8 ms·

Ketamine and its analogs are known to have a rapidly developing and profoundly durable (some even say permanent) tolerance, and I find this is often glossed ove

Ketamine and its analogs are known to have a rapidly developing and profoundly durable (some even say permanent) tolerance, and I find this is often glossed over, especially when studies don't evaluate it over a long enough time period I think Ketamine itself isn't a real solution but hopefully some of the isolated metabolites will be

rincebrain 9y ago
Yeah, I would hope that we find more durable solutions. I know some people have been on it for an extended interval without any sort of tolerance problem, which is how I initially heard about it firsthand, so it's one more of those strange biochemistry things that's inconsistent, because of course it is. The interesting thing, to me, would be figuring out what the method of action is for the effect, in order to replicate it in other drugs, but we'll see. (I'm also curious whether repeating the dense dosages would be effective again for me now, over a year later, or whether the tolerance would be, indeed, permanent.)
- sibeliuss 9y ago
  I'm curious about whether you've tried to push the dosages into more psychedelic ranges and whether that had an effect? Many researchers seem to think that at sub-dissociative levels the effectiveness is less, as the _experience_ of that state is what alleviates the depression, not the chemical (so to speak).
  - rincebrain 9y ago
    Most sub-dissociative levels were probably with nasal sprays; I can assure you, this was definitely dissociative levels every time, via IV. We tried increasing the dosage, which made the dissociation more potent, but had no improved psychiatric benefits for me.
dmix 9y ago
> tolerance. I find this is often glossed over This was specifically and prominently addressed by the article: >> However, at 25 days the effects had levelled out. >> The study's authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective. They see it as a bridge treatment which is temporarily useful until anti-depressants kick in. Because, as it said, after 25 days the benefits begin diminishing... which sounds perfectly reasonable and has the added benefit of reducing the risks of addiction.
- cosmie 9y ago
  I think the durability of that tolerance was what the parent was pointing out. As in, it's potentially only useful as a bridge treatment once. If you decide to lapse your long term anti-depressant after several months and suddenly need another bridge treatment as you ramp back up again, the durability of the tolerance from your initial ketamine treatment would prevent it from being useful the second time.
Steel_Phoenix 9y ago
The supplement and drug industries are constantly finding ways to provide chemistry that will be most specific and bio-available. While this certainly has benefits, I worry that by bypassing precursors, we also often bypass important regulatory steps the body uses to avoid damage. The idea that taking something that fixes a symptom, but then creates a permanent tolerance, makes me think that getting that chemical too directly in the past may have caused the tolerance that caused the initial symptom.

rincebrain 9y ago

Yeah, I would hope that we find more durable solutions. I know some people have been on it for an extended interval without any sort of tolerance problem, which is how I initially heard about it firsthand, so it's one more of those strange biochemistry things that's inconsistent, because of course it is. The interesting thing, to me, would be figuring out what the method of action is for the effect, in order to replicate it in other drugs, but we'll see. (I'm also curious whether repeating the dense dosages would be effective again for me now, over a year later, or whether the tolerance would be, indeed, permanent.)

sibeliuss 9y ago
I'm curious about whether you've tried to push the dosages into more psychedelic ranges and whether that had an effect? Many researchers seem to think that at sub-dissociative levels the effectiveness is less, as the _experience_ of that state is what alleviates the depression, not the chemical (so to speak).
- rincebrain 9y ago
  Most sub-dissociative levels were probably with nasal sprays; I can assure you, this was definitely dissociative levels every time, via IV. We tried increasing the dosage, which made the dissociation more potent, but had no improved psychiatric benefits for me.

dmix 9y ago

> tolerance. I find this is often glossed over This was specifically and prominently addressed by the article: >> However, at 25 days the effects had levelled out. >> The study's authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective. They see it as a bridge treatment which is temporarily useful until anti-depressants kick in. Because, as it said, after 25 days the benefits begin diminishing... which sounds perfectly reasonable and has the added benefit of reducing the risks of addiction.

cosmie 9y ago
I think the durability of that tolerance was what the parent was pointing out. As in, it's potentially only useful as a bridge treatment once. If you decide to lapse your long term anti-depressant after several months and suddenly need another bridge treatment as you ramp back up again, the durability of the tolerance from your initial ketamine treatment would prevent it from being useful the second time.

Steel_Phoenix 9y ago

The supplement and drug industries are constantly finding ways to provide chemistry that will be most specific and bio-available. While this certainly has benefits, I worry that by bypassing precursors, we also often bypass important regulatory steps the body uses to avoid damage. The idea that taking something that fixes a symptom, but then creates a permanent tolerance, makes me think that getting that chemical too directly in the past may have caused the tolerance that caused the initial symptom.