Conditioned Placebo Analgesia Persists When Subjects Know They Are Receiving a Placebo

• We test whether placebo analgesia persists when subjects know they received a placebo.
• We test whether this “open-label” analgesia depends on the amount of conditioning.
• Subjects who have more conditioning continue to show placebo effects independent of expectation for pain relief.
• Conditioning with a placebo before a control impairs subsequent analgesia.

Belief in the effectiveness of a placebo treatment is widely thought to be critical for placebo analgesia. Many types of placebo responses—even those that depend on conditioning—appear to be mediated by expectations that are strengthened as treatment cues are reinforced with positive outcomes. However, placebo effects may occur even when participants are aware they are receiving a placebo. To address the question of whether conditioned placebo analgesia can persist in the absence of expectations, we studied the effects of long (4 days) versus short (1 day) conditioning to a placebo treatment. After an initial placebo test, a “reveal” manipulation convincingly demonstrated to participants that they had never received an active drug. Placebo analgesia persisted after the reveal in the long conditioning group only. These findings suggest that reinforcing treatment cues with positive outcomes can create placebo effects that are independent of reported expectations for pain relief.PerspectiveThis article demonstrates a form of placebo analgesia that relies on prior conditioning rather than current expected pain relief. This highlights the importance of prior experience on pain relief and offers insight into the variability of placebo effects across individuals.