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.