International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization Scheduling Recommendations for Dronabinol and its Stereoisomers, and Oripavine, 75560-75562 [E6-21318]
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Federal Register / Vol. 71, No. 241 / Friday, December 15, 2006 / Notices
product in interstate commerce on or
after June 13, 2007. The agency,
however, does not intend to exercise its
enforcement discretion as outlined in
this paragraph if: (1) A manufacturer or
distributor of an unapproved product
covered by this notice is violating other
provisions of the act; or (2) it appears
that a firm, in response to this notice,
increases its manufacture or interstate
shipment of quinine drug products
above its usual volume during these
periods.
Drug manufacturers and distributors
should be aware that the agency is
exercising its enforcement discretion as
described previously only in regard to
drug products containing quinine that
are marketed under an NDC number
listed with the agency on the effective
date of this notice. Unapproved drug
products containing quinine that are not
currently marketed and listed with the
agency on the effective date of this
notice must, as of the effective date of
this notice, have approved applications
prior to their shipment in interstate
commerce. Moreover, submission of an
application does not excuse timely
compliance with this notice.
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C. Discontinued Products
Some firms may have previously
discontinued the manufacturing or
distribution of products covered by this
notice without removing them from the
listing of their products under section
510(j) of the act. Other firms may
discontinue manufacturing or marketing
listed products in response to this
notice. Firms that wish to notify the
agency of product discontinuation
should send a letter, signed by the firm’s
chief executive officer, fully identifying
the discontinued product(s), including
its NDC number(s), and stating that the
product(s) has (have) been discontinued
and will not be marketed again without
FDA approval, to John Loh (see
ADDRESSES). Firms should also update
the listing of their products under
section 510(j) of the act to reflect
discontinuation of unapproved quinine
products. FDA plans to rely on its
existing records, the results of a
subsequent inspection, or other
available information when it initiates
enforcement action.
This notice is issued under sections
502 and 505 of the act (21 U.S.C. 352)
and under authority delegated to the
Deputy Commissioner for Policy under
section 1410.10 of the FDA Staff Manual
Guide.
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Dated: December 11, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 06–9713 Filed 12–12–06; 11:00 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. 2006N–0493]
International Drug Scheduling;
Convention on Psychotropic
Substances; Single Convention on
Narcotic Drugs; World Health
Organization Scheduling
Recommendations for Dronabinol and
its Stereoisomers, and Oripavine
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is providing
interested persons with the opportunity
to submit written comments concerning
recommendations by the World Health
Organization (WHO) 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 U.S.
position on these proposals for a
meeting of the United Nations
Commission on Narcotic Drugs (CND) in
Vienna, Austria, March 12 to 16, 2007.
This notice is issued under the
Controlled Substances Act.
DATES: Submit written or electronic
comments by January 16, 2007.
ADDRESSES: Submit written comments
to the Division of Dockets Management
(HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852. Submit
electronic comments to https://
www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT:
James R. Hunter, Center for Drug
Evaluation and Research (HFD–9), Food
and Drug Administration, 5600 Fishers
Lane, Rockville, MD 20857, 301–443–
5563, e-mail: james.hunter@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
The United States is a party to the
1971 Convention on Psychotropic
Substances (the 1971 Convention).
Section 201(d)(2)(B) of the Controlled
Substances Act (the CSA) (21 U.S.C.
811(d)(2)(B)) provides that when the
United States is notified under Article 2
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of the 1971 Convention that 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 (the Secretary of
HHS). Section 201(d)(2)(B) requires the
Secretary of HHS, after receiving
notification proposing scheduling, to
publish a summary of such information
in the Federal Register to provide
opportunity for interested persons to
submit comments on the proposed
scheduling action. 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 SecretaryGeneral of the United Nations (the
Secretary-General) regarding the drug
substance dronabinol (INN), including
its stereoisomers, to be considered for
control under the 1971 Convention. The
notification reflects the
recommendations from the 34th WHO
Expert Committee for Drug Dependence
(ECDD), which met in March 2006. In
the Federal Register of December 13,
2005 (70 FR 73775), FDA announced the
WHO ECDD review and invited
interested persons to submit
information for WHO’s consideration.
The United States is also a party to
the 1961 Single Convention on Narcotic
Drugs (the 1961 Convention). The
Secretary of State has received
notification from the Secretary-General
regarding the drug substance oripavine
to be considered for control under the
1961 Convention. The CSA does not
require the Secretary of HHS to publish
a summary of such information in the
Federal Register. Nevertheless, in an
effort to provide interested and affected
persons an opportunity to submit
comments on the WHO ECDD
recommendations for narcotic drugs,
notification on this substance 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 U.S. position
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 on control of
substances under the 1961 Convention.
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Federal Register / Vol. 71, No. 241 / Friday, December 15, 2006 / Notices
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The full text of these notifications
from the Secretary-General is provided
in section II of this document.
II. United Nations Notification
The formal United Nations notification that
identifies the drug substances and explains
the basis for the recommendations is
reproduced below.
Reference: NAR/CL.4/2006
CSS–6/06, CU2006/162
WHO/ECDD 34 (1971C and 1961C)
The Secretary-General of the United
Nations presents his compliments [to the
Secretary of State] and has the honour to
inform the Government that the Acting
Director-General of the World Health
Organization (WHO), pursuant to article 2,
paragraphs 1, 4 and 6, of the Convention on
Psychotropic Substances of 1971 (1971
Convention), has notified the SecretaryGeneral that it is of the opinion that
dronabinol (INN) and its stereoisomers
should be transferred from Schedule II to
Schedule III of the 1971 Convention; and
pursuant to article 3, paragraphs 1 and 3(iii)
of the Single Convention on Narcotic Drugs,
1961, and of that Convention as amended by
the 1972 Protocol (1961 Convention), has
also notified the Secretary-General that it is
of the opinion that oripavine should be
included in Schedule I of the 1961
Convention.
In connection with the notification, WHO
has also submitted advance excerpts from the
report of the Thirty-fourth session of the
WHO Expert Committee on Drug Dependence
(28–31 March 2006) which reviewed the
substances. The excerpts from that report
concerning dronabinol (INN) and its
stereoisomers, recommended for
rescheduling; and oripavine, recommended
for scheduling, are hereby transmitted as
annex II. The excerpts are currently available
in English only, pending receipt of the
official translation from the World Health
Organization.
In accordance with the provisions of article
2, paragraph 2, of the 1971 Convention; and
the provisions of article 3, paragraph 2, of the
1961 Convention, the Secretary-General
hereby transmits the text of the notification
as annex I to the present note. Also in
accordance with the same provisions, the
notification from WHO will be brought to the
attention of the Commission on Narcotic
Drugs, at its next session in March 2007.
Any action or decision taken by the
Commission with respect to this notification,
pursuant to article 2, paragraphs 5 and 6, of
the 1971 Convention, will be communicated
to States Parties in due course. Article 2,
paragraphs 5 and 6, reads as follows:
‘‘5. The Commission, taking into account
the communication from the World Health
Organization, whose assessments shall be
determinative as to medical and scientific
matters, and bearing in mind the economic,
social, legal, administrative and other factors
it may consider relevant, may add the
substance to Schedule I, II, III or IV. The
Commission may seek further information
from the World Health Organization or from
other appropriate sources.
6. If a notification under paragraph 1
relates to a substance already listed in one of
the Schedules, the World Health
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Organization shall communicate to the
Commission its new findings, any new
assessment of the substance it may make in
accordance with paragraph 4 and any new
recommendations on control measures it may
find appropriate in the light of that
assessment. The Commission, taking into
account the communication from the World
Health Organization as under paragraph 5
and bearing in mind the factors referred to in
that paragraph, may decide to transfer the
substance from one Schedule to another or to
delete it from the Schedules.’’
Any action or decision taken by the
Commission with respect to this notification,
pursuant to article 3, paragraph 3 (iii) of the
1961 Convention, will be communicated to
States Parties in due course. Article 3,
paragraph 3 (iii) reads as follows:
‘‘If the World Health Organization finds
that the substance is liable to similar abuse
and productive of similar ill effects as the
drugs in Schedule I or Schedule II or is
convertible into a drug, it shall communicate
that finding to the Commission which may,
in accordance with the recommendation of
the World Health Organization, decide that
the substance shall be added to Schedule I
or Schedule II.’’
In order to assist the Commission in
reaching a decision, it would be appreciated
if any economic, social, legal, administrative
or other factors the Government may
consider relevant to the possible
rescheduling under the 1971 Convention of
dronabinol (INN) and its stereoisomers, as
well as to the possible inclusion of oripavine
under the 1961 Convention, could be
communicated at the latest by 1 December
2006 to the Executive Director of the United
Nations Office on Drugs and Crime, c/o
Secretary, Commission on Narcotic Drugs,
P.O. Box 500, 1400 Vienna, Austria, fax:+43–
1–26060–5885, e-mail:
Renate.Weidinger@unodc.org.
13 October 2006
*
*
*
*
*
Annex II
Recommendation on dronabinol (INN)
Substance identification
Dronabinol (INN) is (6aR,10aR)- 6a,7,8,10atetrahydro-6,6,9-trimethyl-3-pentyl-6-Hdibenzo[b,d]pyran-1-ol. It is the (6aR,10aR)stereoisomer of delta-9-tetrahydrocannabinol
and is also designated (–)- trans-delta-9tetrahydrocannabinol.
Other stereoisomers of delta-9tetrahydrocannabinol are: (6aR, 10aS)-,(6aS,
10aR)- and (6aS, 10aS)-, also known as (–)cis-,(+)-cis-and (+)-trans-, respectively. Delta9-tetrohydrocannabinol has two racemates,
(6aRS, 10aRS)- and (6aRS, 10aSR)-, also
known as (±)-trans- and (±)-cis-, respectively.
Originally, all isomers of
tetrahydrocannabinol were included in
Schedule I of the 1971 Convention. This was
later amended to include seven named
constitutional isomers and their respective
stereochemical variants. The term
‘‘constitutional isomers’’ used above has
recently been introduced by the International
Union of Pure and Applied Chemistry
(IUPAC) to replace the traditionally used
term ‘‘positional isomers’’.
The term ‘‘stereochemical variants’’ used
in the 1971 Convention and mentioned above
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75561
is equivalent to the term ‘‘stereoisomers’’,
which is at present much more widely used
in the chemical and related literature. Both
terms cover geometric isomers and optical
isomers.
Previous review
Delta-9-tetrahydrocannabinol was included
in Schedule I of the 1971 Convention at the
time of its adoption. At its twenty-sixth
meeting, the Committee recommended that
dronabinol be moved to Schedule II, while
keeping the other isomers and their
stereochemical variants in Schedule I (1).
This proposal was rejected at the 11th
Special Session of the Commission on
Narcotic Drugs, and the Committee reviewed
the question again at its twenty-seventh
meeting when it recommended that all the
stereochemical variants of delta-9tetrahydrocannabinol be rescheduled to
Schedule II (2). This recommendation was
adopted by the United Nations Commission
on Narcotic Drugs at its 34th session (3). At
its thirty-second meeting, the Committee prereviewed dronabinol and recommended its
critical review for consideration of the
rescheduling on the grounds that the rate of
abuse of dronabinol was extremely low (4).
Delta-9-tetrahydrocannabinol was critically
reviewed by the Expert Committee on Drug
Dependence at its thirty-third meeting in
September 2002 (5). On the basis of the
available data the Committee considered that
dronabinol should be rescheduled to
Schedule IV of the 1971 Convention.
However, no further procedural steps were
taken. Therefore, the existing critical review
report was updated, including information
from recent scientific publications, to enable
the Committee to finalize the process of
critical review.
Similarity to known substances and effects
on the central nervous system
Dronabinol is the main active principle of
cannabis and has similar effects on mood,
perception and the cardiovascular system.
The cannabis plant contains a ‘‘natural
mixture’’ of around 70 different
cannabinoids, and also contains flavonoids
and terpenes, as well as many other
substances. Therefore the pharmacological
properties of natural cannabis and
dronabinol are not identical.
Dependence potential
Animal studies have demonstrated that,
like other drugs of abuse, dronabinol acts as
a drug reinforcer. Physical dependence, as
shown by withdrawal syndrome following
chronic administration, has also been
demonstrated. Reinforcing effects and
physical dependence have also been
described in human studies.
Actual abuse and/or evidence of likelihood of
abuse
The abuse of dronabinol is currently rare
and there have been very few specific reports
of its occurrence. In response to the WHO
questionnaires only the United States
mentioned instances of abuse of delta-9tetrahydrocannabinol. At present, the
quantity produced by licit manufacture is
limited. In the United States, which is the
major manufacturing country, the abuse of
dronabinol medicinal preparations is
reported to be very low and there are no
reports of diversion of the pharmaceutical
product.
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Therapeutic usefulness
Dronabinol preparations have been used in
a limited number of countries in the
treatment of nausea and vomiting associated
with cancer chemotherapy in patients who
have failed to respond adequately to
conventional antiemetic treatments and in
the treatment of anorexia associated with
weight loss in patients with acquired
immunodeficiency syndrome (AIDS). It has
also been indicated in the treatment of
chronic pain (e.g. in multiple sclerosis,
neuropathic disorders and arthritis),
neurological disorders and appetite loss in
cachexia, and is being evaluated for use in
various other clinical situations.
Recommendation
The Committee reconsidered the
recommendation of the thirty-third Expert
Committee after considering the updated
critical review report. The Committee
concluded that dronabinol constitutes a
substantial risk to public health. However
this risk is different from those related to
cannabis—controlled under the 1961
Convention. The substance has a moderate
therapeutic usefulness and as a result of
continuing clinical research its medical use
is likely to increase. Therefore, the
Committee recommended that dronabinol
(INN) and its stereoisomers should be
rescheduled from Schedule II to Schedule III
of the 1971 Convention.
To avoid legal and forensic chemical
problems that may arise in some countries
when placing stereoisomers of the same
substance under different control systems,
the Committee indicated that the
recommendation pertains to all
stereoisomeric forms of delta-9tetrahydrocannabinol as specified above.
References
1. WHO Expert Committee on Drug
Dependence. Twenty-sixth report. Geneva,
World Health Organization, 1989 (WHO
Technical Report Series, No. 787).
2. WHO Expert Committee on Drug
Dependence. Twenty-seventh report. Geneva,
World Health Organization, 1991 (WHO
Technical Report Series, No. 808).
3. Report of the thirty-fourth session (29
April–9 May 1991). Economic and Social
Council, Commission on Narcotic Drugs,
Official Records, 1991, Supplement No. 4.
New York, United Nations, 1991 (E/1991/24,
E/Cn.7/1991/26).
4. WHO Expert Committee on Drug
Dependence. Thirty-second report. Geneva,
World Health Organization, 2001 (WHO
Technical Report Series, No. 903).
5. WHO Expert Committee on Drug
Dependence. Thirty-third report. Geneva,
World Health Organization, 2003 (WHO
Technical Report Series, No. 915).
Recommendation on oripavine
Substance identification
Oripavine, 3-O-demethylthebaine, or 6,7,8,
14-tetradehydro-4,5-alpha-epoxy-6-methoxy17-methylmorphinan-3-ol is a phenanthrene
alkaloid contained in species of the Papaver
plant. It is a major metabolite of thebaine.
Previous review
Oripavine was pre-reviewed at the thirtythird meeting of the Expert Committee in
2002 (1). The reason for pre-review in 2002
was that oripavine is a substance that is
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convertible into thebaine, and because
thebaine is in turn convertible into
morphine. Thebaine and morphine are both
in Schedule I of the 1961 Convention. Owing
to uncertainties regarding the scheduling of
oripavine based on the additional possibility
of applying the 1988 Convention (2), the
Committee did not finalize this review at its
thirty-third meeting, but asked WHO for
clarification of issues related to the
conversion of precursors into scheduled
substances. Subsequent clarification of these
issues allowed the Committee to come to a
conclusion at its thirty-fourth meeting.
Recommendation
The Committee decided that oripavine is a
substance that is easily convertible into
thebaine and other substances controlled in
Schedule I of the 1961 Convention. Hence,
the Committee recommended that oripavine
be scheduled, like the substances mentioned,
in Schedule I of the 1961 Convention.
References
1. WHO Expert Committee on Drug
Dependence. Thirty-third report. Geneva,
World Health Organization, 2003 (WHO
Technical Report Series, No. 915).
2. United Nations Convention against Illicit
Traffic in Narcotic Drugs and Psychotropic
Substances, 1988. New York, United Nations,
1991.
III. Discussion
Although WHO has made specific
scheduling recommendations for each of
the drug substances, CND is not obliged
to follow the WHO recommendations.
Options available to CND for substances
considered for control under the 1971
Convention include the following: (1)
Acceptance of the WHO
recommendations; (2) acceptance of the
recommendations to control, but control
the drug substance in a schedule other
than that recommended; or (3) reject the
recommendations entirely.
Synthetic delta-9tetrahydrocannabinol (delta–9–THC), or
dronabinol, is the active component of
the drug product Marinol, which is
marketed in the United States as an
antiemetic in the setting of cancer
chemotherapy and for treatment of AIDS
wasting syndrome. Marinol is currently
controlled in Schedule III of the CSA,
and the drug substance dronabinol
(which is the synthetic equivalent of the
natural active component of marijuana,
delta–9–THC) is controlled in Schedule
I of the CSA. The drug substance
dronabinol, including its stereoisomers,
is controlled internationally in Schedule
II of the Psychotropic Convention.
Oripavine is controlled domestically
in Schedule II of the CSA because it is
a derivative of thebaine, opium, and
other opiates. Oripavine is not under
international control.
IV. Comments
Interested persons may submit to the
Division of Dockets Management (see
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ADDRESSES)
written or electric
comments regarding this document.
Submit a single copy of electronic
comments or two paper copies of any
mailed comments, except that
individuals may submit one paper copy.
Comments are to be identified with the
docket number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday.
The abbreviated period for the
submission of comments is necessary to
allow sufficient time for the Secretary of
HHS to carry out the required action
and respond to the United Nations.
Dated: December 6, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6–21318 Filed 12–14–06; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Office of Inspector General
Notice of Program Exclusions
AGENCY:
Office of Inspector General,
HHS.
ACTION:
Notice of program exclusions.
Important Announcement: This is the
final publication of the Office of
Inspector General’s (OIG) monthly
exclusion actions in the Federal
Register. Downloadable files of
exclusion actions taken each month are
available on the OIG’s Web site. In
addition, the Web site has a
downloadable data file and an online
searchable database containing all
exclusion actions currently in effect.
This data is called the List of Excluded
Individuals/Entities (LEIE) and is
located at https://oig.hhs.gov. Click on
EXCLUSIONS DATABASE to access the
LEIE and other important information
about the OIG’s exclusion program.
Program Exclusions: November 2006.
During the month of November 2006,
the HHS Office of Inspector General
imposed exclusions in the cases set
forth below. When an exclusions is
imposed, no program payment is made
to anyone for any items or services
(other than an emergency item or
service not provided in a hospital
emergency room) furnished, ordered or
prescribed by an excluded party under
the Medicare, Medicaid, and all Federal
Health Care programs. In addition, no
program payment is made to any
business or facility, e.g., a hospital, that
submits bills for payment for items or
services provided by an excluded party.
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]]>Agencies
[Federal Register Volume 71, Number 241 (Friday, December 15, 2006)]
[Notices]
[Pages 75560-75562]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E6-21318]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2006N-0493]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; World Health
Organization Scheduling Recommendations for Dronabinol and its
Stereoisomers, and Oripavine
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is providing interested
persons with the opportunity to submit written comments concerning
recommendations by the World Health Organization (WHO) 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
U.S. position on these proposals for a meeting of the United Nations
Commission on Narcotic Drugs (CND) in Vienna, Austria, March 12 to 16,
2007. This notice is issued under the Controlled Substances Act.
DATES: Submit written or electronic comments by January 16, 2007.
ADDRESSES: Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852. Submit electronic comments to https://
www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT: James R. Hunter, Center for Drug
Evaluation and Research (HFD-9), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-443-5563, e-mail:
james.hunter@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
The United States is a party to the 1971 Convention on Psychotropic
Substances (the 1971 Convention). Section 201(d)(2)(B) of the
Controlled Substances Act (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 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 (the
Secretary of HHS). Section 201(d)(2)(B) requires the Secretary of HHS,
after receiving notification proposing scheduling, to publish a summary
of such information in the Federal Register to provide opportunity for
interested persons to submit comments on the proposed scheduling
action. 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 the drug substance dronabinol (INN),
including its stereoisomers, to be considered for control under the
1971 Convention. The notification reflects the recommendations from the
34th WHO Expert Committee for Drug Dependence (ECDD), which met in
March 2006. In the Federal Register of December 13, 2005 (70 FR 73775),
FDA announced the WHO ECDD review and invited interested persons to
submit information for WHO's consideration.
The United States is also a party to the 1961 Single Convention on
Narcotic Drugs (the 1961 Convention). The Secretary of State has
received notification from the Secretary-General regarding the drug
substance oripavine to be considered for control under the 1961
Convention. The CSA does not require the Secretary of HHS to publish a
summary of such information in the Federal Register. Nevertheless, in
an effort to provide interested and affected persons an opportunity to
submit comments on the WHO ECDD recommendations for narcotic drugs,
notification on this substance 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 U.S.
position 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 on control of
substances under the 1961 Convention.
[[Page 75561]]
The full text of these notifications from the Secretary-General is
provided in section II of this document.
II. United Nations Notification
The formal United Nations notification that identifies the drug
substances and explains the basis for the recommendations is
reproduced below.
Reference: NAR/CL.4/2006
CSS-6/06, CU2006/162
WHO/ECDD 34 (1971C and 1961C)
The Secretary-General of the United Nations presents his
compliments [to the Secretary of State] and has the honour to inform
the Government that the Acting Director-General of the World Health
Organization (WHO), pursuant to article 2, paragraphs 1, 4 and 6, of
the Convention on Psychotropic Substances of 1971 (1971 Convention),
has notified the Secretary-General that it is of the opinion that
dronabinol (INN) and its stereoisomers should be transferred from
Schedule II to Schedule III of the 1971 Convention; and pursuant to
article 3, paragraphs 1 and 3(iii) of the Single Convention on
Narcotic Drugs, 1961, and of that Convention as amended by the 1972
Protocol (1961 Convention), has also notified the Secretary-General
that it is of the opinion that oripavine should be included in
Schedule I of the 1961 Convention.
In connection with the notification, WHO has also submitted
advance excerpts from the report of the Thirty-fourth session of the
WHO Expert Committee on Drug Dependence (28-31 March 2006) which
reviewed the substances. The excerpts from that report concerning
dronabinol (INN) and its stereoisomers, recommended for
rescheduling; and oripavine, recommended for scheduling, are hereby
transmitted as annex II. The excerpts are currently available in
English only, pending receipt of the official translation from the
World Health Organization.
In accordance with the provisions of article 2, paragraph 2, of
the 1971 Convention; and the provisions of article 3, paragraph 2,
of the 1961 Convention, the Secretary-General hereby transmits the
text of the notification as annex I to the present note. Also in
accordance with the same provisions, the notification from WHO will
be brought to the attention of the Commission on Narcotic Drugs, at
its next session in March 2007.
Any action or decision taken by the Commission with respect to
this notification, pursuant to article 2, paragraphs 5 and 6, of the
1971 Convention, will be communicated to States Parties in due
course. Article 2, paragraphs 5 and 6, reads as follows:
``5. The Commission, taking into account the communication from
the World Health Organization, whose assessments shall be
determinative as to medical and scientific matters, and bearing in
mind the economic, social, legal, administrative and other factors
it may consider relevant, may add the substance to Schedule I, II,
III or IV. The Commission may seek further information from the
World Health Organization or from other appropriate sources.
6. If a notification under paragraph 1 relates to a substance
already listed in one of the Schedules, the World Health
Organization shall communicate to the Commission its new findings,
any new assessment of the substance it may make in accordance with
paragraph 4 and any new recommendations on control measures it may
find appropriate in the light of that assessment. The Commission,
taking into account the communication from the World Health
Organization as under paragraph 5 and bearing in mind the factors
referred to in that paragraph, may decide to transfer the substance
from one Schedule to another or to delete it from the Schedules.''
Any action or decision taken by the Commission with respect to
this notification, pursuant to article 3, paragraph 3 (iii) of the
1961 Convention, will be communicated to States Parties in due
course. Article 3, paragraph 3 (iii) reads as follows:
``If the World Health Organization finds that the substance is
liable to similar abuse and productive of similar ill effects as the
drugs in Schedule I or Schedule II or is convertible into a drug, it
shall communicate that finding to the Commission which may, in
accordance with the recommendation of the World Health Organization,
decide that the substance shall be added to Schedule I or Schedule
II.''
In order to assist the Commission in reaching a decision, it
would be appreciated if any economic, social, legal, administrative
or other factors the Government may consider relevant to the
possible rescheduling under the 1971 Convention of dronabinol (INN)
and its stereoisomers, as well as to the possible inclusion of
oripavine under the 1961 Convention, could be communicated at the
latest by 1 December 2006 to the Executive Director of the United
Nations Office on Drugs and Crime, c/o Secretary, Commission on
Narcotic Drugs, P.O. Box 500, 1400 Vienna, Austria, fax:+43-1-26060-
5885, e-mail: Renate.Weidinger@unodc.org.
13 October 2006
* * * * *
Annex II
Recommendation on dronabinol (INN)
Substance identification
Dronabinol (INN) is (6aR,10aR)- 6a,7,8,10a-tetrahydro-6,6,9-
trimethyl-3-pentyl-6-H-dibenzo[b,d]pyran-1-ol. It is the (6aR,10aR)-
stereoisomer of delta-9-tetrahydrocannabinol and is also designated
(-)- trans-delta-9-tetrahydrocannabinol.
Other stereoisomers of delta-9-tetrahydrocannabinol are: (6aR,
10aS)-,(6aS, 10aR)- and (6aS, 10aS)-, also known as (-)-cis-,(+)-
cis-and (+)-trans-, respectively. Delta-9-tetrohydrocannabinol has
two racemates, (6aRS, 10aRS)- and (6aRS, 10aSR)-, also known as
()-trans- and ()-cis-, respectively.
Originally, all isomers of tetrahydrocannabinol were included in
Schedule I of the 1971 Convention. This was later amended to include
seven named constitutional isomers and their respective
stereochemical variants. The term ``constitutional isomers'' used
above has recently been introduced by the International Union of
Pure and Applied Chemistry (IUPAC) to replace the traditionally used
term ``positional isomers''.
The term ``stereochemical variants'' used in the 1971 Convention
and mentioned above is equivalent to the term ``stereoisomers'',
which is at present much more widely used in the chemical and
related literature. Both terms cover geometric isomers and optical
isomers.
Previous review
Delta-9-tetrahydrocannabinol was included in Schedule I of the
1971 Convention at the time of its adoption. At its twenty-sixth
meeting, the Committee recommended that dronabinol be moved to
Schedule II, while keeping the other isomers and their
stereochemical variants in Schedule I (1). This proposal was
rejected at the 11th Special Session of the Commission on Narcotic
Drugs, and the Committee reviewed the question again at its twenty-
seventh meeting when it recommended that all the stereochemical
variants of delta-9-tetrahydrocannabinol be rescheduled to Schedule
II (2). This recommendation was adopted by the United Nations
Commission on Narcotic Drugs at its 34th session (3). At its thirty-
second meeting, the Committee pre-reviewed dronabinol and
recommended its critical review for consideration of the
rescheduling on the grounds that the rate of abuse of dronabinol was
extremely low (4).
Delta-9-tetrahydrocannabinol was critically reviewed by the
Expert Committee on Drug Dependence at its thirty-third meeting in
September 2002 (5). On the basis of the available data the Committee
considered that dronabinol should be rescheduled to Schedule IV of
the 1971 Convention. However, no further procedural steps were
taken. Therefore, the existing critical review report was updated,
including information from recent scientific publications, to enable
the Committee to finalize the process of critical review.
Similarity to known substances and effects on the central nervous
system
Dronabinol is the main active principle of cannabis and has
similar effects on mood, perception and the cardiovascular system.
The cannabis plant contains a ``natural mixture'' of around 70
different cannabinoids, and also contains flavonoids and terpenes,
as well as many other substances. Therefore the pharmacological
properties of natural cannabis and dronabinol are not identical.
Dependence potential
Animal studies have demonstrated that, like other drugs of
abuse, dronabinol acts as a drug reinforcer. Physical dependence, as
shown by withdrawal syndrome following chronic administration, has
also been demonstrated. Reinforcing effects and physical dependence
have also been described in human studies.
Actual abuse and/or evidence of likelihood of abuse
The abuse of dronabinol is currently rare and there have been
very few specific reports of its occurrence. In response to the WHO
questionnaires only the United States mentioned instances of abuse
of delta-9-tetrahydrocannabinol. At present, the quantity produced
by licit manufacture is limited. In the United States, which is the
major manufacturing country, the abuse of dronabinol medicinal
preparations is reported to be very low and there are no reports of
diversion of the pharmaceutical product.
[[Page 75562]]
Therapeutic usefulness
Dronabinol preparations have been used in a limited number of
countries in the treatment of nausea and vomiting associated with
cancer chemotherapy in patients who have failed to respond
adequately to conventional antiemetic treatments and in the
treatment of anorexia associated with weight loss in patients with
acquired immunodeficiency syndrome (AIDS). It has also been
indicated in the treatment of chronic pain (e.g. in multiple
sclerosis, neuropathic disorders and arthritis), neurological
disorders and appetite loss in cachexia, and is being evaluated for
use in various other clinical situations.
Recommendation
The Committee reconsidered the recommendation of the thirty-
third Expert Committee after considering the updated critical review
report. The Committee concluded that dronabinol constitutes a
substantial risk to public health. However this risk is different
from those related to cannabis--controlled under the 1961
Convention. The substance has a moderate therapeutic usefulness and
as a result of continuing clinical research its medical use is
likely to increase. Therefore, the Committee recommended that
dronabinol (INN) and its stereoisomers should be rescheduled from
Schedule II to Schedule III of the 1971 Convention.
To avoid legal and forensic chemical problems that may arise in
some countries when placing stereoisomers of the same substance
under different control systems, the Committee indicated that the
recommendation pertains to all stereoisomeric forms of delta-9-
tetrahydrocannabinol as specified above.
References
1. WHO Expert Committee on Drug Dependence. Twenty-sixth report.
Geneva, World Health Organization, 1989 (WHO Technical Report
Series, No. 787).
2. WHO Expert Committee on Drug Dependence. Twenty-seventh
report. Geneva, World Health Organization, 1991 (WHO Technical
Report Series, No. 808).
3. Report of the thirty-fourth session (29 April-9 May 1991).
Economic and Social Council, Commission on Narcotic Drugs, Official
Records, 1991, Supplement No. 4. New York, United Nations, 1991 (E/
1991/24, E/Cn.7/1991/26).
4. WHO Expert Committee on Drug Dependence. Thirty-second
report. Geneva, World Health Organization, 2001 (WHO Technical
Report Series, No. 903).
5. WHO Expert Committee on Drug Dependence. Thirty-third report.
Geneva, World Health Organization, 2003 (WHO Technical Report
Series, No. 915).
Recommendation on oripavine
Substance identification
Oripavine, 3-O-demethylthebaine, or 6,7,8, 14-tetradehydro-4,5-
alpha-epoxy-6-methoxy-17-methylmorphinan-3-ol is a phenanthrene
alkaloid contained in species of the Papaver plant. It is a major
metabolite of thebaine.
Previous review
Oripavine was pre-reviewed at the thirty-third meeting of the
Expert Committee in 2002 (1). The reason for pre-review in 2002 was
that oripavine is a substance that is convertible into thebaine, and
because thebaine is in turn convertible into morphine. Thebaine and
morphine are both in Schedule I of the 1961 Convention. Owing to
uncertainties regarding the scheduling of oripavine based on the
additional possibility of applying the 1988 Convention (2), the
Committee did not finalize this review at its thirty-third meeting,
but asked WHO for clarification of issues related to the conversion
of precursors into scheduled substances. Subsequent clarification of
these issues allowed the Committee to come to a conclusion at its
thirty-fourth meeting.
Recommendation
The Committee decided that oripavine is a substance that is
easily convertible into thebaine and other substances controlled in
Schedule I of the 1961 Convention. Hence, the Committee recommended
that oripavine be scheduled, like the substances mentioned, in
Schedule I of the 1961 Convention.
References
1. WHO Expert Committee on Drug Dependence. Thirty-third report.
Geneva, World Health Organization, 2003 (WHO Technical Report
Series, No. 915).
2. United Nations Convention against Illicit Traffic in Narcotic
Drugs and Psychotropic Substances, 1988. New York, United Nations,
1991.
III. Discussion
Although WHO has made specific scheduling recommendations for each
of the drug substances, CND is not obliged to follow the WHO
recommendations. Options available to CND for substances considered for
control under the 1971 Convention include the following: (1) Acceptance
of the WHO recommendations; (2) acceptance of the recommendations to
control, but control the drug substance in a schedule other than that
recommended; or (3) reject the recommendations entirely.
Synthetic delta-9-tetrahydrocannabinol (delta-9-THC), or
dronabinol, is the active component of the drug product Marinol, which
is marketed in the United States as an antiemetic in the setting of
cancer chemotherapy and for treatment of AIDS wasting syndrome. Marinol
is currently controlled in Schedule III of the CSA, and the drug
substance dronabinol (which is the synthetic equivalent of the natural
active component of marijuana, delta-9-THC) is controlled in Schedule I
of the CSA. The drug substance dronabinol, including its stereoisomers,
is controlled internationally in Schedule II of the Psychotropic
Convention.
Oripavine is controlled domestically in Schedule II of the CSA
because it is a derivative of thebaine, opium, and other opiates.
Oripavine is not under international control.
IV. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electric comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday. The abbreviated period for the submission of comments
is necessary to allow sufficient time for the Secretary of HHS to carry
out the required action and respond to the United Nations.
Dated: December 6, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-21318 Filed 12-14-06; 8:45 am]
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