The effect of dopamine on conditioned placebo analgesia in healthy individuals: a double-blind randomized trial

Better means to control placebo effects are key to optimizing treatment outcomes. Dopamine-based reward and learning mechanisms have been hypothesized to drive placebo effects. Here, we tested whether dopamine augmentation can modulate learned placebo effects.

We performed a randomized, double-blind parallel group study with 70 healthy adult participants to test whether a single oral dose of the dopamine precursor levodopa/carbidopa (100/25 mg) administered before the acquisition of conditioned placebo analgesia enhances the placebo response in an established experimental placebo model using heat pain.

Overall, the observed levels of placebo analgesia in our sample were low and not statistically significant. Levodopa, compared to placebo, only led to a marginal increase in placebo analgesia. Female participants tended to show larger placebo responses than male participants. Within the female subgroup, levodopa showed small-to-moderate effects on placebo analgesia; however, this effect was not statistically significant.

In summary, the present study could not provide evidence for a placebo augmenting effect of levodopa-enhanced dopamine levels in healthy subjects. Further studies are needed to elucidate whether placebo enhancement can be achieved through dopamine augmentation.