Expectancy for Adderall influences subjective mood and drug effects regardless of concurrent caffeine ingestion: A randomized controlled trial

Rationale Nonmedical prescription stimulant use (NPS; use without a prescription or in ways other than prescribed) is common among college students. Despite the potential for negative consequences, students continue engaging in NPS for cognitive enhancement purposes, which may be maintained by expectancy and placebo effects. Objectives This study examined if a placebo administered under the guise of Adderall influenced subjective mood/drug effects and cognitive performance. Furthermore, this study examined if concurrent caffeine ingestion incrementally enhanced Adderall-related placebo effects. Methods Undergraduate students with features that put them at elevated risk for NPS ( N = 121) completed measures of mood and drug effects and cognitive assessments on two separate laboratory visits in this parallel randomized controlled trial. Visit 1 was a baseline control visit, on which no drug was expected or received. On visit 2, subjects were randomized to: (1) expect/receive no drug (control); (2) expect Adderall/receive placebo; or (3) expect Adderall/receive 200 mg caffeine. Results There were several significant condition × visit interactions for subjective effects, including amphetamine effects, energy and efficiency effects, and feeling high. In most cases, participants who expected Adderall reported greater positive subjective effects on visit 2 compared to controls; however, there were generally not incremental enhancements for those ingesting caffeine compared to placebo. There were no significant effects for any cognitive tests. Conclusions Expectation for prescription stimulant effects influenced subjective outcomes in a sample of high-risk college students. These findings may inform expectancy challenge interventions to reduce NPS. Trial registration ClinicalTrials.gov Identifier: NCT03648684.