A psychedelic compound best known for its effects on the brain may help prevent one of chemotherapy's most debilitating side effects – chemotherapy-induced peripheral neuropathy (CIPN), researchers report. In mouse models, as few as two doses of psilocybin given before treatment durably prevented CIPN through multiple cycles of chemotherapy, while preserving both nerve function and the therapies' tumor-killing effects. No previous studies have examined the prophylactic potential of psilocybin for CIPN, the authors say. CIPN is a common and often debilitating consequence of platinum-based cancer treatments. Affecting more than 60% of patients, CIPN causes persistent pain, burning sensation, and numbness. This condition often limits or interrupts potential lifesaving cancer treatment and can greatly reduce the quality of life of survivors. However, despite its clinical burden, there are no effective preventative strategies, and current treatments provide only modest relief. Here, Mario Heles and colleagues investigated psilocybin, a naturally occurring psychedelic compound, as a potential treatment for CIPN.
CIPN is linked to failures in mitochondrial function and the progressive degeneration of the farthest-reaching portions of sensory nerve fibers. Previous research has suggested that psilocybin promotes neural plasticity through the 5HT2A receptor. Because 5HT2A receptors may also influence mitochondrial production and sensory pain pathways, Heles et al. hypothesized that psilocybin could potentially produce lasting remodeling and protection within the nervous system. In tumor-bearing animals undergoing repeated, clinically relevant cycles of platinum- and taxane-based chemotherapy, the authors showed that psilocybin administration before chemotherapy durably prevented CIPN through as many as six chemotherapy cycles without reducing chemotherapy's antitumor effects. "The study reframes CIPN not simply as an inevitable consequence of neuronal injury but as a failure of resilience that may be amenable to early intervention," writes Maria Maiarú in a related Perspective. "The challenge now is to translate these mechanistic insights into carefully designed clinical trials…" she says. Maiarú also notes that the effect of the findings extends beyond chemotherapy-induced neuropathy in terms of potential for disease-modifying approaches to chronic pain.
