Psilocybin may prevent nerve damage caused by chemotherapy

Researchers at the University of Texas MD Anderson Cancer Center have discovered that psilocybin may prevent chemotherapy-induced peripheral neuropathy (CIPN), a common and debilitating side effect of cancer treatment. The findings suggest a biological mechanism that protects nerve endings from the damage typically caused by potent chemotherapy drugs.

In tests using human neurons and mouse models, psilocybin helped maintain the transport of mitochondria to nerve endings. This process is usually disrupted by drugs such as cisplatin, leading to energy failure in the nerves and subsequent sensory loss. In mouse studies, subjects given two doses of psilocybin—equivalent to 25mg in humans—prior to cisplatin treatment exhibited significantly less pain sensitivity than those receiving cisplatin alone. The researchers found that psilocin, the active metabolite of psilocybin, activates the 5HT2A receptor to block the disruption of mitochondrial transport.

The burden of CIPN

Chemotherapy-induced peripheral neuropathy is a widespread complication, affecting approximately 75% of cancer patients undergoing chemotherapy to some extent. The condition is characterized by numbness, tingling, and chronic pain in the extremities. It occurs when chemotherapy drugs disrupt microtubules, preventing essential energy-producing mitochondria from reaching the ends of nerves. This causes the nerves to retract, resulting in long-term sensory impairment.

Currently, medical options for CIPN are limited. Treatments such as the antidepressant duloxetine are used to manage the condition, but they typically provide only moderate pain relief and do not prevent the onset of the neuropathy itself. This research represents a shift toward prevention rather than symptom management.

Clinical implications

Preventing the onset of CIPN could fundamentally change the trajectory of cancer care. Beyond improving the quality of life for survivors, preventing nerve damage could reduce the need for clinicians to lower chemotherapy doses or interrupt treatment cycles due to patient intolerance. Such stability in dosing could potentially lead to better overall cancer survival outcomes.

If these findings are replicated in humans, patients could avoid the long-lasting sensory problems and chronic pain that often persist long after cancer has been successfully treated.

Next steps for human trials

To verify these results in humans, a randomized controlled trial (NCT07227909) is scheduled to begin in November. The study will involve approximately 80 patients diagnosed with breast, colorectal, or head and neck cancer to test the efficacy and safety of the compound.

Despite the promising data, medical experts warn against self-medicating. Researchers at MD Anderson caution that psilocybin has not yet been proven safe or effective for patients undergoing chemotherapy and could interact dangerously with cancer medications.