Nitrous oxide — better known as laughing gas — may provide relief from severe depression, according to a review of clinical evidence.
The review, published in the journal eBioMedicine, analysed previous clinical studies into the effects of medically administered nitrous oxide on adults with major depressive disorder (MDD) and treatment-resistant depression (TRD).
TRD affects nearly half of UK patients, meaning they fail to respond after trying at least two antidepressants.
Researchers from the universities of Birmingham and Oxford, together with Birmingham and Solihull Mental Health NHS Foundation Trust, analysed the results of seven clinical trials that had tested nitrous oxide, which is already used as a pain reliever, in patients with MDD, TRD and bipolar depression.
They found that a single inhalation session of nitrous oxide at a 50 per cent concentration led to “rapid and significant” reductions in depressive symptoms within 24 hours. However, these improvements faded within a week.
Repeated treatments over several weeks produced more sustained benefits, sugand suggested that ongoing dosing may be needed to maintain progress.
Nitrous oxide is thought to act on glutamate receptors in the brain. These receptors play a key role in regulating how brain cells communicate, particularly in circuits involved in mood and emotional regulation.
Kiranpreet Gill, a PhD researcher at the University of Birmingham and first author of the study, said: “This study brings together the best possible evidence indicating that nitrous oxide has the potential to provide swift and clinically significant short-term improvements in patients with severe depression.”
She added: “Our analyses show that nitrous oxide could form part of a new generation of rapid-acting treatments for depression.”
The team also examined the safety and potential side effects of nitrous oxide. Some patients experienced side effects such as nausea, dizziness and headaches, all of which passed quickly and resolved without medical intervention. None of the studies reported short-term safety concerns.
Gill stressed that more research was needed to determine the optimal dose, nitrous oxide’s long-term safety and the best way to use it.
Steven Marwaha, professor of psychology at the University of Birmingham and senior author of the study, said: “This is a significant milestone in understanding the potential of nitrous oxide as an added treatment option for patients with depression who have been failed by current treatments.”
Professor Hamish McAllister-Williams of Newcastle University, who was not involved in the review, said: “This is a very well conducted and comprehensive review of currently available data … However, as the authors point out, the data is far from demonstrating that nitrous oxide is a viable treatment for depressive illness.
“All trials included in the review were small, varied greatly in how the treatment was applied, were of short duration and included a variety of different patient groups.
Laughing gas has been used medically as a pain relief for years, but has also been used illegally as a recreational drug
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“There is also concern that in most studies patients were able to identify whether they were given nitrous oxide or placebo, which may have exaggerated the apparent effects of nitrous oxide. Overall, this review suggests that it is worthwhile looking further into whether nitrous oxide may be a treatment for depression, but that much more research is needed with larger and better designed trials before any conclusions can be drawn.”
Nitrous oxide had grown in popularity as an illegal recreational drug and is usually obtained from cartridges used in whipped cream dispensers. Doctors have reported seeing a significant increase in the number of people presenting with nerve damage as well as bladder and blood problems from overuse of the gas, which is now the second most used recreational drug after cannabis among 16 to 24-year-olds.