Methylone

, methamphetamine and methcathinone.Right: MDA, MDMA, and methylone. Methylone substitutes for MDMA in drug discrimination tests in rodents. Methylone does not substitute for the stimulant amphetamine or for the hallucinogen DOM in animal drug discrimination tests. Further, also in common with MDMA, methylone acts on monoaminergic systems. In vitro, methylone has one third the potency of MDMA at inhibiting platelet serotonin accumulation and about the same in its inhibiting effects on the dopamine and noradrenaline transporters. In acute pharmacological studies of methylone (50–300mg) in humans, the drug produced physiological and psychological effects including increased blood pressure, heart rate, body temperature, pupil dilation, stimulation, euphoria, feelings of well-being, enhanced empathy, increased sociability, and altered perception. The studies found that the effects of methylone were similar to or milder than those of MDMA. ==Interactions==

Pharmacodynamics Methylone acts as a mixed releasing agent and reuptake inhibitor of serotonin, norepinephrine, and dopamine. In comparison to MDMA, it has approximately 3-fold lower affinity for the serotonin transporter, while its affinity for the norepinephrine and dopamine transporters is similar. In contrast to MDMA however, methylone and its metabolites lack significant affinity for the serotonin 5-HT2A and 5-HT2C receptors and do not activate the serotonin 5-HT2B receptor. On the other hand, a subsequent study found that methylone indeed showed no affinity for or agonistic activity at the serotonin 5-HT2A and 5-HT2B receptors, but was a potent and near-full agonist of the serotonin 5-HT2C receptor Gαq pathway, though not of the other assessed Gα pathways of the receptor. Methylone is inactive at the mouse and rat trace amine-associated receptor 1 (TAAR1). Similarly to MDMA, methylone has been found to be a monoaminergic neurotoxin in animals. It has specifically been found to produce serotonergic and dopaminergic neurotoxicity in rodents. The mean elimination half-lives of methylone in humans following oral administration of doses of 50 to 200mg ranged from 5.8 to 6.9hours. The onset of action and duration of action of methylone in humans are 0.5hours and 2.5 to 3.0hours, respectively. ==Chemistry==

Methylone is the substituted cathinone analogue of 3,4-methylenedioxymethamphetamine (MDMA) and the 3,4-methylenedioxy analogue of methcathinone. Synthesis The chemical synthesis of methylone has been described. ==History==

Methylone was first synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s. However, it was subsequently included in The Shulgin Index (2011). The drug was patented by Jacob and Shulgin as a potential antidepressant and antiparkinsonian agent, but was never developed or marketed. This was the first time that methylone was described in the literature. The drug was first described in the scientific literature by 1997. Methylone was encountered as a designer and recreational drug by 2004. It has become a controlled substance in many countries. ==Society and culture==

Names and etymology "Methylone" is also a trademarked brand name for an injectable form of methylprednisolone, a corticosteroid hormone used to treat arthritis and severe allergic reactions; hence, methylone may be confused with it. Aside from context, they can be distinguished by the fact that the name will usually be capitalized when referring to the prescription drug. A proposed alternate name is βk-MDMA, or beta-keto-MDMA. While this nomenclature has not caught on because the name "methylone" became widely used before the conflicting Methylone trademark was noticed, the analogous names for related chemicals βk-MDEA and βk-MBDB have become the established names for those substances. Commercial distribution Analysis of "Explosion" has confirmed that the active ingredient is methylone. Many other formulations marketed as household chemicals, as well as the pure powder, have been sold. Legal status Netherlands In the Netherlands, methylone is not yet listed under the Opium Law, but is covered under the medicine act. Because methylone is not registered officially, it is forbidden to trade in methylone. The Minister of Health has asked the Coordination point Assessment and Monitoring new drugs group (CAM) to gather information about this substance, resulting possibly in an official risk assessment. Until now, no research has been conducted on the toxicity of methylone, so nothing is known about the harmfulness of this new drug. New Zealand In New Zealand, although methylone is not explicitly scheduled and falls outside the strict definitions of an "amphetamine analogue" in the Misuse of Drugs Act, it is considered to be "substantially similar" to methcathinone and is thus considered by law enforcement authorities to be a Class C illegal drug. Methylone was sold in New Zealand for around 6 months from November 2005 to April 2006 as an MDMA substitute, under the name "Ease". The product was withdrawn after legal disputes with the government. United Kingdom In the United Kingdom, methylone is illegal since the 16/04/2010 revision of the misuse of drugs act. Before this it was not specifically mentioned in United Kingdom (U.K.) law as the β-ketone was not covered under the Misuse of Drugs Act. In March 2010, plans were announced to make methylone and other cathinones, Class B drugs, "within weeks". While delayed by dissatisfaction in the Advisory Council on the Misuse of Drugs, the revision was rushed through by the government with little regard for the views of the council. The importation of the compound was banned immediately. Sweden Sveriges riksdag added methylone to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of Oct 1, 2010, published by Medical Products Agency in their regulation LVFS 2010:23 listed as Metylon, 2-metylamino-1-(3,4-metylendioxifenyl)propan-1-on. Methylone was first classified by Sveriges riksdags health ministry Statens folkhälsoinstitut as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Nov 1, 2005, in their regulation SFS 2005:733 listed as 3,4-metylendioximetkatinon (Metylon). Canada Although not listed as a Schedule 1 substance, Health Canada reports that methylone falls under the scheduling as an analogue of amphetamine. However, methylone bears the exact chemical difference between amphetamine and cathinone – and cathinone is listed as not being an analogue of amphetamine, possibly implying that methylone is unscheduled in Canada. The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1; however, methylone was not added. United States In October 2011, the DEA issued an emergency ban on methylone. It was made illegal to possess and distribute. On April 4, 2013, the DEA placed methylone as a Schedule 1 substance under the CSA. • Arizona: :: Effective February 16, 2012, methylenedioxymethcathinone (methylone) was classified as a dangerous drug, making it a felony to knowingly possess, use, possess for sale, manufacture, administer, transport for sale, import into the state, or offer to transport for sale or import into this state, sell, transfer or offer to sell or transfer. A.R.S. 13-3401(6)(c)(xliii), 2012 Ariz. Legis. Serv. Ch. 1 (H.B. 2356). • Florida: :: In January 2011, it was reported that Florida Attorney General Pam Bondi issued an emergency ban on MDPV, Methylone, Mephedrone, 3-methoxymethcathinone, 3-fluoromethcathinone, and 4-fluoromethcathinone as media attention on products labeled as "bath salts" grew. These chemicals are now Schedule I under Florida law. • Louisiana: :: In January 2011, Louisiana Governor Bobby Jindal emergency scheduled 3,4-methylenedioxymethcathinone (methylone), 3,4-methyenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), 4-methoxymethcathinone (methedrone), 4-fluoromethcathinone (flephedrone), and 3-fluoromethcathinone (3-FMC). • Michigan: :: Schedule 1 controlled substance in 2012. • Tennessee: :: On May 5, 2011, Tennessee Governor Bill Haslam signed a law making it a crime to knowingly produce, manufacture, distribute, sell, offer for sale or possess with intent produce, manufacture, distribute, sell, or offer for sale any product containing 3,4-methylenedioxymethcathinone (methylone), 3,4-methyenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), 4-methoxymethcathinone (methedrone), 4-fluoromethcathinone (flephedrone), and 3-fluoromethcathinone (3-FMC). • Texas: :: In September 2011, Texas added 3,4-methylenedioxy-N-methylcathinone to the Penalty Group 2 listing of the Health and Safety Code. Possession of a substance in penalty group 2 is a minimum of a state jail felony. ==Research==

Post-traumatic stress disorder Under the developmental code TSND-201, methylone is under development by Transcend Therapeutics for the treatment of post-traumatic stress disorder (PTSD). The efficacy and safety findings of a phase 2 trial have been published. In April 2026, the FDA issued a National Priority Voucher for the development of methylone for PTSD. ==See also==