Early research suggests that psilocybin, the psychoactive compound found in "magic mushrooms," may help protect peripheral nerves from damage caused by chemotherapy, according to a study published in the journal Science. The study, conducted on mice, found that two doses of psilocybin given before chemotherapy prevented nerve damage that can lead to pain, numbness, and increased sensitivity to cold and touch. This protective effect lasted through up to six rounds of chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) affects about one-third to one-half of people undergoing certain types of chemotherapy. In severe cases, it can force doctors to reduce or stop chemotherapy and may lead to mobility issues, increasing the risk of falls and fractures. This condition is a common and often painful side effect of cancer treatment, and finding ways to prevent or reduce it is a major focus for researchers. The researchers initially aimed to identify compounds that promote neuroplasticity, the brain and nervous system's ability to adapt and reorganize. After testing several psychedelic substances, they found that psilocybin was the most effective in alleviating neuropathy symptoms. The study revealed that psilocybin protected against CIPN through a process called mitochondrial trafficking, which involves moving mitochondria—organelles that produce energy—along microtubules to reach distant nerve endings. In experiments using human sensory neurons and peripheral nerves, the team found that cisplatin, a chemotherapy drug known to cause neuropathy, reduced the number of mitochondria and ATP (adenosine triphosphate, the energy currency of cells) in nerve projections. Psilocybin, however, helped maintain normal mitochondrial movement and ATP levels in these nerve endings. The effect of psilocybin on mitochondrial trafficking was found to rely on the serotonin receptor 5-HT2A, which is also responsible for many of its hallucinogenic effects. A compound called TBG, designed to activate 5-HT2A without causing hallucinations, also protected mice from neuropathy. While the results are promising, the researchers have not yet tested whether psilocybin prevents neuropathy in humans. They are now preparing a clinical trial at MD Anderson Cancer Center to explore this further. This study is part of MD Anderson's Cancer Neuroscience Program, which aims to improve the quality of life for cancer patients by studying how cancer and the nervous system interact.