Laughing Gas Treatment for Depression?

A research study published this week in scholarly journal Biological Psychiatry explores nitrous oxide, aka laughing gas, as a possible treatment for depression.

chaplin-laughing-gas-poster-215The most common use of nitrous oxide is as an anaesthetic for dental work. That’s where most people have experienced its effects. I had my wisdom teeth removed around age 13, and the laughing gas made it a most pleasant and memorable experience, at least until I got home and the effects wore off. Ow.

Back in the day, you occasionally saw people with tanks of laughing gas at college parties or pre-concert tailgates. It’s been a while since I’ve attended either, and I have no idea if young people today still use laughing gas as a recreational drug.

Lead investigator Peter Nagele (Washington University School of Medicine in St. Louis) says,
“We believe therapy with nitrous oxide eventually could help many people with depression.”

Melissa Healy at the LA Times summarizes the experiment:

[R]esearchers compared the effects of an hour of inhaled nitrous oxide with an hour of an inhaled placebo on 20 patients whose depression had failed to yield to standard antidepressants. Each subject had a session of laughing gas as well as a placebo, spaced a week apart, and the researchers gauged the patients’ depressive symptoms two hours after their session, 24 hours later and a week later.

One day after nitrous oxide treatment, three patients reported that their symptoms had disappeared almost completely, while another seven reported significant improvement. Seven patients reported mild improvement in their symptoms. No patients said their symptoms worsened after treatment with nitrous oxide.

A day after they received the placebo treatment, none of the patients reported their depression was virtually gone, and one patient reported feeling worse the next day. But as is common in antidepressant trials, some placebo effect was evident: five patients reported feeling mild improvement and two reported significant improvement in their symptoms a day after receiving the sham treatment.

Washington University anesthesiologist Dr. Peter Nagele said it’s still a mystery why nitrous oxide or ketamine would have such a rapid antidepressant effect, because the molecular mechanics of depression are themselves poorly understood. It’s clear that NMDA receptors — docks throughout the brain at which the neurotransmitter glutamate can anchor — play a key role in depression. But how ketamine or nitrous oxide change glutamate’s action to restore hope and reduce feelings of guilt and worthlessness, said Nagele, “is the million-dollar question.”

It’s not that surprising that depressed people felt better 24 hours after an intensely joyful experience, even one chemically induced. But what about longterm effects? Could this therapy really help “to restore hope and reduce feelings of guilt and worthlessness” for the long run? Or would this treatment, whether onetime or ongoing, exacerbate the cycle of fleeting highs and crashing lows that many depressed people experience? Would nitrous oxide therapy complement or undermine standard antidepressant drugs? Would it be recommended only for extreme cases who get no relief from daily zoloft or prozac or wellbutrin?

In general, I believe that depressed people should avoid self-medicating through recreational alcohol and drug use. Alcohol especially is a depressant, exactly the opposite of what we need, and its short-term anxiety-relieving effects don’t begin to compensate for its depression-heightening effects. The short-term euphoria induced by drugs like heroin, cocaine, meth, ecstasy, etc, is frequently followed by intense dysphoria when the effects wear off, which can be especially excruciating for depression-prone people. Not to mention the dangers of body- and soul-crushing addiction which all these substances, to varying degrees, possess. You’re better off just saying no. That’s not moral judgment, just practical advice.

Nitrous oxide seems to be relatively non-addictive, leaves the body quickly once one stops breathing it, and has relatively mild side effects. Maybe it could someday be one safe, effective part of an anti-depression program for some people, or at least pleasant and harmless. But I remain skeptical for now.

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