3.4 Impact on negatively valenced emotional states related to the pain experience
Both opioid use and chronic pain can disrupt pain modulatory systems, altering not only nociception, the process of encoding noxious stimuli, but also the affective component of pain, which can culminate in pain catastrophizing. This maladaptive state of unrelenting pain is characterized by magnification (heightening the threat value of pain-related stimuli), helplessness (lack of control over pain), and rumination (having a reduced ability to divert one’s focus away from pain-related emotions).
Beyond their impact on neural pathways, psychedelics could also influence the affective and psychological experience of pain, encompassing the feelings of unpleasantness, distress, suffering, and reactions to the long-term implications of living with chronic pain.47 The anterior cingulate cortex (ACC) is a crucial area in processing the emotional and affective aspects of pain.26,48 Psychedelics may modulate these affective aspects by altering activities in the ACC. Studies using task-free fMRI found that psilocybin reduces cerebral blood flow in the ACC, which was associated with the intensity of subjective effects of psilocybin.49 As a result, it is possible that psychedelics might also have the potential to lessen these negative emotions associated with pain. This is supported by evidence suggesting that psilocybin may mitigate similar affective phenomena, such as depressive rumination and obsessive thinking,50 which can resemble the fear of movement seen in chronic pain. Given that depressive and anxiety disorders often co-occur with chronic pain,51 psychedelics may provide a more comprehensive treatment strategy by targeting these affective aspects, which can often be equally hard to discern and equally debilitating for these patients.