Figure 3: Psilocybin as a psychophysical adaptogen in chronic pain rehabilitation.

A: Depicts a strong self-pain enmeshment cycle. The red spots and lightning bolts indicate maladaptive communication between key brain regions responsible for pain processing. The circle to the left also represents one-way top-down control and cognitive bias towards negative self-referential processes mediated by the DMN, SN and FPN, locking the pain patient into acute and recurrent maladaptive cognitive-affective states that give rise to fear avoidance, pain catastrophizing, kinesiophobia, and symptoms of depression and anxiety (Note, red bars imply rigid/entrenched activity patterns). Such preestablished priors are also reinforced by aberrant bottom-up sensorimotor processing and hypervigilance associated with the wounded area. B: Represents a putative pathway through which psilocybin may engender a loosening of the self-pain enmeshment cycle. Alterations in pain related self-conceptions and flexible meaning making processes allow the patient to reevaluate the significance of bottom-up sensorimotor information in a novel way. The circle to the left also notes altered network dynamics between the DMN, SN, and FPN facilitating a reorganization of high-level priors previously prohibiting exercise engagement and increasing other adaptive faculties including increased mood and openness to experience. The subsequent release of entrenched top-down cognitions allows the patient to assume a premorbid identity less encumbered by their pain symptoms. Abbreviations: DMN; Default Mode Network, SN; Salience Network, FPM; Frontoparietal Network; ROM; Range of motion, Enmeshment model adapted from Pincus and Morley (2001).⁷¹