Neurotoxicity of psychoactive substances: A mechanistic overview

The increasing abuse of psychoactive drugs represents a global public health burden, as recurrent exposure to these substances can cause neurodegeneration, premature ageing and negatively impact normal neurodevelopment. Although the basis of such neurotoxic effects is not completely elucidated, compelling evidence has shown that dysregulation of neurotransmission, disruption of mitochondrial function and dynamics, overproduction of ROS, impairment of neuroimmunomodulation, and epigenetic alterations are caused by many psychoactive substances (e.g., alcohol, cannabinoids, opioids, amphetamines and cocaine). Understanding the neurotoxicological profiles of psychoactive substances and the underlying pathways assumes major importance towards reaching improved risk assessment and treatment of drug use disorders. As such, we herein reviewed the most recent updates on the respective drug-induced cellular and molecular mechanisms.