The full spectrum of opioid effects

ongoing

Opioids are irreplaceable and effective analgesics– at the group level. However, clinicians still cannot predict how much pain relief each patient will achieve, nor who will develop addiction. By treating the variability of opioid effects as noise, the group-based efficacy studies fail to explain why opioids relieve pain in some people, but not in others. Here, I will turn the current approach on its head. By harnessing the valuable information inherent in opioids’ variable and diverse effects, I aim to achieve a breakthrough in our ability to predict individual patient responses to opioids and enable effective personalised pain treatment. SpectrO has three main objectives: 1) First, I will employ large-scale data to generate robust and reproducible evidence on the full spectrum of opioid effects and resolve key controversies in the opioid literature (WP1: comprehensive samples). Next, I will hone in on each extreme of the opioid effects spectrum to: 2) Answer why opioid effects are so variable and diverse. A newly discovered human genetic knockout model affords unprecedented insights into human endogenous opioid function, far beyond the current state-of-the-art (WP2: opioid-insensitive sample). 3) Produce randomised controlled evidence at the individual level through a N-of-1 case series with double-blind dose titration for individual dose efficacy determination. WP3 represents a leap forward in opioid research, promising to close the gap between the group-based trials (which show no benefit of long-term opioids) and the clinical experience that some patients do benefit (opioid-sensitive sample). My unique track record in leading large interdisciplinary opioid trials and conducting innovative literature syntheses lends feasibility to this ambitious project. SpectrO will set a new direction for opioid research, offering powerful new resources and methods to resolve key mechanistic questions and urgent public health issues on pain and addiction.