Experimental Medicine studies in psychiatric populations test specific, mechanistic hypotheses related to the biology of
mental illness, by combining well-characterized neurobiological probes and laboratory-based measures of behavioral performance and neurobiology. However, scientific inquiry through the acute administration of
psychoactive drugs to patients with serious
mental illness raises important ethical issues. These issues arise in studies in which the psychostimulant,
amphetamine, is used as an Experimental Medicine probe in patients with
schizophrenia. In this study, we summarize relevant aspects of our experience with acute, laboratory-based challenges of
amphetamine in
schizophrenia patients.
Schizophrenia patients participated in one or more Experimental Medicine studies involving limited doses of
amphetamine with clinical monitoring, over a 4-year period. Acute (within hours of ingestion; collective n = 53), subacute (three active doses over 4 weeks; n = 28), and long-term (mean = 17 months after ingestion; n = 19) effects of
amphetamine ingestion were assessed. In
antipsychotic (AP)-medicated
schizophrenia patients,
amphetamine was associated with no detrimental subjective, autonomic, or functional changes. Symptoms assessed acutely, subacutely, or long term were either unchanged or diminished. No adverse acute, subacute, or long-term consequences from the Experimental Medicine use of
amphetamine in
antipsychotic-medicated
schizophrenia patients were detected. These findings do not address the safety or effectiveness of the use of
amphetamine in unmedicated patients, or as an adjunctive treatment for
schizophrenia. Indeed, it is important to distinguish evidence-based risks of
symptom exacerbation in an Experimental Medicine setting vs. risks associated with long-term, daily clinical use or even misuse of
amphetamine.