Nitric oxide and carbon monoxide can kill in the wrong amount, and your own cells make tiny bursts of both on purpose. Here is the line between a working signal and a poisoning, and why that line never moves.
Part 20 of the Brain Chemistry series. New here? Start with Your Brain Is Not a Gas Tank, the short orientation that explains the four questions every article in this series answers.
What to know
- Nitric oxide and carbon monoxide are gasotransmitters. Cells make small, short-lived, local amounts of each for signaling. That local physiology is not the same thing as breathing either gas from an outside source.
- No amount of outside carbon monoxide exposure is safe or beneficial. The body making a trace amount internally does not make external exposure harmless.
- A carbon monoxide alarm is a safety emergency, not a symptom to sit with. Get everyone outside into fresh air and call 911 or the fire department.
- Nitric oxide and nitrous oxide are different molecules. Nitrous oxide is an anesthetic gas that is sometimes misused. It does not replace or represent nitric oxide signaling.
- A medicine related to nitric oxide, sodium nitroprusside, was tested for schizophrenia. Later, larger trials and a meta-analysis found no overall symptom benefit.
The short answer
Nitric oxide, or NO, and carbon monoxide, or CO, belong to a small category of signals called gasotransmitters. Cells make them in a controlled way for short-range signaling, and unlike most brain chemicals, they are not stored in advance and released from tiny packets. They are made on the spot and cross into nearby cells directly, without needing a classic receptor sitting on the outside of the cell.
Nitric oxide is built from an amino acid called L-arginine by three different enzymes: NOS1, active mainly in certain neurons; NOS2, which switches on during inflammation; and NOS3, central to blood-vessel signaling. Its main target is an enzyme called soluble guanylyl cyclase, which produces cyclic GMP, or cGMP, a second signal involved in neural, blood-vessel, and other body functions.
Carbon monoxide is made mainly as a byproduct when heme oxygenase breaks down heme, the iron-containing part of blood proteins. One version of this enzyme, HO-2, runs constantly in the brain. Another, HO-1, ramps up during stress or injury. Exactly how CO signals inside cells is less well mapped than nitric oxide’s pathway.
Here is the part that matters most: neither gas is simply good or simply bad. A brief, local nitric oxide signal can support how brain connections strengthen over time. A larger or badly timed signal, especially in an already stressed cell, can help create damaging chemistry instead. The same logic applies to carbon monoxide, but with a much sharper edge. The tiny, internal amount your cells produce during normal heme breakdown is not remotely the same thing as inhaling carbon monoxide from a generator, a car, a fire, or a faulty appliance. External CO exposure blocks the blood’s ability to carry oxygen and can injure the brain and heart or kill. No routine FDA-approved psychiatric medicine directly replaces, blocks, or normalizes brain nitric oxide or carbon monoxide signaling.1
Every fact in this article sits on one side or the other of a single line: the tiny amount your own cells make on purpose, and exposure to either gas from an outside source. Confusing the two is where real harm happens. Nitric oxide is used medically only in tightly monitored hospital settings. Carbon monoxide from a generator, a car left running in a garage, a fire, or a malfunctioning furnace or water heater is a poison with no safe recreational or wellness use at any level. The fact that a trace amount occurs naturally inside your own cells is biology, not a health tip.
How each gas is made and how it fades
Three enzymes make nitric oxide, named for where they were first found rather than where they only work. NOS1, or neuronal NOS, sits in selected neurons. NOS2, or inducible NOS, switches on during inflammation and produces a longer-lasting burst. NOS3, or endothelial NOS, is central to how blood vessels relax. Calcium entering a cell often triggers NOS1 and NOS3; NOS2 usually turns on through gene activity after an immune signal.
Once made, nitric oxide does not wait in storage. It moves through nearby cell membranes directly, and at some brain connections it can travel from the receiving side back toward the sending side, adjusting that connection’s strength over time. Its main target is soluble guanylyl cyclase, which builds cGMP, a second signal that changes other proteins and channels. PDE5 inhibitors work one step downstream of this: they slow cGMP’s breakdown rather than adding more NO, extending an existing signal instead of replacing it. Hemoglobin, oxygen, and other molecules consume or transform NO within moments. There is no reuptake system for it the way there is for some other brain chemicals, which is part of why it works well as a local signal and poorly as anything a blood test can capture.
Carbon monoxide comes mainly from heme oxygenase, an enzyme that breaks heme down into three linked products at once: biliverdin, iron, and CO. A steady form of this enzyme, HO-2, runs constantly in the brain. A second form, HO-1, ramps up under stress, inflammation, or injury. Neither version is simply the healthy one or the harmful one; context decides. Locally made CO can bind heme-containing proteins and influence ion channels, blood-vessel tone, and cell energy production in small ways. Once CO comes from outside the body, it binds strongly to hemoglobin instead, forming carboxyhemoglobin, or COHb, which blocks that hemoglobin from carrying oxygen where it is needed. The lungs clear external CO over time, so a COHb level can fall after someone leaves the source or gets oxygen, but that number does not reveal what a brain cell was doing locally, and it does not reliably track how severe the poisoning actually was.2
Meet the main targets
These systems have no single tidy family of surface receptors. Source enzymes and internal sensors are the more useful map.
| Target | Basic action, where it matters, and why you might care |
|---|---|
| NOS1 | Basic action: Makes NO, usually after a calcium signal. Where it matters: Selected neurons and nerve cells. Why you might care: Links cell activity to local plasticity; no selective psychiatric medicine targets it. |
| NOS2 | Basic action: Makes a longer-lasting NO signal after inflammation switches it on. Where it matters: Immune cells, glial cells, inflamed tissue. Why you might care: Can help fight infection or contribute to cell injury, depending on context. |
| NOS3 | Basic action: Makes NO that helps blood vessels relax. Where it matters: Blood-vessel lining and the brain’s blood-vessel network. Why you might care: Central to how many cardiovascular medicines work; not a psychiatric target. |
| Soluble guanylyl cyclase | Basic action: Senses NO and builds cGMP in response. Where it matters: Neurons, blood-vessel muscle, platelets, and more. Why you might care: The key middle step for every NO-based medicine in real use today. |
| HO-2 | Basic action: Runs constantly, breaking down heme into CO, biliverdin, and iron. Where it matters: Brain and blood vessels. Why you might care: The main everyday source of the body’s own tiny CO signal. |
| HO-1 | Basic action: Switches on under stress, injury, or excess heme. Where it matters: Glial cells, immune cells, injured tissue. Why you might care: Can be protective, neutral, or harmful depending on the situation; not a psychiatric drug target. |
Nitric oxide and nitrous oxide are not the same thing
Nitric oxide, NO, and nitrous oxide, N2O, are different molecules with different chemistry, medical uses, and risks. Nitrous oxide is an anesthetic and pain-relief gas used medically, and also a substance that gets misused recreationally. It does not replace nitric oxide signaling and has nothing to do with the gasotransmitter system described here. The FDA has specifically advised consumers not to inhale or misuse retail nitrous oxide products, warning that severe neurologic, blood, psychiatric, and even fatal outcomes can result.3
What the sodium nitroprusside schizophrenia trials taught us
Sodium nitroprusside is an intravenous medicine used in hospitals for hypertensive emergencies, controlled blood-pressure lowering during surgery, and acute heart failure.7 It works through NO-related chemistry that relaxes blood vessels throughout the entire body. An early, small trial reported rapid improvement in acute schizophrenia symptoms after one monitored infusion.
Later, larger trials did not confirm it. A 2019 multicenter trial in outpatients found no meaningful symptom benefit.4 A 2023 meta-analysis combining six randomized trials and 174 participants reached a conservative conclusion: sodium nitroprusside did not relieve schizophrenia symptoms compared with placebo.5
The lesson is not that nitric oxide does nothing in the brain. It is that molecular plausibility, and even one encouraging early result, does not prove clinical usefulness. Sodium nitroprusside also affects blood vessels throughout the entire body and can produce toxic byproducts, so its overall action was never a clean test of one psychiatric brain connection.
The medication-to-signal map
This table stays short on purpose. Routine psychiatric care does not include a direct nitric oxide or carbon monoxide replacement or blocker.
| Medicine | What it does directly, used for, and main tradeoffs |
|---|---|
| Inhaled nitric oxide (INOmax) | What it does directly: Activates soluble guanylyl cyclase in lung blood vessels, raising cGMP. Used for: A specific newborn breathing and blood-flow condition, given with breathing support. Main tradeoffs: Methemoglobin buildup, nitrogen dioxide exposure, low blood pressure, and rebound lung hypertension if stopped abruptly. Not a psychiatric treatment 6. |
| Sodium nitroprusside | What it does directly: NO-related chemistry that relaxes blood vessels throughout the body. Used for: Hypertensive emergencies, controlled blood-pressure lowering in surgery, acute heart failure. Main tradeoffs: Sudden drops in blood pressure and a boxed warning for cyanide toxicity, requiring continuous monitoring. Schizophrenia trials found no overall benefit 7. |
| PDE5 inhibitors | What it does directly: Slow the breakdown of cGMP, extending an existing signal rather than adding NO directly. Used for: Approved nonpsychiatric vascular and urologic uses. Main tradeoffs: Do not replace NO directly and are not psychiatric gasotransmitter treatments. |
| Nitrous oxide (N2O) | What it does directly: A different anesthetic gas, not part of the NO signaling pathway. Used for: Medical anesthesia and pain relief. Main tradeoffs: Misuse of retail products can cause severe neurologic, blood, and psychiatric harm, and death, per FDA warning 3. |
| Carbon monoxide-releasing molecules | What it does directly: Experimental, carrier-dependent controlled CO release. Used for: Early-stage research in inflammation and tissue protection only. Main tradeoffs: Investigational and largely preclinical; carrier toxicity and exposure control are unresolved; no psychiatric approval exists. |
A monitored medical NO gas can help or harm depending entirely on dose and control: it can improve oxygen delivery in a defined newborn condition, or, stopped too abruptly, cause a dangerous rebound. An unmonitored poisoning gas from outside the body, in contrast, only harms. Neither situation runs through a psychiatric benefit, and a side effect from either one does not prove a useful brain target was engaged.
Can these gases be measured?
Not in a way that is useful for psychiatric care. Nitric oxide disappears too fast to measure directly, so studies measure stand-in markers instead, such as nitrate, nitrite, arginine, or citrulline in the blood. These are shaped by diet, oral bacteria, kidney function, and other medicines, which makes them poor stand-ins for a specific brain connection. A 2021 analysis pooling 745 people with major depression and 823 people without it found the overall levels of related blood markers did not differ between the groups,8 a clear example of why one peripheral molecule cannot stand in for brain nitric oxide activity.
Carbon monoxide exposure can be assessed through a blood carboxyhemoglobin level, combined with exposure history and symptoms, but that number does not correlate well enough with how severe a poisoning is to replace a full clinical assessment on its own. Ordinary pulse oximetry, the finger clip used to estimate blood oxygen, can also give an inaccurate reading when carboxyhemoglobin is present.2 No blood, urine, breath, or genetic test can select a psychiatric medicine by diagnosing brain nitric oxide or carbon monoxide status.
Which symptoms need a call, and which need urgent help
Monitor and record, only when there is no suspected carbon monoxide exposure or emergency: a mild, expected headache or dizziness after a prescribed blood-vessel medicine. Log the timing and any blood pressure information your clinician has asked for.
Call the prescriber or pharmacist promptly: new or repeated faintness, marked low-blood-pressure symptoms, a concerning headache, a possible medication interaction, or any unexpected effect from a prescribed nitric-oxide or cGMP-pathway drug.
Call Poison Control at 1-800-222-1222 for a suspected medication overdose, a mix-up, or an uncertain chemical or gas exposure without life-threatening symptoms, and follow its guidance. Do not let that call delay 911 for collapse, seizure, trouble breathing, or inability to wake someone.
If a carbon monoxide alarm sounds, act immediately. Do not search for the source. Move everyone outside to fresh air right away and call 911 or the fire department. Do not go back inside until emergency responders say it is safe.9
Call 911 now for loss of consciousness, seizure, trouble breathing, chest pain, severe confusion, or inability to wake someone. Do not drive yourself after suspected carbon monoxide poisoning. For a suicidal or mental health crisis, call or text 988. If danger is immediate, call 911.
Carbon monoxide poisoning can look like the flu or a psychiatric change. A headache, dizziness, nausea, confusion, or several people becoming ill in the same place all deserve concern. Do not wait for a complete symptom checklist before acting.
What to ask your prescriber
These are conversation starters, not instructions.
- What exact condition is this medicine treating?
- Does it act on nitric oxide production, on soluble guanylyl cyclase, or only on cGMP breakdown further downstream?
- Is the intended effect in the lungs, blood vessels, heart, or somewhere else?
- What improvement should appear first, and how will we track it?
- Which blood-pressure, oxygen, or interaction risks apply to this exact product?
- Does my medicine list include nitrates, blood-pressure drugs, or other substances that could interact with this?
- What should I do if I miss a dose?
- Could stopping this medicine suddenly cause a rebound in the condition it treats?
Bottom line
Your cells make tiny, local bursts of both nitric oxide and carbon monoxide every day, and that is normal, useful biology. It has nothing to do with whether it is safe to breathe either gas from an outside source, and for carbon monoxide the answer is always no. A sounding CO alarm is a get-outside-and-call-911 situation, not a symptom to reason through. On the medicine side, a drug related to nitric oxide looked promising for schizophrenia early on and did not hold up in larger trials, a reminder that a plausible mechanism is not the same as a working treatment. For the broader idea that no single brain chemical works alone, see Your Brain Is Not a Gas Tank.
Frequently asked questions
Does poor memory mean my nitric oxide is low?
No. Nitric oxide plays a role in some plasticity mechanisms, but memory problems have many possible causes and do not point to one enzyme, circuit, or timeframe.
Is carbon monoxide always a poison?
The body makes a tiny local amount during normal heme breakdown, and that part is harmless. Breathing carbon monoxide from an outside source, at any meaningful level, can poison you. The source is what makes the difference, not the molecule itself.
Is nitric oxide the same as nitrous oxide?
No. They are different molecules with different chemistry and different uses. Nitrous oxide is an anesthetic gas that is sometimes misused, and it does not stand in for nitric oxide signaling.
Can a blood nitrate or nitrite test show my brain’s nitric oxide level?
No. Those values are shaped by diet, oral bacteria, the kidneys, and medicines, and they do not reflect what is happening at a specific brain connection.
If sodium nitroprusside affects nitric oxide chemistry, why did the schizophrenia trials fail?
Reaching a molecular target is only one step. The drug also affects blood vessels throughout the body, which can outweigh or obscure any effect on a specific brain circuit.
Can food or supplements safely raise a low nitric oxide level?
No psychiatric nitric oxide deficiency has ever been diagnosed in a person. A supplement or precursor can still affect blood pressure and interact with other medicines, so mechanism alone is not a reason to use one.
Related reading on NP FADY
- Your Brain Is Not a Gas Tank (start here)
- When a Drug Hits Its Target and Still Fails
- What Your Body’s Own Cannabis-Like System Does
- The Quiet Signal Almost Nobody Names
References
1. Brain-focused review of nitric oxide signaling and plasticity. PMC. Accessed August 31, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC7707094/
2. CDC clinical guidance on carbon monoxide poisoning. CDC. Accessed August 31, 2026. https://www.cdc.gov/carbon-monoxide/hcp/clinical-guidance/index.html
3. FDA safety communication advising against inhaling or misusing nitrous oxide products. FDA. Accessed August 31, 2026. https://www.fda.gov/food/alerts-advisories-safety-information/fda-advises-consumers-not-inhale-nitrous-oxide-products
4. 2019 multicenter randomized trial of sodium nitroprusside in outpatients with schizophrenia. JAMA Psychiatry. Accessed August 31, 2026. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2729442
5. 2023 meta-analysis of six randomized sodium nitroprusside trials in schizophrenia. PMC. Accessed August 31, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC10657871/
6. Nitric oxide inhalation (INOmax) prescribing information. DailyMed. Accessed August 31, 2026. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=762b51be-1893-4cd1-9511-e645fc420d3a
7. Sodium nitroprusside prescribing information, boxed warning for cyanide toxicity. DailyMed. Accessed August 31, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=41e11afb-5fa4-4212-889d-1092dbd0702a
8. 2021 meta-analysis of peripheral arginine, ornithine, and citrulline in major depression. PMC. Accessed August 31, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC8636832/
9. CPSC carbon monoxide safety guidance, including the alarm-response sequence. CPSC. Accessed August 31, 2026. https://www.cpsc.gov/Safety-Education/Safety-Education-Centers/Carbon-Monoxide-Information-Center/Carbon-Monoxide-Questions-and-Answers
This article is general education. It is not a diagnosis or a treatment plan. Do not start, stop, share, combine, inhale, expose yourself to, or change a gas, donor medicine, blood-pressure drug, supplement, or psychiatric treatment because of something you read here. Review every prescription, supplement, and substance with your prescriber or pharmacist.
If you or someone you know is in crisis
- Call 911 or go to your nearest emergency room for any life-threatening emergency.
- 988 Suicide & Crisis Lifeline — call or text 988, available 24/7. En español: marque 988 y oprima 2. Veterans: 988 and press 1, or text 838255.
- Crisis Text Line — text HOME to 741741.
- The Trevor Project (crisis support for LGBTQ+ young people) — call 1-866-488-7386, or text START to 678-678.
- National Sexual Assault Hotline (RAINN) — call 1-800-656-HOPE (4673) or text HOPE to 64673; free, confidential, 24/7. Online chat at RAINN.org/hotline.
- National Domestic Violence Hotline — call 1-800-799-SAFE (7233) or text START to 88788; 24/7, help in 200+ languages. Online chat at TheHotline.org. If your phone or computer may be monitored, calling from a safer device is an option.
- Riverside County — Inland SoCal Crisis Helpline 951-686-HELP (4357), 24/7 (Inland SoCal United Way / 211+, in partnership with RUHS-BH); Community Access, Referral, Evaluation and Support (CARES) Line 800-499-3008, 24/7.
- San Bernardino County — Access Unit (Behavioral Health Helpline) 888-743-1478, 24/7; Mobile Crisis/CCRT 800-398-0018 (24/7, all ages) or text 909-420-0560. Arrowhead Regional Medical Center (ARMC) has a dedicated walk-in adolescent psychiatric ER (ages 13–17).
- Children under 13 — call 911 for immediate danger, contact your county's mobile crisis team (they respond to all ages), or go to the nearest pediatric emergency room.
- California Peer-Run Warm Line (non-crisis — someone to talk to) — call or text 1-855-600-WARM (9276); daytime and evening hours, not a 24/7 line.
- NP Fady (non-emergency) — for routine scheduling or questions, call (909) 707-6261. This line is not monitored for emergencies.