Nitrous oxide (NO), 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, NO is proven to be neurotoxic, especially with prolonged, heavy use, which is often unexpected for users. The neurotoxicological mechanism underlying NO-induced neurotoxicity involves inactivation of vitamin B (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 NO-induced peripheral neuropathy is largely unknown, although some research suggests it is not uncommon. Treatment includes immediate cessation of NO use and vitamin B supplementation. Although this treatment often reverses damage, residual symptoms such as limb weakness may persist. Additionally, genetic and dietary factors, such as vitamin B deficiency, may heighten individual vulnerability for NO's detrimental effects.