Ketamine for Depression: How It Works (2024) [video] | Hacker News Reader

Ketamine for Depression: How It Works (2024) [video]

yalemedicine.org

109 pointsViktorRay107 comments

When I was going through a rough time and SSRIs weren't helping, read all the research on what other solutions were out there. Psilocybin seems to be the most effective but is only legal in Oregon and price quotes were $3,500 for one session. Ketamine coupled with TMS (Transcranial Magnetic Stimulation) was the second. Since both are legal and my insurance covered them, opted to choose these. I will say that the various meta-analyses have some conflicting results.

TMS seemed to be pretty effective for me. It feels incredibly silly to have your brain zapped and is a big time commitment (30 days, 1X a day for 10 minutes) but I can't argue with the results.

Ketamine was something else. I did it intravenously, which seemed to be the best way to manage dosage but required going into a clinic. The biggest downside to the whole treatment is that you'll be very drowsy and sometimes down after, and all I wanted to do was go to bed. Taking the Uber home is not pleasant. The esketamine nasal sprays allow you to do it at home at lower dosages.

Once you get over the feeling of leaving your body, it can be quite nice. Overall, it led to unblocking some life time hold ups I had, and made me a better person. I had 5 sessions, 4 of them were overwhelmingly positive. The last was a dark couple hours where I hyperfocused on all my internal fears and failures. It also led to a lot of existential thoughts and questioning the fabric of reality which isn't all bad in small doses. I can see how excessive use could start to be counterproductive, it's good to stay connected to this reality. I don't understand how people use this as a party drug.

I would absolutely recommend it in a controlled setting for limited treatment, but would caution those with addictive personalities to be careful, not to see it as a silver bullet or a crutch, to make sure you're in a neutral mental space and that you're comfortable wherever you're doing it. In tandem, I listened to a fair amount of buddhist podcasts from Joseph Goldstein that helped build out the spiritual/learning side.

I'd like to see psylocibin treatment be more readily available at a lower price across the nation as an alternative.

> Psilocybin seems to be the most effective but is only legal in Oregon and price quotes were $3,500 for one session

That's a completely ridiculous price, about 300-500 times the "street" price of shrooms. In countries that I have familiarity with (not USA), shrooms have always been "technically illegal" drug which law enforcement never actually actively enforced, either formally through procedure (with doses below 100 grams considered fine-only territory), or informally, because the cops just don't take it seriously.

So to me it seems like you're choosing to follow the law even though it would not hurt anyone and you would not get into any trouble, just out of pure principle. That's actually quite impressive.

> That's a completely ridiculous price, about 300-500 times the "street" price of shrooms

I'm not going to argue that the exact rates are justified, but chances are the person you're replying to was referring to psilocybin assisted therapy in clinical settings. So someone would be signing up to pay for having at least one therapist oversee the process, if not physicians and other staff as well. Factor in their time, operating costs, insurance, etc. it shouldn't be a surprise that the legal option will cost considerably more than buying mushrooms in a paper bag :)

> having at least one therapist oversee the process, if not physicians and other staff as well

You know, when they talk about "set and setting", that's exactly what they DON'T have in mind.

Absolutely. I'd never want to do stuff like this in an unfamiliar clinical setting. I'd want to do it at home where I'm safe and have my friends

no, some medical professionals do have a clue.. and many recreational drug users are unaware of rare but very serious health situations.. If some "clinical therapists" with zero empathy and background make a clean white room, then sure, agree.. but here in California, there are more aware medical professionals then you might guess at first

Some people have a very different risk profile to others around getting in trouble with the law. People on immigrant visas, people who would lose security clearance or their job, etc.

Even if you’re not a goody goody by nature, the rational behavior for a green card holder at a nuclear lab is to be good as gold, at high cost.

In most US states you would certainly not want to get caught by law enforcement with 99 grams of mushrooms.

$3,500 seems like they are catering towards an upper class customer with some kind of premium session. I am certain there would be many in Oregon of all places willing to play shaman for much less. The price of shrooms is not the cost though. How much would you need to get paid to trip sit a stranger for 5-6 hours? I am doing nothing this afternoon and $200 an hour doesn't sound worth it if someone offered $1200 right now. That is a lot to deal with. $3,500 is therapy session with a licensed therapist who is going to be very specialized.

Ha, I appreciate that!. My original intent was indeed to follow the law, as well as to have a "clinical" setting. Now, if you look at the pictures of what you're getting for $3,500, it leaves a lot to be desired. It's not even really a premium experience so the cost ratio made no sense.

Having now been very frustrated, I did actually follow up and organized my own session through my network. I found a contact who worked in psychedelic research, and who had led sessions with others with psilocybin, had a couple friends join and rented an amazing AirBNB in the woods, and was ready for a night of exploration. The chocolate bars the provider gave us... didn't work. I was left with an upset stomach and nausea, without any of the benefits. Our provider was really into psytrance as well, which if you've never listened to is an acquired taste. They were understanding about it all, but suffice it to say I haven't attempted anything since.

Ketamine felt like instant addiction -- after one semi-excessive late night spree I was certain I couldn't continue messing with it.

I did TMS a few months ago, and I'm not convinced it really did anything. It's a little frustrating, because no medication seems to work at all for me now.

This is going to sound silly, and I'm not a medical pro, but maybe try fermenting some vegetables and fruit and eat a bit every day?

It's very easy. You cut up vegetables, put them in salt water and let them ferment for a few days to a week. Fermented carrots are really good. I also absolutely love greens fermented in rice water with a little sugar. There are many recipes online, also for lightly fermenting fruit.

Anyway there is pretty strong research on the connection between gut microflora and depression.

Probiotic fermented foods (especially high fiber fermented foods) are a wonder.

>There are many recipes online

There are, and when I search I am overwhelmed by blog spam that does not describe it as simply as you. For those curious like me, can you point to a good resource? Or explain to salt water and ferment part - leave in a sealed jar on the counter? Thanks in advance

Two books to check out:

Sandor Katz: Wild Fermentaion

The Noma Guide to Fermentation

but really it can be as simple as some saltwater and veg in a jar, careful to have then mostly covered with brine. Have to manage releasing pressure, burping it a few times a day is fine. Of course, you can get much fancier if you want, the possibilities are endless.

> Have to manage releasing pressure, burping it a few times a day is fine. Of course, you can get much fancier if you want, the possibilities are endless.

I would at least go slightly fancier: get a lid intended for fermentation that lets gasses out on its own. There are several good designs out there, and your local Target or similar store probably carries a little kit, intended for use with a mason jar, that contains a high quality fermentation lid and a nice stainless steel or glass mechanism to hold your veggies down, for a few dollars.

You will want a lid anyway, and the coated metal two-part lids used for canning jam will be destroyed pretty quickly by regular use for fermentation.

Yes, definitely better to have a lid with an airlock

Here's my quick and dirty recipe for many things including peppers, carrots and kale/collard/mustard greens:

- 3 tablespoons salt to 4 cups non chlorinated water. (for greens I boil a handful of rice in water, discard the rice, add a teaspoon or so of sugar and use that water w/ same salt ratio).

- Cut up the veggies and pack them in a jar. No thick pieces (like a whole carrot is too thick, a carrot stick like your mom may have given you as a child is fine).

- Put a weight on top of the veggies to keep them submerged. A ziplock bag partially filled with water works or they sell special weights and spring loaded jar tops for this.

- Don't seal the jar, gas will be produced. Cover it with a cloth if you like although usually the baggie weight is covered enough.

- Leave it room temperature for about a week. 4-5 days is usually enough but longer produces a more sour taste. I've gone 2 weeks plus no problem.

Put it in the fridge (drain some water if you like), keep it sealed (no air) and that is it. It's pretty simple at the end of the day. Some people weigh things and add 2% salt by weight of veggies/water and there are other methods, but what I listed is how I do it and it works. Key is to keep veggies submerged.

Absolutely anecdotal, but I see a very strong correlated connection between what I eat (and the effect it has on my digestion) and my mood.

Having a regular quantity of fermented foods as part of my diet has a noticeable effect.

Fermented foods are worth trying out, but your milage might vary.

Same thing.

I notice a very strong correlation. Fermented high fiber "living" food and avoiding all preservatives really improves my outlook on life but yep, your mileage may vary.

Easy and cheap enough to try though.

I'm kind of terrified of giving myself botulism (or some other illness), though I do live in NYC, so I don't think it would be too hard to buy fermented pickles if I wanted them...

Chance of botulism is very low because of the salt (and acidity resulting from the fermentation), but yes, there should be live fermented veggies for purchase in NYC.

There are only about 200 cases per year of botulism in the US and most of it is infants (about 70% of the ~200 cases).

When fermenting foods, use water from good source (e.g. bottled water), you must boil water with salt (,sugar, spices ) first, let it cool, and then add it to cleaned, well washed vegetables or fruit. Use clean glass container. Fermenting procedure varies for different veggies / fruit. Maybe first try to buy readily available fermented foods to see if it works for you.

If you find this appealing, make sure to do it with a medical professional. If you still want to try it by yourself, read Felix Hill's suicide note first.

I had to do some digging, but I did find this (who knows if it's legitimate or not)

https://docs.google.com/document/d/1-jBoSEVlryiX1IaSzV4vKuih...

that was something:/

I'm sure it's legitimate. People posted it a few times to HN but it didn't get much discussion. I'm ambivalent about that. It's a fascinating, heartbreaking and gutwrenching document. But given the research on suicide (Werther Effect, etc.) it's probably best not to publicly feature it.

A friend of a friend took MDMA + Ketamine every weekend. K-hole doses. Developed monday-blues which turned into a sort of servere depression as he pressed on. It took a year of abstinence before he felt “normal” again.

Drugs that affect the serotonine system can do this. Burnout from (repeated) overload sort of situation IIUC.

I’m no doctor, but I suspect it’s extra dangerous if you’re already suffering depression.

I couldn’t read the whole note. What a tragedy :'(

Taking MDMA every weekend is like drinking a few glasses of hard liquor every day. Meaning, only completely delusional and uninformed people would think it won't destroy your life.

Of course, many people still do it. But they are fully aware of what road they're taking.

Trust me, the drugs won't do this..

I took MDMA every weekend and it seriously fucked me up. I was depressed for easily a year afterwards.

I suspect even 15 years on I haven’t fully regained my ability to experience joy, but this is impossible to know for sure. I can’t run the counter factual and there are many other variables at play. I was a teenager when I got too deep into MDMA.

i generally consider myself an enemy of psychedelic advocates, because I think they want to make it effectively socially mandatory to do these drugs, which is really bad.

("sure, it's your choice what you put in your body, but a really enlightened person wouldn't be so frightened and closed-minded that they don't want to see what psychedelics can show them...")

of course ketamine for depression has this giant downside risk of adverse effects and psychosis, and we should talk about it more, not just sell it as a safe miracle drug.

however... safe, neutral, bland, boring well-tolerated SSRIs, also have a massive downside risk, in that they can trigger a manic episode, which in severe cases also involves psychosis.

so i find myself in the position of being glad there are different depression treatments for different people, including psychedelics and dissociatives, and hopefully we can find a way to make sure people get sorted to the treatments where they are least exposed to the tail risk side effects.

> i generally consider myself an enemy of psychedelic advocates, because I think they want to make it effectively socially mandatory to do these drugs, which is really bad. > ("sure, it's your choice what you put in your body, but a really enlightened person wouldn't be so frightened and closed-minded that they don't want to see what psychedelics can show them...")

I'm sorry WHAT? I've been to many open airs and other events where MOST of the people around have been under the effect of psychedelic and in other drug-friendly places, and I have never hear manipulative shit like that ever. On the contrary, if I heard people talk about this drugs it was always "it worked for me but might be a bad experience for you", "be safe, don't take it if you're not sure" and "you can always have a great time here completely sober".

i think that "we all want to get high on drugs" situations, like festivals, are actually a lot better. it's about personal choice.

when i talk about psychedelic advocates, i mean the people who think that widespread use of psychedelic drugs would massively improve mental health, make people more productive and happier, etc.

Confusing a minority of fringe members with the reasonable group of "psychedelic advocates" as a whole just delegitimizes the whole movement. There will always be some who take reasonable ideas to absurd extremes.

As a point of comparison: "social drinking advocates" vs. those who like to get blackout drunk every night.

The idea that everyone should be pressured into taking psychedelics is an absurd extreme. Psychedelics can be a powerful catalyst to growing as a person, but they're not a magic potion that makes you grow emotionally, spiritually, and intellectually.

They're likely going to bring your unprocessed ideas and personal issues to the forefront which can be very productive if you want to face them. But those who carry around demons that they've repressed and absolutely don't want to face would probably have a terrible time on psychedelics.

yes agree, and also underlying medical conditions, brain chemistry, long lists of who knows what..

SSRIs are by no means safe or well-tolerated. They have all sorts of severe, life-altering, mostly permanent side effects: https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...

There are countless heartbreaking stories of people who were prescribed these drugs not knowing what they were subscribing to. In many cases, the effects of those drugs are worse than the symptoms they are supposed to alleviate. With "I Don't Wanna Be Me" there's even a song by Type O Negative (from Peter Steele's own experience with Prozac) about the devastating effects SSRIs can have on a person's life.

These drugs are handed out like candy while the physicians prescribing them often point-blank deny any side effects or even attribute those to the illness they are meant to treat.

Psychedelics, on the other hand, have actually been proven to be effective for many syndromes SSRIs are commonly used for and by comparison are very safe when used with proper preparation, medical surveillance, and in the right setting.

The only reason psychedelics are still widely shunned is a Puritan attitude to human well-being: You're not supposed to feel better than the common neutral base level. Any drugs achieving that (alongside with other, more specific and intended medical effects) are maligned and ostracized.

You're saying this as if psychedelics cannot 'have all sorts of severe, life-altering, mostly permanent side effects'.

Yes, they certainly can.

However, the prevalence of side effects with psychedelics is in the single-digit range, whereas with SSRIs you're almost certain to be experiencing some sort of - often severe - side effects for the rest of your life.

this is more or less exactly what i was trying to say. for most people SSRIs are safe, they experience manageable side effects and little health risk. psychedelics and dissociatives seem like they must be really drastic and risky. but actually SSRIs are pretty risky too, there are all these terrible low-probability outcomes.

so it's good we have all options, but ideally we'd have a better way of judging who is safest with which treatment.

With SSRIs you have a one in three chance for any number of the following side effects; many of them permanent, even after discontinuing medication (if you actually manage to do so, since SSRI come with severe withdrawal symptoms):

- sexual dysfunction

- loss of emotion and creativity

- drowsiness

- insomnia (including real fun stuff like night terrors)

- fatigue

- nausea

- tremors

I'd hardly call that safe or manageable.

With even the most potent psychedelics such as LSD, on the other hand, there's merely a one in thousand chance for severe side effects.

I'd go as far as prohibiting the prescription of SSRIs for all but the most severe cases (such as a severe depression where the patient is actually suicidal). For everything else these drugs are commonly used for, e.g., mild depression, OCD, or IBS, there are other - in many cases better - options with far less devastating (if any) adverse effects.

> many of them permanent

Almost none of these would be permanent, and you certainly don't have a 1 in 3 chance of them being permanent. Where did you get that number?

> With even the most potent psychedelics such as LSD, on the other hand, there's merely a one in thousand chance for severe side effects.

This is fucking nuts. We're in a thread about how taking too much can clearly cause weeks of psychosis, and how easy it is to do that. There's nothing wrong with warning about the risks of SSRIs, but to claim you have a 1 in 3 chance of having permanent nausea while, in the same breath, claiming psychedelics are 100x safer, is beyond irresponsible.

> Almost none of these would be permanent

Sexual dysfunction caused by SSRIs in many cases persists for the rest of the patient's life.

> and you certainly don't have a 1 in 3 chance of them being permanent. Where did you get that number?

Those are actual numbers from scientific studies: https://pmc.ncbi.nlm.nih.gov/articles/PMC2719451/

> in the same breath, claiming psychedelics are 100x safer, is beyond irresponsible.

Stating mere facts isn't irresponsible and those are the facts:

When taking SSRIs you have a one in three chance to permanently and severely change your life for the worse.

When taking LSD you have a 1 in 1,000 chance of suffering a psychotic break.

What's irresponsible - and unethical - is twisting and misrepresenting these facts - to the extent of outright lying about the purported innocuousness of SSRI, as is wont in the psychiatric community.

> Sexual dysfunction caused by SSRIs in many cases persists for the rest of the patient's life

You said most symptoms were permanent, don't back down now. Sexual Dysfunction is a pretty broad term, how would you even link it to being affected by an SSRI?

> Those are actual numbers from scientific studies: https://pmc.ncbi.nlm.nih.gov/articles/PMC2719451/

Literally says NOTHING about being permanent, this is about symptoms experienced while on SSRIs. Did you read your own source?

> When taking LSD you have a 1 in 1,000 chance of suffering a psychotic break

Where are you getting this number? It lacks so much context. What dosage gives you a 1/1000 chances of a psychotic break? Are you aware people are just taking whatever amount of Ketamine they feel like?

You seem to be arguing that Ketamine is somehow 300+ times safer than SSRIs as if you can compare the two 1:1. That is now how medication works.

> You said most symptoms were permanent, don't back down now. Sexual Dysfunction is a pretty broad term, how would you even link it to being affected by an SSRI?

There you go: https://www.tga.gov.au/news/safety-updates/updated-warnings-...

https://annals-general-psychiatry.biomedcentral.com/articles...

https://pmc.ncbi.nlm.nih.gov/articles/PMC8061302/

https://rxisk.org/post-ssri-sexual-dysfunction-pssd/

> Where are you getting this number?

There you go (for instance): "Cohen suggests a low rate of prolonged psychotic reactions in LSD users (1.8 per 1000) [19]"

https://www.nature.com/articles/s41380-024-02800-5#Sec35

> Are you aware people are just taking whatever amount of Ketamine they feel like?

Ketamine is a totally different type of drug. Deriving anything about psychedelics from the amount of Ketamine people take is entirely nonsensical.

Buddy, you're doing something called Source Bombing. I've read through 3 of these links and they directly contradict what you argued. I'm not going to waste my free time reading through the rest if you aren't going to bother reading at least one of them yourself.

With regards to Ketamine.

> There you go (for instance): "Cohen suggests a low rate of prolonged psychotic reactions in LSD users (1.8 per 1000) [19]"

That is a description of one of the many studies included in this meta-analysis. This is from the same article.

> Taken together, the effective risk of psychedelic-induced psychosis or worsening of pre-existing psychotic symptoms in schizophrenia -as well as in the early stages of the psychosis spectrum- remains incompletely understood

Also

> Overall quality of studies was low and only few studies (n = 9) could be included in the meta-analysis, hence the presented findings should be interpreted with caution.

> Buddy, you're doing something called Source Bombing.

You're doing something called "Moving the goalposts" by first asking for sources and then complaining because those sources don't support the very narrow construal you seem to be applying to my argument.

Those sources are scientific studies, which by the very nature of the scientific processes of course are open-ended.

> The only reason psychedelics are still widely shunned is ..

no, more complicated than that..

How do you find the right "medical professional"? I spoke to a psychiatric doctor about this recently, and he literally laughed in my face and said its all bogus.

Find providers who don’t seem too eager to give you as many treatments as possible. I’m getting ketamine infusions for pain through a pain specialist but he also treats depressed patients. A pain specialist may be able to help you as much as someone focused on psychiatry as they still know the drug well and often know how to treat depression

I underwent this treatment (Esketamine) a few years ago. I found the acute effects (the "trip") right after taking it quite unpleasant. But as the treatment went on, my mental state improved dramatically.

I agree with you. I dont enjoy the trip. I appreciate that I have ventured into the substrate of our reality but it is not something I desire to experience often.

Trusting the process was great and worked well after 4 IV treatments. There is absolutely something to the plasticity coming from a treatment and being able to get out of a rut.

I knew someone with a horrible addiction/dependence on ketamine and justified it by always talking about how it cured depression like it was a vitamin.

I know people who had horrible addictions to ketamine and adderall (who also had depression and ADHD) who managed to recover from those addictions and years later use them appropriately and in reasonable therapeutic doses on a normal therapeutic schedule for treatment of same.

Anecdotes are not data and abuse potential isn’t really relevant to their clinical utility. Do we need to have a comment about junkies whenever someone mentions that they received fentanyl for a major surgery?

Maybe there’s a danger in 100% of the time discussing this drug’s benefits with no discussion of the risks.

Aren't there always risks with any treatment though? I'm not sure why psychedelics need to be specially called out.

Its a schedule 1 drug for a reason. Many people have used psychedelics and have had permentant changes to their personality.

I think the hippie stereotype is indicative to how damaging psychedelics have on the mind. You look at these people they are happy but something is clearly wrong.

Ketamine is schedule 3. It is regularly prescribed.

Schedule 1 substances basically can’t be prescribed without very special circumstances and permission. (Marijuana is in this class in the USA, strangely enough, along with MDMA.)

Even methamphetamine and cocaine aren’t Schedule 1.

Ketamine is actually a Schedule 3 drug. Schedule 3 drugs have strict regulations but are not on the same level as Schedule 1 drugs. Schedule 1 is the most severe in terms of regulation.

Adderall is Schedule 2.

And marijuana is still schedule 1, surprisingly

i envy those people so very very much. i don't care how wrong it might seem to appear happy, sounds awesome.

They don’t and aren’t.

Were they the director of the Yale Depression Research Center?

and are they hiring?

perks include padded floors and walls in the office (yes they are pushing RTO too), and free adult diapers for when your bladder inevitably fails.

I think I'm out of the loop

I came here to say this. I know someone who had one dose of ketamine for PTSD after a terrible fire. Worked like magic, but being a regular ketamine user is mind altering in a way that isn't good. These days there are quite a few people who are getting ketamine through a doctor on a weekly basis. John C Lilly was a regular ketamine user and his crazy-seeming thinking and writing later in life is an example to avoid and consider.

I've never tried Ketamine but I have tried shrooms, LSD, and DMT. I have never found the effects be to lasting though, regardless of dose. After one or two days I'm always back to baseline.

I've wondered if a similar thing can be how much people are affected by things like Virtual Reality. After the initial five minute first try I never could get very immersed in VR (more than a regular 2D game). I could never feel any fear of height or anything for instance, it didn't grab me.

I've wondered a while if that is a correlation that spans other people. If the people who get blown away by VR would also have large lasting effects of psychedelics, and vice versa.

You should try DXM for an interesting "baby ketamine" experience. Just get the pure Robotussin gelcaps, I wouldn't do less than 2 bottles and actually thats generally a good place to start for a decent 2nd plateau trip without getting into the more crazy upper echelon dissociative effects and experience

Mix with sprite, pour it over some ice, and add a couple of your favorite jolly ranchers. That's the start of a good weekend.

You're thinking of codeine (purple drank). DXM is different

Oh true sorry I hope that didn't undermine your recommendation of recreational megadoses of OTC medication.

I genuinely can't tell if there's some spice in your comment here haha

2 bottles of gelcaps? that seems ill-advised

Its seems crazy right? I mean I guess you can start with one but its best used a bit stronger than that and for a purpose like resetting when you'vr been in a bit of a rut.

Be sure to keep something around to catch any vomit, personally I've almost never not vomited once when it starts to kick in. Have music and media to consume

ehh it wont(ymmv?) kill ya but it sure will rock your world that is certain. truly ill-advised would be to take 60-100mg of benedryl with them, that will shatter reality itself

That would likely ruin it. Deliriants are hell in pills

That's probably too much to be casually recommending on the internet, but this is a real therapy now: https://en.wikipedia.org/wiki/Dextromethorphan/bupropion

As a teen, DXM was a frequent escape. I always liked the 'afterglow', which seemed to lift my mood for a week or afterwards. When I saw the studies come out about ketamine years later, it all made sense.

However, I introduced it to my peer group back then and in college, and there were some that seemed to be slow metabolizers of DXM. Ketamine is shorter in duration and lacks (minimizes) many of the worst aspects of DXM like body nausea/body load.

It has a good resetting effect for sure

Have you been seeing a therapist about your "baseline" state? What do they say about prescriptions for you?

Maybe I should have clarified, I don't have any diagnoses and don't consider myself depressed in the layman usage of the word. The baseline I'm talking about is whatever you call the regular Joe state.

Since I anticipate some people might go "so what lasting effects did you expect?" I guess I'm thinking more about all the amazing stories you read everywhere about psychedelics. Even in movies and media it's usually presented as something that transforms you in one way or another. I've never quite found that to exist.

Have done both clinical Ketamine and Psilocybin therapy.

Ketamine was very interesting. Proper completely dissociative "K-hole" experience. I feel like it helped with Anxiety, but I can't pinpoint "why" from an introspective perspective.

Psilocybin on the other hand. Was a hero dose, and I'm a changed person afterwards.

Could feel the "layers" of my identity being stripped off, almost regression to a more child-like state. Very interesting experience. Had strong synesthesia: sounds would produce colors, colors would produce tastes, fun experience.

Near the peak of the experience I had these strong recurring auditory hallucination of my mothers says all these random words from my youth, these were accompanied by strong feeling of anxiety. After a lot of post-experience integration and reflection I realized that my mothers anxiety about the world was effectively "programmed" into my brain during my upbringing. e.g. Generationally transmitted anxiety.

Therapy always talks about childhood trauma, etc, but actually experiencing it was another level, and really helped me on my journey to being a less anxious person.

Before the Psilocybin experience, I suffered from existential depression: what's the point of living if the sun is going to explode in ~x billion years. Towards the peak of the experience everything was super chaotic, I felt like I was being transported into different realities (e.g. realities with different laws of physics, or different space time geometries). This was hugely anxiety inducing and would otherwise be called a "bad trip." I felt "lost" in this sea of all different realities.

As I was coming down from the peak and started to reintegrate, I had a strong distinct sense of "coming back" to our current reality. It felt like finding a safe tropical island in a sea of chaos: e.g. our currently reality is a safe space and point of stability in a sea of chaos and uninviting realities.

I was truly, deeply, grateful to be able to return to the familiar and it made me really really deeply appreciate myself and the blessing that our reality is to us.

Post the experience I also acquired the ability to observe my emotions from a third person perspective. e.g. rather than feeling "angry" I could tag the emotion "angry" and react accordingly, almost as if I gained ring 0 access to my brain when I previously only have ring 1 access.

All-in-all probably the most profound and healing experience of my life.

  1. Deeply felt and understood my anxiety was generationally passed on from my mother's anxiety,
  2. Eliminated my existential depression, giving me a deep appreciation for the beauty of our reality,
  3. Gave me ring 0 access to my emotions making me a much more stable, calm person.

Beautiful description of your experiences. The psilocybin experience sounds like it was guided by a professional? was it and if so, how did you find that person?

These skills can come from studying ACT though.

Have not tried DMT but have the three others. K is... weird. It's totally different from shrooms and LSD. With those, you can kind of steer your trip. With K, it steers you a bit.

Someone I'm very close to was also addicted, using it for emotional suppression. They're luckily off of it and in therapy but it can get nasty. Fair warning.

> tried Ketamine but I have tried shrooms, LSD, and DMT... After one or two days I'm always back to baseline

You did it wrong. You need to micro-dose psilocybe shrooms over the course of ~30 days.

There’s not only one way that works for all. Glad microdosing works for you

Also, try Amanita Muscaria microdosing that has legal and different active alkaloid (muscimol, not psilocybin), look for the new "Microdosing with Amanita Muscaria" book.

I think for some forms of treatment-resistant depression, no "rapid" treatment can work because the depression has caused physical atrophy, mostly in the hippocampus, over many years. Various studies have shown this atrophy, both in MRI and cadaver studies. So the tissue loss might take years to recover unless we discover some new neurogenic compound (RIP NSI-189). Ketamine, SAINT TMS might still work for other depression though.

The brain doesn’t necessarily need the same exact hardware to do the same function, but in adults if it’s lost they will probably not regain the function without intervention. Neuroplasticity-inducing substances may very well enable the brain to create new connections and rebuild functionality even if the physical neuronal mass does not recover.

This paper suggests as much: “Conversely, chemogenetic activation of ABINs without any change in neuron numbers mimics both the cellular and the behavioral effects of ketamine, indicating that increased activity of ABINs is sufficient for rapid antidepressant effects.”

https://www.nature.com/articles/s41467-022-30386-5

I think it probably correlates with low openness. If you are low in openness, I could see psychedelics having long lasting effects on a person's personality. I have never found the effects to be lasting at all either but my openness is already at 11. If anything, I probably need less.

I wouldn't do Ketamine because I know for a certain type of person, they instantly fall in love with "spiritual heroin". I know almost for certain I am that type of person.

I did this a few times and found it miraculous. The doses were sub k-hole, it just made the world seem cottony and soft. The effect on my psyche was lasting and positive.

A friend who struggles with depression found it useful for a while, but its effects didn't continue after a number of doses.

I would like to try it someday, but I had some really bad trips on dissociative drugs in the past, and I'm worried ketamine will invoke flashbacks.

The low dose lozenges very rarely lead to negative experiences.

It's a blanket fix for all bad trips, but it really does work: Do some MDMA first (just enough to feel the effects, don't go all out). It will put you in a positive state of mind and allow you to experience all the crazy mind-alterations of psychedelics and/or dissociatives without being scared to shit.

MDMA and ketamie synergize nontrivially and strongly. I highly recommend against taking MDMA to ease off the ketamie. If you want to combine them for the resulting experience then power to you, but taking MDMA to make ketamie "simpler" is a very bad idea.

I've taken care of multiple ketamie and MDMA overdoses (in the sense of unexpected effects, not just the amount) and they did not have a good time. (I also know plenty of people that had a blast on the combo, my point is: don't recommend drugs or combos easily.)

Citation needed. Psychonautwiki (very much the most reliable source on these matters) mentions nothing about negative effects of combining MDMA and ketamine: https://psychonautwiki.org/wiki/Ketamine Even calling it 'overdoses' is nonsensical. It has a very clear definition and "did not like the experience" is not it.

The main thing to remember is that combining drugs means taking less of each than when you take them by themselves. As always in all drug use: Dosage, dosage, dosage.

> Even calling it 'overdoses' is nonsensical. It has a very clear definition and "did not like the experience" is not it.

Overdose can mean multiple things, the one you’re referring to is the medicinal overdose with danger to health, and what most people are (exclusively) familiar with. An overdose in the psychological sense is anything that exceeds the desired effect. Someone who wanted to party and quietly sits on a log, occasionally vomiting, unable to stand up, afraid to die, is definitely an overdose in the psychological sense, even without medicinal danger (regular breathing, responding to stimuli, effects stable). The transition from »oops this is too much, oh well« to an overdose is a spectrum.

Psychonautwiki is a very good source, but neither it nor scientific literature has a good overview over individual cases. I know I’m at the base of the pyramid of evidence talking about my work on festivals doing psycare, so even if you doubt the stories me, my colleagues and any techno scene paramedic could tell you, the most important point stands: do not recommend drugs or even combinations to people without medical background. (For that, I can give you papers on e.g. people metabolizing MDMA via the MDA route exclusively for dramatically altered effects.)

Using drugs to treat depression is usually a bad idea unless you have a medical reason.

Drugs for depression get addictive as your body gets instant reward by the pill.

It's sad to see many 1st world countries becoming too dependent of them, instead of achieving happiness and personal goals

For a person (my daughter) who has tried everything under sun (except ECT and psilocybin)for depression and OCD and nothing ever seemed to help, what is the latest on treatment horizon?

Psychedelics + cognitive therapy has a lot of promise. There's a lot of types of psychedelics and therapies to investigate. MDMA with a group of close friends/family in a safe and loving environment is probably the best you could do on your own.

Personally, cold exposure + lots of coffee + engaging work w/ others has been more effective than anything I've found in the healthcare system. Commit to daily work/social obligations, then drink enough coffee until you can will yourself to go everyday. Once it starts to become a habit is when my depression (slowly) will start to lift. If I stop for too long I fall back into the hole.

Have you considered any alternative explanations/diagnosis? Rates of misdiagnosis for psychiatric disorders are significant (even more so in women, anecdotally) and it could be the reason why the treatments aren't working. Depression can manifest as a consequence of untreated ADHD, for example.

Self-diagnosis is generally frowned upon but I think everyone owes it to themselves to at least try to find explanations that they can discuss with professionals.

we tried many avenues here as well 1.vitamin deficiency (she is vitamin D deficient, but it seems common in my race - asian 2. iron deficiency 3. gave magnesium for a while 4. someone diagnosed her for adhd and others disagreed 5. tested for autism. 6. tested for thyroid 7. took some T3/T4

i am thinking we will self pay an MRI.

a partner has been on monthly ketamine therapy for treatment resistant anxiety and depression and it has help them out tremendously. They are still on SSRIs and in regular therapy, but have become far more happy and functional then they were for years before starting ketamine therapy

In all this discussion, I’d like to add a piece of interesting recent scientific discovery regarding the mechanism of action that might well explain the increase in neuroplasticity from psychedelics like psylocibin and LSD and offers hope that we will find drugs that have the positive neuroplasticy increasing effect without causing hallucinations [1].

Below the abstract of the mentioned research (BDNF is Brain Derived Neurotrophic Factor, a kind of growth hormone for the brain), note the 1000 fold(!) higher affinity of the psychedelics:

Psychedelics produce fast and persistent antidepressant effects and induce neuroplasticity resembling the effects of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fluoxetine [= SSRI] and ketamine, act by binding to TrkB, the receptor for BDNF. Here we show that lysergic acid diethylamide (LSD) and psilocin directly bind to TrkB with affinities 1,000-fold higher than those for other antidepressants, and that psychedelics and antidepressants bind to distinct but partially overlapping sites within the transmembrane domain of TrkB dimers. The effects of psychedelics on neurotrophic signaling, plasticity and antidepressant-like behavior in mice depend on TrkB binding and promotion of endogenous BDNF signaling but are independent of serotonin 2A receptor (5-HT2A) activation, whereas LSD-induced head twitching is dependent on 5-HT2A and independent of TrkB binding. Our data confirm TrkB as a common primary target for antidepressants and suggest that high-affinity TrkB positive allosteric modulators lacking 5-HT2A activity may retain the antidepressant potential of psychedelics without hallucinogenic effects.

[1] https://www.nature.com/articles/s41593-023-01316-5

Thread is 6h old and no mention of Elon Musk??

I don't recomend doing it at an afterparty spilling half the bag on the floor and spending most of the night worrying if your "benefactor" will kill you.

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