Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that has been researched for its anti-inflammatory and analgesic properties. There is emerging scientific interest in its potential to reduce certain chemotherapy-induced side effects, particularly neuropathic pain. Several small clinical trials and preclinical studies have explored PEA’s effects on chemotherapy-induced peripheral neuropathy (CIPN), a common and often debilitating side effect of certain chemotherapeutic agents like paclitaxel and oxaliplatin.

For example, a few small-scale human studies have suggested that PEA supplementation may help reduce neuropathic pain in cancer patients, including those experiencing CIPN. These findings are echoed by animal studies where PEA administration reduced markers of nerve inflammation and pain behaviors following chemotherapy treatments. The proposed mechanisms include modulation of mast cell activation, downregulation of inflammatory cytokines, and enhancement of endogenous cannabinoid signaling.

However, while these initial results are promising, the totality of clinical evidence remains limited. Most studies involve small sample sizes, short durations, and at times lack rigorous controls. Systematic reviews and meta-analyses note that more large-scale, high-quality randomized controlled trials are needed to confirm efficacy and establish standardized dosing protocols. Thus, the evidence is promising but preliminary, and PEA should not be considered a replacement for established supportive care in chemotherapy patients.