Reinforcing, subject-rated, and physiological effects of intranasal methylphenidate in humans: a dose-response analysis.

The results of previously published reports suggest that oral methylphenidate has potential for abuse. An increase in insufflation of methylphenidate has been reported recently. To our knowledge, however, there are no published reports that examined the effects of intranasal methylphenidate. The purpose of this experiment was to characterize the reinforcing, subject-rated, and physiological effects of intranasal methylphenidate (0, 10, 20, and 30 mg). Eight volunteers (five males and three females) with recent histories of recreational stimulant use were recruited to participate in this experiment. Drug doses were administered in a double-blind fashion under medical supervision, but for safety purposes they were administered in ascending order. Intranasal methylphenidate increased the crossover point on the Multiple-Choice Questionnaire in a linear fashion, which suggests that intranasal methylphenidate functioned as a reinforcer. Intranasal methylphenidate also produced linear dose-dependent prototypical stimulant-like subjective effects (e.g. increases in ratings of Good Effects and High). Intranasal methylphenidate increased heart rate as a function of dose, but the magnitude of this effect was not clinically significant (i.e. average peak heart rate following administration of the highest dose was less than 82 beats per min). The results of this study suggest that across a range of doses, intranasal methylphenidate produces behavioral effects that are characteristic of abused stimulants. Future studies should test higher doses and directly compare the behavioral effects of intranasal methylphenidate to those of a prototypical abused stimulant (e.g. cocaine).