Anyone tried ketamine?

[lawson415]

I am just learning about NMDA antagonists and I want to try some. Memantine seems to easily and cheaply available. What dose of memantine were you using? Opps- it is Agmatine that is cheaply available. Has anyone tried it?

 

[heapsreal]

I am just learning about NMDA antagonists and I want to try some. Memantine seems to easily and cheaply available. What dose of memantine were you using? Opps- it is Agmatine that is cheaply available. Has anyone tried it?

a cheaper nmda antagonist is dextromethorphan or DMX and is a common ingredient in alot of cough medicines and has been a study showing it was helpful for fibro pain and there is talk that it can help lower benzo tolerance. I have used this and went by the dosage on the bottle which was 45 mg and it has helped with fibro type pain and seem to improve my sleep with benzo's. Its cheap and easy to get at any local pharmacy, robitusson is a common brand that carry this.

 

[lawson415]

Thanks- I see cvs sells lozenges that are pure dmx- will have to check them out. thank you.

 

[Rand56]

I think some words of caution are warranted here if anyone is going to try DXM. Never tried it myself, but I know there are drug interactions people need to be aware of..even some regular supplements too. Maybe these interactions come with only higher doses but just in case someone decides to haphazardly take more than is needed, better to be safe than sorry. I know this info from this site is mainly for people taking it recreationally, but warnings are warnings and people need to be aware of them....

http://www.hipforums.com/newforums/showthread.php?t=309520

Drug Interactions

• Antidepressants of any kind. MAOIs (monoamine oxidase inhibitors) are the worst; DXM + a MAOI will kill you. DXM with other antidepressants can cause serotonin syndrome, an unpleasant and occasionally fatal condition.

• Diet drugs like phentermine, fenfluramine (Redux), or phen-fen. Again, a risk of serotonin syndrome.

• Non-drowsy antihistamines (allergy medicines) like Allegra, Seldane, or Hisminal.

Here is a list of drugs that mixed with DXM can cause Serotonin Syndrome

Monoamine oxidase inhibitors (MAOIs)
Tricyclic antidepressants (TCAs)
Selective serotonin reuptake inhibitors (Zoloft, Prozac, Paxil,
serotonin-norepinephrine reuptake inhibitor
Lexapro, Celexa)
Venlafaxine (Effexor)
Trazodone (Desyrel)
Nefazodone (Serzone)
Meperidine (Demerol)
Chlorpheniramine
Sumatriptan (Imitrex)
Atypical antipsychotic (Zyprexa, Risperdal, Seroquel)
L-dopa
Meridia
Lithium
Valproic acid (Depakene)
Linezolid (Zyvox)
St John's Wort
Ginkgo Biloba
buspirone
tryptophan
montelukast(Singulair)
kanna
Risperidone
Aripiprazole(Abilify)
5-HTP
Diphenhydramine(Benadryl)
MDMA(Ecstasy, XTC)

Also, do not mix DXM and amphetamines. This can put alot of stress on the heart due to the combined effects of increased heart rate and blood pressure. Not to mention risk of serotonin syndrome.

DXM and LSA is also ill-advised as LSA can cause vasoconstriction, in conjunction with DXM's high blood pressure this could be unhealthy for the heart and circulatory system (Thanks BillyX).

 

[lawson415]

Well I am using some of the things on that list so maybe another nmda antagonist might be a good Idea. I just ordered some agmatine- 500 mg caps. Based on what I see on the weight lifter forums I was thinking of 500 mg 3x daily. Any feedback on agmatine?

 

[redaxe]

Bumping this thread to see if anyone here has had any recent experience with Ketamine.

Apparently there was a clinic chain treating people with severe depression using Ketamine injections in Australia but it was forced to close for reasons that aren't really clearly explained.
http://www.smh.com.au/nsw/medical-c...treatment-for-depression-20150217-13h51o.html

http://www.abc.net.au/news/2015-03-...ion-aura-medical-graham-barrett-quits/6345146

http://www.abc.net.au/news/2015-07-...n-offering-ketamine-injections-closes/6616594


Now I don't want to associate depression with CFS/ME but it apparently it acts as a NMDA receptor antagonist and also is found to reset pain receptors so apparently some people with fibro have found relief from it

Dr Jay Goldstein was using it to recover very sick patients. Also to point out he administered the drug by slow IV infusion to reduce negative reactions or tolerance to the drug.
http://www.cfstreatmentguide.com/dr-jay-goldstein-a-z-treatments.html

That said the claims for it successfully treating 75% of people with depression are interesting. If those results are consistent that is an amazing development and hopefully it improves our understanding of the biological cause of depression and reduces the influence of psychiatry. I can also imagine in the long run it might help doctors better distinguish between treatment resistant forms of depression that might include some forms of PEM and extreme fatigue and CFS/ME.

 

[redaxe]

Just in reply to my last post there is a US clinic that advertises Ketamine Injections from Manhattan

http://usketamine.com/

This is an excerpt

Ketamine, a glutamate NMDA receptor antagonist, has been shown to provide rapid antidepressant benefits when given as a subanesthetic dose. In addition, ketamine has been shown to increase synaptic connections and reverse neuronal damage caused by exposure to stress. Intravenous ketamine has been most commonly studied and positive findings for symptom improvement have been reported for people with OCD and posttraumatic stress disorder (PTSD) in addition to depression. More recently, a more simple and patient-friendly route of administration has been developed. Dr. Lapidus was lead-author on a report published in 2014 that demonstrated the safety and rapid efficacy of intranasal ketamine for depression. In addition to quickly relieving symptoms in those suffering from depression, this method of administration appeared to be better tolerated and result in less side effects when compared to intravenous treatment for depression.

The part about increasing synaptic connections and repairing neuron damage I find very intriguing. Since 'brainfog', poor memory and cognitive dysfunction are almost universal symptoms for CFS/ME patients and Montoya's work at Stanford University demonstrating we have diminished white matter.

If I lived in NewYork I would be very interested in trying that therapy out. Maybe others here can comment if they have any experience on this.

 

[Hip]

One thing of interest with ketamine is that oral or intranasal administration of ketamine hydrochloride (ketamine HCl) has been shown to work just as well for depression as IV ketamine (although a study found that with oral or intranasal administration, it took a little longer for the antidepressant effects to kick in, compared to IV).

Oral or intranasal ketamine HCl would be a far more convenient method of administration, compared to having to go to a hospital or clinic to get an IV. Ketamine HCl can be absorbed orally and nasally because it is water soluble, whereas ketamine is not water soluble.

When sold as a street drug (known as "Special K"), it is the ketamine HCl form that is used. This is usually either snorted or injected, and according to this article, the doses required for a full psychonaut trip on ketamine are around 80 mg if injected, and around 250 mg is snorted intranasally. Obviously for antidepressant or ME/CFS use, you would not want to go on such a trip, so much smaller doses than these are employed. For antidepressant purposes, 50 mg was taken intranasally (see below).

Here are some studies and articles on oral and intranasal ketamine HCl for depression:
• Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial — this study used around a 40 mg ketamine HCl oral daily dose on patients.
• A randomized controlled trial of intranasal ketamine in major depressive disorder — this study used 50 mg ketamine HCl intranasally daily on patients
• Ketamine Nasal Spray For Fast-Acting Depression Relief
• How to Use Ketamine for Depression and Anxiety


Note that it says here that:

The bioavailability of ketamine in the body depends on the way it is administered. Compared to IV administration, intramuscular (IM) administration is painful but results in 93% of the bioavailability of IV ketamine. Intranasal (IN) administration results in 25-50% of the bioavailability of IV administration, while oral administration results in only 16-20% of the bioavailability of IV administration

Antidepressant Effects of Ketamine: Mechanism of Action

This study says ketamine antidepressant effect may be mediated via ketamine's activation of mTOR:

Data suggests that the protracted antidepressant-like effects of ketamine are mediated by molecular alterations to the signaling pathway for the mammalian target of rapamycin (mTOR)

Note however there seems to be an optimum dose, and if you go higher, you lose the mTOR activation effect of ketamine:

There is an inverted U-shape associated with ketamine-induced mTOR activation, with higher doses having no effect.

The study also mentions that:

other antidepressants, including 5-HT2C receptor antagonists, citalopram ... all increase mTORC1 levels

Note that mTORC1 is one of the two enzyme complexes that comprise mTOR.

However, the SSRI, sertraline, and the TCA, imipramine, actually have anti-proliferative effects that are mediated by inhibition of mTOR

This study says ketamine's antidepressant effect may come from:
• mTOR activation
• the production and release of BDNF, a neurotrophic factor essential for neuron development, survival, and synaptic plasticity
• increased BDNF signaling via post-synaptic AMPA receptor stimulation
• via ketamine's inhibition of glycogen synthase kinase-3 (GSK-3)



Hydroxynorketamine (ketamine metabolite) Responsible for the Antidepressant Effects

This 2016 article says that a metabolite of ketamine called hydroxynorketamine (HNK) is specifically responsible for the antidepressant effect of ketamine.

(2S,6S)-HNK increases mTOR activation (a marker of the antidepressant activity of ketamine) far more potently than ketamine itself.

(2R,6R)-HNK, unlike ketamine, is not an NMDA receptor antagonist, and produces no dissociative or euphoric effects, it has consequently been concluded that the antidepressant effects of ketamine may in fact not be mediated via the NMDA receptor.



Where to Get Ketamine

List of US doctors that can administer ketamine for depression:
• Ketamine Advocacy Network

In the UK, ReDKITE is a collaboration between clinicians and researchers exploring the use of low dose ketamine as a possible treatment for treatment resistant depression.



S-Ketamine or R-Ketamine?

As well as the ketamine vs ketamine HCl difference, there is also the issue of whether you use S-ketamine, R-ketamine, or just ketamine (the racemic mixture of both). Ketamine is normally a 50% / 50% racemic mixture of S-ketamine and R-ketamine.

This study found pure S-ketamine may be better than the racemic ketamine in terms of minimizing side effects, as S-ketamine seems to have a lower incidence of side effects such as derealisation and hallucinations.

However, this article says R-ketamine is more effective than S-ketamine at treating depression.

S-ketamine is also called Esketamine.



Ketamine has a number of pharmacodynamic effects, and its benefits for depression and/or ME/CFS may derive from several mechanisms:

• Non-competitive antagonist of the NMDA receptor (NMDAR)
• Negative allosteric modulator of the nACh receptor
• Weak agonist of the μ-opioid and κ-opioid receptors (10- and 20-fold less affinity relative to NMDAR, respectively), and very weak agonist of the δ-opioid receptor
• Agonist of the sigma receptor and D2 receptor
• Weak mACh receptor antagonist (10- to 20-fold less affinity relative to NMDAR)
• Inhibitor of the reuptake of serotonin, dopamine, and norepinephrine
• Voltage-gated sodium channel and L-type calcium channel blocker, and HCN1 cation channel blocker
• Inhibitor of nitric oxide synthase

Source: Ketamine - Wikipedia

The ketamine binding site on the NMDA receptor is shown in the following diagram:

Note that dizocilpine (MK-801), which also acts at the same ketamine site on the NMDA receptor, does not have antidepressant effects (see this rat study).


Note: this post was updated on 19 Jan 2017.

 

[redaxe]

Thankyou for that Hip - Makes me think we should have a specific section in the Treatment section of the forum here specifically for neurological approaches.

But good one too for bringing up the point about oral or intranasal administration - that certainly overcomes some difficulties with accessing the drug due to cost.

Sadly though I think it is something that will be out of reach of many of us because its narcotic classification which ends up with restricted access that Xyrem has. While I think I'm having some improvement on Valcyte I would like to go further and try out other approaches. Makes me really envious of you Americans that your medical community is much more proactive with doctors willing to try new therapies as they emerge.
In Australia trying to get any treatment that's a bit off-label is a major hassle. It seems like we had a clinic doing Ketamine injections but pressure from the psych lobby forced them to close <sigh> the same shrinks that are happy to give out SSRIs despite the risks.....

 

[Insomniac]

I tried Ketamine at Dr Goldsteins in 1999. It worked briliantly then stopped. I was unable to up the dose or change delivery method because I then discovered that it was near impossible to obtain in Israel.


If you can get it prescibed in your country I would recommend trying it.

 

[Hip]

I am actually in the UK. Yes, I saw that about the Australian ketamine clinics closing down, although reading about them, they did seem a bit cheap, shabby and profit-oriented, which perhaps is not the best motivation and set-up if you are going to explore a novel antidepressant treatment. You would ideally want academics running such clinics.

 

[Hip]

I tried Ketamine at Dr Goldsteins in 1999. It worked briliantly then stopped.

Can I ask, how long would you say ketamine worked for before it stopped working for you? And what sort of ME/CFS symptoms did it improve?

For me, I am most interested in ketamine's ability to treat anhedonia, which is a comorbid condition I suffer from alongside ME/CFS.

 

[Insomniac]

1st day was great , then it worked a lot less for pain, ever day and by 2 weeks it was useless.

I got tolerance quickly. I wrote to Dr Goldstein and he said to stop taking it as a nasal spray and take it by mouth instead. I then discovered that it was impossible to get in Israel. If it were available here I would be trying it now. I am v.surprised by all the warnings posters give here.

I used the nasal spray in the exact dosage Dr Goldstein says in his book. I can try to look it up when I feel better, if you like.

 

[Hip]

Dr Goldstein says in his book. I can try to look it up when I feel better, if you like.

Yes please, it would be interesting to know what dose he used. I have Dr Goldstein's "Betrayal by the Brain" book, but I cannot find ketamine mentioned in the index.

 

[Insomniac]

I looked up in " Tuning the Brain" p349.
It says he used Ketamine nasal spray 1:10 or 1:1 and oral swirl 1:1
Whatever that means. It is a shame I don't have the original bottle it came in.

I took it for pain and exhaustion, not anhedonia.

 

[Hip]

It says he used Ketamine nasal spray 1:10 or 1:1 and oral swirl 1:1

Thanks for those details. I notice the page you got them from appears to be available to read here on Google books. Dr Goldstein does not seem to give the actual mg ketamine doses used on that page, but just the concentration of the liquid ketamine solution (concentrations of 1:10 or 1:1).

Although nasal sprays are typically metered around 0.1 ml for each spray, so it should be possible to work out the mg dosage of ketamine in each 0.1 ml spray.


Looking that page, Goldstein appears to be using ketamine there as an agent that acts locally on the trigeminal nerve (a nerve which is found in the eyes, nose and mouth), rather than an agent that has a systemic effect. So he may be using lower doses of ketamine for this local purpose.

 

[Thomas]

@redrachel76 I know we discussed this privately but I am yet to be able to try the lidocaine/ketamine infusions here in Toronto because every damn clinic does the infusion in 30-60 minutes and not by Goldstein's preference of 2-3 hours. I guess when you saw Goldstein he only tried the ketamine solution on you and not the IV?

I'm still unsure what to do. I really want to try this treatment but don't want to risk a further deterioration of my condition, which unfortunately continues to deteriorate. I'm tempted to do the 30-60 min infusion but also reluctant considering how many times in BBTB and TTB he warns against this.

Do you think if the dosages were 1/2 of what Goldstein used then it could conceivably be possible to cut the infusion time by half as well??

The other option would be to either go to NYC, assuming I can travel, and have it done there the way I want it. Or push here in Toronto for a prescription of ketamine cream or oral, that are compounded in pharmacies.

Anyone else feel free to chime in

 

[Misfit Toy]

Me. I have the nasal spray. Problem I have with it is that this most recent batch is for whatever reason very strong and yet they say it's the same dose. Could just be my body. I feel woozy and drugged from it.

The last batch was better. I can say it never helped with depression. It helped pain, but never enough.

I would love a lidocaine infusion. I have lidocaine nasal spray for migraines and it does nothing but numb my throat.

 

[Thomas]

I have the nasal spray

Thanks. What is the dose of ketamine you have been prescribed?

 

[Legolas]

Well I am using some of the things on that list so maybe another nmda antagonist might be a good Idea. I just ordered some agmatine- 500 mg caps. Based on what I see on the weight lifter forums I was thinking of 500 mg 3x daily. Any feedback on agmatine?

Hey,

I've been using agmatine for quite a while now. I does seem to help with the fatigue without giving that wired feeling.
What is it doing to you?

I take 1g (2 capsules) 2 times a day.

Funny thing is this seems to be the only supplement that's cheaper here in Belgium than in the USA.
All other supps i buy on iherb. But this i buy from a belgian/dutch webshop.