{"id":47785,"date":"2020-06-16T17:25:08","date_gmt":"2020-06-16T16:25:08","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=47785"},"modified":"2020-06-17T23:41:10","modified_gmt":"2020-06-17T22:41:10","slug":"the-hidden-burden-of-laughing-gas","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2020\/06\/16\/the-hidden-burden-of-laughing-gas\/","title":{"rendered":"The hidden burden of laughing gas"},"content":{"rendered":"<p><span style=\"font-weight: 400\">The frequent presence of silver canisters, or \u201cwhippits,\u201d on our streets (even during the <\/span><a href=\"https:\/\/www.hertfordshiremercury.co.uk\/news\/hertfordshire-news\/broxbourne-residents-disgusted-after-laughing-4079526\"><span style=\"font-weight: 400\">covid-19 lockdown<\/span><\/a><span style=\"font-weight: 400\">) is a visible mark of the increasing incidence of nitrous oxide (N<sub>2<\/sub>O) or laughing gas misuse.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">N<sub>2<\/sub>O is a colourless gas that has long been pharmaceutically indicated for general anaesthesia and analgesia [1]. <\/span><a href=\"https:\/\/www.rudifortson4law.co.uk\/nitrous-oxide-canisters-for-food-use-not-a-medicinal-product\"><span style=\"font-weight: 400\">The sale of N<sub>2<\/sub>O in canisters<\/span><\/a><span style=\"font-weight: 400\">, as a liquefied compressed gas, is permitted if they are designed and intended to be sold as a food additive (for example, a propellant for whipped cream) for commercial purposes. As a result, N<sub>2<\/sub>O canisters are readily available to purchase on the internet (via eBay and Amazon, for example) or via <\/span><a href=\"https:\/\/www.re-solv.org\/wp-content\/uploads\/2019\/06\/APPG-Report-on-NPS-VSA.pdf\"><span style=\"font-weight: 400\">street dealers<\/span><\/a><span style=\"font-weight: 400\">. The supply of N<sub>2<\/sub>O as a recreational drug is illegal under the UK\u2019s <\/span><a href=\"http:\/\/www.legislation.gov.uk\/ukpga\/2016\/2\/contents\/enacted\"><span style=\"font-weight: 400\">Psychoactive Substances Act 2016<\/span><\/a><span style=\"font-weight: 400\">,<\/span><span style=\"font-weight: 400\"> however, this has not acted as a deterrent in illicit drug use.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The misuse of laughing gas is \u201cno laughing matter.\u201d Its misuse in high doses has been associated with dose-dependent <\/span><a href=\"https:\/\/journals.lww.com\/psychopharmacology\/Abstract\/2020\/01000\/Psychiatric_and_Other_Medical_Manifestations_of.12.aspx\"><span style=\"font-weight: 400\">psychiatric<\/span><\/a><span style=\"font-weight: 400\">, <\/span><a href=\"https:\/\/www.gov.uk\/drug-safety-update\/nitrous-oxide-neurological-and-haematological-toxic-effects\"><span style=\"font-weight: 400\">haematological<\/span><\/a><span style=\"font-weight: 400\">,<\/span><span style=\"font-weight: 400\"> and <\/span><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0006899320300019\"><span style=\"font-weight: 400\">neurological<\/span><\/a><span style=\"font-weight: 400\"> adverse effects and even <\/span><a href=\"https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/birthsdeathsandmarriages\/deaths\/articles\/deathsrelatedtovolatilesubstancesandheliumingreatbritain\/2001to2016registrations\"><span style=\"font-weight: 400\">death<\/span><\/a><span style=\"font-weight: 400\">. Adverse effects include <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6906557\/\"><span style=\"font-weight: 400\">pulmonary embolism and deep vein thrombosis<\/span><\/a><span style=\"font-weight: 400\">, <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31522576\"><span style=\"font-weight: 400\">skin hyperpigmentation<\/span><\/a><span style=\"font-weight: 400\">,<\/span><span style=\"font-weight: 400\"> and more <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25977272\"><span style=\"font-weight: 400\">serious neurological damage<\/span><\/a><span style=\"font-weight: 400\"> such as <\/span><a href=\"https:\/\/www.jns-journal.com\/article\/S0022-510X(17)34117-5\/abstract\"><span style=\"font-weight: 400\">paraplegia<\/span><\/a><span style=\"font-weight: 400\">. Neurological damage associated with N<sub>2<\/sub>O is linked to the <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/8250714\"><span style=\"font-weight: 400\">inactivation of vitamin B<sub>12<\/sub><\/span><\/a> (cyanocobalamin) <span style=\"font-weight: 400\">and<\/span> <span style=\"font-weight: 400\">functional B<sub>12<\/sub> deficiency, leading to the methylation of myelin proteins, which, in turn, causes demyelination within the central and peripheral nervous system. These adverse effects are manifested as <\/span><a href=\"https:\/\/jnnp.bmj.com\/content\/90\/e7\/A38.2\"><span style=\"font-weight: 400\">subacute combined degeneration<\/span><\/a> (<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0967586819311336\">pernicious azotaemia<\/a>), <a href=\"https:\/\/www.jns-journal.com\/article\/S0022-510X(15)01247-2\/fulltext\"><span style=\"font-weight: 400\">toxic myelopathy<\/span><\/a><span style=\"font-weight: 400\"> including <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5745895\/\"><span style=\"font-weight: 400\">subacute cervical myelopathy<\/span><\/a><span style=\"font-weight: 400\"> and <\/span><a href=\"https:\/\/pn.bmj.com\/content\/15\/3\/207\"><span style=\"font-weight: 400\">generalised demyelinated polyneuropathy<\/span><\/a><span style=\"font-weight: 400\">, and <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3829298\/\"><span style=\"font-weight: 400\">T2 signal hyperintensity in the spinal cord<\/span><\/a><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/8250714\"><span style=\"font-weight: 400\">.\u00a0<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">These adverse events are even more concerning when the prevalence and usage trends of N<sub>2<\/sub>O are considered. The <\/span><a href=\"http:\/\/www.russellwebster.com\/gds19\/\"><span style=\"font-weight: 400\">2019 Global Drug Survey<\/span><\/a><span style=\"font-weight: 400\"> reported that N<sub>2<\/sub>O\u00a0 was one of the top 10 most popular drugs used by respondents in the previous year. Similarly, the <\/span><a href=\"https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/832533\/drug-misuse-2019-hosb2119.pdf\"><span style=\"font-weight: 400\">2018\/2019 Crime Survey for England and Wales<\/span><\/a><span style=\"font-weight: 400\"> reported that among 16 to 24 year olds in the UK, 8.7% (around 552 000 individuals) had used N<sub>2<\/sub>O in the past year. In this age group, N<sub>2<\/sub>O was the second most popular substance behind cannabis. Survey respondents reported obtaining N<sub>2<\/sub>O from friends, family members, dealers, shops, and the internet. Approximately, a quarter of respondents said that it would be easy to obtain N<sub>2<\/sub>O in less than 24 hours.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">A <\/span><a href=\"https:\/\/www.re-solv.org\/wp-content\/uploads\/2019\/06\/APPG-Report-on-NPS-VSA.pdf\"><span style=\"font-weight: 400\">report for the All Party Parliamentary Group on new psychoactive substances and volatile substances<\/span><\/a> <span style=\"font-weight: 400\">showed that, after volatile substances, pupils\u2019 early experience of drug use (11 years old and younger) was most likely to involve N<sub>2<\/sub>O. Similarly, a 2017<\/span><a href=\"https:\/\/www.tandfonline.com\/doi\/abs\/10.1080\/16066359.2017.1309031\"><span style=\"font-weight: 400\"> study<\/span><\/a><span style=\"font-weight: 400\"> on drug use and misuse across seven universities in Wales showed that the most commonly used drugs were cannabis, followed by ecstasy, cocaine, and N<sub>2<\/sub>O. Its popularity is likely to be linked to its short duration of action and ease of access.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Despite the scarcity of information on the economic and health burden of N<sub>2<\/sub>O, <\/span><span style=\"font-weight: 400\">a number of <\/span><a href=\"https:\/\/academic.oup.com\/bja\/article\/116\/3\/321\/2566058\"><span style=\"font-weight: 400\">unsafe practices<\/span><\/a> <span style=\"font-weight: 400\">of N<sub>2<\/sub>O use have been reported, including inhaling it directly from the nozzle of a whipped cream dispenser, plastic bags, or directly from an N<sub>2<\/sub>O tank. There are also the risks of frequent dosing due to its short duration of action and poly-substance misuse with N<sub>2<\/sub>O. Reported deaths have been caused by sudden cardiac arrhythmias and\/or asphyxiation. When the <\/span><a href=\"https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/birthsdeathsandmarriages\/deaths\/adhocs\/009096drugrelateddeathsinvolvingnitrousoxideinenglandandwales1993to2017\"><span style=\"font-weight: 400\">Office for National Statistics<\/span><\/a><span style=\"font-weight: 400\"> compiled drug related deaths involving N<sub>2<\/sub>O in England and Wales they found that<\/span><span style=\"font-weight: 400\"> on average, five people died from N<sub>2<\/sub>O per year between 2013 and 2017, with a total of 29 people dying between 2010 and 2017.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The number of patients presenting to healthcare services with neurological damage due to N<sub>2<\/sub>O consumption is expected to rise. The puzzling loophole within this current state of affairs is that N<sub>2<\/sub>O misuse is controlled under the Psychoactive Substances Act 2016, and yet N<sub>2<\/sub>O canisters or \u201cwhippets\u201d are readily available to purchase on the internet. It is clear that the lack of clarity around the regulation of these drugs\u2019 supply and use needs to be imminently addressed.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Additional harms from N<sub>2<\/sub>O have been potentially exacerbated by the <\/span><a href=\"https:\/\/www.emcdda.europa.eu\/publications\/topic-overviews\/covid-19-and-people-who-use-drugs_en\"><span style=\"font-weight: 400\">disruption of drug markets<\/span><\/a><span style=\"font-weight: 400\"> during the covid-19 pandemic. This disturbance has created notable <\/span><a href=\"https:\/\/www.unodc.org\/unodc\/press\/releases\/2020\/May\/covid-19-is-changing-the-route-of-illicit-drug-flows--says-unodc-report.html\"><span style=\"font-weight: 400\">shifts in drug consumption trends<\/span><\/a><span style=\"font-weight: 400\">, with the<\/span><span style=\"font-weight: 400\"> shortages of certain illicit drugs leading to increasing consumption of more accessible substances. Since N<sub>2<\/sub>O is legally available via online outlets, it could present a viable alternative for people who use drugs. Many commentators have also expressed fears that the impact of lockdown and its attendant mental health stresses will lead to an increase in harmful use of <\/span><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2215036620301681\"><span style=\"font-weight: 400\">drugs and alcohol<\/span><\/a><span style=\"font-weight: 400\">. Finally, <\/span><span style=\"font-weight: 400\">it is important to note that since N<sub>2<\/sub>O is administered by inhalation, with large amounts possibly leading to hypoxia, it thus risks making users develop possible additional complications if they are infected with the coronavirus.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Tighter regulations around the sale of N<sub>2<\/sub>O online need to be imposed by the government. We would suggest that this should include the provision of identification at purchase, raising the age of sale to people aged over 25, restricting quantities per purchase, and prosecuting those suppliers who are targeting sales of N<sub>2<\/sub>O canisters for recreational purposes. In conjunction with tighter regulations on the sale of N<sub>2<\/sub>O, a harm reduction programme led by healthcare professionals, and with a specific focus on N<sub>2<\/sub>O misuse in young people, needs to be developed and implemented nationally.<\/span><\/p>\n<ol>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">British Pharmacopoeia 2020 (online) &#8211; Volume II &#8211; Monographs: Medicinal and Pharmaceutical Substances \u2013 Nitrous Oxide (Ph. Eur. monograph 0416).<\/span><\/li>\n<\/ol>\n<p><i><span style=\"font-weight: 400\"><strong>Amira Guirguis<\/strong> is a pharmacist and the MPharm programme director at Swansea University Medical School. Her research has included in-field drug detection and classification, harm reduction via pharmacist-led \u201cDrug Checking,\u201d drug education, and public health interventions related to substance misuse.<\/span><\/i><\/p>\n<p><b>Competing interests:<\/b> <span style=\"font-weight: 400\">Amira Guirguis receives and has received funding from grant awarding bodies for drug detection research.<\/span><\/p>\n<p><strong><em>Luigi Martini<\/em> <\/strong><i><span style=\"font-weight: 400\">is the chief scientist at the Royal Pharmaceutical Society. He has a keen interest in pharmacists playing a role in drug education and public health interventions related to substance misuse.<\/span><\/i><\/p>\n<p><b>Competing interests: <\/b>None to declare<\/p>\n<p><strong><em>Mair Davies <\/em><\/strong><i><span style=\"font-weight: 400\">is the former director for Wales at the Royal Pharmaceutical Society. She is also keen for pharmacists to play a part in drug education and public health interventions related to substance misuse.<\/span><\/i><\/p>\n<p><b>Competing interests: <\/b>None to declare.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The frequent presence of silver canisters, or \u201cwhippits,\u201d on our streets (even during the covid-19 lockdown) is a visible mark of the increasing incidence of nitrous oxide (N2O) or laughing [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2020\/06\/16\/the-hidden-burden-of-laughing-gas\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":47786,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[223],"tags":[],"class_list":["post-47785","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-guest-bloggers"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - 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