A controlled oral-dose experiment found later amphetamine exposure after lisdexamfetamine, without a significant reduction in peak drug-liking ratings compared with equimolar d-amphetamine. Delayed delivery did not automatically mean a lower peak subjective effect.
Dolder and colleagues studied 24 healthy volunteers in a randomized double-blind placebo-controlled crossover experiment. Research doses were lisdexamfetamine 100 mg and d-amphetamine 40 mg, selected to be equimolar. Repeated plasma sampling measured amphetamine exposure, while subjective ratings and vital signs characterized effects. These experimental doses and observations are not prescribing instructions.
After lisdexamfetamine, the plasma amphetamine rise had a longer lag and its peak occurred about an hour later on average. Maximum concentrations and total exposure did not significantly differ. Subjective and cardiovascular effects were also delayed, but peak ratings of drug liking and several other subjective effects were not significantly lower. Comparing equal milligram numbers of the two formulations would have asked a different question because lisdexamfetamine contains a linked prodrug moiety.
This was a single-dose oral experiment in healthy volunteers. Subjective liking is relevant to studying misuse potential, but is not observed addiction, compulsive use or a long-term incidence rate. The results cannot simply be transferred to different doses, chronic administration, other routes or every clinical population. Plasma amphetamine also does not identify which formulation was taken without additional exposure information. The study supports separating onset, peak effect and total exposure rather than assuming that a prodrug has a universally weaker effect. It did not measure driving impairment or establish a concentration at which an individual is safe.
See drug levels without a detectable cognitive correlation.