Nitrous Oxide Harm Reduction and Supplements

Disclaimer

If you are experiencing a medical emergency, please call 911.

The information and recommendations provided on this website should be regarded only as anecdotal, and do not constitute medical advice. It has been noted that there is a deficiency in research and useful treatment recommendations concerning N2O and its effects on health. This information is provided with the intent of harm reduction only.

Heavy and prolonged nitrous oxide use does significant damage to the nervous system and circulatory system. It can cause psychosis, addiction, permanent nerve damage and paralysis, anemia, and blood clots that can lead to strokes, deep vein thrombosis, and pulmonary embolisms. Supplements can help delay damage and accelerate the body and brain's healing from damage.

No amount of supplementation will keep a heavy and frequent nitrous user healthy forever. These supplements can reduce the pace of damage and accelerate healing, but it's essential that nitrous use be limited to once every month or few weeks at maximum to maintain long term health. If that isn't possible, you should consider the possibility that you may be in addiction and seek help.

Always consult a qualified healthcare professional for accurate information and guidance.

The Essential Supplements While Using
Blood Tests for Nitrous Users
Secondary Supplements to Protect the Brain and Accelerate Healing
Supplements that May Help with Anhedonia and Psychosis
Prescription Drugs and Psychedelic Treatment for Nitrous Addiction

The Essential Four Supplements:
Reducing Harm While Using

Quick summary: If you're using nitrous oxide, take these four key supplements:
1. L-Methionine, 1-2 grams / day.
2. B12 + B complex, 5,000 mcg / day.
3. Betaine, 1-3 grams / day.
4. Folinic Acid, 10-15 mg / day. For very heavy and prolonged nitrous use.

Read below for more about the reasons, the science, and the dosage.

Nitrous oxide oxidizes B12 inside critical enzymes, including methionine synthase. This turns off key processes in the body. B12 levels may appear fully normal in blood tests, but this is meaningless, as the B12 within those critical enzymes has been oxidized and is ineffective. Once oxidized and inactivated, B12 related enzymes remain stuck in this non-functional state. It takes up to a week or more after nitrous use has ended for your body to recycle these old, disabled enzymes and create a full supply of new, healthy enzymes. It takes weeks more for those enzymes to do their work. Hence the need for multi-week breaks between nitrous oxide sessions.

Our goal in supplementation is to slow the progression of three problems:

1. Nerve damage. Without a molecule called methionine, which the body can't make during or for days after heavy nitrous use, the body can't make or restore myelin, which surrounds the long nerves in the body and helps nerve signals travel back and forth. Nerve transmission slows and breaks down. This leads to tingling, numbness, clumsiness, weakness, and eventually paralysis and the loss of the ability to walk. This is by far the most common long term physical harm from nitrous.

2. Blood clots and stroke. Methionine synthase, which is disabled by nitrous oxide, is also needed by the body to break down a molecule called homocysteine. A buildup of this substance increases the risk of blood clots that can break off and travel to the heart or brain, causing strokes or even death. While this is less common than nerve damage, it has potentially fatal consequences, and has affected many heavy nitrous users.

3. Suppressed bone marrow function and anemia. Heavy nitrous oxide use suppresses the ability of the body to synthesize DNA. This in turn suppresses the ability of your bone marrow to create healthy new blood cells, including the red blood cells that carry oxygen through the body, and white blood cells critical to the immune system. The term for this is megaloblastic anemia. Over time, heavy nitrous users become fatigued, weak, pale, short of breath, and possibly immune suppressed. This is the slowest-progressing of these harms, and will likely only seriously affect people who use nitrous heavily for weeks or months on end without long breaks.

To reduce the risk of these outcomes, there are four essential supplements to take every day before, during, and after nitrous use and for weeks after. The links point to Amazon, but these can be purchased from most drug stores.

Supplement	Why	Dosage
1. L-Methionine	Protect against nerve damage and paralysis. Methionine is essential for making DNA and especially for the myelin sheaths that surround nerves and keep them healthy. The body can’t make methionine without healthy B12 enzymes, but it can absorb methionine from food and supplements such as this one. In addition, L-methionine slows or prevents nerve damage from nitrous in animals and has shown some promise in halting or reversing nitrous nerve damage in humans, even moreso than B12. In addition, high levels of methionine seem to reduce the rate at which nitrous oxide inactivates the vital methionine synthase enzyme and may accelerate the rate at which this enzyme recovers after nitrous use is ended. It's important to understand that, even with B12 supplementation, it may be a week or more after nitrous oxide use has ended before the body is able to make its own methionine and start to make healthy myelin nerve sheaths. Thus, supplementing with L-methionine may be the single most important thing a nitrous user can do to protect against nerve damage or paralysis while using or for days after. Read about the science of methionine in nitrous oxide usage.	1-2 grams / day Up to 3 grams / day for short periods.
2. B12 + B complex [B12 should be methyl-cobalamin.]	Overall nervous system and body health. Providing the body ample B12 improves the ability of the body to produce new, healthy B12 related enzymes since nitrous has disabled the existing supply. B12 supplementation may reduce homocysteine levels and reduce the pace (but not stop) nitrous nerve damage. You still must take breaks from nitrous, as continued nitrous usage will simply oxidize the new B12 in freshly created enzymes as well. It takes days to fully restore the body's stockpile of these important enzymes. B6 and other B vitamins can assist with other bodily functions. B6 in particular also helps lower homocysteine and reduce the risk of blood clots and stroke. B12 should be taken sublingually - held under the tongue. Choose methylated B12 (methylcobalamin - the active form) as some individuals have genetic difficulty converting other forms of B12 into the active form. Read the science of why you should always take B12 and other B vitamins during and after nitrous use.	~5,000 mcg / day
3. Betaine (aka TMG)	Lower risk of blood clots and stroke. Betaine lowers homocysteine levels in a way that doesn't depend on B12 or B12 related enzymes. It does so to a greater extent than B6, especially at high doses. This lowering of homocysteine levels reduces the risk of blood clots and stroke. It's also important to understand that L-methionine, while it protects nerves from damage, can also raise homocysteine levels, making betaine an essential complement. Read about the science of betaine supplementation.	1-3 grams / day Up to 6 grams / day for short periods.
4. Folinic Acid (aka calcium folinate)	Support bone marrow function and blood cell production. A form of folic acid. It improves the ability of the body to synthesize DNA and create healthy blood cells, even when B12 related enzymes are inactivated. (Other forms of folate, including methylfolate, require methionine synthase to function, making them non-functional during nitrous use and for days after.) Nitrous oxide use suppresses bone marrow function and thus new blood cell production after just a few hours of use. For most people, a single session will not cause noticeable problems, as bone marrow function will mostly return within a week. However, frequent or continuous use for long periods of time can result in the body being continually unable to produce a sufficient number of red or white blood cells. As such, this supplement is important for those who use nitrous for long protracted periods or more frequently than once every few weeks. In studies of patients receiving 24 hours of nitrous anesthesia, extremely high dose folinic acid reversed or prevented bone marrow suppression and restored healthy blood cell production. Similar results were found with smaller doses in rats given nitrous for 6 or 12 hours continuously. Note that the dosage suggested involves a very large number of supplement capsules. An alternative is to talk to your physician and request a prescription for Leucovorin, the prescription strength form of folinic acid. Use the reference above or suggest your physician read this paper. ("5-formyltetrahydrofolate" is another name for folinic acid / Leucovorin.)	10-15 mg / day Up to 60 mg / day, divided into four doses, for short periods during active usage.

How long should these supplements be taken?
These should definitely be taken daily during active nitrous use and for days or weeks after. After a protracted period of heavy nitrous use that leads to any symptoms such as brain fog or numbness or tingling, the essential supplements above should be continued until all symptoms have subsided. The amount of all of them can be reduced over time as symptoms improve. B12 can be (but doesn't have to be) dropped to 1,000 mcg / day when symptoms are substantially better, even before they've disappeared entirely. Betaine can be stopped if a homocysteine test shows homocysteine levels are normal, so long as nitrous use has ended. Folinic acid can be ended a week or two after the end of nitrous use, and replaced with much lower dose methylfolate (described below).

Should I take these supplements on days I'm using?
Yes, absolutely. There's a persistent myth that B12 cannot be absorbed by the body during nitrous use. This is somewhere between false and an oversimplification. The body certainly absorbs B12 during nitrous oxide use, and can use it to create new enzymes such as methionine synthase. Some of the new enzymes produced, however, will become oxidized and deactivated by continued nitrous use. That said, some creation of new critical enzymes is better than none. And the other supplements above are not impacted at all by nitrous use. Thus, use of these supplements is a good idea at any time in the cycle of nitrous use. These compounds are also difficult to overdose from. If in doubt, take some both immediately before and immediately after a session using nitrous.

And always take breaks of multiple weeks between sessions of nitrous use.

Should I get B12 injections?
B12 injections are the standard of care for treating nitrous oxide neuropathy. On this site we recommend sublingual B12 as studies have found that high dose sublingual B12 is as effective as IM injections. Sublingual B12 can also be easily and inexpensively purchased in a pharmacy or online. That said, there is some disagreement about how to interpret these studies. So if you can get B12 injections, by all means do so.

At the same time, given that B12 injections are typically not given daily, and the B12 is excreted from the body quickly, continue to take sublingual B12 any day that you're not receiving an injection. And also bear in mind that, for as long as nitrous use continues, L-Methionine is an even more important supplement for nervous system health.

Key Blood Tests for Current and Former Nitrous Oxide Users

As mentioned above, B12 tests can show healthy or normal B12 despite nitrous use and functional B12 deficiency. A B12 test that shows a low reading should be taken seriously. One that shows normal or high levels shouldn't provide one with a false sense of safety. Two other tests which are more revealing are homocysteine and MMA:

1. Homocysteine. Homocysteine builds up during nitrous use and increases the risk of blood clots and stroke.

2. Methylmalonic acid (MMA). This is another molecule that builds up in the body during nitrous use. Elevated levels demonstrate that the body's B12 related enzymes aren't working properly. Bringing MMA levels back to normal is a positive sign.

3. Complete Blood Count (CBC). This test can identify nitrous-caused anemia and bone marrow suppression. Watch for reductions in RBC (red blood cell count), Hgb (Hemoglobin), and Hct (hematocrit); and for increases in MCV (mean corpuscular volume). These indicate that your body has fewer red blood cells and less of the hemoglobin that moves oxygen through your body. Very high dose folinic acid can help with bone marrow function during nitrous use, but only partially, and not forever.

Secondary Supplements to Protect the Brain and Accelerate Healing

Some additional supplements listed below can possibly help in protecting the brain from inflammation and oxidative stress that's caused by nitrous oxide, and in accelerating the restoration of the myelin layer that sheaths neurons. With the exception of methylfolate, the evidence is more speculative and indirect for the supplements below, but they may help, and are very unlikely to hurt.

Supplement	Why	Dosage
Methylfolate	Overall nervous system and body health. Methylfolate is an active form of folate which assists in nerve health, in lowering homocysteine and reducing blood clot risk, and in bone marrow function. It is the most important supplement on this secondary list. Methylfolate will not function during active nitrous use. During active nitrous use, we recommend folinic acid (above), because folinic acid can boost bone marrow function even without functioning B12-related enzymes. Methylfolate is recommended as soon as nitrous use ends. This methylated form of folate is recommended because some individuals with mutations in the MTHFR gene can't convert other forms of folate (such as folic acid or folinic acid) into this active form. But all individuals can use methylfolate directly, so long as nitrous oxide use has ended. Note, a small percentage of older individuals, above age 60 and with a specific genetic variant, may be at risk of side effects from methylfolate supplementation above 800 mcg / day. If you're over 60, consider keeping your dosage below 800 mcg / day. Consult your physician if you're concerned.	800-1,000 mcg/day.
NAC	Brain protection, cravings, mild anti-psychotic. NAC is a potent anti-oxidant and anti-inflammatory with possible antipsychotic properties. It may help protect the brain against the inflammation and oxidization that nitrous causes. It also mildly reduces cravings to multiple drugs and in particular helps balance activity at the NMDA receptor that nitrous oxide blocks.	Up to 3,600 mg / day. Divided into three doses.
ALA (Alpha Lipoic Acid)	Brain protection, powerful anti-oxidant. ALA is one of the most powerful antioxidants known, and has shown evidence of neuroprotective effects in many diseases and conditions. It may help protect the brain from the oxidation and inflammation caused by nitrous use.	1,200 mg / day
Vitamin D	Rebuilding myelin around nerves. Vitamin D has been shown to accelerate the process of remyelination - rebuilding the myelin sheath around nerves that nitrous degrades. Vitamin D has specifically been found to help repair nerve damage in multiple sclerosis, a disease that also attacks myelin. Based on this, there's reason to believe vitamin D may help accelerate the healing from nitrous-induced neuropathy and nerve damage as well.	Up to 5,000 IU / day
Omega 3 Fatty Acids	Brain protection and nerve rebuilding. These substances found in fish oil, particularly EPA, help with multiple mental health conditions, have an anti-inflammatory effect, and seem to help in maintaining and rebuilding the myelin sheath around nerves.	Up to 3 grams / day
Alpha GPC	Brain protection and nerve rebuilding. Alpha GPC is a nutrient that is used in making cell membranes, including the myelin around nerve cells. It may help accelerate the healing from nitrous's damage to myelin sheaths, though no direct studies have been conducted for this. Alpha GPC also raises brain levels of the neurotransmitter acetylcholine, which is crucial for learning and memory, and may assist with post-nitrous brain fog.	1,200 mg / day

Supplements to Help with Nitrous Anhedonia and Psychosis

Heavy and/or prolonged use of nitrous oxide causes psychosis, delusions, paranoia, persecutory delusions, hostility towards others, and full on breaks from reality. Lack of sleep during a nitrous binge often exacerbates this. These symptoms generally go away quickly after nitrous use is ceased and normal sleep is resumed. Symptoms often mostly subside within hours, though sometimes they may linger for days or even weeks.

People recovering from heavy nitrous use also frequently report anhedonia - the inability to feel joy or pleasure. They can report blunted emotions, low motivation, reduced interest in social interaction and activities, isolation, difficulty concentrating, and general apathy. This anhedonia and related symptoms can last for days or weeks after the end of a heavy period of nitrous use.

Long term psychosis or anhedonia that lasts more than days or a few weeks should be evaluated by a psychiatrist. It's possible that heavy nitrous use can trigger lasting psychotic or schizophrenic symptoms that can only be treated by a medical professional.

Nonetheless, there are some supplements that have some promise in reducing anhedonic or schizophrenic symptoms that may be worth trying. These supplements generally have more evidence of effectiveness on the more depressive symptoms (isolation, withdrawal from others, apathy, anhedonia) than on the more manic schizophrenic symptoms (hallucinations, voices in the head). That said, they have some, but inconsistent, evidence of effect on both.

These supplements work in part by boosting or restoring the function of the NMDA receptor. Nitrous oxide blocks this receptor, preventing important signals that help the brain differentiate reality from fantasy from getting through. The supplements below stabilize or boost NMDA signaling in the brain, potentially helping to reverse what nitrous oxide has done in the short term, and possibly helping to restore the brain to its pre-nitrous state if taken over a longer term.

Supplement	Why	Dosage
Sarcosine	Increase NMDA receptor function. Sarcosine is an NMDA "co-agonist". It also increases the levels of glycine in the brain, another NMDA co-agonist. Nitrous oxide blocks the NMDA receptor, reducing the amount of signaling that happens via this pathway in the brain. That causes long lasting changes to brain circuits long after nitrous oxide use has ended. Sarcosine works (gently) in the opposite direction: It increases the amount of signaling that happens at NMDA receptors. By doing so, there's reason to hope that over the long term it may help reform the brain to a state more similar to that previous to nitrous oxide abuse. People who supplement with Sarcosine report increased mental clarity and emotional depth. It's been found to be mildly effective at reducing the more depressive symptoms of schizophrenia, psychosis, and anhedonia. Note that this supplement is likely completely ineffective while nitrous is in the body.	1 - 2 grams / day Start low (500mg/day) and increase over time.
D-Serine	Increase NMDA receptor function. D-Serine is another NMDA co-agonist that increases NMDA receptor function, acting opposite to how nitrous oxide works. It has also been found effective in reducing some of the more depressive symptoms of schizophrenia, psychosis, and anhedonia. Also likely ineffective while nitrous is in the body.	1 - 3 grams / day Start low (500mg-1g) and increase over time.
NAC	NMDA receptor stabilizer, mild anti-psychotic. NAC, mentioned above, is a potent antioxidant that's used in the treatment of multiple mental health disorders, including psychosis. It helps stabilize NMDA receptor function. It's also been found to mildly or moderately reduce cravings for multiple drugs.	Up to 3,600 mg / day, split into 3x 1,200 mg doses.

Medications and Psychedelic Treatments for Nitrous Addiction

Nitrous oxide can be extremely addictive, with extremely high relapse rates and severe damage to one's life. Some addicts describe nitrous as being more difficult to kick than opiates or methamphetamines.

Kicking an addiction and remaining sober afterwards usually requires multi-pronged efforts that include social support, psychotherapy, sobriety meetings and community, willpower, and resolving or removing the conditions that led to addiction in the first place.

Prescription medications, supplements, and psychedelic therapies may all help. None of these is a silver bullet. No trials of medications - or any other treatment approach - specific to nitrous oxide addiction have been published. The following is a list of compounds that may help, based on anecdotal reports from nitrous users and what we can infer from their mechanisms of action and the evidence for these approaches in treating other drug addictions.

In this category especially, we urge you to talk to a psychiatric professional. The below list should be taken as a starting point for conversations with your physician or addiction psychiatrist, and not as direct medical advice itself.

Context - The Neurobiology of Nitrous Addiction
Nitrous oxide blocks the NMDA receptor. This receptor receives signals sent by glutamate, the most prevalent neurotransmitter in the brain, which is itself associated with addiction. The blockage of glutamate at the NMDA receptor leads the brain to release its own opioid molecules (giving nitrous a very mild opioid effect) and causes a surge of dopamine in the brain.

Dopamine is likely the primary culprit in nitrous addiction. Recent studies in rodents have found that blocking one dopamine receptor (the D1 receptor) almost entirely eliminates the addictive properties of nitrous. At a guess, dopamine is the primary culprit in nitrous oxide addiction, the glutamate / NMDA system is the next most important culprit, and the opioid system plays a smaller role than either of those.

Prescription Pharmaceuticals that May Help in Nitrous Addiction & Relapse Prevention
Each of the following has anecdotal reports from at least one nitrous user, as well as biological reasons to believe it may be effective. Consult your psychiatrist before trying any of these prescription medications. They must be prescribed by a physician and used under a physician's care.

Medication	Reason
Acamprosate	NMDA modulator, used in alcoholism. Acamprosate is a medication used in treating alcoholism. It modulates, or balances out, the glutamate / NMDA system, keeping signals from being either too strong or too weak. (Alcohol is also a mild NMDA antagonist.) In alcoholism, acamprosate reduces cravings noticeably. Anecdotal reports from nitrous users suggest that it has made a major difference in at least some individuals' cravings.
Topiramate	Suppresses dopamine spikes, modulates NMDA, used in alcoholism. Topiramate is another medication used in alcoholism, with a similar effect size to acamprosate. Topiramate also modulates the NMDA receptor. It has an added effect which is that it suppresses the size of large dopamine spikes. Those large floods of dopamine happen when an addict feels the urge and anticipation of seeking nitrous, and also happen in response to nitrous use, conditioning the brain to want more. One nitrous addict has stated that they believe topiramate has helped them.
Naltrexone	Opioid receptor blocker, used in alcoholism. Naltrexone is another drug used in alcoholism, but with a different mechanism of action. Naltrexone partially blocks opioid receptors in the brain. It reduces alcohol consumption somewhat, and has a larger effect on opiate addiction. Naltrexone has the least to do with the dopamine and glutamate / NMDA pathways that we think are the largest cause of nitrous addiction, but it has been successfully used in two medical case studies, and at least one other nitrous addict has stated that they've found it helpful in reducing cravings.
An Anti-depressant	Reduce urge to escape stress or sadness. Some users have commented that anti-depressants were useful for them in addressing the underlying conditioning that led to their usage, or in reducing cravings. Different anti-depressants seem to work for different individuals. Bupropion is commonly mentioned in anecdotal reports, and has also been found effective in quitting smoking. There is, however, no strong evidence suggesting any particular anti-depressant. Consider this extremely anecdotal, and discuss with your mental healthcare provider.
Highly speculative: Ecopipam	Experimental D1 dopamine receptor blocker. Finally, and in the most speculative category, is a not-yet-approved drug called Ecopipam. As mentioned earlier, blocking the D1 dopamine receptor in mice almost completely removes the addictive properties of nitrous oxide. There is no drug currently approved for humans that selectively blocks the D1 receptor only. Ecopipam, however, works in this way. It blocks the D1 dopamine receptor but not other related receptors that can lead to severe side effects. It's in late stage testing for the treatment of Tourette's syndrome and could be approved in 2026. It's far too early to actively recommend this drug for treatment of nitrous addiction or nitrous psychosis. We mention it here in the hope that physicians and investigators will take note of its potential use and conduct studies or explore its off-label use in patients with severe nitrous addictions or psychotic episodes.

Psychedelic Therapy for Nitrous Oxide Addiction

Finally, the past few years have seen exploration of the use of psychedelics for addiction treatment and relapse prevention.

Psilocybin, the active ingredient in psychedelic mushrooms, has shown impressive results in small studies for the treatment of alcoholism and for helping people quit smoking. It has also been shown to be an extremely potent antidepressant, comparable to and in many ways stronger in effect than SSRIs, with effects that can last for a year or more after one or two uses, with far fewer side effects. Most intriguingly, studies show that psilocybin helps people reinvent themselves and imagine new ways of being, which may be how it assists in breaking alcohol and nicotine addictions.

These studies use psychedelics in a controlled environment, after all other drug use has ceased. We do not recommend the use of psychedelics in a chaotic environment or while using nitrous as a viable tool for breaking an addiction, as the effects may be chaotic and unpredictable.

One member of our community reported an almost complete end to nitrous cravings after a supervised and guided psilocybin retreat. Another member of our community credits a psychedelic treatment with breaking their addiction to ketamine.

Ketamine has also recently been used in the treatment of depression and of other addictions such as alcoholism. However, ketamine is very similar in its mechanism of action to nitrous oxide. Both of them block the NMDA receptor in the brain. Ketamine is also itself a substance of abuse, with rising rates of addiction. In addition, many nitrous oxide addicts also have a history of ketamine addiction. Finally, at least for depression, ketamine must typically be used at least weekly, as opposed to psilocybin, which has effects for a year or more after one or two sessions. For these reasons, we recommend caution with ketamine. If you've struggled with ketamine in the past, it's wise to avoid it. If you have never struggled with ketamine, and you're interested in trying ketamine for addiction, we stil suggest caution. Only do so as prescribed by a physician. Ketamine usage can rise rapidly and lead to addiction almost as severe and damaging as nitrous addiction.

Psilocybin is likely a safer and longer lasting approach which may help some who struggle with addiction. Psilocybin mushroom retreats that treat addiction through guided or supervised experiences can be found by searching online. If you do opt for this, choose a retreat with many positive reviews and a reputation for safety and a soothing environment.

None of the above should be taken as medical advice.