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.
Table of Contents
The Essential Supplements While Using
Blood Tests for Nitrous Users
Secondary Supplements to Protect the Brain and Accelerate Healing
The importance of exercise.
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 in priority order:
1.
L-Methionine, 1-2 grams / day. This is the single best way to protect yourself from nerve damage.
2. Betaine, 1-3 grams / day. Betaine reduces the chance of blood clots and stroke.
3. B12 + B complex, 5,000 mcg / day. For general nervous system health and recovery.
4. Folate. If you are 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.
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.
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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.
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.
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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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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.
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 |
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| 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.