Tox in The Land: Whip-it! But is it Good?

What are Whip-its?

  • ‘Whip-its’ (aka Laughing Gas; Cartridges; Hippy Crack; N2O, Nangs) are terms for intentionally inhaled Nitrous Oxide.

  • Nitrous oxide is an odorless and colorless gas used in anesthesia and as a propellant (think the last two seconds of a can of whipped cream)

 
 
 



Historical Origins of Recreational Use of Nitrous Oxide

  • In 1772 Nitrous Oxide is discovered by English chemist and philosopher Joseph Priestly

  • In 1800 British chemist Humphry Davy publishes a book about the properties, psychotropic effects included.  

  • Initially, use was fairly limited, with artists, scientists, and medical students utilizing the drug

  • Increased availability of the drug and popular users such as members of the Grateful Dead, caused a surge in the drugs’ popularity in the 1960’s

Clubgoers inhale nitrous oxide on the dance floor during the first annual Halloween party at Studio 54 in 1977

https://www.nytimes.com/2021/01/30/style/nitrous-oxide-whippets-tony-hsieh.html

https://wellcomecollection.org/works/wtdr8dvd/items?canvas=7

https://www.gettyimages.com/detail/news-photo/grateful-dead-lyricist-and-electronic-freedom-foundation-co-news-photo/915950002

User Experience

  • Those who use Nitrous Oxide for recreational purposes describe a brief, euphoric disorientation and depersonalization. Experiences range from an experience of giddiness, to hallucinations, to loss of consciousness.

  • “Basically, at the beginning of the experience one feels what I would call a 'beer buzz'. You are happy and may giggle or find regular things quite amusing. Next, a stage of confusion begins. If one's eyes are kept open you may hallucinate. I quite vividly saw things that could not have possibly existed.” –Testimonial of Nitrous Oxide recreational use

Mechanism of Action by Effect

  • Anesthetic effect- non-competitive NMDA inhibition in the central nervous system.

  • Analgesic- Causes the release of endogenous opioids

  • Anxiolysis- GABA-A activation via voltage-independent Calcium channels

 
 


Adverse Effects

  • Respiratory Depression- Nitrous Oxide in isolation seems to have a limited effect, however when used in conjunction with other agents such as sedatives, hypnotics, or opioids, as it often is when used as a drug of abuse/misuse, it potentiates the depressing effects of these agents. Deaths have occurred with this concomitant usage and resulting traumatic injuries

  • Diffusion hypoxia: After use, Nitrous Oxide enters the alveolar space faster than Nitrogen leaves, this leads to a dilution of the alveolar gases, specifically oxygen, resulting in hypoxia. In fact, many users describe an ‘air-hunger’ phenomenon immediately after use

  • Impairment of DNA synthesis, methylation, and myelin production- Nitrous Oxide irreversibly oxidizes the cobalt ion of cobalamin, rendering cobalamin unusable in its typical role as a co-enzyme in the formation of methionine. This results in a functional deficiency of B12. This can lead to megaloblastic anemia and subacute combined degeneration of the spinal cord, which often presents as paresthesia, ataxia, and flaccid weakness

  • Coagulopathy- More recently, chronic usage of Nitrous Oxide has been implicated in STEMI and Venous Thromboembolism through use-associated hyperhomocysteinemiaresulting from the functional B12 deficiency

Management in Toxicity

  • Neurologic deficits, while some may be permanent based on the degree of damage, can sometimes be reversible

  • Abstinence from Nitrous Oxide is essential to allow for the proper utilization of B12

  • Treatment regimens vary based on practice pattern but typically include either IM or PO formulations of Vitamin B12

  • Symptomatic management for issues of hypoxia, venous thromboembolism, and other associated complications


Nitrous in the News

Vitamin B12

 
 
 

AUTHORED BY: GABE ALAGNA, MD, EM PGY1

FACULTY EDITING BY: LAUREN PORTER, DO

References

  • Brice, L. (n.d.). Grateful dead lyricist and Electronic Freedom Foundation co-founder... Getty Images. https://www.gettyimages.in/detail/news-photo/grateful-dead-lyricist-and-electronic-freedom-foundation-co-news-photo/915950002

  • Davy, H. (1800). Researches chemical and philosophical: Chiefly concerning nitrous oxide or dephlogisticated nitrous air and its respiration / by Humphry Davy. Wellcome Collection. https://wellcomecollection.org/works/wtdr8dvd/items?canvas=7

  • Gillman, M. A. (2019). Mini-Review: A brief history of nitrous oxide (N2O) use in Neuropsychiatry. Current drug research reviews. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637098/

  • Gupta, P. K. (1970, January 1). Mechanism of nanotoxicity. SpringerLink. https://link.springer.com/chapter/10.1007/978-3-031-24287-8_3

  • James , B. (2005). Nitrous Oxide Revelations of God and Eternity. Nitrous oxide - EROWID exp - “nitrous oxide revelations of god and eternity.” https://www.erowid.org/experiences/exp.php?ID=36803

  • Knuf, K. (n.d.). Nitrous oxide - statpearls - NCBI bookshelf. Nitrous Oxide . https://www.ncbi.nlm.nih.gov/books/NBK532922/

  • Marcus, E. (2021, January 30). Nitrous Nation. The New York Times. https://www.nytimes.com/2021/01/30/style/nitrous-oxide-whippets-tony-hsieh.html

  • Schaffer, D., & Goldfine, C. (2021). Nitrous Oxide Misuse and abuse. ACEP Symbol. https://www.acep.org/toxicology/newsroom/jun2021/nitrous-oxide-misuse-and-abuse

  • Shoults, K., & Barbara Mozingo. (2016). case report: Neurological complications of nitrous oxide abuse. BCMJ, vol. 58, no. 4, page(s) 192-194. https://bcmj.org/articles/case-report-neurological-complications-nitrous-oxide-abuse

  • TodayShow. (2022, August 30). Why you now need to be 21 to buy canned whipped cream in New York. TODAY.com. https://www.today.com/food/news/why-you-need-id-to-buy-canned-whipped-cream-in-new-york-rcna45419

  • U.S. National Library of Medicine. (n.d.). Nitrous oxide. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/compound/Nitrous-Oxide

ToxLauren McCaffertytoxicology, medical toxicology