The Administrator has reviewed this final rule in accordance with the Regulatory Flexibility Act (5 U.S.C. 601-612) (RFA) and certifies by its approval that it will not have a significant economic impact on a significant number of small businesses. First, there is no accepted commercial, industrial or medical use for methylone. At least 42 states have already banned the production, distribution, and use of methylone, and all U.S. military personnel are prohibited from possessing and using it. Since the interim planning of October 21, 2011, 30 companies have been registered with the DEA for handling methylone. If the synthetic cannabinoid JWH-018 is used as a reference, since it also has no accepted commercial, industrial or medical use, there are currently 40 companies registered to handle this substance, as it was published on September 1. It was temporarily planned for 9 July 2011 and then permanently added to Schedule I on 9 July 2012 by the Synthetic Drug Abuse Prevention Act 2012. Public Law 112-144, Title XI, Subtitle D, Articles 1151-1153. Based on this, and because there is no evidence of clinical trials with methylone in the scientific and medical literature, the DEA expects the number of companies registered to handle methylone to remain relatively small. Second, there are approximately 1.4 million registrants of controlled substances, representing approximately 381,000 companies affected by this rule. The DEA estimates that 371,000 (97%) of the affected businesses are considered “small businesses” under RFA and Small Business Administration standards. 5 U.S.C.
601(6) and 15 U.S.C. 632. Even if all companies registered to process methylone (30 companies) were considered small businesses, the number of small businesses affected by this rule would not be significant. Concerns about the misuse of methylone and other synthetic cathinones have led many States to control these substances. As of March 2013, at least 42 states had planned or enacted emergency legislation that includes regulatory controls for some or more of the synthetic cathinones, including methylone. In addition, the U.S. armed forces have banned the use of synthetic cathinones such as mephedrone, methylone, and MDPV. Concerns about the pharmacological and potential abuse outcomes considered by the DEA in planning methylone: Several commenters have argued that methylone does not meet the criteria for listing in Appendix I because it does not meet the “high potential for abuse” principle or the “currently no accepted medical use in treatment in the United States” principle. that the CSA require a substance to be listed in Schedule I. 21 U.S.C. 812(b)(1)(A)-(B).
It has been reported that methylone causes a number of side effects characteristic of stimulants such as methamphetamine, amphetamine and cocaine. Side effects associated with methylone consumption include those typical of a sympathomimetic, such as hyperthermia, seizures, hyponatremia, bruxism, sweating, hypertension, tachycardia, headache, palpitations, thirst and mydriasis. Other effects that have been reported from methylone use include psychological effects such as confusion, psychosis, paranoia, hallucinations, combativeness and agitation. Finally, reports of deaths of people abusing methylone suggest that methylone poses a serious threat to public health. Finally, it is also important to mention some limitations of this study. The main limitation of the present study is a relatively small number of subjects in the IVSA experiments (n = 48) and the ICSS experiments (n = 4). One of the most important findings of the present study is that methylone has a relatively low risk of abuse given the lack of LgA escalation. Although it seems unlikely that any dose group would have a significant increase in intake, it is possible that an increase in intake was observed in a subset of animals in other subjects.
Further studies are needed to assess this possibility. In addition, ICSS experiments were conducted with only 4 rats, and it is possible that other subjects would have given statistical significance, since only one trend towards significance (p = 0.09) was observed. Another limitation of the current study is that it was conducted with drug-naïve animals. Although demographics on methylone users are scarce, it is possible that people who have had previous experiences with illicit stimulants are more aware of methylone`s enhancing properties. These possibilities need to be further explored. Finally, it is important to reiterate that although our results suggest stronger strengthening properties of methylone compared to MDMA and weaker strengthening properties compared to MDPV and other prototypical stimulants, our study is the first to show methylone IVSA. Therefore, replication of our initial IVSA results, as well as additional studies directly comparing methylone with MDMA and other psychostimulants, is necessary before firm conclusions can be drawn. Compared to MDMA, it has about 3 times lower affinity for the serotonin transporter (Ki = 242.1 nM for methylone to Ki = 72 nM for MDMA), while its affinity for norepinephrine and dopamine transporters is similar.   Remarkably, methylone`s affinity for monoamine 2 vesicular transporter (VMAT2) is about 13 times lower than that of MDMA.  Purchase orders.
All registrants involved in the distribution of methylone must comply with the requirements of the order form set forth in 21 U.S.C. 828 and 21 CFR 1305. Criminal liability. Any activity involving methylone that is not authorized under the Controlled Substances Act or the Import and Export of Controlled Substances Act or that contravenes the Controlled Substances Act is illegal. The CSA provides that the planning of a drug or other substance may be initiated ex officio by the Attorney General (1); (2) at the request of the Minister of Health of the Department of Health and Human Services (HHS) or (3) at the request of any interested party. 21 U.S.C. 811(a). This action is based on a recommendation from the Assistant Secretary of Health (Assistant Secretary)  of HHS and an evaluation of all other relevant data by the DEA. Given methylone`s current status as an interim Schedule I controlled substance (see “Background” section below), this measure permanently imposes the regulatory controls and criminal penalties in Schedule I on the manufacture, distribution, supply, import and export of methylone and methyl-containing products. In addition, it is also important to mention the differences in leverage pressure behavior for methylone observed in the present study compared to our previous results with MDPV , as these are the first two published studies to establish initial dose-response curves for IVSA of these two synthetic cathinones. In particular, the highest methylone dose tested in the present study (0.5 mg/kg/infusion) resulted in a maximum number of lever presses of approximately 100 after approximately 2 hours of IVSA sessions. In our previous MDPV study, the lowest dose tested (0.05 mg/kg/infusion) resulted in approximately 200 active lever presses after just seven 2-hour IVSA sessions.
While future studies will need to establish full IVSA dose-response curves before direct comparisons can be made between methylone and MDPV, our early results suggest that MDPV is a much more potent enhancer than methylone. On September 8, 2011, the DEA issued a letter of intent to temporarily include 3,4-methylenedioxy-N-methylcathinone (methylone) along with two other synthetic cathinones (4-methyl-N-methylcathinone (mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV)) in accordance with the CSA`s interim planning provisions. 76 FR 55616. As a result, DEA released on the 21st. In October 2011, the Federal Register issued a final order amending 21 CFR 1308.11(g) to temporarily add these three synthetic cathinones to Schedule 21 U.S.C. 811(h) of Schedule I to the CSA, consistent with temporary listing provisions. 76 FR 65371. This final order, effective as of the date of publication, was based on the DEA Administrator`s determination that temporary planning for these three synthetic cathinones was necessary to avoid an imminent threat to public safety as defined in 21 U.S.C.
811(h)(1). At the time of the effective date of the final order, the CSA (21 U.S.C. 811(h)(2) (2011)) required that temporary planning for a substance expire after one year from the date of the provision, and also provided that for the duration of the proceeding under 21 U.S.C. 811(a)(1) With respect to the case, temporary planning for this substance could be extended for up to six months.  According to this provision, the temporary planning for methylone expired on October 20, 2012. Pursuant to 21 U.S.C. 811(h)(2), the DEA administrator ordered an extension through April 20, 2013. 77 FR 64032.
In addition, on October 17, 2012, the DEA issued a Notice of Proposed Rules (NPRM) proposing the permanent addition of methylone to Schedule I of the CSA. 77 FR 63766. This measure complements the planning action proposed in the October 17, 2012 NPRM.