3.3 Neuroplastic effects
In addition to affecting the sensory and inflammatory aspects of pain, psychedelics may also influence chronic pain through their ability to promote neuroplasticity.25 Neuroplasticity is the brain’s ability to reorganize neural pathways and forge new connections.39 Neuroimaging studies have revealed that chronic pain conditions such as chronic low back pain, complex regional pain syndrome, and osteoarthritis are all associated with altered functional connectivity between spatially distinct brain regions.40-43 For example, functional MRI (fMRI) studies have demonstrated that chronic low back pain is associated with a reorganization of functional connectivity between sensory, cognitive, and limbic areas (e.g., nucleus accumbens and the prefrontal cortex [PFC]). It is also associated with a disruption of the default mode network (DMN) — a system of connected brain areas that show increased activity when the individual is passively resting and mind-wandering. These connectivity changes likely reflect maladaptive plasticity and reorganization of functional brain circuits due to persistent pain signaling.40,41 By stimulating neural plasticity and regrowth of connections between brain cells,44 psychedelics could potentially counteract these observed connectivity alterations and remodel the disrupted networks involved in pain. As a result, psychedelics could temporarily disrupt these patterns of brain activity, providing a window for rewiring neural connections and restoring more optimal network functioning. This could potentially disentangle the clustering of sensory, cognitive, and affective components of pain, enabling a transformed understanding of the pain experience.
Relatedly, these compounds have been theorized to be linked with changes in entropy and complexity in brain dynamics,45,46leading to changes that may be helpful in breaking out of rigid cognitive and behavioral patterns. By disrupting these patterns, psychedelics may facilitate the adoption of more adaptive pain-related beliefs, thought processes, and actions.