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Alterations in glutamate and the experience of ego dissolution with psilocybin
- presiozo 6y agoI'm kind of hoping this puts the nail in the coffin with researchers trying to separate the psychedelic effects from the anti-depressant effects so that they can turn it into some kinda pill people have to take every day.
- varjag 6y agoWhy are you hoping for that? Is non-hallucinogenic anti-depressant a bad thing in some way?
- SuoDuanDao 6y agoThe profit motive would clearly prioritize finding an expensive medication that must be taken regularly and indefinitely. Psychedelic research up to now is pointing to small numbers of uses having lasting positive effects. There is a fear that research driven by a profit motive will try to not just not investigate this further but actively gloss over this potential medicine.
- PragmaticPulp 6y ago> The profit motive would clearly prioritize finding an expensive medication that must be taken regularly and indefinitely. The idea that pharmaceutical companies are deliberately avoiding one-time treatments is a myth. If you assume profit is the ultimate motive, there's nothing stopping a pharmaceutical company from charging $10,000 for a long-lasting depression treatment. It's not like pharmaceutical companies are going to stumble upon a perfect treatment and then decline to patent it. Also, patents don't last forever. Common SSRI anti-depressants are available for $4-5/month.
- new2628 6y agoEveryone I've known who took such medication have altered their personalities in noticeable (unpleasant) ways. It may be worth it for the person in question, but one should be aware of it.
- werber 6y agoMaybe I’m too self involved, but I’ve never noticed someone microdosing psychedelics til they have told me
- PragmaticPulp 6y agoSelection bias. Plenty of people take SSRIs with positive experience. They're just not advertising it to the world. People who have bad experiences are much, much more likely to communicate this to other people.
- new2628 6y agoThis may be true, but even in the cases that I mention the experience of those taking the medication was positive, it is just other people who noticed the shift in personality.
- Etheryte 6y agoUnless I'm misunderstanding you completely, what's wrong with that idea? Currently, anti-depressants are a very hit and miss science, leaving many people further frustrated by therapy that was supposed to help them instead. Anything that can move towards better medicine in the future should be a good thing, no?
- themgt 6y agoWhat's wrong is psychedelics already work as-is, but due to stigma around "fun" alterations of consciousness possibly being beneficial (along with desire for a patentable compound that can get through FDA regs), most of the focus has been on how we can go about removing the wetness from water while preserving water's essential useful properties. Regardless of how many years go by and self-reporting along with scientific evidence accumulates that water's wetness is mostly the entire point, and all while people are being thrown in jail for water possession.
- varjag 6y agoIt's not "stigma". People treated from clinical depression hope to be able to function in their normal day lives at work and at home, not just be on a never-ending psychedelic trip.
- themgt 6y agoResearch has focused on long-term (months to years/permanent) benefits from just one or a small handful of psychedelic experiences. It would even be difficult to find marginally responsible "psychonauts" who would recommend attempting a "never-ending psychedelic trip", which regardless wouldn't be physically plausible due to how rapidly the short-term tolerance increases. In short, perhaps do more research on this topic because you're arguing against a position no one has taken.
- erispoe 6y agoThis is not how psychedelics for treatment resistant depression is tested. The most common treatment protocol is a single psychedelics session assisted by 2 therapists (preceded by a few therapy sessions and some follow-ups). Overwhelmingly the evidence point to very significant effects lasting months after the session. This is far from "a never-ending psychedelic trip". If you follow the evidence for the most researched treatment protocol, this would involve a session every year or half-year.
- deathgrips 6y agoIf you take an anti-depressant pill everyday and it solves your problem, why is that bad? Are you hostile to medication in general?
- dTal 6y agoDaily medication, which must be taken without fail in order to have a normal life, is a liability. It can be lost, stolen, or missed. It must be obtained on a regular basis, and carried around on trips. It can be expensive. It can stop working, from tolerance. It can have unpleasant side effects. A one-time, permanent cure is clearly superior. And your closing sentence was unnecessarily combative.
- deathgrips 6y ago>Daily medication, which must be taken without fail in order to have a normal life, is a liability. It can be lost, stolen, or missed. It must be obtained on a regular basis, and carried around on trips. I doubt these are a real problem for people who have a modicum of conscientiousness. >A one-time, permanent cure is clearly superior If you think that big bad pharma companies are keeping people from taking one-time cures for depression, by all means come up with a one-time cure on your own. How do you think one pill can create a permanent structural change in the brain that makes the just-so changes necessary to cure depression forever?
- kranner 6y ago> I doubt these are a real problem for people who have a modicum of conscientiousness. What does conscientiousness have to do with it? You might need to travel or transit through a country which prohibits carrying them. Now you have to cancel the trip or go without the medicine. > by all means come up with a one-time cure on your own This is not helpful. People have the right to ask questions without being asked to devote a lifetime to develop some arbitrary authority (which would then in any case bias them to look for positive results).
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- ketamine__ 6y agoI take a prescribed ketamine lozenge every day. I don't experience any psychedelic effects and I'm fine with that.
- werber 6y agoI’m very curious about how much you take daily and the effects. I’ve read about the super high dosage therapy, and that made a lot of sense to me. Are you just ever so slightly dissociated at all times?
- garbageket 6y agoI dunno about them but, but I get by on 20mg taken weekly. If I miss a dose, it's usually ok. If I miss two, suicidal ideation is my dominant thought pattern. As for effects, I'm a little dizzy for about 30 minutes and I prefer to spend this time napping or in a hot bath.
- GordonS 6y agoNot the OP, but I'm prescribed ketamine for chronic nerve pain. Prescription is for 25mg orally 4-6 times a day, but I find 15mg as effective as 25mg, but with no side effects at all. At 25mg I do feel slightly dizzy for an hour or so. Ketamine has a small, but noticeable effect on the pain - but has had a huge effect on my ability to deal with the pain.
- PragmaticPulp 6y ago> I take a prescribed ketamine lozenge every day. I don't experience any psychedelic effects and I'm fine with that. Many of the researchers and clinics are gravitating toward ketamine regimens that avoid hallucinations entirely, like your current treatment regimen. Ketamine has some inherent anti-depressant effects that don't depend on hallucinating. Unfortunately, many psychedelic proponents have tried to push the narrative in the opposite direction to emphasize the trip. It's unrealistic to expect depressed people to routinely go on psychedelic trips to keep their depression at bay. It's also unrealistic to expect people to trip frequently and not have part of the population start to accumulate weird, irrational ideas from their trips. A medicine that captures the anti-depressant effects without causing a psychedelic trip or really any cognitive distortions at all would be far better than expecting people to trip regularly. I don't understand the aversion to pharmaceutical companies pushing the research in this direction.
- skohan 6y ago> they can turn it into some kinda pill people have to take every day. I feel like this model is a perfect example of how the incentive structure of the pharmaceutical industry runs counter to pursuit of the best outcomes. From what I understand anecdotally, psilocybin taken in moderate doses can have beneficial effects on depression and anxiety which last for weeks or months after the dose. This would be an amazing result by all accounts. A treatment which can be done every 6 weeks and still be effective would mitigate a lot of risks, like possible dependency and any toxicity which might be related to prolonged exposure. It seems to me that gets much closer to what we would refer to as a cure than a treatment. But it seems like most of the clinical research is going into micro-dosing: i.e. how to make this something you would take every day to alleviate symptoms. I just don't understand the benefit of this approach other than the fact that it might be a better business model.
- kortex 6y agoModerate does trips aren't for everyone. The HN crew is full of novelty-seeking, curious, open-minded explorers, already drawn to this sort of experience. Your average, vanilla soccer mom who is largely okay with life but struggles with panic attacks because her brain isn't great at damping the amygdala-cortical loop, may not necessarily be ready/interested in a trip through psychedelic space.
- pharke 6y agoI think the answer to that is to slowly increase the dose over a number of sessions. Starting out with microdosing to get used to the body feeling, then getting used to visual disturbances and the altered mental state, and then graduating to a level that can unlock new perspectives on self and the world. This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.
- vajrabum 6y agoKetamine is being used to good effect these days in major depression. I wonder if they ramp up the doses like that when using it?
- el_nahual 6y agoAll medications have two kinds of effects: therapeutic effects, and any number of side effects. The "problem" with compounds that can alter our state of mind is that, by definition, they can be fun/weird/recreational if taken in meaningful doses. And this, of course, scares the government and the pharmaceutical industry. They are not allowed to sell things which can be used for disorder (read: "recreation"). So the pharma industry must select against these compounds. What we're left with is medication where the active, psychoactive effect is so small that it's of the same magnitude as the side effects. This prevents "abuse". Hence why antidepressants are basically constipation/headache/libido killing pills that kinda maybe change your frame of mind.
- luckydata 6y agothat's not how it works. The anti-depressant, anti-addiction effect can only be achieved through the psychedelic effect since ego dissolution IS what you experience. Through that effect, you get to analyze the "parts" of your psyche without the executive function hiding the discrete parts and that's integral to WHY a psychedelic drug helps with those issues. I don't believe this will ever be a once a week treatment.
- joeberon 6y agoTotally anecdotal but LSD made my depression significantly worse than improving it in any way. I had two proper trips and had a seizure kind of thing at the start of the second one due to the overwhelming visuals (not experienced anything like that before or since). EDIT: to expand, it made me very questioning of my own consciousness and gave me severe and persistent existential dread and fear of death to the point where I felt quite suicidal (which I've _never_ experienced before). I restarted my old anti-depressants which have helped quite a lot but I don't think these feelings will ever truly disappear. Quite honestly it is the one drug I truly regret taking. If you aren't ready to accept what these drugs will show you then it can be a long-lasting and damaging experience, certainly it was for me
- pwr22 6y agoHope your recovery keeps moving in a positive direction :).
- joeberon 6y agoThank you
- dr_dshiv 6y agoCan you share more about the context of the trip? Typically mindset and setting have a big influence. Were you in a safe environment with people you like and trust? Thanks.
- joeberon 6y agoYes, first time was on a canal boat (EDIT: my father-in-law's boat, but he was away) with just my wife. Very safe and secure setting. Second time was at a very small psytrance festival with my wife and her parents. I trust them completely and they are both very nice, and there were not any scary people about.
- PoachedSausage 6y agoAlso hoping you move towards recovery and it sounds like you have good people in your life to support that. I would say that a festival (even small and friendly) is possibly not the ideal place to take psychedelics, unless you're very experienced. If you are particularly prone to paranoia, it can surface with psychedelics (even Cannabis) even in good settings.
- stared 6y agoPersonally, I think that the effective ban on psychedelic research is a crime against science and mental healthcare - given its immense potential. Sure, there are risks, but we routinely use drugs (as in: medications) of far worse side effects! For some reason, reading Grof felt like reading "Solaris" by Lem - on forsaken, unreal research. I am happy to we are slowly starting research into that. I recommend "Realms of the Human Unconscious: Observations from LSD Research" by Stanislav Grof (https://www.amazon.com/Realms-Human-Unconscious-Observations-Research/dp/0285648829 https://www.amazon.com/Realms-Human-Unconscious-Observations...) - he was one of the pioneers into psychedelic research, while it was easy and possible. For many aspects, it is... humbling. It seems that visions/senses/experiences of cosmic unity, or unspoken dread, or going beyond the physical world is more of a common theme of LSD. However, I am torn, when it comes to its lack of skepticism. On one hand side, he hints that some aspects of extrasensory perception (e.g. clear visions of spermatozoid entering an ovum, visions of one's ancestors, etc) can be real, without noting some typical biases (e.g. people reporting coincidences only when they happen). Same, he seems to accept a lot of Freudian stuff uncritically. On the other, I am really happy he didn't censor the stories (or himself!) and share both processed and raw experiences. The overall narration is in the tone of a curious researcher knowing that he may get answers he is not looking for. Overall, I recommend it a lot, keeping in mind that you don't take too religiously his mentions of Freud, Jung, birth matrices and extrasensory perception too literally. But... as a lens/perspective, that (though flawed/simplified) can yet be fertile.
- kortex 6y ago> On the other, I am really happy he didn't censor the stories (or himself!) and share both processed and raw experiences This should be the default reaction when it comes to metaphysical phenomena like ESP, consciousness, and the like. If he had self-censored, that's less of another human's experience shared. Sure, enough off-beat ideas label you as a kook, but I think if we entitled every human to one or two write-off beliefs, without labelling them as a kook, we'd discover more interesting things about the world. It's so easy to go, "that person believes in X, clearly they lack skepticism" and write off every other stance by them. Instead if we the listener accept these data points as "interesting but potentially erroneous" we can build better mental models than if we reject outright ideas contrary to our worldview.
- carapace 6y ago"Set and Setting" https://en.wikipedia.org/wiki/Set_and_setting https://en.wikipedia.org/wiki/Set_and_setting "Of course, the drug dose does not produce the transcendent experience. It merely acts as a chemical key..." — Timothy Leary (who ought to know.)
- Dumblydorr 6y agoFor me, psilocybin removed data filters and allowed my mind to receive data without mental heuristics prejudging my senses. I saw light and not objects, I saw more color where I knew there should be less, and I viewed bugs and plants as other beings occupying the same space as me.
- anoraca 6y agoSo narcissism and egomania could possibly be a result of a bad diet?
- troughway 6y agoWould IF help?
- colordrops 6y ago> Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. This is interesting. Is there any practical techniques on how to induce the latter form of ego dissolution?
- kaikai 6y agoEat mushrooms, apparently.