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.