3-CMC (3-Chloromethcathinone)CAS 1607439-32-6

Buy 3-Chloromethcathinone online.3-Chloromethcathinone (3-CMC), also known as clophedrone, is a synthetic substance belonging to the cathinone class of psychoactive compounds. It is very similar in structure to other methcathinone derivatives such as 3-MMC and 4-CMC.^[1][2] Unlike cathinone, which occurs naturally in the khat 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 its stimulating effects that are described to be similar to the effects of mephedrone and, to a lesser extent, those of MDMA and cocaine.^[2] 3-CMC has been sold online as a designer 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 of 3-MMC, users report reduced effects and a shorter duration in comparison.^[1] Effects include stimulation, euphoria, and increased confidence, libido, and sociability. It can be administered orally or through nasal insufflation.^[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.According to the European 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. 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 other cathinones of which it is known exposure can result in symptoms such as tachycardia, hypertension, and episodes of psychosis.^[2] Users also report other side effects including an increase in body temperature, sweating, anxiety, and dry mouth.^[1]

Specifically, 3-chloromethcathinone (3-CMC) and other ring-substituted methcathinone derivatives act as substrates for monoamine transporters MATs (and subsequently competitive inhibitors), through which they are actively translocated into the cytoplasm of the presynaptic nerve terminal. Once inside the cytosol, they interact with the vesicular monoamine transporter 2 (VMAT2) as substrates, disrupting the vesicular proton gradient and facilitating the collapse of synaptic vesicles. This causes the release of stored neurotransmitters into the cytoplasm.

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The resulting high concentration of cytosolic neurotransmitters subsequently triggers the reversal of MAT transport direction, leading to carrier-mediated efflux of the neurotransmitters into the synaptic cleft.^[14] Furthermore, simple ring-substituted cathinones contrast with traditional amphetamines by lacking significant affinity for the intracellular trace amine-associated receptor 1 (TAAR1). In traditional amphetamine pharmacology, TAAR1 activation triggers intracellular phosphorylation signaling cascades that facilitate and optimize the structural reversal of monoamine transporters (MATs) to allow efficient neurotransmitter efflux.^[15] Because cathinones fail to activate TAAR1, this phosphorylation is absent, rendering carrier-mediated efflux less efficient. Consequently, displaced neurotransmitters tend to accumulate and linger within the cytoplasm rather than being cleanly exported to the synaptic cleft, promoting intracellular auto-oxidation, and faster depletion.^[16]

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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.^[12] 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.^[17]

3-CMC produces hyperlocomotion, a psychostimulant-like effect, in rodents.^[8] It substitutes for cocaine in drug discrimination tests in monkeys.^[18] The drug is less potent in substituting for cocaine than methcathinone, which has been theorized to be due to its greater capacity to induce serotonin release and to thereby inhibit its own reinforcing effects.^[18]

The pharmacology of 3-CMC is expected to be very similar to the pharmacology for other mephedrone analogs (methcathinones).^[12] These molecules interact with monoamine transporters, in particular the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT) . The main function of these transporters is to terminate monoamine transmission by reuptake of the released neurotransmitters. Interaction of psychoactive drugs with the monoamine transporters inhibits this reuptake leading to an increase in the concentration of dopamine, norepinephrine and serotonin in the synaptic cleft.^[13]