Background The recreational abuse of nitrous oxide (NO) is becoming increasingly prevalent within the United Kingdom and across the globe. Chronic abuse can cause nerve and spinal cord damage through the functional inactivation of vitamin B12. We present six cases from a single centre in the United Kingdom between 2016 and 2020 with neurological complications from NO abuse, ranging from paraesthesia to subacute combined degeneration of the spinal cord. Methodology A retrospective review of all neurology admissions to Queen Elizabeth Hospital Birmingham (QEHB) between 2016 and 2020 was conducted to identify patients admitted with a diagnosis of neurological dysfunction (neuropathy or myelopathy) in association with chronic NO misuse. The Prescribing Information and Communication System was used to collect data on demographics, reported NO misuse, presenting symptoms, results of blood tests, nerve conduction studies and treatment regimens. All patients gave verbal consent for inclusion in the case series. Data were anonymised and analysed by the corresponding author. Results All patients were males aged between 22 and 28 years. In all cases, the patients were admitted with the abuse of NO  canisters (ranging from 20 to 500 canisters per session), presenting with a combination of sensory and motor disturbance. Clinical suspicion, in the context of a history of NO abuse, along with elevated blood concentrations of methylmalonic acid (MMA) and homocysteine, and nerve conduction studies, was the cornerstone of the diagnosis. All patients were treated with parenteral vitamin B12, though individual regimens differed, with no standardisation in the duration or frequency of treatment. All patients received intramuscular (IM) vitamin B12 injections during admission, with one patient receiving oral vitamin B12 before being switched to IM vitamin B12 injections. One patient received additional folic acid as a treatment adjunct. Prescriptions were most varied on discharge with huge discrepancies in duration and frequency of vitamin B12 replacement, ranging from no B12 replacement at all to IM injections once weekly for eight weeks.  Conclusions The variability in route, dose and duration of vitamin B12 treatment, along with the variable use of adjunctive therapy reported in the literature, highlights the current lack of consensus in managing NO neurotoxicity.