Association, Kratom:
Summary of State Laws (April 2025), available at <a href="https://legislativeanalysis.org/wp-content/uploads/2025/07/Kratom-Summary-of-State-Laws.pdf">https://legislativeanalysis.org/wp-content/uploads/2025/07/Kratom-Summary-of-State-Laws.pdf</a>. Accessed August 8, 2025.
---------------------------------------------------------------------------

Furthermore, 19 states have enacted model legislation known as the
``kratom consumer protection Act (KCPA),'' which requires that M.
speciosa, mitragynine, or 7-hydroxymitragynine be manufactured safely,
labeled accurately, and distributed appropriately to protect consumer
under a certain age. These states are Arizona, Colorado, Florida,
Georgia, Kentucky, Oklahoma, Maryland, Mississippi, Nebraska, Nevada,
New York, Oregon, Rhode Island, South Carolina, South Dakota, Texas,
Utah, Virginia, and West Virginia. Other states, like Illinois, New
Hampshire, North Carolina, and Tennessee, have bans in some
localities.\42\ Of note, the state of Mississippi has set the limit per
weight basis to one percent of total alkaloid content of 7-
hydroxymitragynine or 0.5 mg per container. DEA's intent to temporarily
control 7-hydroxymitragynine above the specified threshold does not
preempt more restrictive state law regarding the consumption of 7-
hydorxymitragynine and 7-hydroxymitragynine related products.
---------------------------------------------------------------------------

\42\ American Kratom Association, Kratom State Legality and
Legislation, available at <a href="https://www.americankratom.org/aka-in-your-state">https://www.americankratom.org/aka-in-your-state</a>. Accessed on February 26, 2026.
---------------------------------------------------------------------------

Poison Control Center Data (National Poison Data System)

The significance of 7-hydroxymitragynine abuse is demonstrated by
an increasing volume of calls to poison control centers. Reporting for
7-hydroxymitragynine was historically limited within the national
poison data system (NPDS); however, specific data codes for this
substance were recently implemented between February and May 2025.
During the initial tracking period from February 2025 to April 2025,
NPDS recorded a total of 53 case reports involving 7-
hydroxymitragynine. Of these exposure calls, 37 cases involved single-
substance exposure of 7-hydroxymitragynine alone, and 24 cases were
classified as abuse involving other substances in combination with 7-
hydroxymitragynine. Among the single-substance exposure calls, 16 cases
were categorized as intentional abuse, while 13 calls involved moderate
medical outcomes where the patients exhibited pronounced and prolonged
systemic symptoms.
Expanded data from U.S. poison centers indicates a rapid escalation
in reported incidents.\43\ From January 1 through July 31, 2025, there
were 165 exposure cases involving 7-hydroxymitragynine. Of those
reporting exposures to 7-hydroxymitragynine alone, 35 percent of these
cases resulted in serious health problems, and 67 percent of
individuals were treated at a healthcare facility. Patients exposed to
7-hydroxymitragynine frequently exhibit a range of severe physiological
and neurological symptoms, including: gastrointestinal (nausea and
vomiting), neurological (agitation, confusion, loss of consciousness,
and seizure), cardiovascular (sweating, tachycardia, and hypertension),
and respiratory (difficulty breathing). According to HHS' review, users
report several reasons regarding the use of 7-hydroxymitragynine,
including the following:
---------------------------------------------------------------------------

\43\ America's Poison Centers, Health Advisory: Serious
Illnesses Associated with 7-OH Use, available at <a href="https://poisoncenters.org/news-alerts/13531044">https://poisoncenters.org/news-alerts/13531044</a>. Accessed on August 26, 2025.
---------------------------------------------------------------------------

[ssquf] Desired Effects: Euphoria and an opioid-like ``buzz''/high
as motivation for using 7-hydroxymitragynine.
[ssquf] Product Appeal: The availability of ``candy-like''
formulations of some 7-

[[Page 65376]]

hydroxymitragynine tablets, which some users acknowledge as carrying
health risk due to possibility of overconsumption.
[ssquf] Self-Treatment: Claim of 7-hydroxymitragynine therapeutic
value in self-treating pain and anxiety.
[ssquf] Risk Awareness: There is an acknowledgement among users of
products containing 7-hydroxymitragynine that these products can lead
to addiction, withdrawal symptoms, overdose, and other serious health
outcomes, including death.
In summary, the abuse of 7-hydroxymitragynine in the United States
is fueled by its pharmacological similarities to opioid analgesics, a
lack of regulatory controls, and the relative ease of obtaining 7-
hydroxymitragynine products via smoke shops and the internet.\44\
Furthermore, the consumption of 7-hydroxymitragynine alongside other
mind-altering substances may exacerbate the potential acute and long-
term hazards and risks to the user, especially drug dependence. FDA
responded to the increase in sales of 7-hydroxymitragynine products and
unsubstantiated medical claims by issuing warning letters to companies
to protect public safety. Available information from published
literatures and poison control centers suggests that 7-
hydroxymitragynine is used by a diverse population for the self-
treatment of various health conditions. The ingestion of 7-
hydroxymitragynine, a potent opioid, alone or co-ingestion with other
substances, commonly a CNS depressant, is of serious concern. The
poison control center data and popularity of 7-hydroxymitragynine-
products collectively underscores the severity and significance of
abuse of 7-hydroxymitragynine in the United States.
---------------------------------------------------------------------------

\44\ Internet sellers advertise, market, and provide false
medical claims.
---------------------------------------------------------------------------

Mitragynine Pseudoindoxyl

The abuse of mitragynine pseudoindoxyl is concerning due to its
high opioid potency and commercial availability. Mitragynine
pseudoindoxyl products are sold in formulations that facilitate ease of
use, bypass the traditional, lower-alkaloid preparation (chewing leaves
or drinking tea) and provide a highly potent effect that mimics
classical opioids such as morphine.

Deceptive Branding and Market Infiltration of Mitragynine Pseudoindoxyl

Analysis of marketed mitragynine pseudoindoxyl products revealed
misleading marketing strategies with claims that the products are
``kratom.'' Available information on vendor website indicates that the
concentrated alkaloid products often contain more than one alkaloid
with opioid activity (e.g., 7-hydroxymitragynine and mitragynine
pseudoindoxyl). These substances combinations and marketing practices
pose significant safety risk to unsuspecting consumers by exposing them
to high doses of opioids (see Table 1). It is known that repeated use
of opioids can lead to psychological and physical dependence. In fact,
data show that chronic use of 7-hydroxymitragynine has sent users to
opioid detox clinic and the need for opioid use disorder
medication.\45\ Furthermore, these products are labeled for ``strong
mood enhancement'' and ``analgesic properties.'' Finally, the presence
of these products containing mitragynine pseudoindoxyl is deeply
concerning because the identity, purity, and quality of these products'
formulation are uncertain, thus presenting additional safety concerns
for unsuspecting users.
---------------------------------------------------------------------------

\45\ Wightman, R. S., & Hu, D. (2025). A Case of 7-OH
Mitragynine Use Requiring Inpatient Medically Managed Withdrawal.
Journal of Addiction Medicine, 10.1097/ADM.0000000000001558. Advance
online publication.
---------------------------------------------------------------------------

A study of products sold as mitragynine pseudoindoxyl over the
internet found that the 51 unique products sold online as mitragynine
pseudoindoxyl were marketed in child-appealing forms and contained
other opioid alkaloids, with limited consumer safety information. The
serving size varied and alkaloid concentrations for these marketed
products were often higher than those in naturally occurring Mitragyna
speciosa leaves. The analysis revealed that among the products sampled,
71 percent featured a combination of mitragynine pseudoindoxyl and 7-
hydroxymitragynine, while 24 percent contained mitragynine
pseudoindoxyl only. The remaining 6 percent contained combination of
mitragynine pseudoindoxyl and other hydroxymitragynine forms (8-
hydroxymitragynine or 11-hydroxymitragynine).\46\
---------------------------------------------------------------------------

\46\ Wilson, L. L., Chakraborty, S., Eans, S. O., Cirino, T. J.,
Stacy, H. M., Simons, C. A., Uprety, R., Majumdar, S., & McLaughlin,
J. P. (2021). Kratom Alkaloids, Natural and Semi-Synthetic, Show
Less Physical Dependence and Ameliorate Opioid Withdrawal. Cell Mol
Neurobiol., 41(5):1131-1143. doi: 10.1007/s10571-020-01034-7.
---------------------------------------------------------------------------

National E-Commerce of Mitragynine Psuedoindoxyl

Data from online sources show that the availability of mitragynine
pseudoindoxyl products are not isolated to a single region but have
rapidly spread across the United States. Products containing
mitragynine pseudoindoxyl are sold on the internet and are delivered to
most states where there is currently no kratom use restrictions,
suggesting national distribution network facilitated by online sales
and mass-market retail channels. The significance of the abuse of
mitragynine pseudoindoxyl is underscored by the potent opioid
pharmacological profile of these substances and the specific health
warnings acknowledged even by those who are marketing the substances.
Vendor descriptions listed below provide insight into the duration and
pattern of use that characterizes the abuse of these compounds:
Sustained Effect: The duration of effects is reported to last
``several hours.'' \47\ This prolonged duration increases the
likelihood of cumulative effects and potential for toxicity if doses
are repeated.
---------------------------------------------------------------------------

\47\ See Pseudoindoxyl Chewable Tablets--Red Vein--Advanced
Alkaloids Descriptions, <a href="https://cbdamericanshaman.com/pseudoindoxyl-chewable-tablets-red-vein-advanced-alkaloids">https://cbdamericanshaman.com/pseudoindoxyl-chewable-tablets-red-vein-advanced-alkaloids</a>. Accessed January 2026.
---------------------------------------------------------------------------

Deceptive Marketing for Medical Conditions: Despite having no FDA-
approved medical use, these products are explicitly marketed for
``easing stress and tension,'' ``internal calm and reduced
restlessness,'' and as a ``mental clarity.'' \48\ This marketing
encourages individuals with legitimate medical needs to utilize potent,
unlawful opioids as self-treatment.
---------------------------------------------------------------------------

\48\ See Dozo Perks Extremely Potent Pseudoindoxyl Chewable
Tablet Grape 100mg Per Tablet, <a href="https://pureleafkratom.com/products/dozo-perks-100mg-pseudoindoxyl-grape-chewable-tablets-4ct.html">https://pureleafkratom.com/products/dozo-perks-100mg-pseudoindoxyl-grape-chewable-tablets-4ct.html</a>.
Accessed January 2026.
---------------------------------------------------------------------------

Deceptive ``Natural'' Branding: Vendors frequently frame these
substances as ``clean and powerful'' alternatives to traditional
kratom. This branding is used to minimize the perceived risk of what
are highly potent semi-synthetic opioid agonists.
Deceptive Safety Profiles: While products are marketed as a
``midday stress relief'' or ``mental reset,'' the inclusion of warnings
for lethal respiratory depression on retail sites confirms that the
products possess a toxicity profile identical to scheduled opioids.
Low Barrier to Entry: The use of ``fruity'' flavors and
``chewable'' formats (e.g., Fruity Perks) suggests an effort to

[[Page 65377]]

appeal to a broader, potentially younger demographic, significantly
increasing the scope of potential abuse.

Forensic Surveillance and Identification of Mitgragynine Pseudoindoxyl

According to the National Forensic Laboratory Information System
(NFLIS) \49\ database, which collects drug identification results from
drug cases submitted to and analyzed by Federal State and local
forensic laboratories, there has been one report of mitragynine
pseudoindoxyl in New York (queried February 26, 2026). Further,
monographs \50\ by Center for Forensic Science Research and Education
(CFSRE), report that mitragynine pseudoindoxyl (n > 10) have been
detected in at least 10 drug materials.
---------------------------------------------------------------------------

\49\ NFLIS represents an important resource in monitoring
illicit drug trafficking, including the diversion of legally
manufactured pharmaceuticals into illegal markets. NFLIS-Drug is a
comprehensive information system that includes data from forensic
laboratories that handle the nation's drug analysis cases. NFLIS-
Drug participation rate, defined as the percentage of the national
drug caseload represented by laboratories that have joined NFLIS, is
currently 98.5 percent. NFLIS includes drug chemistry results from
completed analyses only. While NFLIS data is not direct evidence of
abuse, it can lead to an inference that a drug has been diverted and
abused. See Schedules of Controlled Substances: Placement of
Carisoprodol Into Schedule IV, 76 FR 77330, 77332 (Dec. 12, 2011).
NFLIS data was queried on December 5, 2025.
\50\ <a href="https://www.cfsre.org/nps-discovery/monographs/mitragynine-pseudoindoxyl">https://www.cfsre.org/nps-discovery/monographs/mitragynine-pseudoindoxyl</a>. Report Date-November 7, 2025. Accessed January 9,
2026; <a href="https://www.cfsre.org/nps-discovery/monographs/dihydro-7-hydroxy-mitragynine">https://www.cfsre.org/nps-discovery/monographs/dihydro-7-hydroxy-mitragynine</a>. Report Date-November 11, 2025. Accessed January
9, 2026.
---------------------------------------------------------------------------

The paucity or lack of seizure data for this substance as reported
in forensic laboratories casework may be due to lack of readily
available analytical reference standards and other analytic challenges.
Specifically, mitragynine pseudoindoxyl is an oxidative metabolite of
7-hydroxymitragynine, and such closely related compounds require
specific method and instrumentation for accurate identification. Also,
since mitragynine pseudoindoxyl is not federally controlled under the
CSA, some forensic laboratories may not analyze and track encounters of
non-controlled substances and thus reporting could be limited.
The population likely to abuse mitragynine pseudoindoxyl appears to
be the same as those abusing Mitragyna speciosa and prescription opioid
analgesics. According to data from the National Survey on Drug Use and
Health (NSDUH),\51\ as of 2021, an estimated 1.7 million people aged 12
years or older used kratom in the past year. The highest users were
among adults aged 26 or older (1.4 million people). The analysis of
2019 NSDUH survey data showed that kratom users base predominately non-
Hispanic White and male. The survey finding also revealed a link
between kratom use and substance use disorder, particularly nonmedical
prescription opioid use disorder, indicative of a strong trend of use
for self-managing opioid dependence.\52\
---------------------------------------------------------------------------

\51\ The NSDUH, formerly known as the National Household Survey
on Drug Abuse (NHSDA), is conducted annually by the Department of
Health and Human Services Substance Abuse and Mental Health Services
Administration (SAMHSA). It is the primary source of estimates of
the prevalence and incidence of nonmedical use of pharmaceutical
drugs, illicit drugs, alcohol, and tobacco use in the United States.
The survey is based on a nationally representative sample of the
civilian, non-institutionalized population 12 years of age and
older. The survey excludes homeless people who do not use shelters,
active military personnel, and residents of institutional group
quarters such as jails and hospitals. The NSDUH provides yearly
national and state level estimates of drug abuse, and includes
prevalence estimates by lifetime (i.e., ever used), past year, and
past month abuse or dependence.
\52\ Palamar, J. J. (2021). Past-Year Kratom Use in the U.S.:
Estimates From a Nationally Representative Sample. Am J Prev Med.,
61(2):240-245: Rogers, J. M., Smith, K. E., Strickland, J. C., &
Epstein, D. H. (2021). Kratom Use in the US: Both a Regional
Phenomenon and a White Middle-Class Phenomenon? Evidence From NSDUH
2019 and an Online Convenience Sample. Frontiers in Pharmacology,
12:789075.
---------------------------------------------------------------------------

Factor 6. What, If Any, Risk There Is to Public Health

7-Hyrdoxymitragynine

7-Hydroxymitragynine has opioidergic and addictive properties.
Available preclinical data demonstrates that 7-hydroxymitragynine has
an abuse potential similar to that of schedule I and II opioids, such
as heroin, morphine, and fentanyl.\53\ The abuse of 7-
hydroxymitragynine presents a severe of risks to public health,
including tolerance, dependence and addiction, respiratory depression,
and death. Public health assessment is further complicated because 7-
hydroxymitragynine is a known metabolite of mitragynine, making it
difficult to distinguish between the ingestion of M. speciosa and other
isolated 7-hydroxymitragynine products.
---------------------------------------------------------------------------

\53\ Alsbrook, S., Pro, G., & Koturbash, I. (2025). From kratom
to 7-hydroxymitragynine: evolution of a natural remedy into a
public-health threat. Pharmaceutical Biology, 63(1), 896-911.
---------------------------------------------------------------------------

FDA-Adverse Event Reporting System (FAERS) for 7-Hydroxymitragynine

On August 11, 2025, DEA queried the FAERS public dashboard for 7-
hydroxymitrragynine and noted that there were 1 case count in 2023, 2
cases in 2024, and 11 cases as of June 30, 2025. Most of the cases
involved drug dependence (n = 6) and withdrawal syndrome (n = 4). A
recent query of the database on February 27, 2026, revealed an increase
in cases involving 7-hydroxymitragynine. The total count for 2025
increased to 66 with 17 new cases already reported for 2026. Of the
total 86 cases currently within the database, 79 cases were reported as
serious, including death. To date, 9 cases within the FAERS database
have resulted in death.

DEA Toxicology Testing Program (DEA TOX) Results for 7-
Hydroxymitragynine

DEA TOX program, which investigates the presence of new
psychoactive substances in biological samples from drug overdoses, has
identified 7-hydroxymitragynine in 85 cases since 2019.\54\ Of these,
55 were fatal and 30 were non-fatal cases. These cases involved both
males and females with a median age of 36. The average concentration of
7-hydroxymitragynine detected in biological samples was 463.23 ng/mL.
Samples often contained other related alkaloids (mitragynine and
mitragynine pseudoindoxyl) or other drug classes, such as opioids
(e.g., fentanyl), benzodiazepines (e.g., bromazolam), and ketamine.
Between 2020 and 2025, there has been a significant increase in the
positive identification of 7-hydroxymitragynine in fatal overdose
cases.
---------------------------------------------------------------------------

\54\ DEA TOX is a surveillance program that aims to detect novel
psychoactive substances in fatal and nonfatal overdose cases within
the United States. From these cases, biological samples, as well as
drug paraphernalia (on limited occasions), are submitted for
analysis by hospitals, medical examiners, poison centers, and law
enforcement nationwide. Queried on March 05, 2026.
---------------------------------------------------------------------------

Case Reports Involving 7-Hydroxymitragynine

In 2025, California,\55\ Pennsylvania,\56\ and Texas health
authorities linked 7-hydroxymitragynine and concentrated extracts to
several illness and overdose cases.\57\ Other notable cases are
summarized in the table below:
---------------------------------------------------------------------------

\55\ LISTING OF DEPARTMENT OF PUBLIC HEALTH PRESS RELEASES,
available at <a href="http://publichealth.lacounty.gov/phcommon/public/media/mediapubhpdetail.cfm?prid=5156">http://publichealth.lacounty.gov/phcommon/public/media/mediapubhpdetail.cfm?prid=5156</a>. October 10, 2025.
\56\ Increased Volume of Calls Related to Kratom/Mitragynine and
7-hydroxymitragynine (7-OH) to Pennsylvania's Poison Centers,
available at <a href="https://www.pa.gov/content/dam/copapwp-pagov/en/health/documents/topics/documents/2025%20HAN/2025-802-%208-4-%20Kratom.pdf">https://www.pa.gov/content/dam/copapwp-pagov/en/health/documents/topics/documents/2025%20HAN/2025-802-%208-4-%20Kratom.pdf</a>.
August 4, 2025.
\57\ Serious Illnesses Associated with 7-OH Use [verbar] Texas
DSHS, available at <a href="https://www.dshs.texas.gov/news-alerts/serious-illnesses-associated-7-oh-use">https://www.dshs.texas.gov/news-alerts/serious-illnesses-associated-7-oh-use</a>. September 2, 2025.

[[Page 65378]]

7-Hydroxymitragynine Case Reports
[2014-2026]
----------------------------------------------------------------------------------------------------------------
Patient
Case report author profile (y/ Primary complication Clinical finding
o male)
----------------------------------------------------------------------------------------------------------------
Broul et al. (2025) \58\.............. 31 Acute Psychosis.......... Severe Self-Harm: Documented 7-
hydroxymitragynine induced
psychosis leading to self-
amputation (ears/genitalia).
Karinen et al. (2014) \59\............ 24 Fatal Overdose........... Fatality: Identified a 7-
hydroxymitragynine blood
concentration of 0.15 mg/L.
Pullman et al. (2026) \60\............ 29 Cardiopulmonary arrest... Naloxone Reversal: Confirmed 7-
hydroxymitragynine causes opioid
respiratory depression
reversible with standard
antagonist drug.
Wightman and Hu (2025) \61\........... 38 Severe Dependence........ Clinical Detoxification: Patient
required inpatient buprenorphine
stabilization for high dose 7-
hydroxymitragynine withdrawal.
----------------------------------------------------------------------------------------------------------------

These 7-hydroxymitragynine products are obtained through unknown
sources, where the identity, purity, and concentration of active
ingredients are often unknown, uncertain, and inconsistent; thus,
posing significant adverse health risks to users. The abuse of 7-
hydroxymitragynine poses a substantial hazard to public safety. 7-
Hydroxymitragynine is being abused for its opioid-like effects and
shares health risks similar to other mu-opioid receptor agonists, such
as morphine (schedule II). With no approved medical use, the positive
identification of 7-hydroxymitragynine in non-fatal and fatal overdose
cases poses threat to public safety. 7-Hydroxymitragyninee products are
obtained through unknown sources (commonly through the internet); the
identity, purity, and quantity of these substances are uncertain and
inconsistent, thus posing significant adverse health risks to users.
---------------------------------------------------------------------------

\58\ Broul, M., Rudenko, X., Bajus, A., Kr[aacute]l, J., Kyenge,
D. M., Sta[ncaron]kov[aacute], Z., & Albrecht, J. (2025). Case
Report: Cannabis and kratom-induced self-amputation of ears and
penis. Frontiers in psychiatry, 16, 1479863.
\59\ Karinen R., Posen J.T., Rogde S., & Vindenes V. (2014). An
accidental poisoning with mitragynine. Forensic Science
International, 245, 29-32.
\60\ Pullman M.K., Raju Kanumuri S.R., Leon J.F., Cutler S.F.,
McCurdy C.R., & Sharma. A. (2026). Cardio-pulmonary arrest in a
patient revived with naloxone following reported use of 7-
hydroxymitragynine. Clinical Toxicology, 64(1), 65-66.
\61\ Wightman, R. S., & Hu, D. (2025). A Case of 7-OH
Mitragynine Use Requiring Inpatient Medically Managed Withdrawal.
Journal of Addiction Medicine, 10.1097. Advance online publication.
---------------------------------------------------------------------------

Mitragynine Pseudoindoxyl

Mitragynine pseudoindoxyl functions as potent MOR agonist. This
mechanism of action is inherently associated with high potential of
abuse, physical dependence, and psychological dependence, consistent
with the effects of controlled schedule I and II opioid substances. As
of early 2026, mitragynine pseudoindoxyl products are sold in smoke
shops, gas stations, and through numerous online marketplaces, often
marketed alongside traditional supplements, which mask their potent
opioid nature. Data from preclinical studies demonstrate that
mitragynine pseudoindoxyl is about 100 times more potent than
mitragynine at the MOR.\62\ Because of the potency of this compound, it
can be abused in smaller, concentrated doses. It has been demonstrated
that mitragynine pseudoindoxyl may cause development of signs of opioid
physical dependence after chronic use in rodents. Pre-clinical studies
demonstrated that chronic twice-daily administration of mitragynine
pseudoindoxyl in rodents induces signs of opioid physical dependence
and withdrawal symptoms in morphine addiction rodent models as
evidenced by increased diarrhea, jumping, and rearing frequency
occurring when naloxone was administered or when treatment with this
alkaloid was tapered.\63\
---------------------------------------------------------------------------

\62\ Id. 13-14.
\63\ Wilson, L.L., Chakraborty, S., Eans, S.O, Cirino, T.J.,
Stacy, H.M., & Simons, C.A., Uprety, R., Majumdar, S., & McLaughlin,
J.P. (2021). Kratom Alkaloids, Natural and Semi-Synthetic, Show Less
Physical Dependence and Ameliorate Opioid Withdrawal. Cell Mol
Neurobiol., 41(5):1131-1143.
---------------------------------------------------------------------------

These products are easily accessible in unregulated retail
environments often with no age restrictions, amplifying public health
concerns, particularly to vulnerable populations. Vendor descriptions
provide insight into the public health threat posed by the abuse of
these compounds:
Rapid Onset: Marketing materials for mitragynine pseudoindoxyl
products emphasize a ``quick onset,'' typically occurring within 10 to
60 minutes, often described as a ``wave of calm clarity,'' ``dual-
action formula featuring 100mg per piece for maximum potency and a
fast-acting hit.'' \64\
---------------------------------------------------------------------------

\64\ See Kama Kratom <a href="https://greatcbdshop.com/product-category/brands/kama-kratom/">https://greatcbdshop.com/product-category/brands/kama-kratom/</a> and Pure Leaf Kratom <a href="https://pureleafkratom.com/kama-kratom/">https://pureleafkratom.com/kama-kratom/</a>. Accessed March 2026.
---------------------------------------------------------------------------

Sustained Effect: The duration of effects is reported to last
``several hours.'' \65\ This prolonged duration increases the
likelihood of cumulative effects and potential for toxicity if doses
are repeated.
---------------------------------------------------------------------------

\65\ Id. 26.
---------------------------------------------------------------------------

Opioid Receptor Activation: Marketing materials explicitly state
that these compounds directly activate opioid receptors and are ``full
agonist at mu receptors,'' providing effects that mirror analgesic and
stimulant effects (``pain relief and mood enhancement'').\66\
---------------------------------------------------------------------------

\66\ Id.
---------------------------------------------------------------------------

As with any MOR agonist, the potential health and safety risks for
users of mitragynine pseudoindoxyl are high. Mitragynine pseudoindoxyl
abuse carries a high risk of cardiotoxicity, hepatic and renal
toxicity, respiratory depression, neurological effects, and physical
dependence and withdrawal. According to data from poison control
centers, from January to July 2025, there have been 1,690 exposure
calls involving kratom, a significant increase from 2024 exposure
calls. According to data from DEA Toxicology Testing Program (DEA
TOX),\67\ between February 2025-February 2026, mitragynine
pseudoindoxyl has been identified in at least 31 overdose cases, of
which 25 were fatal events. Recent monographs by CFSRE report that
mitragynine pseudoindoxyl (n > 10) have been detected in at least 10
toxicology cases. Mitragynine pseudoindoxyl was co-identified with
other kratom alkaloids. The sale of products with combination of high-
potency opioids, explicit marketing for medical ailments, and the
acknowledged potential for life-threatening respiratory depression and
addiction highlights the danger posed by mitragynine pseudoindoxyl and
7-hydroxymitragynine.
---------------------------------------------------------------------------

\67\ DEA TOX is a surveillance program that aims to detect novel
psychoactive substances in fatal and nonfatal overdose cases within
the United States. From these cases, biological samples, as well as
drug paraphernalia (on limited occasions), are submitted for
analysis by hospitals, medical examiners, poison centers, and law
enforcement nationwide. Query date 2/27/2026.

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

[[Page 65379]]

Finding of Necessity of Schedule I Placement To Avoid Imminent Hazard
to Public Safety

In accordance with 21 U.S.C. 811(h)(3), based on the available data
and information summarized above, the uncontrolled manufacture,
distribution, reverse distribution, importation, exportation, conduct
of research and chemical analysis, possession, and abuse of 7-
hydroxymitragynine and mitragynine pseudoindoxyl poses an imminent
hazard to public safety. DEA is not aware of any currently accepted
medical uses for either 7-hydroxymitragynine or mitragynine
pseudoindoxyl in the United States. A substance meeting the statutory
requirements for temporary scheduling, found in 21 U.S.C. 811(h)(1),
may only be placed in schedule I. Substances in schedule I are those
that have a high potential for abuse, no currently accepted medical use
in treatment in the United States, and a lack of accepted safety for
use under medical supervision. Available data and information for 7-
hydroxymitragynine and mitragynine pseudoindoxyl indicate that these
substances have a high potential for abuse, no currently accepted
medical use in treatment in the United States, and a lack of accepted
safety for use under medical supervision. However, because both 7-
hydroxymitragynine and mitragynine pseudoindoxyl have supposedly been
found in trace amounts in some botanical kratom products, this
temporary scheduling order is only temporarily placing 7-
hydroxymitragynine and mitragynine pseudoindoxyl when either substance
alone, or their combined amount if both are present, is above a
specified threshold in schedule I. Individuals should not infer from
this notice of intent that DEA views 7-hydroxymitragynine or
mitragynine pseudoindoxyl below this threshold as safe for consumption.
DEA still views kratom and its two major psychoactive ingredients,
mitragynine and 7-hydroxymtragynine, as drugs of concern.\68\
---------------------------------------------------------------------------

\68\ See <a href="https://www.dea.gov/factsheets/kratom">https://www.dea.gov/factsheets/kratom</a>. See also Drug
Fact Sheet: Kratom.
---------------------------------------------------------------------------

As required by 21 U.S.C. 811(h)(4), the Administrator notified the
Assistant Secretary, via letter dated October 8, 2026 of DEA's
intention to temporarily place 7-hydroxymitragynine and mitragynine
pseudoindoxyl when either substance alone, or their combined amount if
both are present, is above a specified threshold in schedule I.

Conclusion

Although DEA published a notice of intent to temporarily schedule
7-hydroxymitragynine above a specified threshold in the Federal
Register on July 7, 2026, and a temporary order in the Federal Register
that placed mitragynine pseudoindoxyl in schedule I on August 26, 2026,
HHS has since sent a letter dated October 8, 2026, to DEA, in which HHS
now recommends a new threshold for 7-hydroxymitragynine and mitragynine
pseudoindoxyl. Based on this letter, DEA is withdrawing the notice of
intent to control 7-hydroxymitragynine above a specified threshold
elsewhere in this issue of the Federal Register, and it intends to
withdraw the temporary order placing mitragynine pseudoindoxyl and
replace it with a new temporary order.
This notice of intent provides the 30-day notice pursuant to 21
U.S.C. 811(h)(1) of DEA intent to issue the new temporary scheduling
order placing 7-hydroxymitragynine and mitragynine pseudoindoxyl when
either substance alone, or their combined amount if both are present,
is above a specified threshold in schedule I. In accordance with 21
U.S.C. 811(h)(1) and (3), the Administrator considered available data
and information, herein set forth the grounds for his determination
that it is necessary to temporarily schedule 7-hydroxymitragynine and
mitragynine pseudoindoxyl when either substance alone, or their
combined amount if both are present, is above a specified threshold and
finds this placement in schedule I of the CSA is necessary in order to
avoid an imminent hazard to the public's safety. Again, this action
should not be used to infer that DEA views 7-hydroxymitragynine or
mitragynine pseudoindoxyl below this threshold as safe for consumption.
DEA still views kratom and its two major psychoactive ingredients,
mitragynine and 7-hydroxymtragynine, as drugs of concern.\69\
---------------------------------------------------------------------------

\69\ See <a href="https://www.dea.gov/factsheets/kratom">https://www.dea.gov/factsheets/kratom</a>. See also Drug
Fact Sheet: Kratom.
---------------------------------------------------------------------------

The temporary placement of 7-hydroxymitragynine and mitragynine
pseudoindoxyl when either substance alone, or their combined amount if
both are present, is above a specified threshold in schedule I of the
CSA will take effect pursuant to a temporary scheduling order, which
will not be issued before [INSERT DATE 30 DAYS AFTER PUBLICATION IN THE
FEDERAL REGISTER]. Additionally, to avoid an enforcement gap, the
current temporary order that placed mitragynine pseudoindoxyl in
schedule I remains in effect until either it expires or the new
temporary order is published and the previous order is withdrawn,
whichever occurs first. Because the Administrator hereby finds that
this temporary scheduling order is necessary to avoid an imminent
hazard to public safety, it will take effect on the date the order is
published in the Federal Register and remain in effect for two years,
with a possible extension of an additional year, pending completion of
the regular (permanent) scheduling process.\70\ The Administrator
intends to issue a temporary scheduling order as soon as possible after
the expiration of 30 days from the date of publication of this
document. Upon publication of the temporary order, 7-hydroxymitragynine
and mitragynine pseudoindoxyl when either substance alone, or their
combined amount if both are present, is above a specified threshold
will then be subject to the CSA's schedule I regulatory controls and
administrative, civil, and criminal sanctions applicable to the
manufacture, distribution, reverse distribution, importation,
exportation, research, conduct of instructional activities and chemical
analysis, and possession.
---------------------------------------------------------------------------

\70\ 21 U.S.C. 811(h)(1) and (2).
---------------------------------------------------------------------------

The CSA sets forth specific criteria for scheduling drugs or other
substances. Regular scheduling actions in accordance with 21 U.S.C.
811(a) are subject to formal rulemaking procedures ``on the record
after opportunity for a hearing'' conducted pursuant to the provisions
of 5 U.S.C. 556 and 557.\71\ The regular scheduling process of formal
rulemaking affords interested parties appropriate process and the
government any additional relevant information needed to make a
determination. It is DEA's intention to pursue formal rulemaking
proceedings under 21 U.S.C. 811(a) in this instance by gathering the
necessary data and requesting that HHS provide a scientific and medical
evaluation and scheduling recommendation for 7-hydroxymitragynine and
mitragynine pseudoindoxyl pursuant to 21 U.S.C. 811(b). Final decisions
that conclude the regular scheduling process of formal rulemaking are
subject to judicial review.\72\ Temporary scheduling orders are not
subject to judicial review.\73\
---------------------------------------------------------------------------

\71\ 21 U.S.C. 811.
\72\ 21 U.S.C. 877.
\73\ 21 U.S.C. 811(h)(6).
---------------------------------------------------------------------------

Regulatory Analyses

The CSA provides for expedited temporary scheduling actions where
necessary to avoid an imminent hazard to public safety. Under 21 U.S.C.

[[Page 65380]]

811(h)(1), the Administrator (as delegated by the Attorney General)
may, by order, temporarily schedule substances in schedule I. Such
orders may not be issued before the expiration of 30 days from: (1) the
publication of a notice in the Federal Register of the intent to issue
such order and the grounds upon which such order is to be issued, and
(2) the date that notice of the proposed temporary scheduling order is
transmitted to the Assistant Secretary of HHS, as delegated by the
Secretary of HHS.\74\
---------------------------------------------------------------------------

\74\ 21 U.S.C. 811(h)(1).
---------------------------------------------------------------------------

Inasmuch as section 811(h) directs that temporary scheduling
actions be issued by order and sets forth the procedures by which such
orders are to be issued, including the requirement of a publication in
the Federal Register of a notice of intent, the notice-and-comment
requirements of the Administrative Procedure Act (APA), 5 U.S.C. 553,
do not apply to this notice of intent. The APA expressly differentiates
between an order and a rule, as it defines an ``order'' to mean a
``final disposition, whether affirmative, negative, injunctive, or
declaratory in form, of an agency in a matter other than rule making.''
\75\ This contrasts with permanent scheduling actions, which are
subject to formal rulemaking procedures done ``on the record after
opportunity for a hearing,'' and final decisions that conclude the
scheduling process and are subject to judicial review.\76\ The specific
language chosen by Congress indicates its intent that DEA issue orders
instead of proceeding by rulemaking when temporarily scheduling
substances. Given that Congress specifically requires the Administrator
(as delegated by the Attorney General) to follow rulemaking procedures
for other kinds of scheduling actions,\77\ it is noteworthy that, in
section 811(h)(1), Congress authorized the issuance of temporary
scheduling actions by order rather than by rule.
---------------------------------------------------------------------------

\75\ 5 U.S.C. 551(6) (emphasis added).
\76\ 21 U.S.C. 811(a) and 877.
\77\ See 21 U.S.C. 811(a).
---------------------------------------------------------------------------

Even assuming that this notice of intent is subject to the notice-
and-comment requirements of the APA, the AG finds that there is good
cause to forgo those requirements pursuant to 5 U.S.C. 553(b)(B), as
any further delays in the process for issuing temporary scheduling
orders would be impracticable and contrary to the public interest given
the manifest urgency to avoid an imminent hazard to public safety.
Although DEA believes this notice of intent to issue a temporary
scheduling order is not subject to the notice-and-comment requirements
of the APA, DEA notes that in accordance with 21 U.S.C. 811(h)(4), the
Administrator took into consideration comments submitted by the
Assistant Secretary in response to the notice that DEA transmitted to
the Assistant Secretary pursuant to such subsection.
Further, DEA believes that this temporary scheduling action is not
a ``rule'' as defined by 5 U.S.C. 601(2), and, accordingly, is not
subject to the requirements of the Regulatory Flexibility Act (RFA).
The requirements for the preparation of an initial regulatory
flexibility analysis in 5 U.S.C. 603(a) are not applicable where, as
here, DEA is not required by the APA or any other law to publish a
general notice of proposed rulemaking. As discussed above, DEA is
issuing this notice of intent pursuant to DEA's authority to issue a
temporary scheduling order.\78\ Therefore, in this instance, since DEA
believes this temporary scheduling action is not a ``rule,'' it is not
subject to the requirements of the RFA when issuing this temporary
action.
---------------------------------------------------------------------------

\78\ 21 U.S.C. 811(h)(1).
---------------------------------------------------------------------------

In accordance with the principles of Executive Orders (E.O.) 12866
and 13563, this action is not a significant regulatory action. E.O.
12866 directs agencies to assess all costs and benefits of available
regulatory alternatives and, if regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, public health, and safety effects;
distributive impacts; and equity). E.O. 13563 is supplemental to and
reaffirms the principles, structures, and definitions governing
regulatory review as established in E.O. 12866. Because this is not a
rulemaking action, this is not a significant regulatory action as
defined in Section 3(f) of E.O. 12866. In addition, scheduling actions
are not subject to either E.O. 14192, Unleashing Prosperity Through
Deregulation, or E.O. 14294, Fighting Overcriminalization in Federal
Regulations.
This action will not have substantial direct effects on the states,
on the relationship between the national government and the states, or
on the distribution of power and responsibilities among the various
levels of government. Therefore, in accordance with E.O. 13132, it is
determined that this action does not have sufficient federalism
implications to warrant the preparation of a Federalism Assessment.

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, DEA proposes to amend 21 CFR part
1308 as follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

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

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

0
2. In Sec. 1308.11:
0
a. Add paragraphs (h)(96) and (97));
0
b. Remove and reserve paragraph (h)(89).
The addition to read as follows:

Sec. 1308.11 Schedule I

* * * * *
(h) * * *

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

* * * * * * *
(96) 7-hydroxymitragynine (Methyl (E)2-((2S,3S,7aS)-3-ethyl-7a-hydroxy-8-methoxy- 9676
1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate), including its
isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, whenever the
existence of such isomers, esters, ethers, and salts is possible, when that substance alone, or
the combined amount with mitragynine pseudoindoxyl, if both are present, is:
(A) Above a specified threshold concentration, that is, greater than 1 milligram per gram
(for solid powders, encapsulated material, or other solid forms) or greater than 1
milligram per milliliter (for liquid preparations), or
(B) The mass of mitragynine present divided by 7-hydroxymitragynine or the combined mass of
7-hydroxymitragynine and mitragynine pseudoindoxyl, if both are present, is less than 100.

[[Page 65381]]

(97) Mitragynine Pseudoindoxyl (Methyl (E)-2-((1'S,6'S,7'S)-6'-ethyl-4-methoxy-3-oxo- 9672
3',5',6',7',8',8a'-hexahydro-2'H-spiro[indoline-2,1'-indolizine]-7'-yl)-3-methoxyacrylate),
including its isomers, esters, ethers, salts, and salts of isomers, esters, and ethers,
whenever the existence of such isomers, esters, ethers, and salts is possible, when that
substance alone, or the combined amount with 7-hydroxymitragynine, if both are present, is:
(A) Above a specified threshold concentration, that is, greater than 1 milligram per gram
(for solid powders, encapsulated material, or other solid forms) or greater than 1
milligram per milliliter (for liquid preparations), or
(B) The mass of mitragynine present divided by the mass of mitragynine pseudoindoxyl, or the
combined amount of mitragynine pseudoindoxyl and 7-hydroxymitragynine, if both are present,
is less than 100.

* * * * * * *
----------------------------------------------------------------------------------------------------------------

* * * * *

Signing Authority

This document of the Drug Enforcement Administration was signed on
October 8, 2026, by DEA Administrator Terrance C. Cole. That document
with the original signature and date is maintained by DEA. For
administrative purposes only, and in compliance with requirements of
the Office of the Federal Register, the undersigned DEA Federal
Register Liaison Officer has been authorized to sign and submit the
document in electronic format for publication, as an official document
of DEA. This administrative process in no way alters the legal effect
of this document upon publication in the Federal Register.

Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2026-20943 Filed 10-9-26; 12:00 pm]
BILLING CODE 4410-09-P

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