Comparison of the Behavioral and Cardiovascular Effects of Intranasal and Oral d-Amphetamine in Healthy Human Subjects

Recent reports indicate an increase in intranasal use of prescription oral stimulant medication. However, there do not appear to be any published clinical studies that have characterized the behavioral and cardiovascular effects of intranasally administered d-amphetamine, which is commonly prescribed for Attention Deficit Hyperactivity Disorder. In this study, a range of d-amphetamine doses (0, 16, 24, and 32 mg/70 kg) were administered as an intranasal solution delivered using a mucosal atomization device. Equal oral doses were included for comparison. Assessments were conducted before and at regular intervals for 3 hours following drug administration and included self-reported drug-effect questionnaires, cardiovascular indices, a performance task, and 2 measures of impulsivity. d-Amphetamine produced prototypical stimulant effects (eg, increased subject ratings of Stimulated and Like Drug, elevated heart rate and blood pressure, and improved rate and accuracy on the digit symbol substitution task) irrespective of dose, but the onset of these effects was generally earlier following intranasal administration, with significant effects emerging 15 to 30 minutes after intranasal dosing and 45 to 60 minutes after oral dosing. These results demonstrate that intranasal administration of d-amphetamine results in a more rapid onset compared to oral dosing, which could be associated with the popularity of intranasal prescription stimulant use and an enhanced potential for abuse.