Cornelio Vanessa C, Lail Gary, Go Kimberly, Kaur Kiran, Slowik Piotr
Psychiatry, St. John's Episcopal Hospital, Far Rockaway, USA.
Gastroenterology and Hepatology, St. John's Episcopal Hospital, Far Rockaway, USA.
Cureus. 2025 Aug 5;17(8):e89448. doi: 10.7759/cureus.89448. eCollection 2025 Aug.
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.
一氧化二氮（N₂O）滥用已成为一个日益严重的公共卫生问题，尤其是在青少年和青年群体中，他们将其用于娱乐目的。本综述性研究调查了近期以及基础研究中关于长期频繁使用这种挥发性气体所产生的神经精神方面的长期影响。检索了多个临床数据库和期刊档案，如《成瘾医学杂志》《儿童精神病学杂志》《麻醉学杂志》、科学Direct数据库以及《全国药物使用和健康调查》，以查找临床试验、病例报告和公共卫生调查。重点关注了探索与慢性一氧化二氮暴露相关的神经生物学机制、流行病学趋势、临床表现和治疗策略的研究。研究发现，社会经济地位低、同伴影响以及同时使用酒精或大麻等流行病学因素会增加一氧化二氮滥用的可能性。从生物力学角度来看，一氧化二氮通过拮抗N-甲基-D-天冬氨酸受体（NMDA）以及释放内源性阿片类物质发挥作用，改变神经递质动态并导致潜在的成瘾性。长期使用会通过氧化甲钴胺破坏维生素B12代谢，损害髓鞘生成，进而导致脊髓亚急性联合变性。神经影像学研究显示海马体和视觉皮层失活，这与观察到的记忆和感觉处理缺陷相符。青少年使用者经常报告出现抑郁、妄想和激动等精神并发症。通过戒断、补充维生素B12以及使用纳曲酮和阿立哌唑等新兴药物进行早期干预，可以减轻不良后果。开展教育活动、立法控制和学校预防项目等公共卫生举措对于遏制持续的滥用行为至关重要。尽管关注度不断提高，但在理解长期后果、有效治疗方法和全球流行病学模式方面仍存在重大差距。进一步的研究对于制定针对这一高危人群的循证临床指南和预防策略至关重要。
