Kratom Kratom tolerance theory & method to quickly reduce it

[Snafu in the Void]

Kratom has been shown not to downregulate opioid receptors with long term use like other opioids do. In another study, kratom was shown to reduce both tolerance and withdrawal from morphine in rats when administered together.

Unlike Morphine, Long-Term Exposure to Analgesic Mitragynine, 7-Hydroxymitragynine, Paynantheine, and Speciociliatine Alkaloids Does Not Contribute to Antinociceptive Tolerance of μ-Opioid Receptors

Background: Opioids are the most well known antinociceptive alkaloids all over the world, but tolerance and physical dependence are their dominant concerns in clinical applications. In contrast, monoterpene alkaloids are newly considered for their roles in pain management....

www.researchsquare.com

https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2021.35.S1.05506

Due to some recent experimentation with NAC, I am forming a hypothesis about kratom tolerance and a method to rapidly reduce it by using NAC within specific time periods after kratom.

Kratom alkaloids contain both mu opioid agonists as well as antagonists. My hypothesis is that kratom tolerance develops due to accumulation of the opioid antagonists, or that chronic dosing somehow leads the mu opioid antagonists to take more action in the brain than usual. Maybe they have a longer half life attached as antagonists vs agonists. I think NAC may reduce tolerance by "washing out" these antagonists or somehow deactivating or removing them from the receptors.

NAC significantly dampens the euphoria from kratom if taken before or at the same time as kratom. It dampens all dopaminergic drugs, such as amphetamines and cocaine.

However, from my experiments this last week or two, I have noticed that if NAC is taken around 3-5 hours AFTER dosing kratom, I notice a VERY SIGNIFICANT drop in tolerance upon my next dose (as long as I wait for the NAC to leave my system). A couple of weeks ago I quickly went through 3g of 75% mit extract (on top of some regular powder), this caused a huge spike in my tolerance levels. After dosing NAC just once or twice, I noticed that 4-6g of kratom was enough to provide a huge effect to the point where I felt my tolerance to the opioid effects had reset almost completely. I was honestly a bit shocked and this was unexpected. I have found a few anecdotal reports on reddit who also have noticed this effect, whereas the majority of the anecdotal posts are in regards to how it dampens kratom if dosed beforehand.

The one drawback to this method is that dosing NAC after kratom will indeed dampen the remainder of the high. This is why I take it about 3-4 hours after dosing kratom, because by the time it takes for the dampening effect (~60 min onset), the kratom high is mostly gone anyways so it's not an issue. Then, you have to wait an amount of time, dependent on NAC dose, before you can take kratom again or else it will be muted.

Taking NAC after dosing kratom also, for me, seemed to induce withdrawal more quickly than without it. It's not like naloxone where it immediately precipitates withdrawal, it simply seems to speed up the time when withdrawal starts to hits you (by about ~25-35% or so). However, for me it is definitely worth feeling mild withdrawal for an hour or two in exchange for a much stronger buzz. Taking one dose of NAC and then waiting 8-10 hours to dose kratom seemed to reduce my tolerance more than if I had taken a full 24-36 hours off kratom without the NAC.

I am still experimenting, but this is what I have noticed so far:

(These dosage/time suggestions are what worked for me. You may need to adjust based on metabolism rates or other facts.

300mg NAC - wait a minimum of 5-6 hours before dosing kratom (optimally 7hr +)
600mg NAC - wait a minimum of 8-9 hours before dosing kratom (optimally 10-12hr +)
1200mg NAC - I'm less sure about this, as it seems to block kratom for minimum of 16-18+ hours, and it becomes less practical for me personally since I have a difficult time waiting that long between doses.

300mg NAC and 600mg NAC seem to produce similar effect as to tolerance reduction, but definitely more noticeable at 600mg. 1200mg is less practical, as seems to dampen for much longer without a noticeable tolerance reduction greater than 600mg

Unfortunately it seems like there is a tolerance itself to this tolerance reduction mechanism. After doing this for ~10 days (taking 300-600mg a few hours after kratom) I am not getting as much of a tolerance reduction as when I first started. This may be due to my body adjusting to it and creating less glutathione. Obviously glutathione production tolerance is just my uneducated hypothesis, and it may be due to different processes.

*Update/Warning* : NAC should be cycled!! This morning I randomly had a paradoxical effect from it. In the morning when withdrawal hit, instead of taking kratom I took 120mg of L-Dopa, because I've heard it can nearly eliminate the RLS from kratom withdrawal, and also can enhance kratom itself. I just wanted to check it out, was curious. When I took the L-Dopa, it did indeed stop my leg RLS and other withdrawal symptoms, however I immediately gained RLS in my arms which was not present before. I am familiar with RLS in arms from kratom withdrawal but it generally occurs later on day 2 or 3 of cold turkey. I took kratom, but it did NOT fix the arm restlessness! It continued for 14+ hours, regardless of taking any kratom. I was not in withdrawal, but had arm RLS.... it wasn't until the NAC dose completely left my system did the RLS stop.

I found this unusual because both NAC and L-Dopa are prescribed for RLS in people. However, it seems that NAC can paradoxically actually induce RLS if taken for long periods or in high doses, which I had been. It wasn't any issue at all for about 12 days, then hit out of nowhere.

I will be updating this thread/experiment, but for now I advise not to take NAC for more than a week for this purpose, and not to dose more than 600-1000mg per day while attempting to attenuate kratom tolerance.

Back to my theory, I believe NAC works like this because it may be "washing out" the antagonists out of your system, so the next dose hits you harder. Whether this is due to glutathione or something else, I do not know.

Anyways, I would be very curious if anyone wants to attempt this themselves and see if there's something to this. Maybe it's just unique to my body. It's definitely NOT placebo, though.

I have also read an anecdotal report that regular cysteine also has this effect.

and a bit about NAC itself:

Some people may find NAC useful with kratom in other ways, because although it does dampen the euphoria, it also eliminates the anxiety from stimulating kratom batches. While it does dampen the opioid head high, it might not dampen the analgesia. I haven't been able to assess this because I am not usually in pain.

NAC (n-acetyl cysteine) is an amazing drug in it's own right. It acts as a precursor to produce glutathione, which is an extremely powerful antioxidant and vital in all areas and processes in your body. NAC protects and heals the liver, kidney, and other organs. It also protects and repairs dopaminergic pathways in the brain, and is very useful in tapering or withdrawal from dopaminergic drugs (and others).

NAC is mildly psychoactive on it's own. It's mildly stimulating at higher doses (1200mg can keep me up at night, but 600mg doesn't), can reduce anxiety (particularly social anxiety), repetitive thoughts, and compulsive behavior. It has shown remarkable efficacy in treating various mental conditions such as OCD, bipolar and even schizophrenia. I highly suspect it may even be able to treat stimulant psychosis (although I probably wouldn't rely on this if you have better options, or a reason not to go seek medical care).

 

[Hexenstahl]

I keep saying it over and over again, every time someone asks me what they can do to reduce/keep tolerance to opioids low: ultra low dose naltrexone is the answer. Plenty of clinical studies that prove it and even more anecdotal evidence that backs up the research. Many people on the kratom subreddit have used ULDN to dramatically lower their tolerance and I'm using it to keep my tolerance to morphine at a low level (currently at 240mg/day instead of 600mg which I would normally need if I hadn't concomitantly ingested naltrexone in microgram dosages). This method is so successful and reliable that pharmaceutical companies even created a combi-preparation called Oxytrex (oxycodone and ULDN) to study its tolerance obliterating effects. They quickly took it off the shelves as soon as they discovered that it actually does dramatically lower tolerance because it started to decrease their profit margin (less tolerance means patients need less opioids to manage their pain and that in turn leads to less sales).
Here is a guide on how to create a ULDN solution:

ULDN - The magic weapon to reduce and keep tolerance to Opioids low

Ok so I tried everything: Memantine, DXM, Ketamine and just about any NMDA Antagonist to keep my tolerance to Opioids low but none of it worked in a satisfying and reliable way. A while ago I stumbled upon a couple very interesting scientific papers discussing the use of ultra low dose...

bluelight.org

 

[Snafu in the Void]

I keep saying it over and over again, every time someone asks me what they can do to reduce/keep tolerance to opioids low: ultra low dose naltrexone is the answer. Plenty of clinical studies that prove it and even more anecdotal evidence that backs up the research. Many people on the kratom subreddit have used ULDN to dramatically lower their tolerance and I'm using it to keep my tolerance to morphine at a low level (currently at 240mg/day instead of 600mg which I would normally need if I hadn't concomitantly ingested naltrexone in microgram dosages). This method is so successful and reliable that pharmaceutical companies even created a combi-preparation called Oxytrex (oxycodone and ULDN) to study its tolerance obliterating effects. They quickly took it off the shelves as soon as they discovered that it actually does dramatically lower tolerance because it started to decrease their profit margin (less tolerance means patients need less opioids to manage their pain and that in turn leads to less sales).
Here is a guide on how to create a ULDN solution:

ULDN - The magic weapon to reduce and keep tolerance to Opioids low

Ok so I tried everything: Memantine, DXM, Ketamine and just about any NMDA Antagonist to keep my tolerance to Opioids low but none of it worked in a satisfying and reliable way. A while ago I stumbled upon a couple very interesting scientific papers discussing the use of ultra low dose...

bluelight.org

Although this thread is specific to the kratom tolerance mechanism (different to opioids), I've been curious for awhile as to if this works with kratom. Seems nobody has tried it yet to my knowledge. Kratom alkaloids might not work as well for this, unless you have high % isolated 7-OH-mitragynine. I'm curious, though.

NAC is a lot easier to access since it requires no RX script. I've asked for it from doctors a few times and they seem reluctant to give it to me for some reason that is beyond me... maybe because the main reason I say I want it is to prevent alcohol relapse, as well as kratom. I dunno. I hate doctors.

 

[Hexenstahl]

maybe because the main reason I say I want it is to prevent alcohol relapse, as well as kratom

Leave out "Kratom". Just say you want to get your alcohol cravings under control because nothing else has ever worked for you so far and Naltrexone is your last hope to get your life under control. It should be fairly easy to get a script because Naltrexone is not a controlled substance.

If that doesn't work, contact these guys: https://www.ldnscience.org/
A bunch of doctors work for this organisation. Ask them what to tell a doctor in order to get a script. They are much more open to off-label use of naltrexone and you might get in contact with a doctor who is willing to prescribe you Naltrexone. I really recommend you to take this route because it is scientifically proven to work.
I think this might be of interest to you:

 

[Neuroprotection]

very interesting topic here. in regards to NAC supplementation, I want to start by mentioning that this substance is definitely worthwhile regardless of the context of drug use due to its powerful antioxidant effects and ability to replenish glutathione in neurons. now, in terms of its modulatory effects on psychoactive substances including tolerance reversal and dampening of euphoria when taken alongside the drug, this might actually come down to the same mechanism. basically, NAC temporarily decreases presynaptic glutamate release via activation of MGLU2/3 and this results in a calming, possibly antipsychotic, and maybe even slightly amnestic effect. overtime, this can also result in changes to postsynaptic AMPA receptor properties including changes in their subunit composition, conductance/ permeability to different ions, Channel opening frequency and membrane availability.
Why is this important:
Well, the direct effects of a drug, particularly positive ones like euphoria are often attributed to one receptor, For example MU for opioid euphoria. what we often overlook, is that these receptors are only The first step in a huge range of changes which cascade across circuits. interestingly, as the main excitatory neurotransmitter, glutamate and it’s postsynaptic AMPA receptors are often the final pathway and afectors in the mood altering effects of neurotransmitters like dopamine and opioid peptides as well as the exogenous drugs, that modulate or mimic these respectively.
Going back to The interactions between NAC and Kratom we can theorise how these mechanisms might be at play. let’s start with NAC dampening euphoria when taken with kratom. remember that the ability of NAC to suppress glutamate release temporarily calms large areas of the brain including the reward system. this obviously diminishes the immediate pleasurable effects but the suppressive effects on other emotions, like anxiety could also diminish appreciation for any remaining positive effects of the high. on the other hand, with tolerance reversal, The same process of temporarily diminished glutamate release is still at play, but this time postsynaptic AMPA receptors become sensitised. this is analogous to how antipsychotics can cause supersensitivity of the dopamine system, more specifically, the D2 receptors with which they bind. once the NAC is withdrawn and Kratom alkaloids ingested, the super sensitive emotional system is much more susceptible to their effects.

There’s one more thing I almost forgot to mention. i’ve noticed that not only NAC, but other potent antioxidants can diminish drug induced euphoria according to some anecdotes. apparently, this could be directly due to the antioxidant effect suppressing the activity or buildup of ERK1/2 and Delta FOSB in the nucleus accumbens. this is important because Delta FOSB directly and indirectly sensitises reward functions i’m facilitates both the motivational and hedonic aspects of reward.

I’ll post the links to support my opinions soon.

 

[Neuroprotection]

Group II metabotropic glutamate receptors (mGlu2/3) in drug addiction

Drug addiction is characterized by maladaptive decision-making and dysfunctional brain circuitry regulating motivated behaviors, resulting in loss of the behavioral flexibility needed to abstain from drug seeking. Hence, addicts face high risk of relapse ...

www.ncbi.nlm.nih.gov

N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake

N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown.We investigated the hallmark features of addiction that were influenced ...

www.ncbi.nlm.nih.gov

 

[Neuroprotection]

The two links I’ve just posted can somewhat explain the role of NAC in changing the reward system and assisting with abstinence. Something worth mentioning regarding MGLU2 activations ability to temporarily suppress reward, is that this can be taken as an investment. this is because temporary suppression of dopamine and other reward signals by MGLUR2 is met by tremendous sensitisation of the reward system shortly after. I feel like this Study i’m going to link, Which is about molecular hydrogen May still apply to how NAC can suppress euphoria when coadministered with a recreational drug.

https://www.sciencedirect.com/science/article/abs/pii/S0278584619306402

 

[phall]

This method is so successful and reliable that pharmaceutical companies even created a combi-preparation called Oxytrex (oxycodone and ULDN) to study its tolerance obliterating effects. They quickly took it off the shelves as soon as they discovered that it actually does dramatically lower tolerance because it started to decrease their profit margin (less tolerance means patients need less opioids to manage their pain and that in turn leads to less sales).

Isn't this the same as stuff like targin?. I thought these products were quite common nowadays from what blers are saying or is it a different product.

 

[Neuroprotection]

I keep saying it over and over again, every time someone asks me what they can do to reduce/keep tolerance to opioids low: ultra low dose naltrexone is the answer. Plenty of clinical studies that prove it and even more anecdotal evidence that backs up the research. Many people on the kratom subreddit have used ULDN to dramatically lower their tolerance and I'm using it to keep my tolerance to morphine at a low level (currently at 240mg/day instead of 600mg which I would normally need if I hadn't concomitantly ingested naltrexone in microgram dosages). This method is so successful and reliable that pharmaceutical companies even created a combi-preparation called Oxytrex (oxycodone and ULDN) to study its tolerance obliterating effects. They quickly took it off the shelves as soon as they discovered that it actually does dramatically lower tolerance because it started to decrease their profit margin (less tolerance means patients need less opioids to manage their pain and that in turn leads to less sales).
Here is a guide on how to create a ULDN solution:

ULDN - The magic weapon to reduce and keep tolerance to Opioids low

Ok so I tried everything: Memantine, DXM, Ketamine and just about any NMDA Antagonist to keep my tolerance to Opioids low but none of it worked in a satisfying and reliable way. A while ago I stumbled upon a couple very interesting scientific papers discussing the use of ultra low dose...

bluelight.org

I’ve read many positive anecdotes about this, but I can’t help but have some reservations as well. I am by no means doubting what you say, but rather, since you seem educated on the topic or at least are passionate about it, I was hoping you could clarify these. my main concern is that it sounds too good to be true unless there is some context to it. Would you say ULDN reverses all aspects of opioid tolerance including tolerance to the euphoric effect, or is it only analgesic tolerance that is reversed?
Could ULDN be used to reverse tolerance completely in the absence of opioids?
I must say, I heard one amazing anecdote of a woman who became addicted to prescription opioids for quite a few years. Although she successfully detoxified and stayed sober for years, unfortunately she developed persistent post-withdrawal depression, which didn’t improve at all with prolonged abstinence. The doctors tried everything including many antidepressants and antianxiety medications but nothing worked. if I remember correctly, she resumed opioid use for a while and her depression disappeared, but she didn’t want to live her life addicted to opioids. however, The next time she detoxified, she followed it up with ULDN and the post withdrawal depression completely lifted.

 

[Hexenstahl]

@Neuroprotection
It doesn't completely reverse tolerance. In other words, ULDN does not make your brain opioid naive again where doing opioids feels like the first few times, but it definitely brings back a good portion of that feeling and also prolongs the high + decreases withdrawals from opioids. That's good enough for me honestly. I suggest you read through both my ULDN thread as well as the many anecdotal reports on Reddit (the opiates and kratom subreddit) to get a good idea of what ULDN actually does to your brain. Also, read as many studies as you can. They are incredibly fascinating.

If all this was too good to be true, we wouldn't have that many people with positive experiences. Also, pharma-companies don't fuck around with placebos, they fuck around with what actually works (see Oxytrex). I couldn't believe it myself first until I found my sweet spot and felt how with each dose my tolerance dropped a little more. Now I can simply maintain my dose, knowing that it won't increase and also enjoy a good buzz. It really is a miracle drug.

 

[Neuroprotection]

@Neuroprotection
It doesn't completely reverse tolerance. In other words, ULDN does not make your brain opioid naive again where doing opioids feels like the first few times, but it definitely brings back a good portion of that feeling and also prolongs the high + decreases withdrawals from opioids. That's good enough for me honestly. I suggest you read through both my ULDN thread as well as the many anecdotal reports on Reddit (the opiates and kratom subreddit) to get a good idea of what ULDN actually does to your brain. Also, read as many studies as you can. They are incredibly fascinating.

If all this was too good to be true, we wouldn't have that many people with positive experiences. Also, pharma-companies don't fuck around with placebos, they fuck around with what actually works (see Oxytrex). I couldn't believe it myself first until I found my sweet spot and felt how with each dose my tolerance dropped a little more. Now I can simply maintain my dose, knowing that it won't increase and also enjoy a good buzz. It really is a miracle drug.

That’s great thank you. I have actually read through all these things in the past, but I honestly sometimes find people on this site can provide insight equally as valuable, if not more so than scientific studies and it definitely compliments them. that’s why I wanted to check with you if my understanding was correct. although, ULDN might not completely reverse opioid tolerance, it does a pretty good job as you said. Furthermore, I’m hopeful that it could be a major step in uncovering key downstream events behind opioid tolerance on which scientist can do further work. thanks again for clarifying these things for me.

 

[Jnowhere]

I didn't catch what ULDN stands for? Or if it has a generic name?

 

[Snafu in the Void]

I didn't catch what ULDN stands for? Or if it has a generic name?

Naltrexone in doses much lower than typically prescribed for.

"Ultra Low Dose Naltrexone"

 

[Jnowhere]

Thank you

 

[Snafu in the Void]

Man, there are some incredibly complex mechanisms I have been experiencing during this experiment of mine that are further confusing me.

4 days ago when I had the weird RLS experience after taking L-Dopa, after which NAC seemed to stop decreasing kratom tolerance, may have been what threw something off. Magnesium Glycinate & L-Theanine are also adding to this complexity. I should not have taken those.

I took 2 days off from taking NAC, then tried again this morning with 600mg and it does not produce the effect that it did a few days prior. It is no longer resetting my kratom tolerance, at all, zero.

What is confusing me is this, about 7 days ago I started taking 200-400mg of Magnesium Glycinate at night to aid in sleep, trying to help with waking up in kratom withdrawal, as well as general purpose because I have been jogging daily and my muscles have a hard time relaxing due to this. At first, I had a great response to it. Greatly helped get me to sleep, anxiety reduction, and just generally felt great with less muscle aches. A couple days after taking it I was experiencing greater than usual anxiety after coffee one morning so I took 200mg of l-theanine. This is when something really threw me off, and also when the NAC seemed to stop reducing kratom tolerance and inducing kratom withdrawal (this was around the same time I took the L-Dopa).

I have had bad reactions to l-theanine in the past, likely due to alcoholism sensitizing my glutamate receptors. AFTER taking the l-theanine just once, the magnesium glycinate started giving me HORRIBLE anxiety, physical agitation, and dissociation - it felt almost exactly like glutamate rebound from acute alcohol withdrawal. Awful.

Glycine sensitizes the glutamate receptor, and I have also been taking bromazolam recently which has been battling GABA/glutamate equilibrium, so I can see how I would have a paradoxical response to both magnesium glycinate & theanine. Can't take those anymore.

NAC is supposed to modulate glutamate in a positive way, but now seems to be possibly adding to glutaminergic excitement, but somewhere between all of these things I'm having rather extreme paradoxical reactions to it all, except for the kratom. Kratom feels normal again, and tolerance is back to where it was before I started this experiment.

Anyways, I have since halted my experiment. Will update later when my neurochemistry is more stabilized...

 

[Snafu in the Void]

This experiment has left me even more confused than when I began as to the mechanism at play between kratom and NAC. It has been 4 days since I've taken any NAC and my tolerance seems like it was never effected long term, it seems higher than when I started actually.

It may not be about washing the alkaloids out, but maybe some sort of other effect. I've noticed there is a slight "rebound" to NAC's effects, namely the psychoactive ones and it's benefits treating OCD/rumination/compulsiveness. It's possible that during this rebound the MOR or dopamine pathways are sensitized, seeming to produce a lowering of tolerance, when in actuality it doesn't.

Maybe also worth noting that when I started this experiment, my tolerance was very high and was taking very high doses of kratom. I gradually lowered my dose throughout, then the effect seemed to stop working. It is possible the effect is strongest with higher tolerances.

The anxiety issue I was experiencing stopped after 48hr since last dose of NAC. I'm still unclear as to what caused that. It may have been magnesium glycinate itself, or in combination with NAC. I noticed 20-40mg of DXM would help with the anxiety, so I suspect it has something to due with excessive glutamate excitation. NAC also regulates glutamate, but is supposed to do it in a calming way. Magnesium glycinate is supposed to be calming, but is known to have paradoxical anxiety. Glycine does sensitize the NMDA receptor after all.

 

[Snafu in the Void]

Also, just as an update, dosing NAC daily for a few weeks produced a long lasting blunting effect on kratom euphoria that lasted somewhere around 10-14 days. It also significantly blunted other things, like nicotine.

I would only recommend NAC to people who are trying to quit or taper kratom or other addictions. It's an interesting supplement, though. It should be cycled or taken occasionally.

 

[Neuroprotection]

Man, there are some incredibly complex mechanisms I have been experiencing during this experiment of mine that are further confusing me.

4 days ago when I had the weird RLS experience after taking L-Dopa, after which NAC seemed to stop decreasing kratom tolerance, may have been what threw something off. Magnesium Glycinate & L-Theanine are also adding to this complexity. I should not have taken those.

I took 2 days off from taking NAC, then tried again this morning with 600mg and it does not produce the effect that it did a few days prior. It is no longer resetting my kratom tolerance, at all, zero.

What is confusing me is this, about 7 days ago I started taking 200-400mg of Magnesium Glycinate at night to aid in sleep, trying to help with waking up in kratom withdrawal, as well as general purpose because I have been jogging daily and my muscles have a hard time relaxing due to this. At first, I had a great response to it. Greatly helped get me to sleep, anxiety reduction, and just generally felt great with less muscle aches. A couple days after taking it I was experiencing greater than usual anxiety after coffee one morning so I took 200mg of l-theanine. This is when something really threw me off, and also when the NAC seemed to stop reducing kratom tolerance and inducing kratom withdrawal (this was around the same time I took the L-Dopa).

I have had bad reactions to l-theanine in the past, likely due to alcoholism sensitizing my glutamate receptors. AFTER taking the l-theanine just once, the magnesium glycinate started giving me HORRIBLE anxiety, physical agitation, and dissociation - it felt almost exactly like glutamate rebound from acute alcohol withdrawal. Awful.

Glycine sensitizes the glutamate receptor, and I have also been taking bromazolam recently which has been battling GABA/glutamate equilibrium, so I can see how I would have a paradoxical response to both magnesium glycinate & theanine. Can't take those anymore.

NAC is supposed to modulate glutamate in a positive way, but now seems to be possibly adding to glutaminergic excitement, but somewhere between all of these things I'm having rather extreme paradoxical reactions to it all, except for the kratom. Kratom feels normal again, and tolerance is back to where it was before I started this experiment.

Anyways, I have since halted my experiment. Will update later when my neurochemistry is more stabilized...

Really sorry to hear what you’ve been through. my advice would be to immediately discontinue as many potentially psychoactive supplements and drugs as you can so long as doing so won’t provoke any serious withdrawal. I’ve actually changed my opinion on NAC and now I think NAC should only be used as an antioxidant at low-dose, not as a mood altering drug/Brain hacking supplements. as I said previously on this thread, NAC temporarily decreases presynaptic glutamate release, likely leading to sensitisation of postsynaptic AMPA receptors. of course, that would in tern lead to much greater neuronal excitability. that may well explain your anxiety symptoms. by acting as an NMDA agonist, things like glycine could stimulate unwanted LTP and make your symptoms worse.
To be honest, I suggest you start supplementing with relatively non-neuroactive compounds like vitamin C and vitamin E which could help your brain deal with any oxidative stress as it re-establishes normal balance. If you are successful, which I’m very sure you will be, try to avoid supplements or drugs that directly mess with the glutamate system. it is very easy to forget that The line between A nutrient, pharmacologically active compound and a powerful psychoactive drug can be blurred with small changes to chemical structure, or even the dosage taken can cause that line to be crossed. to slightly
Contradict what I said earlier, I would suggest you take some taurine, perhaps on an as needed basis, to help calm your nerves and promote recovery. Taurine can protect against glutamate toxicity, but is also required for many other brain processes. just don’t mix it with a ton of other substances.
I read similar experiences to yours when it comes to poly substance use or abuse especially when it comes to nootropics. this is because there are so many possible pharmacodynamic and pharmacokinetic interactions that may occur on so many different levels. this may lead to a downward spiral where one tries to self medicate for a negative interaction between two other drugs with a third drug, Only to make things worse or for new side-effects to emerge, To which the response may be introducing yet another drug. The only way to break the cycle is to eliminate as many substances as possible. ideally, One should aim for a period of sobriety/abstinence, to give the brain time to re-establish homeostasis.
I’m actually going to start a thread on polydrug use, and your experience was the main inspiration for this.
I wish you all the best and I hope you make a full recovery. Please let us know how you are getting on.

 

[Hrecoveryfool]

This experiment has left me even more confused than when I began as to the mechanism at play between kratom and NAC. It has been 4 days since I've taken any NAC and my tolerance seems like it was never effected long term, it seems higher than when I started actually.

It may not be about washing the alkaloids out, but maybe some sort of other effect. I've noticed there is a slight "rebound" to NAC's effects, namely the psychoactive ones and it's benefits treating OCD/rumination/compulsiveness. It's possible that during this rebound the MOR or dopamine pathways are sensitized, seeming to produce a lowering of tolerance, when in actuality it doesn't.

Maybe also worth noting that when I started this experiment, my tolerance was very high and was taking very high doses of kratom. I gradually lowered my dose throughout, then the effect seemed to stop working. It is possible the effect is strongest with higher tolerances.

The anxiety issue I was experiencing stopped after 48hr since last dose of NAC. I'm still unclear as to what caused that. It may have been magnesium glycinate itself, or in combination with NAC. I noticed 20-40mg of DXM would help with the anxiety, so I suspect it has something to due with excessive glutamate excitation. NAC also regulates glutamate, but is supposed to do it in a calming way. Magnesium glycinate is supposed to be calming, but is known to have paradoxical anxiety. Glycine does sensitize the NMDA receptor after all.

Great info all around with this…Kratom is tricky. I found dosage not effective from 1-3g, but effective 4-6g, then too much 9-12g(weird wobbles feeling)…when I lowered tolerance, I went from 8-9g/dosages 3-4x day, and got down to >2g/dosages 3-4x/day. Over that time so mainly weird things happened as I adjusted and it seems what you are describing is a lot of normal balancing of just lowering Kratom tolerance. Not saying NAC didn’t play a role but even taking Kratom again after low doses to mild/higher doses proved to be greater effects for 1-2 days then it’s almost like your brain goes right back to that level, you don’t feel great and you lower tolerance again to lower doses and the same damn weird feelings come back until you stabilize for like 5-6 days with the same low doses…i took black seed oil, magnesium, turmeric and drank electrolytes powder. I wonder how much just lowering doses caused these feelings, versus what NAC actually did. It makes sense what you wrote but maybe the effects from NAC were substantial at higher Kratom doses versus lower Kratom doses. Really any Kratom dose under 2-3g barely hits MU receptors, higher doses activates that more…so if dosing Kratom lower like you did with tapering, maybe it was too much of a taper in Kratom dosages or maybe the NAC did wash out the lowered tapered dosages quicker, hence the withdrawal symptoms. The NAC I have also has ashwagandha, NAC, L-dopa, thenine and tyrosine in it. I think adding the l-dopa with NAC counters the depletion NAC takes away from the brain.

 

[Skorpio]

Does the glycine from magnesium glycinate get into the brain?

I always thought our brains did a good job keeping amino acid neurotransmitters from dietary sources from flooding the brain and affecting neurotransmission.