Objective: Classical conditioning of insulin effects was examined in health
y humans using a placebo-controlled design. This study examined whether sub
jects who experienced a conditioned stimulus (CS) paired with insulin in th
e acquisition phase of a conditioning protocol would show a conditioned dec
rease of blood glucose when receiving the CS with a placebo injection in th
e test phase. Methods: Twenty healthy male students were assigned either to
group 1, which received insulin (0.035 IU/kg IV), or to group 2, which rec
eived IV saline on 4 consecutive days (acquisition). On day 5 (test), both
groups were injected with saline. The CS was an olfactory stimulus. Blood g
lucose, serum insulin, plasma glucagon, plasma catecholamines, serum cortis
ol, and symptoms were repeatedly measured during each session. Results: In
the test phase, group 1 reacted with a significantly larger decrease of blo
od glucose after presentation of the CS than group 2. Within group 1, a lar
ger conditioned blood glucose decrease was associated with features that en
hance classical conditioning (ie, intensity of the unconditioned response a
nd 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 a
fter CS presentation. Groups also tended to differ in cortisol and neurogly
copenic symptoms after CS presentation. Conclusions: Conditioned effects in
blood glucose are in accordance with the predictions. As a result of the e
xploratory analyses, our data also provide hints about conditioned changes
in insulin, counterregulatory hormones, and symptoms.