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

Abstract

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.

Keywords: methionine; myelopathy; neurotoxicity; nitrous oxide; peripheral neuropathy; vitamin B12.

FIGURE 1

The molecular pathways involved in N₂O‐induced neurotoxicity.