Mephedrone, a substituted β-keto amphetamine banned in the UK in 2010, continues to be used recreationally. Users compare its effects to MDMA (ecstasy), but preclinical data reveal key differences. Both drugs enhance locomotor activity and change rectal temperature in rodents, but mephedrone's effects are shorter due to its rapid metabolism and short plasma half-life. Unlike MDMA, mephedrone has no pharmacologically active metabolites and little evidence of inducing neurotoxic decreases in monoamine concentrations. Both drugs induce dopamine and serotonin release, but mephedrone's effect on serotonin release is more marked. Mephedrone shows high abuse liability, supporting self-administration at higher rates than MDMA, and its pharmacological profile differs from other cathinones as well.
Mephedrone, a synthetic cathinone, produces different effects on body temperature and brain chemistry than MDMA (ecstasy) in rats. MDMA caused sustained decreases in rectal and tail temperature, while mephedrone caused only a transient drop in rectal temperature and a prolonged decrease in tail temperature. In contrast, cathinone and methcathinone raised rectal temperature. MDMA reduced serotonin and certain metabolites in several brain regions, whereas cathinone and methcathinone increased the dopamine metabolite homovanillic acid and serotonin metabolite 5-HIAA in the striatum. Mephedrone increased plasma noradrenaline, which was blocked by certain receptor antagonists. The adverse effects of cathinones in humans cannot be extrapolated from MDMA data.
Rats exposed to both neonatal PCP and post-weaning isolation (dual-hit) showed reduced parvalbumin, a marker of GABAergic interneurons, in multiple frontal cortical regions, while isolation-only rats showed reductions only in prelimbic/infralimbic cortex. The dual-hit rats also had increased microglial activation in medial/ventral orbitofrontal cortex and elevated IL-6 in frontal cortex, changes not seen with isolation alone. These neurochemical deficits—involving GABA and inflammation—parallel those in schizophrenia, supporting the dual-hit model's use for testing therapies targeting excitatory-inhibitory imbalance or neuroinflammation.