Strategies for detecting subclinical monoamine depletions in humans

Given the reported increase in the recreational use of controlled substance analogs such as MDMA and related drugs, it is important to determine whether these drugs produce neurotoxic effects in humans. Several strategies available for detecting preclinical neurotoxicity to dopamine and serotonin neurons have been discussed, and their strengths and limitations have been listed. In addition, some promising strategies that are still in the development stage (e.g., PET) have been mentioned. None of the available methods for detecting neurotoxicity is conclusive; therefore, converging lines of evidence will be essential to provide convincing indication of subclinical neurotoxicity in humans. Such studies will help define the public health risk of recreationally used drugs. Furthermore, documentation and determination of drug-induced neurotoxic changes may shed light on the pathophysiology of idiopathic neurodegenerative diseases involving monoaminergic neurons in humans and could be useful in the development of new treatment strategies. Finally, detailed neuropsychiatric evaluation of individuals with confirmed subclinical serotonergic neurotoxicity may enhance knowledge regarding the functional role of brain serotonin neurons in health and disease.