Disclaimer
If you are experiencing a medical emergency, please call 911.
The information and recommendations provided on this website
do not constitute medical advice. It's been noted that there's a deficiency in accurate and useful health information regarding N2O.
This information is provided with the intent of harm reduction only. If you have questions or comments, please contact info@no2n2o.org.
Heavy and prolonged nitrous oxide causes multiple health problems:
1. Nerve damage including numbness, tingling, weakness, lack of coordination, and eventual paralysis.
2. Blood clots which can be extremely serious, possibly leading to heart attack, stroke, or death.
3. Anemia, fatigue, and shortness of breath from impaired ability to make healthy red blood cells.
4. Addiction. Nitrous is one of the most psychologically addictive compounds known.
5. Psychosis including paranoia, delusions, persecutory delusions, full breaks from reality, and hostile speech and behavior.
Supplements can help delay damage and accelerate the body and brain's healing from damage. However, no amount of supplementation will keep a heavy and frequent nitrous
user healthy forever. 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're
in addiction and seek help.
Always consult a qualified healthcare professional for further guidance. We encourage you to also share this guide with your healthcare provider.
Table of Contents
The Physical
1. The Essential Supplements While Using
2. Blood Tests for Nitrous Users
3. Secondary Supplements to Protect the Brain and Accelerate Healing
4. Exercise for Recovery.
The Mental
5. Anhedonia and Psychosis: Supplements that May Help
6. Nitrous Addiction: Medications
7. Nitrous Addiction: Psychedelic Therapy
1. The Essential Four Supplements:
Reducing Harm While Using
Quick summary: If you're using nitrous oxide, take these four key supplements in priority order:
1.
L-Methionine, 1-2 grams / day. This is the primary supplement shown to delay nitrous nerve damage for active users.
It is the most important supplement on our list. It helps even while actively using and should be taken throughout use and for 1-2 weeks after. (Note: If you're at high risk of blood clots, take the same dose of SAMe instead.)
2. Betaine, 1-3 grams / day. Betaine reduces the chance of blood clots and stroke. It also somewhat slows nitrous nerve damage. It works even while using.
3. B12 + B complex, 5,000 mcg / day. For general nervous system health and recovery. It might help while using, and can start helping immediately upon ending. Take immediately after each use, even before going to bed if in a multi-day binge.
4. Folate. If you're not actively using nitrous, choose 800 - 1000 mcg / day of Methylfolate. If you are still actively using, methyfolate is ineffective, and you should instead take
Folinic Acid, 10-15 mg / day.
Read below for more about the reasons, the science, and the dosage.
How Nitrous Does Its Damage
Nitrous oxidizes and de-activates critical enzymes in your body that contain B12. The most obvious
problems people face (nerve damage and blood clots) are mostly a result of de-activation of an enzyme called
methionine synthase. Methionine synthase breaks down a molecule called homocysteine and turns
it into a molecule called methionine. During and after heavy nitrous use, because this enzyme is broken,
your body can't make methionine and builds up far too much homocysteine.
1. Nerve Damage: Methionine is necessary for your body to make DNA, to make the myelin sheaths around your nerves, and to make
red blood cells. Without methionine, 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.
If nerve damage progresses too far, it can become permanent.
2. Blood Clots: Homocysteine, meanwhile, can cause blood clots if its levels get too high. Because nitrous has damaged the
enzyme that normally breaks down homocysteine, levels of it build up, increasing the odds of blood clots that can potentially
lead to thrombosis, embolism, strokes, and even death. Blood clots are far less common than nerve damage
but can be extremely serious and even deadly.
3. Bone Marrow Suppression and Anemia: The absence of methionine and damage to other enzymes also means that your body
can't produce fully healthy DNA, which particularly hurts your body's ability to create fast-turnover cells
including red blood cells. This causes megaloblasic anemia, a condition in which you have fewer healthy
red blood cells, and those you do have are larger and misformed. Over time, heavy
nitrous users become fatigued, weak, pale, short of breath, and possibly immune suppressed.
When you quit using nitrous, your body can rebuild its stores of critical enzymes like methionine synthase, but the process
takes an average of
10 or so days. Supplementation can help. But this is why it's essential to take multi-week breaks between uses of
nitrous oxide, to give your body time to rebuild its store of enzymes, and to give those enzymes time to catch
up on maintenance of your nervous system, red blood cells, and so on.
What Supplementation Does
Our goal in supplementation is to raise your body's level of
methionine (both directly and by helping your body make its own) and to
lower your body's levels of homocysteine.
To do this, 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.
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How long should these supplements be taken?
These should definitely be taken daily during active nitrous use and for days or weeks after.
L-Methionine can be ended at the 10 day mark if there is concern about blood clots. For those with health
homocysteine tests, continue to take L-methionine until all symptoms have resulved.
After a protracted period of heavy nitrous use that leads to any symptoms such as brain fog or
numbness or tingling, the other three essential supplements above should be continued until all symptoms
have subsided. 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. L-Methionine and betaine, in particular, have been shown to protect
the nervous system's health during active nitrous oxide use. And betaine lowers the risk of
blood clots even during nitrous use. Contrary to myth, B12 can be absorbed during nitrous use and
immediately after. Whether B12 helps during active use is unknown, but it certainly helps in
recovery, starting immediately.
Supplements are cheap. Your health is precious. When in doubt, err on the side of the supplements.
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. But definitely take daily sublingual B12, even if receiving injections.
2. 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.
3. 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.
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4. Exercise: A Foundational Tool for Recovery and Healing
While supplements are vital to mitigate damage from nitrous oxide use, no supplement can replace the healing effects of regular, intentional physical movement. Exercise is among the most powerful, evidence-backed strategies to support recovery—both from addiction and from the biological consequences of B12 inactivation.
Why Exercise Matters for Nitrous Users
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1. Accelerates Neurological Repair.
Physical activity promotes the regeneration of myelin—the insulating sheath around nerves that nitrous damages by inactivating B12-dependent enzymes. Aerobic exercise, in particular, increases levels of brain-derived neurotrophic factor (BDNF), a molecule essential for neuronal repair, neuroplasticity, and remyelination. -
2. Restores Dopamine Balance and Reduces Cravings.
One of the most insidious aspects of nitrous addiction is its hijacking of the brain’s dopamine system. Exercise—especially consistent aerobic activity like biking, jogging, or fast-paced walking—naturally boosts dopamine and serotonin, improving mood, motivation, and reward sensitivity. -
3. Reverses Fatigue, Weakness, and Anemia.
Chronic nitrous use can suppress bone marrow function, leading to anemia, muscle weakness, and persistent fatigue. While supplements like folinic acid and B12 address the biochemical cause, exercise stimulates red blood cell production, enhances cardiovascular efficiency, and helps rebuild lost muscular strength. -
4. Restores Motivation and Reduces Anhedonia.
Anhedonia—the inability to feel pleasure—is a common withdrawal symptom. Exercise increases endorphins, enhances emotional regulation, and reactivates reward pathways dulled by nitrous abuse.
Suggested Protocol
You don’t need to be an athlete to benefit. Start slow. Build steadily.
- Beginner (first 2–4 weeks):
10–15 minutes of brisk walking or gentle stretching per day. Focus on consistency over intensity. - Intermediate (weeks 4–8):
20–30 minutes of light cardio (walking, cycling, swimming) 3–5 days per week. Add 1–2 sessions of light strength training using body weight or resistance bands. - Advanced (after 2–3 months):
Work up to 150 minutes of moderate-intensity exercise per week. Include mobility work (yoga, dynamic stretching), strength training, and aerobic activity.
Note: If you have peripheral neuropathy or numbness from nitrous use, consult a medical professional or physical therapist before starting weight-bearing exercise.
Exercise isn’t optional. It’s medicine. Just as you wouldn’t skip your B12, don’t skip your movement. It’s one of the most effective and underutilized tools in the nitrous recovery toolkit—accessible, empowering, and profoundly healing.
5. 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.
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6. Medications 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 the
prescription medications.
They must be prescribed by a physician and used under a physician's care.
| Medication | Reason |
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| Supplements: NAC, D-serine, Sarcosine | These supplements listed earlier on the section on psychosis and anhedonia may help both with cravings and with restoring the brain to its pre-nitrous-oxide state. NAC in particular has been shown to moderately reduce cravings for multiple drugs. All three modulate the NMDA receptor in some way. |
| 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. |
7. Psychedelic Therapy for Nitrous 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. Read their story: "Psilocybin mushrooms healed me from my addiction". 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.