HOUSTON, SEPTEMBER 3, 2026 ― In a breakthrough study, researchers at The University of Texas MD Anderson Cancer Center discovered that psilocybin given before chemotherapy prevented the onset of nerve injury in preclinical models, even after repeated treatment cycles, which could help prevent pain, numbness and other common chemotherapy side effects.
The study, published in Science and co-led by Moran Amit, M.D., Ph.D. , professor of Head and Neck Surgery , and Patrick Dougherty, Ph.D. , professor of Pain Medicine , uncovers a previously unrecognized neuroprotective role of serotonin receptors and suggests psilocybin as a first-in-class intervention for the prevention of chemotherapy-induced peripheral neuropathy .
"There is an urgent need for treatments that prevent nerve injury without interfering with lifesaving chemotherapy," Amit said. "These findings offer important insights into how psilocybin may protect nerves before damage occurs, rather than treating symptoms after they become persistent. At UT MD Anderson, we are actively exploring the multiple facets of psychedelics to pursue interventions that improve the lives of our patients."
What is chemotherapy-induced peripheral neuropathy and how does it affect patients?
Chemotherapy is a common treatment that is beneficial for many cancer types, but it can also damage normal cells, including nerves. This peripheral neuropathy, or nerve injury, can result in many of the side effects associated with chemotherapy, such as pain, increased sensitivity to cold, numbness and loss of sensation, all of which can persist beyond treatment. Some patients may also experience changes that impact their balance or ability to continue life-saving treatments, significantly impacting their quality of life. Established nerve injury often is irreversible, and existing treatments offer limited benefits.
What is psilocybin and how could it prevent nerve injury?
Psilocybin is a naturally occurring psychedelic compound that currently is under investigation for neuropsychiatric and neurological disorders. Psilocybin can temporarily allow the brain to reorganize itself and form new neuron branches that could help avoid nerve injury.
In this study, the researchers used several preclinical models to examine the effects of psilocybin on nerves and evaluate whether it could be used to prevent peripheral neuropathy after chemotherapy.
How did the researchers discover the neuroprotective effects of psilocybin?
The researchers discovered that psilocybin directly affects the peripheral nervous system through serotonin 5-HT2A receptors. In preclinical models, as few as two doses of psilocybin given before chemotherapy prevented hypersensitivity to cold, protected sensory nerve endings and preserved touch sensation while also maintaining chemotherapy's antitumor activity. These results were consistent even when models were given repeated chemotherapy cycles with cisplatin, paclitaxel and docetaxel.
Blocking the 5-HT2A pathway reversed these neuroprotective effects, while using a non-hallucinogenic compound that activates the same receptors produced similar protection to psilocybin.
Additionally, researchers found that cisplatin depleted mitochondria – the structures that produce energy inside cells – and reduced their movement inside nerve fibers. Further, psilocybin activated a specific signaling pathway that preserved mitochondrial trafficking after chemotherapy, maintaining adequate energy levels at the nerve endings.
"Psilocybin does more than reduce pain signals by protecting the nerves, themselves, through energy delivery," Dougherty said. "This neuroprotective effect could help patients withstand the stress of chemotherapy, maintaining sensation, mobility and quality of life during treatment and long into survivorship."
What does this mean for patients and what's next for this research?
These preclinical findings are the basis for an upcoming Phase 2 clinical trial (NeuroGuard, NCT07227909) evaluating psilocybin during chemotherapy in patients with multiple cancer types to determine whether the mechanisms observed in this trial translate to clinically meaningful reductions in peripheral neuropathy. Other ongoing trials, led by Amit, currently are examining the effects of psilocybin-assisted psychotherapy for patients with anxiety and/or depression.
These studies are part of UT MD Anderson's Cancer Neuroscience Program, a comprehensive initiative that examines the interactions between cancer and the nervous system, taking a multidisciplinary approach to enhance patient quality of life.
