Research News: New Insights Into How Ketamine Stops Depression
Today in high impact science Research News we discuss a publication from Nature titled "Ketamine blocks bursting in the lateral habenula to rapidly relieve depression." Where researchers from Zhejiang University in China have been studying the mechanism behind which Ketamine has its anti-depressive effects.
I am sure many of you know the name of the drug Ketamine, or Special K as it might be called in a "street pharmaceutical" format. It's a fairly commonly used anesthetic in surgeries, as it gives people a trance like state, where the sensation of pain is reduced and also has the convenient effect of causing memory loss. [2], which is perfect for surgery. Its use as a street drug stems from the fact that it also can induce hallucinations, but it also has other effects.
For instance it is a very very fast acting anti depressant compound. With a single dose in as little as 30 minutes it can result in a long lasting antidepressant in people. [3] This has been hypothesized in the past to revolve around ketamine's interaction with the N-methyl-D-aspartate receptor (NMDA Receptor).
NMDA Receptor
The NMDA receptor is actually a glutamate (amino acid) binding receptor, that gets its name because in addition to binding glutamate it also binds very specifically to the compound N-methyl-D-aspartate. It's commonly found in our bodies and is what is known as an excitotoxin, in that it destroys nerve cells, by over exciting them.
Ketamine however, is an antagonist of this receptor, in this case it stops the NMDA receptor from firing.
Mechanism of Action of Ketamine
What the researchers identified is that the blocking of the NMDA receptor by ketamine in a particular section of the brain called the lateral habenula resulted in antidepressive effects in both mouse and rat models.
The researchers explored this phenomenon from a variety of angles, finding increased neuronal firing ("bursting") in the lateral habenula region in depressed brains. Which were not found in non-depressed brains. The researchers also observed that these "bursting" patterns observed could be removed by the addition of an "anti-depressant" concentrations of the Ketamine. An interesting observation but they were not yet satisfied.
They explored further to determine the mechanistic cause of the observed change in neuron firing patterns. They found through varying the concentrations of ketamine used, that the bursting activity was due to the actions of the NMDA receptors, and also found that the alleviation of bursting could be re-instituted by providing high concentrations of the NMDA receptors normal substrate (NMDA itself).
Impact
The authors have convincingly illustrated that the relationship between neuronal burst firing in the lateral habenula and a depression-like state is strong. They have also shown that the very rapid, anti-depression activities of Ketamine are related to the compounds ability to alleviate that burst firing state. They identified the mechanism by which this happens (blocking the NMDA Receptor) and have opened up a whole new target for the development of future fast acting anti-depression medications, hopefully without the other antithetic like properties of ketamine.
Sources
- https://www.nature.com/articles/nature25509
- https://www.drugs.com/pro/ketamine-injection.html
- https://www.ncbi.nlm.nih.gov/pubmed/10686270
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I feel like a lot of drugs can cure depression but is it actually good as long term on health ?
Nothing cures depression, its just treated. Good long term on health? Depends on the context in which a drug is used.
Ketamine can have profound long term effects from single intervention (without behavioral therapy used in concert with it), which do seem to fade over weeks.
I attended a 'Grand Round' at BIDMC a few years ago about ketamine and depression, where the researchers stated that their preliminary data suggested that ketamine had far better long term effects on treatment-resistant depression than many of the commonly employed techniques!
The Ketamine produces psychological dependence and long-term physical dependence.
It also produces short-term tolerance can produce serious and unpredictable effects and eventually produces irreversible brain effects.
It is important to take into account that there are several types of depression, which are: major depression, dysthymia, bipolar disorder and post-partum depression.
Depending on the problem, treatment for depression may be necessary in two ways: pharmacological and psychotherapy.
HAH never imagined my university would be featured in one of your articles!!! But yes, Zhejiang University is known all over china for the HUGE amount of papers that gets published every year!!
I read about this research in one of the newsletters I think. The key would be to find a way to specifically target the lateral habenula (I know this is much easier said than done), but a widespread blockade of NMDA to treat depression might have unforeseeable side effects, given glutamate is the major excitatory neurotransmitter of the CNS. But blockade of NMDA receptors is already a known mechanism to prevent progression of neurodegenerative diseases, Who knows if this new line of research will link some underlying neurodegenerative process with depression.
Clearly they are doing some really impactful science there!
Well that is the goal, now that one knows what to target, ways to specifically get there can be devised.
What if only brief blockade is sufficient to treat depression for an extended period of time? Sure long term inhibition would affect a variety of other pathways, but perhaps that isnt necessary?
Now there is where things could get interesting.
Would be the ideal scenario, but so far I don't think there is any medication available that is able to do this for depression, or any other medication that I know of working on CNS neurotransmitter in this fashion.
Temporary inhibition having "significantly" long term action is yet alien, but definitely something that deserves attention!! Would definitely save the patients of so many unnecessary side effects, not to mention long term, potentially permanent damage to the CNS and even the risk of developing tolerance or dependence. Yes, this would definitely help with the issue of tolerance or dependence developing with so many of the CNS drugs.
I agree... I've read a book about depression (Depression and its Treament, just don't recall the author) one of the best thing the we could give to those people have depression is LOVE and understanding.
I don't have a medical background but I 've read those medicines for people has depression only alleviate their suffering .
👍👍😎
Hey, @justtryme90. This is a great post! There are so many new applications being seen for ketamine recently. In the compounding pharmacy that I used to work at, we filled prescriptions for a plethora of different reasons. I have read and heard a lot about the usefulness for depression in the medical community, but there are many other reasons to be excited about ketamine's partial antagonistic effects!
I talk a bit about ketamine for treatment of PTSD in this post if you are interested!
I will certainly be following you and looking out for more posts like this! Cheers :)
Thats a nice post, you should consider including the #steemstem tag so the curators might not miss subsequent ones.
Yeah, I only more recently became aware of the steemstem project. I am so impressed by it, and want to thank you so much for your work, @justtryme90. You have helped create an amazing ecosystem of informative and enjoyable content!!!
I just wrote a more molecular neuroscience dense article using the #steemstem tag this morning: Molecules to Mental States: Psychological Stress and Cell Death. Thanks so much again!
Also, a typo that I noticed: "Ketamine however, is an agonist of this receptor, in this case it stops the NMDA receptor from firing."
It is actually a selective antagonist, which as you state reduces the excitability of the neuron.
It's always nice to know they're looking into how these things actually work, may see more targeted drugs in the future come from this research, although there aren't that many negative side-effects it seems from paired ketamine/therapy sessions.
But what does cinnamon toast crunch cure?
Whoops! Thanks for pointing that out. :)
@justtryme90 Thank you. You have supported my material. This is the biggest payout I will receive on steemit. It's nice that there is appreciated classical music. I do not need anything, you can even not respond to a message. Just zashchel say thank you.
People who go through strong depressions can take their lives and perhaps other people's lives, this drug would help to reduce the number of deaths by people who are upset.
Wow!
This is so so amazing
I've got no regrets following you I'm a botanist.
And I think following you I will get to be exposed more.
Hope such essential drug won't be too expensive as well?
This is not an essential drug, but it does have potential uses outside of anesthesia.
So much to learn not just in chemistry but in life as well.
Many who are suffering with depression in my country, Philippines, are taken by death. And in some point of life, there are still many out there, refering to other countries, are in the same tract as us.
I don't know much 'bout science, which I wish I would, so I'm having a hard time understanding every scientific word :(
But then, I Still find this article truly helpful and knowledgeable in every way.
I started following you to start my journey in understanding science even more. :)
@smafey
Great post @justtryme90.. thanks for sharing
Doubt it. People are afraid of using their brains.
yes, but if they start using their brain they can do anything @justtryme90
What if we charge per minute? That could add incentive!
Charge people to use their own brains?
It was intended to come off as an overt joke, but I am certainly not a comedian!
It is so informative post. Great Invention. Thanks for sharing
Thanks
awasome and invention post...sometimes everybody effect depression...so depression remove drug by Ketamine.very well post......
Thank you