International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization; Scheduling Recommendations; Dronabinol (delta, 7064-7070 [2019-03662]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 84, Number 41 (Friday, March 1, 2019)]
[Notices]
[Pages 7064-7070]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-03662]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-N-0767]


International Drug Scheduling; Convention on Psychotropic 
Substances; Single Convention on Narcotic Drugs; World Health 
Organization; Scheduling Recommendations; Dronabinol (delta-9-
tetrahydrocannabinol) and its Stereoisomers; Cannabis, Cannabis Resin, 
Extracts and Tinctures; Cannabidiol Preparations; and Pharmaceutical 
Preparations of Cannabis; 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 comments about the 
World Health Organization (WHO) recommendations to impose international 
manufacturing and distributing restrictions, under international 
treaties, on certain drug substances. 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, March 18-22, 
2019. This notice is issued under the Controlled Substances Act (CSA).

DATES: Submit either electronic or written comments on the notice by 
March 14, 2019. The short time period for the submission of comments is 
needed to ensure that the U.S. Department of Health and Human Services 
(HHS) may, in a timely fashion, carry out the required action and be 
responsive to the United Nations.

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 14, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of March 14, 2019. Comments received 
by mail/hand delivery/courier

[[Page 7065]]

(for written/paper submissions) will be considered timely if they are 
postmarked or the delivery service acceptance receipt is on or before 
that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
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 https://www.regulations.gov.
     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:
     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.
     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-2019-N-0767 for ``International Drug Scheduling; Convention on 
Psychotropic Substances; Single Convention on Narcotic Drugs; World 
Health Organization; Scheduling Recommendations; Cannabis and Cannabis 
Resin; Dronabinol (delta-9-tetrahydrocannabinol); Tetrahydrocannabinol 
(Isomers of delta-9-tetrahydrocannabinol); Extracts and Tinctures of 
Cannabis; Cannabidiol Preparations; Preparations Produced Either by 
Chemical Synthesis or as Preparation of Cannabis; Request for 
Comments.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday.
     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 https://www.regulations.gov. 
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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: James R. Hunter, Center for Drug 
Evaluation and Research, Controlled Substance Staff, Food and Drug 
Administration, 10903 New Hampshire Ave. Bldg. 51, Rm. 5150, Silver 
Spring, MD 20993-0002, 301-796-3156, james.hunter@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: 

I. Background

    The United States is a party to the 1971 Convention on Psychotropic 
Substances (1971 Psychotropic 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 Psychotropic Convention that the 
CND proposes to decide whether to add a drug or other substance to one 
of the schedules of the 1971 Psychotropic 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 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 two substances to be considered for 
deleting from the 1971 Psychotropic Convention. This notification 
reflects the recommendation from the 41st WHO Expert Committee for Drug 
Dependence (ECDD), which met in November 2018. In the Federal Register 
of October 10, 2018 (83 FR 50938), FDA announced the WHO ECDD review 
and invited interested persons to submit information for WHO's 
consideration.
    The full text of the notification from the Secretary-General is 
provided in section II of this document. 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 Single Convention). The Secretary of State has 
received a notification from the Secretary-General regarding several 
substances to be considered for changes in 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

[[Page 7066]]

opportunity to submit comments regarding the WHO recommendations for 
narcotic drugs, 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 
Single Convention.

II. United Nations Notification

    The formal notification from the United Nations that identifies the 
drug substances and explains the basis for the recommendations is 
reproduced as follows (non-relevant text removed):

    Reference: NAR/CL.3/2019
    WHO/ECDD41; 1961C-Art.3, 1971C-Art.2 CU 2019/36/DTA/SGB (A)

    The Secretary-General of the United Nations presents his 
compliments to the Secretary of State of the United States of America 
and has the honour to inform the Government that on 28 January 2019, he 
received a notification from the Director-General of the World Health 
Organization (WHO), pursuant to article 3, paragraphs 1, 3, 5, and 6 of 
the Single Convention on Narcotic Drugs of 1961 as amended by the 1972 
Protocol (1961 Convention), and article 2, paragraphs 1, 4, and 6 of 
the Convention on Psychotropic Substances of 1971 (1971 Convention), 
with the following recommendations regarding the review of cannabis and 
cannabis-related substances as follows:

--Cannabis and cannabis resin
    To be deleted from Schedule IV of the 1961 Convention.

--Dronabinol (delta-9-tetrahydrocannabinol)

    To be added to Schedule I of the 1961 Convention.
    To be deleted from Schedule II of the 1971 Convention, subject to 
the CND's adoption of the recommendation to add dronabinol and its 
stereoisomers (delta-9-tetrahydrocannabinol) to Schedule I of the 1961 
Convention.

--Tetrahydrocannabinol (Isomers of delta-9-tetrahydrocannabinol)

    To be added to Schedule I of the 1961 Convention subject to the 
CND's adoption of the recommendation to add dronabinol and its 
stereoisomers (delta-9-tetrahydrocannabinol) to Schedule I of the 1961 
Convention.
    To be deleted from Schedule I of the 1971 Convention, subject to 
the CND's adoption of the recommendation to add tetrahydrocannabinol to 
Schedule I of the 1961 Convention on Narcotic Drugs.

--Extracts and tinctures

    To be deleted from Schedule I of the 1961 Convention.

--Cannabidiol preparations

    To give effect to the recommendation of the fortieth meeting of the 
ECDD that preparations considered to be pure cannabidiol (CBD) should 
not be scheduled within the International Drug Control Conventions by 
adding a footnote to the entry for cannabis and cannabis resin in 
Schedule I of the 1961 Convention to read, ``Preparations containing 
predominantly cannabidiol and not more than 0.2 percent of delta-9-
tetrahydrocannabinol are not under international control.''
    Preparations produced either by chemical synthesis or as 
preparation of cannabis, that are compounded as pharmaceutical 
preparations with one or more other ingredients and in such a way that 
delta-9-tetrahydrocannabinol (dronabinol) cannot be recovered by 
readily available means or in a yield which would constitute a risk to 
public health.
    To be added to Schedule III of the 1961 Convention.
    In accordance with the provisions of article 3, paragraph 2 of the 
1961 Convention, and article 2, paragraph 2 of the 1971 Convention, the 
Secretary-General hereby transmits the notification as annex I to the 
present note. The relevant extract from the report of the 41st meeting 
of the WHO Expert Committee on Drug Dependence is hereby transmitted as 
annex II. For time reasons, this notification and its annexes I and II 
are transmitted in English only. The notification will be transmitted 
in French and Spanish as soon as it becomes available.
    Also in accordance with the same provisions, the notification from 
WHO will be brought to the attention of the 62nd session of the 
Commission on Narcotic Drugs (from 14 to 22 March 2019) in document E/
CN.7/2019/12, which will be made available on the website of the 62nd 
session of the CND: https://www.unodc.org/unodc/en/commissions/CND/session/62_Session_2019/session-62-of-the-commission-on-narcotic-drugs.html.
    To assist the Commission in reaching a decision, it would be 
appreciated if the Government could communicate any comments it 
considers relevant to the recommendations made by WHO regarding changes 
in the scope of control of cannabis and cannabis-related substances 
under the 1961 Convention, namely:

--Cannabis and cannabis resin
--Dronabinol (delta-9-tetrahydrocannabinol)
--Tetrahydrocannabinol (Isomers of delta-9-tetrahydrocannabinol)
--Extracts and tinctures
--Cannabidiol preparations;
--Preparations produced either by chemical synthesis or as preparation 
of cannabis, that are compounded as pharmaceutical preparations with 
one or more other ingredients and in such a way that delta-9-
tetrahydrocannabinol (dronabinol) cannot be recovered by readily 
available means or in a yield which would constitute a risk to public 
health; as well any economic, social, legal, administrative or other 
factors that it considers relevant to the recommendations made by WHO 
regarding changes in the scope of control of cannabis and cannabis-
related substances under the 1971 Convention, namely:
--Dronabinol (delta-9-tetrahydrocannabinol)
--Tetrahydrocannabinol (Isomers of delta-9-tetrahydrocannabinol)

1 February 2019

Annex I

Letter Addressed to the Secretary-General of the United Nations From 
the Director-General of the World Health Organization, 24 January 2019
    ``The forty-first meeting of the WHO Expert Committee on Drug 
Dependence (ECDD) convened from 12 to 16 November 2018 at WHO 
headquarters in Geneva. Following recommendations made by the fortieth 
ECDD in June 2018 regarding the pre-review of cannabis and cannabis-
related substances, the forty-first ECDD carried out critical reviews 
of these substances to determine the most relevant level of 
international control for cannabis and cannabis-related substances and 
whether the World Health Organization (WHO) should recommend changes in 
their level of control.
    In addition, the forty-first WHO ECDD reviewed ten New Psychoactive 
Substances (NPS), five of which are synthetic opioids; and two pain-
relieving medicines, pregabalin and tramadol. The recommendations 
regarding these substances are communicated to you through a separate 
letter under the same date as this letter.
    The review of cannabis and cannabis-related substances was carried 
out in relation to Resolution 52/5 of the Commission on Narcotic Drugs, 
in which the Commission stated that it looked forward to an updated 
report on cannabis by the Expert Committee.

[[Page 7067]]

    With reference to Article 3, paragraphs 1, 3, 5, and 6 of the 
Single Convention on Narcotic Drugs (1961), as amended by the 1972 
Protocol, and Article 2, paragraphs 1, 4, and 6 of the Convention on 
Psychotropic Substances (1971), I am pleased to submit recommendations 
of the forty-first meeting of the ECDD regarding the review of cannabis 
and cannabis-related substances as follows:

Cannabis and cannabis-related substances

--Cannabis and cannabis resin

    To be deleted from Schedule IV of the Single Convention on Narcotic 
Drugs (1961).

--Dronabinol (delta-9-tetrahydrocannabinol)

    To be added to Schedule I of the Single Convention on Narcotic 
Drugs (1961).
    To be deleted from Schedule II of the Convention on Psychotropic 
Substances (1971), subject to the CND's adoption of the recommendation 
to add dronabinol and its stereoisomers (delta-9-tetrahydrocannabinol) 
to Schedule I of the Single Convention on Narcotic Drugs (1961).

--Tetrahydrocannabinol (Isomers of delta-9-tetrahydrocannabinol)

    To be added to Schedule I of the Single Convention on Narcotic 
Drugs (1961), subject to the CND's adoption of the recommendation to 
add dronabinol and its stereoisomers (delta-9-tetrahydrocannabinol) to 
Schedule I of the Single Convention on Narcotic Drugs (1961).
    To be deleted from Schedule I of the Convention on Psychotropic 
Substances (1971), subject to the CND's adoption of the recommendation 
to add tetrahydrocannabinol to Schedule I of the Single Convention on 
Narcotic Drugs (1961).

--Extracts and tinctures

    To be deleted from Schedule I of the Single Convention on Narcotic 
Drugs (1961).

--Cannabidiol preparations
    To give effect to the recommendation of the fortieth meeting of the 
ECDD that preparations considered to be pure CBD should not be 
scheduled within the International Drug Control Conventions by adding a 
footnote to the entry for cannabis and cannabis resin in Schedule I of 
the Single Convention on Narcotic Drugs (1961) to read ``Preparations 
containing predominantly cannabidiol and not more than 0.2 percent of 
delta-9-tetrahydrocannabinol are not under international control.''

--Preparations produced either by chemical synthesis or as preparation 
of cannabis, that are compounded as pharmaceutical preparations with 
one or more other ingredients and in such a way that delta-9-
tetrahydrocannabinol (dronabinol) cannot be recovered by readily 
available means or in a yield which would constitute a risk to public 
health

    To be added to Schedule III of the Single Convention on Narcotic 
Drugs (1961).
    The assessments and findings on which they are based are set out in 
detail in the forty-first report of the WHO Expert Committee on Drug 
Dependence. An extract of the report is attached in Annex 1 of this 
letter.
    I am very pleased with the ongoing collaboration between WHO, the 
United Nations Office on Drugs and Crime (UNODC), and the International 
Narcotics Control Board (INCB), and in particular, how this 
collaboration has benefited the work of the WHO Expert Committee on 
Drug Dependence (including through the participation of UNODC and INCB 
in the forty-first meeting of the ECDD), and more generally, the 
implementation of the operational recommendations of the United Nations 
General Assembly Special Session (UNGASS) 2016.''

Annex II

Extract From the Report of the 41st Expert Committee on Drug Dependence

5. Cannabis and Cannabis-Related Substances

5.1 Cannabis and Cannabis Resin

    In the 1961 Single Convention on Narcotic Drugs, cannabis and 
cannabis resin are described, respectively, as the flowering or 
fruiting tops of the cannabis plant (excluding the seeds and leaves 
when not accompanied by the tops) from which the resin has not been 
extracted and as the separated resin, whether crude or purified, 
obtained from the cannabis plant. Reference to cannabis below will be 
taken to also include cannabis resin. Of the many compounds in 
cannabis, delta-9-tetrahydrocannabinol ([Delta]9-THC) is the principal 
psychoactive constituent of cannabis, while CBD is also present but is 
not psychoactive.
    Following consumption of cannabis, the adverse effects experienced 
include dizziness and impairment of motor control and cognitive 
function. As a result of the effects on movement and cognition, 
cannabis use can impair driving. There are particular risks of cannabis 
use reported for children, such as respiratory depression, tachycardia 
and coma. The adverse effects of cannabis consumption are similar to 
those produced by [Delta]9-THC alone.
    There are also a number of adverse effects associated with long-
term cannabis use, particularly increased risk of mental health 
disorders such as anxiety, depression, and psychotic illness. Chronic 
regular cannabis use is particularly problematic for young people 
because of its effects on the developing brain.
    Cannabis can cause physical dependence in people who use the drug 
daily or near daily. This is evidenced by the onset of cannabis 
withdrawal symptoms that occur upon abstinence; these symptoms include 
gastrointestinal disturbance, appetite changes, irritability, 
restlessness and sleep impairment. Clinical diagnostic guidelines such 
as DSM-5 and ICD-10 recognize cannabis dependence and other disorders 
related to cannabis use.
    The Committee considered information regarding the therapeutic 
indications of cannabis and ongoing research into its possible medical 
applications. A number of countries permit the use of cannabis for the 
treatment of medical conditions such as chemotherapy-induced nausea and 
vomiting, pain, sleep disorders, and spasticity associated with 
multiple sclerosis. The Committee recognized the limited robust 
scientific evidence on the therapeutic use of cannabis. However, some 
oral pharmaceutical preparations of cannabis have therapeutic 
advantages for treatment of conditions such as certain forms of pain 
and epilepsy. Preparations of cannabis are defined as a mixture, solid, 
or liquid containing cannabis and are generally subject to the same 
measures of control as cannabis and cannabis resin as per Article 2.3 
of the 1961 Single Convention on Narcotic Drugs.
    Cannabis and cannabis resin are included in Schedule I and Schedule 
IV of the 1961 Single Convention on Narcotic Drugs. Substances that are 
included in both these Schedules are particularly liable to abuse and 
to produce ill-effects and have little or no therapeutic use. Other 
substances that are included in both Schedules I and IV are fentanyl 
analogues, heroin, and other opioids that are considered especially 
dangerous. Use of all these substances is associated with a significant 
risk of death, whereas cannabis use is not associated with such risk.
    The evidence presented to the Committee did not indicate that 
cannabis plant and cannabis resin were particularly liable to produce 
ill-effects similar to the effects of the other substances in Schedule 
IV of the 1961

[[Page 7068]]

Single Convention on Narcotic Drugs. In addition, preparations of 
cannabis have shown therapeutic potential for treatment of pain and 
other medical conditions such as epilepsy and spasticity associated 
with multiple sclerosis. In line with the above, cannabis and cannabis 
resin should be scheduled at a level of control that will prevent harm 
caused by cannabis use and, at the same time, will not act as a barrier 
to access and to research and development of cannabis-related 
preparation for medical use.
    The Committee concluded that the inclusion of cannabis and cannabis 
resin in Schedule IV is not consistent with the criteria for a drug to 
be placed in Schedule IV.
    The Committee then considered whether cannabis and cannabis resin 
were better placed in Schedule I or Schedule II of the 1961 Single 
Convention on Narcotic Drugs. While the Committee did not consider that 
cannabis is associated with the same level of risk to health as most of 
the other drugs that have been placed in Schedule I, it noted the high 
rates of public health problems arising from cannabis use and the 
global extent of such problems and, for these reasons, recommended that 
cannabis and cannabis resin continue to be included in Schedule I of 
the 1961 Single Convention on Narcotic Drugs.
     Recommendation 5.1: The Committee recommended that 
Cannabis and Cannabis Resin be deleted from Schedule IV of the 1961 
Single Convention on Narcotic Drugs.

5.2 Dronabinol (delta-9-tetrahydrocannabinol; [Delta]9-THC)

    The main psychoactive substance in the cannabis plant is one of the 
four stereoisomers of delta-9-tetrahydrocannabinol ([Delta]9-THC). This 
substance has therapeutic uses and is sometimes known by its 
international non-proprietary name dronabinol. It is currently placed 
in Schedule II of the 1971 Convention on Psychotropic Substances.
    At the time of the adoption of the 1961 Single Convention on 
Narcotic Drugs, scientific research had not identified [Delta]9-THC as 
the main psychoactive compound in cannabis. Subsequently, [Delta]9-THC 
was included in the 1971 Convention on Psychotropic Substances at its 
inception. In previous ECDD reviews, the active and naturally occurring 
stereoisomer of [Delta]9-THC known as dronabinol had been considered in 
a synthetic form as a pharmaceutical preparation. Following a 
recommendation from the 27th ECDD, dronabinol was placed in Schedule II 
of the 1971 Convention on Psychotropic Substances. The Commission on 
Narcotic Drugs, however, did not adopt a subsequent recommendation to 
place dronabinol in Schedule III of the 1971 Convention on Psychotropic 
Substances.
    The Committee noted that whereas in these previous ECDD reviews 
[Delta]9-THC, and especially its active stereoisomer dronabinol, had 
been considered in a synthetic form as a pharmaceutical preparation, 
[Delta]9-THC today also refers to the main psychoactive component of 
cannabis and the principal compound in illicit cannabis-derived 
psychoactive products. Some of these products contain [Delta]9-THC at 
concentrations as high as 90 percent. Butane hash oil is an example of 
a high purity [Delta]9-THC illicit cannabis-derived product that has 
recently emerged and is being used by heating and inhalation of the 
vapor. In such high purity illicitly derived forms, [Delta]9-THC 
produces ill-effects, dependence, and abuse potential that is at least 
as great as for cannabis, which is placed in Schedule I of the 1961 
Single Convention on Narcotic Drugs.
    A substance liable to similar abuse and productive of similar ill-
effects as that of a substance already scheduled within the 1961 Single 
Convention on Narcotic Drugs would normally be scheduled in the same 
way as that substance. As [Delta]9-THC is liable to similar abuse as 
cannabis and has similar ill-effects, it meets the criteria for 
inclusion in Schedule I of the 1961 Single Convention on Narcotic 
Drugs. It was further recognized that cocaine, the principal active 
compound in coca, is placed along with coca leaf in Schedule I of the 
1961 Single Convention on Narcotic Drugs and morphine; the principal 
active compound in opium is placed with opium in the same schedule. 
Placing [Delta]9-THC, the principal active compound in cannabis, in the 
same schedule as cannabis would be consistent with this approach.
    Based on requests received from Member States and information 
received from other United Nations agencies, the Committee understood 
that placing [Delta]9-THC under the same Convention and in the same 
schedule as cannabis, Schedule I of the 1961 Single Convention on 
Narcotic Drugs, would greatly facilitate the implementation of the 
control measures of the Conventions in Member States. Accordingly:
     Recommendation 5.2.1: The Committee recommended that 
dronabinol and its stereoisomers (delta-9-tetrahydrocannabinol) be 
added to Schedule I of the 1961 Single Convention on Narcotic Drugs.
    As indicated in the ``Guidance on the WHO review of psychoactive 
substances for international control,'' to facilitate efficient 
administration of the international control system, it is not advisable 
to place a substance under more than one Convention. Accordingly:
     Recommendation 5.2.2: The Committee recommended the 
deletion of dronabinol and its stereoisomers (delta-9-
tetrahydrocannabinol) from the 1971 Convention on Psychotropic 
Substances, Schedule II, subject to the Commission's adoption of the 
recommendation to add dronabinol and its stereoisomers (delta-9-
tetrahydrocannabinol) to Schedule I of the 1961 Single Convention on 
Narcotic Drugs.

5.3 Tetrahydrocannabinol (Isomers of delta-9-tetrahydrocannabinol)

    There are currently six isomers of tetrahydrocannabinol (THC) 
listed in Schedule I of the 1971 Convention on Psychotropic Substances. 
These six isomers are chemically similar to delta-9-
tetrahydrocannabinol ([Delta]9-THC), which is currently listed in 
Schedule II of the 1971 Convention on Psychotropic Substances, but 
which the Committee has recommended deleting from this Schedule and 
including in Schedule I of the 1961 Single Convention on Narcotic 
Drugs.
    While these six isomers are chemically similar to [Delta]9-THC, 
there is very limited to no evidence concerning the abuse potential and 
acute intoxicating effects of these isomers. There are no reports that 
the THC isomers listed in Schedule I of the 1971 Convention induce 
physical dependence or that they are being abused or are likely to be 
abused so as to constitute a public health or social problem. There are 
no reported medical or veterinary uses of these isomers.
    While the Committee recognized that available evidence has not 
demonstrated abuse and ill-effects of these isomers similar to those 
associated with [Delta]9-THC, it noted that, due to the chemical 
similarity of each of the six isomers to [Delta]9-THC, it is very 
difficult to differentiate any of these six isomers from [Delta]9-THC 
using standard methods of chemical analysis. The Committee understood 
that placing these six isomers under the same Convention and in the 
same Schedule as [Delta]9-THC would facilitate the implementation of 
international control of [Delta]9-THC, as well as assist Member States 
in the implementation of control measures at country level. 
Accordingly:
     Recommendation 5.3.1: The Committee recommended that

[[Page 7069]]

tetrahydrocannabinol (understood to refer to the six isomers currently 
listed in Schedule I of the 1971 Convention on Psychotropic Substances) 
be added to Schedule I of the 1961 Single Convention on Narcotic Drugs, 
subject to the Commission's adoption of the recommendation to add 
dronabinol (delta-9-tetrahydrocannabinol) to the 1961 Single Convention 
on Narcotic Drugs in Schedule I.
    As indicated in the ``Guidance on the WHO review of psychoactive 
substances for international control,'' to facilitate efficient 
administration of the international control system, it is not advisable 
to place a substance under more than one Convention. Accordingly:
     Recommendation 5.3.2: The Committee recommended that 
tetrahydrocannabinol (understood to refer to the six isomers currently 
listed in Schedule I of the 1971 Convention on Psychotropic Substances) 
be deleted from the 1971 Convention on Psychotropic Substances, subject 
to the Commission's adoption of the recommendation to add 
tetrahydrocannabinol to Schedule I of the 1961 Single Convention on 
Narcotic Drugs.

5.4 Extracts and Tinctures of Cannabis

    Extracts and tinctures of cannabis are preparations that are 
produced by application of solvents to cannabis and that are currently 
placed in Schedule I of the 1961 Single Convention on Narcotic Drugs. 
These include both medical preparations such as that containing an 
approximately equal mixture of delta-9-tetrahydrocannabinol 
(dronabinol; [Delta]9-THC) and cannabidiol and non-medical preparations 
with high concentrations of [Delta]9-THC such as butane hash oil. While 
the medical extracts and tinctures are administered orally, those 
produced and used illicitly are normally inhaled following heating and 
vaporization.
    The Committee recognized that the term Extracts and Tinctures of 
Cannabis as cited in the 1961 Single Convention on Narcotic Drugs 
encompasses these diverse preparations that have psychoactive 
properties as well as those that do not. The Committee also recognized 
that the variability in psychoactive properties of these preparations 
is due principally to varying concentrations of [Delta]9-THC, which is 
currently scheduled in the 1971 Convention on Psychotropic Substances, 
and that some extracts and tinctures of cannabis without psychoactive 
properties and including predominantly cannabidiol have promising 
therapeutic applications. The fact that diverse preparations with a 
variable concentration of delta-9-THC are controlled within the same 
entry ``Extract and Tinctures'' and the same schedule, is a challenge 
for responsible authorities that implement control measures in 
countries.
    As per the 1961 Single Convention on Narcotic Drugs, preparations 
are defined as mixtures, solid, or liquid containing a substance in 
Schedule I or II and are generally subject to the same measures of 
control as that substance. The Committee noted that, by this 
definition, the 1961 Single Convention on Narcotic Drugs may cover all 
products that are ``extracts and tinctures'' of cannabis as 
``preparations'' of cannabis and also, if the Committee`s 
recommendation to move dronabinol to Schedule I of the 1961 Single 
Convention on Narcotic Drugs was followed, as ``preparations'' of 
dronabinol and its stereoisomers. Accordingly:
     Recommendation 5.4: The Committee recommended deleting 
Extracts and Tinctures of Cannabis from Schedule I of the 1961 Single 
Convention on Narcotic Drugs.

5.5 Cannabidiol Preparations

    At its 40th Meeting, the ECDD considered a critical review of 
cannabidiol and recommended that preparations considered to be pure 
cannabidiol should not be scheduled within the International Drug 
Control Conventions. Cannabidiol is found in cannabis and cannabis 
resin but does not have psychoactive properties and has no potential 
for abuse and no potential to produce dependence. It does not have 
significant ill-effects. Cannabidiol has been shown to be effective in 
the management of certain treatment-resistant, childhood-onset epilepsy 
disorders. It was approved for this use in the United States in 2018 
and is currently under consideration for approval by the European 
Union.
    Cannabidiol can be chemically synthesized or it can be prepared 
from the cannabis plant. The approved medication (Epidiolex) is a 
preparation of the cannabis plant. The Committee noted that medicines 
without psychoactive effects that are produced as preparations of the 
cannabis plant will contain trace amounts of delta-9-
tetrahydrocannabinol ([Delta]9-THC; dronabinol). The cannabidiol 
preparation approved for the treatment of childhood-onset epilepsy, 
Epidiolex, contains not more than 0.15 percent [Delta]9-THC by weight 
and has no effects indicative of potential for abuse or dependence. In 
keeping with the recommendation that preparations considered pure 
cannabidiol not be controlled and recognizing that trace levels of 
[Delta]9-THC may be found in such preparations, such as the 
concentration of 0.15 percent in Epidiolex, while acknowledging that 
chemical analysis of [Delta]9-THC to an accuracy of 0.15 percent may be 
difficult for some Member States:
     Recommendation 5.5: The Committee recommended that a 
footnote be added to Schedule I of the 1961 Single Convention on 
Narcotic Drugs to read: ``Preparations containing predominantly 
cannabidiol and not more than 0.2 percent of delta-9-
tetrahydrocannabinol are not under international control.''

5.6 Pharmaceutical Preparations of Cannabis and Dronabinol (delta-9-
tetrahydrocannabinol)

    There are currently two main types of registered medicines that 
contain delta-9-tetrahydrocannabinol ([Delta]9-THC; dronabinol).
    One type is a preparation of cannabis that contains both the 
psychoactive [Delta]9-THC and the non-psychoactive cannabidiol in 
approximately equal concentrations, e.g., Sativex. This is used for the 
treatment of spasticity due to multiple sclerosis.
    A second type contains only [Delta]9-THC as the active compound and 
is used for the treatment of anorexia associated with weight loss in 
patients with Acquired Immune Deficiency Syndrome (AIDS) and for nausea 
and vomiting associated with cancer chemotherapy in patients who have 
failed to respond adequately to conventional antiemetic treatments.
    Currently, approved medicines with [Delta]9-THC as the only active 
compound use synthetically produced [Delta]9-THC, e.g., Marinol, 
Syndros, although it is possible in the future that medicines with 
equivalent amounts of [Delta]9-THC could be prepared from cannabis. 
There is no difference in the therapeutic effects or adverse effects of 
synthetic [Delta]9-THC compared to [Delta]9-THC from the cannabis 
plant.
    These medicines are all taken orally and are approved for use in a 
number of countries.
    The evidence concerning the use of these [Delta]9-THC containing 
medicines is that they are not associated with problems of abuse and 
dependence and they are not diverted for the purpose of non-medical 
use.
    The Committee recognized that such preparations are formulated in a 
way that they are not likely to be abused, and there is no evidence of 
actual abuse or ill-effects to an extent that would justify

[[Page 7070]]

the current level of control associated with Schedule I of the 1961 
Single Convention on Narcotic Drugs for cannabis-based preparations 
such as Sativex and the level of control associated with Schedule II of 
the 1971 Convention on Psychotropic Substances, for preparations using 
synthetic delta-9 THC, e.g., Marinol and Syndros.
    To impede access to these medicines and in reference to Article 3.4 
of the 1961 Single Convention on Narcotic Drugs:
     Recommendation 5.6: The Committee recommended that 
preparations containing delta-9-tetrahydrocannabinol (dronabinol), 
produced either by chemical synthesis or as a preparation of cannabis, 
that are compounded as pharmaceutical preparations with one or more 
other ingredients and in such a way that delta-9-tetrahydrocannabinol 
(dronabinol) cannot be recovered by readily available means or in a 
yield which would constitute a risk to public health, be added to 
Schedule III of the 1961 Convention on Narcotic Drugs.

III. Discussion

    At this time, it is uncertain whether the above notification from 
WHO of recommendations for proposed scheduling action on cannabis and 
cannabis related substances will be acted upon by 62nd session of the 
Commission on Narcotic Drugs (from 14 to 22 March 2019). The Bureau of 
the 62nd Commission is currently considering whether to postpone voting 
on the cannabis-related recommendations until the reconvened meeting in 
December, or the 63rd session of the Commission on Narcotic Drugs, 
March 2020. If voting is deferred to a later date the comment period 
will be reopened.
    Although WHO has made specific scheduling recommendations for each 
of the drug substances, the CND is not obliged to follow the WHO 
recommendations. Options available to the CND for substances considered 
for control under the 1971 Psychotropic Convention include the 
following: (1) Accept the WHO 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.
    Cannabis, also known as marijuana, is a plant known by biological 
names Cannabis sativa or Cannabis indica. It is a complex plant 
containing multiple cannabinoids and other compounds, including the 
psychoactive substance THC and other structurally similar compounds. 
Cannabinoids are defined as having activity at cannabinoid 1 and 2 (CB1 
and CB2, respectively) receptors. Agonists of CB1 receptors are widely 
abused and are known to modulate motor coordination, memory processing, 
pain, and inflammation, and have anxiolytic effects. Marijuana is the 
most commonly used illicit drug in the United States.
    The principal cannabinoids in the cannabis plant include THC, CBD, 
and cannabinol. These substances are controlled in Schedule I under the 
CSA. The synthetically derived single pure stereoisomer, delta-9-
tetrahydrocannabinol (also known as dronabinol) is the active 
ingredient in two approved drug products in the United States, MARINOL 
(dronabinol) capsules, also available as a generic, and SYNDROS 
(dronabinol) oral solution. MARINOL is controlled in Schedule III, 
while SYNDROS is controlled in Schedule II under the CSA. Both MARINOL 
and SYNDROS are approved to treat anorexia associated with weight loss 
in patients with AIDS, and nausea and vomiting associated with cancer 
chemotherapy in patients who have failed to respond adequately to 
conventional treatment.
    CBD is another cannabinoid constituent of the cannabis plant. In 
the United States, one CBD-containing product, Epidiolex oral solution, 
has received marketing approval by the FDA for the treatment of 
seizures associated with two rare and severe forms of epilepsy, Lennox-
Gastaut syndrome and Dravet syndrome, in patients 2 years of age and 
older. On September 28, 2018, the Drug Enforcement Administration 
placed FDA-approved product Epidiolex to be marketed into Schedule V of 
the CSA. Currently, CBD that is not contained in an FDA-approved 
product with less than 0.1 percent THC is controlled as a Schedule I 
substance under the CSA. CBD is not specifically listed in the 
schedules of the 1961, 1971, or 1988 International Drug Control 
conventions.
    FDA, on behalf of the Secretary of HHS, invites interested persons 
to submit comments on the notifications 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 WHO 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 substances under the 1971 Psychotropic 
Convention at the CND meeting in March 2019.
    Comments regarding the WHO recommendations for control of Cannabis 
and Cannabis Resin; Dronabinol (delta-9-tetrahydrocannabinol); 
Tetrahydrocannabinol (Isomers of delta-9-tetrahydrocannabinol); 
Extracts and Tinctures of cannabis; Cannabidiol Preparations; 
Preparations Produced Either by Chemical Synthesis or as Preparation of 
Cannabis; 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.

    Dated: February 25, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-03662 Filed 2-28-19; 8:45 am]
 BILLING CODE 4164-01-P