Research News: New Insights Into How Ketamine Stops Depression

in #steemstem7 years ago (edited)

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.


The molecular structure of ketamine

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

NMDA Structure

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

  1. https://www.nature.com/articles/nature25509
  2. https://www.drugs.com/pro/ketamine-injection.html
  3. 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.

Zhejiang University

Clearly they are doing some really impactful science there!

The key would be to find a way to specifically target the lateral habenula

Well that is the goal, now that one knows what to target, ways to specifically get there can be devised.

but a widespread blockade of NMDA to treat depression might have unforeseeable side effects

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?

Who knows if this new line of research will link some underlying neurodegenerative process with depression.

Now there is where things could get interesting.

What if only brief blockade is sufficient to treat depression for an extended period of time?

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!!!

Molecules to Mental States: Psychological Stress and Cell Death. Thanks so much again!I just wrote a more molecular neuroscience dense article using the #steemstem tag this morning:

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.

After discovering more of the science behind how Special K reduces symptoms of depression, researchers are now looking into the mechanisms behind Frosted Flake's ability to alleviate pain and Froot Loop's strange ability to help insomnia patients.

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?

Scientists are still unsure how Cinnamon Toast Crunch works, they're investigating differences in childrens' neural activity after its consumption that allow for the resultant synesthesia and visual profiling of flavor.

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.

Keeping the side effects aside, Ketamine is doing great job in treatment resistant depression.

Indeed, mechanistic understanding such as that revealed in this article will be useful going forward to better understanding depression causes as well.

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


ae3ec0ed-d39e-44d8-b3cb-30fbc1682630.jpgGreat 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!
thinking-face.png

Charge people to use their own brains?

It was intended to come off as an overt joke, but I am certainly not a comedian!

Es bueno saberlo

It is so informative post. Great Invention. Thanks for sharing

awasome and invention post...sometimes everybody effect depression...so depression remove drug by Ketamine.very well post......

Sounds great, however, do they mention something in the paper about physical or mental addiction to ketamine?

This was a mechanistic paper, it wasn't looking at the effects on a person.

Qt well explained and informative post

Have a look on my work too if u dont mind and comment is appreciated @justtryme90

Great!!!!

Long used as an anaesthetic and analgesic, most people familiar with ketamine know of it for this purpose. Others know it as a party drug that can give users an out-of-body experience, leaving them completely disconnected from reality. Less well known is its growing off-label use in the USA for depression, in many cases when other options have been exhausted.

Less well known is its growing off-label use in the USA for depression, in many cases when other options have been exhausted.

Yep, and up until this study, nobody had a clue how it actually worked in that regard.

When rats take special K they're happy, but when I take it I apparently need to "stop making a scene" and "put my pants back on." Ridiculous.

Something about put your hands behind your back, anything you say or do can be used against you in a court of law.

You gave an important news I liked your post. I'm looking forward to your next post

Special K sounds interesting; I thought I know many types of street drugs, but this one is my first time of hearing it. Some of these street "pharmacists" sure know how to get their high virtually off any drug that has other uses in the world.

Well that's a necessity for selling drugs illegally :)

This is some pretty amazing research work I must say. Indeed depression is a small but mighty evil terrorising a terrifying number and percentage of the world's population from time to time and on a daily basis too. So articles like this actually do go a long way. Thanks for sharing this jtm :)

Thanks for reading.

  1. Does this drug have a level of dependence?
  2. What kind of depression is this medication indication?
  1. yes
  2. I do not know the specifics of the types of depression in which ketamine is know to be effective.

Very educative post. Thanks for sharing.

Its use as a street drug stems from the fact that it also can induce hallucinations, but it also has other effects.

Especially when waking up from it, I can even see it happen in animals, they get afraid of things that aren't there at all!
Every time people hear I'm a vet student they either ask for ketamine or for equiboost (horse testosterone), didn't know the street name was special K, I guess @justtryme90 has some street knowledge!

I guess @justtryme90 has some street knowledge!

You pick up on a few things when people joke about stuff when working for Pharma.

Very interested post, thanks alot for your upvote me..!.

great post......nice one.......

Dear @justtryme90, I am very grateful for you and thank you for visiting my blog @acehnature.

If you are willing to give me a chance to communicate via email with you.

My email : aalaiddin@gmail.com

Thank for you and thank for all. 😊😊😊.

Your correction is almost good sir.I like your post.Thanks for sharing.IMG_3437.GIF

Nice @justtryme90 👍👍👍👍

Are you telling me that the box of Special K cereal in my cupboard wasn't actually cereal and thats why my parents told me not to "eat" it?

Just kidding, however I should add: "post well written" etc etc, all the usual spam. Anyways onto the meat of my comment, so ketamine (commonly referred to as a horse tranquilizer) has anti-depressive properties to it? So it has 3 uses: hallucinate, be happy, and forget the pain of a surgery (or life in the case for depressed patients)

Basically every drug that can be used as an antidepressent can be easily sold on the street and make yo tons of money (though I mean kids at my high school got caught with dollar store spices thinking it was pot :/ )

(though I mean kids at my high school got caught with dollar store spices thinking it was pot :/ )

Lol. A brilliant future ahead of that one.

beautiful and awakening post....will be following u for more scientific revelations now

Thank you, that is very kind.

I really like your post @justtryme90

That is a good post... Thank you for share it...
You are the best.. Good luck..
May God always bless you 😃😃😃😃😃

Your post is very good and perfect. thank you for accepting me.

The simple life we ​​are living today has been possible only due to science. Your writing is very good and will help you to know more about our lives. Thank you.
And because of the steemit we get all these news more quickly.

Wow, this is quite groundbreaking actually! As a nurse we often use ketamine for sedating patients, just before they get spinal anasthesia. Also of course, growing up in Holland ketamine is a well known street drug in the clubbing life.

Cool to know this is also a new discovered feature. Definitely spamming my co workers and bosses with this type of info to dig deeper into this topic

There is a variety of literature out there describing its effeciveness against depression (especially depression which does not respond to other treatments). Unfortunately ketamine is still not a good option because of the other side effects.

What makes this literature so impactful is the identification of the mechanism by which Ketamine is having this antidepressive effect. Opening the door for the development of new compounds which will work this same way, but with out the other effects of ketamine.

That would be really revolutionary if that type of development could actually be achieved!

Modern medicine is beautiful sometimes, just the money involved in it is often such a disaster

hai master, thanks for the help. we can greet each other.

Good post @justtryme90 . For healthy

wow, nice bro!

Fantastic post, very useful.
Thank you so much..!.

a post full of information thanks I like @justtryme90

I would never have thought a drug like this for use in depression, but it makes sense. Shame it's not further along, I know so many that could benefit from it. Thank you for bringing this to light.

Informative post thank you for sharing @justtryme90

I just know ketamine. a very useful post I will definitely follow you

Nice post @justtryme90 i love biology science.

Great work .
Proudly chemist

Interesting post!
I don't write about science because i don't feel skilled enough on any specific field but science and science fiction are my passions... also traveling :)
gonna follow you!

We must each follow our interests in blogging, if science fiction is your passion then keep driving there :)

I haven't done any post about science or science fiction yet... I'm not sure how to engage a post on those issues... I may try when I run out of traveling stories... :)

Its not easy to get an engaging post with science material. I am still trying to figure my way around it and I've been learning for almost 2 years now... ugh.

seemt to me your doing a pretty good job!
I hope to get somewhere close to that with my kind of posts...

This post very interesting for me ..
Thank my freind ..Im resteem this post ..
You are smart

Thank for your vote my freind ...
I do not suspect.
You are the best

amazing...the medical science is growing up to all class of people. i think this research is very effective for us. thanks for your sharing to us.i will waiting for your next informative post.

@upvote & @resteem done


we know SSRI has more anti-depressant effect than TCA.but is ketamine best than SSRI??
dear @justtryme90 good research..@upvote & @resteem done

but is ketamine best than SSRI??

It's different then SSRI, works seemingly in different situations, and is definitely faster in action. This is not a case of better/worse but orthogonal.

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