Nitrous oxide (N2O) misuse is widespread in the UK. Although it is well known that it can cause devastating myeloneuropathy, psychiatric presentations are poorly described. There is little understanding of who it affects, how it presents, its mechanism of action and principles of treatment. We begin this article with a case study. We then review the literature to help psychiatrists understand this area and deal with this increasing problem, and make diagnosis and treatment recommendations. We describe a diagnostic pentad of weakness, numbness, paraesthesia, psychosis and cognitive impairment to alert clinicians to the need to urgently treat these patients.