Psychoactive Bath Salts and Neurotoxicity Risk

Synthetic cathinones are new designer drugs that possess hallucinogenic and psychostimulant properties, and are designed to mimic the effects of illegal substances such as cocaine, amphetamines, and 3.4-methylenedioxymethamphetamine (ecstasy) and to produce rewarding effects, circumventing existing laws and penalties. Synthetic cathinones, also referred to as 'bath salts', have become popular particularly among young people since the mid-2000s. Similar to other psychomotor stimulants, synthetic cathinones have the potential to increase monoamine concentration in the synaptic cleft by targeting the plasma membrane transporters of dopamine, norepinephrine, and serotonin. Because of their structural similarities to amphetamines, it has been suggested that synthetic cathinones may have a neurotoxicity profile similar to that of their amphetamine congeners. Therefore, it has been hypothesized that synthetic cathinones may induce neurotoxicity on monoamine nerve endings in the striatum, hippocampus, and cortex. To date, with regard to synthetic cathinone neurotoxicity, parameters such as monoamine depletion, biosynthetic enzyme inhibition, cytotoxicity, generation of reactive oxygen species, pro-oxidation status, and the ability to induce neuroinflammation were investigated in both in vitro and in vivo experimental studies. Compared with amphetamines, synthetic cathinones appear to have more moderate effects than their amphetamine congeners in terms of neurotoxic effects. However, many synthetic cathinone users take these substances simultaneously with other substances such as benzodiazepines, amphetamines, ecstasy, tetrahydrocannabinol, and ethanol and this abuse can modify their neurotoxic effects. Hence, it is important to understand the underlying mechanism of early neurotoxic effects in case of polysubstance use. In this review, we aimed to present up-to-date information on the abuse potential of synthetic cathinones, their legal status, mechanism of action, and particularly their neurotoxic effects.