Notice2026-03914
International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; Scheduling Recommendations; N-Pyrrolidino Isotonitazene; N-Desethyl Etonitazene; Coca Leaf; MDMB-FUBINACA; Request for Comments
Primary source
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Published
February 27, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is providing interested persons with the opportunity to submit written comments concerning recommendations to impose international manufacturing and distributing restrictions on certain drug substances, under international drug control treaties. The comments received in response to this notice will be considered in preparing the United States' position on these proposals for a meeting of the United Nations Commission on Narcotic Drugs (CND) in Vienna, Austria, in March 9-13, 2026. This notice is issued under the Controlled Substances Act (CSA).
Full Text
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<title>Federal Register, Volume 91 Issue 39 (Friday, February 27, 2026)</title>
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[Federal Register Volume 91, Number 39 (Friday, February 27, 2026)]
[Notices]
[Pages 9865-9870]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-03914]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-N-1628]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; Scheduling
Recommendations; N-Pyrrolidino Isotonitazene; N-Desethyl Etonitazene;
Coca Leaf; MDMB-FUBINACA; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is providing
interested persons with the opportunity to submit written comments
concerning recommendations to impose international manufacturing and
distributing restrictions on certain drug substances, under
international drug control treaties. The comments received in response
to this notice will be considered in preparing the United States'
position on these proposals for a meeting of the United Nations
Commission on Narcotic Drugs (CND) in Vienna, Austria, in March 9-13,
2026. This notice is issued under the Controlled Substances Act (CSA).
DATES: Submit either electronic or written comments by March 5, 2026.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before March 5, 2026. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of March 5, 2026. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2026-N-1628 for ``International Drug Scheduling; Convention on
Psychotropic Substances; Single Convention on Narcotic Drugs;
Scheduling Recommendations; N-Pyrrolidino isotonitazene; N-Desethyl
etonitazene; Coca leaf; MDMB-FUBINACA; Request for Comments.'' Received
comments, those filed in a timely manner (see ), will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the
[[Page 9866]]
``Search'' box and follow the prompts and/or go to the Dockets
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852,
240-402-7500.
FOR FURTHER INFORMATION CONTACT: Edward (Greg) Hawkins, Center for Drug
Evaluation and Research, Controlled Substance Staff, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5110, Silver
Spring, MD 20993-0002, 301-796-0727, <a href="/cdn-cgi/l/email-protection#ca8faebdabb8aee4a2abbda1a3a4b98aacaeabe4a2a2b9e4ada5bc"><span class="__cf_email__" data-cfemail="8dc8e9faecffe9a3e5ecfae6e4e3fecdebe9eca3e5e5fea3eae2fb">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
The United States is a party to the 1971 Convention on Psychotropic
Substances (1971 Convention). Section 201(d)(2)(B) of the CSA (21
U.S.C. 811(d)(2)(B)) provides that when the United States is notified
under Article 2 of the 1971 Convention that the CND proposes to decide
whether to add a drug or other substance to one of the schedules of the
1971 Convention, transfer a drug or substance from one schedule to
another, or delete it from the schedules, the Secretary of State must
transmit notice of such information to the Secretary of Health and
Human Services (Secretary of HHS). The Secretary of HHS must then
publish a summary of such information in the Federal Register and
provide opportunity for interested persons to submit comments. The
Secretary of HHS must then evaluate the proposal and the comments
received from interested persons, and furnish a recommendation to the
Secretary of State that shall be binding on the representative of the
United States in discussions and negotiations relating to the proposal.
As detailed in the following paragraphs, the Secretary of State has
received notification from the Secretary-General of the United Nations
(the Secretary-General) regarding one substance to be considered for
control under the 1971 Convention. Section 201(d)(2)(B) of the CSA
requires the Secretary of HHS, after receiving a notification proposing
scheduling, to publish a notice in the Federal Register to provide the
opportunity for interested persons to submit information and comments
on the proposed scheduling action.
The United States is also a party to the 1961 Single Convention on
Narcotic Drugs (1961 Convention). The Secretary of State has received a
notification from the Secretary-General regarding three substances to
be considered for control under this convention. The CSA does not
require HHS to publish a summary of such information in the Federal
Register. Nevertheless, to provide interested and affected persons an
opportunity to submit comments regarding the recommendations for drugs
under the 1961 Convention, the notification regarding these substances
is also included in this Federal Register notice. The comments will be
shared with other relevant Agencies to assist the Secretary of State in
formulating the position of the United States on the control of these
substances. The HHS recommendations are not binding on the
representative of the United States in discussions and negotiations
relating to the proposal regarding control of substances under the 1961
Convention.
II. United Nations Notification
The United Nations identified the drug substances and explains the
basis for the scheduling recommendations as follows:
Substances Recommended To Be Added to Schedule I of the Single
Convention (1961)
--N-Pyrrolidino isotonitazene
IUPAC name: 5-Nitro-2-[4-(2-propoxy)benzyl]-1-[2-pyrrolidin-1-
yl]-1H-benzo[d]imidazole
Alternate names: Isotonitazepyne
--N-Desethyl etonitazene
IUPAC name: 2-[(4-Ethoxyphenyl)methyl]-N-ethyl-5-nitro-1H-
benzimidazole-1-ethanamine
Substance Recommended To Be Retained in Schedule I of the Single
Convention (1961)
--Coca leaf
IUPAC name: n/a
Substance Recommended To Be Added to Schedule II of the
Psychotropic Convention (1971)
--MDMB-FUBINACA
UPAC name: Methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-
carboxamido)-3,3-dimethylbutanoate
Additional Information Regarding Substances To Be Added to Schedule
I of the Single Convention on Narcotic Drugs (1961)
N-Pyrrolidino Isotonitazene
Substance Identification
N-Pyrrolidino isotonitazene (IUPAC name: 5-nitro-2-(4-(2-
propoxy)benzyl]-1-[2-(pyrrolidin-1-yl)ethyl]lH-benzo[d] imidazole,
also known as isotonitazepyne) is a 5-nitro-2-benzylbenzimidazole
synthetic opioid.
N-Pyrrolidino isotonitazene has been described as a crystalline
solid and has also been detected in falsified pharmaceuticals,
appearing as coloured tablets.
Review History
N-Pyrrolidino isotonitazene has not previously been reviewed and
is not currently under international control. Information was
brought to the review committees' the attention that the substance
is manufactured clandestinely, poses a risk to public health and has
no recognized therapeutic use.
Similarity to Known Substances and Effects on the Central Nervous
System
The chemical structure and pharmacological effects of N-
pyrrolidino isotonitazene closely resemble those of N-pyrrolidino
protonitazene, which is controlled under Schedule I of the Single
Convention on Narcotic Drugs of 1961.
Studies in animals have demonstrated that N-pyrrolidino
isotonitazene is a full agonist at [mu]-opioid receptors, with
greater potency than morphine and fentanyl. Its effects are blocked
by the opioid antagonist, naltrexone.
Convertibility Into Controlled Substances
It is not known whether N-pyrrolidino isotonitazene can be
converted into a controlled substance.
Dependence Potential
No controlled studies of the dependence potential N-pyrrolidino
isotonitazene in animals or humans have been reported. As it is a
potent [mu]-opioid receptor agonist, it would be expected to produce
dependence similar to that of other opioids, such as morphine and
fentanyl.
Actual Abuse and/or Evidence of Likelihood of Abuse
In animals, N-pyrrolidino isotonitazene had effects suggestive
of an abuse potential similar to that of morphine and fentanyl. Its
potency was greater than that of morphine and fentanyl. These
effects were blocked by the opioid antagonist naltrexone. Euphoria
and self-management of opioid withdrawal have been described by
people who report its use.
Other Health Harms
The presence of N-pyrrolidino isotonitazene has been reported in
many countries in many regions, although the extent of use is
unknown. N-Pyrrolidino isotonitazene has been analytically confirmed
in fatal and non-fatal cases of overdose, including in cases in
which it was the only substance detected.
Detection of N-pyrrolidino isotonitazene in falsified
pharmaceutical drugs in many countries and regions indicates a risk
of unintentional use and harm.
Therapeutic Usefulness
N-Pyrrolidino isotonitazene is not known to have any therapeutic
use.
Recommendation
N-Pyrrolidino isotonitazene, also referred to as
isotonitazepyne, is a synthetic opioid that is liable to abuse and
produces effects similar to those of other opioids that are
controlled under Schedule I of the 1961 Single Convention on
Narcotic Drugs. Its use causes substantial harm, including death. It
has no known therapeutic use.
Recommendation: The Committee recommended that N-pyrrolidino
isotonitazene, also referred to as isotonitazepyne, be added to
Schedule I of the 1961 Single Convention on Narcotic Drugs.
N-Desethyl Etonitazene
Substance Identification
N-Desethyl etonitazene (IUPAC name: 2-[(4-ethoxyphenyl)methyl]-
N-ethyl-5-nitro-lH-
[[Page 9867]]
benzimidazole-1-ethana mine) is a 5-nitro-2-benzylbenzimidazole
synthetic opioid. N-Desethyl etonitazene has been described as a
crystalline solid and as a yellow or beige powder. It has been found
in falsified pharmaceutical opioid tablets.
Review History
N-Desethyl etonitazene has not previously been reviewed and is
not currently under international control. Information was brought
to the attention of the reviewers that the substance is manufactured
clandestinely, poses a risk to public health and has no recognized
therapeutic use.
Similarity to Known Substances and Effects on the Central Nervous
System
N-Desethyl etonitazene is a metabolite of etonitazene, which is
controlled under Schedule I of the 1961 Convention on Narcotic
Drugs.
Studies of receptor binding indicate that N-desethyl etonitazene
is a full agonist at [mu]-opioid receptors, with greater potency
than morphine and fentanyl.
Convertibility Into Controlled Substances
It is not known whether N-desethyl etonitazene can be converted
into a controlled substance, although this is theoretically
possible.
Dependence Potential
No controlled studies of the dependence potential of N-desethyl
etonitazene in animals or humans have been reported. As it is a
potent [mu]-opioid receptor agonist, it would be expected to produce
dependence similar to that produced by other opioids, such as
morphine and fentanyl.
Actual Abuse and/or Evidence of Likelihood of Abuse
The presence of N-desethyl etonitazene has been reported in at
least 10 countries, although the extent of use is unknown.
Other Health Harms
At least three deaths have been reported in which N-desethyl
etonitazene was analytically confirmed, including when no other
opioids were involved. N-Pyrrolidino etonitazene has also been
analytically confirmed in non-fatal overdoses. The detection of N-
pyrrolidino etonitazene in falsified pharmaceutical drugs indicates
a risk of unintentional use and harm.
Therapeutic Usefulness
N-Desethyl etonitazene is not known to have any therapeutic use.
Recommendation
N-Desethyl etonitazene is a synthetic opioid that is liable to
abuse and produces ill effects similar to those produced by other
opioids that are controlled under Schedule I of the 1961 Single
Convention on Narcotic Drugs. It could theoretically be converted
into a controlled substance, although this has not been
demonstrated. Its use causes substantial harm, including death. It
has no known therapeutic use.
Recommendation: The Committee recommended that N-desethyl
etonitazene be added to Schedule I of the 1961Single Convention on
Narcotic Drugs.
Substances To Remain in Schedule I of the Single Convention on
Narcotic Drugs (1961)
Coca Leaf
Substance Identification
Coca leaf is defined in the 1961 United Nations Single
Convention on Narcotic Drugs as the leaf of the coca bush, except
when all ecgonine, cocaine and any other ecgonine alkaloid have been
removed. ``Coca bush'' refers to the plant of any species of the
genus Erythroxylon. ``Coca leaf preparations'' refer to mixtures or
products containing the coca leaf (in whole or in part). This
excludes isolated alkaloids such as cocaine and ecgonine, which are
controlled separately under the Convention.
More than 250 Erythroxylum species exist, including four primary
cultivated varieties. Coca leaf cultivation is most prevalent at
high altitudes in the Andean region and in the Amazon basin but is
increasingly being reported in other parts of the Region of the
Americas. Coca leaf is cultivated from plants grown from seeds or
cuttings. Plants can produce leaves for 20-30 years.
Coca leaves are similar in appearance to those of Laurus
nobilis, the most common characteristic trait in all species being a
darker color on the upper than on the underside of the leaf and two
lines parallel to the midrib of the leaf.
Coca leaf preparations are marketed as branded products. They
include teas, nutritional supplements, and essential oil. Coca
leaves can be pulverized finely into a greenish powder.
Coca leaf products are traditionally administered by two primary
routes: chewing and infusion. Chewing of coca leaves is widespread
and culturally accepted in the Andean highlands. The process
involves placing a wad of dried leaves in the buccal cavity, either
alone or with an alkaline substance such as lime or sodium
bicarbonate to enhance extraction of alkaloids into the oral mucosa.
Coca leaves are also infused in water and consumed as tea. Coca leaf
flour (finely ground coca leaves) can be used to make a strong tea
and is sold as a nutritional supplement.
Review History
Coca-leaf chewing was discussed at the 3rd (1952) and 4th (1954)
meetings of the Expert Committee on Drugs Liable to Produce
Addiction, which concluded that it was a form of addiction. Coca
leaf was subsequently placed under Schedule I of the 1961 Single
Convention on Narcotic Drugs.
In 1992, a pre-review of coca leaf was conducted and the
reviewers considered that coca leaf was appropriately scheduled
under the 1961 Convention, as cocaine is readily extractable from
the leaf.
In 2023, an official request from a Member State for a critical
review of coca leaf. A critical review was initiated, for conclusion
in 2025.
Similarity to Known Substances and Effects on the Central Nervous
System
Coca leaf contains a mix of alkaloids, flavonoids, terpenes,
tannins, and phenols. Cocaine and ecgonine are naturally occurring
alkaloids of note in the coca leaf. The total alkaloid content is
0.5-2.4%, depending on the species, growth environment, and stage of
leaf development. Cocaine, one alkaloid in the leaf, is produced in
significant amounts in cultivated varieties of the Erythroxylum
species, whereas wild species contain either none or only small
quantities of this alkaloid. When present, the cocaine content of
cultivated species varies among regions from 0.11% to 1.02% of the
weight of dried coca leaf. Absorption of alkaloids from coca leaf
depends on the route of administration, the quantity of leaves used,
the type of alkali added, and if masticated, the duration of
mastication. The plasma concentrations of cocaine resulting from
coca leaf chewing or ingestion may overlap with plasma
concentrations of cocaine resulting from cocaine use by inhalation
or injection.
It has been demonstrated in animal models that coca leaf
alkaloids affect the central nervous system, including decreasing
food intake. Some coca leaf extracts increase locomotor activity,
while others do not. The stimulant effects of coca leaf in animal
models may be due to inhibition of monoamine re-uptake. Local
anesthetic effects have also been observed in animal models.
People who chew coca leaf report mild psychostimulant effects,
including euphoria, and have described it as an ``energizer''.
Increased heart rate and blood pressure and vasoconstriction have
also been reported. Analgesic effects of high-dose coca leaf
preparations have been attributed to a local anesthetic effect.
Convertibility Into Controlled Substances
Coca leaf contains cocaine, a naturally occurring alkaloid that
can be processed to obtain coca paste. Coca paste is filtered and
dried to obtain cocaine base, which is further processed to obtain
cocaine hydrochloride. By chemical definition, the manufacture of
cocaine from coca leaf is an extraction; however, the reference in
the Guidance document for the understanding of this term reads as
follows:
A substance is convertible if it is of such a kind as to make
it, by the ease of the process and by the yield, practicable and
profitable for a clandestine manufacturer to transform the substance
in question into controlled drugs.
Obtaining coca paste from coca leaf and purification of
different forms of cocaine from coca paste are straightforward and
do not require special expertise or equipment. Except for kerosene,
the chemicals and reagents used in these processes are listed in the
United Nations Convention against Illicit Traffic in Narcotic Drugs
and Psychotropic Substances of 1988.
Most coca leaf is used for clandestine manufacture of cocaine in
at least some countries. It is estimated that 1 ha of coca bush
cultivation produces approximately 4.2 tons of fresh coca leaves per
year; 1 ton of fresh leaves produces approximately 1.5 kg of coca
paste or 1.4 kg of cocaine base; 1 kg of cocaine base results in
roughly 0.9 kg of cocaine hydrochloride, which typically contains
about 85% pure cocaine. Cocaine production has increased
significantly in several countries, in parallel with increased coca
bush cultivation. Some countries have reported historically high
levels in recent
[[Page 9868]]
years. Globally, a 34% increase in cocaine production was reported
in 2023 over the previous year.
The 1961 Convention lists both coca leaf and cocaine as
controlled substances under Schedule 1. Accordingly, as coca leaf is
used to manufacture cocaine, one controlled substance (cocaine) is
made from another (coca leaf), thereby meeting the Convention's
criterion for convertibility.
Dependence Potential
No controlled studies in animal models of the dependence
potential of coca leaf were identified.
A few studies in humans assessed development of a dependence
syndrome with coca leaf. Older ethnographic studies did not describe
tolerance, withdrawal symptoms, or compulsive patterns of use;
however, a recent epidemiological study of more than 1300 people who
chewed coca leaf found that 2.3% of those who reported ever chewing
coca leaf met the ICD-10 criterion for dependence.
People who met the criterion had a lower quality of life than
people who did not. Two countries in different geographical regions
reported presentations for drug dependence treatment related to coca
leaf use. No studies were available that provided robust evidence to
determine the prevalence of coca leaf dependence.
Actual Abuse and/or Evidence of Likelihood of Abuse
In a model of drug discrimination in animals, high-dose
preparations of coca leaf produced effects that closely resembled
those of cocaine.
Many countries in various regions have reported nonmedical use
of coca leaf and increasing numbers of seizures of coca leaf.
Other Health Harms
Few high-quality data are available on the acute toxicity
associated with coca leaf. No fatal overdoses have been documented
after traditional use of coca leaf, although coca leaf may not
readily be differentiated from cocaine in biological samples from
such cases.
Reported adverse effects of chewing coca leaf appear to be
limited. They include oral problems (including risk of oral
carcinoma) and cardiovascular, intestinal, hormonal, and
neurological issues.
Therapeutic Usefulness
The potential therapeutic effects of various Erythroxylum
species have been investigated in vitro and in animal models. Recent
investigations have been conducted of its antioxidant, antibiotic,
anticancer, antihypertensive, antidiabetic, and neuroprotective
effects. For example, some Erythroxylum species may have anticancer
effects, comparable to those of standard chemotherapy agents in some
cases; however, the activity varies with different extracts and cell
lines. Similarly, studies in vitro and in vivo show variable but
sometimes strong antioxidant and anti-inflammatory effects. In
humans, use of E. coca by chewing and drinking tea reduced post-meal
glucose in people with no underlying metabolic disorder. Overall,
studies in animals and humans suggest that coca leaf may have some
therapeutic applications, although the evidence is limited.
Traditional use of coca leaf in Andean regions includes chewing
and infusion to increase energy and prevent altitude sickness,
although evidence of its usefulness for treating altitude sickness
is mixed. Its use as a nutritional supplement is limited by its
cocaine content. Use of coca leaf for the manufacture of
pharmaceutical and industrial products has decreased with time. In a
few countries, preparations of coca leaf are used as traditional
herbal medicines. Use of coca leaf is permitted under national
legislation in some countries when practiced within traditional or
cultural contexts.
Recommendation
The Expert Committee, when deciding whether to recommend
international control, decides whether a substance: ``{l) is liable
to similar abuse and productive of similar ill-effects as the
substances in Schedule I or Schedule II; or (2) is convertible into
a substance already in Schedule I or Schedule II.'' The reference in
the Guidance document for the understanding of this term reads as
follows:
A substance is convertible if it is of such a kind as to make
it, by the ease of the process and by the yield, practicable and
profitable for a clandestine manufacturer to transform the substance
in question into controlled drugs.
In the 1961 Single Convention on Narcotic Drugs, coca leaf is
defined as the leaf of the coca bush, except when all ecgonine,
cocaine, and any other ecgonine alkaloids have been removed. Coca
leaf and cocaine are classified as distinct substances under
Schedule I of the 1961 Single Convention. The simplicity of
extracting cocaine from coca leaf and its high yield and
profitability are well known.
Accordingly, conversion of coca leaf into cocaine constitutes
production of one substance (cocaine) in Schedule I from another
substance in Schedule I (coca leaf), thereby meeting the
Convention's criterion for convertibility. The Committee also
reviewed evidence of a marked increase in coca leaf cultivation and
in the production of cocaine-related substances, in the context of
significant, increasing public health concern about cocaine use. In
that context, the Committee considered that reducing or removing
existing international controls on coca leaf could pose an
especially serious risk to public health.
The evidence presented in the critical review and other
information considered by the Committee indicate that traditional
coca leaf use by chewing or in tea does not appear to pose a
particularly serious public health risk, although the safety of
long-term use is not well documented. In addition, it was recognized
that coca leaf has an important cultural and therapeutic
significance for Indigenous peoples and other communities and that
there are exemptions for traditional use of coca leaf in certain
national frameworks. Emerging research may support the therapeutic
applications of coca leaf; however, the current body of evidence
does not provide a robust basis for such use.
Recommendation: The Committee recommended that coca leaf be
retained in Schedule I of the 1961 Single Convention on Narcotic
Drugs.
Substances To Be Added to Schedule IV of the Psychotropic
Convention (1971)
MDMB-FUBINACA
Substance Identification
MDMB-FUBINACA {IUPAC name: Methyl 2-{[1-{4-
fluorobenzyl)indazole-3-carbonyl]amino{time} -3,3-dimethylbutanoate)
is a synthetic cannabinoid with a stereogenic centre (C2), which can
exist as two stereoisomers (enantiomers): methyl (25)-2-{[1-(4-
fluorobenzyl)indazole-3-carbonyl]amino{time} -3,3-dimethylbutanoate
and methyl (2R)-2-{[1-{ 4-fluorobenzyl)i ndazole-3-
carbonyl]amino{time} -3,3-dimethylbutanoate.
MDMB-FUBINACA has been described as a powder (usually white) and
has been found sprayed onto herbal products. It is often marketed as
dried leaves or powder and sold in e-liquids for vaping.
Review History
MDMB-FUBINACA has not previously been reviewed and is not
currently under international control. Information was brought to
the reviewers attention that this substance is manufactured
clandestinely, poses a risk to public health and has no recognized
therapeutic use.
Similarity to Known Substances and Effects on the Central Nervous
System
MDMB-FUBINACA is a synthetic cannabinoid that binds to CBl and
CB2 receptors with high affinity and is a potent full agonist at
both receptors. Its effects are similar to those of other potent CBl
agonists that are currently controlled under Schedule II of the
Convention on Psychotropic Substances of 1971. No controlled studies
of the effects of MDMB-FUBINACA have been reported. In animals, it
has been shown to produce behavioral effects consistent with delta-
9-THC, with the effects lasting many hours. In humans, it produces
symptoms typical of high doses of cannabinoids, including agitation
or sedation, vomiting, short-term memory loss, salivation,
rhinorrhoea, mydriasis, tachycardia and anxiety.
Convertibility Into Controlled Substances
MDMB-FUBINACA can be chemically modified to produce structurally
related synthetic cannabinoids such as ADB-FUBINACA. The yields and
prevalence of such conversions are, however, uncertain.
Dependence Potential
No studies of the dependence potential of MDMB-FUBINACA in
animals or humans have been reported. Its effects at CB1 receptors
suggest that it would produce dependence similar to that produced by
delta-9-THC and other synthetic cannabinoid receptor agonists.
Countries in two regions reported presentations for treatment of
drug dependence due to the use of MDMB-FUBINACA.
Actual abuse and/or evidence of likelihood of abuse:
In an animal model predictive of abuse potential, MDMB-FUBINACA
had effects
[[Page 9869]]
similar to delta-9-THC. No studies have been conducted to determine
the likelihood of abuse of MDMB-FUBINACA in humans.
Other Health Harms
MDMB-FUBINACA use has been associated with mortality and
morbidity in several countries, including a large number of non-
fatal poisonings. Documented adverse effects include agitation or
sedation, vomiting, short-term memory loss, salivation, rhinorrhoea,
mydriasis, tachycardia and anxiety, similar to those seen with
delta-9-THC and other synthetic cannabinoid receptor agonists. The
increased detection of MDMB-FUBINACA has been linked to emergence of
a simplified one-step synthesis method, which requires readily
available precursor chemicals.
Therapeutic Usefulness
MDMB-FUBINACA is not known to have any therapeutic use.
Recommendation
MDMB-FUBINACA is a synthetic cannabinoid receptor agonist
administered by smoking plant material sprayed with the substance or
inhaling vapor after heating. Its mode of action suggests the
potential for dependence and the likelihood of abuse. Its use has
been associated with a range of severe adverse effects, including
death. These effects are similar to those produced by other
synthetic cannabinoids that are placed in Schedule II of the
Convention on Psychotropic Substances of 1971.
MDMB-FUBINACA has no therapeutic use.
Recommendation: The Committee recommended that MDMB-FUBINACA be
added to Schedule II of the Convention on Psychotropic Substances of
1971.
III. Discussion
Although specific scheduling recommendations for each of the drug
substances have been made, the CND is not obliged to follow those
recommendations. Options available to the CND for substances considered
for control under the 1971 Convention include the following: (1) accept
the recommendations; (2) accept the recommendations to control but
control the drug substance in a schedule other than that recommended;
or (3) reject the recommendations entirely.
N-Pyrrolidino isotonitazene (isotonitazepyne) is a synthetic opioid
of the benzimidazole class that is similar in structure to
isotonitazene. In vitro binding and activity data indicate that
isotonitazepyne is approximately 10-fold more potent at the mu opioid
receptor than fentanyl. Isotonitazepyne has been detected in several
toxicology cases in the United States, Europe, and Australia. Common
adverse events of opioid agonists include nausea, vomiting,
constipation, pruritus, dizziness, sedation, and respiratory
depression, where significant respiratory depression can lead to death.
Based on in vitro pharmacology and case reports, substances in the
nitazepyne class are expected to produce euphoria and have a high
potential for abuse and physical dependence. Repeated non-medical use
would likely result in tolerance, physical dependence, and withdrawal
effects consistent with other potent opioids. There are no commercial
uses or approved medical uses for isotonitazepyne in the United States.
Isotonitazepyne is controlled in Schedule I under the CSA and will not
require additional permanent controls domestically if it is placed in
Schedule I of the 1961 Single Convention.
N-Desethyl etonitazene is a synthetic opioid of the nitazene class
that is similar in structure to etonitazene. In vitro binding and
activity data indicate that N-desethyl etonitazene is approximately 10-
fold more potent at the mu opioid receptor than fentanyl. In animal
behavior studies it produced subjective effects that were
indistinguishable from morphine. As a result, it is assumed that
metonitazepyne will have an abuse potential similar to that of other
opioid agonists and produce adverse events that include nausea,
vomiting, constipation, pruritus, dizziness, sedation, and respiratory
depression, where significant respiratory depression can lead to death.
In the United States, N-Desethyl etonitazene was detected in 2
toxicology cases; however, other NPS or other drugs of abuse were
detected in these individuals and could have been a contributing factor
to the fatality. According to the NFLIS database, N-Desethyl
etonitazene was first detected in 2023, and there have been seven
confirmed law enforcement seizures to date. There are no commercial
uses or approved medical uses for N-Desethyl etonitazene in the United
States. N-Desethyl etonitazene is controlled in Schedule I under the
CSA and will not require additional permanent controls domestically if
it is placed in Schedule I of the 1961 Single Convention.
Coca leaf is defined by the 1961 United Nations Single Convention
on Narcotic Drugs as the leaf of the coca bush, except when all
ecgonine, cocaine, and any other ecgonine alkaloids have been removed.
Coca leaf is consumed through two primary mechanisms (1) direct chewing
of the leaves, which also involves placing the leaves in the buccal
cavity, and (2) extraction of the alkaloids for oral consumption as
through a tea. The coca leaf contains several substances; alkaloids,
flavonoids, terpenes, and phenols, several of which either are, or can
be easily converted, into substances with known abuse potential and
physical dependence. People who chew coca leaves have reported
psychostimulant effects such as euphoria and increased energy. The coca
leaf contains cocaine, a known stimulant with a high potential for
abuse. The coca leaf is used to clandestinely manufacture cocaine which
is illicitly distributed throughout the world. In the U.S., federal law
enforcement reported seizing more than 91,600 kg of cocaine in the
first half of 2025 alone. According to the National Survey on Drug Use
and Health, approximately 470,000 U.S. residents age 12 or older
reported past-year use of cocaine in 2023, with the National Center for
Health Statistics reporting 29,918 overdose deaths involving cocaine in
the same year. Cocaine is approved as a nasal and topical analgesic in
the U.S., and is controlled in schedule II under the CSA. Coca leaf
(leaves), which contains cocaine, is also controlled in Schedule II
under the CSA. Domestic scheduling actions on the coca leaf will not be
necessary regardless of the outcome of the vote for coca leaf to remain
in Schedule I of the 1961 Convention.
MDMB-FUBINACA is a semi-synthetic cannabinoid which functions as an
agonist of the cannabinoid 1 (CB1) receptor. MDMB-FUBINACA is reported
to produce similar effects as tetrahydrocannabinol (THC) after smoking
or oral administration. In animals, MDMB-FUBINACA produced suppression
of locomotor activity, analgesia, hypothermia, and ring mobility
similar to delta-9-THC. MDMB-FUBINACA also fully substituted for the
effects of THC in a drug discrimination study. It was first identified
in law enforcement seizures in the U.S. in 2017 and has since been
identified in 824 drug seizures. There are no commercial or approved
medical uses for MDMB-FUBINACA. MDMB-FUBINACA is controlled in Schedule
I under the CSA and will not require additional permanent controls
domestically if it is placed in Schedule II of the 1971 Psychotropic
Convention.
FDA, on behalf of the Secretary of HHS, invites interested persons
to submit comments on the recommendations from the United Nations
concerning these drug substances. FDA, in cooperation with the National
Institute on Drug Abuse, will consider the comments on behalf of HHS in
evaluating the scheduling recommendations. Then, under section
201(d)(2)(B) of the CSA, HHS will recommend to the Secretary of State
what position the United States should take when voting on the
recommendations for control of
[[Page 9870]]
substances under the 1971 Convention at the CND meeting in March 2025.
Comments regarding the recommendations for control of N-pyrrolidino
isotonitazene, N-desethyl etonitazene, and coca leaf under the 1961
Single Convention will also be forwarded to the relevant Agencies for
consideration in developing the U.S. position regarding narcotic
substances at the CND meeting.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-03914 Filed 2-26-26; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on February 27, 2026.
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