U.S. Department of Justice Drug Enforcement Administration Background, Data and Analysis of Synthetic Cathinones: Mephedrone (4-MMC), Methylone (MDMC) and 3,4-Methylenedioxypyrovalerone (MDPV) Prepared by Office of Diversion Control, Drug and Chemical Evaluation Section Washington, D.C. 20537 August 2011 Background The Comprehensive Crime Control Act of 1984 (Pub. L. 98-473), which was signed into law on October 12, 1984, amended section 201 of the Controlled Substances Act (CSA) (21 U.S.C. 811) to give the Attorney General the authority to temporarily place a substance into Schedule I of the CSA for one year without regard to the requirements of 21 U.S.C. 811(b) if he finds that such action is necessary to avoid imminent hazard to the public safety. 21 U.S.C. 811(h); 21 CFR 1308.49. If proceedings to control a substance are initiated under 21 U.S.C. 811(a)(1), the Attorney General may extend the temporary scheduling up to six months. 21 U.S.C. 811(h)(2). Where the necessary findings are made, a substance may be temporarily scheduled if it is not listed in any other schedule under section 202 of the CSA (21 U.S.C. 812) or if there is no exemption or approval in effect under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) for the substance. 21 U.S.C. 811(h)(1). The Attorney General has delegated his authority under 21 U.S.C. 811 to the Administrator of the Drug Enforcement Administration (DEA). 28 CFR 0.100. Section 201(h)(4) of the CSA (21 U.S.C. 811(h)(4)) requires the Administrator to notify the Secretary of Health and Human Services of her intention to temporarily place a substance into Schedule I of the CSA.1 The Administrator has transmitted notice of her intent to place 4- methyl-N-methylcathinone (mephedrone), 3,4-methylenedioxy-N-methylcathinone (methylone) 1 The Secretary of Health and Human Services has delegated to the Assistant Secretary for Health of the Department of Health and Human Services the authority to make domestic drug scheduling recommendations. and 3,4-methylenedioxypyrovalerone (MDPV) in Schedule I on a temporary basis to the Assistant Secretary by letter dated June 15, 2011. The Assistant Secretary responded to this notice by letter dated July 25, 2011, and advised that based on review by the Food and Drug Administration (FDA) there are currently no investigational new drug applications (INDs) or approved new drug applications (NDAs) for MDPV, mephedrone, or methylone. The Assistant Secretary also stated that the Department of Health and Human Services has no objection to the temporary placement of MDPV, mephedrone, and methylone into Schedule I of the CSA. DEA has taken into consideration the Assistant Secretary‟s comments. As MDPV, mephedrone, and methylone are not currently listed in any schedule under the CSA, and as no exemptions or approvals are in effect for MDPV, mephedrone, and methylone under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355), DEA believes that the conditions of 21 U.S.C. 811(h)(1) have been satisfied. Any additional comments submitted by the Assistant Secretary in response to this notice, including whether any exemptions or approvals come into effect for the substances in question under the Federal Food, Drug, and Cosmetic Act, shall also be taken into consideration before a final order is published. 21 U.S.C. 811(h)(4). To make a finding that placing a substance temporarily into Schedule I of the CSA is necessary to avoid an imminent hazard to the public safety, the Administrator is required to consider three of the eight factors set forth in section 201(c) of the CSA (21 U.S.C. 811(c)). These factors are as follows: the substance‟s history and current pattern of abuse; the scope, duration and significance of abuse; and what, if any, risk there is to the public health. 21 U.S.C. 811(c)(4)-(6). Consideration of these factors includes actual abuse, diversion from legitimate channels, and clandestine importation, manufacture, or distribution. 21 U.S.C. 811(h)(3). A substance meeting the statutory requirements for temporary scheduling (21 U.S.C. 811(h)(1)) may only be placed in Schedule I. Substances in Schedule I are those that have a high potential for abuse, no currently accepted medical use in treatment in the United States, and lack accepted safety for use under medical supervision. Available data and information for mephedrone, methylone, and MDPV indicate that these three synthetic cathinones have a high potential for abuse, no currently accepted medical use in treatment in the United States, and lack accepted safety for use under medical supervision. This review document provides an evaluation of the criteria for this determination for the synthetic cathinones mephedrone, methylone, and MDPV, as of August 2011. Introduction Mephedrone, methylone, and MDPV are synthetic cathinones (also commonly referred to as substituted cathinones or cathinone derivatives) that share many similarities with the Schedule I stimulants cathinone and methcathinone. Evidence indicates that these synthetic cathinones are being abused for their psychoactive properties. These substances are falsely marketed as “research chemicals,” “plant food,” or “bath salts.” They are sold at smoke shops, head shops, convenience stores, adult book stores, and gas stations and can also be purchased on the Internet. The packages of these commercial products usually contain the warning “not for human consumption” most likely in an effort to circumvent statutory restrictions for these substances. Evidence from law enforcement and poison control centers indicates that the abuse of synthetic 2 cathinones appears to be widespread and is growing. The American Association of Poison Control Centers (AAPCC)2 reported that, as of July 31, 2011, poison control centers have received 4,137 calls relating to human exposures to “bath salts” for this year (AAPCC, 2011). These calls were received in poison centers in at least 47 states and the District of Columbia. In 2009, the National Forensic Laboratory Information System (NFLIS) registered 15 reports from 8 states containing these three synthetic cathinones.3 However, in 2010, there were 560 reports from 29 states related to these substances registered in NFLIS, and from January to March 2011 there were 391 reports. An additional 435 reports to NFLIS were captured from April to June 2011 for a total of 826 reports from January to June 2011.4 Mephedrone, methylone, and MDPV have no known medical use in the United States and evidence demonstrates that these substances are being abused by individuals as there have been reports of emergency room admissions and deaths associated with the abuse of these substances. These substances have become a serious drug abuse threat. In light of the above information and to protect the public health and safety, DEA is proposing and intends to temporarily place these synthetic cathinones in Schedule I of the CSA. Under the CSA, before DEA can temporarily schedule a substance, the Administrator must notify the Assistant Secretary for Health, delegate of the Secretary of Health and Human Services (HHS), of her intentions. In accordance with Section 201(h)(4) of the CSA, the Assistant Secretary for Health was notified on June 15, 2011. To make a finding that placing a substance temporarily into Schedule I of the CSA is necessary to avoid an imminent hazard to the public safety, the Administrator is required to consider three of the eight factors set forth in section 201(c) of the CSA (21 U.S.C. 811(c)). These factors are as follows: the substance‟s history and current pattern of abuse; the scope, duration and significance of abuse; and what, if any, risk there is to the public health. Pursuant to this action, DEA has reviewed the three factors under the CSA (21 U.S.C. 811(c)(4)-(6)) required for temporary scheduling of mephedrone, methylone, and MDPV. Synthetic cathinones Synthetic cathinones are a class of β-ketone amphetamines. Synthetic cathinones include but are not limited to mephedrone, methylone, MDPV, butylone, 4-fluoromethcathinone (4- FMC), 3-fluoromethcathinone (3-FMC), 4-methoxymethcathinone (methedrone), 4-methyl-N- ethylcathinone (4-MEC), ethylone, buphedrone, dimethylcathinone, diethylcathinone, and 3,4- methylenedioxy- -pyrrolidinopentiophenone (MDPBP). Synthetic cathinones, like cathinone, methcathinone, and amphetamine, are central nervous system stimulants and have been reported to induce subjective effects similar to those induced by Schedule I and II stimulants. Consequently, synthetic cathinones are being abused for their stimulant effects. Synthetic cathinones are also reported to be abused for their hallucinogenic effects. Like Schedule I and II 2 AAPCC is a non-profit, national organization that represents the poison control centers of the United States. 3 NFLIS is a DEA sponsored database for seized items analyzed by federal, state, and local forensic laboratories. 4 Analyzed on August 24, 2011. 3 stimulants, synthetic cathinones effect monoamine transmission. Synthetic cathinones have been shown to bind to monoamine transporters for dopamine, serotonin, and noradrenaline in the brain and promote release of these monoamines (Cozzi et al., 1998; Cozzi et al., 1999; Fuwa et al., 2007; Nagai et al., 2007; Kehr et al., 2011; Sogawa et al., 2011). Increased monoamine concentration in the central nervous system is thought to be involved in the stimulant and hallucinogenic effects of the phenethylamine class of drugs (Dal Cason et al., 1997). Mephedrone, methylone, and MDPV are the most commonly encountered synthetic cathinones. These three substances represent more than 98% (1,401 of 1,429) of the synthetic cathinones that have been encountered by law enforcement, as reported to NFLIS. Of all the reports (1,429) of synthetic cathinones recorded by NFLIS from January 2009 to June 2011, 55% (791) were MDPV, 23% (331) were mephedrone, and 20% (279) were methylone.