6.1.1. Choice of pain- and opioid-related outcomes
A careful selection of pain- and opioid-related outcomes is necessary to provide clinically relevant evidence. As discussed in this review, the pain experience is multifaceted, composed of sensory, affective, and cognitive components. Therefore, a combination of mechanistic human laboratory studies and clinical trials broadly examining various components of the pain experience is warranted to understand the analgesic effects of psychedelics. Early analgesic signals may be identified using a combination of laboratory pain techniques, such as quantitative sensory testing (QST),120 a psychophysical tool to reliably assess analgesia and pain modulation121; along with psychological constructs assessing cognitive-affective components of pain (i.e., pain attentional bias, pain catastrophizing, self-efficacy, and fear avoidance).6,122 Quantifiable outcomes will be key to assessing pain-related functioning. These include measures of physical functioning and activity (e.g., pedometer count). The specific choice of pain-related outcomes can be tailored to the needs of each clinical population.
Likewise, the experience of using opioids, whether medically or non-medically, is also complex and multifaceted. Human laboratory studies are well-suited to identify the potential therapeutic effects of early stages of opioid withdrawal, various types of opioid craving (e.g., pain-, stress-, and cue-induced craving), and acute changes in hedonic states associated with chronic opioid exposure (e.g., hypohedonia and anhedonia).123,124 Longer-term clinical trials should include real-world outcomes such as the success of induction onto MOUD, treatment retention, adherence to MOUD, and the MOUD doses required to suppress craving and withdrawal. Studies specifically including persons with co-occurring OUD and chronic pain are required since a third of people with OUD also have chronic pain and this population has unique clinical needs and treatment trajectories. In summary, a comprehensive assessment of pain- and opioid-related outcomes is paramount to generate clinically pertinent evidence.