Amid the rise of psychedelics in the mental health space, researchers have begun to explore psilocybin as a potential treatment for chemotherapy-induced peripheral neuropathy.
A study published September 3 in Science showed that giving psilocybin prior to chemotherapy prevented the development of pain hypersensitivity caused by neurotoxic chemotherapies, with protection maintained up to 8 months in mice.
“This study is opening a new avenue for research on how to prevent those toxicities and how to expand the world of psychedelics and their different indications,” said Moran Amit, M.D., Ph.D., professor of head and neck surgery at The University of Texas MD Anderson Cancer Center and lead study author.
Chemotherapy-induced peripheral neuropathy (CIPN) is characterized by tingling, numbness or pain in the hands or feet. These sensations can arise during chemotherapy treatments in up to 68% of patients and affect nearly 30% of patients beyond six months.
Current treatments for CIPN include ice packs on the hands while receiving chemotherapy or Eli Lilly’s Cymbalta, a serotonin-norepinephrine reuptake inhibitor (SNRI), shown to give small amounts of symptomatic relief, explained Gregory Jones, M.D., assistant professor in the department of psychiatry at The University of Texas MD Anderson Cancer Center.
Psilocybin is a natural psychedelic compound found in many species of mushrooms. Once ingested, it acts as a prodrug that the body converts to psilocin, which acts as a serotonin 5-HT2A receptor agonist.
In the body, bundles of peripheral neurons make up nerve endings that are always stretching out to distal areas, such as the skin. This extension takes energy, which comes in the form of adenosine triphosphate (ATP) from the body’s natural energy source, the mitochondria.
When the body is exposed to chemotherapy, the nerves freeze and stop extending to distal sites, which can cause nerve endings to die if they cannot get back to distal sites quickly after the chemotherapy clears the body, Patrick Dougherty, Ph.D., professor of pain medicine at MD Anderson and lead study author, explained.
In the study, psilocybin given to mice before chemotherapy activated the serotonin 2a (5-HT2a) receptors on peripheral neurons and preserved mitochondrial transport down these cells, which is required for nerve survival.
“The 5-HT2a agonist [psilocybin] is speeding the transport machinery to get mitochondria back down to those distal sites to support them as they now recover from that, as the toxins cleared and the system starts to try to work like normal again,” Dougherty said.
The researchers uncovered this mechanism by using live cell imaging of mitochondria in human peripheral nerves in a dish, where they observed psilocybin preserving the active transport of mitochondria down the nerves.
Amit emphasized the importance of carefully regulating the dosing of psilocybin and monitoring patients post-treatment: “To do this uncontrolled outside of the clinical trial settings would be [irresponsible] and it might be even dangerous,” Amit said. “But in the settings that we've created here at MD Anderson, we are doing this in a safe manner.”
In April 2026, President Donald Trump ordered the FDA to prioritize reviews of psychedelic drugs for the treatment of mental illness. But prior to that push, Big Pharmas were already riding the psychedelics wave.
A year ago, AbbVie penned a $1.2 billion deal for Gilgamesh Pharmaceutical’s bretisilocin program for patients with major depressive disorder. Then in March 2026, Otsuka Pharmaceutical paid $700 million for Transcend Therapeutics and its MDMA analog for patients with post-traumatic stress disorder.
More recently, Eli Lilly acquired AtaiBeckley for $2.8 billion upfront.
Newer players are getting in on the action too, such as Jupiter Neurosciences, which shelled out $3.3 million upfront for Canada's PharmAla Biotech, in turn acquiring the U.S. rights to an MDMA drug to treat neuropsychiatric disorders.
In about a month, the researchers are launching the phase 2 interventional NeuroGuard trial assessing the efficacy of psilocybin in preventing CIPN in patients undergoing chemotherapy for breast, colorectal and head and neck cancers.