Anyone tried ketamine?

Hip

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What dose of progesterone do you need?
I usually take around 8 mg of progesterone, by placing 0.5 grams of my progesterone cream on my skin (the progesterone cream I have contains 17 mg progesterone per 1 gram of cream).

I've taken higher amounts of progesterone, but it caused some mild adverse effect (I think it caused disturbed sleep, but I can't remember).

By the way, just came across an interesting anxiolytic drug that is said to be as potent as benzodiazepines, but has no tolerance/addiction effects, or drowsiness effect: etifoxine, which can be obtained prescription-free here, here or here. Interestingly, etifoxine helps regenerate peripheral nerves too. I may buy some of this to try out.


For anti-anxiety purposes, you might like my list of 29 supplements that I found effective for anxiety. From that list, to block NMDA receptors, high dose transdermal magnesium applied from head to toe two or three times daily I found effective.

Snorting arginine pyroglutamate is another good one. For me though the best anti-anxiety supplement is N-acetyl glucosamine (NAG.).
 
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For anti-anxiety purposes, you might like my list of 29 supplements that I found effective for anxiety. From that list, to block NMDA receptors, high dose transdermal magnesium applied from head to toe two or three times daily I found effective.
I'm interested in this class of drugs not so much for anxiety although thays a nice benefit , but for severe pain, and for sound sensitivity, essentially looking for something with strong dissociative anesthetic properties
 
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the way, just came across an interesting anxiolytic drug that is said to be as potent as benzodiazepines, but has no tolerance/addiction effects, or drowsiness effect: etifoxine, which can be obtained prescription-free here, here or here. Interestingly, etifoxine helps regenerate peripheral nerves too. I may buy some of this to try out.
How come I haven't heard of this before? Looks incredible on paper. Do you know of any experience reports with it ??? I think I will be buying it and trying myself
 

Hip

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I'm interested in this class of drugs not so much for anxiety although thays a nice benefit , but for severe pain, and for sound sensitivity, essentially looking for something with strong dissociative anesthetic properties
Yes, appreciate that. But it's possible that supplements which reduce NMDA activation, or boost GABA activation, may help. If you look at the theory of central sensitivity syndrome (CSS), the idea is that pain may be amplified to a higher level than normal in the central nervous system, and I believe NMDA activation from high glutamate is implicated in this CSS amplification. I can't remember the details, as it has been a while since I looked into CSS.

However, the idea of glutamate/NMDA activation being behind pain amplification makes sense, since the NMDA receptor is basically the volume or gain control on a neuron. The more you turn up NMDA, the more the neuron amplifies its inputs, and thus creates a stronger output.

My theory is that if this excessive NMDA activation (and neuron output amplification) occurs in the circuits of the brain that mediate anxiety, then this excessive amplification may cause ramped up anxiety, and you will suffer from generalized anxiety disorder, as I did.

But if this excessive NMDA activation occurs in CNS circuits which are involved in pain signal transmission, then maybe instead you get ramped up pain.



Anyway, some of the supplements in my list of 29 I believe work by reducing NMDA activation, so possibly they might work for pain. The high-dose transdermal magnesium helps block NMDA receptors. Oral magnesium will not work, as bowel flushing prevents you from taking high doses. (I have not tried memantine, which blocks the NMDA receptor, so I cannot compare magnesium to that; but I found transdermal magnesium had noticeable effects on anxiety).

The N-acetyl glucosamine I suspect works because it may reduce brain inflammation, and inflammation in the brain produces copious amounts of glutamate, which activates the NMDA receptor. So if you use anti-inflammatories which work in the brain and CNS, you are targeting the root cause of the NMDA activation, which is the glutamate produced from brain inflammation.
 
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Hip

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and for sound sensitivity
The only thing I found which helped substantially reduce my sound sensitivity is very low dose amisulpride, which I have taken daily since 2012. Amisulpride is very similar to Abilify, which quite a few ME/CFS patients are currently experimenting with, and finding benefits.



How come I haven't heard of this before? Looks incredible on paper. Do you know of any experience reports with it ??? I think I will be buying it and trying myself
I only came across etifoxine a few days ago, so know very little at this point. I've seen surprising few reports about positive effects online.

What I have read is that etifoxine causes too many severe adverse effects, such as liver toxicity, colorectal damage and a severe decrease in platelets. This I believe is the reason it's use is not more widespread.

So it's a drug that needs to be approached with caution, and may be best used just occasionally, when you have a bad day, rather than continuously.



Doesn't look good.
 
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Doesn't look good
it doesn't, but then again, it's a single report. I I elsewhere, the literature suggests adverse events are fairly rare. I would rather take it under a docroes doctors supervision , like in europe, but I'm not totally put off trying it

I remember. a similar horror story written about progesterone , which is one of the safest hormones, and being worried about it, but single one off reports are hard to know what to make of. If there were even two serious adverse event experience reports I would rpobably be way more concerned.
The only thing I found which helped substantially reduce my sound sensitivity is very low dose amisulpride, w
I wonder if that means bromantane, being dopaminergic , would significantly help.
 
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Yeah, I am not sure how Olney's lesions arise, but I think it's only a potential issue at high levels of long-term dosing.
There are no in vivo studies on olneys lesions in humans in any dissociative anesthetic, including dxm and ketamine, at least at therapeutically relevant doses.​
I was wrong. The lower end of this : In 2013 a study using magnetic resonance imaging showed brain lesions in ketamine addicts (using from 0.2g twice a week up to 1g daily for 0.5 up to 12 years) with severity depending on the duration of addiction and daily intake of ketamine. Cortical atrophy and holes in superficial white matter are seen early on. After 4 years of addiction lesions spread throughout the brain and damage is evident in the pons and other deeper brain structures.[10]...
Is not that high dose, and is concerning
 
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Doesn't sound good.
It doesn't sound great. Maybe I'm lucky to have bladder issues bc going off my regular daily k dose could be good just to prevent these lesions, provided I don't have them already. .. are these visible on ordinary MRI? I know until this study I was confident this wasn't replicable in ketamine users that weren't doing big doses regularly ... ugh.
 
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: In 2013 a study using magnetic resonance imaging showed brain lesions in ketamine addicts (using from 0.2g twice a week up to 1g daily for 0.5 up to 12 years) with severity depending on the duration of addiction and daily intake of ketamine. Cortical atrophy and holes in superficial white matter are seen early on. After 4 years of addiction lesions spread throughout the brain and damage is evident in the pons and other deeper brain structures.[10]...
Takeaways here are that the low end of the addict's they studied are pretty similar doses to some of the higher end of therapeutic dosing!! But it's one study... I wonder if there are resp0nses or criticisms to it. I'd like to show this to anyone interested in therapeutic ketamine
 
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Yes, appreciate that. But it's possible that supplements which reduce NMDA activation, or boost GABA activation, may help. If you look at the theory of central sensitivity syndrome (CSS), the idea is that pain may be amplified to a higher level than normal in the central nervous system, and I believe NMDA activation from high glutamate is implicated in this CSS amplification. I can't remember the details, as it has been a while since I looked into CSS.

However, the idea of glutamate/NMDA activation being behind pain amplification makes sense, since the NMDA receptor is basically the volume or gain control on a neuron. The more you turn up NMDA, the more the neuron amplifies its inputs, and thus creates a stronger output.

My theory is that if this excessive NMDA activation (and neuron output amplification) occurs in the circuits of the brain that mediate anxiety, then this excessive amplification may cause ramped up anxiety, and you will suffer from generalized anxiety disorder, as I did.

But if this excessive NMDA activation occurs in CNS circuits which are involved in pain signal transmission, then maybe instead you get ramped up pain.



Anyway, some of the supplements in my list of 29 I believe work by reducing NMDA activation, so possibly they might work for pain. The high-dose transdermal magnesium helps block NMDA receptors. Oral magnesium will not work, as bowel flushing prevents you from taking high doses. (I have not tried memantine, which blocks the NMDA receptor, so I cannot compare magnesium to that; but I found transdermal magnesium had noticeable effects on anxiety).

The N-acetyl glucosamine I suspect works because it may reduce brain inflammation, and inflammation in the brain produces copious amounts of glutamate, which activates the NMDA receptor. So if you use anti-inflammatories which work in the brain and CNS, you are targeting the root cause of the NMDA activation, which is the glutamate produced from brain inflammation.
What about this drug that's normally used for alcohol withdrawal... I'm wondering if it could help with dependence on other gabaergics
PharmacodynamicsEdit
The pharmacodynamics of acamprosate are complex and not fully understood;[11][12][13] however, it is believed to act as an NMDA receptor antagonist and positive allosteric modulator of GABAA receptors.[12][13]

Its activity on those receptors is indirect, unlike that of most other agents used in this context.[14] An inhibition of the GABA-B system is believed to cause indirect enhancement of GABAA receptors.[14] The effects on the NMDA complex are dose-dependant; the product appears to enhance receptor activation at low concentrations, while inhibiting it when consumed in higher amounts, which counters the excessive activation of NMDA receptors in the context of alcohol withdrawal.[15]

The product also increases the endogenous production of taurine.[15]

Ethanol and benzodiazepines act on the central nervous system by binding to the GABAA receptor, increasing the effects of the inhibitory neurotransmitter GABA (i.e., they act as positive allosteric modulators at these receptors).[12][4] In chronic alcohol abuse, one of the main mechanisms of tolerance is attributed to GABAA receptors becoming downregulated (i.e. these receptors become less sensitive to GABA).[4] When alcohol is no longer consumed, these down-regulated GABAA receptor complexes are so insensitive to GABA that the typical amount of GABA produced has little effect, leading to physical withdrawal symptoms;[4] since GABA normally inhibits neural firing, GABAA receptor desensitization results in unopposed excitatory neurotransmission (i.e., fewer inhibitory postsynaptic potentials occur through GABAA receptors), leading to neuronal over-excitation (i.e., more action potentials in the postsynaptic neuron). One of acamprosate's mechanisms of action is the enhancement of GABA signaling at GABAA receptors via positive allosteric receptor modulation.[12][13] It has been purported to open the chloride ion channel in a novel way as it does not require GABA as a cofactor, making it less liable for dependence than benzodiazepines. Acamprosate has been successfully used to control tinnitus, hyperacusis, ear pain and inner ear pressure during alcohol use due to spasms of the tensor tympani muscle.[medical citation needed]

In addition, alcohol also inhibits the activity of N-methyl-D-aspartate receptors (NMDARs).[16][17] Chronic alcohol consumption leads to the overproduction (upregulation) of these receptors. Thereafter, sudden alcohol abstinence causes the excessive numbers of NMDARs to be more active than normal and to contribute to the symptoms of delirium tremens and excitotoxic neuronal death.[18] Withdrawal from alcohol induces a surge in release of excitatory neurotransmitters like glutamate, which activates NMDARs.[19] Acamprosate reduces this glutamate surge.[20] The drug also protects cultured cells from excitotoxicity induced by ethanol withdrawal[21] and from glutamate exposure combined with ethanol withdrawal.[22]

The substance also helps re-establish a standard sleep architecture by normalizing stage 3 and REM sleep phases, which is believed to be an important aspect of its pharmacological activity.[15]
 

Hip

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