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    Memantine for anxiety disorders? 
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    toothpastedog's Avatar
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    Anyone know anything about using Memantine for GAD/social phobia?

    Need to get back on some kind of meds for anxiety. After trying god knows everything and then some, I'm left with feeling like lorazepam is my best shot at this point. That said, I'm very wary of using gabaergics to control anxiety, as their use is fairly limited in my case (regular use isn't so wonderful for clarity of mind ime). Probably will have to bite the bullet and see about lorazepam, but not exactly very excited about using this as my frontline pharmacological approach to anxiety disorder.

    I've been interested in trying Memantine for some time now, but never had the chance for lack of access. I've benefited tremendously from NMDAr antagonists, albeit with the costs that come with using drug illegally or via preparations that are not exactly safe to use at therapeutic dosages for psychiatric disorders. Probably the only class of drugs/substances I've ever used that seem to have truly made a sustainable, long term difference with symptoms of GAD, social phobia or PTSD.

    Saw a trial is going on for Memantine+Lexapro at the university a couple weeks ago. Didn't realize they were now being using for psychiatric stuff like GAD. While I didn't spend too much time looking, I was only able to find one study that's now six years old: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420624/

    Thing is, I'd really prefer not having to get back on SSRIs or similar drugs just to get access to Memantine. Did not have very positive experiences with the five or six SSRIs and similar meds I've tried when it comes to anxiety disorders or PTSD. Wellbutrin came close to making a noticeable difference, but that was only when I used it in conjunction with methadone (and I'd prefer to avoid using opioids for psychiatric stuff).

    All thoughts appriciated.
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    Hi,

    So, I'm hoping you're still around. Am interested to hear, based on what's in your posting, your story, and mental disposition. I imagine that, after taking drug after drug and not benefiting much, you've begun looking elsewhere. That's my case, anyhow. What I am curious to know about is your current mental state, your diagnoses, and how're you're currently doing. Namely however, I am wanting to know how PTSD and anxiety manifest for you, and to which extent they affect your ability to work, play, socialize and manage all aspects of your life, or the ability to enjoy your life. If you respond, and are interested, I'd tell more of my story and "issues", but for now, I'll keep that very short --->

    In 2005, while in Afghanistan, I was badly injured. Sustained a TBI and have since been diagnosed with PTSD and a slough of other ridiculousness. What I mainly wanted to relay is that, due to what I can only describe as cognitive decline and an increasingly depressing inability to deal with stress and 'life', my life has, over the past few years become nearly completely unpleasant, mostly unmanageable, and things only seem to be worsening (life really just does not seem worthwhile, AT ALL, most days, and is a sort of a trans-literal 'hell'). Most days I'm so f'ed out of my mind that I cannot think straight, process information well or at all, comprehend even the most basic concepts, and I have to go through life essentially faking everything, as to seem the most normal version of my'self' as possible and to not seem odd, obtuse, rude or just straight up crazy. And then, every once in a while, with no warning of onset, for who knows why or how, I'll experience brief moments of mental clarity, where I feel relatively normal, and like I CAN take on the world's challenges, and I look FORWARD to social engagements, and I DO see the beauty in things, and I DO feel rather connected to those within my presence and I DO feel connected with reality, and I DO HAVE A SENSE OF SELF. These occurrences happen once of twice a month and last for 10 minutes, up to as long as 1 hour.

    Of course, there are many other things to discuss, like, the impacts these issues have on my life, other health ailments, such as insomnia (its affects), and so on.

    Anyway -- I said I'd keep it short. That's short. If you're still available on this forum, and are willing and wishing to discuss these things further, that would be great. Hope to hear from you.

    P.S. I've recently applied to MAPS to be involved in their MDMA studies, and may be going to the Nee Haven Vet Center in Connecticut next month for an intensive Ketamine trial study. I'm looking into other things as well, such as psilocybin, LSD, and other things, but for now, given the legality of those things, and my uneasiness about trying them (as to not fuck myself up beyond all repair), I'm easing into this stuff slowly.
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    #3
    My situation relates to yours, glovedeath. Military finishes with us an then toss us aside. With my clearance, I can't even tell the doctors the shit that has me fucked up and not sleeping. It's ridiculous.
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    #4
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    Hey buddy,

    Skip to the 3rd paragraph for the meat'n taters.

    First off, I like the profile name. Exactly how I feel. This one, namely. As for your clearance, I wonder what you mean about that. I'm not wishing to know about it, but, if you're out of the military, what's holding to you the tenants of your "sworn secrecy." Fuck all that BS. Of course, perhaps I'm just misinterpreting your conveyed messages. What I'm TRYIN'ta say is, you should be able to tell whoever, whatever. All keeping secrets really does is muddle up the mind (subjectively speaking, of course), IF, said secrets aren't of righteous make-up. If what you know, but aren't willing or think you're unable to share, is just some bullshit that you're not about, fuck it, don't keep it. Not to say that you should find a CNN rep and spill the beans, but, I think you'd be alright in tellin' a doc. If you don't wanna tell ur doc cuz u can't trust him/her (probably true), then PM me. I've got a possible solution for that.

    Indeed they do toss us aside, don't they. When you can no longer or are no longer willing to support their f-ed agenda, or when you die doing so, they'll just send their recruiters to the nearest highschools again, and get more sorry, unwitting, indoctrinated and conditioned young kids to fill those boots, and pick up where you may have left off.

    Man, onto the real shit. I'd like to hear about what you're struggling with. Expressly, the 'issues' you have, and why you're on this forum. If you can't do that on here, I'd be on board with chatting via VPN (which I could help you set up if you don't know how). I'm curious to know of what ails you, and, not that I think I can be of much or any help, I would like to hear what's on your mind, and how these things that bother you, disrupt your life. I'd expound on my own shit if you're up 4 a dialogue.

    Be well buddy -- MC

    P.S. Have you ever heard of psychedelic assisted psychotherapy? Also, which state/country are you in?
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    Bluelighter mr peabody's Avatar
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    Bluelighter ashwolf22101's Avatar
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    On the topic of Memantine:

    Do you guys know if it can be absorbed topically? I would think the bioavailability of it would be very poor in this form...

    I know a patient who has a pharmacy personally compound it into a cream for her and she swears by it.

    Resident neurologist says it?s impossible, but patient shows difference.
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    Bluelighter mr peabody's Avatar
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    Memantine has obliterated my depression and social anxiety

    Hey all, just wanted to briefly share my experience here. I have ADHD, best described as the "Ring of Fire" subtype if you buy into the Amen Clinics' categorizations. My flavor comes with all the core features, along with anger, 'mood swings', brain fog, depression and anxiety, including terrible social anxiety, making eye contact a painful experience.

    I've been on Namenda (memantine) for about a month and a half; I've been on Namenda XR 21 mg for about a month. While it does not seem to help directly with the core ADHD symptoms, it has almost entirely eliminated my depression and social anxiety (and I believe has decreased my anxiety in general). The effect has been so profound that a couple of days after switching to my current dosage and formulation (I started on the instant release, which btw is being discontinued in August), I seemed to experience at least a few hours of rapid synaptogenesis, in which my perceptions of the world seemed new (or encoded differently) and I felt that I was learning it all over again.

    During this period, novelty seemed to cause a euphoric sensation, which I found concerning but thankfully was short-lived and manageable by throttling the novelty, which otherwise might have been overwhelming. To a much lesser degree this process seems to continue (without euphoria), as I occasionally seem to relearn things that I had perceived differently when I was depressed. Also, I have found that my coordination has improved, best evidenced by my improved pool playing. For the first time in my life, I have been able to feel relatively normal and content, and comfortable around other people, becoming far more extroverted. I no longer constantly worry about being judged, and do not feel inferior to the people around me. Eye contact is pleasurable rather than painful, as is exerting my will and expressing my desires. I am able to truly enjoy physical and emotional intimacy now. I see people more for who they truly are (their pain, their anxiety, their joy, etc.). The list goes on, but I'll end it here.

    My best guess regarding the mechanism by which memantine has been effective is this:

    - proinflammatory cytokines/mediators cause astrocytes to downregulate glutamate transporters EAAT-1 and EAAT-2 (underactivity of EAAT-1 in general may explain my intolerance to sub-chronic aspartame exposure)

    - Due to underactivity of these astrocytic glutamate transporters, either (1) excessive glutamate builds up in the synapses and causes oversaturation/downregulation/desensitization of the glutamate receptors, or (2) presynaptic release or synthesis of glutamate is downregulated to compensate. In light of the efficacy of memantine, (2) would seem to depend upon the use of presynaptic NMDA receptors to regulate release or synthesis, which is rather dubious, so I lean toward (1). If (2) were shown to be true, it would raise a concern regarding excitotoxicity.

    - (Assuming (1) above) memantine reduces the effect of excessive glutamate on NMDA receptors, allowing them to function more normally, through e.g. upregulation/translocation/sensitization, turning down/off natural pathways guarding against excitotoxicity. In other words, shifting the balance of stimulation from tonic to phasic.

    Of course, plenty of downstream effects on other neurotransmitter "systems" are then possible.

    I am hoping the reason the remainder of my ADHD symptoms have not been resolved is due to the fact that I am merely dealing with one of the effects of reduced synaptic glutamate clearance. I am presently looking into ways to upregulate EAAT-1 or EAAT-2 or (less desirably) antagonize the various other glutamate receptors. In the meantime, I continue to use Vyvanse, albeit at a reduced dosage. I am hoping to try ceftriaxone (unfortunately only available via IV or IM routes) or celecoxib to see whether they treat my brain fog and hyperactivity and comfortably replace memantine, Vyvanse, and omega-3s.

    In case anyone is curious, my current best guess at the etiology of my ADHD is the rs6565113 variant of the CDH13 (T-Cadherin) gene. This is statistically linked to ADHD and is likely to have significant inflammatory implications. (The state of knowledge regarding CDH13 is still rudimentary but highly intriguing.)

    Btw, I have a naturally high level of testosterone and a very youthful appearance, and I am aware of the possibility that properly treating my ADHD will normalize these traits, but that price would be well worth paying.

    I could go on, but I think I've covered all the big stuff. Btw for those who are interested in memantine but are unable to get it, you may consider trying gentian root, which I've found to be relaxing and likely also works via NMDA receptors.

    I hope this helps someone! I'm sure there are lots of people out there who, like me, have tried the standard treatments for depression and anxiety and been gravely disappointed. I'd be happy to answer questions regarding my experiences or thought processes, so fire away but please stay on topic and don't get off into the weeds trying to show how smart you are.

    I do not seem to be experiencing any side effects. I tapered and stopped Cymbalta (which did not seem to help me) after starting memantine and this seems to have caused "brain zaps" which are still tapering off - I believe this is unrelated to the memantine but am mentioning it just in case.

    https://www.longecity.org/forum/topi...ocial-anxiety/
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    #8
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    Hey Mr. Peabody,

    Thanks a lot for the link to that page. Very useful and interesting information.

    Good deal. Big preesh!!

    Be well!!
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    Bluelighter mr peabody's Avatar
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    ^ Just ran across this:

    Mechanism of action of memantine


    Memantine is a clinically useful drug in many neurological disorders, including Alzheimer's disease. The principal mechanism of action of memantine is believed to be the blockade of current flow through channels of N-methyl-d-aspartate (NMDA) receptors — a glutamate receptor subfamily broadly involved in brain function. Surprisingly, other drugs that block NMDA receptor channels, such as ketamine, exhibit serious deleterious effects. The unusual therapeutic utility of memantine probably results from inhibitory mechanisms shared with ketamine, combined with actions specific to memantine. These potentially important differences between memantine and ketamine include effects on gating of blocked channels and binding of memantine to two sites on NMDA receptors. Because modulation of NMDA receptor activity can increase or decrease excitability of neuronal circuits, subtle differences in the mechanisms of action of NMDA receptor antagonists can strongly impact on their clinical effects.

    The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism.

    Excitotoxic neuronal cell death is mediated in part by overactivation of N-methyl-d-aspartate (NMDA)-type glutamate receptors, which results in excessive Ca2+ influx through the receptor's associated ion channel. Physiological NMDA receptor activity, however, is also essential for normal neuronal function. This means that potential neuroprotective agents that block virtually all NMDA receptor activity will very likely have unacceptable clinical side effects. For this reason many previous NMDA receptor antagonists have disappointingly failed advanced clinical trials for a number of neurodegenerative disorders. In contrast, studies in our laboratory have shown that the adamantane derivative, memantine, preferentially blocks excessive NMDA receptor activity without disrupting normal activity. Memantine does this through its action as an uncompetitive, low-affinity, open-channel blocker; it enters the receptor-associated ion channel preferentially when it is excessively open, and, most importantly, its off-rate is relatively fast so that it does not substantially accumulate in the channel to interfere with normal synaptic transmission.

    https://www.longecity.org/forum/topi...ocial-anxiety/
    Last edited by mr peabody; 07-08-2018 at 02:03.
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