Amphetamines, including methamphetamine and MDMA, are psychostimulants abused for their stimulant, euphoric, empathogenic, and hallucinogenic effects. These effects arise from acute increases in dopamine and serotonin neurotransmission. Beyond these acute effects, the drugs cause persistent damage to dopamine and serotonin nerve terminals through mechanisms such as excitotoxicity, mitochondrial damage, and oxidative stress. The review also covers emerging non-neuronal mechanisms that may contribute to this damage and the neuropsychiatric consequences of terminal damage. It compares methamphetamine and MDMA to other abused substances like cathinone (khat) and novel synthetic amphetamines known as 'bath salts'.
Psychedelic and empathogenic compounds hold therapeutic potential but are expensive and complex to study, with significant safety concerns. This review examines eight late-phase medicinal psychedelic studies in the FDA approval pipeline, including the FDA's denial of Lykos Therapeutics' New Drug Application for MDMA-assisted psychotherapy for PTSD. It also discusses California legislative proposals to legalize psychedelic compounds for adult use as a cheaper alternative, though these proposals lack thorough drug safety evaluation. The authors argue that the FDA should remain the appropriate agency to evaluate and approve these therapeutics.