Rodent experiments found rewarding and reinforcing effects of lisdexamfetamine, alongside dopamine changes in isolated tissue preparations. These results support dependence-liability research, but do not quantify addiction risk during oral human treatment.
The study tested conditioned place preference in mice using intraperitoneal lisdexamfetamine and self-administration in rats using intravenous infusions. Cocaine served as a behavioral positive control. These are preclinical experiments rather than clinical case reports or human treatment trials.
Place preference measures time spent in a drug-associated environment. Self-administration measures operant responding for drug delivery. Neither endpoint is identical to the clinical syndrome of dependence in a person.
The researchers also exposed striatal synaptosomal preparations to lisdexamfetamine and methamphetamine and measured dopamine using HPLC with electrochemical detection. Methamphetamine served as the positive comparator in that assay.
Those measurements concerned dopamine in a tissue-based experimental system, not lisdexamfetamine or amphetamine concentrations in human blood. The biochemical exposures also differed from the repeated behavioral procedures. Observing both effects does not itself prove that the measured dopamine change caused the behavioral effect.
Lisdexamfetamine is a prodrug of d-amphetamine, but the study’s injected and isolated-tissue conditions do not reproduce ordinary oral clinical dosing. Route, metabolism, exposure profile and species affect how the results should be generalized.
The authors acknowledged limitations of the single-exposure biochemical assay and the need for further analytical work. The study supports potential reward and reinforcement under its experimental conditions. It cannot establish human incidence of dependence, predict a particular patient’s outcome or identify an impairment threshold.
Read our analysis of dependence-event interpretation in human surveillance.
Potential for Dependence on Lisdexamfetamine – In vivo and In vitro Aspects. doi:10.4062/biomolther.2016.080.