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They should not be lumping ketamine in with all the other psychedelics which act on the serotonin 2A receptor. I’m hesitant to say ketamine is a psychedelic at all.

Regardless, I find .25 mg of Klonopin can get rid of my depression as well, they’ve known for a long time that depression has a strong linked glutamate excitation in certain parts of the brain.

Chronic benzo administration can cause depression, so that might not work for everyone.

I'd argue that the term "psychedelic dissociative" accurately captures what ketamine can be.

I do not take it chronically and no one should. I take it once, as needed. Works for a few days.

And chronic ketamine use can cause depression as well:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035802/

All these drugs are not the answer. It is much more likely there is a fundamental immune dysfunction causing the depression. IMHO, all mood disorder patents should be seen by rheumatologists, not psychiatrists.

https://en.wikipedia.org/wiki/Anti-NMDA_receptor_encephaliti...

FYI: I have Sjogren's Syndrome and Discoid Lupus

Amongst psychedelic therapists it’s pretty normal to include Ketamine under the rubric of psychedelics these days, even though receptor purists might still object. Same is true of MDMA. From a subjective experience there’s no doubt that it’s different, but at psychedelic dose ranges most psychonauts will characterize it is a psychedelic experience, and ketamine can produce experiences every bit as weird and life altering as the tryptamines.

One interesting line of research on thinking about new ways to characterize this that they all can be characterized as re-opening critical periods of development. Gul Dolen at Johns Hopkins is spearheading this, and this interview with her is worth a listen.

https://www.iheart.com/podcast/1119-psychoactive-84544756/ep...

Higher (recreational) doses of ketamine can induce extremely interesting states that I would definitely classify as "psychedelic" in effect.

It is an interesting drug.

There are also subjectively different effects between racemic ketamine and pure S-ketamine. I have never been able to try pure R-ketamine, it just doesn't seem to be available.

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.

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/

10 mg of Prozac will do the same thing to me, but that’s just my genetics.

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.
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.
That sounds frightening. What do yo mean by 'experience only so many deaths' ?
As they say, "Six million ways to die, choose one"
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.
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?
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.
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.

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.
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?

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 :)

It's so wonderful to hear that you were able to overcome this.
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.
> Exempting the 3-4 hours post treatment

What do you experience during that time?

Some visual distortions, difficulty focusing, occasional nausea, slow speech, feeling groggy.
Regular SSRI had the same effect for me.
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-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.

What is your moral injury? I admit I have guilt from working in big tech too, but how did it affect your mental health?
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.

I took ten years of Big Tech. Now I'm back and loving it with more awareness.
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.
For me, I found the purpose as my role is to solve puzzles. Ketamine gave me a sense of spirit that we are all connected in this life, and gave me insights that are hard to describe. However, I believe there is value in waking up and solving puzzles for the sake of solving puzzles and it may not be time to leverage it in the commerce (if at all).
Growing up in a catholic household, what I mostly felt as a kid was cognitive dissonance and guilt... but to each their own.
Parenting is hard.
I figure it's easier when your main goal is raising your child as a life-loving person, instead of a good Catholic.
There's lots of ways that crafting a moral compass around being a "life-loving person" can go wrong too.

It's a hard problem.

You can say that about any kind of life philosophy.

However, children are born as life-loving creatures. It seems reasonable that it's easier to keep them that way while teaching them how to function in this world, than to force onto them rigid unnatural habits (for example, many Christians consider sexuality a bad thing, and teach their children to be ashamed of their sexuality, except in this very special case of being married to someone; or they take the "respect your parents" command too seriously, effectively ridding their child of all rights to any kind of personal integrity - "I am your parent, you shall respect me, no matter what I do"), which lead to frustration of the child, which leads to resistance, which leads to frustration of parents, which leads to general unhappiness and mistrust.

But even if we completely disregard the complexity of raising children - Christianity is, in its essence, a suffering fetish. The symbol of Christianity is a man suffering on a cross. I do not believe that that kind of imagery doesn't have harmful effects on young children.

I understand that you have a specific problem with Christians. However, you should be aware that your examples aren’t just wrong but more like caricatures of what’s actually in the Bible.

The TLDR on the Bible is John 3:16-21. You’ve probably heard the first sentence, but I encourage you to read the full paragraph and then compare it with the characterization you shared here.

> However, you should be aware that your examples aren’t just wrong

I've personally witnessed every single thing I've written, so they can't be completely wrong. I was also raised in a Christian family, in a Christian neighborhood, so I'm pretty sure that what I've observed is at the very least plausible.

> The TLDR on the Bible is John 3:16-21.

You should note that Bible is huge, full of contradictions and open to interpretation. You should also note that many Christians have never even read the Bible, and don't follow it to the word, but rather follow the culture of their peers, which is usually focused on observable behaviors (don't eat X, don't work on Y, don't do Z, etc.), rather than deeper, more complex points (love thy neighbor as you love yourself, turn the other cheek, who is without sin - throw the first stone, etc.).

Note that (except for the "suffering fetish" comment) I'm not even trying to tackle the Bible or Christianity as a philosophy here. I'm talking strictly about the sociological aspects of religion.

“I’m talking strictly about the sociological aspects...”

Life is hard. Individuals consistently fail to act with everyone’s best interests in mind. This is true of all people and all groups of people at all scales.

The offensive thing about Christians is that they’re a people that have acknowledged that they aren’t behaving appropriately in the first place and have come to the conclusion that they want to behave accordingly to the standard set in the Bible. It’s completely understandable that when they don’t live up to that standard that others are put off.

When everyone is out there living their own truth, it can be offensive to learn about a group of people who reject the idea of their own truth and put their trust in the God of the Bible. It’s especially understandable that folks are quick to judge them for their hypocrisy when they fail to live up to that standard.

> Life is hard. Individuals consistently fail to act with everyone’s best interests in mind.

Yes, but Christianity gives people the excuse not to question their core beliefs - they just confess, repent, blame it all on Satan and carry on with business as usual.

> The offensive thing about Christians is that they’re a people that have acknowledged that they aren’t behaving appropriately in the first place and have come to the conclusion that they want to behave accordingly to the standard set in the Bible

The offensive thing about Christians is that they are constantly trying to impose rules from the Bible upon other people (e.g. abortion laws in southern US).

> When everyone is out there living their own truth, it can be offensive to learn about a group of people who reject the idea of their own truth and put their trust in the God of the Bible.

In other words, Christians consider themselves eternally right, and everyone else eternally wrong, no matter what evidence is provided.

You mentioned the concept of repentance. The biblical concept of repentance requires action to restructure the way you do things and is mutually exclusive with "business as usual". Anyone who is doing the BAU part skipped the repent part.

Regarding laws, we live in a representative republic where anyone can vote for any representative to act in their interests. If you would prefer that we remove the rights of Christians to vote because they tend to vote for policies that you don't support, well, that's a very different type of government. Historically, in the US, we have gone to great lengths to give marginalized groups the right to vote.

Finally, a Christian is simply a person who has decided that they will organize their life according to the standard defined in the Bible in preference to other options. Other people make decisions to organize their lives in other ways. It seems like you are willing to tolerate folks in the latter camp, but hold a special animosity towards folks in the former camp. Do we not each have our own autonomy?

> The biblical concept of repentance requires action to restructure the way you do things and is mutually exclusive with "business as usual".

That's your interpretation. The behavior I have observed is different.

> Historically, in the US, we have gone to great lengths to give marginalized groups the right to vote

Christians in the US are not marginalized.

> Finally, a Christian is simply a person who has decided that they will organize their life according to the standard defined in the Bible in preference to other options. Other people make decisions to organize their lives in other ways. It seems like you are willing to tolerate folks in the latter camp, but hold a special animosity towards folks in the former camp. Do we not each have our own autonomy?

Read about paradox of tolerance: https://en.wikipedia.org/wiki/Paradox_of_tolerance

In order for society to remain tolerant towards everyone, it must not tolerate intolerance. Christianity (as well as many other popular religions) is not tolerant, no matter how much that word appears in its holy books - just look at the history.

Ok, I wish you the best, but I don't think it's productive to continue this conversation. Sadly, you've decided to take the position that Christians should have their right to vote curtailed along with their rights to make decisions for themselves. That's a strongly authoritarian position for an American to take. I hope you'll reconsider.
> I don't think it's productive to continue this conversation. Sadly, you've decided to take the position that Christians should have their right to vote curtailed

If that's all you took away from this conversation, then I agree - it's for the best to end it now. But I'll try to elaborate anyway.

I am not taking the position that Christians should have their right to vote curtailed, I'm taking the position that nobody, not even Christians, should have the right to impose their own standards upon others, unless they made sense outside of the Christian worldview. Abortion laws only make sense in the Christian worldview (and maybe a few other, equally intolerant, worldviews). The fact that Christians are the majority in the US only makes it de-facto a Christian state, while still pretending to be a secular democracy.

Here's a thought experiment:

If Talibans somehow became a majority in the US, would you still consider it "their right" to vote away the democracy and establish Sharia Law?

I'll make an exception because you've asked a good question that I think will help illuminate our different viewpoints.

> If Talibans somehow became a majority in the US, would you still consider it "their right" to vote away the democracy and establish Sharia Law?

Yes. The current form of government in the United States is a representative republic that has a constitution that defines processes for dramatic change including a constitutional convention that allows for open-ended changes to the constitution itself.

I don't have a divine right to the land, water, or air here.

> Yes.

That's were we disagree. I believe there are some human freedoms that nobody has the right to deny. I suppose I'm just an idealist.

> The current form of government in the United States is a representative republic that has a constitution that defines processes for dramatic change including a constitutional convention that allows for open-ended changes to the constitution itself.

I'm sure the goal of such openness of constitution was to protect the liberty of people, not to open doors for authoritarianism.

How do we enumerate which human freedoms that nobody has the right to deny? What if there isn't consensus? If there isn't consensus and they are just imposed by fiat, then you've simply come around to authoritarianism from the other direction.
That's a hard question, like any other question concerning human freedom. I suppose a good rule of thumb is "if you're not forced to subject yourself to it, you don't get a say in it".
I am in no way diagnosing, but I have Bipolar Disorder, so did my mother and my brother. I say things like this which you wrote when I am hypomanic/manic:

"As I reflect on this, I’ve concluded that I exist with the divine purpose of bringing beauty into the world. Beauty and elegance require tremendous suffering because having taste is expensive."

It is kind of typical of the condition.

I know nothing I saw will convince you that the state you are living in is not a balanced state because I have been there as well and no one could tell me otherwise, so I get it.

That's fair, and there is context I intend to talk about more in a couple of future posts. I left my big tech job as a E8 (senior principal-ish) as I just got so bored.

I retired from big tech, but it wasn't until ketamine until I could reset to a new baseline and be truly grateful for my present state. Now, I do what I want when I want and the spiritual experience helps me be ok with doing my Thang without too much judgement.

I work on my platform, and I recently started to paint.

> It is kind of typical of the condition.

It can be, but it’s not exclusive to it.

It’s good that you’ve identified cues that helps you check in on your own well-being, and it’s good that you have concern for others and want to help them, but please be mindful not to inadvertently shit on someone else’s sundae in the process.

Seeing your life in spiritual terms and identifying yourself with a purpose is a common and healing experience, especially during transformative points in one’s life — like coming out of a depression, finding love, overcoming adversity, or even reading a book or exploring a new faith that resonates strongly.

For some people, those feelings can get out of control and it’s good for people who face that pattern to be aware of what may be warning signs for them, but the same behavior is often a normal and healthy experience for others. Without other signs of concern, it might be kinder let others be than to suggest they question their own recovery.

most of what you said is fair, but as a Taoist, I do not see a semi euphoric state as being a normal condition, or even a condition that can be a sustained for a long period of time. There’s a saying, that a strong wind does not blow all day.

With these rushes of neurotransmitters, the receptor density on our neurons changes to adapt to them. This is a truth that we all need to understand. This is how the strong wind ends.

I’m afraid that people will be obsessed with trying to sustain this type of bliss when a more healthy approach would be to look for a neutral state. Absent of the constant highs and lows.

I admire your concern for people, but you might be getting a little bit ahead of the data when you start imagining others getting obsessed and develop your own fears for their sake.

But I’d also mention, as a fellow student of balance, that it can be found amidst great highs and lows and not just in the absence of them. Acrobats exhibit tremendous balance. :)

Whatever I’m just a homeless schizaffective bipolar fuck who actually thinking about killing himself right now so who cares.
988 Suicide & Crisis Lifeline

We can all help prevent suicide. The Lifeline provides 24/7, free and confidential support for people in distress, prevention and crisis resources for you or your loved ones, and best practices for professionals in the United States.

https://988lifeline.org/

Thanks. Better now. Took a bunch of klonopin, managed to talk to a friend who is a therapist.
Ketamine has a nice rate limiter of $500 per session and at most once a month. I just had a booster, but I can't imagine myself doing it again for a while.

I do believe a neutral state is ideal, but that requires highs and lows to define. For a variety of reasons, it's very easy to get stuck in a down position for a variety of reasons.

Having some ups is also a lot better than always being down.

Congrats ok your success.

Congratulations on healing from moral injury and good luck with your interesting project!
> 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.

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.

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.

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?
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.
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.

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.
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.

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
Yes, this. IMHO, there are two type of depression, both immune mediated, and both drive my glutamate/GABA imbalance. One is high glutamate the other is high GABA, either effecting different region of the brain.

This imbalance affects serotonin and norepinephrine release.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311508/

And this change is mediated by the immune system. Glutamate is now known as an immunomodulator.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997749/

No doubt, but that applies to all depression treatments. Most of which have a far higher risk of side effects, and many of which take weeks or months to show an effect if they do work.

Ketamine treatment takes an hour, with virtually no chance of side effects, and you'll know if it works within a few hours. Even if it only works for a tiny percentage of depression sufferers, it should be first line treatment. As it is, it seems to work for a reasonably large percentage of people.

Not just that it's important to remember that many studies have questioned whether antidepressants are at all better than placebo for the treatment of depression in the first place. [1] Some say no, some say yes statistically significant but not meaningful clinically. [2]

The reality is psychedelics may be the only meaningful medical treatment we actually have for depression.

[1] https://www.webmd.com/mental-health/news/20080227/antidepres...

[2] https://www.frontiersin.org/articles/10.3389/fpsyt.2019.0040...

It's great to see psychedelics being considered more and more for tackling mental health conditions, but I'd still like to see the discussion extended to include:

a) Other ways of achieving peak experiences and senses of connectedness, wonder and awe, be that mindfulness/meditation, being out in nature, flow states, breathwork etc. which are more often accessible to everyone, for free and without needing to involve big pharma and may have less side effects, supported where necessary with the same complimentary (talking) therapies that run alongside the psychedelics.

b) Challenging some of the potential underlying causes, I'm not suggesting this will apply in all cases, but stress/burn-out, financial pressures, lack of meaning, lack of connectedness, pressure from social media, inequality etc.

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

"Likewise, repeated ketamine administration increased adult hippocampal neurogenesis"

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/

"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."

The frequency of these kind of posts followed by anecdotes about how it worked for the commenter (who I believe btw) makes me a little uneasy. Somewhere buried in the discussion eventually is a comment from a relevant professional urging caution in interpreting and reacting to these news reports and anecdotes. Now with something as serious as this I would not at all object to such cautions being placed a bit more prominently. This isn’t reckless use of goto being discussed but something much more serious. Anyway, I just wanted to get that off my chest. Perhaps it’s just me, don’t take it as a holier than thou attitude.
Something much more serious for many people is the specter of suicide looming over them.

Caution is useful, but it’s not always an unalloyed good.

Chemotherapy isn’t healthy or safe, but the thing it’s used to stop is even worse.

As someone who has taken extremely heavy doses of some very, very potent psychedelics (LSD, DMT, ketamine, mescaline and psilocybin), I am inclined to agree with you. I acknowledge that some people experience great benefits from psychedelics, but the current push to label psychedelics as mental health miracle solution doesn't sit right with me.

Make no mistake: these chemicals are not to be trifled with. People with underlying mental health issues - the poeple who would be most interested in using psychedelics - are at heavy risk of exacerbating their illnesses. Even outside of those special cases, I've seen normal people become heavily affected by bad trips. I simply don't think that there is enough scientific literature on the adverse effects of psychedelics. I also do not like the heavy focus on the "spiritual" aspects that these drugs are believed to confer: are you really transcending, or are you just so heavily intoxicated that you believe you are and no longer have the rational capabilities to convince yourself otherwise?

If I can end on just a little anecdote myself, I personally believe that heavy psychedelic use is especially counterproductive to technical/knowledge-based work. I did barely any work during the year that I was experimenting with these drugs. I was so content with my life as it was that I simply didn't feel the urge to exert myself. I was becoming soft, more predisposed to magical thinking. I believed that psychedelics had revealed unto me truths about how society should be run, how life should be and the true nature of mathematics. But I didn't know a damn thing! I just lost the inclination to actually analyse my ideas (or notions, because they barely qualified as ideas), instead being content to just accept them as they were. After a long stretch of abstinence from these drugs, I realised how worthless most of these notions actually were. I also deeply regretted the amount of time I spent taking these notions seriously, as well as the amount of time I had wasted in thinking that I had actually been experiencing any spiritual truths.

Thanks for sharing your experience. Most stories I read online about psychedelics are overwhelmingly positive, so much that it feels like you’d be missing out on life if you didn’t try it. It’s good to read your kind of stories too.
> I was becoming soft, more predisposed to magical thinking.

My experience is only with microdosing LSD and psilocybine mushrooms, however this 'softness' does ring true to me.

The good part with microdosing though is that it doesn't last anywhere near a year, while the positive effects I've felt and the deep conclusions I reached about myself and life in general I think will last a lifetime.

LSD has especially helped me get pretty much completely rid of anxiety in a particularly tense moment of my life. It has also 'thawed' some more ingrained thought patterns and ideas I had about things.

What you are saying makes me wonder whether there is a correlation between predisposition towards magical thinking (spirituality, religiosity, etc.) and effectiveness of psychedelics?

And for that matter could there be an equivalent of psychedelics for various types of AIs?

As my stoner friend says, “you just gotta believe, bro”

Believe what tho?

Your skepticism is warranted. Psychedelics are a hot topic and journalists have been promoting a lot of one-sided articles that make them sound like miracle cures. In clinical practice, ketamine can be useful as part of a recovery and treatment strategy, but it's not really an effective long-term treatment due to the short duration of effects (1-2 weeks post dosing) and the unsustainable nature of the drug (tolerance builds to the anti-depressant effect with repeated dosing).

Some ketamine treatment providers are running very professional and well-staffed businesses (source: had to do a lot of due diligence on the industry for a potential investment) but some of the others are shockingly under-qualified to be administering high doses of ketamine to patients with little evaluation. The regulatory bodies are slowly catching up to some of these providers and instituting stricter regulations. While there is some therapeutic potential, it needs to be delivered in the context of a long-term treatment strategy rather than just giving someone ketamine over and over again (as some unscrupulous providers will gladly do as long as the patient is willing to pay).

Honestly, I find HN's obsession with "professionals" annoying. For long-tail conditions, the professionals are frequently far less informed than fellow sufferers.

During the beginning of the pandemic, people on HN were telling us that N95 masks do nothing without official fit training. Bro, official fit training is something you can easily sub with a free video from 3M's website. It's this hopeless obsession with "official" and "professional" and shit like that when any reasonably intelligent individual can work through stuff themselves.

The one side effect of regular ketamine use in particular of having it recrystallize in your bladder, ripping it to shreds, is something I wonder if we're going to see more of in the medical literature in the future.

That said it's a pretty interesting wonder drug of sorts for a ton of different things, for example preventing further excitotoxic damage from brain injury

Psychedelics are illegal not because they create hallucinations but rather because they help break down the hallucinations we have about the world. In the land of the blind, the one eyed man is a hallucinating idiot.
One of my favorite stories about psychedelic experiences is a friend's coworker dosing acid one weekend, coming back in on Monday, saying "I hate it here" and quitting on the spot. They went on to travel and start their own company, and are doing great for themselves.

In my experience, psychedelics really help tear down the justifications we put up for the BS we tolerate in our daily lives and can help you connect with what you really appreciate and want in life. Definitely helped me realize the kind of person I want to be and appreciate the good things in my life. And similarly to the story about the coworker quitting, my tolerance for BS is nil, now, too.

psychedelics really help tear down the justifications we put up for the BS we tolerate in our daily lives

Thing is you can do that with an extended weekend of fasting/meditation and solitude in the woods. Bring a notepad and pencil if you really want to lock in the new perspective. Bonus is that fasting is also widely known to be healthy.

Plus how do you really know the causative agent of change was the drugs, what if there was already the underlying emotional desire to do something and having the experience was more about creating the justification to act?

Surely one of your psychedelic insights had to be how little agency we really have. We easily back-fill reasoning and stories to happenings that were bound to happen anyway. Our brains always want a story for cause and effect, but so much of what happens occurs outside of our control or awareness. It's like riding on a rollercoaster and proudly claiming "yea I decided to make it do a loop"

>what if there was already the underlying emotional desire to do something and having the experience was more about creating the justification to act?

That's definitely part of it, and I think kind of what OP was alluding to in that the experience allows you to dissolve many of the cognitive habits you've built up over your life, allowing you to experience an extremely honest perception of your own mind.

I'm not sure if you've tried it yourself, but I have yet to find any other way to achieve that level of clarity. I understand in theory that a lot of people find their way there by meditation, but I don't have the discipline or attention span to get there.

Psychedelics are a way of making that state of being accessible to those who may lack the ability or the motivation to get there through other means.

I'll also say that of those I know who partake in both, psychedelics still offer incredibly powerful and profound experiences even to those who practice meditation seriously for years or decades.

experience an extremely honest perception of your own mind.

Is it though? Does walking into the fun-house mirror room really produce an accurate reflection of who you are?

An altered perspective accompanied by an intense emotional experience doesn't necessarily indicate any real truth was uncovered.

You can have some quite profound experiences on 3-5 day water/electrolyte fasts as well. When the body is stripped of the energy necessary to maintain psychological defense mechanisms and cognitive habits, they peel away quite well there too. Highly recommended for the time-sensitive and impatient spiritual journeyman.

It seems you're badmouthing psychadelics, while advocating for achieving the same effects without the use of drugs. Why does it matter if someone has a similar experience with a different method?

Also, not everyone can just hop into the woods, alone, for days on end without food. Although that sounds like fun to me, I get horrible migraines if I don't eat regularly. What then? Is vomiting up my last bit of bile huddled in excruciating pain in the middle of the woods going to be some profound experience? Possibly, but psychadelics are an easier method for someone like me (and can be just as natural, in the case of mushrooms/ayahuasca/mescaline/etc).

If that were true, we would likely see a greater variety of discourse and testimonies from people who use hallucinogens.

On the contrary, they tend to sound surprisingly similar in terms of world-view to each other. Once you experience hallucinogens yourself, it becomes pretty clear why that might be.

The obvious conclusion is, of course, that hallucinogens unlock an objective, common reality. That's not what the depth and quality of the observations produced suggest, however.

This comment seems to contradict itself. Can you clarify your position?
I saw Ketamine remove depression immediately after a single dose in a loved one. Thought it was magic, because it was, a lifetime of depression just evaporated like nothing. But then came the psychosis. Nearly got stabbed in my sleep because a voice told them to do that.

So... let's just say I think there are other explanations, too.

A word of caution: Ketamine treatment is far from standardized. Most of the clinical studies I've read aren't using doses that produce profound psychedelic trips. The more professional clinics seem to have settled on dosing regimens that produce mild impairment, but not the full-blown dissociative trips described in many of these articles.

Meanwhile, there are a lot of questionable ketamine clinic providers popping up all over the country that give much higher doses. Some of them promote the psychedelic angle heavily in their marketing materials, as it has become a major revenue generator from patients who read articles like this one. While a single medium to high dose of ketamine may not produce marked negative effects, some of the high-dose, repeat-dosing regimens used by alternative therapy providers are in the range where I'd begin to be very concerned about lasting damage.

I would strongly caution anyone curious about ketamine treatment to stick to the lower-dose clinics and providers. Avoid anyone trying to sell you on "psychedelic therapy" or who has a reputation on the internet of providing excessively large doses. Also keep in mind that the antidepressant effects are short-lived, so plan to engage with traditional long-term treatment (therapy and/or antidepressants) to create a lasting strategy for yourself when the short-term effects of the ketamine wear off.

This would be far more helpful if you included the dose ranges you allude to, how many you think are required to cause damage, and threw in a few citations.
Does anyone know what the therapeutic ranges are at different clinics? I'm currently in IV infusion clinic where they start at 0.5 mg/kg, and increase by 0.1 per session. They are trying to target having a light psychedelic experience during the infusion, as they've found that gives the desired antidepressant effects later on, but not so much so as to be really far out, or to be frightening, totally out of body, or loss of consciousness at all.

I'm told the max therapeutic dose they administer is somewhere between 1-2mg/kg, and I believe anesthetic effects come on somewhere in between 2-4mg/kg? Anesthesia doses are administered much faster, so I'm sure that it's not a direct comparison.

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I've wondered: what are the chances that big pharma will attempt to suppress these medicines that compete with their patentable products, like seems to be the case with the majority of drugs caught up in "the war on drugs"?
My opinion? They’ll start marketing and selling it as well.

Just like a hundred years ago people believed putting cocaine into everything was great, we’ll do the same.

These drugs may work for some, but we don’t know the effects at scale. Who knows maybe in a 100 years we will think damn they were really doing that? Meanwhile we’ll all be hitting some new drug that someone found out about from some ancient civilization. Then we will find out why they are ancient.

There are many personal anecdotes about how one treatment was a game changer. I don't doubt them, but as the article says, it doesn't work for everyone. I am posting this as a counterweight to all the glowing reports.

My wife has some chronic health conditions (EDS and ME/CFS and depression); I'm sure they are at least partially related. While ramping off of one antidepressant in anticipation of trying something different, her depression came roaring back, so the doctor prescribed ketamine infusions. It didn't help at all.

Part of the problem was the clinic. One of the (correct) refrains about psychedelics is the importance of "set and setting". To the employees, this was just one of eight infusions they were going to do that day and it was all very routine, but for someone who has never experienced psychedelics, an attentive, caring, gentle environment would have helped a lot. Being a woman, it was tremendously anxious for her to go into a closed room with a male nurse she had never met before and give up consciousness and control for half an hour. Having a different nurse every time wasn't great for building trust. There were some other things too, but ultimately the main thing was she experienced no benefit.

if it's so dependent on the environment, then the drug just doesn't work in general, meaning it's not viable.

if doctors are unable to find ways to make a drug work and predict it, then it's pointless.

A 4 days vacation every month will have better results, and it's something most therapists and psychiatrist also say, that lifestyle matters.

If a drug cannot do better than lifestyle change, then the drug doesn't work.

I think you’re oversimplifying the human brain a bit here. The point of psychedelic therapy is to forcibly reset your cognition.

It is very much like turning your brain off and on again.

Therapy tries to change your perspective, but the therapist has to go through your conscious mind to reshape your subconscious.

Psychedelics go around the conscious part, directly flooding your mind with thoughts and forcing you to redo your perspective from the ground up. This is more uncontrolled than therapy, but sometimes the conscious barrier is too strong.

I’m no doctor though, just a person with some perspective

ah, interesting. So you have a medically qualified background to back up those claims?
I ask a lot of questions to my psychiatrist
Some cancer patients respond well to a given chemotherapy while others don't. Some people get vaccinated and gain protection while others get sick. Some people smoke marijuana and get euphoria while others get paranoid, and others are unaffected. I guess those drugs are nonviable and pointless.

To someone suffering from clinical depression or an anxiety disorder, your cavalier suggestion to just take a four day vacation is laughable.

If people who spend their lives wrestling with difficult issues and you think you can just chime in with an obvious solution, it is a good clue that perhaps you don't fully understand the issues.

I found a single practitioner that did muscle injections instead of an IV so no nurses or anesthesiologists are present. I'm in a cozy room with nice, low lighting, my music, and he leaves the room during the treatment. It feels like going into someone's home. He has a camera to monitor and has come in when I've gotten restless.

Being in a home-like setting isn't for everyone though, so when I guide people to Ketemine treatments I ask them if they are more comfortable in a hospital environment and If so, I recommend the IV clinics.

Is this the "science" rag that just decided to censor any research that paints any "groups" in a bad light[1]? Yeah, nature.com is compromised, we need sources with more integrity.

[1]https://archive.ph/xvuBk

Braxia (a canadian company) recently acquired KetaMD to expand their US footprint with their ketamine clinics. I believe something between shrooms and K is the future for depression.
Has anyone had bad experience taking this drug as a treatment for depression? I’m on my third SSRI and am quite desperate to find something to improve my “quality of mind”.
Plenty, see erowid.org. It’s vital to note that the therapy used in combination with these medicines appears to be a key component in all trials I’ve read into—simply taking mushrooms themselves, for example, doesn’t guarantee any positive outcome.

Anecdotally, many people report self-guided use of psychedelics to have been transformative for their own mental health, but it’s equally important to not blind yourself to the very real risks posed in doing so. I don’t say this to discourage you, but rather encourage you to really dive into the topic and learn as much factual information as you can, particularly before undertaking any treatment.

Ketamine therapy has made a significant improvement to my quality of life but it’s a shame it’s not FDA approved for depression / anxiety and thus not available on insurance. The cost is a barrier for people who could benefit from it.

I am hoping that MAPS ( https://www.maps.org ) will one day undertake clinical trials for ketamine, although this seems to not be on their radar right now.