3-Chloromethcathinone (3-CMC), also known asclophedrone, is a synthetic substance belonging to thecathinone class ofpsychoactive compounds. It is very similar in structure to other methcathinone derivatives such as3-MMC and4-CMC.[1][2] Unlikecathinone, which occurs naturally in thekhat plant Catha edulis, 3-CMC is not found in nature and is solely produced through chemical synthesis.[2][3]
First detected in 2014, 3-CMC gained attention for itsstimulating effects that are described to be similar to the effects ofmephedrone and, to a lesser extent, those ofMDMA andcocaine.[2] 3-CMC has been sold online as adesigner drug mainly in European countries such as Germany, Poland, the Netherlands, and Sweden.[4][5][6] It is a controlled substance in many countries.[2]
The perceived effects are said to resemble those of3-MMC, users report reduced effects and a shorter duration in comparison.[1] Effects include stimulation,euphoria, and increasedconfidence,libido, andsociability. It can be administeredorally or through nasalinsufflation.[1][2]
The acute effects of 3-CMC last 1 to 4 hours, depending on the administration method. After effects, like difficulty sleeping, can last 3 to 12 hours longer.[1]
3-CMC has been available in Europe since 2014.[2] According to theEuropean Monitoring Centre for Drugs and Drug Addiction (EMCDDA) it has been detected in 25 European countries with the majority of drug seizures in Poland and the largest quantities in the Netherlands.[2] The amount of 3-CMC seized in Europe has increased yearly from 2014 to 2021 indicating an increase in production and availability.[2] Large seizures of 3-CMC by customs are reported to originate from India.[2]
There are limited amounts of research available on the effects of 3-CMC. The effects are likely comparable to those of othercathinones of which it is known exposure can result in symptoms such astachycardia,hypertension, and episodes ofpsychosis.[2] Users also report other side effects including an increase in body temperature,sweating,anxiety, anddry mouth.[1]
Information on the toxicity of 3-CMC is scarce, with only exploratorycytotoxicity studies conducted.[2][7] Between November 2019 and June 2021, the EMCDDA reported ten deaths linked to 3-CMC exposure in Poland (7 cases) and Sweden (3 cases).[2] Other substances were found in six cases, withalcohol being the only additional substance in two cases.[2] Causes of death included multi-organ trauma caused by a traffic accident, toxic effects of 3-CMC, and intoxication with various substances.[2] Details such as dosage and administration routes are lacking.
The chemical name of 3-chloromethcathinone (3-CMC) is 1-(3-chlorophenyl)-2-(methylamino)-1-propanone. It is a N-alkylated and ring-substituted cathinone derivative. The drug is theanalogue ofbupropion in which itsN-tert-butyl group has been replaced with anN-methyl group.[8][9] Another related compound is3-chlorocathinone (3-CC).[8][9]
3-CMC is achloromethcathinone, which has two other positional isomers, namely 2-CMC and 4-CMC.[2] These differ in the position of the chlorine atom on thephenyl ring. As well as 3-CMC, these molecules are both knowndesigner drugs.
Since 3-CMC contains a chiral center, there are two enantiomers, namely (S)-3-CMC and (R)-3-CMC. The products are most likely on the market as aracemic mixture of the two enantiomers, since separation would result in very high costs.[2]
Additionally 3-CMC and other mephedrone analogs aremonoamine releasing agents (MRAs). They are transported into the cytoplasm of the nerve terminal through the monoamine transporters where they increase in the release ofmonoamine neurotransmitters. Releasers are thought to be more effective at raising monoamine levels since they enhance the pool of neurotransmitters available for release.[12][13]
Psychostimulants differ in their relative affinity for DAT, SERT and NET. In a study done on brain cells of male rats 3-CMC was found to interact on a relatively similar level with DAT and NET as mephedrone, while it interacts significantly less with SERT.[10] Another study done on male rats also concludes that 3-CMC causes more release of dopamine in proportion to serotonin whereas mephedrone releases relatively more serotonin.[13]
Cathinones are typically metabolized in the body through processes such asoxidation, reduction,hydrolysis, and conjugation reactions, primarily occurring in the liver.
There is still limited information about the metabolism of 3-CMC in humans or animals, as it has not been extensively studied. However, a mechanism has been proposed for the biotransformation processes of 3-CMC based on the metabolism of structurally similar cathinones, which involves the formation of several metabolites, including dihydro-3-CMC,N-desmethyl-3-CMC, andN-desmethyl-dihydro-3-CMC.[16][17]
As of March 2022, theEuropean Commission has taken new measures to control the psychoactive substance of 3-CMC. This decision is based on a risk assessment conducted by theEU Drugs Agency (EMCDDA) in November 2021.[18]
Since 3-CMC was prohibited in China (October 2015),[19] it was found that most of the production was manufactured in India and little of the substance supply originates from inside Europe.[18]
Several European countries were ahead of the European Commission report by (generically) controlling the substance. Nowadays, in almost all countries 3-CMC is prohibited.[2]
^Odoardi S, Romolo FS, Strano-Rossi S (August 2016). "A snapshot on NPS in Italy: Distribution of drugs in seized materials analysed in an Italian forensic laboratory in the period 2013-2015".Forensic Science International.265:116–120.doi:10.1016/j.forsciint.2016.01.037.hdl:10446/145558.PMID26874736.
^Advisory Council on the Misuse of Drugs (31 March 2010)."Consideration of the cathinones". Archived from the original on 8 December 2010.
^abKohut SJ, Fivel PA, Blough BE, Rothman RB, Mello NK (October 2013). "Effects of methcathinone and 3-Cl-methcathinone (PAL-434) in cocaine discrimination or self-administration in rhesus monkeys".Int J Neuropsychopharmacol.16 (9):1985–1998.doi:10.1017/S146114571300059X.PMID23768644.
