A cognitive-battery experiment found no significant average amphetamine benefit, but apparent benefits in lower-scoring participants and worsening in higher scorers. The authors could not rule out regression to the mean as a contributor to that subgroup pattern.
Chou and colleagues studied 60 healthy adults in a double-blind placebo-controlled crossover experiment with amphetamine 20 mg. The MATRICS Consensus Cognitive Battery measured multiple domains and a composite. Analyses examined the whole sample and subgroups defined by placebo scores and selected personality characteristics. This was not a treatment trial in patients with schizophrenia.
Amphetamine produced subjective and autonomic effects without significantly changing the overall composite or individual domain scores across the full sample. Changes were inversely related to placebo performance: lower placebo scorers tended to improve, and higher scorers tended to worsen. Defining groups by one measurement can select unusually low or high observations that move toward typical values on retesting, creating an apparent response difference.
The investigators evaluated but could not exclude that statistical explanation. The pattern should not be converted into a reliable rule that amphetamine helps every low performer and harms every high performer. It also does not establish a clinically useful personality-based prescribing test. A drug effect on mood or vital signs is not evidence of a cognitive benefit when the cognitive comparison is null. The study is useful for designing future trials with independent baseline assessments and prespecified subgroups, while leaving patient efficacy and individual prediction unresolved.
See a null treatment-specific executive-function comparison.