The Role of Glutamatergic Signaling in Major Depressive Disorder

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With a focus on the implications for treatment-resistant depression, this on-demand webcast features a presentation by Dr. Rakesh Jain on how the emerging knowledge base regarding glutamate in MDD can be translated to improve clinical outcomes.
© 2018 NACCME, an HMP Company

[@josecardona1050]

With much sincerity and honesty I confess that I have reveled in this presentation. Dr. Rakesh possesses magical communication skills. Thank you for your contribution to science.

[@whbclaire]

We need more doctors like him. I'm a medical director in CME and I am already trying to figure out what program we can recruit him for.

[@aphysique]

@@whbclaire what would you suggest as medication for anxiety & or depression.. Benzo's really helped in previous yrs, however they cause worse signaling & the normal baseline of anxiety I do believe are elevated if one doesn't tke these meds all the time?

[@goodintentions1302]

As a 73 years old highschool graduate woman, treatment resistant depressed person who deals with as yet unhealed childhood SA by a number of family members, Lupus, Hashimoto's, a left frontal meningioma, Chronic Regional Pain Syndrome, extremely severe sleep apnea with Central Sleep Apnea being primary, this starting to play spontaneously after a video I'd chosen... What a blessing! Although I don't understand everything, I know other things to research. I've had to be my own advocate & I've always been a reader who researches my issues. I'm disappointed that doctors still try to convince me to take another antidepressant & have never mentioned ketamine. I'm finally taking LDN, which has helped me with neck & back pain, as well as CRPS, after years of trying to convince doctors who either didn't know about it, or believed pain medication, with detrimental side effects was a better idea. In my area of the country, doctors tend to move away so it hasn't an option to stay with one primary care doctor. Thank You for sharing this! I'll definitely be listening to this several times. ☮️🙏🏼

[@goodintentions1302]

I also want to add that within the first few minutes I went to my kitchen & took the L-glutamine supplement I purchased for my gut. ☮️💞🙏🏼

[@marshahines3171]

@@goodintentions1302Bravo🌀🙏🏽💙 Good for you to continue your own research & journey for your mental/emotional health. Much • Much Admiration! I’m finding a Ketamine therapist who integrates with Internal Family Systems therapy. Bright future if docs pay attention! ❤

[@VapidVulpes]

Presence of psychiatric symptoms, and the absence of wellness. Such a great way of putting it!

[@toddbukauskas8804]

I was so sad when I realized the presentation was over. It's okay, I'll just watch it again.

[@yeastspread3433]

That glutamate into glutamine, is what causes the inflammation in brain nerve cells, which presents as depression/anxiety in the cognitive experience, I almost missed the glycin in the reaction chain and didn't realise the implication. It's why any inflammatories such as tumeric/cumin/lions/panadol mane work so well to reverse the brain fog, it was just an inflammation issue. Thank you, I was able to end 14 years of anxiety and depression with the information from this lecture, the most important lecture of my life. I have a very good autobiographical memory (as does everyone in my family) and now I can revisit my memories without being overwhelmed and just learn and observe now.

[@Army1SGRetired]

If I may ask, how did you end your anxiety and depression?

[@yeastspread3433]

@@Army1SGRetired For me, a mix of functional mushroom teas (no psychaleics) did most of the work. I suspect lion's mane was the most important one (beta gloucons and anti inflamitories for the brain). I used a mix of Lions mane, Reishi, Chaga and Turkeys tale. I suspect the main issue on a chemical level effecting my conscious experience was inflammation of my nerve cells (brain fog and anxiety symptoms tracked back to this). So I did as much as I could to reverse that, and supply the beta gloucons (in lion's mane, of even oats) to heal the damage, lead to a massive improvement personally. While I can still experience sadness/regret, it passed much faster and doesn't stay with me long. It's not like being in any antidepressants I've had. The other half of the equation was finding my way to increase VTA dopamine flow. The most dominate and sustainable pattern appears to be setting a long term ethical life goal that feels like it's a 50/50 change, and thats stimulates the VTA dopamine.

[@dawnlokki4734]

L thiamine and magnesium glycanate also.

[@yeastspread3433]

@@Army1SGRetired in the end. I had to find a way to look at my trauma, and recover from it. And it all comes out as tears. When we "bottle up our feelings" they litteryally get stuck in our body "the body keeps the score" and I suspect it's this glutamate/GABA/glutamine cycle. But once you heal one trauma, you will forever have tools and a way to heal all your traumas, and it's just a matter of time. I strongly recommend lion's mane as a tea, to re-grow the neurons we loose after so many years of depression and anxiety (which slowly melts the pre-frontal cortex).

[@Army1SGRetired]

@@yeastspread3433 thanks for sharing what worked for you and I'm so glad to hear you have made such great progress!

[@VapidVulpes]

Yes, these next two slides are indeed exactly why I came here. This worked so amazingly well, that I have been able to learn how to love myself in a way that I had never knew I needed for 35 years of my life. All I want to do now is better understand this mechanism and all of the related mechanisms so that I can do what this substance has done for me, on my own with my own brain chemistry and exercise and life and diet and everything in between. Absolutely amazing stuff! Such a great lecturer! Thank you so much for this!

[@lifeisfun_28]

I could listen to him all day long!! Amazing stuff! Thank you for posting it in KZbin

[@lorenatorres8705]

This conference is so insightful and complete... thank you very much Professor!

[@baileybayer9462]

The concepts, information, and resources within this presentation could change the way we look at the mechanisms of the brain forever. Truly one of the most important lectures I have ever seen, thank you

[@belugabath]

Dr Rakesh one of best speakers I have seen Dr Agresti

[@cxdyjak]

Dr Jain, It is always such a joy to hear you speak and take complex material and processes and make them entertaining and simple. It was a pleasure working with you while I was at Eisai. Thank you!

[@yeetlord-to9jr]

"so essential that is's nonessential" took me a minute to figure that one out

[@SarahJones-kp9bq]

I love this guys ability to take complex chemistry and make it understandable and accessible using picture thinkin & concepts we already understand. Very engaging and gifted effective commicator, he could teach teach you anything using this method! Love it. So very interesting 👌

[@swarajjoye]

Hi Rakesh, what a mind blowing presentation. Excellent work. I appreciate your time, effort, research, dedication and commitment in preparing this presentation. I couldn't agree more on all suggestions and treatments. I would like to add on few suggestions if you don't mind. In addition to Glutamate based therapy, Ketamine, or Esketamine, physical exercise and meditation. Dietary and fluid consumption is also as important as the above, especially have a diverse gut bacteria, gut bacteria. In recent researchers, our gut have millions of neurons which cleverly interact with the brain neurotransmitters, serotonin, dopamine, Glutamate, and others. Food high in magnesium and zinc. Good Sleep hygiene. Glutamate therapy is no doubt the most effective intervention for treatment resistant depression, but we also need to emphasise on healthy eating and sleep hygiene. In this current era, many food are destroying our gut colony, we haven't got a diversity gut bacteria. We rely on fast food, process food, and sadly enough increase use of pesticides.

[@The_Tiffster]

Phenomenal presentation! It takes superior skill and talent to deliver this type of information in a manner that is so engaging and interest-provoking! I love his passion! I could listen to him talk all day!

[@JustT0m752]

This should be a TED TALK!

[@popurikrishna5776]

Amazing presentation! Fantastic delivery! thank you for your contribution

[@brucehutchinson9527]

Totally transformative concepts. Mind-blowing figuratively and literally.

[@LaurieRojas]

this is the best deep dive into Ketamine research for MDD

[@INounCf]

Apparently i just discovered a gem of a channel?

[@pssix03]

So awesome, brought tears of joy to my eyes ❤❤

[@greggl.friedmanmd7512]

Excellent Psychiatry Video. 5 Stars. By Gregg L. Friedman MD

[@buddhabrot3]

Thank you for this inspiring talk

[@akshu251]

I am a new fan of Dr. Rakesh Jain. I am new to the field and somehow this is the first video that I watched. This presentation motivated me to learn more. Thank you.

[@krishnavaddadi9829]

Excellent presentation Thank you

[@arthurmorgan7729]

Excellent lecture, thank you!

[@seanjurkowski7166]

Great talk! Thank you, Dr Jain.

[@sandragee2864]

Rakesh, That was an awesome lecture!! I love your enthusiasm and as usual, your clear explaination. Like the geek that I am, I saved it on my youtube list.

[@sandragee2864]

Rakesh - HaHa!!! I am listening to this presentation again. I shared the link with a patient of mine who is a fellow physician who just seems so fixated on adderall and dopamine for his ADD. I hope your presentation helps him see why psychiatry is a medical specialty. I do appreciate your big picture view.

[@spadress]

I love this dudes style of presentation :D

[@POLYLIVING]

Magnificent narrative! Thank u so much for all your hard work✨👏🙂

[@thedownwarddoug6642]

Jeff Goldblums greatest performance yet

[@JustT0m752]

This is my 2nd time listening to this lecture. It will not be my last!

[@sarapanzarella97]

I found the first half great. As someone who has suffered from not being able to handle excess glutamate my whole life and finding ways to mitigate it - I am drawn to any good presentation on the subject. But where the medical field always seem to miss their mark is the WHY - in this case why does the individual have this problem with glutamate in the first place? Not everyone has issues it - before shooting at your goal in the dark look at the individuals genetics and then tailor your treatment - your outcomes will be much better. Like I have a ton of variants in the GAD1 genes that are suppose to make GAD67 enzyme - which converts glutamate to GABA - help me with that and you will help me in my journey instead of a "lets try this and see if it works".

[@hiljim01]

as i said in my reply you should look at dr holton's work with gulf war and fibromyalgia.

[@aug.jam.1]

Ketamine helped me tremendously. No more panic attacks, no more suicidal thoughs, less stress and no more depression. Almost immediately after my first intravenous session. I use no other anti depressants anymore

[@dakshinamurti]

hello. do you have to use it all your life? what is the dose/frequency? also, does it in any way negatively impact libido or sexual function?

[@aug.jam.1]

@@dakshinamurti oh no, I only had 5 sessions at the hospital. After that I have never had it again luckily.

[@JustT0m752]

Awesome presentation!

[@soleyeiny]

Estonish presentation, thanks!

[@HairGlitter]

This guy is brilliant

[@theallin1mentalhealthchann914]

I'm a provider and received Ketamine Infusions IV and now at home. You can get at home treatments which are sent to your home, sublingual (under the tongue) or nasal for less than $400 for a month of treatment. This is less than cost of an infusion, includes the MD, prescriber, staff. The reason is the prescription of Ketamine is typically $30. Im a licensed provider in 10 states and it is more of a cure than anything I have seen by far. PTSD/OCD/Treatment Resistant Depression in me and better than I have ever been in 20 years.

[@tim40gabby25]

Interesting. Do you have any reference which summarises the system you describe? I'd appreciate that. UK concerned parent here.

[@theallin1mentalhealthchann914]

@@tim40gabby25 Hi Andrew, what are you exactly looking for? Companies that provide this or research articles? If you are looking for research you can watch/research videos here, testimonals of patients and providers plus I read research articles I found, I also watched a hour long conference in Australia with a MD among other MD's in his 7 year experience conducting Ketamine treatment...hope this helps or starts the process...

[@tim40gabby25]

@@theallin1mentalhealthchann914 Thank you. This is what the Net does best. Starts the process. Prof Nutt in the UK is the man, I'm guessing we're a tadge behind. SSRIs are old school now. The synaptogenesis within 15 mins under the influence of ketamine is interesting, is'nt it?

[@theallin1mentalhealthchann914]

@@tim40gabby25 Yes sir, did my 5th oral treatment last night actually, better everytime. No words to how amazing it is...I did research a year before diving in and glad I did both!

[@georginarandolphgirl66]

How long did you have to take it for and were you also resistent to medications?

[@gosilat1234]

Thank you.

[@amasvodka]

Thank you!

[@RealGirlLive]

Ketamine is a miracle. It cured my suicidal depression. I’m so glad psychiatry is going deeper into glutamate and nmda. In the future I hope for a pill that can provide the antidepressant affects of ketamine without the “trippy” affects

[@aphysique]

Wasn't it super expensive

[@tim40gabby25]

"effects", but great comment :)

[@chgofirefighter]

I did 2 treatments and ketamine hasn’t done much of anything, but there’s a 6 protocol but I was hoping. for “something” but?

[@chgofirefighter]

@@aphysique there’s foundations that helps with treatment, serenity foundation is one of them.

[@RealGirlLive]

@@aphysique look up dr Scott smith treatments. His are 250

[@RealProfessionalHumanBeing]

Thank you so much for this.

[@JABDUDE]

love this guy

[@hiljim01]

I would have appreciated some discussion of diet. With so many dietary additives that work thru the glutamate system that seems to be low hanging fruit. I would look at the work of dr holton with gulf war veterans that is amazing and very relevant to this talk. BUT this talk is amazing sir excellent work and i love that it is on youtube now i can watch it a few times so i can force it into my brain. thanks for your hard work.

[@Ami-ej4yh]

Amazing lecture, thank you. How would I get these lecture slides please?

[@defforadio6428]

Very nice!

[@icanduo]

I wish I could afford the IV injection. I'm trying the sublingual next week. I hope it works as well as IV form.

[@santicruz4012]

Awesome presentation, Dr Jain :) I would like to learn more about this topic. Could you please send me the references?

[@richg9578]

I look forward to the moment and that buried moments do, and now that's over til tomorrow, but can you and I minfulfullness x

[@nadaashraf9715]

That was an awesome lecture! thanks a lot for this presentation, but can you send me the powerpoint. it will help me a lot through my studies. thanks again

[@jeffmyers7062]

this is a very interviewed video!

[@specialist-in-tech]

Wow. And this is more than 4 years ago. How come so few psychiatrists adopting this in their practices ? FDA approval problems ? Malpractice worries ? In ability to understand, regulate or manage ? No use of blood tests for glutamate toxicity ?

[@JustT0m752]

Am I the only one that feels like this is too good to be true? As much as I enjoy the presenter's energy, I can't help but feel this is a infomercial. I was literally waiting for him to say "but wait there's more, if you call within the next 30 minutes we will also include a sense of humor and an overall feeling wellness.

[@cristinatorregiani3144]

It IS an inforemecial. Have you seen one of the first slides, where the ties he has with big Pharma are listed? This is infomercial for the very expensive Spravato. That said, an infomercial is not necessarily advertising a bad product. It could be indeed a new important huge step indeed. Btw, anybody here scared about mayor activation) because I am. mayor activation helps neurodegenesus yes, but also proliferation of other, not wanted, cell -aka cancer.

[@owlymcowlface7893]

It's like we've been looking at the nodes as causation and ignoring the network and network traffic to make an IT based analogy..

[@joakazia7425]

I hope someone can help with my question- how does ketamine cause sedation when it increases glutamate release from neurones? (I thought glutamate was an excitatory neurotransmitter?) Thank you.

[@popurikrishna5776]

can I use your slides for presentation of grand rounds in our psychiatric department on the clinical use of ketamine

[@MarionFiedlerMusic]

Dang. My world just changed.

[@word2RG]

I you could boost GABA, would that also eventually increase Glutamate?

[@rebekkad.2092]

My husband has a severe glutamatergic dysfunction and NAC seems to be the single most important supplement in his daily life. It is fast acting and has helped tremendously with his depression and anxiety. Thank you for this video.

[@sigikah3916]

Try l-serine. It will be converted to d-serine via racemase action. D-serine has similarities to ketamine.

[@criticadorauniversal]

glutamatergic dysfunction and adaptogenic plant?

[@dawnlokki4734]

I believe my long term use of xanax/lorazepam is what keeps my glutamate high.. When it's effect stops inbetween doses my glutamate goes high... Yes, you are so accurate as I have clinical deppresion... Anxiety disorders.. Currently using magnesium chloride magnesium glycanate and chloride. L thiamine stacked with nasal breathing to bring back balance...... glutamate excitotoxicity... It's real.....

[@BrianSmith-lo3mj]

Thank you for pointing that out ... because I believe the long term use of Clonazepam (Klonopin) does the same thing to me.

[@woolfy02]

So what do the people with TRD rely on without access to esketamine? Isn't there a few mood stabilizers that work on NDMA in some form?

[@Clem62]

dextromethorphan

[@buddhabrot3]

To be honest dextromethorphan is for me not really helpful in treating depression. It is in the management of pain. The feeling of it isn't really pleaseant. Amitriptilyne is a NMDA Antagonist as well es fluoxetine or gabapentin (non competitive). Lithium is involved in controlling excitotoxicity of glutamate in different brain areas. You could try these. And get them completely legal from your psychiatrist. If youre really desperate ( like I am) you can try huperzin A. D,L-phenylalanine or cat's claw, ibogaine or if you get your hands on it minocycline (antibioticum) which are nmda antagonists and antiinflammation. But the last things I mentioned there is not a lot of research whatsoever so be careful, especially mixing with other psychotrope medications which is nothing I can recommend in any way. You could also try to target gaba wich should be a lot easier. Maybe ask your psychiatrist for gabapentine, maybe pregabaline or other moodstabilizers, lamotrigine, valproate,lithium.....

[@buddhabrot3]

Edit: dont take ibogaine this was a bad advise

[@dmanzawsome]

The ammino acid in tea called l-theanine is an NDMA antagonist perhaps it might be a usefull tool for one that cannot get other glutamate altering substances.

[@Aerafae]

Suprised no one has said it but agmatine is perfect for this

[@tim40gabby25]

If you have no time for Q&A, prune your slides. I propose lectures are entirely Q&A, as the slides should be viewed before those carbon footprint intense flights. Not a popular view, I expect. Old UK medic here, just saying :)

[@subodhgautam649]

So when are we expecting troriluzole Sir...with due respect sir..?

[@user-mj8wi6du7m]

i bet cocaine , amphetamine , opioids , will improve symptoms of depression as well. but is it save ? is ketamine save in the long run ? does ketamine really works because of its effects on nmda or there is also another pathways ? why he is so sure ?

[@kihntagious]

The ketamine relieved the major depressive disorder for me. The deep everpresent down I had is gone

[@facelessstateofmind]

The most potent and abundant neurotransmitter in the brain… Hmmm, maybe research should have started with glutamate to begin with…

[@fulltimecasualnz]

NAC helps

[@Zooman160]

Do high levels of glutamate in the urine mean high levels of glutamate in the brain

[@johnathanabrams8434]

When glutamate reaches toxic levels and creates apopticic changes in the dorsal horn inhibitory interneurons pharmaceuticals and cognitive behavioral therapy no longer do anything.

[@douglaserickson2866]

Applause

[@roksanamarkova2821]

this guy is giving major Jeff Goldblum vibes :D

[@Arcticnick]

So 'regulate glutamate'

[@Baghuul]

I never new Dinesh D'souza was a neuroscientist.

[@ARTDEVGRU247]

😂😂😂😂🤦‍♂️

[@timmeagher5662]

What are psychiatrists? Babies? It's like he's teaching 4 year olds neuroscience.

[@cynigirl1utube160]

Ketamine didn't help me

[@katherenewedic8076]

really one thing for cause, effect, and treatment? no science here. undoubtedly your assistance and such did some research. and your dramatics devalue your words.