• N&PD Moderators: Skorpio | thegreenhand

Low dose Ketamine depression treatment and Klonopin interaction

bflost2016

Greenlighter
Joined
Jul 12, 2016
Messages
5
I have been waiting for ketamine infusion treatments for depression to be offered where I live, but it could be years before that happens, and the closest facility is 600 miles away, my insurance won't cover it out of network, so i can't really afford it.

In lieu of supervised treatments, I have secured liquid pharmaceutical ketamine, and prepared it to be taken sublingually, based on recommendations from another site, to dilute 1g of ketamine with 200 drops of water. Each drop therefore equated to 5mg.

Background: I have treatment resistant depression and have been treated without success for the last 30 years. I have taken every type of medication that is on the market with no long-term success.

I have also been taking 1mg of prescribed Klonopin for several years to treat Insomnia. I’ve never been able to sleep well, and never feel rested. I also take 20mg of prescribed dextrostat in the mornings.

So I started the K testing this weekend and took twice sublingually.

Day 1 - 10mg 1PM, 10mg 4pm– no noticeable effects, but my sleep was very relstless, and I was more groggy than normal in the morning, but felt relatively ok after a few hours.

Day 2 – I took 20 mg at 1 pm with no noticeable effects. This time my sleep was restless again and I actually slept to 3PM (very out of character) and felt out of it the whole day and even more down than normal. I’m a little nervous to continue this experiment if this is going to continue. I’ve paused to evaluate if I need to make some changes.

Is the Klonopin causing this reaction? If so I could avoid the Klonopin the same day I take the Ketamine.

Is the sublingual method an acceptable way to take the Ketamine for this purpose?
Obviously, I would rather do this in a formal manner, through a provider that would offer IV.

Is there a recommended dosage for treatment of depression?

Lastly, is it possible to find a source to administer this through IV?

Thanks!
 
Ketamine could cause the restless sleep, but it`s probably not dangerous.
Try to avoid taking ketamine with benzos, even low doses of benzos could interrupt the antidepressant effect of the ketamine.
Also make sure you have racemic ketamine, it`s far more effective in treating depression than S-Ketamine. (metabolites of the R-Ketamine part of the racemic ketamine which are important).

Ketamine sublingually could work, intravenous administration works probably better (however neither sublingual nor IV did really work for me; had only a weak effect).
For IV you need a drip to infuse over ~40min a dose of ~0.5 mg/kg, (it`s done in that way in most studies because it seems to work better for depression if it`s not infused at once).
I did these infusions at home because costs for the therapy are ridiculous (ca. 350€ for a single infusion and you need a lot, at home costs for a infusion are < 10€).

Basically you have to experiment with the dosage (range ~0.3mg/kg - 0.7mg/kg) , 0.5mg/kg is a guide value to start.

There is little experience and optimal dose varies for every person; recent studies suggest that the anti-depressant effect of ketamine might be less effective in men, because the concentration of the metabolite mainly responsible for the antidepressant effect is lower in men in general.

In most ketamine therapies you get a series of 5,6 or 7 infusions in a week or so, then every few weeks (as needed) a "booster" infusion to refresh the antidepressant effect.

Sublingual ketamine needs to be taken more often, you have to experiment too. (basically same dosage as intravenous, maybe a bit more)
 
Couldn't one just use subcutaneous injections instead of IV drip? Even IM would not absorb right away... though is less gradual than SQ.

Can't you follow a course on doing IM injection meant for diabetics? I don't know how they learn..

3'.- / 4'-Mono/dihydroxynorketamine type compounds are thought to be responsible right? But of the R-isomer? Thats interesting. But why don't they just administer that... it would have to get cleared first through the many stages of trials, or less so being known metabolites?
Also, it makes me wonder about the analogous metabolites of other dissociatives like MXE.

Enteral route should produce more norketamine via first pass, but the losses are also likely so substantial that it is not viable...
 
I'm most worried the worsening of the depression and malaise. It's mostly worn off after a couple of days, but since I have to increase the dosage in order to start feeling the therapeutic effects, I am worried that this could exacerbate my ongoing issues.

Also, how can you tell if it's racemic or S-ketamine? The brand is Cheminova, but I can't find any indication of the type. I did review the post below, but it confused me more than anything saying that "Most ketamine is racemic, i.e. it is composed of equal parts S/(+) and R/(-) ketamine."
http://www.bluelight.org/vb/threads/447697-Ketamine-Subthread-Isomers-R-and-S-Ketamine

Lastly, how hard is it to administer a infusion yourself? Is there a guide available? I imagine that it would be hard to keep from your significant others living with you, as I would rather they not know.

Thanks
 
You have only taken a very small dose of ketamine, so you don`t have to worry about that.
If the label on the vial is like "Ketamine HCl" or so it`s racemic ketamine, the S-Isomer would be explicitly denoted. (and R-Ketamine is not available on the market).
Also typical concentration of ketamine in pharmaceutical vials is 50mg/ml and S-Ketamine 25mg/ml.
This site describes the findings of that very interesting study: https://www.nih.gov/news-events/news-releases/ketamine-lifts-depression-byproduct-its-metabolism

Solipsis is right, you could also administer the ketamine IM, which is quite easy and probably more effective than the sublingual route.
There are a lot of tutorials on youtube for example on how to do a IM injection.
I read a post of someone a few weeks ago on another forum (post was of 2014) who uses IM injections for his depression (1 per week, > 0.5mg/kg).
 
I've been using this as a loose guide - http://howtousepsychedelics.org/ketamine/. This page does not mention the IM or subcutaneous options, but I believe that IM is more effective than subcutaneous. I'm open to either as long as I get the dosage correct.

I believe the latest "breakthrough" research does point to (2R,6R)-hydroxynorketamine as the molecule responsible for the positive response, but as you stated, it will take years for them to get this to the point where it’s an actual medication.

There have been other studies that point to alternative compounds such as Sacosine, which is a NMDAR enhancer, and can act as a anti-depressant in a similar fashion as Ketamine, which (according to this study) blocks N-methyl-D-aspartate receptor (NMDAR). (http://www.medscape.com/viewarticle/815027)

The length of time it takes any of these options to reach the market is frustrating, and even then, the cost is prohibitive. It’s $600 per infusuion in the US if you are close enough to a clinic.
 
Parenteral BA is about 90-93% (not counting the lossy intranasal), the main difference between IM and SQ should not be loss but kinetics - it just takes longer for SQ to absorb but it ultimately ends up in your blood without being first-pass filtered. For people looking for a better and clearer onset, IM is better, but at these quite low doses I don't think acute tolerance is of concern and it was mentioned above that an IV drip is considered better, stretching out administration.. SQ should mimic that more than IM does. If you choose for IM, I think it would be rather because of reasons of not wanting to get problems with injecting in those tissue layers. I don't think I ever did SQ on purpose myself but seems like it needs a little more finesse.

Why is it so expensive??

If you find learning to do IM a little tricky to learn on yourself, I suppose you could practice on pig tissue a butcher has to spare, same as tattooing is practiced?

Racemic is composed of equal parts R-isomer and S-isomer yes, like the thread said: meaning racemic, when there are only two isomers as with plain ketamine, consists of 50% of R-ket and 50% S-ket... so racemic is not itself a pure form of ketamine like say pure S-isomer is, it is a mixture of the isomers. I guess it can be confusing cause you wouldn't assume that what you consider a pure substance is in some sense a mixture (with regard to stereoisomerism), and in other sense 'pure' (its all ket).
 
3'.- / 4'-Mono/dihydroxynorketamine type compounds are thought to be responsible right?

Nope, this theory has already been disproven:

(2S,6S)-HNK was tested and was found to increase the function of the mammalian target of rapamycin (mTOR), a marker of the antidepressant activity of ketamine, far more potently than ketamine itself (0.05 nM for (2S,6S)-HNK, 10 nM for (S)-norketamine, and 1,000 nM for (S)-ketamine (esketamine), respectively), an action that was observed to correlate closely with their ability to inhibit the α7-nicotinic acetylcholine receptor.[5][6][7] This finding has led to a call of reassessment of the understanding of the rapid antidepressant effects of ketamine and their mechanisms.[8] However, subsequent research has found that dehydronorketamine, which is a potent and selective antagonist of the α7-nicotinic acetylcholine receptor similarly to HNK, is inactive in the forced swim test at doses up to 50 mg/kg in mice, and this is in contrast to ketamine and norketamine, which are effective at doses of 10 mg/kg and 50 mg/kg, respectively.[9]

They only did a very indirect test (mTOR functioning), and the more direct test (forced swim) clearly shows that it's ketamine and (5 times less potently) norketamine.

It's still all about ketamine itself and not about hydroxynorketamine.

Just like it's still all about NMDA channel blocking and not about α7-nicotinic antagonism.

Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in forced swim test: Role of activity at NMDA receptor
 
I've been using this as a loose guide - http://howtousepsychedelics.org/ketamine/. This page does not mention the IM or subcutaneous options, but I believe that IM is more effective than subcutaneous. I'm open to either as long as I get the dosage correct.

I believe the latest "breakthrough" research does point to (2R,6R)-hydroxynorketamine as the molecule responsible for the positive response, but as you stated, it will take years for them to get this to the point where it’s an actual medication.

There have been other studies that point to alternative compounds such as Sacosine, which is a NMDAR enhancer, and can act as a anti-depressant in a similar fashion as Ketamine, which (according to this study) blocks N-methyl-D-aspartate receptor (NMDAR). (http://www.medscape.com/viewarticle/815027)

The length of time it takes any of these options to reach the market is frustrating, and even then, the cost is prohibitive. It’s $600 per infusuion in the US if you are close enough to a clinic.

Sarcosine is a type 1 glycine transporter inhibitor, and thus it increases synaptic glycine concentrations and increases NMDAr activation.
 
... in vitro, of course. Sarcosine is also N-methyl-glycine, which is 1 carbon off of the simplest amino acid possible. SO I doubt it's orally active :p
 
... in vitro, of course. Sarcosine is also N-methyl-glycine, which is 1 carbon off of the simplest amino acid possible. SO I doubt it's orally active :p

True, which is why massive dosages are used to achieve clinical effect.

I reckon the methyl group confers poor substrate selectivity so that sarcosine isn't taken up a lot by peripheral cells. Otherwise it might start incorporating itself into proteins (if it did do this to a big extent it would definitely not be used even in clinical trials). I suspect anyway that the methyl group also makes it a poor substrate for glycine tRNA. Anyway, there is reason to believe there are sarcosine transporters actively taking up sarcosine into the brain, because sarcosine is an intermediate in glycine synthesis from choline.

I'm still confused and suspicious over its pharmacokinetics though. It clearly shows clinical efficacy for both schizophrenia and depression (https://www.ncbi.nlm.nih.gov/pubmed/21936588 https://www.ncbi.nlm.nih.gov/pubmed/23562005), so it would be good if someone else can chime in on this topic and explain how sarcosine is able to reach the brain.
 
also sorry for picking up thread from a long time ago. It fit my topic , sort of, and I didnt want to try and start a new one. I assumed I couldnt anyway. Any thoughts are greatly appreciated
 
^ sounds like whatever you ended up getting wasn't ketamine or was really heavily cut
 
Top