Comparison of the hot-plate pain effect between three inhalation methods and subcutaneous injection of heroin

Heroin, a widely abused opioid, is frequently consumed via inhalation; however, the majority of existing studies have focused on traditional administrations. This study aimed to compare the analgesic effects of heroin across different deliveries to elucidate the unique characteristics of inhalation. Two distinct inhalation exposure systems (nasal and systemic) were established and validated for stability. Liquid chromatography-tandem mass spectrometry was used to quantify blood concentrations of heroin and its metabolite 6-monoacetylmorphine following subcutaneous injection and three intratracheal/inhalation administrations, establishing dose-concentration linearity for cross-comparison at equivalent blood concentration levels. The analgesic of heroin across four different administrations were assessed by the hot plate pain test while comparing outcomes based on both blood and intracerebral drug concentrations. The findings indicated that both inhalation systems exhibited stable drug delivery, with linear correlations between exposure chamber concentration, administered dose, and resultant blood concentration. A logarithmic correlation was identified between the administration duration and blood concentration levels. Analgesic assessments revealed that significantly enhanced effects in both inhalation groups compared to subcutaneous injection, despite lower delivered doses. At the median effective dose (ED 50 ), olfactory bulb drug concentrations in inhalation were approximately eight-fold higher than in subcutaneous and intratracheal groups, while blood concentrations showed no statistical difference. This study validated that inhaled heroin produces stronger analgesic effects than subcutaneous injection, likely attributed to the mechanism of direct brain entry via the olfactory pathway, which enhances psychoactive potency. These findings highlight the distinct pharmacological properties of inhaled heroin, providing critical insights into its abuse potential.