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Ketamine analog methoxetamine for treatment resistant depression?

N

nosher1

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Apr 9, 2011
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Hello,

Many research studies have established that ketamine is likely one of the best antidepressants in the world, providing rapid, substantial relief for 70+% of treatment resistant patients who had failed to improve on many previous drug trials. The antidepressant effect is believed to be related to the NMDA receptor antagonism.

Is there reason to believe that the ketamine analog methoxetamine would be equally effective for treatment resistant depression? Both are NMDA receptor antagonists, but they are clearly different compounds with different effects.

I am very curious about this because I have suffered from treatment resistant depression for many years. Ketamine is not being offered by any local doctors for depression since it is not FDA approved for that use (I live in the US). Even though doctors in the US are allowed to prescribe any FDA approved drug for "off-label" uses, no doctors in the area where I live are doing this with ketamine.

Also, I think my MDMA use several years ago made my depression much worse. Could ketamine and/or methoxetamine help reverse mood problems related to MDMA use?

Thanks!
Norman
 
Quite so! I tried it for the first time at a low dose a few days ago and felt that even after the major effects wore off, I was left with strong anti depressant effects. I've lived with depression for most of my life and been on various medications throughout but none worked for an extended period of time, if at all. I also saw various therapists which didn't help any either.

So yes, I would say so, I personally am just staying away from regular use as MXE has been known to be habit forming from various users accounts. I'm not sure if this would apply to you but for my personal experiences, I don't want to get carried away. I haven't with any drug really besides Marijuana but I don't want to give myself the chance as addiction runs in my family.
 
I was wondering this.
So far Ketamine has successfully treated my depression. Mine goes in phases, i have a manic episode i feel like im so great, the feeling is like when on drugs then later on it switches to an evil depressed side.

Since i started ketamine 50 - 100mg every 3 days,
I have noticed a drastic change. 4 weeks into it now, and in this time i have found work, i can get up on a dull gloomy day like today (which i would usually feel really depressed) and it dont bother me at all.

I would also wonder if MXE has this potential
 
If you can manage sticking to a set dosage regime and not start dosing everyday then its worth a shot. MXE dosed daily and such will just lead to problems. I would advise dosing maybe once weekly or so to avoid tolerance and the like. Though IDK if once a week dosing would be adequately effective.
 
My experience is that Ketamine works well for depression, but has many drawbacks, is addictive, and you need to really control yourself using it. That is, no fun in k-hole land. Stick to small doses.

MXE simply works better for depression for a few reasons. It lasts longer. It is also an effective DARI. It takes longer (in my experience) to build tolerance. And you can use much smaller doses.

Some people think you can use an NDMA antagonist once a week, once a month, once a day, or small doses throughout the day. There is no one way that will work best for everyone. But you should try to use it "as needed" and keep your doses "as small as will work" either way.
 
To paraphrase Jam on ketamine for it's anti-depressant and nootropic potential, use needs to stay below recreational quantities to receive the maximum amount of benefits from it. Deviating from the set regime can diminish the potential for therapeutic benefits. Even one time use of recreational levels can have short term cognitive deficits. The NMDARs are important in spatial memory, learned behaviors, etc., so disrupting the NMDARs firing and LTP can result in a shortfall in these areas. With sub-threshold doses the NMDARs are not completely blocked and can still create new memories, learned behaviors, and LTP, and even prevent the decay of LTPs, giving the possibility of longer retention in memory for example. So having a regiment with chronic recreational doses would have negative benefits rather than what you are actually trying to achieve. Occasional recreational doses may be fine but will still have a period post use of diminished cognitive abilities.

Sadly there doesn't seem to be much testing with arylcyclohexylamine non-competitive antagonists for cognitive or anti-depressant properties at sub-threshold doses (recreational) in part to their inherent dissociative properties. This probably also prevents exploration into arylcyclodexylamines for exploration in another NMDAR (specifically NMDAR sub-type specific) drugs, which may be a good thing or bad thing for finding potential therapeutic agents. Its sad though seeing so many studies purely talking about recreational levels or anesthetic levels of these nmda-antagonists, as it really only shows one side of these drugs, ignoring the therapeutic values of them. Though, they do show the recreational doses can not be used with out cognitive deficiencies resulting.

Un-competitive antagonists like memantine or adamantine/derivatives seem to be where a lot of research seems to be located at the moment. The positive action of memantine is that it is a channel blocker than can be dislodged easily, allowing for activity at the receptors to take place when need be. The non-competitive antagonist bind at a different location than endogenous agonist glutamate, so their activity continues (diminished activity of the agonist) even with glutamate interacting with the receptor. So with high doses this limits the functionality of the NMDAR, which plays a vital role in many processes.

I personally have seen great results with ketamine for SAD and GAD, AD(H)D (impulsive, inattentive, and hyperactive), and depression. Though, I limited myself on modifying behaviors and cognitive functions during and post administration of the drug, as I was using it pretty recreationally and daily.
 
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People need to stop publicizing MXE so much because their going to make it illegal before I get to try it...
 
ive heard good things about using low dose MXE for its antidepressant effects. ive heard only a couple tiny doses are needed per day and tolerance doesnt rise too quickly. the big issue people tend to run into is the urge to use larger doses for its dissociative effects.
personally, i wouldnt be able to stick to a strict dosing regimen and id end up bustin out lines every night which would cause its only problems. however, if you think you could control yourself i think this may be a decent option for your unfortunate depression.
 
I tried it for a while, I liked it. I would IM 1-2mg when I wake up and then maybe 1-2mg on lunch. Provided stimulation as well as more free-flowing thoughts. Relieved depression from life, made it seem really easy to handle.
 
I became interested in using MXE as an antidepressant after reading Jamshyds ketamine regiment. I was not interested in psychedelic effects, and started taking 5 to 10 mg sublingually, 3 to 4 times a day. After around 4 days, I really started to feel good. It felt as though it fixed my brain, and I could now think clearly and was much less overwhelmed and paralysed by hopelessness. Unfortunately, it only lasted about five weeks until tolerance set in, and even 40 mg I could barely feel, with no more AD effects. That was 4-5 months ago, and my tolerance is still is really high. I should add that I've never used dissociatives, and haven't smoked cannabis in two years. Looking back, the antidepressant effect actually had some hypomanic aspects to it. I filled up a notebook with my new ideas and insights about my life,relationships, workmates, and society in general. As I read my notes now they still make total sense to me, but it was coming fast and furious. Jamshyd has a post about the difference between antidepression and hypomania. I'd like to try ketamine, but don't have access to any, thats why I tried MXE.
 
I personally don't understand dosing more than once day. The anti-depressant effects of ketamine are seen to last upwards of a week, of course this dose vary from person to person. However, I still couldn't see dosing more than once a day being that beneficial unless confronted with a crisis which needs to be resolved quickly. Dosing even 10mg once a day with ketamine gave me lasting anti-depressant effects that were very noticeable for a tleast 3-4 days.
 
I've never been a big fan of either however my bf is in love with k. He used to do it wayyy too often (three times a week?). It can be very dangerous when used in excess though. Like any drug, it has it's side effects so be careful! My bf used to take it whenever he was depressed. He has stopped that and will only use it maximum twice a week - well usually once a week one week and twice a week the next week (due to our partying schedule, lol). He's getting off of it. But I think it helped his depression a bit.
 
What would be a non-recreational but therapeutic dosage for methoxetamine to treat depression? For me the difference between 10mg and 30mg is pretty large.
 
What about low-dose DXM (dextromethorphan) for depression?

MXE and ketamine are both NDMA antagonists and both appear to have antidepressant properties at low doses (with ketamine having been proven in several clinical studies to be a great antidepressant, at least in the short term). DXM is also an NDMA antagonist. Has anyone had success with using low doses of DXM over the long term to treat depression? If so, what dose and frequency is good for the long-term management of depression? I'm not referring to relieving depression by getting high on DXM but rather a true antidepressant effect that lasts after the drug itself is no longer in your system.
 
nosher1 said:
MXE and ketamine are both NDMA antagonists and both appear to have antidepressant properties at low doses (with ketamine having been proven in several clinical studies to be a great antidepressant, at least in the short term). DXM is also an NDMA antagonist. Has anyone had success with using low doses of DXM over the long term to treat depression? If so, what dose and frequency is good for the long-term management of depression? I'm not referring to relieving depression by getting high on DXM but rather a true antidepressant effect that lasts after the drug itself is no longer in your system.
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I've been interested in this myself. Heres what was mentioned on another forums who used it for SA http://www.socialanxietysupport.com/forum/f30/dextromethorphan-30279/ . Somewhere on google, I can't find it right now a guy/gal did 50mg daily or proposed that he was but he never updated the thread so no idea how it would go. Personally though I always get a icky depression feeling after consectitive uses. Perhaps doses under plateau 1 would be effective. My tolerance has led me on to other things though but I'd very much like to revisit DXM if it could have anti depressive effect similar to Ketamine(although doubtful from what people have told me/ ive read).
 
nosher1 in my case a 3rd platoe trip dxm kill my depression for atleast 2 weeks
ive tried really low doses(sub 1st plato) and it lifts my mood during the day but nothing longer
 
What nobody else had mentioned in response to your question is the biggest problem with attempting to use other similar drugs in place of actual (R,S)-ketamine as an antidepressant. Ketamine is metabolized into (2S,6S;2R,6R)-hydroxynorketamine (HNK) in the body, and this particular metabolite is "essential for [ketamine's] antidepressant effects" according to the journal 'Nature.' ( http://www.nature.com/nature/journal/v533/n7604/abs/nature17998.html ) The NMDA action of these drugs has shown potential in helping with chronic depression by forming new and stronger connections, as well as repairing old connections, in the brain and brain stem of depressed and chronically stressed people where these connections have basically atrophed, but other NMDA agonists still don't have this 'antidepressant-essential' metabolite of ketamine so on their own they won't ever stack up against ketamine in that department as far as we know.

I'm in the same position as you, OP. I've had severe treatment-resistant depression since I was a child, my first depression diagnosis coming at the age of 1 year. I've tried just about everything under the sun including what seemed like thousands of different medications and lifestyle changes and even 14 rounds of ECT which did nothing beneficial for me while severely crippling my memory. This is an old thread and now Ketamine is approved for depression and there are doctors administering it for this all over the country but I live too far from any of them.
 
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Is that the pathway involving mTOR they are talking about there? Anyway yes that mechanism works at low dosages and may not have much to do with mood enhancing effects of higher doses... so I don't know about MXE but do find that there are AD-like effects that do last for a bit just like ketamine's, something I can't say about 3-MeO-PCP even if the acute mood enhancing effects of that are very powerful and convincing.
Seems important to make that distinction in 'therapeutic effect' in order to avoid abusing such drugs for the wrong reasons and misconceptions about their potential.
 
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