Study Finds Low Doses of “Laughing Gas” a Fast, Effective Treatment for Severe Depression

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Woman Receiving Nitrous Oxide

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In a stage 2 scientific trial, scientists discovered a one-hour inhalation session with 25% laughing gas gas enhanced anxiety signs for over 2 weeks.

A brand-new research study at the University of Chicago Medicine and Washington University discovered that a single inhalation session with 25% laughing gas gas was almost as reliable as 50% laughing gas at quickly easing signs of treatment-resistant anxiety, with less negative negative effects. The research study, released today (June 9, 2021) in Science Translational Medicine, likewise discovered that the results lasted a lot longer than formerly thought, with some individuals experiencing enhancements for upwards of 2 weeks.

These results reinforce the proof that non-traditional treatments might be a practical choice for clients whose anxiety is not responsive to normal antidepressant medications. It might likewise supply a quickly reliable treatment choice for clients in crisis.

Often called “laughing gas,” laughing gas is often utilized as an anesthetic that supplies short-term discomfort relief in dentistry and surgical treatment.


In a short clip, Peter Nagele talks about the significance of this research study and its outcomes. Credit: UChicago Medicine

In a previous research study, the private investigators checked the results of a one-hour inhalation session with 50% laughing gas gas in 20 clients, discovering that it resulted in fast enhancements in client’s depressive signs that lasted for a minimum of 24 hours when compared to placebo. However, numerous clients experienced unfavorable negative effects, consisting of queasiness, throwing up and headaches.

Charles Conway

A big portion of clients don’t react to basic antidepressant treatments, so it’s important to discover treatments that assist these clients, according Charles R. Conway, M.D., a teacher of psychiatry at Washington University. The fast enhancements in lots of research study clients recommends laughing gas might assist individuals with treatment-resistant anxiety. Credit: Matt Miller

“This investigation was motivated by observations from research on ketamine and depression,” stated Peter Nagele, MD, Chair of Anesthesia and Critical Care at UChicago Medicine. “Like nitrous oxide, ketamine is an anesthetic, and there has been promising work using ketamine at a sub-anesthetic dose for treating depression. We wondered if our past concentration of 50% had been too high. Maybe by lowering the dose, we could find the ‘Goldilocks spot’ that would maximize clinical benefit and minimize negative side effects.”

In the brand-new research study, the private investigators duplicated a comparable procedure with 20 clients, this time including an extra inhalation session with 25% laughing gas. They discovered that even with just half the concentration of laughing gas, the treatment was almost as reliable as 50% laughing gas, however this time with simply one quarter of the unfavorable negative effects.

Furthermore, the private investigators took a look at clients’ depression ratings after treatment over a longer time course; while the last research study just examined anxiety signs as much as 24 hours after treatment, this brand-new research study carried out extra examinations over 2 weeks. To their surprise, after simply a single administration, some clients’ enhancements in their anxiety signs lasted for the whole assessment duration.

“The reduction in side effects was unexpected and quite drastic, but even more excitingly, the effects after a single administration lasted for a whole two weeks,” stated Nagele. “This has never been shown before. It’s a very cool finding.”

These results suggest pledge for laughing gas as a quick and reliable treatment for those struggling with extreme anxiety that stops working to react to other treatments, such as SSRIs, a typical kind of antidepressant medication.

Peter Nagele

Peter Nagele, M.D., teacher and chair of the Department of Anesthesia & Critical Care at the University of Chicago, has actually been studying the capacity of laughing gas as an antidepressant for the previous years. Credit: University of Chicago

“A significant percentage — we think around 15% — of people who suffer from depression don’t respond to standard antidepressant treatment,” stated Charles Conway, MD, Professor of Psychiatry and Director of the Treatment Resistant Depression and Neurostimulation Clinic at Washington University School of Medicine.

“These ‘treatment-resistant depression’ patients often suffer for years, even decades, with life-debilitating depression. We don’t really know why standard treatments don’t work for them, though we suspect that they may have different brain network disruptions than non-resistant depressed patients. Identifying novel treatments, such as nitrous oxide, that target alternative pathways is critical to treating these individuals.”

Despite its “laughing gas” track record, clients who get such a low dose really go to sleep.

“They’re not getting high or euphoric, they get sedated,” Nagele stated.

While it stays difficult to get non-traditional treatments for anxiety accepted in the mainstream, scientists hope that these outcomes, and other comparable research studies, will open the minds of unwilling doctors towards the distinct homes of these drugs.

“These have just been pilot studies,” stated Nagele. “But we need acceptance by the larger medical community for this to become a treatment that’s actually available to patients in the real world. Most psychiatrists are not familiar with nitrous oxide or how to administer it, so we’ll have to show the community how to deliver this treatment safely and effectively. I think there will be a lot of interest in getting this into clinical practice.”

With more comprehensive public approval, Nagele hopes that these outcomes can open doors for those clients who are having a hard time to discover appropriate treatments for their anxiety.

“There is a huge unmet need,” he stated. “There are millions of depressed patients who don’t have good treatment options, especially those who are dealing with suicidality. If we develop effective, rapid treatments that can really help someone navigate their suicidal thinking and come out on the other side — that’s a very gratifying line of research.”

Reference: “A Phase 2 Trial of Inhaled Nitrous Oxide for Treatment-Resistant Major Depression” 9 June 2021, Science Translational Medicine.
DOI: 10.1126/scitranslmed.abe1376

The research study was supported by an Independent NARSAD Investigator Grant from the Brain and Behavior Research Foundation. Additional authors consist of Frank Brown, Nisha Jain, and Robert Gibbons of UChicago and Ben J. Palanca, Britt Gott, Linda Barnes, Thomas Nguyen, Willa Xiong, Naji C. Salloum, Gemma D. Espejo, Christina N. Lessov-Schlagger, Wayland W.L. Cheng, Helga Komen, Branden Yee, Jacob D. Bolzenius, Alvin Janski and Charles F. Zorumski of Washington University School of Medicine.

About the University of Chicago Medicine & Biological Sciences

The University of Chicago Medicine, with a history going back to 1927, is among the country’s leading scholastic health systems. It unifies the objectives of the University of Chicago Medical Center, Pritzker School of Medicine and the Biological Sciences Division. Twelve Nobel Prize winners in physiology or medication have actually been connected with the University of Chicago Medicine. Its primary Hyde Park school is house to the Center for Care and Discovery, Bernard Mitchell Hospital, Comer Children’s Hospital and the Duchossois Center for Advanced Medicine. It likewise has ambulatory centers in Orland Park, South Loop and River East in addition to associations and collaborations that develop a local network of care. UChicago Medicine uses a complete variety of specialty-care services for grownups and kids through more than 40 institutes and centers consisting of an NCI-designated Comprehensive Cancer Center. Together with Harvey-based Ingalls Memorial, UChicago Medicine has 1,296 accredited beds, almost 1,300 going to doctors, over 2,800 nurses and about 970 citizens and fellows.



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