Early treatment can reverse nitrous oxide effects

Subacute combined degeneration: Nitrous oxide and gastritis.


Nitrous oxide, also known as “whippets” or “laughing gas,” is easy to get online for recreational use. However, using it can lead to severe consequences like paralysis. The good news is that if doctors diagnose and treat patients quickly, the damage can be reversed. It’s essential to be aware of nitrous use and to screen for it to ensure early treatment and prevent serious complications.

In 2020, nitrous oxide was the second most popular recreational drug for 16- to 24-year-olds in the U.K., after cannabis. In the U.S., its use is increasing rapidly, with nearly 13 million Americans aged 12 and older misusing it, according to a 2019 survey. Some experts are concerned that the COVID pandemic may have worsened its misuse.

When people inhale nitrous oxide for fun, it can harm the body’s ability to use vitamin B12. This is risky because B12 protects nerves in the brain and spinal cord. Long-term use of nitrous oxide can cause various health problems, including nerve damage and psychosis.

In a case study from October 2023, Yale School of Medicine researchers emphasized the importance of doctors thoroughly checking patients with symptoms of B12 problems. They say quick action can successfully treat even severe consequences.

Tova Gardin, MD, neuroimmunologist and psychiatrist at Yale School of Medicine and first author of the study, said, “Recreational nitrous oxide use is increasing. If we treat our patients early, we can reverse serious neurologic complications. So, it’s important to know about nitrous use, and it’s important to screen for it.”

Nitrous oxide is a clear gas used as a sedative in dental and medical procedures. People also buy it to make whipped cream fluffy. Inhaling can make you feel happy or relaxed, but it can also cause headaches, dizziness, anxiety, or fainting.

Recreational use of nitrous oxide started in the late 1700s, soon after it was invented by Joseph Priestly in 1772. Chemist Humphry Davey hosted parties where people inhaled the gas from a bag. These gatherings helped discover the drug’s pain-relieving effects. By the mid-1800s, dentists and doctors used it for numbing during procedures. It’s widely used in dentistry for sedation, surgeries, childbirth, and other anesthetics.

Recreational use of nitrous oxide has become prevalent because it’s legal and easy to obtain. It’s widespread at underground parties and music festivals, with many young people misusing it. Unfortunately, those using it for fun often don’t realize how risky it can be due to its easy availability.

Gardin said, “It was shocking to me when I visited a popular retail website and typed in ‘nitrous oxide,’ the products algorithmically suggested to be bought together were those that would be used for substance use—not for whipped cream.”

The case study shows that when treating the effects of nitrous oxide, doctors must carefully evaluate the situation. The research was prompted by a man in his 30s who experienced numbness, weakness, and difficulty walking after using nitrous oxide regularly for four to five months. 

Through a detailed clinical history and an MRI scan, the doctors identified abnormalities in his dorsal column, a nerve pathway related to sensory function. The diagnosis was subacute combined degeneration of the spinal cord, explaining his symptoms.

Gardin said, “Next, the team looked for any concomitant causes of vitamin B12 deficiency. They performed a blood test and found that the patient’s level of B12 was in the normal range. However, further testing revealed he had elevated levels of two metabolites of vitamin B12—methylmalonic acid and homocysteine. “This gave us a clue that the patient had some sort of difficulty with B12 metabolism.”

The doctors conducted tests to check for antibodies related to intrinsic factors and gastric parietal cells, which could indicate pernicious anemia, a rare autoimmune disorder affecting vitamin B12 absorption. The patient indeed had this condition.

To reverse the effects of nitrous oxide, the first step was to stop using it completely. Then, the doctors treated the patient with a seven-day course of intramuscular vitamin B12, followed by weekly injections for a month. He will need monthly B12 treatment for life, along with physical and occupational therapy. Mental health care services were also recommended for substance use.

After treatment, the patient recovered sensation and regained the ability to walk. The doctors stress the importance of early intervention and additional screening for B12 issues, ensuring patients receive necessary neurological and psychiatric care.

Gardin stressed that nitrous oxide use is more widespread than many realize. Patients showing neurologic or psychiatric symptoms from nitrous oxide use should be quickly checked for other vitamin B12 issues. Treating chronic nitrous oxide complications needs a team approach, dealing with all the underlying neurologic and psychiatric causes. 

Regular nitrous oxide use can create a cycle where it causes B12 issues, leading to symptoms that reinforce nitrous oxide use. Comprehensive neurologic and psychiatric care is crucial for treating and preventing relapse in chronic nitrous oxide users.

Journal reference:

  1. Tova Michal Gardin, Annie Yang, et al., Subacute combined degeneration of the spinal cord in a patient with nitrous oxide use and autoimmune atrophic gastritis. BMJ. DOI: 10.1136/bcr-2023-254727.


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