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Old 02-09-2011, 01:16 AM   #1 (permalink)
 
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Lightbulb How to use ketamine as an antidepressant

This was posted on bluelight and i have permission from the guy to post it here, this is only for people that are treatment resistant, for them it can be a lifesaving option.


This is in the middle of being re-written, but should be perfectly useful as-is - Jam, Nov. 22nd, 2010

This is a work in progress, and hopefully it will still be a work in progress after I die. I shall update every time I add something. This is a preliminary and very rough draft, and I expect every word to change by the time I am done editing it. The procedure, however, remains relatively constant, so you can take it from here. Please feel free to ask any questions or leave any comments you have in this thread.


The following document is the result of several requests from people both on and off BL to write up on the way I use Ketamine medicinally to cure my manic-depression (and yes, I am diagnosed with "Bipolar II with co-morbid Dysthemia and anxiety", in case you were wondering). I have been doing this for 4 years and nothing but good came out of it.

It is tragic that such a medicine remains illegal and largely stigmatized (even within the drug-using community).


DISCLAIMERS:

a. I am neither a medical doctor nor a pharmacologist. My knowledge in either area is amateur at best. I am simply sharing something that has worked for me and a handful of others. Notice how the procedure is written in the first-person. This is for a reason. Therefore, if this doesn't work for you, or if you have doubts, or if you try it and screw up, then I'm sorry, but I am not responsible for that.

b. This is for the truly melancholic depressed people. If you're depressed because you haven't had sex in 2 weeks, then this guide is NOT for you. My point is: There are several types of depression, and there are several cures. This is not for someone who is simply feeling down. This guide is for those who truly suffer from an incurable depression that is out of their hands.

c. That said, over the years that I've been hammering this procedure out, many new people have tried it, and I heard nothing but praise for it. I literally have not received a single complaint yet. And while I am personally convinced of its safety at this point, please do keep in mind that research regarding safety is just starting to surface, and caution is still important.

NOTE that throughout this procedure it is assumed that one has no other drugs in one's system, including Cannabis. Nicotine seems to be acceptable.



PART I: Science
Full Bibliography available below.

Recent Findings and Discussion:

Read this thread for the latest research on the area as well as my notes which complement this procedure.

When I wrote the first draft of this document, interest in Ketamine's antidepressant action was just starting to break in to the scientific mainstream, even though a Glutamate-based model of depression had been in existence for a while. Dissociative Anaesthetics carry a huge stigma, and one can only be happy that this stigma is only just beginning to be outweighed by the possibilities presented with this theory.

Since then, especially over the last year, there has been an explosion of interest in Ketamine's antidepressant effects, generating a wholesome body of scientific literature that aims at this specific quality of Ketamine rather than discussing it as a side-topic.

My current, amateur, and personal opinion reflecting on these studies follows. Feel free to skip.

Ketamine is an extremely complex drug, pharmacologically-speaking. It has an immensely wide therapeutic window being active with as little as 5mg and as much as 2g while maintaining safety. Unlike most drugs which simply intensify in effect as the dose is raised, Ketamine seems to morph into what looks like several different drugs, depending on dosage. On the very high end, it acts as an anaesthetic, it is considered an essential medicine internationally, and its safety as an anaesthetic is established beyond all doubts by years of use on all kinds of animals, including human children. Just now, the scientific community is awakening to the effects of lower (several magnitudes in order) doses as possessing apparently miraculous antidepressant effects. Somewhere between contentment and anaesthesia is the realm of entheogenic experience - a property of Ketamine exploited by shamans, party-goers, and even recognized, if not used, by a few licensed therapists (e.g. Grof).

Of course, I will not be talking about anaesthetic use in this document. Nor will I be talking about Entheogenic/Psycholytic use of this medicine here, as this is a vast and wonderful subject to which justice cannot be done in a simple forum post. If interested, I refer you to Karl Jansen's authoritative classic, Ketamine: Dreams and Realities. This can be ordered from the MAPS website where proceeds can go for a good cause.

It is therefore conceivable that the antiquated neuropharmacological paradigm of trying to tie the effects of a drug or a psychiatric disorder to a single neurotransmitter, particularly in the case of melancholia, has long expired. It is time to look for something else that takes into account both big AND small phenomena, and arrive at an emergent hypothesis that accounts for both itself and its constituents.


Evidence for Safety in Antidepressant Use:


RESULTS: Ketamine elicited minimal positive psychotic symptoms. Three patients experienced significant but transient dissociative symptoms. Side effects during and after each ketamine infusion were generally mild. The response criterion was met by nine patients after the first infusion as well as after the sixth infusion. The mean (SD) reduction in MADRS scores after the sixth infusion was 85% (12%). Postketamine, eight of nine patients relapsed, on average, 19 days after the sixth infusion (range 6 days-45 days). One patient remained antidepressant-free with minimal depressive symptoms for >3 months.

CONCLUSIONS: These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.

aan het Rot M, Collins KA, Murrough JW, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol. Psychiatry. 2010;67(2):139-145..
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Old 02-09-2011, 01:17 AM   #2 (permalink)
 
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A nice summary of recent Findings:

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Rao TS, Andrade C. Innovative approaches to treatment - refractory depression: The ketamine story. Indian J Psychiatry [serial online] 2010 [cited 2010 Nov 23];52:97-9. Available from: http://www.indianjpsychiatry.org/tex.../52/2/97/64573

[Full Article Available Free]


A Few Examples of Recent Research:

RESULTS: Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week.

CONCLUSIONS: Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.


Zarate CA, Singh JB, Carlson PJ, et al. A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression. Arch Gen Psychiatry. 2006;63(:856-864.

----

Depression is prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Here, two cases are reported in which a single oral dose of ketamine provided rapid and moderately sustained symptom relief for both depression and anxiety. In addition, no adverse effects were noted. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the effectiveness of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care. Ketamine may be a promising safe, effective, and cost-effective rapid treatment for depression and anxiety in this population.

Irwin SA, Iglewicz A. Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care. J Palliat Med. 2010;13(7):903-908.

-----

RESULTS: Suicidal ideation scores decreased significantly on the SSI as well as on the suicide subscales of other rating instruments within 40 minutes; these decreases remained significant through the first 4 hours postinfusion (P < .001). Ten subjects (30%) had an SSI score ≥ 4 at baseline; all these scores dropped below 4 (9 dropped by 40 minutes and 1 by 80 minutes). For those patients with a starting score below 4 on the SSI, only 1 reached a score of 4. Depression, anxiety, and hopelessness were significantly improved at all time points (P < .001).

CONCLUSIONS: Suicidal ideation in the context of MDD improved within 40 minutes of a ketamine infusion and remained improved for up to 4 hours postinfusion. Future studies with ketamine in suicidal ideation are warranted due to the potential impact on public health.

Diazgranados N, Ibrahim LA, Brutsche NE, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20673547 [Accessed November 23, 2010].

-----

There are scores more research, with more being added daily. I will be updating this and adding to it periodically, as with the bibliography.
PART II: My Procedure
This is still under construction, but should be useful as-is.

Preliminaries:

Below is a list of things that I personally use for this procedure. If you are unable to get one or any of the below things, I suppose you can use your eyeballs and intuition, and hope that your intuition doesn’t want a buzz, but actually wants to heal.

What is recomended:
- A limited supply of the purest Ketamine one can get, in powder form.
- A “bumper” or bullet or any device that will give out a calculated dose.
- A mg scale.

EDIT: Actually the IM route seems to be ideal. If at all capable of obtaining sealed medical vials and know proper sterile IM technique, then by all means.

Even after all this is obtained, the most important part is SELF CONTROL. Setting a strict budget or getting a limited supply is a good way to do that. Precision in dosing does not seem too critical [Edit: Further experimentation revealed to me that the more precise the dosing, the better - and that an ideal dose is 12mg], as long as that saturation is attained and maintained (more on that later). The reason self-control is critical is so that therapeutic relief of the disease itself is attained rather than having its symptoms masked with a "K-hole." I will detail below a series of “checkpoints” that will tell you whether you are still on track or not.

Some notes: It is unfortunate that Ketamine does not work well rectally, and I am not rich enough to experiment with oral administrtion although I imagine it should work just as well. I don't know if IMing is a good idea, unless you enjoy looking like a pincushion! [EDIT: Further experimentation revealed that IM is perhaps the BEST method as it allows for a calculated dose] IVing is out of question, and I can only call it abuse. IMO, if this eventually turns out to be a legit medical practice, a controlled-release transdermal patch would be ideal. But for now, intranasal seems to be the most convenient method. I have attempted to make nasal sprayers but found them useless as the dose delivered per spray is very low and too much spraying leads to lots of drips and will indubitably form halos of crusty stuff around your nostrils...

About isomers: I have not worked with pure s-Ketamine or pure r-Ketamine, so I cannot speak for these. I have, however, worked with the racemate (most commonly available, and likely what you’re getting) and another brand reported 8:2 ratio of s:r, respectively. The latter is the Ketamine I’ve been using therapeutically for the past 4 and a bit years, as it is much less tempting to abuse than the racemate, while the latter would be my personal choice for entheogenic or IV experiments.

EDIT: Recently the above has come to be questioned. I can say with certainty that most of what I used was Racemic. I also had the chance to try s-Ketamine since and found it to be less useful.

A note on dosing: I used to basically make my own bumps/lines and eyeball a dose. Since this is something that will be done several times daily for several days, measuring each dose individually is simply impractical. What happened is that I decided to just walk into a local headshop and buy a “bumper” – if you don’t know what that is, it is a simple device designed to produce a consistent small dose out of a chamber containing a large amount of powder. I used the scale several times to figure out the average dose that this bumper will produce, and it was perfect: 10 – 20mg for each bump.
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Old 02-09-2011, 01:18 AM   #3 (permalink)
 
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The actual procedure:

It really doesn’t matter how you decide to start. On some occasions, I’d take a recreational dose, and after that, work from there. Other times, I simply start with the smallest dose possible. The bottom line is that what is done in the first couple of days seems to be of little consequence to the regimen, as long as some amount of Ketamine is constantly supplied. (This is what leads me to believe that the desired effect is a result of some kind of receptor saturation).

Here is my own thought on this: A recreational dose for a start may allow for some introspection , or even just a bit of fun to take one’s mind off things. The follow up would then be a maintained and controlled intake of small doses to achieve a very specific state (lets call it “a state of balance”), completely different from the usual effects of Ketamine.

Going back to what was said earlier, I say what happens in the first few days seems of little consequence because it has become apparent to me that this “state of balance” will simply not manifest until after a few days of constant use. So here is what I do:

After the initial dose, I wait until I feel completely sober, and I take my first dose (from here on, “dose” will mean 2 bumps, one in each nostril). I then wait an hour and take the dose again. If I feel I got too buzzed, I wait two hours until I redose. Don’t worry – eventually one will only need 4 – 5 doses per day, but the beginning is always a tricky calibration between a buzz and “tuning in” to that state of balance. [EDIT: Later experimentation with precise dosing via IM showed that several tiny doses per day are more effective than a few big ones]. This first stage is the most difficult one, and one that admittedly resembles simple abuse and denial thereof, (but bear with me)... in fact it may cause negative side effects such as headache, ataxia, confusion, and even nausea (none of which should be too severe – if they are, you’re abusing it!). All these effects should subside by the end of the second day (Edit: this is definitely consistent, I made two experiments since writing the first draft and reproduced this faithfully).

EDIT: In the two years following the writing of this document, I underwent this procedure many times, with a number of them using precise dosing via IM. All is still consistent, but I have noted that in some cases the nausea CAN be severe enough to cause vomiting, generally intensifying at the end of day 1, yet also consistent is the fact that as soon as it is purged, it goes and never returns, no matter how much you take or how long I take it for. The fact that I experienced this most severely when I was severely depressed suggests that it could very well be psychosomatic and that the purging is a cathartic experience.

This goes on until that state of balance is attained. It will become apparent after the fact that one feels clear-headed, motivated, content (note: content, not manic or euphoric) and completely sober and NORMAL (a word very rare in the world of bipolar people), and that those effects now seem independent of the exact moment one takes a new dose (you were that way, and you simply continue to be that way after you dose rather than experiencing a shift in consciousness). At that point, it seems like a certain saturation is attained, and this state of balance becomes one’s new “baseline”. It truly feels as though some switches have been switched off and a couple of new ones have been switched on.

And from here, one can dose less frequently per day. The trick is not to fall into the trap of trying to catch a buzz while maintaining this state – because you can, by simply taking a higher dose than usual. I CANNOT STRESS THIS ENOUGH. What is fascinating is that if I willingly decide to catch a buzz or even an entheogenic experience, when I return to baseline, my baseline will actually be that state of balance, not my bipolar “sobriety”.

I REPEAT: THE MOST IMPORTANT THING IN THIS WHOLE PROCEDURE IS RESISTING THE URGE TO GET HIGH. Two years after writing this articles, I received nothing but good reports except from two people, and both admitted to having succumbed to abusing the drug by binging on recreational doses.

Another pointer that that state as been attained is that one can maintain it overnight while one sleeps without the need to wake up for a scheduled dose. One’s sleeping patterns are no longer affected (as use of small doses of K can cause amphetamine-like stimulation), and one wakes up feeling fine, not hung-over, or manic, or depressed - just fine. Of course, a morning dose is definitely recommended to maintain that. How many times a day one must redose seems to be entirely dependent on one’s brain chemistry. Eventually it always balances out.

Once that week is over (or the limited amount of Ketamine is depleted), this state of balance should remain for at least 2-3 weeks, assuming no other drugs were taken. I have no idea how this would turn out for the chronic cannabis smoker, since I do not partake in cannabis regularly.

One thing I recently discovered accidentally is that Gabapentin seems to "fortify" and maintain the state of balance for longer (it potentiates Ketamine for me anyway), but I'd have to try this again on my next regimen.

EDIT: Gabapentin was used in two regimens since the first draft was written, and has proven to be a fantastic tool in this regard. Gabapentin has become second only to Ketamine as a wonder-drug in my world.

EDIT2: I have absolutely no doubt that Gabapenin works wonders to "Rekindle" the effect. I have also found that using Hydergine concurrently with the procedure tends to enhance the effects.

Some checkpoints to make sure you're on the right track:

- By day 4, are you still stumbling when you walk, dizzy, slurring your speech, or getting any other clear symptoms of intoxication? If so, STOP! You've been abusing.

- By day 5, if you feel "loopy", then you're abusing.

- Panic Attack? While K is known to be a panic-free drug. Getting a panic attack as a direct result of taking K is, IME, a sign of having binged on very high doses. The best thing to do, IME, is if you've taken a high dose to taper down to a 10mg or so dose.

- Are you drinking more often, or taking more drugs than you used to? Another bad sign. I have found that the above procedure has an anti-addictive property, and I have actually used it to help myself quit benzos and codeine. I don't yet have enough info to make the claim that it definitely cures addiction, though.

- A seemingly universal (ie. from everyone that gave me feedback) effect of this procedure is that it makes one a more pleasant person to deal with. If you've been getting complaints about some serious personality changes, then look back and make sure you're doing everything properly.

- By day 7, do you notice no improvement, despite having followed this procedure faithfully, calibrated your weights, and followed the checkpoints? Then perhaps this is simply not for you.


In conclusion, I sincerely hope this is helpful to you. If you have any questions, please post them in this thread.



PART III: Some Idiosyncrasies and Intrigues

My personal experience w.r.t. the method of action, without getting into biochemical jargon which I am simply not qualified enough to discuss, is as follows:

It appears that Ketamine interacts with two separate "systems" or "circuits" (nerve-related). One is excitatory, the other inhibitory (let as call them a and b). The body, in turn, reacts as Ketamine wears off, with inhibitory and an excitatory reactions in the respective systems (let's call them x and y). It appears that this can be "harmonically" exploited by re-dosing the ketamine as these reactions start up such that Ketamine's inhibitory action (b) synergizes with excitatory reaction (x), and Ketamine's excitatory action (a) synergizes with the body's inhibitory reaction (y).

I am sorry if this is confusing, but it is the best I can articulate what my body is telling me.

Interestingly, while I have never had a particular interest in Chinese medicine, it appears that the Taoist model is more helpful in this particular instance: from my limited understanding, the Chinese posit that the body had active currents (Yin) and Passive ones (Yang), and that good health is obtained by balancing these two currents through a healthy lifestyle (cf. Chia).

My experience has repeatedly shown me that a successful Ketamine therapy course will, at its best, result not only in a sense of contentment and balance, but also a moment of clarity when the body feels absolutely at peace, as though a gentle wave of frothy, lukewarm (just right) water has washed upon it. Incidentally, much later, I realized that the Chinese use this very metaphor to explain the state of balanced health.

Does this prove the Chinese model correct? I have no idea. But here is to hoping Ketamine bridges the gap between Modern and Traditional medicines!

[More to be added]

PART IV: First-hand Accounts Feedback

[To Do]

PART V: Bibliography.

[To Do]

Update History:
  • November 22nd, 2008: Finally gave it a proofread (heh, about time), fleshed out some parts, and added several updates (some important) since the first draft.
  • November 20th, 2010: Updated with several edits. To be ironed out and rewritten soon.
  • November 22nd, 2010: 2 Year Anniversary!! Added entire new section (Part I), and edited typos out of Part II.
[/QUOTE]
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Old 02-09-2011, 01:36 AM   #4 (permalink)
 
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mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Nanxin Li, Boyoung Lee, Rong-Jian Liu, Mounira Banasr, Jason M. Dwyer, Masaaki Iwata, Xiao-Yuan Li, George Aghajanian and Ronald S. Duman*
+ Author Affiliations

Laboratory of Molecular Psychiatry, Center for Genes and Behavior, Departments of Psychiatry and Neurobiology, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
*To whom correspondence should be addressed. E-mail: ronald.duman@yale.edu
ABSTRACT

The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications. However, the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified. We observed that ketamine rapidly activated the mammalian target of rapamycin (mTOR) pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rats. Moreover, blockade of mTOR signaling completely blocked ketamine induction of synaptogenesis and behavioral responses in models of depression. Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.
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Old 02-09-2011, 01:37 AM   #5 (permalink)
 
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I personally don't like the idea of any glutamate or nmda antagonist as an antidepressant. I think its bad long term and will effect memory and learning, although acutely it could be used as a reset for synaptogenesis.
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Old 02-09-2011, 01:47 AM   #6 (permalink)
 
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I personally don't like the idea of any glutamate or nmda antagonist as an antidepressant. I think its bad long term and will effect memory and learning, although acutely it could be used as a reset for synaptogenesis.
The idea here is to use it for several days and then benefit from the antidepressant for a few weeks.

Personally i dont see a problem with that and use MXE everyday, but i also want it for tolerance, i'm not much into cognitive enhancement and am not bothered by cognitive decline i wont even notice.
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Old 02-09-2011, 02:00 AM   #7 (permalink)
 
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yes so we both agree it is better in acute use.
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Old 02-09-2011, 08:26 AM   #8 (permalink)
 
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Interesting. I can't see me ever having a chance to try it but I'll not rule it out entirely. Things are going pretty well at the moment for me on the depression front so I'm happy with my current regime for the time being at least.
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Old 02-09-2011, 09:00 AM   #9 (permalink)
 
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Interesting. I can't see me ever having a chance to try it but I'll not rule it out entirely. Things are going pretty well at the moment for me on the depression front so I'm happy with my current regime for the time being at least.
I'm sure this should work with methoxetamine too. But if your current regime works, there's not much reason to try it.
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Old 02-09-2011, 09:16 AM   #10 (permalink)
 
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Originally Posted by crayzyMed View Post
I'm sure this should work with methoxetamine too. But if your current regime works, there's not much reason to try it.
Yeah i'd try it with MXE if I was going to. If only to ensure the consistent strength of the dose, which is so varied with different batches of ket from my experience.
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Old 02-09-2011, 09:33 AM   #11 (permalink)
 
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Very interesting. I'm not in position to experiment just now, without a supply, but this is something I'll keep in mind..thanks for posting!
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Old 02-23-2011, 02:49 AM   #12 (permalink)
 
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Ok this sounds unbelievable.

Severely depressed patient achieved remission within hours from use of very low dose of ketamine. And the effects sustained for about a week.

This is beyond belief.
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Old 02-23-2011, 02:52 AM   #13 (permalink)
 
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If this treats my anhedonia/dysthimia

I will be over the moon

Doing karate, taekwondo, yoga, kung fu at the same time
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Old 02-23-2011, 02:59 AM   #14 (permalink)
 
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i would recommend buprenorphine/suboxone for treatment resistant depression before this, personally. For ketamine to work youd have to take it so rarely imo.
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Old 02-23-2011, 03:04 AM   #15 (permalink)
 
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Yea i know suboxone is also used for treatment resistant depression and the results were also astonishing.

But this is entirely something else. Its like a reset button being hit on your brain.

Moreover the risk of addiction is higher with suboxone.
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Old 02-23-2011, 03:06 AM   #16 (permalink)
 
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The route of administration is tricky.

The dosing is even more tricky.

I don't know how im going to handle this.

This applies for both buprenorphine and ketamine.

Strictly talking about treating depression.
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The route of administration is tricky.

The dosing is even more tricky.

I don't know how im going to handle this.

This applies for both buprenorphine and ketamine.

Strictly talking about treating depression.
Ketamine is much more complicated to deal with. It might induce some neurogenesis but thats not for sure a good thing, it could be in response to damage in fact. The whole premise between electroconvulsive therapy is to damage the brain so it starts secreting high levels of bdnf/ngf and other growth factors. Then you hope everything re-connects right. lol
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Old 02-23-2011, 06:04 AM   #18 (permalink)
 
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Dont you think using an opiate to treat depression is comparatively dangerous.

I mean the tolerance rapdily builds up lightning fast

imagine u started with 0.2mg and next 2 days you are on 2mg...doesnt sound good to me.

Anyways i will give it a go at Ketamine.

Initial dose will be around 75mg.

and then i will ease the dose as soon i have reached the peace of enlightment.
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Old 02-23-2011, 06:21 AM   #19 (permalink)
 
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LOL.

Where the hell did ECT came from in the midst of Ketamine?

ECT is the last thing on my mind in terms of depression relief. It has nothing to do with mechanism of action of ketamine.

ketamine exerts its anti-depressant effect by
  1. blocking NMDA glutamate receptors (stronger than memantine)
  2. inhibiting GABA interneurons
  3. disinhibition of AMPA recepters
  4. induction of mTOR
  5. and finnaly synaptogenesis

all of which takes place in the prefrontal cortex.
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Old 02-23-2011, 06:44 AM   #20 (permalink)
 
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Originally Posted by bben View Post
Ketamine is much more complicated to deal with. It might induce some neurogenesis but thats not for sure a good thing, it could be in response to damage in fact.
Does it mean that ketamine is effective as forced neurogenesis inducer on the level, on which it cause neurotoxicity (NAN)? As I understand, low doses were considered above...If the answer to the question is affirmative, one can risk to take semi-toxic doses of DXM, causing Olney's lesions to provoke restoring neurogenesis, and also hope that "everything re-connects right"
And one more question: what is special about ketamine? Would be other NMDA-antagonist (MK-801, phencyclidine) effective? I saw an article, attributed antidepressant action of NMDA-antagonists to NR2B receptor subtype, that's why dextromethorphan (or actually its metabolite), more selective for the NR2A receptor, does not fit to this purpose. Don't know how it is related to neurogenesis issues, but there is a connection to 5HT1(a) receptor (sic!).
And one more note: tianeptine do the similar thing, reversing stress-induced neurodegradation, and NMDA/AMPA glutamate receptors are also involved in its action. But i can't stack all this raw material in one consistent scheme... Hope someone more capable will give the explanation!
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