Translated from our German original by AI. The German text was researched, written, and edited by the Psychedelia Foundation team and remains the authoritative version.
A new study points to a possible approach for preventing chemotherapy-induced peripheral neuropathy (CIPN). In several mouse models, psilocybin prevented the sensory disturbances caused by neurotoxic chemotherapy drugs from developing. The researchers backed the findings with work on human nerve cells and tissue.
CIPN is among the common side effects of certain chemotherapies, particularly platinum compounds and taxanes. It can cause pain, cold sensitivity, numbness and impaired touch perception, and it can persist for long periods. There is still no established drug treatment that reliably prevents it.
In the experiments, mice received two doses of psilocybin before chemotherapy began. The treatment prevented heightened pain sensitivity from developing, even over repeated chemotherapy cycles. The protective effect lasted up to eight months in the models studied. In tumor-bearing mice, the antitumor effect of the chemotherapy was preserved, and no changes were found in the immune cytokines examined.
Further experiments suggested that the effect is mediated through the serotonin 5-HT2A receptor. The neuroprotective effect apparently did not depend on the psychedelic activity of psilocybin: a non-psychedelic 5-HT2A agonist achieved comparable protection in these experiments.
The researchers identified the maintenance of mitochondrial transport along the axons of sensory nerve cells as a possible mechanism. Mitochondria supply the nerve endings with energy. The chemotherapy drugs studied impaired this transport and thereby reduced the energy supply to the nerve endings far from the cell body. Psilocybin prevented this disruption and so preserved the structure and function of the peripheral nerve endings.
The researchers link the effect to a signaling cascade of TrkB, Akt, PAK5, MAP2 and KIF5B that is involved in transporting mitochondria within the axons. They also observed a normalization of the changes in cortical electrical activity brought on by the chemotherapy.
The work was not carried out in animals alone. The researchers also examined sensory neurons derived from human stem cells, freshly isolated human peripheral nerves and skin biopsies. The results support the assumption that the network linked to the 5-HT2A receptor for mitochondrial regulation is also present in the human nervous system.
This does not yet establish that psilocybin prevents chemotherapy-induced neuropathy in humans. The efficacy data come from preclinical models. Clinical trials now have to determine whether the neuroprotective effect carries over to cancer patients, and whether psilocybin or non-hallucinogenic 5-HT2A agonists are suitable and safe for this purpose.
The study was published in Science in September 2026. The findings open up a possible new line of research into preventing a side effect of certain cancer therapies that has so far been difficult to treat.
