The following is a summary of “Amphetamines modulate fentanyl-depressed respiration in a bidirectional manner,” published in the February 2023 issue of Drug and Alcohol Dependence by Elder et al.

The opioid epidemic remains a critical public health emergency confronting the United States. The escalating incidence of overdose fatalities can be attributed to the widespread utilization of Fentanyl and other synthetic opioid agonists. These substances are frequently employed as replacements for other opioids and are also added to psychostimulants as adulterants. Fatalities associated with opioids are commonly attributed to fatal respiratory depression. However, the impact of concurrent usage of psychostimulants and opioids on respiratory toxicity remains uncertain. Given the notable surge in cases of psychostimulant overdose by more than three times since 2013, with approximately half of these cases involving opioids, this is a crucial matter to address.

The respiratory effects of Naloxone, d-amphetamine (AMPH), and (±)-methamphetamine (METH) were assessed about basal and fentanyl-induced depression. Minute volume (MVb) was measured on conscious, ambulatory mice using whole-body plethysmography. This aimed to assess the respiratory depression caused by fentanyl and how it was affected by varying doses of the experimental drugs. The administration of Naloxone resulted in an immediate reversal of respiratory depression caused by fentanyl, but only at the maximum tested dose of 10 mg/kg. Under basal conditions, both amphetamine (AMPH) and methamphetamine (METH) demonstrated bidirectional effects on minute ventilation (MVb), resulting in notable (P ≤ 0.05) reductions followed by increases in respiration as the dosage escalated.

In a state of depression, the reciprocal impacts of amphetamine (AMPH) and methamphetamine (METH) on breathing were intensified, thereby aggravating and subsequently reversing the depressive effects of fentanyl as the dosage was escalated. Based on the findings, concurrent usage of amphetamines and fentanyl may exacerbate respiratory depression. However, it is possible that the monoaminergic properties of amphetamines could be utilized to alleviate the effects of a fentanyl overdose.

Source: sciencedirect.com/science/article/abs/pii/S037687162200477X