A controlled trial detected no correlation between dexamphetamine plasma concentrations and the cognitive outcomes it measured. That result limits a simple concentration-to-performance interpretation within this experiment; it does not prove that concentration is irrelevant at every dose or in every population.
Pfoser-Poschacher and colleagues randomized 60 healthy men to a single oral dose of dexamphetamine 30 mg, zolpidem 5 mg or placebo, with 20 participants per group. Attention, alertness and working memory were assessed at baseline and three and eight hours after dosing. Venous blood was processed to plasma, and drug concentrations were measured using liquid chromatography–mass spectrometry.
Mean dexamphetamine plasma concentrations were 70.8 ng/mL at three hours and 45.9 ng/mL at eight hours. These were plasma measurements of dexamphetamine after a known administered dose. They should not be relabeled as whole-blood methamphetamine concentrations or applied directly to an uncharacterized roadside specimen. Drug, matrix, timing and route are part of the result.
The investigators found no detectable relationship between plasma drug concentration and any measured cognitive outcome. Dexamphetamine reduced sustained-attention omissions relative to placebo at eight hours, but that benefit was not demonstrated at three hours, when mean plasma concentration was higher. Working-memory outcomes did not significantly change. The time course therefore did not support assuming that the higher measured concentration necessarily produced the larger tested cognitive effect.
The study tested one dose in healthy men and sampled only selected times and tasks. Restricted concentration ranges, sample size and individual variability can limit detection of a relationship. It also did not measure on-road driving. The findings cannot identify a concentration that guarantees safe performance or establish an impairment threshold. They demonstrate why a measured drug level, a subjective drug effect and a specific cognitive test result must be evaluated as related but distinct pieces of evidence.
See also the importance of identifying exactly what a measurement represents.