Addiction Medicine Made Easy | Fighting back against addiction

Laughing Gas Addiction Isn't Funny (Update from 2024)

• Casey Grover, MD, FACEP, FASAM

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Exploring the growing problem of recreational nitrous oxide use and its serious medical complications, including paralysis and permanent nerve damage. I share personal patient cases and investigate how this addictive substance is readily available in smoke shops and even on Amazon with minimal warning labels.

• Multiple patients experiencing serious neurological complications from recreational nitrous oxide use
• Personal investigation revealing easy access to nitrous oxide on Amazon marketed for whipped cream making
• How nitrous oxide depletes vitamin B12, leading to potential spinal cord and peripheral nerve damage
• Examination of labeling issues with commercial nitrous oxide products
• Comprehensive overview of nitrous oxide's history, effects, and recreational use patterns
• Medical complications including acute risks (seizures, cardiac issues) and chronic effects (neurological damage)
• Treatment approaches focusing on vitamin B12 supplementation and addiction therapies
• Growing prevalence of nitrous oxide use, especially among young people

Remember that treating addiction saves lives. If you or someone you know is struggling with substance use, please reach out for professional help.

To contact Dr. Grover: ammmadeeasy@fastmail.com

Speaker 1:

Welcome to the Addiction Medicine Made Easy podcast. Hey there, I'm Dr Casey Grover, an addiction medicine doctor based on California's Central Coast. For 14 years I worked in the emergency department, seeing countless patients struggling with addiction. Now I'm on the other side of the fight, helping people rebuild their lives when drugs and alcohol take control. Thanks for tuning in. Let's get started.

Speaker 1:

Today we are going to be talking about nitrous oxide. I have a number of patients that use it recreationally. It's a substance that we use at the hospital, where it's often referred to as laughing gas. It has amnestic and anesthetic qualities and it can also be euphoric. Now you might be wondering where patients who use it recreationally get it. Well, it turns out that this stuff is fairly easy to get. I was under the impression that you had to buy a can of whipped cream to get it. If you didn't know, nitrous oxide is the propellant used in cans of whipped cream that you buy at the grocery store. It's actually the gas that is in the can that pushes out the whipped cream. However, I have recently learned that they sell nitrous oxide at smoke shops In fact, the local smoke shop that I have gone to a few times to do my own research on how Kratom is sold, carries it. I actually found this out, as I said, when I was going to go to the smoke shop to buy Kratom and while I was waiting for the person to ring up my purchase, I noticed that there was a section for nitrous oxide and they sold multiple different products.

Speaker 1:

Unfortunately, I've recently heard from a few of my patients who have relapsed on nitrous oxide. One of them is a young man who was using it for several months. He actually got some tingling in his feet after using it for quite a while and fortunately he realized it was from the nitrous oxide and he stopped. He actually appears to be doing fairly well. Unfortunately, I have another patient who is a young female and she is not doing so well. She was recently in the hospital for this. I actually haven't seen her discharge summary, but she has significant weakness in her legs which, unfortunately, is one of the known medical complications of nitrous oxide use. Nitrous oxide, as we will hear later in this episode, can cause significant nerve damage. So as I was talking to this second patient about how she was doing, I asked her about where she was getting her nitrous oxide and if it had any warning labels on it and I was just curious does the product say that recreational use can lead to significant medical complications? And she said no. So I figured I was going to need to go back to the smoke shop and pick up one of the packages and see how the product was labeled. But she told me that she was getting her nitrous oxide from amazon and I thought, huh, I need to investigate this more.

Speaker 1:

So this morning, while I was out walking my dog, I opened up the Amazon app on my phone and indeed you can buy nitrous oxide on Amazon and it's actually sold for people who want to make homemade whipped cream, and I thought wait, wait, wait, wait, wait. This is the dumbest idea ever. Why are we selling an addictive and harmful substance as a propellant for whipped cream? There must be a better option. So I went on some food blogs and websites about food and apparently not.

Speaker 1:

Nitrous oxide is apparently the best propellant for some foods, including whipped cream. Nitrous oxide makes the whipped cream really fluffy and light, which is what makes people like it so much. I don't know about all of you, but I'm going to guiltily fess up that I have absolutely on multiple occasions, squirted whipped cream out of the can right into my mouth. It's just so light, fluffy, sweet and delicious, and unfortunately a lot of that is from nitrous oxide Bummer. So I was pretty frustrated by what I found.

Speaker 1:

So I went back to Amazon and wanted to see who was selling it and how they were labeling it. I found two companies fairly quickly that sell nitrous oxide in canisters and they both sell it as being used for homemade whipped cream and they had some selling points that it's easy to use and easy to connect to other tubes, and one of them even had a sales pitch that homemade whipped cream is so much better than what is sold in stores. Now, in terms of the product labeling for these two products, one of them said specifically that the nitrous oxide was for food use only. It was not to be used medically and not to be consumed recreationally, and they actually warned that there were adverse effects that could happen to a person's health if it were used recreationally. Unfortunately, it appears to be an international company, so there were some typos in that warning phrase. It was still intelligible, but at least there was a clear warning that the nitrous oxide was only to be used in food preparation, it was not for human consumption and that human consumption would lead to health consequences. And the second company did not mention anything at all about it being only to be used for food preparation. And as my dog's walk went on, I kept looking and unfortunately I kept finding more and more companies that were selling more and more nitrous oxide products. So this is where I am at.

Speaker 1:

We have a harmful substance that is addictive and can be used recreationally. Regular use can be harmful and unfortunately you can buy it in smoke shops and you can even buy it on Amazon, and the warnings are terrible or non-existent. Now, as I mentioned, when people do use it recreationally, there are some bad health consequences that can occur. The biggest issue is that nitrous oxide use depletes our B vitamins, particularly B12, and this can lead, when there is significant vitamin B deficiency, to spinal cord injury and peripheral nerve injury. In some cases the damage is reversible With vitamin B supplementation. In other cases it is permanent.

Speaker 1:

I do have one patient who no longer sees me, as he prefers to see psychiatry as opposed to addiction medicine, and he is actually wheelchair-bound from a spinal cord injury because of his addiction to nitrous oxide. So my poor patient this week. I'm sending her good vibes and I hope she's healing quickly. And as I was talking to her about what she was going through, I realized I needed to refresh my memory on how to treat nitrous oxide addiction and the consequences of nitrous oxide use. And fortunately, we covered this topic on this podcast back in January of 2024. And I actually went back and read my notes from that episode so that I was able to help her understand what was going on and we were able to come up with a treatment plan. So I know I needed a refresher on nitrous oxide and I'm assuming many of you may as well.

Speaker 1:

So with that, let's go back right now and re-listen to that earlier podcast episode on nitrous oxide addiction. It provides an overview of nitrous oxide as in how it's used, the complications of nitrous oxide use and how to treat actual nitrous oxide addiction. It is an incredibly good review of this very important topic. I will apologize, it's fairly dry, but there is so much good content, alright, here we go. I am actually really excited about this episode today.

Speaker 1:

I have had two of my patients recently let me know that they were using nitrous oxide and this was a substance that I didn't know very much about. I have seen cases of neurologic symptoms that have developed after nitrous oxide use, and it was a subject on my board exam. But I didn't know much more than that, and if you've been listening to this podcast for a while, you know that if I don't understand something in addiction medicine, it's time for a podcast episode. So, with that in mind, I wanted to put together an episode to provide an overview on the misuse of nitrous oxide and fortunately, I found some great papers on the topic. Our first article is entitled Recreational Nitrous Oxide Abuse Prevalence, neurotoxicity and Treatment. It was published in the journal Neurotoxicity Research in 2021, and Yan Yuan Sheng is the lead author. So let's get started digging into this article. It is actually a review article and it provides an overview of the topic of nitrous oxide use and recreational use in general.

Speaker 1:

The article begins with an introduction section that gives a great history and background on nitrous oxide. It was first synthesized in 1772, but wasn't used medically until 1844, when it was used by an American dentist to provide anesthesia for a dental extraction. The term laughing gas comes from an early description of the compound as able to cause stamping or laughing. Current uses of nitrous oxide include as a propellant for whipping cream, as a fuel booster in the auto industry and as an inhaled anesthetic in the medical field. The authors go on to note that the recreational use of nitrous oxide has been on the rise in recent decades. According to the authors, common street names of the substance include hippie, crack and whippets. When used recreationally, nitrous oxide is usually inhaled through a balloon or bulb, and this process may be referred to as nagging or nanging. Nitrous oxide produces effects in the human body within seconds after inhalation. The effects, which include analgesia, euphoria and hallucination, peak at one minute after inhalation and disappear within minutes without any sort of hangover effect. Some users may use nitrous oxide frequently within a few-hour period.

Speaker 1:

The authors move on to look at the epidemiology of recreational nitrous oxide use. They begin by noting that nitrous oxide is legal in most countries and can be easily purchased from the Internet. Rates of use vary by country, with some of the highest use being from the United Kingdom, with nearly 39% of the population in the United Kingdom having used nitrous oxide recreationally at least once in their lives. However, in all countries, recreational use of nitrous oxide is increasing. Rates of recreational nitrous oxide use have doubled in the United States between 2003 and 2015, and in a study of more than 30 countries. Rates of recreational nitrous oxide use have doubled between 2014 and 2019. Another trend seen with recreational nitrous oxide use is that the use in young people is increasing. A study in one US state found that as many as 16% of teens had used nitrous oxide within the past year. Another study looking at youth in New Zealand found that 12% of teens had used nitrous oxide within the past year. And finally, back in the US, data from the US Poison Control System showed that the prevalence of nitrous oxide use was highest in the 12 to 17 year old age group.

Speaker 1:

The authors move on to look at the health harms of nitrous oxide use. They start by noting that the mechanisms of nitrous oxide toxicity have not been fully elucidated and then go on to examine some hypotheses. They first look at acute toxicity. Nitrous oxide is more water-soluble than oxygen, so once it is inhaled, it is absorbed across the alveoli of the lungs faster than oxygen. This results in a dilution of the amount of oxygen being absorbed by the lungs, which results in decreased oxygen delivery to the brain. According to the authors quote a healthy person can tolerate this type of hypoxia in a well-ventilated space, but for persons with epilepsy, heart disease or other comorbidities it may induce seizures, arrhythmias or even respiratory or cardiac arrest. End quote.

Speaker 1:

The authors then move on to look at chronic toxicity. Chronic use and long-term exposure to nitrous oxide can lead to damage to the nervous system, which can include myelopathy and peripheral neuropathy, mental health symptoms such as delusion, delirium and depression, venous thromboembolism, anemia and skin disorders. The authors note that the majority of these complications are due to vitamin B12 deficiency from the nitrous oxide use. The authors then go on to note that in animal models, nitrous oxide exposure is actually the most effective way to induce vitamin B12 deficiency. The authors then go on to go through a deep biochemical explanation of how nitrous oxide causes B12 deficiency and how it causes the adverse health effects of nitrous oxide use. It's pretty detailed. I'll leave it to you to check out the paper if you want to dig in to the detailed biochemical explanation.

Speaker 1:

The authors then move on to discuss other ways, besides inducing B12 deficiency, that nitrous oxide causes adverse health effects. First, nitrous oxide causes NMDA antagonism, leading to neuronal cell death and damage to mitochondria within the cells. And second, nitrous oxide alters cerebral blood flow and the synthesis and release of multiple neurotransmitters, including norepinephrine, dopamine and serotonin, which leads to neurotoxicity. The authors then pivot to look at the clinical manifestations of the adverse health effects of nitrous oxide use. First, they look at acute exposure. Acute inhalation of nitrous oxide can cause respiratory irritation, interstitial emphysema and pneumomediastinum. When high concentrations of nitrous oxide are used, or when it is used repeatedly in an enclosed space, patients may experience hypoxia, asphyxia, arrhythmia or sudden cardiac death. Next, the authors look at chronic exposure.

Speaker 1:

The most common adverse health effects from chronic nitrous oxide use are neurological. Patients may develop myeloneuropathy, subacute combined degeneration, peripheral neuropathy or myelopathy. And, if you're wondering, subacute combined degeneration refers to demyelination of the spinal cord and white matter of the brain. Along with peripheral neuropathy. Most common symptoms that patients who use nitrous oxide recreationally experience are paresthesia, gait instability and weakness. One study found that lower limb involvement was more common than upper limb involvement. Movement disorder symptoms such as dystonia have been observed with nitrous oxide use, but are rare. As dystonia have been observed with nitrous oxide use, but are rare, the authors note that the main reason for these neurologic conditions is from the vitamin B12 deficiency caused by chronic nitrous oxide use. Neurologic conditions developing from nitrous oxide use are therefore more common in patients with pre-existing or co-existing vitamin B12 deficiency.

Speaker 1:

The authors move on noting that venous thromboembolic disease can be caused by nitrous oxide use, which has been reported in several cases, and the authors conclude with a list of other complications of recreational nitrous oxide use, including depression, anxiety, mania, agranulocytosis, thrombocytopenia, anemia, myelosuppression and skin hyperpigmentation. Now, all of these conditions develop with recurrent nitrous oxide use, but there does not appear to be a known dose and duration of use that causes them. The authors then move on to discuss dependence and tolerance. They note that current research does not indicate that regular nitrous oxide use causes physical dependence, but use can become compulsive and habitual. With regular nitrous oxide use, tolerance does develop, so higher amounts may be used to achieve the desired effects in regular users.

Speaker 1:

Next, the authors looked at what testing could be ordered when caring for a patient with recreational nitrous oxide use. First, due to reductions in vitamin B12 levels, a CBC may be considered, as it can show anemia, thrombocytopenia, myelosuppression and an elevated MCV level. A vitamin B12 level could also be checked, but the authors note that serum levels are not always a reliable indicator of the amount of B12 in tissue. As nitrous oxide has a very short half-life, there is no serum test to detect its use. When looking at patients with neurological symptoms. Mri is the best test to assess for spinal cord lesions or other nervous system lesions caused by recreational nitrous oxide use.

Speaker 1:

And finally, the authors conclude this article with a discussion of the treatment of nitrous oxide use, as well as the prognosis. It's important to note that this paper is published in a neuroscience journal, so they are focusing on the neurological symptoms. They begin by noting that there are no treatment guidelines for the treatment of recreational nitrous oxide use. Cessation of nitrous oxide is the primary treatment to reverse any adverse health effects that develop from recreational nitrous oxide use, along with vitamin B12 supplementation. The authors note that there is no consensus on dosing of vitamin B12 supplementation, but common treatment regimens include intramuscular vitamin B12 at a dose of 1,000 micrograms every day or every other day for a week, then once weekly for four to eight weeks, then once a month after that. There is also some evidence that high-dose oral vitamin B12 can be used instead of intramuscular, at a dose of 1,000 to 2,000 micrograms orally. The authors note that while most neurological symptoms will improve with vitamin B12 supplementation, some patients may have permanent neurological effects. The authors conclude this article with a brief summary and a reminder of the overall theme from this article that recreational nitrous oxide use is on the rise and carries significant health risks.

Speaker 1:

So this was a great paper looking at recreational nitrous oxide use and the medical complications from use, but I felt the discussion on treatment was lacking. They really just recommended stopping nitrous oxide use. But I felt the discussion on treatment was lacking. They really just recommended stopping nitrous oxide use. What therapies can help our patients stop using? And I was wondering are there medications that can be used off-label to control cravings? So I dove back into the literature and there is article after article on the medical complications of nitrous oxide use, after article on the medical complications of nitrous oxide use, but I couldn't find anything on how to treat the behavior of nitrous oxide use. I finally found another article that discussed inhalant use in general, which provided some insight. The article is entitled the Clinical Assessment and Treatment of Inhalant Abuse and it was published in the Permanente Journal in 2023, with Sina Radparvar as the sole author. Unfortunately, the article discusses the misuse of all different inhalants rather than just focusing on nitrous oxide specifically. Oh well, so the article has a section on the treatment of inhalant use disorder, so I jumped ahead to that.

Speaker 1:

The author reviews the literature on medications for inhalant use disorder, and it's largely small studies, case reports and case series. One small study found that baclofen at a dose of 50 mg per day reduced cravings for inhalants. Another study found that baclofen at a dose of 50 mg per day reduced cravings for inhalants. Another study found that lamotrigine at a dose of 100 mg per day reduced cravings for inhalants. A case report found that buspirone at a dose of 40 mg per day reduced cravings for inhalants. And a second case report found that risperidone at a dose of 0.5 mg per day reduced cravings for inhalants. And a second case report found that risperidone at a dose of 0.5 milligrams per day reduced cravings for inhalants. And a final study found that carbamazepine and haloperidol reduced psychiatric symptoms associated with inhalant use.

Speaker 1:

The author then moves on to look at behavioral interventions for inhalant use. Quote treatment should address the emotional, social, academic, cultural and demographic factors related to inhalant abuse. Treatment options include cognitive behavioral therapy, dialectical behavioral therapy, group therapy, individual therapy, family therapy and teachers about the harms of inhalant use, to prevent use in the first place. Additionally, the author notes that education about identifying behaviors that can suggest inhalant use is needed so that, once inhalant use is identified, treatment can be initiated promptly to prevent the harms of long-term inhalant use. And that is the end of the second article. It's time to wrap up this episode with some take-home points.

Speaker 1:

Number one nitrous oxide is a gas that is used medically as an anesthetic that has potential for misuse and recreational use. It is also used as a propellant in whipped cream. 2. Nitrous oxide, when used recreationally, is usually inhaled from a balloon or bulb. After inhalation, effects are felt within seconds, peak within one minute and wear off within a few minutes. Patients using nitrous oxide will feel analgesia and euphoria and may hallucinate. Number three recreational nitrous oxide use is on the rise in multiple countries and is a common recreational drug in youth.

Speaker 1:

4. Adverse health effects of acute nitrous oxide use include seizures, hypoxia, cardiac arrhythmia and cardiac arrest. 5. Adverse health effects of chronic nitrous oxide use include damage to the nervous system, mental health symptoms, venous thromboembolism, anemia and skin changes. Number six many of nitrous oxide's adverse health effects from chronic use are the result of vitamin B12 depletion caused by the nitrous oxide. Number seven when patients experience adverse health effects from chronic nitrous oxide use, the treatment is vitamin B12 repletion and cessation of nitrous oxide use. 8. There are no FDA-approved medications to reduce the use of nitrous oxide, but there are some small studies and case series of medications that have been used to reduce cravings to use. And number nine treatment of problematic nitrous oxide use involves behavioral interventions such as cognitive behavioral therapy, group therapy, individual therapy and motivational enhancement.

Speaker 1:

Before we wrap up, a huge thank you to the Montage Health Foundation for backing my mission to create fun, engaging education on addiction, and a shout out to the nonprofit Central Coast Overdose Prevention for teaming up with me on this podcast. Our partnership helps me get the word out about how to treat addiction and prevent overdoses about how to treat addiction and prevent overdoses To those healthcare providers out there treating patients with addiction. You're doing life-saving work and thank you for what you do For everyone else tuning in. Thank you for taking the time to learn about addiction. It's a fight we cannot win without awareness and action. There's still so much we can do to improve how addiction is treated. Together we can make it happen. Thanks for listening and remember treating addiction saves lives.