Preclinical Data Show Psilocybin Cuts Chemotherapy-Induced Peripheral Neuropathy Incidence by 40 Percent in Rodent Models

Researchers at Johns Hopkins and the University of Maryland administered 1 mg/kg psilocybin or vehicle to Sprague-Dawley rats one day before a standard paclitaxel regimen. Over four weeks they tracked von Frey filament thresholds, intra-epidermal nerve fiber density, and inflammatory cytokines. Psilocybin-treated animals retained 60 percent higher sensory thresholds and showed 35 percent less axonal loss than controls, effects that persisted after drug clearance.

The mechanism appears to involve 5-HT2A receptor-mediated anti-inflammatory signaling and enhanced BDNF expression rather than direct analgesia. This aligns with emerging human data on psilocybin for chronic pain and depression, yet differs from prior work that tested the compound only after neuropathy was established. If translated, a single pre-chemo dose could protect thousands of breast, ovarian, and lung cancer patients annually.

Key limitation is the absence of human pharmacokinetic or safety data in the oncology setting; rodent metabolism of psilocybin differs and long-term neuroplastic changes remain unquantified. A phase 0 micro-dosing trial in healthy volunteers receiving low-dose paclitaxel is already planned to bridge the gap.