Effects of opioids and stimulants on the respiratory system

Drug overdose remains an urgent public health concern as it is a leading cause of fatal injury in the United States, with approximately 90% being attributed to opioid-induced respiratory depression from synthetic opioids. This statistic is primarily driven by the rise in the use of fentanyl, a potent synthetic opioid and its increased use in combination with stimulant drugs. The rise in the combined use of opioids and stimulants raises questions about pharmacological and physiological interactions, and its implication for the treatment of their addictive consequences and of overdoses. Though opioid-related fatalities are due to respiratory depression and stimulant fatalities predominantly from cardiac disruption, co-use creates interactions that remain under studied. Similarly, how medications designed to treat opioid use disorder impact respiration has been mostly neglected. Here, we review preclinical and clinical studies on the effects of opioids and stimulants on respiration, focusing on brainstem respiratory nuclei, and explore implications for advancing prevention and treatment strategies for drug-related overdose.