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 uses nitrous oxide gas, commonly known as laughing gas, to see if it can quickly help people with OCD. It targets individuals with OCD because they often struggle with persistent and distressing thoughts and behaviors. The gas might work by altering brain chemicals to improve mood and reduce symptoms.

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 nitrous oxide safe for human use?

Nitrous oxide is generally considered safe when used properly in medical settings, such as for anesthesia and pain relief. However, excessive or recreational use can lead to side effects like dizziness, memory issues, and vitamin B12 deficiency, which can cause nerve damage if not addressed. ^{1 2 3 4 5}

How is nitrous oxide different from other drugs for OCD?

Nitrous oxide is unique because it is an inhaled gas traditionally used for anesthesia, and it may offer a novel approach for treating OCD by potentially affecting brain chemistry differently than standard medications. Unlike typical OCD treatments, which are often pills or therapy, nitrous oxide is administered through inhalation, providing a different experience and possibly faster effects. ^{2 6 7 8 9}

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Recreational nitrous oxide use: Prevalence and risks. [2022]

2. Netherlands 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. [2022]

3. United States 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. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Recreational Nitrous Oxide Abuse: Prevalence, Neurotoxicity, and Treatment. [2021]

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Spain pubmed.ncbi.nlm.nih.gov

[Use of nitrous oxide in Uruguay]. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

Nitrous oxide for the treatment of psychiatric disorders: A systematic review of the clinical trial landscape. [2022]