KetTolerance
Greenlighter
- Joined
- Jun 14, 2026
- Messages
- 3
Hello everyone. As many knows - ketamine can induce long term and almost permanent tolerance.
I was not aware about it until it happened.
My goal is to learn all about this condition and collect any cases that can change this tolerance.
I will be glad to see your experience and insights about it.
My story:
What i got:
I want to fix my nervous system back, i'm concerned about it.
I miss the high, but i concerned by that serious consequences.
Thanks God that i'm pretty functional and can live my life almost like before.
I have almost normal memory and mental abilities - not dumb, not shaking, not something like that.
So, cognition works "almost normal" (maybe 10-15% difference from baseline), but i can't get high at all (maybe 1/10th or less of baseline) - pretty interesting how it's possible.
Because any other drugs leave you more predictable compensation like sleepiness from stimulants, lack of sleep and appetite from cannabis, and withdrawals from opioids.
Please don't abuse dissociatives if you feel reduction of effects - permanent tolerance is not a joke. It alters personality and you can't be sedated for surgery.
Please share your expreience how and what changed your response to ketamine on permanent tolerance.
Can you get high on cannabis? Can you feel tobacco if you're using it?
Have you tried racetams and magnesium and how it affected your permanent tolerance?
Does stimulants like amphetamine does something for permanent tolerance?
Or caffeine, or any other medication - if you noticed something or know exact timeline and dosage, please share.
Let's beat this thing and find reliable way how to reverse this changes.
Later i'll write about what i found. About gabaergic interneurons, calmodulin, magnesium block, internalization, AMPA and NMDA.
Ketamine is possibly works by reducing "brakes" of gabaergic interneurons and boost glutamate, calcium influx and depolarization.
With permanent tolerance you probably can't get that surge because of upregulation and/or downregulation of nmda receptors (at different locations) and/or different subunits, and changes in other pathways (like different GABA influx to pyramid neurons - not depend on NMDA blocking anymore like before).
Also there may be epigenetic mechanism of receptors and enzymes synthesis, like that control glutamine synthesis, internalization and subunits.
Alcohol and cannabis "loss of magic" is probably mediated by same pathways, because i can't get high from cannabis.
I was not aware about it until it happened.
My goal is to learn all about this condition and collect any cases that can change this tolerance.
I will be glad to see your experience and insights about it.
My story:
I'm 27 year old male and had long journey with dissociatives.
At school ages i tried DXM many times and there was no tolerance. Effects was "sharp", "clean" and good.
At 20 years old i tried many dissos like ketamine and MXE. It was two binges by 1 month everyday use and 6 months not using dissociatives between.
First binge i can't remember tolerance build up, but remember depression 2 months after i stopped.
But i did many drugs like mephedrone, so maybe it's not related.
I notice depression as possible first signs of temporary changes in glutamate system because glutamate action not feels like exact emotions and feelings, it's easily can mask to something other. Like tiredness and lack of motivation from other addictions. Because many things goes to that pathways.
I want to map every change in all stages of permanent tolerance development.
It's actually gradually builds up and you can notice exact signs. I will write it below.
Second time i remember 4 things: reduced effects, irritability and mental tiredness, feeling like brain "hot" from hyperactivation with ketamine (when tolerance got me first time and i tried to use it again), and about few months of unconscious depression after.
But after that, i had good high for long time. Years after being sober.
(That depression feels like hopeless, lack of motivation, like you can't be happy and lack this healthy pleasant cognitive euphoria vibes from good activities like walking, conversation, music and sleep.)
And this time, i've done ketamine for a year and a half and it suddenly stopped working.
When i started after years of being sober, effects was good, strong, k holes, doses like 80-300mg by few times per session.
I used too much, maybe every 1-3 days.
Permanent tolerance came was like a day before it was ok, and next day effects suddenly disappeared!
I remember i desperately tried to boost the dose and had some weak visuals like from that rotating optic illusion, but the deepness of the effect was failing like demolition of old tower!
Like in an hour effects just deflated to about 10% of something regular.
At school ages i tried DXM many times and there was no tolerance. Effects was "sharp", "clean" and good.
At 20 years old i tried many dissos like ketamine and MXE. It was two binges by 1 month everyday use and 6 months not using dissociatives between.
First binge i can't remember tolerance build up, but remember depression 2 months after i stopped.
But i did many drugs like mephedrone, so maybe it's not related.
I notice depression as possible first signs of temporary changes in glutamate system because glutamate action not feels like exact emotions and feelings, it's easily can mask to something other. Like tiredness and lack of motivation from other addictions. Because many things goes to that pathways.
I want to map every change in all stages of permanent tolerance development.
It's actually gradually builds up and you can notice exact signs. I will write it below.
Second time i remember 4 things: reduced effects, irritability and mental tiredness, feeling like brain "hot" from hyperactivation with ketamine (when tolerance got me first time and i tried to use it again), and about few months of unconscious depression after.
But after that, i had good high for long time. Years after being sober.
(That depression feels like hopeless, lack of motivation, like you can't be happy and lack this healthy pleasant cognitive euphoria vibes from good activities like walking, conversation, music and sleep.)
And this time, i've done ketamine for a year and a half and it suddenly stopped working.
When i started after years of being sober, effects was good, strong, k holes, doses like 80-300mg by few times per session.
I used too much, maybe every 1-3 days.
Permanent tolerance came was like a day before it was ok, and next day effects suddenly disappeared!
I remember i desperately tried to boost the dose and had some weak visuals like from that rotating optic illusion, but the deepness of the effect was failing like demolition of old tower!
Like in an hour effects just deflated to about 10% of something regular.
1.Tolerance starts as a plateau - you can't break through this level of effects. And it tend to weaken to zero in few times.
It's possible to feel something stronger with large doses, but it barely works non linearly and doses are dangerous.
Some times i tried and got only dim effect. Not deep, not strong. Like not much receptors now involved.
Maybe like stronger affinity dissos will do more effects, but weaker may be lack of time to do any effects because it "washed" out of receptor too fast.
NMDA receptors also consists of 4 subunits and it naturally can have different affinities and responses to ketamine-like drugs.
Maybe different binding site still working - i don't know and don't want to test right now.
That big doses felt like brain reduce effects very fast, like if have less or more receptors and can't got necessary concentration to block transmission or induce glutamate.
And effects despite being stronger was not "deep and sparkling" like normal. It was more muffeled and blunt. Like a buzz but not that sharp crystallized feelings and thoughts.
Binding affinity, ion channels (and GPCR ) receptors depends on concentration of ligand, but permanent tolerance to ketamine may (or may not) respond to stronger dissos (like o-PCE vs ketamine, or PCP, or MK-801).
2.Being sober for 1 month vs 1 other month is not the same.
Time not really helps in predictively manner. I even got much more results after 1 week than after 1 month - details below.
3.Before when i had strong dissociation, i also had sleepy feeling after end of action.
With tolerance this sleepiness became weaker and went away. No effect no sleepiness, at least for me.
4.Slurry speech and ataxia went away about 9 months before permanent tolerance.
5.Face numbing and pleasant buzz started to disappear 3 months before permanent tolerance.
6.Time loops and disorientation went away about 9 to 6 months too.
This timeline could help figure out what brain areas depend on this changes and concentration distribution in brain (where more or less it was and how strong it changed neurons).
7.There was motivation, will and happiness decline every time i tried to use ketamine again to test tolerance - it's just not working.
And it lasts for week, but later i probably adapted to this and depression is not severe like first time permanent tolerance kicked in.
By the way - i had depression even when i had strong effects, so it might be glutamate depletion/reduction or something like this, not really related to tolerance. I even had suicidal thoughts after massive abuse. Effects was strong, but my brain was like really messed by so much action.
I'm was like i'm losing myself and want to stop abuse and that wasted state.
8.I can't get high from weed, alcohol, tobacco - effects just dim too! If you know this sparkling flowing feeling - i have not this all.
BUT i've got it again after my tolerance was reduced for some time.
9.After day tolerance kicked me or when i try use ketamine to test it - i have some king of distracted from reality feeling. Not dissociation, but like i'm not "in the moment".
Like perception feels "cold" and less detailed, like less feeling about something you see, less associations.
And racetams can give that feeling back. And it does something with tolerance too.
10. One month ago i had successfully temporary change in my tolerance - i was able to get high, but only once.
BUT week ago i was unable to feel anything!
First week for 5 days i used aniracetam and started to feel jittery. And when i stopped and used ketamine 2 days after - i had no effects.
I was mentally tired and started to use magnesium citrate to calm down. Like 400mg per day, for 5 days on second week.
My conclusion was: if aniracetam is not working, maybe magnesium will work.
And guess what? When i tried ketamine again - i was able to feel effects from small doses and was able to dissociate like i haven't for few months before, even after 1 months breaks!
I used magnesium before ketamine too, but next times it not help.
And just magnesium after not restored tolerance.
11.When i started magnesium, i started to feel more "in the moment", more this calm aesthetic feel of perception when you looking at something.
Before successful dissociation i was sure that it will be ok! Actually, i was falsely sure before too. But this time a lot of things changed and i was almost normal again - much more deep emotions, feeling, sleep, thoughts, cognition.
12.And i got pleasant feelings from weed and tobacco what i haven't for long time too after tolerance drop recently, but it went away.
13.I still enjoy orgasm even when i can't enjoy cannabis. And i was unable to finish when i was dissociated and even when i just tried to test tolerance with small dose of ketamine and had no dissociation.
But it definitely stronger when tolerance less. But not many times, maybe 1.5 or less.
Ability to finish goes back after two hours.
14.Before permanent tolerance, even small doses got me that headspace and feeling of energy, probably because of rise of glutamate after blocking of gabaergic interneurons. Like better speed without side effects.
15.I had reduction of tolerance to cannabis after using opioids for two months too. Long time ago.
16.Once i had no effects but still raised the dose untill it started to appear like before, like some kind of concentration was needed to block enough receptors.
17.Cannabis with ketamine gave me synergistic effects (before permanent tolerance).
18.With opioids it was like i'm going to lose consciousness without any additional pleasant effects or buzz, just passing out not even dreams (before permanent tolerance).
19.Magnesium before tolerance drop (recently) gave me some very subtle feels of deja vu too.
20.Before permanent tolerance i had subtle deja vu feel from aniracetam every time.
21.Feels like i'm less overwhelming excited by something in my life, like can't feel overwhelming strong anger, euphoria - and this changes my will.
I learned to control it, but at first if felt like i lobotomy. Now i'm active and motivated, but still less than before.
Aniracetam really helps and probably not needed every time, it's just goes better after 1 week after using any ketamine.
When i had no tolerance, i had probably same decline for 1 week or so after binge, but now it feels like less energy.
Unfortunately, reduced tolerance effects went away after 1 day of use - but effects like was 70% of normal level!
This is really promising with that problem.
It's possible to feel something stronger with large doses, but it barely works non linearly and doses are dangerous.
Some times i tried and got only dim effect. Not deep, not strong. Like not much receptors now involved.
Maybe like stronger affinity dissos will do more effects, but weaker may be lack of time to do any effects because it "washed" out of receptor too fast.
NMDA receptors also consists of 4 subunits and it naturally can have different affinities and responses to ketamine-like drugs.
Maybe different binding site still working - i don't know and don't want to test right now.
That big doses felt like brain reduce effects very fast, like if have less or more receptors and can't got necessary concentration to block transmission or induce glutamate.
And effects despite being stronger was not "deep and sparkling" like normal. It was more muffeled and blunt. Like a buzz but not that sharp crystallized feelings and thoughts.
Binding affinity, ion channels (and GPCR ) receptors depends on concentration of ligand, but permanent tolerance to ketamine may (or may not) respond to stronger dissos (like o-PCE vs ketamine, or PCP, or MK-801).
2.Being sober for 1 month vs 1 other month is not the same.
Time not really helps in predictively manner. I even got much more results after 1 week than after 1 month - details below.
3.Before when i had strong dissociation, i also had sleepy feeling after end of action.
With tolerance this sleepiness became weaker and went away. No effect no sleepiness, at least for me.
4.Slurry speech and ataxia went away about 9 months before permanent tolerance.
5.Face numbing and pleasant buzz started to disappear 3 months before permanent tolerance.
6.Time loops and disorientation went away about 9 to 6 months too.
This timeline could help figure out what brain areas depend on this changes and concentration distribution in brain (where more or less it was and how strong it changed neurons).
7.There was motivation, will and happiness decline every time i tried to use ketamine again to test tolerance - it's just not working.
And it lasts for week, but later i probably adapted to this and depression is not severe like first time permanent tolerance kicked in.
By the way - i had depression even when i had strong effects, so it might be glutamate depletion/reduction or something like this, not really related to tolerance. I even had suicidal thoughts after massive abuse. Effects was strong, but my brain was like really messed by so much action.
I'm was like i'm losing myself and want to stop abuse and that wasted state.
8.I can't get high from weed, alcohol, tobacco - effects just dim too! If you know this sparkling flowing feeling - i have not this all.
BUT i've got it again after my tolerance was reduced for some time.
9.After day tolerance kicked me or when i try use ketamine to test it - i have some king of distracted from reality feeling. Not dissociation, but like i'm not "in the moment".
Like perception feels "cold" and less detailed, like less feeling about something you see, less associations.
And racetams can give that feeling back. And it does something with tolerance too.
10. One month ago i had successfully temporary change in my tolerance - i was able to get high, but only once.
BUT week ago i was unable to feel anything!
First week for 5 days i used aniracetam and started to feel jittery. And when i stopped and used ketamine 2 days after - i had no effects.
I was mentally tired and started to use magnesium citrate to calm down. Like 400mg per day, for 5 days on second week.
My conclusion was: if aniracetam is not working, maybe magnesium will work.
And guess what? When i tried ketamine again - i was able to feel effects from small doses and was able to dissociate like i haven't for few months before, even after 1 months breaks!
I used magnesium before ketamine too, but next times it not help.
And just magnesium after not restored tolerance.
11.When i started magnesium, i started to feel more "in the moment", more this calm aesthetic feel of perception when you looking at something.
Before successful dissociation i was sure that it will be ok! Actually, i was falsely sure before too. But this time a lot of things changed and i was almost normal again - much more deep emotions, feeling, sleep, thoughts, cognition.
12.And i got pleasant feelings from weed and tobacco what i haven't for long time too after tolerance drop recently, but it went away.
13.I still enjoy orgasm even when i can't enjoy cannabis. And i was unable to finish when i was dissociated and even when i just tried to test tolerance with small dose of ketamine and had no dissociation.
But it definitely stronger when tolerance less. But not many times, maybe 1.5 or less.
Ability to finish goes back after two hours.
14.Before permanent tolerance, even small doses got me that headspace and feeling of energy, probably because of rise of glutamate after blocking of gabaergic interneurons. Like better speed without side effects.
15.I had reduction of tolerance to cannabis after using opioids for two months too. Long time ago.
16.Once i had no effects but still raised the dose untill it started to appear like before, like some kind of concentration was needed to block enough receptors.
17.Cannabis with ketamine gave me synergistic effects (before permanent tolerance).
18.With opioids it was like i'm going to lose consciousness without any additional pleasant effects or buzz, just passing out not even dreams (before permanent tolerance).
19.Magnesium before tolerance drop (recently) gave me some very subtle feels of deja vu too.
20.Before permanent tolerance i had subtle deja vu feel from aniracetam every time.
21.Feels like i'm less overwhelming excited by something in my life, like can't feel overwhelming strong anger, euphoria - and this changes my will.
I learned to control it, but at first if felt like i lobotomy. Now i'm active and motivated, but still less than before.
Aniracetam really helps and probably not needed every time, it's just goes better after 1 week after using any ketamine.
When i had no tolerance, i had probably same decline for 1 week or so after binge, but now it feels like less energy.
Unfortunately, reduced tolerance effects went away after 1 day of use - but effects like was 70% of normal level!
This is really promising with that problem.
I want to fix my nervous system back, i'm concerned about it.
I miss the high, but i concerned by that serious consequences.
Thanks God that i'm pretty functional and can live my life almost like before.
I have almost normal memory and mental abilities - not dumb, not shaking, not something like that.
So, cognition works "almost normal" (maybe 10-15% difference from baseline), but i can't get high at all (maybe 1/10th or less of baseline) - pretty interesting how it's possible.
Because any other drugs leave you more predictable compensation like sleepiness from stimulants, lack of sleep and appetite from cannabis, and withdrawals from opioids.
Please don't abuse dissociatives if you feel reduction of effects - permanent tolerance is not a joke. It alters personality and you can't be sedated for surgery.
Please share your expreience how and what changed your response to ketamine on permanent tolerance.
Can you get high on cannabis? Can you feel tobacco if you're using it?
Have you tried racetams and magnesium and how it affected your permanent tolerance?
Does stimulants like amphetamine does something for permanent tolerance?
Or caffeine, or any other medication - if you noticed something or know exact timeline and dosage, please share.
Let's beat this thing and find reliable way how to reverse this changes.
Later i'll write about what i found. About gabaergic interneurons, calmodulin, magnesium block, internalization, AMPA and NMDA.
Ketamine is possibly works by reducing "brakes" of gabaergic interneurons and boost glutamate, calcium influx and depolarization.
With permanent tolerance you probably can't get that surge because of upregulation and/or downregulation of nmda receptors (at different locations) and/or different subunits, and changes in other pathways (like different GABA influx to pyramid neurons - not depend on NMDA blocking anymore like before).
Also there may be epigenetic mechanism of receptors and enzymes synthesis, like that control glutamine synthesis, internalization and subunits.
Alcohol and cannabis "loss of magic" is probably mediated by same pathways, because i can't get high from cannabis.
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