Rare but relevant: Nitrous oxide and peripheral neurotoxicity, what do we know?

Nitrous oxide (N2O), used medically as an anaesthetic, has gained popularity as a recreational drug, with rising prevalence particularly among young adults. While its reinforcing and addictive potential remains debated, N2O is proven to be neurotoxic, especially with prolonged, heavy use, which is often unexpected for users. The neurotoxicological mechanism underlying N2O-induced neurotoxicity involves inactivation of vitamin B12 (cobalamin), which disrupts methionine synthesis, essential for maintaining the myelin sheath. This can result in demyelinating diseases, including generalized demyelinating polyneuropathy (GDP). Clinical incidence of N2O-induced peripheral neuropathy is largely unknown, although some research suggests it is not uncommon. Treatment includes immediate cessation of N2O use and vitamin B12 supplementation. Although this treatment often reverses damage, residual symptoms such as limb weakness may persist. Additionally, genetic and dietary factors, such as vitamin B12 deficiency, may heighten individual vulnerability for N2O's detrimental effects.