Recreational nitrous oxide use: Prevalence and risks
Graphical abstract
Introduction
Nitrous oxide or N2O, also known as laughing gas, was first synthesized in 1775 by Joseph Priestley. N2O mixed with 30% oxygen is regularly used as an anesthetic in dental surgery and ambulances, where its short duration of action is an important advantage. Since nitrous oxide is a very stable, chemically inert, and bacteriostatic gas that leaves no taste or odor, it is also widely used in whipped cream charging bottles (steel bulbs containing 10 ml pressurized N2O). Other applications are found in oil industry to trace leaks and car racing to speed combustion.
Since Victorian times when ‘laughing gas parties’ were popular, nitrous oxide is also used as an inhalant drug. About two decades ago, N2O became increasingly known as an inhalant drug, in the scene known as “Hippy Crack”, especially in some clubs and music festivals.
Section snippets
Mechanism of action
The precise mechanism of how N2O induces analgesia or anesthesia is not well understood (Schallner and Goebel, 2013). A number of different receptors have been proposed to mediate the anesthetic effect of N2O, e.g. dopamine receptors, a2-adrenergic receptors, benzodiazepine (GABA-A) receptors and glutamatergic N-methyl-d-aspartic acid (NMDA) receptors (Maze and Fujinaga, 2001). The most often proposed mechanism for N2O-induced anesthesia is inhibition of excitatory glutamatergic
Medical use
N2O has a very low solubility in blood and adipose tissue and thus equilibration is rapidly achieved. N2O has the lowest lipid solubility and the fastest onset of all inhalation agents. N2O has a long clinical tradition as a relatively safe anesthetic. With a minimum alveolar concentration (the concentration providing anesthesia in 50% of patients) of 105% (v/v) in oxygen, the potency of N2O as an inhalation anesthetic is relatively low. In addition to anesthesia, N2O has been used as an
Recreational use
Nitrous oxide is increasingly popular among recreational drug users for its euphoric effects. It is typically inhaled, sometimes referred to as ‘nagging’ or “nanging”, commonly from bulbs (Fig. 1) or balloons. The non-refillable steel bulbs (or whippits) contain some 10 ml of nitrous oxide in liquid form under pressure (7–9 bar), which is equivalent to 4 L of gas under normobaric conditions. For recreational use, the bulbs are mostly released into a balloon using a metal cracker. Larger
Prevalence of recreational use
Among clubbers in Amsterdam, 71% of Dutch respondents had ever used nitrous oxide (men 75%, women 68%) and 33% had done so in the past month (Nabben et al., 2014). Life time use of nitrous oxide in this group was relatively high among youngsters under twenty (75%) and young adults in their early twenties (78%) compared to other age categories (Nabben et al., 2014). Between 2008 and 2013, N2O use among clubbers and ravers in The Netherlands increased 10-fold with a last month prevalence in 2013
Toxicity
Until 1956, when Lassen et al. reported megaloblastic bone-marrow changes following prolonged N2O exposure (Lassen et al., 1956), N2O was regarded as completely innocuous and enjoyed the reputation for being the safest general anesthetic (Sund and Berthelsen, 1994). For more than a century it was believed that N2O was an inert gas and it had been used without any serious side effect published in literature. This is generally still true as long as nitrous oxide is used for short episodes.
Dependency
Abuse and dependence liability has been a matter of political and scientific debate. Some argued that the gas is known since the 18th century and that abuse was seldom reported (Gillman, 1992). However, others have reported an elevated risk for N2O misuse, abuse, and dependence in professionals who have ready access to the substance (e.g. hospital staff, dentists, and medical students) (Rosenberg et al., 2015, Blanton, 2006). In the scientific literature, quite a number of cases have been
Legal status
Nitrous oxide is a legal drug and relatively easy available. Nitrous oxide can be legally sold for catering and other legitimate reasons, but its sale in gas-filled balloons on festivals and clubs intended for human recreational use is in many countries not allowed. In the UK such practice violates the Medicines Act which has initiated the Medicines and Healthcare Products Regulatory Agency (MHRA) to control the drug's supply under section 52 of the 1968 Medicines Act (ACMD, 2015). Similarly,
Summary and conclusion
Recreational use of N2O is emerging in some countries mainly in the club and festival scene. In most cases, N2O is used very modestly (>90% use monthly or less) and its use is relative safe. However, neurological and hematological effects may occur following heavy (>50 to 100 bulbs per session) or prolonged high dose use due to N2O induced vitamin B12 deficiency. Users should be informed about these potential serious side effect and doctors should be informed about the treatment of these
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