2015-01408. International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization; Scheduling Recommendations; AH-7921; Gamma-Butyrolactone; 1,4-Butanediol; Ketamine; 9 Additional ...

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 and to request an informal public meeting 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 and/or public meeting will be considered in preparing the United States position on these proposals for a meeting of the United Nations Commission on Narcotic Drugs (CND) in Vienna, Austria, in March 2015. This notice is issued under the Controlled Substances Act (the CSA).

DATES:

Submit either electronic or written comments by February 26, 2015. Submit requests for a public meeting on or before February 6, 2015. (For additional information, see also section IV of this document).

ADDRESSES:

Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 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, [e-mail].

SUPPLEMENTARY INFORMATION:

I. Background

The United States is a party to the 1971 Convention on Psychotropic Substances (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 Psychotropic Convention that the CND proposes to decide whether to add a drug or other substance to one of the schedules of the 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 13 substances to be considered for control under the Psychotropic Convention. This notification reflects the recommendation from the 36th WHO Expert Committee for Drug Dependence (ECDD), which met in June 2014. In the Federal Register of December 30, 2013 (78 FR 79465), 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 a substance to be considered for control under this convention. The CSA does not require HHS to publish a summary of such information in the Federal Register. Nevertheless, in an effort to provide interested and affected persons an opportunity to submit comments regarding the WHO recommendations for narcotic drugs, the notification regarding 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 position of the United States on the control of this substance. 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:

Reference:

NAR/CL.11/2014

WHO/ECDD36; 1961C-Art.3; 1971C-Art.2

CU 2014/288/DTA/SGB

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 the Director-General of the World Health Organization (WHO), pursuant to article 3, paragraphs 1 and 3 of the Single Convention on Narcotic Drugs of 1961 as amended by the 1972 Protocol (1961 Convention) and article 2, paragraphs 1and 4 of the Convention on Psychotropic Substances of 1971 (1971 Convention) notified the Secretary-General of the following recommendations:

AH-7921 be placed in Schedule I of the 1961 Convention

and

Gamma-butyrolactone (GBL)

1,4-butanediol

25B-NBOMe (2C-B-NBOMe)

25C-NBOMe (2C-C-NBOMe)

25I-NBOMe (2C-I-NBOMe)

be placed in Schedule I of the 1971 Convention

and

N-benzylpiperazine (BZP)

JWH-018

AM-2201

3,4-methylenedioxypyrovalerone (MDPV)

Methylone (beta-keto-MDMA)

Mephedrone

be placed in Schedule II of the 1971 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. Also in accordance with the same provisions, the notification from WHO will be brought to the attention of the fifty-eighth session of the Commission on Narcotic Drugs, 9-17 March 2015.

His Excellency

Mr. John Kerry

Secretary of State of the United States of America

In connection with the notification, WHO has also submitted the relevant extract from the report of the thirty-sixth session of the WHO Expert Committee on Drug Dependence which is hereby transmitted as annex II.

Reference is made to the notification concerning the proposed recommendation for international control of mephedrone (4-methylmethcathinone) by the Government of the United Kingdom of Great Britain and Northern Ireland and to the respective note NAR/CL.2/2014 of 7 February 2014 of the Secretary-General to all Member States.

Furthermore reference is made to the notification concerning the proposed recommendation for international control of ketamine by the Government of the People's Republic of China and to the respective note NAR/CL.4/2014 of 14 March 2014 by the Secretary-General to all Member States, as well as to the recommendation of the Expert Committee on Drug Dependence related to ketamine (see annex I, page 2).

In order to assist the Commission in reaching a decision, it would be appreciated if the Government could communicate any economic, social, legal, administrative or other factors that it considers relevant to the possible scheduling of the afore-mentioned substances under the 1961 Convention and the 1971 Convention, at the latest by 30 January 2015 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: [phone], email: [e-mail].

17 December 2014

NAR/CL.11/2014

Annex I

Annex I

Letter Addressed to the Secretary-General of the United Nations From the Director-General of the World Health Organization

“With reference to Article 2, paragraphs 1, 4 and 6 of the Convention on Psychotropic Substances (1971) and Article 3, paragraphs 1, 3 and 5 of the Single Convention on Narcotic Drugs (1961), as amended by the 1972 Protocol, and following the 36th meeting of the Expert Committee on Drug Dependence in June 2014, I am pleased to submit recommendations of the World Health Organization.

The recommendations are that:

—AH-7921, be placed in Schedule I of the Single Convention on Narcotic Drugs (1961), that:

—Gamma-butyrolactone (GBL); 1,4-butanediol; 25B-NBOMe (2C-B-NBOMe); 25C-NBOMe (2C-C-NBOMe) and 25I-NBOMe (2C-I-NBOMe), be placed in Schedule I of the Convention on Psychotropic Substances (1971) and that:

—N-benzylpiperazine (BZP); JWH-018; AM-2201; 3,4-methylenedioxypyrovalerone (MDPV); Methylone (beta-keto-MDMA); Mephedrone, be placed in Schedule II of the Convention on Psychotropic Substances (1971).

The recommendations and the assessments and findings on which they are based are set out in detail in the Report of the 36th Expert Committee on Drug Dependence, which is the Committee that advises me on these issues. An extract of the Committee's Report is attached in Annex 1 to this letter.

A notification has been made by the United Kingdom of Great Britain and Northern Ireland, pursuant to article 2, paragraphs 1 and 3 of the Convention on Psychotropic Substances, 1971 concerning a proposed recommendation for international control of mephedrone. The Expert Committee critically reviewed this substance and considered that the degree of risk to public health and society associated with the abuse liability of mephedrone is substantial and therefore considered that the evidence of its abuse warranted its placement under international control, in Schedule II of the Convention on Psychotropic Substances (1971).

Following a notification under Article 2, paragraph 1 of the Convention on Psychotropic Substances (1971) by the Government of the People's Republic of China concerning proposed recommendation for international control of ketamine, the Expert Committee critically reviewed this substance, following its previous critical reviews of ketamine at its 35th and 34th meeting and the pre-review undertaken at its 33rd meeting. The information provided by China with its notification to the Secretary-General was brought to the Expert Committee's attention. The Expert Committee's assessment was that ketamine “is widely used as an anaesthetic in human and veterinary medicine, and is included in the WHO Model List of Essential Medicines and the WHO Model List of Essential Medicines for Children as well as in many national lists of essential medicines”. The Expert Committee found that it was presented with “compelling evidence [. . .] about the prominent place of ketamine as an anaesthetic in developing countries and crisis situations”. While the Expert Committee “acknowledged the concerns raised by some countries and UN organizations”, it stated that “ketamine abuse currently does not appear to pose a sufficient public-health risk of global scale to warrant scheduling” and recommended “that ketamine not be placed under international control at this time”. “Countries with serious abuse problems may decide to introduce or maintain control measures, but should ensure ready access to ketamine for surgery and anaesthesia for human and veterinary care”.

During its meeting, the Expert Committee also discussed the importance of having reliable and sufficient data that could inform the review process in particular for New Psychoactive Substances (NPS), acknowledging the fact that more and more NPS will likely be reviewed in the future, for which data will not always be readily available. UNODC and WHO will hold an international experts consultation in December 2014 to identify selection criteria for prioritisation of NPS to be reviewed by the Committee as well as relevant indicators, methods and tools for data collection on NPS.

I am very pleased with the ongoing collaboration between WHO, UNODC and INCB for improving access to controlled medicines while preventing misuse and trafficking and for preparing the Special Session of the United Nations General Assembly on the World Drug Problem in 2016.”

NAR/CL.11/2014

Annex II

Annex II

Extract From the Report of the 36th Expert Committee on Drug Dependence

Substance recommended to be scheduled in Schedule I of the Single Convention on Narcotic Drugs (1961), as amended by the 1972 Protocol:

AH-7921

AH-7921 is an N-substituted cyclohexylmethylbenzamide and is chemically 3,4-dichloro-N-{[1-(dimethylamino)cyclohexyl]methyl}benzamide.

AH-7921 had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that AH-7921 is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

AH-7921 is an opioid with “morphine-like” effects. The Committee considered that the degree of risk to public health and society associated with the abuse liability and accompanying evidence warranted its placement under international control. The Committee recommended that AH-7921 be placed in Schedule I of the Single Convention on Narcotic Drugs (1961), as amended by the 1972 Protocol.

Substances recommended to be scheduled in Schedule I of the Convention on Psychotropic Substances (1971):

Gamma-butyrolactone (GBL)

Gamma-butyrolactone (GBL) is chemically oxolan-2-one. GBL can be synthesised from gamma-hydroxybutyric acid (GHB) or tetrahydrofuran.

During the discussion of GHB at the 34th Meeting of the WHO Expert Committee on Drug Dependence (ECDD), the Committee “noted information relating to the abuse of GBL itself (convertible to GHB in the body) and suggested this substance for pre-review”. Based on the evidence presented in the pre-review of GBL during its 35th Meeting, given its close association with GHB, and the recommendation made by the Committee to reschedule GHB from Schedule IV to Schedule II of the Convention on Psychotropic Substances (1971), the Committee recommended that a critical review of GBL be undertaken.

The Committee considered that the degree of risk to public health and society associated with the abuse liability of GBL is especially serious. Whilst the Committee recognized widespread and important industrial use, it has no defined therapeutic usefulness. The Committee considered that the evidence of its abuse warranted its placement under international control within Schedule I of the Convention on Psychotropic Substances (1971).

1,4-butanediol

1,4-butanediol (butane-1,4-diol, 1,4-BDO or 1,4-BD) is one of four stable isomers of butanediol.

During the discussion of gamma-hydroxybutyric acid (GHB) at its 34th Meeting, the Committee “noted information relating to the abuse of 1,4-BD itself (convertible to GHB in the body) and suggested this substance for pre-review”. Based on the evidence presented in the pre-review of GBL during its 35th Meeting, given its close association with GHB, and the recommendation made by the Committee to reschedule GHB from Schedule IV to Schedule II of the Convention on Psychotropic Substances (1971), the Committee recommended that a critical review of 1,4-BD be undertaken.

1,4-butanediol produces its effects in the body through the in vivo formation of the scheduled substance GHB. The Committee considered that the degree of risk to public health and society associated with the abuse liability of 1,4-butanediol is especially serious. Whilst the Committee recognized widespread and important industrial use, it has no defined therapeutic usefulness. The Committee considered that the evidence of its abuse warranted its placement under international control within Schedule I of the Convention on Psychotropic Substances (1971).

25B-NBOMe

25B-NBOMe (2C-B-NBOMe) is chemically 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine.

25B-NBOMe had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that 25B-NBOMe is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

The Committee noted the challenges associated with the evidence base concerning the substance. The Committee considered that the degree of risk to public health and society associated with the abuse liability of 25B-NBOMe is especially serious. Whilst the Committee noted its use in medical research, it has no recorded therapeutic use.

The Committee considered that the evidence of its abuse warranted its placement under international control and recommended that 25B-NBOMe be placed in Schedule I of the Convention on Psychotropic Substances (1971).

25C-NBOMe

25C-NBOMe (2C-C-NBOMe) is chemically 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine.

25C-NBOMe had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that 25C-NBOMe is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

The Committee noted the challenges associated with the evidence base concerning the substance. The Committee considered that the degree of risk to public health and society associated with the abuse liability of 25C-NBOMe is especially serious. Whilst the Committee noted its use in medical research, it has no recorded therapeutic use. The Committee considered that the evidence of its abuse warranted its placement under international control and recommended that 25C-NBOMe be placed in Schedule I of the Convention on Psychotropic Substances (1971).

25I-NBOMe

25I-NBOMe (2C-I-NBOMe) is chemically 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine.

25I-NBOMe had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that 25I-NBOMe is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

The Committee noted the challenges associated with the evidence base concerning the substance. The Committee considered that the degree of risk to public health and society associated with the abuse liability of 25I-NBOMe is especially serious. Whilst the Committee noted its use in medical research, it has no recorded therapeutic use. The Committee considered that the evidence of its abuse warranted its placement under international control and recommended that 25I-NBOMe be placed in Schedule I of the Convention on Psychotropic Substances (1971).

Substances recommended to be scheduled in Schedule II of the Convention on Psychotropic Substances (1971):

N-benzylpiperazine (BZP)

N-benzylpiperazine (BZP) is an aryl-substituted piperazine and is chemically 1-benzyl-1,4-diazacyclohexane.

BZP was pre-reviewed at the 35th ECDD meeting and based on the reported psychostimulant effects, evidence of abuse and adverse effects, the Expert Committee concluded that a critical review was warranted.

BZP has been shown to have effects similar to amphetamine. The Committee considered that the degree of risk to public health and society associated with the abuse liability of BZP is substantial. Its therapeutic usefulness has been assessed to be little, as it is not currently licensed for use. The Committee considered that the evidence of its abuse warranted its placement under international control. The Committee recommended that BZP be placed in Schedule II of the Convention on Psychotropic Substances (1971).

JWH-018

JWH-018 is chemically naphthalen-1-yl(1-pentyl-1 H-indol-3-yl)methanone.

JWH-018 had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that JWH-018 is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

The Committee noted the challenges associated with the evidence base concerning the substance. The Committee noted analytically confirmed cases of non-fatal and fatal intoxications involving JWH-018. The Committee therefore considered that the degree of risk to public health associated with the abuse liability of JWH-018 is substantial. Its therapeutic usefulness has been assessed to be none. As per the Guidance on the WHO review of psychoactive substances for international control, higher regard was made to the substantial public health risk as opposed to the lack of therapeutic usefulness [p.18, paragraph 56, penultimate sentence]. The Committee recommended that JWH-018 be placed under international control in Schedule II of the Convention on Psychotropic Substances (1971).

AM-2201

AM-2201 is chemically [1-(5-fluoropentyl)-1 H-indol-3-yl]-naphthalen-1-ylmethanone.

AM-2201 had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that AM-2201 is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

The Committee noted the challenges associated with the evidence base concerning the substance. The Committee noted analytically confirmed cases of non-fatal and fatal intoxications involving AM-2201. The Committee therefore considered that the degree of risk to public health associated with the abuse liability of AM-2201 is substantial. Its therapeutic usefulness has been assessed to be none. As per the Guidance on the WHO review of psychoactive substances for international control, higher regard was made to the substantial public health risk as opposed to the lack of therapeutic usefulness [p.18, paragraph 56, penultimate sentence]. The Committee recommended that AM-2201 be placed under international control in Schedule II of the Convention on Psychotropic Substances (1971).

3,4-methylenedioxypyrovalerone (MDPV)

3,4-methylenedioxypyrovalerone (MDPV) is chemically (R,S)-1-(1,3-benzodioxol-5-yl)-2-(pyrrolidin-1-yl)pentan-1-one.

MDPV had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that MDPV is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

The Committee considered that the degree of risk to public health and society associated with the abuse liability of MDPV is substantial. Its therapeutic usefulness has been assessed to be none. The Committee considered that the evidence of its abuse warranted its placement under international control. As per the Guidance on the WHO review of psychoactive substances for international control, higher regard was made to the substantial public health risk as opposed to the lack of therapeutic usefulness [p.18 paragraph 56, penultimate sentence]. The Committee recommended that MDPV be placed in Schedule II of the Convention on Psychotropic Substances (1971).

Methylone (bk-MDMA)

Methylone (beta-keto-MDMA) is chemically (R,S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one.

Methylone had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that methylone is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm and that it has no medical use.

The Committee considered that the degree of risk to public health and society associated with the abuse liability of methylone is substantial. Its therapeutic usefulness has been assessed to be none. The Committee considered that the evidence of its abuse warranted its placement under international control. As per the Guidance on the WHO review of psychoactive substances for international control, higher regard was made to the substantial public health risk as opposed to the lack of therapeutic usefulness [p.18, paragraph 56, penultimate sentence]. The Committee recommended that methylone be placed in Schedule II of the Convention on Psychotropic Substances (1971).

Mephedrone

Mephedrone (4-methylmethcathinone, 4-MMC) is chemically (R,S)-2-(methylamino)-1-(4-methylphenyl)propan-1-one.

Mephedrone had not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO's attention that mephedrone is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any party. Preliminary data collected from literature and different countries indicated that this substance may cause substantial harm. A critical review was further undertaken by the Committee given that the Government of the United Kingdom of Great Britain and Northern Ireland had made a notification concerning a proposed recommendation for international control of mephedrone (4-methylmethcathinone), under article 2, paragraphs 1 and 3 of the Convention on Psychotropic Substances, 1971.

The Committee considered that the degree of risk to public health and society associated with the abuse liability of mephedrone is substantial. Its therapeutic usefulness has been assessed to be none. The Committee considered that the evidence of its abuse warranted its placement under international control. As per the Guidance on the WHO review of psychoactive substances for international control, higher regard was made to the substantial public health risk as opposed to the lack of therapeutic usefulness [p.18, paragraph 56, penultimate sentence].

The Committee recommended that mephedrone be placed in Schedule II of the Convention on Psychotropic Substances (1971).

III. Discussion

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 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.

AH-7921, or 1-(3,4-dichlorobenzamidomethyl)cyclohexyldimethylamine, is an opioid analgesic drug substance selective for the µ-opioid receptor. The WHO ECDD met in June 2014 and recommended that AH-7921 be placed in Schedule I of the 1961 Single Convention. AH-7921 is not controlled under the CSA in the United States. As such, additional controls will be necessary to fulfill U.S. obligations if AH-7921 is controlled under Schedule I of the 1961 Single Convention.

Gamma-butyrolactone (GBL) is used as an industrial solvent. GBL can be converted in the body to the central nervous system depressant drug gamma-hydroxybutyric acid (GHB). GBL is controlled as a List I chemical in the United States under the CSA. The WHO ECDD met in June 2014 and recommended that GBL be placed in Schedule I of the Psychotropic Convention. Additional controls will be necessary to fulfill U.S. obligations if GBL is controlled under Schedule I of the Psychotropic Convention.

1,4-Butanediol is used as an industrial solvent for manufacturing and also used for the synthesis of GBL. 1,4-Butanediol can also be converted to the central nervous depressant drug GHB. It has no medical use in the United States. 1,4-Butanediol is not controlled under the CSA in the United States, but it is subject to controls in several States under state law. 1,4-Butanediol was reviewed by the WHO ECDD at its 36th meeting, at which the WHO ECDD recommended that 1,4-butanediol be placed in Schedule I of the Psychotropic Convention. Additional controls will be necessary to fulfill U.S. obligations if 1,4-butanediol is controlled under Schedule I of the Psychotropic Convention.

The substances 25B-NBOMe (2C-B-NBOMe), 25C-NBOMe (2C-C-NBOMe), and 25I-NBOMe (2C-I-NBOMe) are synthetic 2C phenethylamine substances and were developed for use in mapping and investigating the serotonin receptors in the mammalian brain. The WHO ECDD at its 36th meeting recommended that 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe be placed in Schedule I of the Psychotropic Convention. On November 15, 2013, 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe were temporarily placed in Schedule I of the CSA under the temporary scheduling provision of section 201(h) of the CSA. These provisions provide the Attorney General with the authority to temporarily place a substance into Schedule I of the CSA for 2 years, without regard to the requirements of 21 U.S.C. 811(b), if he finds that such action is necessary to avoid an imminent hazard to the public safety. In addition, if proceedings to control a substance are initiated under 21 U.S.C. 811(a)(1), the Attorney General may extend the temporary scheduling for up to 1 year (21 U.S.C. 811(h)(2)). Therefore, considering the previously mentioned time limitations of temporary scheduling under section 201(h) of the CSA, additional controls will be necessary to fulfill U.S. obligations if 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe are controlled under Schedule I of the Psychotropic Convention.

N-benzylpiperazine (BZP) is used as an intermediate in chemical synthesis but has been taken orally as either powder or tablets and by other routes, including smoking or snorting. It has no medical use in the United States. The WHO ECDD at its 36th meeting recommended that BZP be placed in Schedule II of the Psychotropic Convention on Psychotropic Substances (1971). BZP is controlled in Schedule I under the CSA in the United States. As such, no additional controls will be necessary to fulfill U.S. obligations if these substances are controlled under Schedule II of the Psychotropic Convention.

The substances 1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-018) and [1-(5-fluoropentyl)-1H-indol-3-yl]-1-naphthalenyl-methanone (AM-2201) are classified as synthetic cannabinoids with pharmacological properties like tetrahydrocannabinol. The WHO ECDD at its 36th meeting recommended that JWH-018 and AM-2201 be placed in Schedule II of the Psychotropic Convention. These two substances are controlled in Schedule I under the CSA in the United States. As such, no additional controls will be necessary to fulfill U.S. obligations if JWH-018 and AM-2201 are controlled under Schedule II of the Psychotropic Convention.

The substances 3,4-methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy-N-methylcathinone (beta-keto-MDMA; methylone), and 4-methylmethcathinone (4-MMC; mephedrone) are classified as synthetic cathinones in the phenethylamine class and are structurally and pharmacologically similar to amphetamine. The WHO ECDD at its 36th meeting recommended that MDPV, methylone, and mephedrone be placed in Schedule II of the Psychotropic Convention. MDPV, methylone, and mephedrone are controlled in Schedule I under the CSA in the United States. As such, no additional controls will be necessary to fulfill U.S. obligations if these three substances are controlled under Schedule II of the Psychotropic Convention.

In addition to the above substances recommended for international control by the WHO Expert Committee at its 36th meeting, the United Nations Economic and Social Council published recommendations for action to be taken by the CND at the March 2015 meeting (http://www.un.org/​Docs/​journal/​asp/​ws.asp?​m=​E/​CN.7/​2015/​7). Among these recommendations is that the CND should decide whether it wishes to place ketamine in Schedule I of the Psychotropic Convention or, if not, what other action, if any, might be required. Pursuant to article 2, paragraph 1, of the Convention on Psychotropic Substances of 1971, the Government of China, in its correspondence dated 8 March 2014, notified the Secretary-General of the United Nations that China recommended that ketamine be placed in Schedule I of the 1971 Convention. In accordance with article 2 of the Psychotropic Convention, this proposal has been recommended for consideration by the CND.

Ketamine is classified as a rapid-acting general anesthetic agent used for short diagnostic and surgical procedures that do not require skeletal muscle relaxation. It is marketed in the United States as an injectable. Ketamine is controlled in Schedule III of the CSA in the United States. It is not controlled internationally under the Convention on Psychotropic Substances or the Single Convention on Narcotic Drugs. The WHO Expert Committee on Drug Dependence reviewed ketamine at its 34th, 35th, and 36th meetings. Ketamine is controlled in schedule III of the CSA in the United States, and additional controls may be necessary to fulfill U.S. obligations if ketamine is controlled under Schedule I of the Psychotropic Convention. 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 Psychotropic Convention at the CND meeting in March 2015.

Comments regarding the WHO recommendations for control of AH-7921 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.

IV. Submission of Comments and Opportunity for Public Meeting

Interested persons may submit either electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments 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, and will be posted to the docket at http://www.regulations.gov.

FDA does not presently plan to hold a public meeting. If any person believes that, in addition to written comments, a public meeting would contribute to the development of the U.S. position on the substances to be considered for control under the Psychotropic Convention, a request for a public meeting and the reasons for such a request should be sent to James R. Hunter (see FOR FURTHER INFORMATION CONTACT) on or before February 6, 2015.

The short time period for the submission of comments and requests for a public meeting is needed to ensure that HHS may, in a timely fashion, carry out the required action and be responsive to the United Nations.

Dated: January 21, 2015.

Leslie Kux,

Associate Commissioner for Policy.