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How Ketamine Defeats Chronic Depression

Discussion in 'Other Health News and Research' started by Waverunner, Oct 5, 2012.

  1. Waverunner

    Waverunner Senior Member

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    Current anti-depressants often take weeks to months in order for them to work. The problem is, that for some patients, they don't work at all. It seems that there is more about depression, than a lack of serotonin. Yale scientists claim to have made a breakthrough, by making the finding, that neurotrophic factors (which nourish the brain and are important for the survival and connection of neurons) could be at the root of treatment resistant depression. Moreover connections between neurons (sense and store information) seem to play a very important role for a healthy brain. Stress can decrease the connections between neurons and cause fatal consequences for patients, who later commit suicide because of a severe, detrimental effect on them. Current anti-depressants do not work on BDNF (brain-derived-neurotrophic-factor) but Ketamine does. A single, small dose of Ketamine, within 24 hours, significantly increases the connections between neurons and therefore cured the symptoms of depression in certain patients. This could be the biggest breakthrough in depression research in the last half century (see below).

    http://www.sciencedaily.com/releases/2012/10/121004141747.htm

    ScienceDaily (Oct. 4, 2012) — Many chronically depressed and treatment-resistant patients experience immediate relief from symptoms after taking small amounts of the drug ketamine. For a decade, scientists have been trying to explain the observation first made at Yale University.
    Today, current evidence suggests that the pediatric anesthetic helps regenerate synaptic connections between brain cells damaged by stress and depression, according to a review of scientific research written by Yale School of Medicine researchers and published in the Oct. 5 issue of the journal Science.
    Ketamine works on an entirely different type of neurotransmitter system than current antidepressants, which can take months to improve symptoms of depression and do not work at all for one out of every three patients. Understanding how ketamine works in the brain could lead to the development of an entirely new class of antidepressants, offering relief for tens of millions of people suffering from chronic depression.
    "The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in a half century," said Ronald Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and Professor of Neurobiology.
    Duman and George K. Aghajanian, also professor of psychiatry at Yale, are co-authors of the review.
    Understanding how ketamine works is crucial because of the drug's limitations. The improvement in symptoms, which are evident just hours after ketamine is administered, lasts only a week to 10 days. In large doses, ketamine can cause short-term symptoms of psychosis and is abused as the party drug "Special K."
    In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. Research at Yale has shown that damage of these synaptic connections caused by chronic stress is rapidly reversed by a single dose of ketamine.
    The original link between ketamine and relief of depression was made at the Connecticut Mental Health Center in New Haven by John Krystal, chair of the department of psychiatry at Yale, and Dennis Charney, now dean of Mt. Sinai School of Medicine, who helped launch clinical trials of ketamine while at the National Institute of Mental Health.
    Efforts to develop drugs that replicate the effects of ketamine have produced some promising results, but they do not act as quickly as ketamine. Researchers are investigating alternatives they hope can duplicate the efficacy and rapid response of ketamine.


    August59, merylg and heapsreal like this.
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Things i have read relating to this is that ketamine is a NMDA receptor antagonist and can protect neurons from excess glutamate affects. dextromethorphan which is commonly found in an over the counter cough suppressant and has NMDA antagonistic effects has been found effective in studies on fibromyalgia pain. NMDA antagonists have also been mentioned to slow down benzo and stimulant tolerance. There are so many different neurotransmitters that react in different ways that are just unknown. I think its an interesting subject. Will watch the video now.

    cheers!!!
    August59 and Waverunner like this.
  3. Waverunner

    Waverunner Senior Member

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    Thanks, Heaps. I just wanted to look for Ketamine alternatives but I gotta have lunch first. Have a great day.
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    The strange thing about the video that they say ketamine rapidly reverses depression, now in my line of work i have seen and administered this drug to patients and honestly it would stop just about any psychological or neurological problems. It turns people into the guy in the movie 'Weekend at bernies'. So its no suprise that there are effects straight away, but it is interesting how it supposedly repairs neurons. Twenty years ago dr jay goldstein was saying this was one of the best treatments he had seen for cfs/me, now im not saying cfs is a form of depression but im referring to the neurological aspects of cfs/me, im sure we have damage done to our noggins from chronic infections and immune activation and this could be a treatment to repair the damage that has been done once we have sorted the cause/infections etc etc.

    I think a possible angle for us to treat neurological issues we have is possible looking into nootropic supplements, some of which have NMDA antagonistic qualities like ketamine but then also very different

    ps dont ask me for ketamine, its tightly controlled in my workplace and i wont be trying this under my own steam or i would end up behind bars. But if you break your leg and im working, i can try and fix some of those broken neurons at the same time we fix your leg, ;). it is a dangerous drug if people dont understand this medication or have certain ongoing health issues.
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  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    NMDA antagonist/ketamine alternatives, as already mentioned dextromethorphan, huperzine A, memantine. to name 3.
  6. Legolas

    Legolas

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    Ketamine being beneficial for depression is kinda old news, really old news almost. But its good they now seems to be digging deeper. Ketamine is indeed a NMDA antagonist, and this is probably the way it relieves depression. Ketamine itself cannot be used due to side effects.
    The NMDA receptor consists of subunits, some only appaering in certain parts of the brain. The one pharmacuetical companies are trying to target is the NR2B subunit, because targeting this would cause less side effects. There are some product in the pipeline. I've written about this in a other topic.
    http://forums.phoenixrising.me/index.php?threads/anyone-tried-ketamine.4020/

    I'm still convinced NMDA receptor play a crucial part in the pathogenesis of CFS/ME. And I hope we will be able to benefit from this evolution.

    http://www.neuropinc.com/depression.aspx
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  7. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I have seen accounts written of people with cfs/me who have had medical procedures done and have been anaesthatised for them and afterwards gone into remmission. I have always wondered if ketamine was used or another drug that works on similar receptors. Good to see they are looking into how it works. I suppose in away its like rituximab, it helps cfs/me now they just have to understand how it does this.
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  8. Marco

    Marco Old blackguard

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    I've been pondering glutamate a lot recently (in connection with ME/CFS but not exclusively).

    Stablon (tianeptine) is another atypical antidepressant that has demonstrated remarkable clinical effectiveness in major depressive disorder that is often resistant to traditional SSRI's. The interesting fact about tianeptine is that its efficacy does not conform to the monoamine hypothesis of depression as tianeptine may actually lower serotonin levels. An investigation into the neurobiological properties of tianeptine (McEwen et al, 2010) concludes :

    Converging lines of evidences demonstrate actions of tianeptine on the glutamatergic system, and therefore offer new insights into how tianeptine may be useful in the treatment of depressive disorders.”

    Well worth a detailed read :


    The neurobiological properties of Tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation

    Bruce S. McEwen, Sumantra Chattarji, David M. Diamond, Thérèse M. Jay, Lawrence P. Reagan, Per Svenningsson, and Eberhard Fuchs

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902200/
  9. voner

    voner Senior Member

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    Interesting discussion! I Sometimes end up pondering about glutamate and NMDA In my Quest to get some sort of understanding of what is going on my body.

    Ketamine is Sometimes promoted as a possible wonder drug for pain, but the realities of it is that it is a highly controlled substance here in the United States. I can't imagine it's ever going to be very easy to obtain. I actually had it infused once with Dr. Goldstein, and it was an experience! He sure was a very unique Clinician. Very independent and very intellectual and very dogged in his efforts.

    I did not know about the Efforts to develop a more specific and NMDA Antagonist. Good news.

    In my quest to damp down pain, I tried something called transcranial direct stimulation (tDCS). It is also being experimented with, With some reported success, for depression. One of the more recent research papers I read on it said that, After stimulation, the area underneath the stimulation pad had increased and lingering levels of glutamate. This was confusing to me, because glutamate & NMDA Were supposed to Propagate pain, But tDCS has been reported to decrease pain.......

    Guess it just once again shows that The biochemistry inside the human body is extraordinarily complicated, and we still Have a lot to learn.
  10. Waverunner

    Waverunner Senior Member

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    Dextromethorphan could be worth a try but I don't know if it boosts BDNF (I couldn't find any studies). Tianeptine does increase BDNF in the hippocampus.

    http://www.ncbi.nlm.nih.gov/pubmed/21367535

    Dextromethorphan shares pharmacological properties in common with antidepressants and, in particular, ketamine, a drug with demonstrated rapid-acting antidepressant activity. Pharmacodynamic similarities include actions on NMDA, μ opiate, sigma-1, calcium channel, serotonin transporter, and muscarinic sites. Additional unique properties potentially contributory to an antidepressant effect include actions at ß, alpha-2, and serotonin 1b/d receptors. It is therefore, hypothesized that dextromethorphan may have antidepressant efficacy in bipolar, unipolar, major depression, psychotic, and treatment-resistant depressive disorders, and may display rapid-onset of antidepressant response.


    The NeurOp drug hasn't started phase I, so it will take at least 5 more years, till it could become available.
  11. Legolas

    Legolas

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    If i recall well, the problem with dextromethorphan is that it is eliminated too fast. There used to be a trial listed on clinical trials.gov in which it was combined with an inhibtor of the CYP molecule that breaks its down, so it's half live would rise. It was used in a fibromyalgia population. Don't know the results.
  12. Waverunner

    Waverunner Senior Member

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    Yeah, I just read some instruction leaflet. Everything that inhibits the P-450 system (like Cimetidine), seems to lead to increased concentrations of dextromethorphan but this is no good solution. I wonder if low dose Ketamine would be an option like LDN.
  13. voner

    voner Senior Member

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    Here's a post about the ketamine and depression study by a pain doctor that I follow. She's a very active clinician in the area of pain, and uses Various delivery forms of ketamine, low-dose Naltrexone, etc. She is a voice of experience.


    http://painsandiego.com/2012/10/05/...ves-depression-by-restoring-brain-connections


    If you poke around her website you can find information on the different delivery forms of ketamine and other substances.
  14. xrayspex

    xrayspex Senior Member

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    Voner
    that PM physician is intriguing. I am a bit confused on how LDN would tie in with ketamine though? I tried LDN for 6 months a few years ago and it helped some for pain mngmt but ultimately made me depressed in a way I have never been before,fortunately I was able to get out of that rut shortly after going off of it. I think for me LDN blocked me from feeling happiness from any source even in minute dose.
  15. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Its possible that you metabolize LDN very slowly and it blocks your opiod receptors for too long (so your endorphins are blocked). Did you ever try taking it every other or every third day?

    One reason to take it at night is so that you will be asleep while your receptors are blocked, but for some, this continues through the next day.

    Sushi
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  16. voner

    voner Senior Member

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    xrayspec,

    Sushi's idea sounds quite possible to me.

    Chronic pain still Seems to be a black box. Low-dose Naltrexone seems to be a bit of a black box also. Many people don't benefit from it, but then again, they may not be using the right dosages length of time etc.

    You might look at Nancy L Sajben's website and see if there some way to contact her, I think I remember reading a bunch of responses she puts out on her website that are evidently from questions from patients.... She is certainly very well researched and educated on pharmaceutical options for pain management.
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  17. August59

    August59 Daughters High School Graduation

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    I am only speculating, but the years of constant inflammation we are under I think would produce the same effect in the brain as stress would. The years of physical stress is, I'm speculating, reducing our bDNF to very low levels and if that is the case a safer variant of Ketamine sure would be a very welcoming treatment. Question for the brainiacs - Could low doses of ketamine in it's present formulation administered say 2 times a week result in very risky side effects?

    This has got to get the attention of big pharma and there will be big money dropped into these studies to try to get something to market. A 50 million dollar investment for a 50 billion dollar return looks very good to the board of directors!
  18. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Maybe a similar reason why klonopin helps but its just the tolerance to klono that stops it working??? I suppose the sedation has some way of reducing inflammation or maybe the speed at which inflammatory cytokines are produced. I think increasing GABA has nmda antagonistic effects. I would say ketamine is possibly a much stronger nmda antag then we commonly have available??

    cheers!!!
  19. Waverunner

    Waverunner Senior Member

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    Does anyone know, how low doses of ketamine feel? Do people get drowsy after the administration or is this only true for normal/high doses?
    vli likes this.
  20. Marco

    Marco Old blackguard

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