How Nitrous Oxide Affects the Brain: A Potent Neurochemical Cocktail

Once an analgesic in minor medical procedures, nitrous oxide is now more commonly known for its distortive effects from recreational use.

Nitrous oxide goes by many street names, including laughing gas, whippets, nos, N2O, and balloons. Despite the substance’s gross popularity, N2O’s effects on the brain are unlikely to leave you laughing.

Below, we’ll discuss how nitrous oxide impacts the brain and how this gives rise to its distortive, analgesic, and anxiety-reducing effects.

Please note that inhalation and recreational use of nitrous oxide can pose significant risks to your health. We strongly recommend you avoid using nitrous oxide without proper medical supervision or consultation with a licensed health professional.

How Does Nitrous Oxide Affect the Brain?

Nitrous oxide research still has a long way to go before it fully uncovers the impact N2O has on the brain.

However, evidence suggests that nitrous oxide has three main effects on the brain:

1. Analgesic (pain relieving)
2. Anxiolytic (anxiety-reducing)
3. Euphoric (feeling intense excitement or happiness)

Some claim that the substance’s analgesic and distortive effects are due to the antagonism of NMDA receptors. Yet, others attribute its trifold functioning to three neurological effects:

• Blocking neurotransmitters by GABAA receptors
• Inhibiting pain signals through norepinephrine release
• Stimulating the brain’s reward system

Alongside these neurochemical changes, nitrous oxide inhalation suppresses the body’s stress system by setting off the release of prolactin and inhibiting cortisol (your body’s main stress hormone).

Which Neurochemicals are Released in the Brain when using NO2?

Despite the vast array of research on the matter, experts are still attempting to grasp nitrous oxide’s effect on the brain in its entirety.

What current evidence does reveal is that nitrous oxide triggers a variety of neurochemical changes:

• Release of dopamine, endogenous endorphins, and various natural opioids in the brain.
• Neuromodulator release in the spinal cord—these are the messengers that aid the communication between synapses.
• Inhibition of cortisol release, reducing physiological stress.
• Release of the stress hormone prolactin, maintaining homeostasis in the face of stress.

Some researchers believe this neurochemical effect is responsible for N2O’s analgesic effects.

Laughing Gas and the Brain: Frequently Asked Questions

Does Nitrous Oxide Harm the Brain?

Nitrous oxide inhalation displaces oxygen in the lungs, potentially leading to oxygen deprivation in some prolonged exposure cases.

Certain inhalation practices are more likely to lead to oxygen deprivation as they inhibit oxygen inhalation after use, which naturally reverses nitrous oxide’s hypoxic effects. These include:

• Placing a bag over the head
• Inhaling directly from the tank or canister
• Filling a room with nitrous oxide.

Brain cell death can occur within as little as 1 minute of persistent oxygen deprivation.

Does Nitrous Oxide Increase Dopamine Levels?

Evidence shows a significant increase in dopamine levels in the nucleus accumbens of rats after 40 minutes of nitrous oxide inhalation.

Researchers state that this is likely due to a rise in dopamine release, not a reduction in its re-uptake. However, this remains unconfirmed.

More evidence is needed to identify whether this effect generalizes to the human population.

Does Nitrous Oxide Affect Serotonin?

A study looking at the effects of nitrous oxide in rodents found that a 15-minute exposure of 70% nitrous oxide elicits a rise in serotonin in the cerebral cortex (the prefrontal cortex specifically) but not in the hypothalamus.

This demonstrates that nitrous oxide’s effect on serotonin is region specific.

Again, as this experiment uses a rodent sample, we can’t necessarily generalize these results to humans.

How Does Nitrous Oxide Send You To Sleep?

Electroencephalogram (EEG) recordings find that N2O inhalation is associated with large-amplitude slow-delta waves — the exact frequency detected when we are in a deep sleep.

However, the waves nitrous oxide produces are double the size of a typical deep doze.

Interestingly, this only continues for three minutes, even when nitrous oxide inhalation continues. Researchers suggests nitrous oxide may affect the brain stem, blocking signals that would otherwise keep you awake.

Researchers also postulate that, as nitrous oxide doesn’t bind to specific receptors in the thalamus and cortex, the brain receives fewer excitatory signals, which causes loss of consciousness. This is potentially what the slow waves depict.

What is the Mechanism of Action in the Brain for Nitrous Oxide?

Nitrous oxide’s precise mechanism of action remains largely elusive.

Despite this, experts posit theories of how nitrous oxide produces its distortive, analgesic, and anxiolytic effects based on their research.

Nitrous Oxide as an NMDA Antagonist

Nitrous oxide is an N-methyl-D-aspartate (NMDA) antagonist. However, it isn’t the only one! NMDA receptor antagonists refer to a class of drugs, including:

• Ketamine
• Dextromethorphan (present in cough medicines)
• Phencyclidine (also called “angel dust”)
• Methoxetamine (or “MXE”)

This group of drugs inhibits the action of the NMDA receptor. NMDA receptors are present at most excitatory synapses.

Here, they respond to the neurotransmitter glutamate. Inhibition of the NMDA receptor can lead to several symptoms often reported after nitrous oxide use:

• Hallucinations
• Paranoid delusions
• Confusion
• Agitation
• Mood alterations
• Concentration difficulties

Some experts claim the NMDA receptor’s antagonism gives rise to its analgesic, hypnotic, and sedative effects.

However, others highlight nitrous oxide’s trifold functionality as the primary driver.

Nitrous Oxide and Its Trifold Functionality

Professionals from the Bethesda Family and Greensboro Kids Dentistry Practices claim that nitrous oxide works via a three-pronged approach:

1. It reduces anxiety by causing GABAA receptors to block certain neurotransmitters.
2. It triggers a chemical process, including the release of norepinephrine to inhibit pain signals; this supposedly has an analgesic effect.
3. It stimulates the body’s reward pathway, including dopamine release, which gives nitrous oxide’s characteristic euphoric effect.

Whatever the mechanism of action, nitrous oxide inhalation elicits several interesting effects, including the apparent ‘slowing down’ of the brain.

Does Nitrous Oxide Slow Down the Brain?

Users report the feeling of their body and brain slowing down briefly after nitrous oxide inhalation. Does this observation have scientific standing?

Evidence shows that nitrous oxide does indeed decrease cognitive processes by reducing the speed of information processing in frequency bands directly related to mental processes.

Lee and colleagues propose that this may be due to the drug’s sedative effects.

Research also indicates nitrous oxide impairs psychomotor performance, reducing reaction times and slowing down thinking speed.

Final Note

Nitrous oxide has many effects on the brain, inhibiting some chemicals, triggering the release of others, and slowing certain processes down while increasing the frequency of others.

While there is still a lot to learn about nitrous oxide’s neurological effects, we know it has three distinct mechanisms of action: anxiety reduction, analgesia, and euphoria.

Together, these effects make nitrous oxide a popular recreational substance.