Discovery reveals how low-dose ketamine, a 'lifesaving' drug for major depression, alleviates symptoms within hours

Medical Xpress / University at Buffalo / Molecular Psychiatry ^ | Nov. 13, 2024 | Ellen Goldbaum / Jamie A. Abbott et al

[ConservativeMind]

Neuroscientists have identified the binding site of low-dose ketamine, providing critical insight into how the medication alleviates symptoms of major depression in as little as a few hours with effects lasting for several days.

Ketamine has been used since the 1960s as an anesthetic, but in 2000, the first trial of far lower doses of ketamine proved its rapid efficacy in treating major depression and suicidal ideation.

Traditional antidepressants take months to kick in, which increases the risk for some patients to act on suicidal thoughts during treatment. Ketamine provides almost instant relief from depressive symptoms and remains effective for several days and up to a week after administration.

Ketamine binds to a class of neurotransmitter receptors called N-methyl-D-aspartate (NMDA) receptors.

"We demonstrate in this article how ketamine at very low concentrations can affect the activity of only select populations of NMDA receptors," says Popescu.

NMDA receptors are present throughout the brain and are essential for maintaining consciousness. For this reason, she explains, drugs that act indiscriminately on all NMDA receptors have unacceptable psychiatric side effects.

"We believe that the selectivity we uncovered in our research explains how low-dose ketamine can treat major depression and prevent suicides in people with depression," Popescu says.

Popescu's lab is among a handful in the world with the expertise to quantify the process by which NMDA receptors become active. This allowed Popescu and her colleagues to identify and measure what exactly changed during the NMDA activations when ketamine was present at very low doses versus when it was present at high (anesthetic) doses.

"The mechanism we uncovered suggests that at low doses, ketamine will only affect the current carried by receptors that had been active in the background for a while, but not by synaptic receptors, which experience only brief, intermittent activations," she continues.

[ConservativeMind]

Ketamine in low doses appears to selectively target receptors that have been active, seemingly engaged in causing active symptoms, while not affecting other normal or necessary receptors used occasionally.

It looks like ketamine has a reason to work, making it less mystical for use in treating depression.

[ConservativeMind]

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[Flaming Conservative]

The ketamine Clinic in Tulsa charges $2,000 for the first treatment and $1500 for subsequent treatments, insurance doesn’t cover. (prices ~ 5 years ago at one specific clinic).

[clee1]

Low dose ketamine is also a good adjunctive to pain meds.

[ridesthemiles]

THINK THAT IS WHAT KILLED MATTHEW PERRY

[ThanhPhero]

Less expensive is vitamin D, either as sunshine or D3 supplements. Chronic depression and manic depression is not uncommon among Vietnamese city women who cover up altogether when they go outside. I have convinced two friends in Khánh Hòa to wear short sleeves and go hatless outside in the morning and midafternoon. Their depression problems evanesced in a day. They have convinced their friends and relatives to get sunshine on their skin and Trang tells me that, with her proselytization of sunshine and the general adoption of western fashions there are fewer women all covered up and depression is progressively less common. Almost all such depression is lack of vitamin D.

[Rad_J]

I had ketamine treatments a few times a month for a year.

The first 4 were intervenes. The rest were prescribed for a compounding pharmacy as a ketamine nasal spray. 5 doses for $50.

Then the FDA outlawed the non-name brand nasal spray form. Now it’s like $1000 a dose so I stopped.

I loved ketamine. No side affects. Non addictive.

[steve86]

“Almost all such depression is lack of vitamin D.”

Baseless claim.

[steve86]

Now that’s good science (I hope). Synaptic receptor activation vs. background receptor activation.

[wgmalabama]

I know someone who has chronic pain whose pain meds were not working. It actually caused normal pain to be worse. There is a medical term /condition to describe this condition. Ketamine therapy/ infusion reset the situation. I am very glad they received benefit from it. I don’t think they were able to walk away from the pain meds but that’s a different issue Physical dependence on a medication cannot be undone that quickly for those meds. Pain meds take a long term to ween off or a very quick but risky quick cold turkey approach.

[steve86]

Thanks for the personal anecdote. My smaller town has a clinic run by ARNPs that offers both the IV route and nasal spray (esketamine or Spravato). I believe the IV administration is around $400 and the spray is higher, like you say. Both act as NMDA receptor antagonists.

[spankalib]

Less expensive is vitamin D, either as sunshine or D3 supplements...Their depression problems evanesced in a day...Trang tells me that, with her proselytization of sunshine...Almost all such depression is lack of vitamin D.

I must say, that is an excellent, if unusual descriptive sentence. Even more so if your native tongue is not English!

I enjoy writing, poetry, etc. Well done Thanh!

[ThanhPhero]

Based firmly in first person experience with now more then half a dozen people I have dealt with. I discovered that on line when I was researching manic depression. I found two research doctors who had found that "The only effective treatment for Depression is sunshine- vitamin D." I get someone started on D3 supplements or, in Việt Nam, being outside under that subtropical sun un short sleeves. The results are obvious immediately for someone who is in depression and for others whose depression is episodic or what used to be called "manic depression" the results are obvious when they go a long time without being depressed.

Look it up yourself, it's easy, unless you want to continue to believe that only prescription medications could possibly be useful.