Recreational Nitrous Oxide Use: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Vivi Li and Version 1 by Julaine Allan.

Nitrous oxide (N2O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N2O use is difficult to quantify but appears to be increasing. Research on N2O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disisparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people was collated and synthesised. 

  • nitrous oxide
  • N2O
  • nangs
  • systematic review
  • harm reduction
  • drug use
  • substance addiction
  • health risks
  • psychological harm

1. Introduction

The pleasurable and intoxicating effects of psychoactive substances result in widespread use. However, deaths and injury from psychoactive substance use, particularly among young people, are a global public health problem [1,2][1][2]. Harm reduction is an evidence-based approach to reducing adverse consequences from the use of psychoactive substances, recognising eliminating use is not necessarily realistic or desirable [3]. Harm reduction strategies can be applied in different ways. For example, at a policy level such as the funding of supervised drug consumption sites, at a service level such as gender-specific services or information in different languages; and at an individual level with personalised advice according to the drug used and patterns of use. Drug use occurs on a spectrum ranging from occasional experimentation through to using multiple times a day when highly dependent on a substance. Understanding the benefits and problems associated with different drugs and patterns of use is an important part of creating contextually and physiologically relevant harm reduction strategies [4]. Psychoactive substances vary greatly in the way they change mental states and in potential harms including those caused while intoxicated and others because of regular or prolonged use.
Nitrous oxide (N2O) is a dissociative anaesthetic that is sometimes used recreationally. Once inhaled, N2O is quickly absorbed into the bloodstream through the lungs; then, it travels rapidly to the brain and the rest of the body. The gas produces a rapid rush of euphoria, heightened consciousness, disassociation, and feelings of floating and excitement, lasting approximately one minute [5]. N2O is used within the medical and dental fields for anaesthetic, sedation, and pain relief purposes. Beyond its medical use, N2O is used as a fuel booster in the racing industry and in the food industry as an aerosol spray propellant [6].
N2O is readily available at supermarkets and convenience stores in small metal bulbs used to produce whipped cream. It is cheap to purchase—each bulb costs approximately $1 AUD. Legalities around the sale of N2O vary between countries. For example, there are no legal measures to control the sale of N2O in Amsterdam because it is considered relatively safe and moderately used [7]. In contrast, Australia’s states and territories have made it an offence to supply canisters that hold N2O to anyone suspected of using it for recreational purposes. However, it is not an offence to inhale it [8]. Australian legal systems have difficulty monitoring the selling or purchasing of N2O for recreational use [9]. In the UK, plans to criminalise the use of N2O are being discussed because of concerns that use and related harms are growing [10].
The prevalence of N2O use is difficult to quantify but appears to be increasing. Misuse among medical and dental professionals because of easy access and methods of controlled administration has been documented [11]. Media reports regarding N2O use are common and are fuelling the UK parliament’s concerns about rising prevalence and harms [12]. For example, a ‘Google’ news search on N2O brings up 2790 results of news stories related to N2O recreational use between 2018 and 2021. The news stories range from high-profile celebrities being caught on camera using N2O to young people dying in situations where N2O use is implicated (e.g., [13,14][13][14]). There are frequent reports in UK local media about parties and events resulting in N2O canisters littering public areas.
Most research reporting N2O prevalence has used self-selected samples of people who use drugs such as the Global Drug Survey [15] and in Australia, the National Ecstasy and Related Drugs Reporting System [9]. However, both these sources report year on year increases in use of N2O and that young people are the most frequent users. It is important to note that N2O use can be under-reported due to its short-lived effects, inability to be detected through drug testing and because it is often used with other drugs [16]. However, the observed upward trend is concerning because not only is N2O easy to access at a low cost and sold in bulk but because of a lack of information for people using the drug [17].
Research on N2O harms and patterns of use are limited. Some studies have identified both minor and chronic harms associated with N2O use including death by asphyxiation, psychiatric sequelae such as psychosis and physical symptoms, such as burns or frostbitten skin and the depletion of B12 levels from prolonged use of N2O resulting in neurological damage [18,19,20,21][18][19][20][21]. Other harms are related to intoxication: for example, falling over or losing consciousness whilst under the influence of N2O [18]. However, patterns, benefits and social factors related to N2O use have not been explored in detail. The lack of information readily available to decision-makers, practitioners, educators, and young people makes it difficult to provide contextualised harm reduction strategies to minimise any risks involved in N2O use.

2. Policy Implications

There was limited inclusion of policy or legislative responses in any published studies. Three studies identified ease of purchase as a factor in increasing prevalence including availability in retail shops [54][22] and online [50][23] even after the UK’s psychoactive substances legislation. In the EU, restrictions on N2O purchase were imposed because of health concerns rather than a relationship to drug-related crime [45][24]. One study noted the risks of N2O use were underestimated in policy and legislative responses to drug use. For example, there was no mention of volatile substance abuse (VSA) including N2O, in the UK Government’s 2017 Drug Strategy, although VSA caused the same number of deaths as MDMA [37][25]. Only one publication suggested harms were overstated [43][26]. However, this publication was an opinion piece with a weak rating. Drug Science [43][26] concluded that media campaigns are driving concern, and the problem to be addressed by policy or legislation is canisters littering party sites rather than the use of N2O. That conclusion about lack of harms was not shared. Several studies highlighted that the prevalence appears to be increasing worldwide (e.g., [32,45,62][24][27][28]) and therefore is an issue for policy makers to consider because a small proportion of heavy users are at risk of acute harms [17,33][17][29]. Nabben [34][30] reported an increase in nitrous oxide-related traffic accidents in the Netherlands, noting that most users believe the drug is safe and has no lasting effects and therefore not understanding the risks of driving during or after N2O use.

3. Service Delivery—Assessment, Treatment and Education

N2O use risks are generally underestimated. For example, the majority (91.6%, n = 99) of those who had heard of N2O were not aware of any side effects associated with its use and believed the drug was safe [7,34,35][7][30][31]. However, Ehirim et al. [35][31] was the only study with a strong quality rating. Formal assessment of N2O use rarely occurs in treatment services. When identified, reports of N2O misuse do not fit the criteria for substance dependence and therefore may be underestimated because only two to three DSM-5 criteria are identified during assessment. However, Criterion 1 (Taking the substance in larger amounts or over a longer period than was intended) is positive in 98% of cases included in the review by [47][32]. The capacity of services to respond to people who use N2O is complicated by the lack of a formal screening tool and N2O use presenting with other drug use [48][33]. Furthermore, one study suggests people who inhale volatile substances including N2O rarely access treatment services [37][25]. Leigh and Maclean [37][25] suggest mental health services might be first point of contact for vulnerable solvent users rather than drug and alcohol services. Information for young people or clinicians about N2O harms appears to be limited or unavailable. Three studies noted N2O is not included in drug education programs [7[7][22][34],53,54], and another high-quality study reported young people believe more information/education is needed to raise awareness of harms [35][31]. The majority of respondents in that study (60%, n = 86) chose the scale value of 10 (extremely important) as to how important it is to educate young people about the effects of N2O [35][31]. In relation to where to intervene, one study suggested that because N2O is most often consumed via balloons at festivals and in clubs, this is the best type of intervention site [33][29]. Another study recommended using influencers in media campaigns with the aim to decrease the risks of heavy nitrous oxide use and improve treatment access [34][30]. Because driving is impaired for up to 30 min after exposure to N2O, information for N2O users about risks of traffic accidents was recommended [7].

4. Individuals

Recreational nitrous oxide use is popular with young people. In one study, most respondents (77.1%, n = 108) had heard of N2O and 27.9% (n = 39) had taken N2O in the past 12 months [33][29]. Three studies [35,53,54][22][31][34] found males were more likely to use N2O than females. For example, N2O was more popular among males at 39.0% (n = 16) compared to females at 24.7% (n = 23) [35][31], and in another survey, 15% of men and 9% of women in NZ had used N2O [53][34]. However, no statistically significant association between age and N2O use was found [35][31]. That is, N2O is not exclusively a young person’s drug. Leigh and Maclean [37][25] identified an increasing prevalence of deaths from volatile substances including N2O and that the age profile of those dying is older than the typical user profile [37][25]. One high-quality study investigating substance use disorders found that while most users use infrequently, and their use is not associated with significant harm, N2O was ‘overused’ by men, adolescents and young adults [47][32]. Another study confirmed that frequent N2O use is associated with hallucinations and confusion and persistent numbness and accidental injury [33][29]. The quantity associated with problematic N2O use varies. Studies identified 300 canisters per week [50][23], 40–60 per day [40][35] and 50–100 bulbs taken per session by heavy users to remain intoxicated [7]. Worryingly, regular users appear to be increasing the amount they use both in days of use per month and amount used at each session [9,32][9][27]. However, patterns of N2O use have not been thoroughly investigated nor have the benefits that prompt use. The case reports found N2O use was typically overlooked, and that people deny using it [60][36]. In some cases, serious degeneration and limb paralysis is observed before N2O problems are identified [42][37], suggesting scope for earlier identification and intervention. Common presentations indicating problematic N2O use include muscle weakness, stumbling and spinal cord problems [41,49][38][39]. One person was in a wheelchair for a year before the problem of N2O use was diagnosed [42][37]. Ng [53][34] suggested that with an increasing proportion of vegetarianism, many young people have a higher risk of nutritional deficiencies, further increasing their risk of subacute combined degeneration of the spinal cord. Other case studies reported strokes [59][40] and thrombosis [57][41]. Neuropsychiatric symptoms were also identified [60][36]. One case study made a connection to psychosis and schizophrenia, concluding that N2O use may be a causative factor in the development of psychotic symptoms [58][42]. However, this was only one study and a speculative finding. Addressing N2O harms for individuals currently relies on medical intervention particularly B12 injections. There was one report of an individual who injected themselves with B12 on the advice of a friend, which resolved their symptoms [44][43]. However, one-third or 29% of people with N2O problems will not have B12 deficiency [56][44]. The most significant limitation of the case reports is that the outcome of medical interventions is not reported. The follow-up of individuals in case reports is rare and was identified as difficult when people do not return for check-ups [42][37]. Therefore, ongoing symptoms of misuse and success of interventions is unknown.

References

  1. Hall, W.; Patton, G.; Stockings, E.; Weier, M.; Lynskey, M.; Morley, K.; Degenhardt, L. Why young people’s substance use matters for global health. Lancet Psychiatry 2016, 3, 265–279.
  2. The United Nations Office on Drugs and Crime. World Drug Report 2018 Retrieved from Vienna, Austria; The United Nations Office on Drugs and Crime: Vienna, Austria, 2018.
  3. Pauly, B. Harm Reduction Through a Social Justice Lens. Int. J. Drug Policy 2008, 19, 4–10.
  4. Boyd, J.; Lavalley, J.; Czechaczek, S.; Mayer, S.; Kerr, T.; Maher, L.; McNeil, R. “Bed Bugs and Beyond”: An ethnographic analysis of North America’s first women-only supervised drug consumption site. Int. J. Drug Policy 2020, 78, 102733.
  5. Alcohol and Drug Foundation. Nitrous Oxide. 2021. Available online: https://adf.org.au/drug-facts/nitrous-oxide/ (accessed on 11 November 2021).
  6. Randhawa, G.; Bodenham, A. The increasing recreational use of nitrous oxide: History revisited. Br. J. Anaesth. 2015, 116, 321–324.
  7. Van Amsterdam, J.; Nabben, T.; van den Brink, W. Recreational nitrous oxide use: Prevalence and risks. Regul. Toxicol. Pharmacol. 2015, 73, 790–796.
  8. Government of South Australia. Controlled Substances Act 1984. 2021. Available online: https://www.legislation.sa.gov.au/LZ/C/A/CONTROLLED%20SUBSTANCES%20ACT%201984.aspx (accessed on 11 November 2021).
  9. National Ecstasy and Related Drugs Reporting System. Australian Drug Trends 2020: Key Findings from the National Ecstasy and Related Drugs Reporting System (EDRS) Interviews. 2020. Available online: https://ndarc.med.unsw.edu.au/resource/australian-drug-trends-2020-key-findings-national-ecstasy-and-related-drugs-reporting (accessed on 11 November 2021).
  10. Bright, S.; Barratt, M. Whipping Cream Canisters Have Many Uses Beyond ‘Nangs’. Banning Them Isn’t Necessary. 2021. Available online: https://theconversation.com/whipping-cream-canisters-have-many-uses-beyond-nangs-banning-them-isnt-necessary-164870 (accessed on 2 February 2022).
  11. Thompson, A.; Leite, I.; Lunn, M.; Bennett, D. Whippits, nitrous oxide and the dangers of legal highs. Pract. Neurol. 2015, 15, 207–209.
  12. Campell, D. Nitrous Oxide Useres Unaware of Health Risks, Nurses Warn. 2019. Available online: https://www.theguardian.com/society/2019/may/21/nitrous-oxide-users-unaware-of-health-risks-nurses-warn (accessed on 2 February 2022).
  13. 9 News. Police Probe If ‘Nangs’ Contributed to Teen Schoolie Death. 2018. Available online: https://www.9news.com.au/national/hamish-bidgood-schoolies-death-gold-coast-nitrous-oxide/8b4ea488-8de0-4f64-9c8c-5402f28471bb (accessed on 2 February 2022).
  14. Berlin, S. Anit-Hazing “Colins Law” Named after Sutdent Who Died Now in Effect in Ohio. 2021. Available online: https://www.newsweek.com/anti-hazing-collins-law-named-after-student-who-died-now-effect-ohio-1637072#:~:text=Collin’s%20Law%2C%20Ohio’s%20new%20legislation,a%20hazing%20incident%20in%202018 (accessed on 2 February 2022).
  15. Winstock, A. Global Drug Survey. United Kingdom. 2019. Available online: https://www.globaldrugsurvey.com/wp-content/themes/globaldrugsurvey/results/GDS2019-Exec-Summary.pdf (accessed on 11 November 2021).
  16. Lacy, B.; Ditzler, T. Inhalant abuse in the military: An unrecognized threat. Mil. Med. 2007, 172, 388–392.
  17. Asmussen, F.; MacLean, S.; Herold, M. Nitrous oxide use among young people-new trends, policy challenges, and knowledge gaps. Drugs Alcohol Today 2020, 20, 383–392.
  18. Australian National Drug & Alcohol Research Centre. Nitrous Oxide. 2021. Available online: https://ndarc.med.unsw.edu.au/resource/nitrous-oxide-0 (accessed on 11 November 2021).
  19. Baran, K.C.; van Munster, I.G.; Vries, A.D.; Gardien, K.L.; van Trier, T.; Pijpe, A. Severe nitrous-oxide frostbite injuries on the rise in The Netherlands; let’s raise awareness. Burns 2020, 46, 1477–1479.
  20. Hwang, J.; Himel, H.; Edlich, R. Frostbite of the face after recreational misuse of nitrous oxide. Burns 1996, 22, 152–153.
  21. Quax, M.; Van Der Steenhoven, T.; Bronkhorst, M.A.; Emmink, B. Frostbite injury: An unknown risk when using nitrous oxide as a party drug. Acta Chir. Belg. 2020, 122, 140–443.
  22. Policing and Crime Statistics. Drugs Misuse: Findings from the 2018/19 Crime Survey for England and Wales. Retrieved from United Kingdom; 2019. Available online: https://www.gov.uk/government/statistics/drug-misuse-findings-from-the-2018-to-2019-csew (accessed on 11 November 2021).
  23. Johnson, K.; Mikhail, P.; Kim, M.; Bosco, A.; Huynh, W. Recreational nitrous oxide-associated neurotoxicity. J. Neurol. Neurosurg. Psychiatry 2018, 89, 897.
  24. European Crime Prevention Network (EUCPN). Recommendation Paper: Preventing the Misuse of Nitrous Oxide. 2021. Available online: https://eucpn.org/document/recommendation-paper-preventing-the-misuse-of-nitrous-oxide (accessed on 11 November 2021).
  25. Leigh, V.; MacLean, S. Silent deaths: A commentary on new mortality data relating to volatile substance abuse in Great Britain. Drugs Alcohol Today 2019, 19, 86–96.
  26. Drug Science. House of Commons Debate Briefing for MPs: Tackling the Misuse Nitrous Oxide. 2020. Available online: https://drugscience.org.uk/wp-content/uploads/2020/07/Briefing-House-of-Commons-Debate_NitrousOxide_21072020.pdf (accessed on 11 November 2021).
  27. Grigg, J.; Lenton, S. Increasing Trends in Self-Reported Use of Nitrous Oxide among WA EDRS Samples. 2019. Available online: https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/WA%20EDRS%20Nitrous%20Oxide%20Bulletin_FINAL_DOI.pdf (accessed on 11 November 2021).
  28. Zheng, D.; Ba, F.; Bi, G.; Guo, Y.; Gao, Y.; Li, W. The sharp rise of neurological disorders associated with recreational nitrous oxide use in China: A single-center experience and a brief review of Chinese literature. J. Neurol. 2020, 267, 422–429.
  29. Kaar, S.; Ferris, J.; Waldron, J.; Devaney, M.; Ramsey, J.; Winstock, A. Up: The rise of nitrous oxide abuse. An international survey of contemporary nitrous oxide use. J. Psychopharmacol. 2016, 30, 395–401.
  30. Nabben, T.; Weijs, J.; van Amsterdam, J. Problematic Use of Nitrous Oxide by Young Moroccan-Dutch Adults. Int. J. Environ. Res. Public Health 2021, 18, 5574.
  31. Ehirim, E.; Naughton, D.; Petróczi, A. No Laughing Matter: Presence, Consumption Trends, Drug Awareness, and Perceptions of “Hippy Crack” (Nitrous Oxide) among Young Adults in England. Front. Psychiatry 2017, 8, 312.
  32. Fidalgo, M.; Prud’homme, T.; Allio, A.; Bronnec, M.; Bulteau, S.; Jolliet, P.; Victorri-Vigneau, C. Nitrous oxide: What do we know about its use disorder potential? Results of the French Monitoring Centre for Addiction network survey and literature review. Subst. Abus. 2019, 40, 33–42.
  33. Garakani, A.; Jaffe, R.; Savla, D.; Welch, A.; Protin, C.; Bryson, E.; McDowell, D. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature. Am. J. Addict. 2016, 25, 358–369.
  34. Ng, J.; O’Grady, G.; Pettit, T.; Frith, R. Nitrous oxide use in first-year students at Auckland University. Lancet 2003, 361, 1349–1350.
  35. Butzkueven, H.; King, J. Nitrous oxide myelopathy in an abuser of whipped cream bulbs. J. Clin. Neurosci. 2000, 7, 73–75.
  36. Wong, S.; Harrison, R.; Mattman, A.; Hsiung, G. Nitrous Oxide (N2O) nduced Acute Psychosis. Can. J. Neurol. Sci. 2014, 41, 672–674.
  37. Choi, C.; Kim, T.; Park, K.; Lim, O.; Lee, J. Subacute Combined Degeneration Caused by Nitrous Oxide Intoxication: A Report of Two Cases. Ann. Rehabil. Med. 2019, 43, 530–534.
  38. Chen, T.; Zhong, N.; Jiang, H.; Zhao, M.; Chen, Z.; Sun, H. Neuropsychiatric Symptoms Induced by Large Doses of Nitrous Oxide Inhalation: A Case Report. Shanghai Arch. Psychiatry 2018, 30, 56–59.
  39. Ghobrial, G.; Dalyai, R.; Flanders, A.; Harrop, J. Nitrous oxide myelopathy posing as spinal cord injury. J. Neurosurg. 2012, 16, 489–491.
  40. Den Uil, S.; Vermeulen, E.; Metz, R.; Rijbroek, A.; de Vries, M. Aortic arch thrombus caused by nitrous oxide abuse. J. Vasc. Surg. Cases Innov. Tech. 2018, 4, 80–82.
  41. Sun, W.; Liao, J.; Hu, Y.; Zhang, W.; Ma, J.; Wang, G. Pulmonary embolism and deep vein thrombosis caused by nitrous oxide abuse: A case report. World J. Clin. Cases 2019, 7, 4057–4062.
  42. Kim, S.; Lee, S.; Bang, M. Double-sidedness of “laughing gas” on the N-methyl-d-aspartate receptor: A case report of acute psychosis associated with nitrous oxide-induced hyperhomocysteinemia. Schizophr. Res. 2019, 208, 475–476.
  43. Edigin, E.; Ajiboye, O.; Nathani, A. Nitrous Oxide-induced B12 Deficiency Presenting With Myeloneuropathy. Cureus 2019, 11, e5331.
  44. Seed, A.; Jogia, M. Lessons of the month: Nitrous oxide-induced functional vitamin B12 deficiency causing subacute combined degeneration of the spinal cord. J. R. Coll. Physicians Lond. 2020, 20, E7–E9.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Feedback