Abstract
Nitrous oxide (N₂O) misuse represents a growing public health issue, particularly among adolescents and young adults, who use it recreationally. This scoping review investigates recent and foundational studies on the long-term neuropsychiatric effects associated with prolonged and frequent use of this volatile gas. Various clinical databases and journal archives, such as those of the Journal of Addiction Medicine, Journal of Child Psychiatry, Journal of Anesthesiology, Science Direct, and National Survey of Drug Use and Health, were queried for clinical trials, case reports, and public health surveys. Emphasis was placed on studies exploring the neurobiological mechanisms, epidemiological trends, clinical manifestations, and treatment strategies associated with chronic N₂O exposure. The search revealed epidemiological factors like low socioeconomic status, peer influence, and concurrent use of alcohol or cannabis increased the likelihood of N₂O misuse. Biomechanically, N₂O acts via N-methyl-D-aspartate receptor (NMDA) receptor antagonism and endogenous opioid release, altering neurotransmitter dynamics and leading to potential dependence. Chronic use disrupts vitamin B12 metabolism by oxidizing methylcobalamin, impairing myelin production,n and leading to subacute combined degeneration of the spinal cord. Neuroimaging studies reveal deactivation of the hippocampus and visual cortices, aligning with observed memory and sensory processing deficits. Psychiatric complications such as depression, delusions, and agitation are frequently reported in adolescent users. Early intervention through cessation, vitamin B12 supplementation, and emerging pharmacologic agents such as naltrexone and aripiprazole can mitigate adverse outcomes. Public health initiatives such as educational campaigns, legislative control, and school-based prevention programs are critical to curbing ongoing misuse. Despite increasing attention, significant gaps remain in understanding long-term outcomes, effective treatments, and global epidemiological patterns. Further research is essential to develop evidence-based clinical guidelines and preventative strategies tailored to this at-risk population.