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Ketamine is a magical drug, I've told this story a hundred times on HN but it cured my depression overnight. I was given a large hit of it by a doctor after a

Ketamine is a magical drug, I've told this story a hundred times on HN but it cured my depression overnight. I was given a large hit of it by a doctor after a horrible accident, I went into a K-hole and had a spiritual experience, but even more profound was the effect it had for 4 to 6 months after. It was like a veil had been lifted from my mind, the simplest pleasures of life made me happy, like smelling fresh coffee or feeling the sun on my skin. I had been living in misery for decades and suddenly I was awake and lucid and happy.

FollowingTheDao 4y ago
Oh I’ve had that experience, and I’m just bipolar. Ketamine has been known to trigger hypomania and mania in patients. https://pubmed.ncbi.nlm.nih.gov/33587793/ https://pubmed.ncbi.nlm.nih.gov/33587793/ 10 mg of Prozac will do the same thing to me, but that’s just my genetics.
- ad404b8a372f2b9 4y ago
  I don't think that was it for me, though I see the parallels. I just wasn't miserable, the examples I gave were the highlights but really the core of it was that life felt tolerable. Looking at the hypomania symptoms I didn't exhibit any, beside the elevated mood.
whiskyagogo 4y ago
It replaced my lifelong fear (terror?) of death with what I can honestly say is now curiosity. You can experience only so many deaths in your mind before you learn to be comfortable with the idea.
- staticassertion 4y ago
  That sounds frightening. What do yo mean by 'experience only so many deaths' ?
  - askafriend 4y ago
    As they say, "Six million ways to die, choose one"
  - gratitoad 4y ago
    At times I’ve become convinced that all of experienced reality is narrowing to a point and about to wink into nothingness, and myself along with it. It’s hard to explain, but it’s very convincing at the time. So as I experienced this sort of unraveling of the universe I have to confront the idea of my own non-being. Until I come out of it and realize it was all in my head :) Even my early, terrified experiences felt like therapy, like the pain was well spent, so to speak.
    - staticassertion 4y ago
      Sure, I was just curious. So essentially throughout the experience you felt as if things were sort of 'narrowing' and, inevitably, you would too. And with this repeating over and over again it forced you to confront and eventually move beyond a fear of death?
- TaupeRanger 4y ago
  I'm watching the Netflix doc "How to Change Your Mind" about this subject. They use similar language: e.g. that psilocybin causes terminal cancer patients to view death with "curiosity". I find that really interesting, because implicit in this "curiosity" must be the idea of consciousness existing after death...otherwise what would be curious about it? You just die and there's nothing otherwise. So I wonder if, e.g. atheists or non-spiritually inclined folks have the same experiences in these drugs.
  - krrrh 4y ago
    I’m basically an atheist and ketamine assisted psychotherapy did change my background fear of mortality very much in a before and after sort of way. It felt more like a different relationship to time and free will. Like a realization that the universe existed and unfolded like a cellular automata and I was integrated within that. Talking to the very experienced therapist afterwards he summed up my scattered thoughts as, “you resolved your determinacy.” I still don’t believe in an afterlife other than in the abstract sense that that the brief existence of me as a point of consciousness was impacted by all that came before it and will have had an impact on all that comes after. I would say more calmness and more acceptance are better descriptions than curiosity. Like a lot of psychedelic experience, there’s an underlying neurological phenomenon and common subjective experience that gets differently interpreted based on your background beliefs. It’s like the DMT experience of entities is very differently interpreted as inter-dimensional elves by those DMT smokers who have read a lot of Terrance McKenna, as plant spirits by Amazonian ayahuasca drinkers, and as channeled spirits or Christian saints by Daimistas.
- ad404b8a372f2b9 4y ago
  After my spiritual experience 2 years ago, my latent worry / conceptual fear of death was also replaced with curiosity. But I was coincidentally faced with death recently and was disappointed to see my primal terror is still alive and well.
- etaioinshrdlu 4y ago
  I am not convinced that a ketamine-induced feeling of death is at all relatable to actual death. There is plenty of neural activity remaining. Is it possible you're just convinced it feels like death?
  - gratitoad 4y ago
    The point isn’t how similar (or not) the experiences in my mind are to actual death, it’s that at those times I’m convinced I am experiencing not just death, but total annihilation of my consciousness which is my personal best guess about what happens to us when we die. It’s not the moments leading up to death I’ve feared, it’s non-being and attachment to my own thoughts. So then when I’ve experienced a series of “welp, here we go, I’m on my way to nothingness” and dealt with that terror in those moments, I’ve had the opportunity to accept that fate and even embrace the unknown. And now that I’m not gripped by existential terror when I think of my own death, I find myself wondering if I’ll be surprised to find something else on the other side of it. And that’s way more fun :)
- sibeliuss 4y ago
  It's so wonderful to hear that you were able to overcome this.
dundercoder 4y ago
Seconded. For me however, its a monthly treatment for an hour in an office run by an anesthesiologist. The difference is night and day compared to any SSRI, SNRI, or TCA I've ever been on. Exempting the 3-4 hours post treatment, no ill side effects either.
- greymalik 4y ago
  > Exempting the 3-4 hours post treatment What do you experience during that time?
  - dundercoder 4y ago
    Some visual distortions, difficulty focusing, occasional nausea, slow speech, feeling groggy.
fassssst 4y ago
Regular SSRI had the same effect for me.
mathgladiator 4y ago
Been there, and I just did a booster. I'm now very happy as I plug along on my project without any negative judgement: https://www.adama-platform.com/2022/07/02/the-path-of-the-monastic-code-machine.html https://www.adama-platform.com/2022/07/02/the-path-of-the-mo... I'm doing silly things for silly reasons, and I've never been this happy and at peace. It let me heal from the moral injury of working in big tech for a decade.
- birdyrooster 4y ago
  What is your moral injury? I admit I have guilt from working in big tech too, but how did it affect your mental health?
  - mathgladiator 4y ago
    I worked at Meta, and I'm not woke. I have more to write on this, but I was able to grind as I had interesting work. I got bored even as an E8, and I squeezed the last potential out as I mentored and helped others grew.
  - thelittleone 4y ago
    I took ten years of Big Tech. Now I'm back and loving it with more awareness.
- programmarchy 4y ago
  Cool project. You seem like a fun and interesting person. I genuinely mean that!
  - mathgladiator 4y ago
    Thanks!
- ad404b8a372f2b9 4y ago
  Very interesting. I've long sought the divine in the machine but haven't found a satisfactory avenue to pursue it so I went back to Catholicism instead. It provides answers to our suffering that hedonism ignores.
PragmaticPulp 4y ago
> but even more profound was the effect it had for 4 to 6 months after. It's important to note that this is an atypically long duration. In clinical studies, the duration of effects is more around 1-2 weeks. It's possible that the overall experience (including surviving an accident and getting a "second lease on life") was the trigger for 4-6 months of improvement, not just the medication you were given once. That's why, in clinical practice, ketamine is more successfully used in conjunction with typical long-term treatments such as SSRIs and therapy. Some studies used a sequence of 6 treatments spread out over months in an attempt to kickstart the recovery, but it's generally not sustainable as a solo therapy.
- ad404b8a372f2b9 4y ago
  It definitely wasn't because of the accident, my life is ruined lol and at the time I was in horrific pain. But I can accept the timeline could be non-typical. It could also be the huge dose, the studies I've seen use lighter doses.
  - nibbleshifter 4y ago
    Smaller doses of ketamine (recreational doses) taken via nose tend to alleviate depression and anxiety for me for 1-2 weeks, depending on how much of it I do. I've been meaning to travel sometime to a clinic for the infusion therapy (that comes with some talk therapy) as where I am now its nearly impossible to source clean ketamine reliably. Pretty mild doses of psilocybin mushrooms tend to have a longer lasting effect (a month or so), and extremely large doses can work for a half a year or so.
- fragmede 4y ago
  Therapy is really key to sustainable improvement from ketamine, and I worry that it's just being given to patients without the therapy aspects, and what are they doing to do when it stops working for them?
- krrrh 4y ago
  The shorter duration is also more common with lower dose IV infusions. There is evidence that higher concentrations (usually delivered infra-muscularly or sublingually), and the k-hole experience OP describes delivers more long lasting results. In the Ketamine Assisted Psychotherapy space, there is a lot of criticism of the infusion model of a nurse managing simultaneous infusions on several patients at sub-psychedelic doses as a cash treadmill, as opposed to a deeper psychedelic experience which can be more costly to deliver because ideally it demands pre and post integration plus administering to a group can be problematic if someone experiences a “bad trip”. With some preparation and screening a lot of the doses in a series can be managed at home though.
colechristensen 4y ago
Here's a reminder: "Depression" is just a label put on a cluster of symptoms to make diagnoses consistent across medical providers. It is definitely not a singular condition with one cause and a consistent treatment across patients. It is likely a multitude of conditions which will respond differently to many treatments. Some people with a depression diagnosis will be very disappointed with ketamine treatment.
- ad404b8a372f2b9 4y ago
  Yes, your mileage may vary, as they say. Our bodies are all unique and so are our responses. It was a miracle for me, it might be completely ineffective for someone else.
  - colechristensen 4y ago
    I think it is more, or different than "our bodies are unique" and something else entirely. Saying someone has "depression" is like saying someone has "a stomach ache". The stomach ache might be Crohn's, an ulcer, food poisoning, or the aftermath of too many hot wings. All would show at least a somewhat similar cluster of symptoms, different based on the person, but all "stomach ache". Imagine the same for depression, but we don't necessarily have the labels or causes pinned down very well. There probably are many conditions under depression that we'll eventually have good diagnoses for and consistent treatments for, just not yet. It's not a matter of "everybody is unique" but that the science and testing is quite primitive so far and only some of the distinctions and treatments have been worked out.
    - tsol 4y ago
      Depression is a symptom, not exactly an illness. I mean we often treat it like one-- and call that Major Depressive Disorder-- but I expect in the future we'll be able to break it down to 'inflammatory disorder causing symptoms of depression', 'trauma disorder leading to symptoms of depression', etc
- FollowingTheDao 4y ago
Overtonwindow 4y ago
Ketamine also has the effect of creating neuroplasticity in the 24 hours or so following administration. Even the nasal spray.
- thatcat 4y ago
  Source?
  - zone411 4y ago
    https://pubmed.ncbi.nlm.nih.gov/31830487/ https://pubmed.ncbi.nlm.nih.gov/31830487/ "Rodent studies also demonstrate that ketamine rapidly increases BDNF and VEGF release and/or expression in the medial PFC (mPFC) and hippocampus, leading to increase in the number and function of spine synapses in the mPFC and enhancement of hippocampal neurogenesis." https://pubmed.ncbi.nlm.nih.gov/27106168/ https://pubmed.ncbi.nlm.nih.gov/27106168/ "Likewise, repeated ketamine administration increased adult hippocampal neurogenesis" https://pubmed.ncbi.nlm.nih.gov/31310776/ https://pubmed.ncbi.nlm.nih.gov/31310776/ "Our results demonstrate that a single ketamine administration promotes adult neurogenesis in the ventral hippocampus quite selectively" (mice) And a review about psychedelics in general: https://pubmed.ncbi.nlm.nih.gov/34566723/ https://pubmed.ncbi.nlm.nih.gov/34566723/ "Studies (n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment."
bhedgeoser 4y ago
Sorry if this comment comes off as ignorant. I've never taken ketamines and my only experience with ketamines is this game: https://thrilldawill.itch.io/mr-krabs-overdoses-on-ketamine https://thrilldawill.itch.io/mr-krabs-overdoses-on-ketamine . What do you think of it?

FollowingTheDao 4y ago

Oh I’ve had that experience, and I’m just bipolar. Ketamine has been known to trigger hypomania and mania in patients. https://pubmed.ncbi.nlm.nih.gov/33587793/ https://pubmed.ncbi.nlm.nih.gov/33587793/ 10 mg of Prozac will do the same thing to me, but that’s just my genetics.

ad404b8a372f2b9 4y ago
I don't think that was it for me, though I see the parallels. I just wasn't miserable, the examples I gave were the highlights but really the core of it was that life felt tolerable. Looking at the hypomania symptoms I didn't exhibit any, beside the elevated mood.

whiskyagogo 4y ago

It replaced my lifelong fear (terror?) of death with what I can honestly say is now curiosity. You can experience only so many deaths in your mind before you learn to be comfortable with the idea.

staticassertion 4y ago
That sounds frightening. What do yo mean by 'experience only so many deaths' ?
- askafriend 4y ago
  As they say, "Six million ways to die, choose one"
- gratitoad 4y ago
  At times I’ve become convinced that all of experienced reality is narrowing to a point and about to wink into nothingness, and myself along with it. It’s hard to explain, but it’s very convincing at the time. So as I experienced this sort of unraveling of the universe I have to confront the idea of my own non-being. Until I come out of it and realize it was all in my head :) Even my early, terrified experiences felt like therapy, like the pain was well spent, so to speak.
  - staticassertion 4y ago
    Sure, I was just curious. So essentially throughout the experience you felt as if things were sort of 'narrowing' and, inevitably, you would too. And with this repeating over and over again it forced you to confront and eventually move beyond a fear of death?
TaupeRanger 4y ago
I'm watching the Netflix doc "How to Change Your Mind" about this subject. They use similar language: e.g. that psilocybin causes terminal cancer patients to view death with "curiosity". I find that really interesting, because implicit in this "curiosity" must be the idea of consciousness existing after death...otherwise what would be curious about it? You just die and there's nothing otherwise. So I wonder if, e.g. atheists or non-spiritually inclined folks have the same experiences in these drugs.
- krrrh 4y ago
  I’m basically an atheist and ketamine assisted psychotherapy did change my background fear of mortality very much in a before and after sort of way. It felt more like a different relationship to time and free will. Like a realization that the universe existed and unfolded like a cellular automata and I was integrated within that. Talking to the very experienced therapist afterwards he summed up my scattered thoughts as, “you resolved your determinacy.” I still don’t believe in an afterlife other than in the abstract sense that that the brief existence of me as a point of consciousness was impacted by all that came before it and will have had an impact on all that comes after. I would say more calmness and more acceptance are better descriptions than curiosity. Like a lot of psychedelic experience, there’s an underlying neurological phenomenon and common subjective experience that gets differently interpreted based on your background beliefs. It’s like the DMT experience of entities is very differently interpreted as inter-dimensional elves by those DMT smokers who have read a lot of Terrance McKenna, as plant spirits by Amazonian ayahuasca drinkers, and as channeled spirits or Christian saints by Daimistas.
ad404b8a372f2b9 4y ago
After my spiritual experience 2 years ago, my latent worry / conceptual fear of death was also replaced with curiosity. But I was coincidentally faced with death recently and was disappointed to see my primal terror is still alive and well.
etaioinshrdlu 4y ago
I am not convinced that a ketamine-induced feeling of death is at all relatable to actual death. There is plenty of neural activity remaining. Is it possible you're just convinced it feels like death?
- gratitoad 4y ago
  The point isn’t how similar (or not) the experiences in my mind are to actual death, it’s that at those times I’m convinced I am experiencing not just death, but total annihilation of my consciousness which is my personal best guess about what happens to us when we die. It’s not the moments leading up to death I’ve feared, it’s non-being and attachment to my own thoughts. So then when I’ve experienced a series of “welp, here we go, I’m on my way to nothingness” and dealt with that terror in those moments, I’ve had the opportunity to accept that fate and even embrace the unknown. And now that I’m not gripped by existential terror when I think of my own death, I find myself wondering if I’ll be surprised to find something else on the other side of it. And that’s way more fun :)
sibeliuss 4y ago
It's so wonderful to hear that you were able to overcome this.

dundercoder 4y ago

Seconded. For me however, its a monthly treatment for an hour in an office run by an anesthesiologist. The difference is night and day compared to any SSRI, SNRI, or TCA I've ever been on. Exempting the 3-4 hours post treatment, no ill side effects either.

greymalik 4y ago
> Exempting the 3-4 hours post treatment What do you experience during that time?
- dundercoder 4y ago
  Some visual distortions, difficulty focusing, occasional nausea, slow speech, feeling groggy.

fassssst 4y ago

Regular SSRI had the same effect for me.

mathgladiator 4y ago

Been there, and I just did a booster. I'm now very happy as I plug along on my project without any negative judgement: https://www.adama-platform.com/2022/07/02/the-path-of-the-monastic-code-machine.html https://www.adama-platform.com/2022/07/02/the-path-of-the-mo... I'm doing silly things for silly reasons, and I've never been this happy and at peace. It let me heal from the moral injury of working in big tech for a decade.

birdyrooster 4y ago
What is your moral injury? I admit I have guilt from working in big tech too, but how did it affect your mental health?
- mathgladiator 4y ago
  I worked at Meta, and I'm not woke. I have more to write on this, but I was able to grind as I had interesting work. I got bored even as an E8, and I squeezed the last potential out as I mentored and helped others grew.
- thelittleone 4y ago
  I took ten years of Big Tech. Now I'm back and loving it with more awareness.
programmarchy 4y ago
Cool project. You seem like a fun and interesting person. I genuinely mean that!
- mathgladiator 4y ago
  Thanks!
ad404b8a372f2b9 4y ago
Very interesting. I've long sought the divine in the machine but haven't found a satisfactory avenue to pursue it so I went back to Catholicism instead. It provides answers to our suffering that hedonism ignores.

PragmaticPulp 4y ago

> but even more profound was the effect it had for 4 to 6 months after. It's important to note that this is an atypically long duration. In clinical studies, the duration of effects is more around 1-2 weeks. It's possible that the overall experience (including surviving an accident and getting a "second lease on life") was the trigger for 4-6 months of improvement, not just the medication you were given once. That's why, in clinical practice, ketamine is more successfully used in conjunction with typical long-term treatments such as SSRIs and therapy. Some studies used a sequence of 6 treatments spread out over months in an attempt to kickstart the recovery, but it's generally not sustainable as a solo therapy.

ad404b8a372f2b9 4y ago
It definitely wasn't because of the accident, my life is ruined lol and at the time I was in horrific pain. But I can accept the timeline could be non-typical. It could also be the huge dose, the studies I've seen use lighter doses.
- nibbleshifter 4y ago
  Smaller doses of ketamine (recreational doses) taken via nose tend to alleviate depression and anxiety for me for 1-2 weeks, depending on how much of it I do. I've been meaning to travel sometime to a clinic for the infusion therapy (that comes with some talk therapy) as where I am now its nearly impossible to source clean ketamine reliably. Pretty mild doses of psilocybin mushrooms tend to have a longer lasting effect (a month or so), and extremely large doses can work for a half a year or so.
fragmede 4y ago
Therapy is really key to sustainable improvement from ketamine, and I worry that it's just being given to patients without the therapy aspects, and what are they doing to do when it stops working for them?
krrrh 4y ago
The shorter duration is also more common with lower dose IV infusions. There is evidence that higher concentrations (usually delivered infra-muscularly or sublingually), and the k-hole experience OP describes delivers more long lasting results. In the Ketamine Assisted Psychotherapy space, there is a lot of criticism of the infusion model of a nurse managing simultaneous infusions on several patients at sub-psychedelic doses as a cash treadmill, as opposed to a deeper psychedelic experience which can be more costly to deliver because ideally it demands pre and post integration plus administering to a group can be problematic if someone experiences a “bad trip”. With some preparation and screening a lot of the doses in a series can be managed at home though.

colechristensen 4y ago

Here's a reminder: "Depression" is just a label put on a cluster of symptoms to make diagnoses consistent across medical providers. It is definitely not a singular condition with one cause and a consistent treatment across patients. It is likely a multitude of conditions which will respond differently to many treatments. Some people with a depression diagnosis will be very disappointed with ketamine treatment.

ad404b8a372f2b9 4y ago
Yes, your mileage may vary, as they say. Our bodies are all unique and so are our responses. It was a miracle for me, it might be completely ineffective for someone else.
- colechristensen 4y ago
  I think it is more, or different than "our bodies are unique" and something else entirely. Saying someone has "depression" is like saying someone has "a stomach ache". The stomach ache might be Crohn's, an ulcer, food poisoning, or the aftermath of too many hot wings. All would show at least a somewhat similar cluster of symptoms, different based on the person, but all "stomach ache". Imagine the same for depression, but we don't necessarily have the labels or causes pinned down very well. There probably are many conditions under depression that we'll eventually have good diagnoses for and consistent treatments for, just not yet. It's not a matter of "everybody is unique" but that the science and testing is quite primitive so far and only some of the distinctions and treatments have been worked out.
  - tsol 4y ago
    Depression is a symptom, not exactly an illness. I mean we often treat it like one-- and call that Major Depressive Disorder-- but I expect in the future we'll be able to break it down to 'inflammatory disorder causing symptoms of depression', 'trauma disorder leading to symptoms of depression', etc
FollowingTheDao 4y ago

Overtonwindow 4y ago

Ketamine also has the effect of creating neuroplasticity in the 24 hours or so following administration. Even the nasal spray.

thatcat 4y ago
Source?
- zone411 4y ago
  https://pubmed.ncbi.nlm.nih.gov/31830487/ https://pubmed.ncbi.nlm.nih.gov/31830487/ "Rodent studies also demonstrate that ketamine rapidly increases BDNF and VEGF release and/or expression in the medial PFC (mPFC) and hippocampus, leading to increase in the number and function of spine synapses in the mPFC and enhancement of hippocampal neurogenesis." https://pubmed.ncbi.nlm.nih.gov/27106168/ https://pubmed.ncbi.nlm.nih.gov/27106168/ "Likewise, repeated ketamine administration increased adult hippocampal neurogenesis" https://pubmed.ncbi.nlm.nih.gov/31310776/ https://pubmed.ncbi.nlm.nih.gov/31310776/ "Our results demonstrate that a single ketamine administration promotes adult neurogenesis in the ventral hippocampus quite selectively" (mice) And a review about psychedelics in general: https://pubmed.ncbi.nlm.nih.gov/34566723/ https://pubmed.ncbi.nlm.nih.gov/34566723/ "Studies (n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment."

bhedgeoser 4y ago

Sorry if this comment comes off as ignorant. I've never taken ketamines and my only experience with ketamines is this game: https://thrilldawill.itch.io/mr-krabs-overdoses-on-ketamine https://thrilldawill.itch.io/mr-krabs-overdoses-on-ketamine . What do you think of it?