Amphetamine is a potent central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered in 1887 and exists as two enantiomers: levoamphetamine and dextroamphetamine. The mode of therapeutic action in ADHD is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. At higher dosages, they cause release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems. Amphetamine may also act as a direct agonist on central 5-HT receptors and may inhibit monoamine oxidase (MAO). In the periphery, amphetamines are believed to cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming affect. The drug interacts with VMAT enzymes to enhance release of DA and 5-HT from vesicles. It may also directly cause the reversal of DAT and SERT. Several currently prescribed amphetamine formulations contain both enantiomers, including Adderall, Dyanavel XR, and Evekeo, the last of which is racemic amphetamine sulfate. Amphetamine is also prescribed in enantiopure and prodrug form as dextroamphetamine and lisdexamfetamine respectively. Lisdexamfetamine is structurally different from amphetamine, and is inactive until it metabolizes into dextroamphetamine.

Cathinone is one of the biologically active alkaloids found in the khat shrub (Catha edulis). Due to its psychoactive properties, khat has been known and utilized for ages by the inhabitants of East Africa and the northeastern parts of Arabian Peninsula. In many regions, chewing of freshly collected khat leaves (thus liberating cathinone, which affects the central nervous system) is considered a matter of culture and local tradition. Because of their structural similarity to amphetamine, cathinone and its analogs are often denoted as “natural amphetamines”, and the only structural difference between amphetamine and cathinone is the presence of a carbonyl group in the α-position of cathinone’s side chain. Similar to amphetamine, cathinone and its analogs are characterized by stimulating, euphoric, and empathogenic properties. Due to their effects on the central nervous system, the first synthetic cathinone derivatives were synthesized for medicinal purposes in the early twentieth century, but they began attracting wider attention around the year 2000. At that time, synthetic cathinones were included in a broader group of psychoactive compounds denoted as “legal drugs” or “designer drugs”