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International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization; Scheduling Recommendations; Dronabinol (delta
This document has a comment period that ends in 11 days. (03/14/2019)AGENCY:
Food and Drug Administration, HHS.
ACTION:
Notice; request for comments.
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 Start Printed 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 Start Printed Page 7066opportunity
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: http://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.Start Printed 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 (Δ9-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 Δ9-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 Start Printed Page 7068Single
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; Δ9-THC)
The main psychoactive substance in the cannabis plant is one of the four stereoisomers of delta-9-tetrahydrocannabinol
(Δ9-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 Δ9-THC as the main psychoactive compound in cannabis.
Subsequently, Δ9-THC was included in the 1971 Convention on Psychotropic
Substances at its inception. In previous ECDD reviews, the active and
naturally occurring stereoisomer of Δ9-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 Δ9-THC, and especially its active
stereoisomer dronabinol, had been considered in a synthetic form as a
pharmaceutical preparation, Δ9-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
Δ9-THC at concentrations as high as 90 percent. Butane hash oil is an
example of a high purity Δ9-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, Δ9-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 Δ9-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 Δ9-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 Δ9-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
(Δ9-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 Δ9-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 Δ9-THC, it noted that,
due to the chemical similarity of each of the six isomers to Δ9-THC, it
is very difficult to differentiate any of these six isomers from Δ9-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 Δ9-THC would facilitate the implementation of international
control of Δ9-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 Start Printed Page 7069tetrahydrocannabinol (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; Δ9-THC) and cannabidiol and non-medical preparations with
high concentrations of Δ9-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 Δ9-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 (Δ9-THC; dronabinol).
The cannabidiol preparation approved for the treatment of
childhood-onset epilepsy, Epidiolex, contains not more than 0.15 percent
Δ9-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 Δ9-THC may be found in such preparations, such as the
concentration of 0.15 percent in Epidiolex, while acknowledging that
chemical analysis of Δ9-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 (Δ9-THC; dronabinol).
One type is a preparation of
cannabis that contains both the psychoactive Δ9-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
Δ9-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 Δ9-THC as the only active compound use synthetically produced Δ9-THC, e.g.,
Marinol, Syndros, although it is possible in the future that medicines
with equivalent amounts of Δ9-THC could be prepared from cannabis. There
is no difference in the therapeutic effects or adverse effects of
synthetic Δ9-THC compared to Δ9-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 Δ9-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 Start Printed Page 7070the
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
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