Psychedelic drugs take on depression
nature.com
nature.com
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.
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 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.
Is it possible you're just convinced it feels like death?
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 :)
What do you experience during that time?
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.
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.
It's a hard problem.
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.
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.
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.
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.
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.
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?
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.
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?
> 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.
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.
"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.
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 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.
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.
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. :)
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.
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.
Congrats ok your success.
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 could also be the huge dose, the studies I've seen use lighter doses.
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.
"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.
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.
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.
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.
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...
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.
"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."
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.
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.
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.
And for that matter could there be an equivalent of psychedelics for various types of AIs?
Believe what tho?
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).
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.
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
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 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.
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
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.
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.
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.
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"
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.
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.
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).
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.
So... let's just say I think there are other explanations, too.
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.
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.
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.
For me, whatever I experienced was definitely something. https://www.adama-platform.com/2022/07/02/the-path-of-the-mo...
I'd argue that the term "psychedelic dissociative" accurately captures what ketamine can be.
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
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...
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.
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.
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.
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.