Starting strong: A descending analgesic dosing scheme enhances pain relief compared to a conventional ascending dosing scheme

Managing pain while minimizing opioid-related harm remains a central clinical challenge. Enhancing drug-related placebo effects has been proposed as one strategy for reducing opioid consumption, yet current dosing guidelines which recommend starting analgesic treatment at a low dose and titrating upward may inadvertently generate negative treatment expectations, since initial drug encounters are often associated with minimal pain relief. This study tested whether the inverse approach of a descending dosing scheme that starts with a strong analgesic dose more effectively enhances placebo-related analgesia than the conventional ascending scheme. Eighty-two healthy participants underwent a heat pain paradigm involving a sham analgesic treatment delivered at three different efficacy levels (low, medium, high). Participants were randomly assigned to a descending (high-to-low) or ascending (low-to-high) treatment-history sequence before receiving an identical, medium-intensity treatment during a subsequent test phase. The descending group showed significantly greater pain relief during the test phase than the ascending group, despite receiving identical treatment. These findings suggest that initiating analgesic treatment with a high, effective dose can amplify placebo-related analgesia relative to conventional dosing schemes, offering a potential strategy for reducing cumulative opioid use without compromising pain relief.