Assessment of human abuse potential of dasotraline compared to methylphenidate and placebo in recreational stimulant users

Abstract Aims The aim of this study was to evaluate the abuse potential of dasotraline, a novel dopamine and norepinephrine reuptake inhibitor with slow absorption ( t max , 10–12 h) and elimination ( t 1/2  = 47–77 h) that is in development for the treatment of attention deficit hyperactivity disorder (ADHD). Methods Recreational stimulant users ( N  = 48) who had specific experience with cocaine, and who were able to distinguish methylphenidate (60 mg) versus placebo in a qualification session, were randomized, in a 6-period, double-blind, crossover design, to receive single doses of dasotraline 8 mg, 16 mg, and 36 mg, methylphenidate (MPH) 40 mg and 80 mg, and placebo. The primary endpoint was the Drug Liking Visual Analog Scale (VAS) score at the time of peak effect (E max ). Results There were no significant differences between the 3 doses of dasotraline and placebo on the drug liking VAS at E max , and on most secondary endpoints. Both doses of MPH had significantly higher VAS-drug liking scores at E max relative to both placebo ( P P P P Conclusions In this study, dasotraline was found to have low potential for abuse, which may be, in part, related to its established pharmacokinetics (PK) profile, which is characterized by slow absorption and gradual elimination.