[Federal Register Volume 63, Number 214 (Thursday, November 5, 1998)]
[Proposed Rules]
[Pages 59751-59753]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29571]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration
[DEA-180P]

21 CFR Parts 1308 and 1312


Schedules of Controlled Substances: Rescheduling of Synthetic 
Dronabinol (Martinol; (-)-9-(trans)-
Tetrahydrocannabinol in Sesame oil and Encapsulated in Soft Gelatin 
Capsules) From Schedule II to Schedule III.

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: This proposed rule is issued by the Acting Deputy 
Administrator of the Drug Enforcement Administration (DEA) to remove 
the Food and Drug Administration (FDA) approved drug product containing 
dronabinol [Marinol; (-)-x-69-
(trans)-tetrahydrocannabinol in sesame oil and encapsulated in soft 
gelatin capsules] from Schedule II and place it into Schedule III of 
the Controlled Substances Act (CSA). This proposed action is based on 
an evaluation of the relevant data by the DEA and a recommendation from 
the Assistant Secretary for Health of the Department of Health and 
Human Services (DHHS)

[[Page 59752]]

that the FDA-approved dronabinol product [Marinol; (-)-
9-(trans)-THC in sesame oil and encapsulated in 
soft gelatin capsules] be rescheduled from Schedule II to Schedule III. 
If finalized, this action will impose the regulatory controls and 
criminal sanctions of Schedule III on those who handle dronabinol and 
products containing dronabinol.

DATES: Comments, objections and requests for a hearing must be received 
on or before December 7, 1998.

ADDRESSES: Comments, objections and requests for a hearing should be 
submitted in quintuplicate to the Acting Deputy Administrator, Drug 
Enforcement Administration, Washington, DC. 20537; Attention: DEA 
Federal Register Representative/CCR.

FOR FURTHER INFORMATION CONTACT: Frank Sapienza, Chief, Drug and 
Chemical Evaluation Section, Drug Enforcement Administration, 
Washington, DC. 20537, 202-307-7183.

SUPPLEMENTARY INFORMATION: Dronabinol is the synthetic equivalent of 
the (-)-isomer of 9-(trans)-tetrahydrocannabinol 
[9-(trans)-THC], which is the major psychoactive 
component of Cannabis sativa L. (Marijuana). Dronabinol, under the 
trade name Marinol. was approved for marketing by the FDA 
on May 31, 1985 for the treatment of nausea and vomiting associated 
with cancer chemotherapy. Dronabinol [Marinol; (-)-
9-(trans)-THC in sesame oil and encapsulated in 
soft gelatin capsules], but not THC itself, was transferred from 
Schedule I to Schedule II of the CSA on May 13, 1986, in accordance 
with 21 U.S.C. 811(a) and the FDA approval of a new drug application 
for Marinol capsules. The rescheduling of 
Marinol was based on a recommendation from the Assistant 
Secretary for Health which also stated that THC should remain in 
Schedule I. Marinol's indications were expanded on December 
22, 1992 to include the treatment of anorexia associated with weight 
loss in patients with AIDS.
    On February 3, 1995, UNIMED Pharmaceuticals, Inc. petitioned the 
Administrator of the DEA to reschedule dronabinol formulations from 
Schedule II to Schedule III. This request involves only dronabinol 
[synthetic (-)-9-(trans)-THC], specifically the 
product Marinol (dronabinol in sesame oil in a soft gelatin 
capsule). Prior to a review of the data in the petition, the DEA had to 
determine whether the rescheduling of dronabinol formulations to 
Schedule III was possible, in light of the control of THC in Schedule 
II of the 1971 Convention on Psychotropic Substances. The DEA concluded 
that control of dronabinol formulations in Schedule III of the CSA was 
possible and would meet the requirements of Schedule II of the 
convention provided that THC remained in Schedule I or II of the CSA 
and that 21 CFR 1312.30 was amended to require import and export 
permits for international transactions involving dronabinol.
    On December 11, 1996, UNIMED Pharmaceuticals, Inc. submitted a 
supplement to its petition to reschedule dronabinol formulations from 
Schedule II to Schedule III. This supplement provided data regarding 
the pharmacokinetics of Marinol, additional data about the 
chemistry of the product and studies regarding the actual abuse of the 
Marinol product. This information specifically addressed 
the criteria required to be considered under the CSA.
    On August 7, 1997, after gathering the necessary data, the DEA sent 
its review document and a letter to the Acting Assistant Secretary for 
Health, DHHS requesting a scientific and medical evaluation of the 
available data and a scheduling recommendation on dronabinol, as 
required by 21 U.S.C. 811(b).
    On September 11, 1998, the Acting Assistant Secretary for Health 
sent to the DEA a letter recommending that dronabinol 
(Marinol; (-)-9-(trans)-THC in sesame 
oil and encapsulated in soft gelatin capsules) be transferred from 
Schedule II to Schedule III of the CSA. Enclosed with the September 11, 
1998 letter was a document prepared by the FDA entitled ``Basis for the 
Recommendation for Rescheduling Marinol Capsules from 
Schedule II to Schedule III of the CSA.'' In this document, the FDA 
defines the Marinol product as ``an FDA approved drug 
product containing synthetically produced dranabinol dissolved in 
sesame oil and encapsulated in soft gelatin capsules (2.5 mg, 5 mg, and 
10 mg per dosage unit.'' The document contained a review of the factors 
which the CSA requires the Secretary to consider [21 U.S.C. 811(c)].
    The factors considered by the Acting Assistant Secretary for Health 
and the DEA with respect to dranabinol were:
    (1) Its actual or relative potential for abuse;
    (2) Scientific evidence of its pharmacological effect, if known;
    (3) The state of current scientific knowledge regarding the drug or 
other substance;
    (4) Its history and current pattern of abuse;
    (5) The scope, duration, and significance of abuse;
    (6) What, if any, risk there is to the public health;
    (7) Its psychic or physiological dependence liability; and
    (8) Whether the substance is an immediate precursor of a substance 
already controlled under this subchapter.
    The pharmacological and behavioral effects of dronabinol are 
comparable to those of 9-THC, marijuana and other 
active cannabinoids. There are few scientific studies that directly 
evaluate the pharmacologeutical and behavioral effects of the product 
Marinol to indicate that there are differences in its abuse 
liability compared to oral THC. Nevertheless, there is little evidence 
of actual abuse of Marinol, despite modest annual increases 
in the total number of prescriptions written. Despite dronabinol's THC-
like abuse liability, there are several factors that deter its actual 
abuse and trafficking. These factors include dronabinol's formulation 
in sesame oil, the improbability that the THC would be extracted from 
the product and abused by another route of administration, and its 
delayed onset of effects. Although excessive use of Marinol 
may result in the development of psychological dependence, there has 
been no evidence of such use. The scientific data reviewed to date and 
the minimal evidence of actual abuse and trafficking support the 
transfer of dronabinol to Schedule III of the CSA.
    Relying on the scientific and medical evaluation and the 
recommendation of the Assistant Secretary for Health in accordance with 
section 201(b) of the CSA (21 U.S.C. 811(b)), and the independent 
review of the DEA, the Acting Deputy Administrator of the DEA, pursuant 
to sections 201(a) and 201(b) of the CSA (21 U.S.C. 811(a) and 811(b)), 
finds that:
    (1) Based on information now available, dronabinol 
(Marinol) has a potential for abuse less than the drugs or 
other substances in Schedules I and II.
    (2) Marinol [(-)-9-(trans)-THC in 
sesame oil and encapsulated in soft gelatin capsules] is an FDA 
approved drug product and has a currently accepted medical use in 
treatment in the United States; and
    (3) Abuse of dronabinol [Marinol;           (-)-
9-(trans)-THC in seasame oil and encapsulated in 
soft gelatin capsules] may lead to moderate or low physical dependence 
or high psychological dependence.
    Based on these findings, the Acting Deputy Administrator of the DEA 
concludes that dronabinol [Marinol;           (-)-
9-(trans)-THC in sesame oil and encapsulated in 
soft gelatin capsules]

[[Page 59753]]

should be removed from Schedule II and placed into Schedule III of the 
CSA.

Special Provisions Regarding Import/Export Authorization

    Dronabinol is internationally controlled in Schedule II of the 1971 
Convention on Psychotropic Substances, to which the United States is a 
party. Under the special obligations of the Convention, Article 12 
defines provisions relating to international trade relative to Schedule 
II substances. Specifically, signatory countries are required to issue 
import/export permits/authorizations to import or export a Schedule II 
substance. Due to its international control status, import/export 
permits for dronabinol still will be required despite the proposed 
transfer of dronabinol to Schedule III of the CSA.
    In accordance with 21 CFR 1312.13(b) ``[t]he Administrator may 
require that such non-narcotic controlled substances in Schedule III as 
he shall designate by regulation in Sec. 1312.30 of this part be 
imported only pursuant to the issuance of an import permit'' (21 U.S.C. 
952(b)(2)). Similarly, the DEA could require export permits for 
Schedule III non-narcotic substances (21 CFR 1312.23(b) and 21 U.S.C. 
953(e)(2)).
    Currently, there are no Schedule III non-narcotic substances for 
which the Administrator requires an import/export permit. However, in 
accordance with 21 CFR 1312.30, this proposed designation of dronabinol 
as a Schedule III non-narcotic substance requiring an import/export 
permit is necessary for the United States to remain in compliance with 
the Convention.
    Interested persons are invited to submit their comments, objections 
or requests for a hearing, in writing, with regard to this proposal. 
Requests for a hearing should state, with particularity, the issues 
concerning which the person desires to be heard. All correspondence 
regarding this matter should be submitted to the Acting Deputy 
Administrator, Drug Enforcement Administrator, Washington, DC 20537. 
Attention: DEA Federal Register Representative/CCR. In the event that 
comments, objections, or requests for a hearing raise one or more 
issues which the Acting Deputy Administrator finds warrant a hearing, 
the Acting Deputy Administrator shall order a public hearing by notice 
in the Federal Register, summarizing the issues to be heard and setting 
the time for the hearing.
    In accordance with the provisions of the CSA (21 U.S.C. 811(a)), 
this action is a formal rulemaking ``on the record after opportunity 
for a hearing.'' such proceedings are conducted pursuant to the 
provisions of 5 U.S.C. 556 and 557 and, as such, are exempt from review 
by the Office of Management and Budget pursuant to Executive Order 
(E.O.) 12866, section 3(d)(1). The Acting Deputy Administrator, in 
accordance with the Regulatory Flexibility Act (5 U.S.C. 605(b)), has 
reviewed this proposed rule and by approving it certifies that it will 
not have a significant economic impact on a substantial number of small 
entities. Dronabinol products are prescription drugs used to treat 
nausea due to cancer chemotherapy and AIDS wasting. Handlers of 
dronabinol are likely to handle other controlled substances used to 
treat cancer or AIDS, which are already subject to the regulatory 
requirements of the CSA. Further, placement of dronabinol in Schedule 
III of the CSA will mean a significant decrease in the regulatory 
requirements for persons handling dronabinol products.
    This rule will not result in the expenditure by State, local and 
tribal governments, in the aggregate, or by the private sector, of 
$100,000,000 or more in any one year, and it will not significantly or 
uniquely affect small governments. Therefore, no actions were deemed 
necessary under provisions of the Unfunded Mandates Reform Act of 1995.
    This rule is not a major rule as defined by section 804 of the 
Small Business Regulatory Enforcement Fairness Act of 1996. This rule 
will not result in an annual effect on the economy of $100,000,000 or 
more; a major increase in costs or prices; or significant adverse 
effects on competition, employment, investment, productivity, 
innovation, or on the ability of United States based companies to 
compete with foreign based companies in domestic and export markets.
    This rule will not have substantial direct effects on the United 
States, on the relationship between the national government and the 
United States, or on the distribution of power and responsibilities 
among the various levels of government. Therefore, in accordance with 
E.O. 12612, it is determined that this rule, if finalized, will not 
have sufficient federalism implications to warrant the preparation of 
Federalism Assessment.

List of Subjects

21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Narcotics, Prescription drugs.

21 CFR Part 1213

    Administrative practice and procedure, Drug traffic control, 
Exports, Imports, Narcotics, Reporting requirements.

    Under the authority vested in the Attorney General by section 
201(a) of the CSA (21 U.S.C. 811(a)), and delegated to the 
Administrator of the DEA by the Department of Justice regulations (28 
CFR 0.100) and redelegated to the Deputy Administrator pursuant to 28 
CFR 0.104, the Acting Deputy Administrator hereby proposes that 21 CFR 
parts 1308 and 1312 be amended as follows:

PART 1308--[AMENDED]

    1. The authority citation for 21 CFR part 1308 continues to read as 
follows:

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


Sec. 1308.12  [Amended]

    2. Section 1308.12 is proposed to be amended by removing paragraph 
(f)(1) and redesignating the existing paragraph (f)(2) as (f)(1).
    3. Section 1308.13 is proposed to be amended by adding a new 
paragraph (g)(1) to read as follows:


Sec. 1308.13  Schedule III.

* * * * *
    (g) Hallucinogenic substances.

(1) Dronabinol (synthetic) in sesame oil and encapsulated in a
 soft gelatin capsule in a U.S. Food and Drug Administration
 approved product................................................   7369

[Some other names for dronabinol: (6aR-trans)-6a,7,8,10a-tetrahydro-
6,6,9-trimethyl-3-pentyl-[6H-dibenzo[b,d]pyran-1-ol] or (-)-delta-9-
(trans)-tetrahydrocannabinol]

PART 1312--[AMENDED]

    1. Section 1312.30 is proposed to be amended by adding a new 
paragraph (a) to read as follows:


Sec. 1313.30  Schedule III, IV and V non-narcotic controlled substances 
requiring an import and export permit.

* * * * *
    (a) Dronabinol (synthetic) in sesame oil and encapsulated in a soft 
gelatin capsule in a U.S. Food and Drug Administration approved 
product.
* * * * *
    Dated: October 29, 1998.
Donnie R. Marshall,
Acting Deputy Administrator, Drug Enforcement Administration.
[FR Doc. 98-29571 Filed 11-4-98; 8:45 am]
BILLING CODE 4410-09-M