ObjectiveClassical conditioning of insulin effects was examined in healthy humans using a placebo-controlled design. This study examined whether subjects who experienced a conditioned stimulus (CS) paired with insulin in the acquisition phase of a conditioning protocol would show a conditioned decrease of blood glucose when receiving the CS with a placebo injection in the test phase.MethodsTwenty healthy male students were assigned either to group 1, which received insulin (0.035 IU/kg IV), or to group 2, which received IV saline on 4 consecutive days (acquisition). On day 5 (test), both groups were injected with saline. The CS was an olfactory stimulus. Blood glucose, serum insulin, plasma glucagon, plasma catecholamines, serum cortisol, and symptoms were repeatedly measured during each session.ResultsIn the test phase, group 1 reacted with a significantly larger decrease of blood glucose after presentation of the CS than group 2. Within group 1, a larger conditioned blood glucose decrease was associated with features that enhance classical conditioning (ie, intensity of the unconditioned response and intensity of the CS). Furthermore, in group 1, there was an increase of baseline insulin from day 1 to day 5 and a tendency for insulin reduction after CS presentation. Groups also tended to differ in cortisol and neuroglycopenic symptoms after CS presentation.ConclusionsConditioned effects in blood glucose are in accordance with the predictions. As a result of the exploratory analyses, our data also provide hints about conditioned changes in insulin, counterregulatory hormones, and symptoms.