U.S. Department of Justice

Drug Enforcement Administration

Schedule of Controlled Substance: Placement of 3,4-Methylenedioxy-Nmethylcathinone (Methylone) into Schedule I

Background, Data, and Analysis:

Eight Factors Determinative of Control and 

Findings Pursuant to 21 U.S.C. 812(b) 

Prepared by:

Office of Diversion Control, Drug and Chemical Evaluation Section

8701 Morrissette Drive, Springfield, Virginia 22152

October 2012
Page 2 of 36

I. Background

Methylone is a synthetic cathinone (also commonly referred to as substituted cathinones or 

cathinone derivatives) that shares many similarities with the Schedule I substances cathinone,

methcathinone, and 3,4-methylenedioxymethamphetamine (MDMA) and Schedule II stimulants

amphetamine, methamphetamine, and cocaine. Evidence indicates that methylone and other 

synthetic cathinones, like amphetamine, methamphetamine and cocaine, are being abused for 

their psychoactive properties. These synthetic cathinone substances are falsely marketed as 

“research chemicals,” “plant food,” or “bath salts.” They have been 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.

Methylone has no known medical use in the United States but evidence demonstrates that 

methylone is being abused by individuals and has become a serious public health threat. 

Consequently, there have been documented reports of emergency room admissions and deaths 

associated with the abuse of methylone (Boulanger-Gobeil et al., 2012; Pearson et al., 2012; 

Warrick et al., 2012). Methylone has been reported to cause a number of adverse effects that are 

characteristic of sympathomimetic agent such as amphetamine, methamphetamine, and cocaine

(ACMD, 2010; Karila and Reynaud, 2010; Boulanger-Gobeil et al., 2012; Pearson et al., 2012; 

Warrick et al., 2012). Adverse effects associated with the consumption of methylone include 

palpitations, hyperthermia, seizures, hyponatremia, bruxism, sweating, hypertension, 

tachycardia, headache, palpitations, thirst, mydriasis, tremor, fever, sweating, and hypertension 

(ACMD, 2010; Karila and Reynaud, 2010; Boulanger-Gobeil et al., 2012; Pearson et al., 2012;

Warrick et al., 2012). Other effects that have been reported from the use of methylone include 

psychological effects such as confusion, psychosis, paranoia, hallucinations, combativeness, and 

agitation. The possibility of death for individuals abusing methylone also indicates that 

methylone is a serious public health threat (Boulanger-Gobeil et al., 2012; Pearson et al., 2012;

Warrick et al., 2012). 

Evidence from poison centers and law enforcement indicates that the abuse of synthetic 

cathinones like methylone is widespread. According to a press release from the American 

Association of Poison Control Centers (AAPCC),1there were 304 exposure calls related to 

synthetic cathinones in 2010 and 6,138 calls in 2011 (AAPCC, 2012). As of September 10, 

2012, poison centers received 2,251 calls relating to human exposures to bath salts. These calls 

were received in poison centers representing at least 47 states and the District of Columbia. Both 

the National Forensic Laboratory Information System (NFLIS), a Drug Enforcement 

Administration (DEA) sponsored program that systematically collects drug identification results 

 

1 AAPCC is a non-profit, national organization that represents the poison control centers of the United 

States.
Page 3 of 36

and associated information from drug cases analyzed by state, local, and federal forensic 

laboratories, and the System To Retrieve Information from Drug Evidence (STRIDE), a federal 

database for the drug samples analyzed by DEA forensic laboratories, registered encounters of 

methylone (see Factor 1 and Factor 5). In 2009, NFLIS registered 4 reports in state and local law 

enforcement laboratories from 3 states containing methylone.

2 However, in 2010, there were 71

reports from 18 states related to methylone, in 2011 there were 1,655 reports from 41 states, and 

in 2012 there were 1,067 reports from 36 states. From January 2009 to June 2012, 220 drug 

exhibits pertaining to the trafficking, distribution and abuse of methylone were recorded in the 

STRIDE database (which reports data from 6 DEA laboratories).

State public health and poison centers have warned of the dangers associated with the use of 

synthetic cathinones and their associated products being found on the designer drug market. In 

response to the abuse of methylone and other synthetic cathinones, as of September 2012, at least 

42 states have emergency scheduled or enacted legislation placing regulatory controls on some 

or many of the synthetic cathinones including mephedrone, methylone, MDPV and/or a defined 

general class of cathinones. At least 27 states specifically control methylone. Numerous local 

jurisdictions have also placed controls on methylone and other synthetic cathinones. All five 

branches of the U.S. military prohibit military personnel from possessing or using synthetic 

cathinones including methylone.

On October 21, 2011, the Administrator of the Drug Enforcement Administration (DEA) 

published a Final Order in the Federal Register temporarily placing methylone, along with two 

other synthetic cathinones (4-methyl-N-methylcathinone (mephedrone) and 3,4-

methylenedioxypyrovalerone (MDPV)) into Schedule I of the Controlled Substances Act (CSA) 

upon finding that these substances pose an imminent threat to public safety. 76 FR 65371. 

Pursuant to 21 U.S.C. 811(b) and after gathering the necessary data, in a letter dated 

March, 30, 2012, DEA requested from the Department of Health and Human Services (HHS) a 

scientific and medical evaluation and a scheduling recommendation for methylone and two other 

synthetic cathinones (mephedrone and MDPV). On July 9, 2012, President Obama signed the 

Food and Drug Administration Safety and Innovation Act (Pub. L. 112-144) (FDASIA), which 

amended several provisions of the CSA. In particular, the FDASIA amended Schedule I of 

section 202(c) of the CSA to include mephedrone and MDPV, but not methylone. On August

14, 2012, pursuant to 21 U.S.C. 811 (b) and (c), HHS provided DEA with the following 

scientific and medical evaluation and scheduling recommendation: “Basis for the 

Recommendation to Place 3,4-Methylenedioxymethcathinone (Methylone) and its Salts in 

Schedule I of the Controlled Substances Act (CSA).” This evaluation recommended that

methylone be added to Schedule I of the CSA. 

 

2 Analyzed on September 12, 2012, state and local forensic drug reports. The 2012 drug reports are likely 

to be incomplete as of September 12, 2012, due to laboratory reporting lag time
Page 4 of 36

The CSA requires the Administrator of the DEA, as delegated by the Attorney General,3to 

determine whether HHS’s scientific and medical evaluation and all other relevant data constitute 

substantial evidence of potential for abuse such that the substance should be scheduled. 

21 U.S.C. 811(b).

 

3

28 CFR 0.100(b).
Page 5 of 36

II. Eight Factors Determinative of Control

Pursuant to 21 U.S.C. 811(c), DEA must consider eight factors in making any finding of 

substantial evidence of potential for abuse, including the necessary data and law enforcement 

information relevant thereto.

Factor 1: Its Actual or Relative Potential for Abuse

Methylone is a synthetic cathinone (-keto-phenethylamine) of the larger phenethylamine 

structural class (e.g., amphetamines, cathinones, 2C compounds, aminoindanes, etc.). Other 

synthetic cathinones include but are not limited to mephedrone (Schedule I), MDPV (Schedule 

I), 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). Although the abuse potential of methylone in humans has

not been tested, the available data indicate that the pharmacological actions of methylone is

similar to those of Schedule I and II substances such as cathinone (Schedule I), methcathinone

(Schedule I), MDMA (Schedule I), amphetamine (Schedule II), methamphetamine (Schedule II), 

and cocaine (Schedule II) which have a high potential for abuse (see information below and in 

Factor 2). 

a. Legislative History and Determination of Abuse Potential 

The legislative history of the CSA provides four factors to consider in determining whether a 

particular drug or substance has potential for abuse:4

i. There is evidence that individuals are taking the drug or other substance in amounts 

sufficient to create a hazard to their health or to the safety of other individuals or to the 

community; or

ii. There is significant diversion of the drug or substance from legitimate drug channels; or

iii. Individuals are taking the substance on their own initiative rather than on the basis of 

medical advice from a practitioner licensed by law to administer such drugs; or

iv. The drug is a new drug so related in its action to a drug or other substance already listed 

as having a potential for abuse to make it likely that the drug or other substance will have 

the same potential for abuse as such drugs, thus making it reasonable to assume that there 

may be significant diversion from legitimate channels, significant use contrary to or 

without medical advice, or that it has a substantial capability of creating hazards to the 

health of the user or to the safety of the community.

 

4 Comprehensive Drug Abuse Prevention and Control Act of 1970, H.R. Rep. No. 91-1444, 91st Cong., 

Sess. 1 (1970); 1970 U.S.C.C.A.N. 4566, 4601.
Page 6 of 36

i. Individuals are taking methylone in amounts sufficient to create a hazard to their 

health or to the safety of other individuals or to the community.

According to HHS, a number of case reports and case series have shown that individuals take

methylone and products containing methylone in amounts sufficient to induce adverse health

effects similar to those induced Schedule I and II substances such as by amphetamine, 

methamphetamine, cocaine, and MDMA (HHS, 2012). These effects included elevated body 

temperature, increased heart rate, respiratory exchange, and blood pressure, seizures, extreme 

anxiety leading to panic attacks, and the precipitation or exacerbation of psychotic episodes 

(Shimizu et al., 2007; Boulanger-Gobeil et al., 2012; Pearson et al., 2012). Further HHS states 

that several reports from emergency room and medical examiners cases indicate that methylone 

use is associated with deaths (Warrick et al., 2011; Pearson et al., 2012). Further, law 

enforcement encounters suggest the occurrence of a fatal automotive accident caused by a driver 

under the influence of a product containing methylone and there is a reported incident of a

homicide perpetrated by an individual under the influence of methylone (Marinetti et al., 2011; 

Cawrse et al., 2012). 

ii. Significant diversion of methylone from legitimate channels and/or ease with which 

drug can be obtained.

Since October 21, 2011, methylone has been temporarily controlled in Schedule I and has

thus not been legally available unless for research purposes. However, individuals have been 

purchasing methylone from internet vendors, gas stations, convenience stores, and head shops, 

while other reports indicate U.S. military personnel have likewise been purchasing and abusing 

synthetic cathinones. These products are commonly marketed as “legal highs” under a variety of 

product names (e.g., White Dove, Euphoria, Dynamite, Tranquility, Explosion and others) and 

with a disclaimer “not for human consumption.” 

Additionally, large seizures of methylone containing products have occurred by law 

enforcement and the U.S. Customs and Border Protection (CBP) (see Factor 5). The National 

Forensic Laboratory Information System (NFLIS) details over 2,500 reports from state and local 

forensic laboratories identifying methylone in drug related exhibits for a period from June 2008

to June 2012 from 42 states. 

iii. Individuals are taking methylone on their own initiative rather than on the basis of 

medical advice from a practitioner licensed by law to administer such substance. 

According to HHS, there is currently no accepted medical use for methylone and no medical 

practitioner is currently licensed by law to administer methylone (HHS, 2012). Indeed, the U. S. 

Food and Drug Administration (FDA) has not evaluated or approved a new drug application 

(NDA) for methylone for any therapeutic indication, and no investigational new drug (IND) 

application is currently active.
Page 7 of 36

iv. Methylone is so related in their action to a substance already listed as having a potential 

for abuse to make it likely that they will have the same potential for abuse as such 

substance, thus making it reasonable to assume that there may be significant diversions 

from legitimate channels, significant use contrary to or without medical advice, or that 

they have a substantial capability of creating hazards to the health of the user or to the 

safety of the community.

According to HHS, in preclinical studies methylone produces pharmacological effects similar 

to those produced by the Schedule I substance, MDMA and Schedule II stimulants such as 

amphetamine, methamphetamine, and cocaine (HHS, 2012). Likewise, the pharmacological 

profile (as inferred from its toxicological profile observed in emergency room and medical 

examiner cases) of methylone in humans is similar to that from preclinical studies. For example, 

HHS also states that methylone blocks the reuptake of dopamine, serotonin, and norepinephrine 

into nerve terminals and stimulates the release of the same neurotransmitters from nerve 

terminals leading to increase in extracellular levels of the same in nucleus accumbens. Similarly, 

the serotonergic profile of methylone is similar to that of MDMA. In locomotor and drug 

discrimination studies, methylone shares substantial similarities to the Schedule I and II 

stimulants methamphetamine, MDMA, amphetamine, and cocaine.

According to HHS, published studies also report that methylone has pharmacological effects 

similar to amphetamine, methamphetamine, MDMA, and cocaine. In these studies, methylone 

has been demonstrated to increase serotonin release and to inhibit serotonin and dopamine 

reuptake in rat brain synaptosomes and in cells expressing the dopamine transporter (DAT), 

norepinephrine transporter (NET), and the serotonin transporter (SERT) (Cozzi et al., 1999; 

Nagai et al., 2007; Sogawa et al., 2011; National Institute on Drug Abuse (NIDA), 2012; HHS, 

2012). Like methamphetamine and MDMA, methylone elicited the release of dopamine, 

norepinephrine and serotonin from cells expressing the DAT, NET, and SERT (Sogawa et al., 

2011; Nagai et al., 2007). Methylone, similar to MDMA, also increased extracellular serotonin 

and dopamine in rat brain (Baumann et al., 2011). Increased monoamine concentrations in the 

central nervous system (CNS) is thought to be involved in stimulant and hallucinogenic effects 

of the phenethylamine class of drugs (Dal Cason et al., 1997). In drug discrimination assays, 

methylone substituted for MDMA and amphetamine, which suggests that methylone will likely 

produce subjective effects in humans similar to these substances and have a similar pattern of 

abuse (Dal Cason et al., 1997; Balster and Bigelow, 2003). Studies also showed methylone to be 

a weak locomotor stimulant (Baumann et al., 2011; Lopez-Arnau et al., 2012; Miyazawa et al., 

2012; NIDA, 2012). The data from studies conducted by the National Institute on Drug Abuse 

(NIDA) contract researchers are consistent with this (see Table 6 and Factor 2).

In light of the above mentioned similarities between methylone and other Schedule I and II 

substances of abuse, it is reasonable to assume that there will be significant diversion of 

methylone; significant use of methylone contrary to or without medical advice; and that 

methylone has a substantial capability of creating hazards to the user or the safety of the 

community. In fact, the available evidence as presented above and elsewhere in this document 

(see Factors 4, 5 and 6) supports the above statements.
Page 8 of 36

b. Actual or Relative Abuse Potential

i. Animal Studies

Drug Discrimination Studies

The drug discrimination paradigm is used as an animal model of human subjective effects. 

This procedure provides a direct measure of stimulus specificity of a test drug in comparison 

with a known standard drug, or a neutral stimulus (e.g. injection of saline water). In the drug 

discrimination paradigm, if a new drug or substance has discriminative stimulus effects in 

animals similar to a known drug of abuse, it is highly likely that this new drug will produce 

pharmacological effects (including subjective effects) in humans similar to the known drug of 

abuse and would be similarly abused by humans (Balster and Bigelow, 2003; Panlilio and 

Goldberg, 2007). 

At the time of temporary scheduling of methylone, DEA requested that the National Institute 

on Drug Abuse (NIDA) conduct pharmacological studies including drug discrimination studies

on methylone (NIDA, 2011). The data from these studies as well as the data published in the 

scientific literature demonstrate that the discriminative stimulus effects of methylone are similar 

to those of the Schedule I and II substances amphetamine, methamphetamine, cocaine, and 

MDMA (Dal Cason, 2007; NIDA, 2011; HHS, 2012). In contrast, methylone does not substitute 

for 2,5-dimethoxy-4-methylphenethylamine (DOM), a Schedule I hallucinogen (Dal Cason et al., 

1997). The results of these studies are summarized below in Table 1 and can also be found in 

Factor 2. 

Table 1. Summary of Drug Discrimination Studies Involving Methylone

Training Drug (Dose)

Methamphetamine (1 mg/kg) Cocaine (10 mg/kg) MDMA (1.5 mg/kg) DOM (1 mg/kg)

Methylone Full substitution Full substitution Full substitution No substitution

ii. Clinical Studies and Case Reports

According to HHS, methylone has not been evaluated in human abuse liability studies (HHS, 

2012). Furthermore, no studies have been undertaken to evaluate the toxicology and safety of 

methylone in humans.

c. Actual Abuse

Available information demonstrates that methylone, like Schedule I and II substances, is 

being abused for its psychoactive effects. 

Forensic Laboratory Data

The National Forensic Laboratory Information System (NFLIS) is a program sponsored by 

DEA's Office of Diversion Control. NFLIS compiles information on exhibits analyzed in state 
Page 9 of 36

and local law enforcement laboratories. The System to Retrieve Information from Drug 

Evidence (STRIDE) is a DEA database which compiles information on exhibits analyzed in 

DEA laboratories. NFLIS and STRIDE together capture data for all substances reported by 

forensic laboratory analyses. More than 1,700 unique substances are reported to these two 

databases.

Methylone has been encountered by law enforcement as reported in NFLIS.5 NFLIS details 

2,797 reports from state and local forensic laboratories identifying methylone in drug related 

exhibits for a period from January 2009 to June 2012 from 42 States (Table 2 and Table 3). In 

2009, the NFLIS registered 4 reports from 3 states containing methylone. However, in 2010, 

there were 71 reports from 18 states related to methylone registered in NFLIS, in 2011 there 

were 1,655 reports from 41 states, and in 2012 there were 1,067 reports from 36 states. 

Methylone represents approximately 26% (2,797/10,798) of all the reports involving synthetic 

cathinones that have been reported to NFLIS from 2009 to 2012. 

Table 2. Synthetic Cathinones – Number of Exhibits (State and Local)

2009 2010 2011 2012* TOTALS

Methylone 4 71 1,655 1,067 2,797

Mephedrone 9 231 305 25 570

MDPV 2 304 3,143 1,327 4,776

Other Synthetic Cathinones‡12 34 972 1,637 2,655

TOTAL Synthetic Cathinones 27 640 6,075 4,056 10,798

*January – June 2012

NFLIS database was queried on 9/12/2012 for state and local forensic laboratory drug reports.

‡ Other synthetic cathinones include 3,4-dimethylmethcathinone (3,4-dmmc), 3,4-methylenedioxyethylcathinone 

(ethylone), 4'-methoxy-alpha-pyrrolidinopropiophenone (moppp), 4'-methyl-alpha-pyrrolidinopropiophenone (4-

meppp), 4-methyl-n-ethylcathinone (4-mec), alpha-pyrrolidinobutiophenone (alpha-pbp), alphapyrrolidinopentiophenone (-pvp), butylone (ß-keto-n-methylbenzo-dioxylpropylamine), dibutylone, dimethylone, 

ethylcathinone, fluoromethcathinone, mdpbp, mdppp, ethcathinone, ethedrone (4-methoxymethcathinone), 

naphthylpyrovalerone (naphyrone), pentedrone (2-(methylamino)-1-phenylpentan-1-one), pentylone (ß-ketomethylbenzodioxolylpentanamine), pyrovalerone, substituted cathinone (not specifically identified)

Table 3. Number of States where Methylone was Identified (State and Local)

2009 2010 2011 2012* TOTAL STATES

Methylone 3 18 41 36 42

*January – June 2012

NFLIS database was queried on 9/12/2012; State and local forensic laboratory drug reports

STRIDE also details reports from federal forensic laboratories identifying methylone in drug 

related exhibits for a period from January 2009 to June 2012 (Table 4). Data from the forensic 

laboratory database STRIDE, a federal database for the drug samples analyzed by DEA forensic 

 

5 State and local forensic drug reports from January 2009 to June 2012, analyzed on September 12, 2012. 

The 2012 drug reports are likely to be incomplete as of September 12, 2012, due to laboratory reporting 

lag time.
Page 10 of 36

laboratories, indicate illicit activity involving methylone. From 2009 to 2012, Federal law 

enforcement authorities encountered 220 drug exhibits pertaining to the trafficking, distribution 

and abuse of methylone.

Table 4. Methylone Exhibits (Federal)

2009 2010 2011 2012* TOTALS

Methylone 1 7 107 105 220

*January – June 2012

STRIDE database was queried on 9/12/2012 by date submitted to federal forensic laboratories

Concerns over the abuse of methylone and other synthetic cathinones have prompted many 

states to control these substances. As of September 2012, at least 42 states have emergency 

scheduled or enacted legislation placing regulatory controls on some or many of the synthetic 

cathinones including mephedrone, methylone, MDPV and/or a defined general class of 

cathinones. At least 27 states specifically control methylone. These states include Alabama, 

Arizona, Arkansas, Delaware, Florida, Georgia, Rhode Island, Illinois, Indiana, Kansas, 

Kentucky, Louisiana, Maine, Maryland, Minnesota, Mississippi, Nebraska, New Jersey, New 

Mexico, Ohio, Oklahoma, Pennsylvania, Tennessee, Texas, Utah, Virginia, and Wyoming. In 

addition, the U.S. Armed Forces prohibited the use of synthetic cathinones including 

mephedrone, methylone or MDPV. Internationally, several member countries of the European 

Union have enacted laws placing controls on the possession and/or sale of one or more of these 

substances (Winstock et al., 2010; European Monitoring Centre for Drugs and Drug Addiction 

(EMCDDA), 2011).

Table 5. List of States where Methylone was Identified

States with Exhibits from 2009-2012*

Methylone Alabama Arizona Arkansas California Colorado

Connecticut Florida Georgia Hawaii Illinois

Indiana Iowa Kansas Kentucky Louisiana

Maine Maryland Massachusetts Michigan Minnesota

Mississippi Missouri Nebraska Nevada New Hampshire

New Jersey New Mexico New York North Carolina North Dakota

Ohio Oklahoma Pennsylvania South Carolina Tennessee

Texas Utah Virginia Washington West Virginia

Wisconsin Wyoming

*January – June 2012

NFLIS database was queried on 9/12/2012 by submission, state and local forensic laboratory drug reports.

U.S. Customs and Border Protection (CBP)

At selected United States ports of entry, the U.S. Customs and Border Protection (CBP) has 

encountered shipments of products containing methylone. Of all the shipments of synthetic 

cathinones reported to DEA, the most commonly encountered synthetic cathinone was 

methylone. As of July 2012, methylone was identified in 127 of 330 shipments encountered by 

CBP from June 2008 to July 2012. These shipments of methylone were in powdered form 

ranging from 1 gram to multi-kilogram quantities. Other synthetic cathinones encountered by 

CBP were MDPV, mephedrone, 4-MEC, butylone, fluoromethcathinone, and dimethylcathinone. 
Page 11 of 36

Most of the shipments of these synthetic cathinones that contained methylone originated in 

China and were destined for delivery throughout the United States to places like Alaska, 

Arizona, Arkansas, California, Colorado, Florida, Hawaii, Illinois, Kansas, Louisiana, 

Oklahoma, Oregon, Missouri, Nevada, New Mexico, Tennessee, Texas, Washington, and West 

Virginia. 

Other Encounters of Methylone

Methylone has also been identified during the toxicological screening of individual human 

urine samples. Redwood Toxicology Laboratory screened over 2000 urine samples for the 

following 14 designer stimulants: amphetamines [3,4-methylenedioxyamphetamine (MDA), 

MDMA, 3,4-methylenedioxymethamphetamine (MDEA), methylbenzyldioxolylbutanamine 

(MBDB)], cathinones [(methylone, ethylone, butylone, cathinone, methcathinone, MDPV, 

mephedrone)] and designer piperazines [N,N-benzylpiperazine (BZP), 1-(3-

trifluoromethylphenyl)-piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP)] (Rana et 

al., 2011). Six of these 14 designer stimulants were detected in 159 urine specimens of which 

21% (33/159) were methylone either alone or in combination with other substances. The other 

substances detected were MDPV, mephedrone, butylone, TFMPP, and BZP. A similar study that 

screened urine samples (209) from attendees of a methadone maintenance program in the 

Republic of Ireland found that 13.9% (29) of samples were positive for mephedrone and 3.3% 

(7) were positive for methylone (McNamara et al., 2010; EMCDDA, 2011). 

U.S. Drug Courts have communicated concerns related to the abuse of synthetic cathinones

because drug courts have detected methylone in human urine samples during mandatory periodic 

drug screens. Drug courts were developed to achieve a reduction in recidivism and substance 

abuse among nonviolent, substance abusing offenders by increasing their likelihood for 

successful rehabilitation through early, continuous, and intense judicially supervised treatment, 

mandatory periodic drug testing, and the use of appropriate sanctions and other rehabilitation 

services. Drug courts analyze specimens from participants for new and existing drugs of abuse. 

Drug courts submitted to DEA 18 reports from the analysis of biological specimens that

contained synthetic cathinones. Methylone was mentioned in 5 of these reports.

6

 Other 

substances detected included mephedrone, MDPV, butylone, lidocaine, benzocaine, and MDMA. 

It is possible that drug court participants abuse synthetic cathinones because they believe that 

these substances are legal and, thus, they can avoid being charged with violating their parole by 

using synthetic cathinones.

Information from poison centers indicates that the use of synthetic cathinones which likely

include methylone is widespread (see Factor 4). AAPCC reported in a press release that poison

centers took 304 calls in 2010 regarding synthetic cathinones exposures and 6,138 calls in 2011

(AAPCC, 2012). As of September 12, 2012, poison centers received 2,251 calls relating to these 

 

6

Some specimens contain more than one cathinone.
Page 12 of 36

products as of this year. These calls were received in poison centers representing at least 47 

states and the District of Columbia. Although methylone may not be specifically identified 

during exposure calls or identified by toxicology testing by AAPCC, it is likely that some of 

these retail products described by the callers contained methylone, based on the identification of 

methylone in approximately 26% of all synthetic cathinones related exhibits reported to NFLIS 

from January 2009 to June 2012 (Table 2).

Summary

In summary, evidence indicates that methylone has a high potential for abuse. According to 

HHS’s scientific and medical evaluation and scheduling recommendation, methylone is a CNS

stimulant that shares many similarities with the Schedule I stimulants cathinone and 

methcathinone and Schedule II substances, MDMA, amphetamine, methamphetamine, and 

cocaine (HHS, 2012). Methylone has no known medical use in the United States but evidence 

demonstrates that methylone is being abused by individuals for its psychoactive effects. 

Methylone has been encountered by law enforcement throughout the United States as reported in 

NFLIS and in STRIDE databases suggesting that individuals are abusing methylone. Evidence 

of the abuse of methylone is confirmed by drug courts. Drug court reports have identified 

methylone in specimens from drug court participants. Methylone has also been identified during 

the toxicological screening of individual human urine samples which also demonstrates that 

individuals are abusing this substance. In addition, information from poison centers indicates 

that the use of synthetic cathinones which likely include methylone is widespread. In 

conclusion, these encounters of methylone through law enforcement, drug screenings, and poison

center data indicate that methylone is a popular drug of abuse and has a high abuse potential.

Factor 2: Scientific Evidence of its Pharmacological Effects, if Known

HHS states in their recommendation to place methylone in Schedule I of the CSA that based 

on the results of preclinical studies and the toxicological profile observed in emergency room 

cases and medical examiner cases it is probable that methylone produces pharmacological effects 

in humans that are similar to those produced by the Schedule I and II substances, amphetamine, 

methamphetamine, cocaine, and MDMA (HHS, 2012). These studies are described below.

In addition to data from published studies, contract researchers for the National Institute on 

Drug Abuse (NIDA) also provided data on the pharmacological effects of methylone. Studies 

conducted by NIDA included drug discrimination, locomotor activity assays, and in vitro 

receptor binding and functional assays. 

Preclinical In Vivo Studies – Behavioral Effects

The available published scientific studies and studies by NIDA evaluating the behavioral 

effects of synthetic cathinones in animals suggest that methylone produces pharmacological 

effects in animals that are similar to those produced by methamphetamine, cocaine, and MDMA. 

Behavior studies included drug discrimination, conditioned place preference, and locomotor 

activity studies.
Page 13 of 36

The drug discrimination paradigm is an accepted animal model used to predict subjective 

effects of substances in humans (Balster and Bigelow, 2003). In NIDA-sponsored drug 

discrimination studies, methylone fully substituted with ED50 values of 1.47 mg/kg and 2.66 

mg/kg for the Schedule II stimulants, cocaine (ED50 = 2.73 mg/kg) and methamphetamine (ED50

= 0.34 mg/kg), respectively (Table 6). This data is consistent with a published report on 

discriminative stimulus effects of methylone (Dal Cason et al., 1997). Methylone (ED50 = 2.36 

mg/kg) fully substituted for amphetamine (ED50 = 0.33 mg/kg) or MDMA (ED50 = 1.60 mg/kg) 

in rats trained to discriminate amphetamine (training dose = 1 mg/kg) or MDMA (training dose = 

1.5 mg/kg), respectively, from saline. In contrast, methylone did not substitute for the DOM

(training dose = 1 mg/kg), a Schedule I hallucinogen (Dal Cason et al., 1997).

The conditioned place preference (CPP) paradigm is a preclinical behavioral model used to 

study the reinforcing effects (rewarding or aversive) of drugs (Stolerman, 1992; Prus et al., 

2009). CPP tests are able to detect addictive substances. Psychostimulants, such as 

amphetamine and cocaine, often produce a robust CPP. In the conditioned place preference test, 

mice treated with of methylone (intraperitoneal doses of 2.5 and 5.0 mg/kg) developed CPP

confirming that methylone, like methamphetamine, has a rewarding effect (Miyazawa et al. 

2011). 

Stimulant effects can be quantified using locomotor activity studies. Stimulants like 

amphetamine and methamphetamine enhance physical performance. Several studies show that 

methylone, like methamphetamine and cocaine, is a CNS stimulant (Baumann et al., 2011; 

Lopez-Arnau et al., 2012; Miyazawa et al., 2012; NIDA, 2012). In NIDA-sponsored locomotor 

activity studies, treatment with the compound methylone resulted in time- and dose-dependent 

stimulation of locomotor activity in doses from 3 to 30 mg/kg (Table 6). Stimulant effects of 3 

and 10 mg/kg occurred within 10 minutes following injection and lasted 60 to 120 minutes. 

Based on the 30-minute time period in which maximal stimulant effects occurred (0 to 30 

minutes following injection), an ED50 of 1.5 mg/kg was calculated. The maximal stimulant effect 

of methylone was 87% of the maximal stimulant effect of methamphetamine and 82% that of 

cocaine. In comparison, treatment with methamphetamine resulted in time- and dose-dependent 

stimulation of locomotor activity following 0.5 to 4 mg/kg with stimulant effects occurring 

within 10 minutes following injection and lasting 130 to 310 minutes. The ED50 of 

methamphetamine was estimated at 0.48 mg/kg. Treatment with cocaine resulted in time- and 

dose dependent stimulation of locomotor activity following 10 to 40 mg/kg with stimulant 

effects of 10 and 20 mg/kg occurring within 10 minutes following injection and lasting 120 to 

170 minutes. The ED50 of cocaine was estimated at 7.2 mg/kg.
Page 14 of 36

Table 6. Summary of In Vivo NIDA Studies Regarding Methylone in Rodents

In Vivo Study

Locomotor Activity 8-hr test

Effect & ED50

Duration of Action (DOA)

% stimulation

Drug Discrimination 

Cocaine

(TD = 10 mg/kg)

Effect & ED50

Drug Discrimination 

Methamphetamine 

(TD = 1 mg/kg) 

Effect & ED50

Methylone Stimulant

ED50 =1.5 mg/kg

DOA = 120 min

87% methamphetamine stimulation

82% cocaine stimulation

Full substitution

ED50= 1.47 mg/kg

Full substitution

ED50= 2.66 mg/kg

Methamphetamine Stimulant

ED50 = 0.48 mg/kg

DOA = 310 min

Full substitution

ED50= 0.34 mg/kg

Cocaine Stimulant

ED50 = 7.2 mg/kg

DOA = 170 min

Full substitution

ED50= 2.73 mg/kg

ED50 for locomotor activity studies is the median effective dose that produces 50% maximum locomotor activity

ED50 for drug discrimination studies is the dose at which the subjects would be expected to make 50% of their 

responses on the drug-appropriate lever

TD is the training dose used for the drug discrimination study

Results from several published studies are consistent with those from the NIDA-sponsored 

study regarding stimulant activity. In mice that have been given methylone by oral 

administration, methylone (5 - 100 mg/kg), like MDMA and methamphetamine, significantly 

increased locomotor activity (Miyazawa et al., 2012). The maximum increase in locomotor

activity for methylone occurred at 50 mg/kg. In comparing the effects of these three substances 

administered to mice at a equivalent dose of 0.205 mmol/kg (which is equivalent to 50 mg/kg 

methylone) on locomotor activity, methylone increased locomotor activity more than 

methamphetamine or MDMA. 

Intravenous (IV) administration of methylone, like MDMA and methamphetamine, is a 

psychomotor stimulant (Baumann et al., 2011). The effects of methylone in stimulating 

locomotor activity is similar to that of MDMA but weaker (i.e., less potent) than that of 

methamphetamine. IV administration (IV) of methylone (1.0 mg/kg) also produced an increase 

in locomotor activity that was 5- fold above baseline. Similarly, MDMA (IV, 1.0 mg/kg) 

increased in locomotor motor activity 5- fold above baseline. In contrast, methamphetamine (IV, 

1.0 mg/kg) increased locomotor motor activity 30- fold above baseline. In addition, methylone 

at 100 mg/kg increased body temperature and respiratory rate and produced salivation and 

piloerections.

DEA notes that in a similar study investigating the effects of methylone and other synthetic 

cathinones on locomotor activity, subcutaneous administration of methylone (5 – 25 mg/kg), like 

MDMA (5 mg/kg), dose-dependently increased locomotor activity in mice (Lopez-Arnau et al., 

2012). 
Page 15 of 36

Preclinical In Vitro Studies - Receptor Binding Profile

Contract researchers for NIDA investigated the affinity and functional effects of methylone 

at serotonin and dopamine receptors using radioligand binding and functional assays (Table 7).

DEA notes that in radioligand binding and functional assays done by NIDA, methylone has 

very low affinity for the serotonin (5HT)1A, 5HT2A and 5HT2C receptors. Methylone has very 

low affinity (63,280 nM) for the 5HT1A receptor and is a partial agonist with very low potency 

(143,000 nM). Methylone has very low affinity (48,500 nM) for the 5HT2A receptor and is an 

antagonist with very low potency (159,000 nM). Methylone has very low affinity (11,770 nM) 

for the 5HT2C receptor and is a weak antagonist with very low potency (>1 mM). Methylone has 

very low to no measurable affinity (>10,000 nM) for the dopamine D1, D2, D3 and D4.4 receptors.

Table 7. Affinity of Methylone to Serotonin and Dopamine Receptors and Function in Transfected Clonal Cells

Methylone 5HT1A 5HT2A 5HT2C D1 D2 D3 D4.4

Ki

 63,280 nM 48,500 nM 11,770 nM >10 M >10 M >10 M >10 M 

EC50

Maximal Stimulation

143,000 nM 

47%

 >1 mM 

 <3%

>1 mM 

<1%

IC50

Maximal Inhibition

159,000 nM 

 84.7%

>1 mM 

28%

Radioligands were [

3H]8-OH-DPAT for serotonin (5HT)1A, [125I]DOI for 5HT2A and 5HT2C, [3H]SCH23390 for 

dopamine (D)1, [3H]YM-09151-2 for D2, D3, and D4.4

EC50 is the drug concentration giving half-maximal acceleration/ stimulation of [35S]GTPS binding for 5HT1A

receptors and inositol-1-phosphate (IP) production for 5HT2A and 5HT2C receptors in HEK cells

IC50 is the drug concentration giving half-maximal inhibition on IP formation in HEK cells 

Preclinical In Vitro Studies – Binding and Functional Activity at Biogenic Amine Transporters

The available published scientific studies and studies by NIDA evaluating the 

pharmacological activity of synthetic cathinones on animals suggest that methylone, like 

Schedule I and II substances, affects monoamine neurotransmission. Studies conducted by NIDA 

contract researchers show that methylone has low affinity for the dopamine (DAT), serotonin 

(SERT), and norepinephrine (NET) transporters, however, it is a substrate for these sites based 

on inhibition of uptake and release studies (Table 8). 

DEA notes that in functional assays with transporter cell lines (human embryonic kidney 

(HEK) cells expressing the cDNA for the human dopamine, serotonin, or norepinephrine 

transporter), methylone is an uptake blocker with low potency at the DAT and NET. Methylone 

is an uptake blocker with very low potency at the SERT and no measurable effect at the vesicular 

monoamine transporter 2 (VMAT2). The rank order of potency for inhibition of uptake for 

methylone was NET=DAT>SERT whereas the rank order for cocaine is NET= SERT= DAT. 

DEA also notes that in functional assays with transporter cell lines (HEK cells expressing the 

cDNA for the human dopamine, serotonin, or norepinephrine transporter), methylone causes 

release of neurotransmitters via the transporters. Methylone has partial efficacy and very low 

potency at releasing neurotransmitter via the DAT. Methylone has substantial efficacy and very 

low potency at releasing neurotransmitter via the SERT. Methylone has very high efficacy and 
Page 16 of 36

low potency at releasing neurotransmitter via the NET. Methylone has low efficacy at releasing 

neurotransmitter via the VMAT2. The rank order for release by methylone was 

NET>SERT=DAT. The rank order for release by methamphetamine is NET=SERT>DAT.

Table 8. Effect of Methylone on Human Monoamine Transporters in Transfected HEK cells

Transporter Binding - Ki Uptake Inhibition - IC50 Release - EC50, Maximal Stimulation

Methylone Serotonin 95,500 nM 1,920 nM 6,700 nM, 78%

Dopamine 5,020 nM 343 nM 11,800 nM, 41%

Norephinephrine 16,500 nM 234 nM 444 nM, 152%

Vesicular >10 M >100 M (5HT) >100 M, 22% (NE)

Cocaine Serotonin 234 nM 257 nM

Dopamine 552 nM 370 nM

Norephinephrine 1,380 nM 218 nM

Methamphetamine Serotonin 22,450 nM, 97.6%

Dopamine 400 nM, 101.9%

Norephinephrine 128 nM, 92.7%

Vesicular 867,000 nM 4,720 nM (5HT) 147,000 nM, 96% (NE)

Ki values are binding affinity values; Radioligand was [

125I]RTI-55

IC50 value is the drug concentration giving half-maximal inhibition

EC50 value is the drug concentration giving half-maximal acceleration/ stimulation

5HT is serotonin; NE is norepinephrine

The above-mentioned data from the studies performed by the NIDA contract researchers are 

consistent with the several published reports on the effects of methylone of inhibition of uptake 

and release of neurotransmitters. These studies are described below.

DEA notes that in rat brain synaptosomes, methylone inhibited the uptake of dopamine (IC50

= 0.56 M), serotonin (IC50 = 0.23 M), and norepinephrine (IC50 = 0.53 M) (Lopez-Arnau et 

al., 2012). 

In rat brain synaptosomes, methylone inhibited the uptake of dopamine (IC50 = 2.9 M), 

serotonin (IC50 = 2.3 M), and norepinephrine (IC50 = 0.74 M) (Nagai et al., 2007). In 

comparison, MDMA, cocaine, and methamphetamine also inhibited the uptakes of these 

neurotransmitters in rat brain synaptosomes. The IC50 values for these Schedule I and II 

substances for the inhibition of dopamine, serotonin, and norepinephrine were 1.4 M, .072 M, 

and 0.66 M for MDMA, 0.85 M, 2.1 M, and 0.34 M for cocaine, and 0.37M, 4.0 M, and 

0.20 M for methamphetamine, respectively.

Methylone, like methamphetamine, methcathinone and MDMA, potently inhibits 

monoamine transporters (Cozzi et al., 2008, 2009). In human platelet cells that naturally express 

the SERT, methylone (IC50 = 5.75 mM) was half as potent as methamphetamine (IC50 = 11.6 

M), six-fold more potent than methcathinone (IC50 = 34.6 M), and 2.7- fold less potent than 

MDMA (IC50 = 2.14 M) in inhibiting platelet serotonin accumulation. Methylone also 

inhibited the uptake of dopamine (IC50 = 0.819 M) and noradrenaline (i.e., norepinephreine)

(IC50 = 1.22 M) in C6 glial cells that express the rat DAT or the human NET, respectively.

Methylone, like methamphetamine, dose-dependently inhibited the uptake of dopamine (IC50

= 2.84 M), serotonin (IC50 = 8.42 M), and norepinephrine (IC50 = 0.48 M) in Chinese 

hamster ovary (CHO) cells expressing the rat DAT, SERT, or NET. Like methamphetamine, 
Page 17 of 36

methylone was more potent at inhibiting the uptake of dopamine than serotonin (Sogawa et al., 

2011). 

In addition to inhibiting the uptake of neurotransmitters, methylone, like methamphetamine

and MDMA, has monoamine releasing activity (Nagai et al., 2007; Baumann et al., 2011; 

Sogawa et al., 2011). 

Methylone stimulated the release of dopamine (EC50 = 0.38 M), serotonin (EC50 = 0.22 

M), and norepinephrine (EC50 = 93 nM) in rat brain synaptosomes (Nagai et al., 2007). 

MDMA and methamphetamine were potent releasers of these neurotransmitters. The EC50

values for the release of dopamine, serotonin, and norepinephrine were 0.20 M, 58 nM, and 86 

nM for MDMA and 28 nM, 0.79 M, and 11 nM for methamphetamine, respectively. In 

contrast, cocaine did not stimulate the release of these neurotransmitters. MDMA was more 

potent in releasing serotonin than dopamine, and methamphetamine was more potent in releasing 

dopamine than serotonin. However, methylone was nearly equipotent at releasing these two 

neurotransmitters (i.e., dopamine and serotonin).

DEA notes that methylone, like MDMA and methamphetamine, stimulated the release of 

radiolabeled substrates by the dopamine transporter (EC50 = 133 nM), serotonin transporter

(EC50 = 242 nM), and norepiniephrine transporter (EC50 = 152 nM) in rat brain synaptosomes in 

an equipotent manner (Baumann et al., 2011). The profile of neurotransmitter release by 

methylone resembled that of MDMA (dopamine transporter, EC50 = 51 nM; serotonin 

transporter, EC50 = 50 nM; and norepinephrine transporter, EC50 = 50 nM) than that of 

methamphetamine (norepinephrine transporter, EC50 = 8.5 nM; serotonin transporter, EC50 = 

1291 nM; and NET, EC50 = 14 nM) which was most potent at stimulating release at the 

norepinephrine and dopamine transporter.

DEA notes that methylone, like methamphetamine, induced the release of dopamine, 

serotonin, and norepinephrine from CHO cells expressing the rat DAT, SERT, or NET (Sogawa 

et al., 2011). 

Preclinical In Vivo Studies – Functional Activity at Biogenic Amine Transporters

In laboratory studies using microdialysis technique, intravenous administration of methylone 

(0.3 and 1.0 mg/kg), like MDMA and methamphetamine, increased extracellular concentrations 

of dopamine and serotonin in rat brain (nucleus accumbens) (Baumann et al., 2011). In these 

studies, the effects of methylone resembled those of MDMA such that methylone, although less 

potent than MDMA (0.3 and 1.0 mg/kg), had a greater effect on extracellular serotonin 

concentration than dopamine concentration. In contrast, methamphetamine (0.3 and 1.0 mg/kg) 

preferentially increased extracellular dopamine rather than serotonin.

Preclinical In Vitro Studies – Cytotoxicity

Studies show that methylone, like MDMA, can be cytotoxic to liver cells (Nakagawa et al., 

2009; Sogawa et al., 2011). Incubation of hepatocytes (liver cells) with methylone or MDMA 

caused cell death (Nakagawa et al., 2009). In addition, high concentrations of methylone 
Page 18 of 36

induced the release of lactate dehydrogenase (LDH), an indication of decreased cell viability, in 

cells that stably expressed the SERT (Sogawa et al., 2011). However, methylone in combination 

with methamphetamine had a synergistic cytotoxic effect on CHO cells that expressed the DAT, 

NET, or SERT. These data suggest that using methylone alone and in combination with other 

psychoactive substances may cause damage to liver cells. 

Summary

The above mentioned data indicate that methylone produces pharmacological effects that are 

similar to those produced by Schedule I and II substances methamphetamine, cocaine, and 

MDMA. Methylone, like methamphetamine, amphetamine, and cocaine is a CNS stimulant and

produces locomotor stimulant effects in mice. (Baumann et al., 2011; Lopez-Arnau et al., 2012; 

Miyazawa et al., 2012; NIDA, 2012). Methylone substitutes for MDMA, cocaine, or

amphetamine in rats trained to discriminate MDMA, cocaine, or amphetamine from saline, 

respectively (Dal Cason et al., 1997; NIDA, 2011). Methylone, like methamphetamine, 

produced rewarding effect as studied in CPP tests (Miyazawa et al. 2011). Methylone is an 

inhibitor of dopamine, serotonin and norepinephrine uptake and also causes the release of these 

neurotransmitters in the CNS (Nagai et al., 2007; Cozzi et al., 2009; Sogawa et al., 2011; 

Baumann et al., 2011; Lopez-Arnau et al., 2012). Furthermore, studies show that methylone, 

like MDMA, can be cytotoxic to liver cells (Sogawa et al., 2011). Based on the results of

preclinical studies, HHS postulates that in humans, methylone is likely to produce 

pharmacological effects similar to those produced by amphetamine, methamphetamine, cocaine, 

and MDMA.

Factor 3: The State of Current Scientific Knowledge Regarding the Drug or Other 

Substance

HHS also considered the state of current scientific knowledge regarding methylone (HHS, 

2012). A summary of HHS’s findings is provided below.

Chemical Structure

Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone (-ketophenethylamines) of the larger phenethylamine structural class (e.g., amphetamines, cathinones,

2C compounds, aminoindanes). Methylone shares the core phenethylamine structure with 

substitutions at the -position, -position on the phenyl ring, and nitrogen atom (Figure 1). The 

addition of a beta-keto (β-ketone) substituent to the phenethylamine core structure produces a 

group of substances with a -keto-phenethylamine core structure. Methylone incorporates a keto 

functional group [carbonyl, (C=O)] at the -position on the ethylamine side chain and the

nitrogen atom is substituted with an alkyl group, methyl. The -position is also substituted with 

an alkyl group (methyl) giving two stereoisomeric forms for methylone (racemic mixtures). The 

phenyl ring is substituted with a methylenedioxy moiety.
Page 19 of 36

Figure 1. Chemical Structures for General Phenethylamines, -Keto phenethylamine, and Methylone

1

2

3

4

5

NH2

6





general phenethylamine structure

with positional designations

 

O

NH2

-keto phenethylamine

 

O

O

O

H

N

CH3

CH3

methylone

3,4-methylendioxy-N -methylcathinone

 

Chemistry and Physical Properties

Table 9. The Chemical and Physical Properties for Methylone

Substance Methylone

CAS # 186028-79-5; 191916-41-3 (+); 186028-80-8 (hydrochloride)

Systematic name: 

IUPAC, CAS, etc.

1-(benzo[d][1,3]dioxol-5-yl)-2-(methylamino)propan-1-one

Common Name bk-MDMA; 3,4-methylenedioxy-N-methylcathinone

Molecular Formula C11H13NO3

Exact Mass 207.09

Melting point 226-228oC (free base ?; Dal Cason, 1997); 244 + 3

oC (hydrochloride salt; Lipomed); 

213-216oC (TRC CoA)

Appearance Off-white solid, crystalline solid (hydrochloride)

Synthesis

Methylone may be prepared by general procedures as detailed in the scientific and patent 

literature (Collins, 2011). The scientific literature suggests that methylone was first synthesized 

in 1994. This substance can be prepared from its corresponding ketone by a two-step synthesis. 

To date, clandestine synthetic operations have not been encountered pertaining to this substance,

but the procedures for the clandestine synthesis of methylone could be easily adapted from 

established procedures.

Metabolism and Pharmacokinetics

Metabolism studies have been conducted for methylone (Kamata et al., 2006; Katagi et al., 

2010; Meyer and Maurer, 2010; Meyer et al., 2010). In general, humans metabolize synthetic 

cathinones to their corresponding amphetamines followed by reduction of the beta-keto group to 

the corresponding alcohol (Meyer and Maurer, 2010). Specifically, methylone is demethylated 

and subsequently O-methylated as well as N-dealkylated to produce the metabolites 3,4-

methylenedioxycathinone (MDC), 4-hydroxy-3-methoxymethcathinone (HMMC) and 3-

hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MeO-MC) (Meyer and Maurer, 2010; Kamata 

et al., 2006; Katagi et al., 2010). These metabolites, MDC, HMMC, and 3-OH-4-MeO-MC have 

been found in the urine sample of humans who consumed methylone and rats administered 

methylone via intraperitoneal injection (Kamata et al., 2006; Katagi et al., 2010). Analytical 
Page 20 of 36

methods for the better detection of these substances in biological specimens continue to be 

developed by laboratories (Katagi et al., 2010; Meyer et al., 2010). 

Medical Application

Research in anti-depressant and anti-parkinson agents resulted in the synthesis and patenting 

of methylone in 1996 (Jacob and Shulgin, 1996). However, there is no evidence that methylone 

has a legitimate non-research use and according to HHS there are no approved human drug 

products, NDAs, or INDs that contain methylone (HHS, 2012). DEA is not aware of any 

currently accepted medical use for methylone. In addition, HHS states that there are no studies 

published in the scientific and medical literature indicating clinical use of methylone. In a letter 

dated June 15, 2011, the Administrator of the DEA notified the Assistant Secretary for Health, 

Department for Health and Human Services about the agency’s intention to temporarily place 

three synthetic cathinones, mephedrone, methylone, and MDPV, in Schedule I and solicited

comments, including whether there is an exemption or approval in effect for the substances in 

question under the Federal Food, Drug and Cosmetic Act. In a letter dated July 25, 2011, the 

Assistant Secretary for Health responded to this request and informed DEA that there were no 

current INDs or approved NDAs for these synthetic cathinones.

A drug has a “currently accepted medical use” if all of the following five elements have been 

satisfied: the drug’s chemistry is known and reproducible; and there are adequate safety studies; 

and there are adequate and well-controlled studies proving efficacy; and the drug is accepted by 

qualified experts; and the scientific evidence is widely available. 57 FR 10499. According to 

HHS, methylone has not been evaluated in human abuse liability studies (HHS, 2012). 

Furthermore, no studies have been undertaken to evaluate the toxicology and safety of methylone

in humans. DEA notes that although the chemistry of methylone is known and has been 

reproduced, there are no controlled studies proving efficacy or safety studies. Thus, methylone 

has no currently accepted medical use and there is a lack of accepted safety for use of methylone

under medical supervision.

Summary

Methylone is a β-ketophenethylamines (i.e., synthetic cathinone) that is structurally and 

pharmacologically similar to amphetamine, MDMA, cathinone and other related substances. 

Research in anti-depressant and anti-parkinson agents resulted in the synthesis and patenting of 

methylone. However, according to HHS, there are no known therapeutic applications for 

methylone, there are no approved drug products containing methylone in the United States, and 

there are no current INDs or approved NDAs for methylone. Thus, there is a lack of accepted 

safety for use of this substance under medical supervision. 

Factor 4: Its History and Current Pattern of Abuse

Methylone is a synthetic cathinone that emerged on the United States’ illicit drug market in 

2009 and prior to its temporary control was promoted as being a ‘legal’ alternative to cocaine, 

methamphetamine, and MDMA. Methylone and other synthetic cathinones are falsely marketed 

as “research chemicals,” “plant food,” or “bath salts.” Products containing methylone have been
Page 21 of 36

sold at smoke shops, head shops, convenience stores, adult book stores, and gas stations and can 

also be purchased on the Internet. It is commonly encountered in the form of powders, capsules, 

and tablets. The packages of these retail products usually contain the warning “not for human 

consumption,” most likely in an effort to circumvent statutory restrictions for methylone and 

other synthetic cathinones. Some products found to contain methylone include, but are not 

limited to: Explosion, Tranquility, Pure, White Dove, Euphoria, Dynamite, and others.

An independent analysis (queried March 2012) of AAPCC data that was procured by DEA 

revealed the following information regarding synthetic cathinones which likely includes

methylone. Methylone may not be specifically identified during exposure calls as the caller may 

be unaware of the actual ingredients in the retail product. In addition, AAPCC does not verify 

the identification of the product or its ingredients that have been indicated by the caller to have 

been consumed. However, despite these uncertainties it is likely that some of these retail 

products contain methylone based on the identification of methylone in products obtained from 

seizures by law enforcement. 

Figure 2. 

Source: The American Association of Poison Control Centers (AAPCC) National Poison Data System.

The following AAPCC data is nominally different than what was reported in the AAPCC’s 

Bath Salts Data press release (see Factor 5) because DEA receives quarterly updates from 

AAPCC and cases may change as they are closed or additional information is received. 

According to these data, in 2010 (July – December), the poison centers received 304 exposure 

calls regarding synthetic cathinones and in 2011 (January – December) they received 6,137 

3 14 20 20 64

183

301

489

639601

719 745

680

600

511

401

231220

0

100

200

300

400

500

600

700

800

Jul

'10

Aug

'10

Sep

'10

Oct

'10

Nov

'10

Dec

'10

Jan

'11

Feb

'11

Mar

'11

Apr

'11

May

'11

Jun

'11

Jul

'11

Aug

'11

Sep

'11

Oct

'11

Nov

'11

Dec

'11

Number of Exposure Calls

Month/Year

Number of Synthetic Cathinone ("Bath Salts") Exposure 

Calls 

to U.S. Poison Centers 

July 2010 - December 2011
Page 22 of 36

synthetic cathinone exposure calls (Figure 2). Exposure calls refer to actual or potential human 

exposure to a synthetic cathinone (e.g., inhalation, ingestion, topical exposure). The calls 

represented exposed individuals from all 50 states, the District of Columbia, and a category 

identified as “overseas/US military/diplomatic.” 

Most of the synthetic cathinones reported by the poison centers were identified as “bath 

salts.” A large majority (91.9%) of the exposures were by intentional abuse, misuse, or 

suspected suicide. The most common known forms of the synthetic cathinones were identified 

as powder/granules and tablets/capsules/caplets. Most of the exposures (70.7%) were described 

as acute.

7

 Exposures described as acute-on-chronic8or chronic9accounted for 8.4% and 10.6% 

of the cases, respectively. Another 10.3% of the exposures were of unknown chronicity. Males 

accounted for 70% of all exposures from July 2010 to December 2011. In every age group, more 

males than females were exposed to synthetic cathinones. Most of the exposed individuals were 

aged 18-25 years (34.1%) and 26-35 years (28.3%). A few of the callers (1.2%) identified the 

exposed individuals as being in their 20s. Also, 18.7% of the persons were 36-50 years of age. 

AAPCC data also identified the most common route of administration for the synthetic 

cathinones as inhalation/nasal.

Information from published scientific studies indicate that the most common routes of 

administration for methylone is ingestion by swallowing capsules or tablets or nasal insufflation 

by snorting the powder (ACMD, 2010; Boulanger-Gobeil et al., 2012; Prosser and Nelson, 

2012). Other methods of intake for synthetic cathinones included rectal administration, ingestion 

by “bombing” (wrapping a dose of powder in a paper wrap and swallowing) and intramuscular 

injection (Karila and Reynaud, 2010; Kelly, 2011). 

In agreement with the findings of AAPCC data, information from the scientific literature and 

law enforcement suggest that the main users of methylone (or synthetic cathinones) are young 

adults (Shimizu et al., 2007; Boulanger-Gobeil et al., 2012; Cawrse et al., 2012; Kovacs et al., 

2012; Pearson et al., 2012). These substances are popular with youths with males appearing to 

abuse methylone more than females. Data also suggest that these substances are used by other 

population groups such as mid-to-late adolescents and older adults (Marinetti et al., 2011; 

Cawrse et al., 2012).

 

7 The AAPCC describes an acute chronicity as a single, repeated or continuous exposure occurring over a 

period of eight hours or less.

8 Acute-on-chronic is a single exposure that was preceded by a continuous, repeated, or intermittent 

exposure occurring over a period exceeding eight hours.

9 Chronic is a continuous, repeated, or intermittent exposure to the same substance lasting longer than 

eight hours.
Page 23 of 36

Users report that the effects of synthetic cathinones occur a few minutes to 15 minutes after 

administration, depending on the synthetic cathinone and the route of administration, and the 

effects can last up to three hours (ACMD, 2010; Karila and Reynaud, 2010; Kelly, 2011;).

Poison center data also indicate that the clinical effects of synthetic cathinones most commonly 

last 8 to 24 hours (23.0%) followed by a duration of 2 to 8 hours (15.7%) and 24 hours to 3 days 

(15.5%). 

Like Schedule I stimulants, methylone has been reported to cause stimulant related 

psychological and somatic effects such as headache, nausea, palpitation, increased sex drive, and 

excessive sweating, hypertension, hyperthermia, and tachycardia (Shimizu et al., 2007; 

Boulanger-Gobeil et al., 2012; Kovacs et al., 2012; Pearson et al., 2012). Other adverse effects 

reported by users include bruxism (teeth grinding), paranoia, suppressed appetite, insomnia, 

hallucinations, addiction/dependence, nausea/vomiting, agitation, and confusion.

The reported average amount of use of methylone ranged widely (from approximately 100 to 

250 milligrams) depending on the substance, duration of intake, and route of administration

(Shimizu et al., 2007; Karila and Reynaud, 2010; Kelly, 2011). The typical oral dose reported 

for methylone ranged from 100 to 250 mg (Kelly, 2010). 

There is evidence that methylone may be co-ingested with other substance. Substances 

reported to have been used in combination with methylone is: other synthetic cathinones (e.g., 

mephedrone, ethcathinone, butylone and MDPV.), pharmaceutical agents (e.g., lidocaine, 

caffeine, oxymorphone, clonazepam, and dextromethorphan), or other recreational substances 

(e.g., amphetamine, methamphetamine, cocaine, barbiturates, phencyclidine, cannabinoids, 5-

MeO-MIPT, 4-OH-DIPT) (Shimizu et al., 2007; ACMD, 2010; Katagi et al., 2010; DEA, 

2011a,b ; Marinetti et al., 2011; Boulanger-Gobeil et al., 2012; Cawrse et al., 2012; Kovac et al., 

2012; Pearson et al., 2012; Warrick et al., 2012). Multiple drug use is confirmed by investigative 

toxicology reports from drugs screens of drug abusers. Additionally, forensic analysis of seized 

and purchased synthetic cathinone products revealed that some products contained multiple

substances. This finding also confirms that co-ingestions are likely.

Summary

Methylone is a synthetic cathinone that emerged on the United States’ illicit drug market in 

2009 and prior to its temporary control was promoted as being a ‘legal’ alternative to cocaine, 

methamphetamine, and MDMA. Methylone is falsely marketed as “research chemicals,” “plant 

food,” or “bath salts” and has been sold at smoke shops, head shops, convenience stores, adult 

book stores, and gas stations and can also be purchased on the Internet under a variety of product 

names (White Dove, Explosion, Tranquility etc.). It is commonly encountered in the form of 

powders, capsules, and tablets. The packages of these commercial products usually contain the 

warning “not for human consumption”. AAPCC reported a large number of toxic exposures to 

these products. A large majority of these exposures were by intentional abuse, misuse, or 

suspected suicide. Most of these exposures were described as acute. AAPCC data also 

identified the most common route of administration for the synthetic cathinones as 

inhalation/nasal. Information from published scientific studies indicate that the most common 

routes of administration for methylone is ingestion by swallowing capsules or tablets or nasal 
Page 24 of 36

insufflation by snorting the powder. Evidence from poison centers, published case reports, and 

law enforcement encounters suggest that the main users of methylone are young adults (Shimizu 

et al., 2007; Boulanger-Gobeil et al., 2011; Cawrse et al., 2012; Kovac et al., 2012; Pearson et 

al., 2012). These substances are popular among youths and young adults with males appearing 

to abuse methylone more than females. There is evidence that methylone may be co-ingested 

with other substances including other synthetic cathinones, pharmaceutical agents, or other 

recreational substances.

Factor 5: The Scope, Duration, and Significance of Abuse

The popularity of methylone and other synthetic cathinones as recreational drugs has 

increased since they first appeared on the United States’ illicit drug market in 2009. These 

substances are increasingly prevalent and abused throughout the United States. Possible reasons 

for the increased abuse (besides eliciting MDMA and amphetamine-like effects) of methylone

and other synthetic cathinones may be attributed to their ease of availability, price, and legal 

status. Based on findings in the European designer drug market, an additional explanation that

has been provided is that some cathinones are being sold as ecstasy/MDMA (Griffiths et al., 

2010). Griffiths and colleagues (2010) further stated that cathinones are growing in importance 

as ‘legal’ alternatives and end-users are seeking out specific substances due to a growing 

awareness. Methylone is readily available from the Internet, retail suppliers (e.g., head shops, 

tobacco shops, convenience stores, adult book stores, and gas stations) or street dealers. These 

substances can also be bought in bulk quantities (e.g., 100 g to over 5 kg) as indicated by 

seizures of these substances by law enforcement. Companies located in China are primarily 

responsible for the trafficking of these substances from overseas. The perceived noncontrolled 

status of synthetic cathinones, in general, may give synthetic cathinones an added appeal 

(Measham et al., 2010). 

Evidence of the abuse of methylone is confirmed by drug courts. Drug court reports have 

identified methylone and other synthetic cathinones (e.g., mephedrone, MDPV, and butylone) in 

urine specimens submitted for testing by drug court participants confirming the abuse of these 

substances by supposedly former recovering drug abusers. Drug courts analyze specimens from 

participants for new and existing drugs of abuse. Drug courts submitted to DEA 18 reports from 

the analysis of biological specimens that contained synthetic cathinones. Methylone was 

mentioned in 5 of these reports.

Studies suggest that methylone or other synthetic cathinones may be used as an alternative to 

illicit substances with stimulant effects (ACMD, 2010). ACMD reported that mephedrone and 

“Toot” (most commonly identified as a mixture of butylone and methylone) were popular among 

users of heroin (ACMD, 2010). 

Evidence from law enforcement indicates that the abuse of methylone is widespread. In 

2009, the National Forensic Laboratory Information System (NFLIS), a DEA sponsored database 
Page 25 of 36

for exhibits analyzed by state and local forensic laboratories, registered 4 reports from 3 states 

containing of methylone (Table 2 and Table 3 in Factor 1).

10 However, in 2010, there were 71

reports from 18 states related to methylone registered in NFLIS, and in 2011 there were 1,655

reports from 41 states. From January to June 2012 there were 1,067 reports from 36 states

related to methylone. According to the System to Retrieve Information from Drug Evidence 

(STRIDE) (which reports data from 6 DEA laboratories), a federal database for drug items 

analyzed by DEA forensic laboratories, law enforcement authorities encountered a number of 

drug exhibits and filed a number of cases pertaining to the trafficking, distribution and abuse of 

methylone (Table 4 in Factor 1). The forms of exhibits encountered were mainly as powders, 

crystals, resins, tablets, or capsules. In 2009, STRIDE registered 1 exhibit pertaining to 

methylone. In 2010, there were 7 exhibits pertaining to the trafficking, distribution and abuse of 

methylone. In 2011, 107 drug exhibits pertaining to the trafficking, distribution and abuse of 

methylone were recorded in the STRIDE database and in 2012 there were 105.

In addition to reports involving methylone that have been recorded in NFLIS and STRIDE, 

DEA received reports from police departments regarding their seizures of methylone. 

The New Hampshire Forensic Laboratory reported to DEA seizures of confiscated

substances that were confirmed by forensic analysis to contain methylone. These substances 

were received from law enforcement departments located throughout the state of New 

Hampshire. Substances submitted were of various forms and amounts. The following are 

examples of some of these substances that contained methylone: 0.10g white powder, capsules 

with off-white powder, capsules with white powder, 0.54 g of white powder and 2.64 g of tan 

powder, and various colored powders in capsules that also contained butylone and pentylone. 

The Forensic Science Center in Illinois submitted a report to DEA detailing substances that 

were analyzed and confirmed to contain methylone. Substances analyzed consisted of capsules 

containing white powder, plastic bag containing white powder consistent with methylone, plastic 

bag containing white powder consistent with methylone, MDPV and other synthetic cathinones.

DEA forensic laboratories have analyzed drug exhibits received from state, local, or federal 

law enforcement agencies that were found to contain methylone. 

The Las Vegas Metropolitan Police Department submitted 44 illicitly manufactured tablets 

(10 peach and round and imprinted with a trefoil radiation symbol, 34 red and round and 

imprinted with the Motorola logo) to the Harris County Institute of Forensic Sciences Drug 

Chemistry Section for analysis. Laboratory analysis of the 10 peach tablets identified 

methamphetamine, methylone, and caffeine. The red tablets were identified to be methylone and 

caffeine (DEA, 2011a).

 

10 Analyzed on September 12, 2012, state and local forensic drug reports. The 2012 drug reports are 

likely to be incomplete as of September 12, 2012, due to laboratory reporting lag time.
Page 26 of 36

The Harris County Institute of Forensic Sciences Drug Chemistry Section (Texas) received 

submissions of tablets confirmed to contain MDPV, TFMPP, and caffeine. A syringe containing 

MDPV, oxymorphone, methylone, and lidocaine was also seized (DEA, 2011b).

The Harris County Institute of Forensic Sciences Drug Chemistry Section (Texas) also 

received submissions of four clear capsules from law enforcement in Houston, Texas. The 

capsules were confirmed to contain mephedrone and methylone (DEA, 2011c).

The DEA South Central Laboratory received submissions of a blue-black sealed packet 

labeled “White Dove Bath Salt” that contained a white powder and a small ziplock bag labeled 

“Night Cap Bath Bomb 500 mg” that contained a tan powder. Analysis of the substances 

identified methylone in both samples (DEA, 2011d).

The DEA Mid-Atlantic Laboratory received eight packets labeled “HappeeGRO” from 

Alcohol, Tobacco, Firearms, and Explosives agents (Virginia). Analysis of the off-white powder 

in the packet identified methylone (DEA, 2011e) 

At selected United States ports of entry, the U.S. Customs and Border Protection (CBP) has 

encountered shipments of products containing methylone. The most commonly identified 

synthetic cathinone was methylone. Methylone was first encountered in 2009. As of July 2012, 

of 330 synthetic cathinones shipments encountered from June 2008 to July 2012, 127 of these 

shipments contained methylone. Most of the shipments of these synthetic cathinones that 

contained methylone originated in China and were destined for delivery throughout the United 

States to places like Alaska, Arizona, Arkansas, California, Colorado, Florida, Hawaii, Illinois, 

Kansas, Louisiana, Oklahoma, Oregon, Missouri, Nevada, New Mexico, Tennessee, Texas, 

Washington, and West Virginia.

Evidence from poison centers indicates that the abuse of synthetic cathinones like methylone

is widespread. AAPCC reported in a press release that as of September 10, 2012, poison centers

took 304 calls regarding synthetic cathinones exposures in 2010 and 6,138 calls in 2011 

(AAPCC, 2012). As of September 10, 2012, poison centers have received 2,251 calls relating to 

exposures of these products for this year. These calls were received in poison centers

representing at least 47 states and the District of Columbia.

Concerns over the abuse of methylone and other synthetic cathinones have prompted many 

states to control these substances. As of September 2012, at least 42 states have emergency 

scheduled or enacted legislation placing regulatory controls on some or many of the synthetic 

cathinones including mephedrone, methylone, MDPV and/or a defined general class of 

cathinones. At least 27 states specifically control methylone. These states include Alabama, 

Arizona, Arkansas, Delaware, Florida, Georgia, Rhode Island, Illinois, Indiana, Kansas, 

Kentucky, Louisiana, Maine, Maryland, Minnesota, Mississippi, Nebraska, New Jersey, New 

Mexico, Ohio, Oklahoma, Pennsylvania, Tennessee, Texas, Utah, Virginia, and Wyoming. In 

addition, the U.S. Armed Forces prohibited the use of synthetic cathinones including 

mephedrone, methylone or MDPV. Internationally, several member countries of the European 

Union have enacted laws placing controls on the possession and/or sale of one or more of these

substances (Winstock et al., 2010; EMCDDA, 2011).
Page 27 of 36

Summary

Methylone is a popular recreational drug that first appeared on the United States’ illicit drug 

market in 2009. Evidence that methylone is being abused is confirmed by drug courts, calls to 

poison centers, and encounters by law enforcement. Methylone has been identified in specimens 

from individuals submitted for testing by drug court participants. Evidence from poison centers 

also indicates that the abuse of synthetic cathinones like methylone is widespread. Evidence of 

the increased abuse of methylone is supported by law enforcement encounters of methylone. 

DEA forensic laboratories have analyzed drug exhibits received from state, local, or federal law 

enforcement agencies that were found to contain methylone. The National Forensic Laboratory 

Information System (NFLIS) details over 2,500 reports from state and local forensic laboratories 

identifying methylone in drug related exhibits for a period from January 2009 to June 2012 from 

42 states. Additionally, large seizures of methylone have occurred by law enforcement and the 

U.S. Customs and Border Protection (CBP). Concerns over the abuse of methylone have 

prompted at least 27 states to control methylone.

Factor 6: What, If Any, Risk There is to the Public Health

HHS reported that public health risks resulting from the abuse of methylone relate primarily 

to the ability of this drug to induce adverse events that are characteristic of CNS stimulants

(HHS, 2012). HHS cited several published case reports in the medical literature that involved 

individuals who sought emergency care for the abuse use of methylone. Deaths from the abuse 

of methylone were also cited by HHS. These reports are described below.

These reports also come from law enforcement, forensic laboratories, and public health 

officials that have reported toxic exposure to methylone and other synthetic cathinones 

demonstrating the public health risks associated with these substances. 

Adverse Effects of Methylone

Methylone has been reported to cause a number of stimulant-like adverse effects (Shimizu et 

al., 2007; ACMD, 2010; Karila and Reynaud, 2010; Boulanger-Gobeil et al., 2012; Pearson et 

al., 2012). The clinical presentation of intoxication from methylone shares some features seen 

with MDMA and stimulants like cocaine. Clinical case reports indicate that these methylone

produces a number of stimulant-like adverse effects such as palpitations, seizures, vomiting, 

sweating, headache, hyperthermia, mydriasis, hypertension, tachycardia and hyper-reflexia 

(Shimizu et al., 2007; ACMD, 2010; Karila and Reynaud, 2010; Boulanger-Gobeil et al., 2012; 

Pearson et al., 2012; Warrick et al., 2012). Other adverse effects associated with the 

consumption of methylone as reported by users include nausea, bruxism (teeth grinding), 

paranoia, muscular tension, agitation, anxiety, tremor, fever, and sweating (ACMD, 2010; Karila 

and Reynaud, 2010). Hyperthermia can be a serious adverse effect and can lead to metabolic 

acidosis, rhabdomyolysis, renal failure, disseminated intravascular coagulation, coma, and death. 

Serious adverse effects including hyperthermia have resulted in documented hospital emergency 

department (ED) admissions from the ingestion of methylone.
Page 28 of 36

DEA notes that studies show that methylone, like MDMA, can be cytotoxic to liver cells. 

Incubation of hepatocytes (liver cells) with methylone or MDMA caused cell death (Nakagawa 

et al., 2009). In addition, high concentrations of methylone induced the release of lactate 

dehydrogenase (LDH), an indication of decreased cell viability, in cells that stably expressed the 

SERT (Sogawa et al., 2011). However, methylone in combination with methamphetamine had a 

synergistic cytotoxic effect on cells that expressed the DAT, NET, or SERT. This finding is 

particularly important because there have been reports of abuse of synthetic cathinones in 

combination with other drugs of abuse. These data suggest that using methylone alone and in 

combination with other psychoactive substances may cause damage to liver cells. Indeed a case 

of liver toxicity was reported in the scientific literature. Boulanger-Gobeil et al. (2012) 

described a 22-year-old female who developed rhabdomyolysis (liver injury occurs in 25% of 

patients with rhabdomyolysis (Huerta-Alardin et al., 2004)) after ingesting a product called 

“legal ecstasy” which was analyzed to be a mixture of methylone and ethcathinone.

Case Reports Involving Methylone

As described below, numerous individuals have presented at emergency departments following 

exposure to methylone or products containing methylone. 

Boulanger-Gobeil et al. (2012) described a case of a 22-year-old female developed 

rhabdomyolysis after ingesting “legal ecstasy” which was analyzed to be a mixture of methylone 

and ethcathinone. She also suffered from recurrent seizures, severe hyponatremia (abnormally 

low concentration of sodium in the blood), nystagmus (involuntary rapid eye movement), 

hyperreflexia, and bruxism. All her symptoms resolved after treatment that required 

hospitalization. 

DEA notes that Katagi et al. (2010) reported two cases of acute toxicity from the confirmed 

ingestion of methylone. A 19-year-old male was taken to the emergency department suffering 

from dementia after ingesting an unknown amount of methylone powder. In the second case, a

29-year-old male was taken to the emergency department suffering from acute toxicity after 

taking an unknown amount of a mixture of methylone and a hallucinogen.

Some of these individuals under the influence of methylone have acted violently and 

unpredictably causing harm, or even death, to themselves or others. 

Shimizu et al. (2007) reported a case of acute drug intoxication from the ingestion of a 

mixture of methylone and 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MIPT) powder. 

A 27-year-old Japanese male presented to the emergency room after taking approximately 200 

milligrams of powder that was analyzed to be a mixture of methylone and 5-MeO-MIPT powder 

by oral ingestion that he purchased over the Internet. According to the report, the subject was 

transported to the hospital after reportedly acting strangely. At the hospital, the subject had an 

elevated heart rate and blood pressure, while exhibiting dilated pupils and sweating. The 

patient’s symptoms resolved after five hours of treatment.

DEA notes that Cawrse et al. (2012) described the death of a 38-year-old male by suicide and 

a 35-year-old female by homicide. The 35-year-old male was found dead in bed with a gunshot 
Page 29 of 36

wound to the head which was determined to be the cause of death. The 38-year-old female who 

was the girlfriend of the 38-year-old male was found unresponsive in bed with a wound on her 

neck and a gunshot wound to the head. She died at the scene and her cause of death was cutting 

wound of neck and gunshot wound to the head. Toxicology tests identified methylone in 

specimens from these individuals.

Individuals suspected of driving under the influence of intoxicating substances have been found 

to have positive test results for methylone. Some of these incidents involving methylone 

intoxications have resulted in the deaths of individuals suspected of driving while under the 

influence of these drugs.

Marinetti et al. (2011) reported the death of a 37-year-old male who was involved in a motor 

vehicle accident in which the decedent was at fault. The Miami Valley Regional Crime 

Laboratory identified methylone, MDPV, THC, and a THC product in blood specimen from this 

individual. DEA notes that in another case reported by Marinetti et al. (2011), a 30-year-old 

male was found passed out in a vehicle. The individual was charged with having weapons while 

under disability. Toxicology testing identified methylone, MDPV, clonazepam, and other 

substances in blood specimens from this individual.

Fatalities Involving Methylone

There are at least three reported deaths in which methylone was ruled as the cause of death by 

the medical examiner or after an autopsy. 

A 19-year-old female who took a pill known as “Molly” collapsed and recovered then 

complained of not feeling well (Pearson et al., 2012). Thereafter, she was observed to have 

seizures. Emergency personnel were called and the decedent was transported to the hospital. At 

the hospital she suffered cardiac complications and despite efforts to save her life she died. 

Toxicology tests identified methylone in specimens from the decedent. No other recreational 

substances were detected. The medical examiner concluded that the cause of death was 

methylone intoxication.

Pearson et al. (2012) also described the death of a 23-year-old male. The decedent was 

witnessed to take what was thought to be LSD at a club. The decedent was acting erratically and 

irrationally and so the decedent was removed from the club and placed in the back of a van by 

securing the decedent to a chair using saran wrap. Sometime later, the decedent was found 

having seizures. Emergency personnel was called and the decedent was transported to the 

hospital. The decedent was suffering from various ailments such as hyperthermia. Despite 

efforts to save his life the decedent died 45 minutes after his arrival at the hospital. The medical 

examiner listed the cause of death as intoxication by methylone.

In another incident reported by Pearson et al. (2012), the death of a 23-year-old male 

suspected of using methylone was described. The decedent was walking in and out of traffic and 

acting belligerently. The decedent was detained by law enforcement and transported to the 

hospital. The decedent had a high temperature and subsequently went into respiratory failure. 

After several attempts by medical personnel to stabilize the decedent, he died. Toxicology 
Page 30 of 36

testing identified methylone in specimens from this individual. The medical examiner listed the 

cause of death as intoxication by methylone.

Methylone has also been implicated (i.e., the primary cause of death is not methylone toxicity) in 

drug induced overdose deaths. 

Warrick et al. (2012) described the death of a 24-year-old female who ingested two capsules 

of what was thought to be “Ecstasy” at a concert. After being found unconscious by emergency 

personnel, the decedent was taken to the emergency department. The comatose patient suffered 

from hyperthermia, tachycardia, mydriasis, tachypnea and some tremors. Despite efforts to save 

her life the decedent died. Toxicology tests identified methylone and butylone in specimens 

from this individual. Laboratory analysis also identified methylone and butylone in the powder 

obtained from a capsule that was found on the decedent. The cause of death by the medical 

examiner was serotonin syndrome secondary to methylone and butylone.

DEA notes additional publications that involve a death involving methylone. Cawrse et al.

(2012) described the death of a 19-year-old male. The decedent died while performing a physical 

fitness assessment. Toxicology tests identified methylone in specimens from this individual. 

The cause of death was cardiac arrest associated with methylone. A death of a 39-year-old male 

was reported by Wyman et al. (2011). Family members indicated that the male, who had a 

history of schizophrenia, depression, and drug abuse, had been snorting “bath salts.” The subject 

was found dead in his bed. Empty jars of “bath salts” (TranQuility and Infinity) and synthetic 

cannabinoids (Demon and Flame) were found in the trash. A toxicological screen detected 

MDPV distributed among multiple tissues, urine and blood samples from the decedent. Other 

substances detected were nicotine, cotinine, pseudoephedrine, m-chlorophenylpiperazine and 

methylone. The cause of death was acute MDPV intoxication.

Kovacs et al. (2012) described the case of a 16-year-old male that lost consciousness at a 

party. The decedent died of sudden cardiac death at the hospital after attempts to save his life 

were unsuccessful. The decedent suffered from cardiac malformation and bronchial asthma. 

Toxicology test identified methylone in the specimens from this individual. The authors 

concluded that the predisposing factors along with methylone may have resulted in the sudden 

cardiac death of this individual.

Identification of Products Containing Methylone or Other Synthetic Cathinones

The products containing methylone and other synthetic cathinones often do not bear labeling 

information regarding their ingredients or the health risks and potential hazards associated with

these products. In addition, products may not contain the expected active ingredients. Thus, 

individuals who purchase these products likely have insufficient knowledge of the exact product 

contents. This lack of information poses significant risk to users who may not know what they 

are purchasing or the risk associated with the abuse of those products. In a study that analyzed 

products offered for sale over a 6 month period, there was significant variation in the active 

substance (i.e., the products did not contain the expected active ingredients or products marketed 

to contain a specific legal substance contained a different substance) in one quarter (5 of 20) of 

the products that were purchased (the same named products such as Head rush, Pure bliss, or 
Page 31 of 36

Xtacy were purchased repeatedly during a 6 month period) and tested (Davies et al., 2010). In a 

separate study, the analysis of a specific brand name synthetic cathinone product (e.g., white 

lightening), that appeared identical in packaging but obtained at different locations, revealed 

different synthetic cathinones as the primary ingredient (Spiller et al., 2011). In this study, 

methylone was identified in 6 of the 15 bath salt products purchased for the analyses. A study by 

Brandt et al. (2010) showed that 70% of the products analyzed contained an illicit substance. 

Another study showed that there was poor quality of product information (Schmidt et al., 2010). 

Of 1,308 products evaluated, 40% (524) did not list ingredients, 92% (1,202) failed to list any 

side effects, and 86% (1,129) failed to list any warnings about potential interactions with other 

substances or medications. Since abusers obtain these drugs through unknown sources, the 

purity of these drugs is uncertain presenting another level of risk to users (EMCDDA, 2011). 

Thus, the limited knowledge about product content and its purity and lack of information about 

its effects pose significant risks to the users.

Summary

In summary, available evidence on the overall public health risks associated with the use of 

methylone indicate that this substance can cause acute health problems leading to ED 

admissions, violent behaviors causing harm to self or others, and motor vehicle accidents if 

driving while intoxicated or can cause death. Additionally, products containing methylone and 

other synthetic cathinones often do not bear labeling information regarding their ingredients and 

if they do, it may not contain the expected active ingredients or identify the health risks and 

potential hazards associated with these products. Adverse effects include those typical of a 

sympathomimetic agent including tachycardia, headache, palpitations, agitation, anxiety, 

mydriasis, tremor, fever or sweating, and hypertension (Shimizu et al., 2007; ACMD, 2010; 

Karila and Reynaud, 2010; Boulanger-Gobeil et al., 2012). Other effects, with possible public 

health risk implications, that have been reported from the use of these substances include

psychological effects such as psychosis, paranoia, hallucinations, and agitation (Shimizu et al., 

2007; ACMD, 2010; Karila and Reynaud, 2010; Pearson et al., 2012). Finally, the reports of 

death for individuals abusing methylone indicates that it is are a serious public health threat. 

Factor 7: Its Psychic or Physiological Dependence Liability

According to HHS, there are no studies or case reports that document the psychic or 

physiological dependence potential of methylone (HHS, 2012). However, HHS states that 

because methylone shares pharmacological properties with those of the Schedule I and II 

substances amphetamine, methamphetamine, cocaine, and MDMA, it is probable that methylone 

has a dependence profile similar to that of these substances which are known to cause substance 

dependence.

Factor 8: Whether the Substance is an Immediate Precursor of a Substance Already 

Controlled Under this Subchapter

Methylone is not considered to be an immediate precursor of any controlled substance of the 

CSA as defined by Title 21, U.S.C § 802(23).
Page 32 of 36

III. Findings for Schedule Placement Pursuant to 21 U.S.C. 812(b)

21 U.S.C. 812(b) requires the evaluation of a substance’s abuse potential, accepted medical 

use, and safety for use under medical supervision for placement in the CSA as a controlled 

substance. After consideration of the above eight factors determinative of control of a substance 

(21 U.S.C. 811(c)), and a review of the scientific and medical evaluation and scheduling 

recommendation provided by HHS, DEA finds that methylone meets the three criteria for 

placement in Schedule I of the CSA pursuant to 21 U.S.C. 812(b)(5).

1) Methylone has a high potential for abuse.

According to HHS, data from animal, human, and epidemiological studies described in the 

scientific literature demonstrate that methylone has a high potential for abuse. The profile of 

pharmacological effects of methylone is similar to that of the Schedule I and Schedule II 

substances amphetamine, methamphetamine, cocaine, and MDMA. In addition, law 

enforcement data suggests that the abuse of methylone is widespread in the United States as 

indicated by the increased encounters of methylone by law enforcement in various regions of the 

United States. Based on these findings by HHS and DEA, DEA concludes that methylone has a 

high potential for abuse.

2) Methylone has no currently accepted medical use in treatment in the United States.

According to HHS, methylone has no approved medical use in the United States, does not 

have an approved NDA, and is not currently marketed in the United States in an FDA-approved 

drug product. A drug has a “currently accepted medical use” if all of the following five elements 

have been satisfied: the drug’s chemistry is known and reproducible; and there are adequate 

safety studies; and there are adequate and well-controlled studies proving efficacy; and the drug 

is accepted by qualified experts; and the scientific evidence is widely available. According to 

HHS, there are no published clinical studies involving methylone. DEA has also not found any 

references to clinical studies involving methylone in the scientific and medical literature. 

Although the chemistry of methylone is known and has been reproduced, as mentioned above 

there are no clinical studies involving methylone. Thus, methylone has no currently accepted 

medical use in treatment in the United States.

3) There is a lack of accepted safety for use of methylone under medical supervision. 

According to HHS, methylone has no approved medical use, has not been investigated as a 

new drug, and its safety for use under medical supervision has not been determined. In addition, 

methylone has not been evaluated in human abuse liability studies and no studies have been 

undertaken to evaluate the toxicology and safety of methylone in humans. Thus, HHS concluded 

that there is a lack of accepted safety for use of methylone as a medication. Therefore, DEA 

concludes that there is a lack of accepted safety for use of methylone under medical supervision.
Page 33 of 36

References

AAPCC. American Association of Poison Control Centers. 2012. Bath Salts Data. Updated 

September 10, 2012.

ACMD. Advisory Council on the Misuse of Drugs. 2010. Consideration of the cathinones. 

(Iversen). London.

Balster RL, Bigelow GE. 2003. Guidelines and methodological reviews concerning drug abuse 

liability assessment. Drug and Alcohol Dependence, 70: S13-40.

Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman 

RB, Ruoho AE, Cozzi NV. 2011a. The designer methcathinone analogs, mephedrone and 

methylone, are substrates for monoamine transporters in brain tissue. 

Neuropsychopharmacology. 37: 1192-1203.

Boulanger-Gobeil C, St-Onge M, Laliberte M, Auger PL. 2012. Seizures and hyponatremia 

related to ethcathinone and methylone poisoning. Journal of Medical Toxicology, 8: 59-61.

Brandt SD, Sumnal HR, Measham F, Cole J. 2010. Analysis of second-generation ‘legal highs’ 

in the UK: Initial findings. Drug Testing and Analysis, 2: 377-382.

Cawrse BM, Levine B, Jufer RA, Fowler DR, Vorce SP, Dickson AJ, Holler JM. 2012. 

Distribution of methylone in four postmortem cases. Journal of Analytical Toxicology. 36: 434-

9. 

Collins M. 2011. Some new psychoactive substances: precursor chemicals and synthesis-drive 

end-product. Drug Testing and Analysis, 3: 404-416. 

Cozzi N, Sievert M, Shulgin A, Peyton J, Ruoho A. 1999. Inhibition of plasma membrane 

monoamine transporters by β-ketoamphetamines. European Journal of Pharmacology, 381: 63-

69.

Cozzi N, Sievert M, Shulgin A, Peyton J, Ruopho A. 1998. Methcathinone and 2-methylamino1-(3,4-methylenedioxyphenyl)propan-1-one selectively inhibit plasma membrane catecholamine 

reuptake transporters. Society for Neuroscience Abstracts, 24: 381-388. 

Dal Cason T, Young R, Glennon R. 1997. Cathinone: An investigation of several N-alkyl and 

methylenedioxy-substituted analogs. Pharmacology Biochemistry and Behavior, 58: 1109-1116.

Davies S, Wood DM, Smith G, Button J, Ramsy J, Archer R, Holt DW, Dargan PI. 2010. 

Purchasing ‘legal highs’ on the Internet-is there consistency in what you get? QJM: An 

International Journal of Medicine, 103: 489–493.
Page 34 of 36

DEA. 2011a. Drug Enforcement Administration. Ecstasy mimic tablets (actually containing 

methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and caffeine seized in Las 

Vegas, Nevada. Microgram, 44: 21.

DEA. 2011b. 3,4-Methylenedioxypyrovalerone (MDPV) tablets seized in Houston, Texas. 

Microgram, 44: 41.

DEA. 2011c. Capsules containing 4-methylmethcathinone (mephedrone) and 3,4-

methylenedioxymethcathinone (methylone, MDMC) seized in Houston, Texas. Microgram, 44: 

72.

DEA. 2011d. Bath salts (actually containing 3,4-methylenedioxymethcathinone 

(methylone,MDMC) and 3,4-methylenedioxypyrovalerone (MDPV) and creatine) seized in Saint 

Tammany Parish, Louisiana. Microgram, 44: 61.

DEA. 2011e. 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone 

(methylone, MDMC) packets seized in Bristol, Virginia. Microgram, 44: 63.

EMCDDA. European Monitoring Centre for Drugs and Drug Addiction. 2011. Report of the 

risk assessment of mephedrone in the framework of the Council Decision on new psychoactive 

substances. Luxembourg: Publications Office of the European Union, doi: 10.2810/40800.

Griffiths P, Lopez D, Sedefov R, Gallegos A, Hughes B, Noor A, Royuela L. 2010. Khat use 

and monitoring and issues for the future. Journal of Ethnopharmacology, 132: 578-583.

HHS, Department of Health and Human Services. 2012. Basis for the recommendation to place 

3,4-methylenedioxymethcathinone (methylone) and its salts in Schedule I of the Controlled 

Substances Act (CSA). Dated August 14, 2012.

Huerta-Alardin AL, Varon J, Marik PF. 2004. Bench-tobedside review: Rhabdomyolosis-an 

overview for clinicians. Critical Care, 9: 158-159.

Jacob P III, Shulgin. 1996. Novel N-substituted-2-amino-3’,4’-methylene-dioxypropiophenones. 

Patent Cooperation Treaty (PCT) International Applications, PCT/US06/09603.

Kamata HT, Shima N, Zaitsu K, Kamata T, Miki A, Nishikawa M, Katagi M, Tsuchihashi H. 

2006. Metabolism of the recently encountered designer drug, methylone, in humans and rats. 

Xenobiotica, 36: 709-723.

Karila L, Reynaud M. 2010. GHB and synthetic cathinones: clinical effects and potential 

consequences. Drug Testing and Analysis, 3: 552-559.

Katagi, M, Zaitsu K, Shima N, Kamata H, Kamata T, Nakanishi K, Nishioka H, Miki A, 

Tsuchihashi H. 2010. Metabolism and forensic toxicological analyses of the extensively abused 

designer drug methylone. TIAFT Bulletin, 40: 30-35.
Page 35 of 36

Kelly J. 2011. Cathinone derivatives: A review of their chemistry, pharmacology and toxicology. 

Drug Testing and Analysis, 3: 439-453.

Kovacs K, Tooth AR, Kereszly EM. 2012. A new designer drug: Methylone related death. 

Orvosi Hetilap (Hungarian Medical Journal), 153: 271-276.

López-Arnau R, Martínez-Clemente J, Pubill D, Escubedo E, Camarasa J. 2012. Comparative 

neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and 

methylone. British Journal of Pharmacology, 167: 407-420. 

Marinetti L, Antonides H, Watson J. 2011. Drugs in the news: More on bath salts. ToxTalk, 35: 

11-13.

McNamara S, Stokes S, Coleman N. 2010. Head shop compound abuse amongst attendees of 

The Drug Treatment Centre Board. Irish Medical Journal, 103: 134-137.

Measham F, Moore K, Newcombe R, Welch Z. 2010. Tweaking, bombing, dabbing and 

stockpiling: the emergence of mephedrone and the perversity of prohibition. Drugs and Alcohol 

Today. 10: 14-21.

Meyer MR, Maurer HH. 2010. Metabolism of designer drugs of abuse: An updated review. 

Current Drug Metabolism, 11: 468-482.

Meyer MR, Wilhelm J, Peters PT, Maurer HH. 2010. Beta-keto amphetamines: studies on the 

metabolism of the designer drug mephedrone and toxicological detection of mephedrone, 

butylone, and methylone inurine using gas chromatography-mass spectrometry. Analytical 

Bioanalytical Chemistry, 397: 1225-1233.

Miyazawa M, Kojima T, Nakaji S. 2011. Behavioral and rewarding effects of methylone, an 

analog of MDMA in mice. Hirosake Medical Journal, 62: 56-71.

Nagai F, Nonaka R, Satoh K, Kamimura H. 2007. The effects of non-medically used 

psychoactive drugs on monoamine neurotransmission in rat. European Journal of Pharmacology, 

559: 132-137.

Nakagawa Y, Suzuki T, Tayama S, Ishii H, Ogata A. 2009. Cytotoxic effects of 3,4-

methylenedioxy-N-alkylamphetamines, MDMA and its analogues, on isolated rat hepatocytes. 

Archives of Toxicology, 83: 69-82.

NIDA, National Institute of Drug Abuse. 2011. Contract N01DA-7-8872 .

NIDA, 2012. Inter-Agency Agreement No. NIDA AD12013.

Panlilio LV, Goldberg SR. 2007. Self-administration of drugs in animals and humans as a model 

and an investigative tool. Addiction, 102: 1863-1870.
Page 36 of 36

Pearson JM, Hargraves TL, Hair LS, Massucci CJ, Frazee CC 3rd, Garg U, Pietak BR. 2012. 

Three fatal intoxications due to methylone. Journal of Analytical Toxicology, 36: 444-451.

Prosser JM, Nelson LS. 2012. The toxicology of bath salts: A review of synthetic cathinones. 

Journal of Medical Toxicology, 8: 33-42.

Prus AJ, James JR, Rosecrans JA. 2009. Conditioned Place Preference. In: Buccafusco JJ, editor. 

Methods of Behavior Analysis in Neuroscience. 2nd edition. Boca Raton (FL): CRC Press; 

Chapter 4. Available from: http://www.ncbi.nlm.nih.gov/books/NBK5229/.

Rana S, Uralets V, Ross W. 2011. Routine screening of human urine for 14 new designer 

stimulants found in “bath salts.” Society of Forensic Toxicologist (SOFT) & The International 

Association of Forensic Toxicologist (TIAFT) Joint international Conference & Exposition on 

forensic and Analytical Toxicology, 25 – 30 September 2011. P099.

Schmidt MM, Sharm A, Schifano F, Feinmann C. 2010. “Legal highs” on the net-Evaluation of 

UK-based Websites, products and product information. Forensic Science International, 206: 92-

97.

Shimizu E, Watanabe H, Kojima T, Hagiwara H, Fujisake M, Miyatake R, Hashimoto K, Iyo M. 

2007. Combined intoxication with methylone and 5-MeO-DIPT. Progress in NeuroPsychopharmacology & Biological Psychiatry. 31: 571-573.

Sogawa C, Sogawa N, Ohyama K, Kikura-Hanajiri R, Goda Y, Sora I, Kitayama. 2011. 

Methylone and monoamine transporters: Correlation with toxicity. Current Neuropharmacology, 

9: 58-62.

Spiller HA, Ryan ML, Weston RG, Jansen J. 2011. Clinical experience with and analytical 

confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. 

Clinical Toxicology, 49: 499-505.

Stolerman I. 1992. Drugs of abuse: behavioral principles, methods and terms. Trends in 

Pharmacological Sciences, 13: 170-176.

Warrick BJ, Wilson J, Hedge M, Freeman S, Leonard K, Aaron C. 2012. Lethal serotonin 

syndrome after methylone and butylone ingestion. Journal of Medical Toxicology. 8: 65-68. 

Winstock A, Mitcheson L, Marsden. 2010. Mephedrone: still available and twice the price. The 

Lancet, 376: 1537.

Wyman JF, Lavins ES, Sofalvi S, Armstrong EJ, Engelhart DA, Boggs PD, Taylor SM, Naso 

CK, Stibley JM, Snell KD, Wilkins LD, Gubanich KM, Mazzola CD, Norris RN, Blum LM, 

Miller FP. 2011. Death by “bath salts”: Postmortem tissue distribution of MDPV following lethal 

Intoxication. Society of Forensic Toxicologist (SOFT) & The International Association of 

Forensic Toxicologist (TIAFT) Joint international Conference & Exposition on forensic and 

Analytical Toxicology, 25 – 30 September 2011. O90.