Recreational nitrous oxide use: Prevalence and risks

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Highlights

  • Recreational use of nitrous oxide is emerging.

  • No major side effects in moderate use.

  • Heavy use induces vitamin B12 deficiency leading to peripheral neuropathy.

  • Early sign of peripheral neuropathy is numbness in fingers.

  • Users are advised to consult physician when these signs appear.

Abstract

Nitrous oxide (N2O; laughing gas) is clinically used as a safe anesthetic (dentistry, ambulance, childbirth) and appreciated for its anti-anxiety effect. Since five years, recreational use of N2O is rapidly increasing especially in the dance and festival scene. In the UK, N2O is the second most popular recreational drug after cannabis. In most countries, nitrous oxide is a legal drug that is widely available and cheap. Last month prevalence of use among clubbers and ravers ranges between 40 and almost 80 percent. Following one inhalation, mostly from a balloon, a euphoric, pleasant, joyful, empathogenic and sometimes hallucinogenic effect is rapidly induced (within 10 s) and disappears within some minutes. Recreational N2O use is generally moderate with most users taking less than 10 balloons of N2O per episode and about 80% of the users having less than 10 episodes per year. Side effects of N2O include transient dizziness, dissociation, disorientation, loss of balance, impaired memory and cognition, and weakness in the legs. When intoxicated accidents like tripping and falling may occur. Some fatal accidents have been reported due to due to asphyxia (hypoxia). Heavy or sustained use of N2O inactivates vitamin B12, resulting in a functional vitamin B12 deficiency and initially causing numbness in fingers, which may further progress to peripheral neuropathy and megaloblastic anemia. N2O use does not seem to result in dependence. Considering the generally modest use of N2O and its relative safety, it is not necessary to take legal measures. However, (potential) users should be informed about the risk of vitamin B12-deficiency related neurological and hematological effects associated with heavy use.

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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