Nitrous Oxide for Obsessive-Compulsive Disorder

Overseen By Sindu Menon, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Drug interactions

Disqualifiers: Pregnancy, Nursing, Unsafe conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether nitrous oxide, a common gas for pain relief, can quickly alleviate symptoms of obsessive-compulsive disorder (OCD). It involves two groups: one receives nitrous oxide mixed with oxygen, while the other receives a placebo mixture of nitrogen and oxygen. Suitable participants have been diagnosed with OCD and find their symptoms significantly impact daily life. Participants must be able to safely pause their current medications. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to early-stage treatment evaluation.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that you need to tolerate a treatment-free period and cannot use medications that might increase risk. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nitrous oxide is generally safe and well-tolerated when used in moderation. Studies have found it can be safely used in low doses for conditions like depression. However, heavy or prolonged use can lead to a vitamin B12 deficiency, potentially causing nerve issues. For obsessive-compulsive disorder (OCD), nitrous oxide appears promising and typically does not cause serious side effects. Overall, it is considered a tolerable option for many people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for OCD?

Researchers are excited about using nitrous oxide for Obsessive-Compulsive Disorder (OCD) because it offers a novel approach compared to the standard treatments like SSRIs or cognitive behavioral therapy. Unlike these traditional options, which can take weeks to show benefits, nitrous oxide might provide faster relief by acting on the brain’s neurotransmitters more directly. This gas, commonly used as a sedative in dentistry, could potentially reduce OCD symptoms in just a single session, making it a game-changer for rapid intervention.

What evidence suggests that nitrous oxide might be an effective treatment for OCD?

Research has shown that nitrous oxide, or laughing gas, might quickly reduce symptoms of obsessive-compulsive disorder (OCD). In this trial, participants in the experimental arm will receive a treatment of 50% oxygen and 50% nitrous oxide for 60 minutes. Earlier studies demonstrated that just one inhalation of nitrous oxide offered fast symptom relief for people with OCD. This method differs from usual treatments and is under study for its rapid effects. Although more information is needed to confirm its effectiveness, early results are encouraging. ^{1 2 4 6 7}

Who Is on the Research Team?

Peter J van Roessel, MD, PhD

Principal Investigator

Stanford Univeristy

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with a primary diagnosis of OCD who have severe symptoms. Participants must be able to give informed consent and go through a treatment-free period. It's not open to those on conflicting medications, with certain psychiatric or medical conditions, or women who are pregnant or nursing.

Inclusion Criteria

I understand and can agree to the study's procedures and risks.

I can go without treatment for a while.

My primary diagnosis is OCD.

Exclusion Criteria

I am not taking any medications that could interfere with the trial.

Your medical or mental health conditions may put you at risk and it's not safe for you to participate.

You are currently pregnant or nursing a baby.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single inhalation of either nitrous oxide or nitrogen for 60 minutes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for improvement in OCD symptoms using the YBOCS scale

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Nitrous Oxide

Trial Overview The study is testing if inhaling nitrous oxide can quickly help improve OCD symptoms compared to inhaling nitrogen (a non-active gas). The idea is that the anesthetic properties of nitrous oxide might offer rapid relief from the distress caused by OCD.

How Is the Trial Designed?

Group I: Experimental: Nitrous Oxide Experimental Treatment 1 Intervention

OCD participants in this arm will receive 50%oxygen/50% nitrous oxide admixture for 60 minutes.

Group II: Control: Nitrogen Placebo Group 1 Intervention

OCD participants in this arm will receive 50%oxygen/50% nitrogen admixture for 60 minutes.

Nitrous Oxide is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Nitrous oxide for:

• Anesthesia
• Pain relief
• Hypoxic respiratory failure in neonates

Approved in United States as Nitrous oxide for:

• Anesthesia
• Pain relief
• Hypoxic respiratory failure in neonates

Approved in Canada as Nitrous oxide for:

• Anesthesia
• Pain relief
• Hypoxic respiratory failure in neonates

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Brain & Behavior Research Foundation

Collaborator

Trials

63

Recruited

2,900+

Published Research Related to This Trial

Nitrous oxide (N2O) is widely used as a safe anesthetic and has a rapid onset of euphoric effects when inhaled recreationally, particularly among clubbers and festival-goers, with usage rates between 40% and 80%.

While N2O is generally considered safe for moderate use, heavy or sustained use can lead to vitamin B12 deficiency and associated neurological issues, highlighting the need for user education about these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recreational nitrous oxide use: Prevalence and risks. van Amsterdam, J., Nabben, T., van den Brink, W.[2022]

Nitrous oxide (N2O) is commonly used as an anesthetic and analgesic, but its recreational abuse, particularly among young adults, poses significant health risks, especially to the nervous system.

Long-term N2O abuse can lead to irreversible neurological damage, making it crucial to discontinue use and provide timely vitamin B12 supplementation for recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recreational Nitrous Oxide Abuse: Prevalence, Neurotoxicity, and Treatment. Xiang, Y., Li, L., Ma, X., et al.[2021]

A 25-year-old male experienced acute psychosis and sensorimotor ataxia due to nitrous oxide abuse, which was linked to a confirmed vitamin B12 deficiency and length-dependent polyneuropathy.

Treatment involved abstaining from nitrous oxide and supplementing vitamin B12, highlighting the importance of addressing vitamin deficiencies and substance abuse in managing nitrous oxide toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral polyneuropathy and acute psychosis from chronic nitrous oxide poisoning: A case report with literature review. Sood, R., Parent, T.[2023]

Preliminary studies indicate that nitrous oxide (N2O) may have rapid-acting effects on symptoms of depression, particularly in treatment-resistant cases, based on a review of five published articles and ongoing trials.

There are currently 10 ongoing clinical trials exploring the use of N2O for various psychiatric disorders, with larger sample sizes expected in future studies, which may help confirm its efficacy and long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide for the treatment of psychiatric disorders: A systematic review of the clinical trial landscape. Liu, H., Kerzner, J., Demchenko, I., et al.[2022]

A 22-year-old woman developed severe health issues, including polyneuropathy and pancytopenia, due to recreational nitrous oxide use, which caused a functional vitamin B12 deficiency and increased homocysteine levels.

After receiving vitamin B12 supplementation and rehabilitation, the patient showed significant recovery, highlighting the importance of recognizing and treating the serious complications associated with nitrous oxide abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide-induced polyneuropathy, pancytopenia and pulmonary embolism: a case report. Parein, G., Bollens, B.[2023]

A systematic review identified 59 cases of nitrous oxide (N2O) use disorder and 17 cases of EMONO use disorder, highlighting the potential for addiction, especially when used in larger quantities and for longer durations than intended.

The study suggests that N2O use disorder can develop not only from recreational use but also from medical exposure, indicating a need for careful monitoring of its use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrous oxide: What do we know about its use disorder potential? Results of the French Monitoring Centre for Addiction network survey and literature review. Fidalgo, M., Prud'homme, T., Allio, A., et al.[2020]

A case of acute nitrous oxide poisoning in a 72-year-old male during surgery highlights the risks associated with incorrect administration of medical gases, emphasizing the importance of proper assembly and handling in clinical settings.

The study suggests that immunohistochemical markers like E-selectin, P-selectin, and HIF 1-α can aid forensic pathologists in diagnosing N2O-related deaths, providing a potential method for identifying hypoxic insults even when traditional signs are nonspecific.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lethal nitrous oxide (N2O) intoxication during surgery: the contribution of immunohistochemistry in identifying the cause of death: a case report. Cioffi, A., Cecannecchia, C., Bosco, MA., et al.[2023]

In a study of 104 surgical patients and 80 anesthesiologists in Uruguay, only 29.8% of patients received nitrous oxide (N2O) during anesthesia, indicating a significant decline in its use.

Most anesthesiologists (77.5%) reported using N2O recently, but many cited reasons for not using it, such as its unavailability and concerns about postoperative nausea, suggesting a shift towards newer anesthetic agents with better safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of nitrous oxide in Uruguay]. Fernández, P., Andruskevicius, M., Cristiani, F.[2019]

Chronic abuse of nitrous oxide (N2O) in pediatric patients can lead to serious neurological issues, including symptoms like limb numbness and weakness, as seen in a study of 9 patients diagnosed with N2O-induced spinal cord degeneration.

Vitamin B12 deficiency was common among these patients, and while all received B12 supplementation and recovered muscle power within 2 months, some experienced lasting sensory deficits, highlighting the importance of prompt treatment to prevent permanent damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recreational nitrous oxide abuse related subacute combined degeneration of the spinal cord in adolescents - A case series and literature review. Lan, SY., Kuo, CY., Chou, CC., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03826693

NCT03826693 | Efficacy of Nitrous Oxide in OCD: Pilot Study Study Overview​​ This study investigates whether the commonly used and well-tolerated inhaled anesthetic nitrous oxide can rapidly improve symptoms of OCD.

2. clinicaltrial.be clinicaltrial.be/en/details/65381?per_page=100&only_recruiting=1&only_eligible=0&only_active=0

Efficacy of Nitrous Oxide in OCD: Pilot Study This study seeks to explore whether a single inhalation of nitrous oxide gas may bring about rapid symptom relief in OCD. Trial design.

3. withpower.com withpower.com/trial/phase-3-compulsive-personality-disorder-3-2021-6b89b

Nitrous Oxide for Obsessive-Compulsive Disorder Trial Overview The study is testing if inhaling nitrous oxide can quickly help improve OCD symptoms compared to inhaling nitrogen (a non-active gas). The idea ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7801912/

Investigational and Experimental Drugs to Treat Obsessive ... This study seeks to explore whether a single inhalation of nitrous oxide gas may bring about rapid symptom relief in OCD. Nitrogen is used as ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1670500/full

Nitrous oxide use and psychiatric disorders: a retrospective ... Results: Out of 287 screened records, 22 patients (7.67%) reported a N2O use history, with a positive statistical relationship between younger ...

6. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp-rj.2024.200207

Nitrous Oxide in the Treatment of Depression: A Brief Review Nitrous oxide (N2O) as an inhaled gas is an anesthetic agent that has shown promise as a treatment for depression at subanesthetic doses. ... N2O ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2667174325000588

Antidepressant Effects of Nitrous Oxide in Major ... In the current study, our aim was to investigate the efficacy, safety, and likely optimal dose of nitrous oxide in adults with major depressive disorder (MDD).