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

Abstract

Rationale: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Analgesia; Conditioning; Experimental pain; Human; L-DOPA; Placebo.