Effects of Gabapentinoids on Heroin-Induced Ventilatory Depression and Reversal by Naloxone

Despite an increasing prevalence of gabapentinoids (gabapentin and pregabalin) in opioid overdose deaths, little research has evaluated potentially harmful interactions between gabapentinoids and opioids. This study sought to determine the effects of gabapentinoids on the ventilatory depressive effects of heroin and their reversal by naloxone. Rats were given gabapentin, pregabalin, or saline prior to receiving increasing doses of heroin while ventilation was monitored using whole-body plethysmography. In some sessions naloxone was administered following the largest dose of heroin. The primary outcomes of this study were minute volume and Pause. Heroin dose-dependently reduced minute volume and increased Pause. Administration of naloxone dose-dependently reversed the effects of heroin on ventilation. Gabapentinoids did not alter the ventilatory depressive effects of heroin alone but reduced the potency of naloxone to reverse heroin-induced ventilatory depression. These preliminary findings emphasize the need for further research evaluating interactions between gabapentinoids and opioids related to substance misuse and overdose.