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LSD-like molecules counter depession without the trip
- GenerocUsername 4y agoDoubt. It's maybe possible that LSD (and per the article, LSD-like chemicals) has a chemical effect on depression, but based on the fact that MANY different psycadelics exhibit similar anti depression abilities, it seems more likely that it is the actual experience of the trip that confers most of the benefit.
- desro 4y ago[citation needed]
- rippercushions 4y agoThere is significant evidence that MDMA, LSD and psilocybin, which are all psychedelic drugs but wildly different chemically, have a significant impact on depression. https://en.wikipedia.org/wiki/Psychedelic_therapy https://en.wikipedia.org/wiki/Psychedelic_therapy
- waffleiron 4y agoEvery single one of these has an effect on serotonin receptors, there are a lot of clinical antidepressants that don’t make you trip but affect serotonin. So I don’t think this is actually proof of the trip being needed
- eurasiantiger 4y agoThere’s also some evidence that those serotonergic antidepressants actually worsen depression and make it chronic.
- deleted 4y ago[deleted]
- rippercushions 4y agoThe difference is that antidepressants have a temporary effect on serotonin levels and thus need to be taken continuously, while a "trip" on psychedelics appears to actually be able to rewire your brain, so a single dose can have permanent or at least much more long-lasting effects.
- GavinMcG 4y ago“It’s possible that consuming glucose (and other forms of sugar) has an effect on weight gain, but based on the fact that MANY different foods exhibit similar weight-related effects, it seems more likely that it is the actual experience of flavor that makes the body convert calories to fat.”
- sheen 4y agoI heard an interesting counterploint the other day. I think the statement is completely unfounded but figured I'd share because it sounds reasonable... "Memories are formed by neural pathways, and it is these memories / correlations that form a basis for (some) mental illness. Taking psychedelics can help take another perspective on these memories and rewrite these these pathways / correlations."
- phnofive 4y agoThis is specifically true for some phobias: https://ec.europa.eu/research-and-innovation/en/horizon-magazine/triggering-original-fear-memories-could-treat-phobias-and-ptsd https://ec.europa.eu/research-and-innovation/en/horizon-maga...
- Sugimot0 4y agoWow this sheds some new light on an anecdotal experience if mine: I once watched a climber free climb a moderate 30 meter route me and my friends had just completed with ropes, and he mentioned his LSD hallucination was peaking as he saw us at the top. I considered that maybe climbers like him have exceptionally higher risk tolerance or a habituated comfort with psychedelics and climbing. However, as someone with a reasonable amount of exposure to both of those (separately), it still baffled me. This feels like a more palatable explanation in tandem with higher risk tolerances and habituation.
- sheen 4y agoGreat read. Thanks for sharing!
- 4y ago
- galaxyLogic 4y agoMaybe it's part of the "actual experience" that you don't feel depressed any more. The hallucinations, who needs those. Therapeutically what matters is the increased feeling of well-being that lasts for weeks if not longer.
- Out_of_Characte 4y agoThe hallucinations do really help. Its very difficult to be depressed when all the trees are dancing and shining. LSD and the likes also avoids congnitive hallucinations in most people so you're perfectly aware that it's just the wind.
- peanut_worm 4y agoWhat is a “cognitive hallucination”? LSD can absolutely change your thought patterns
- sterlind 4y agoset and setting. 2C-E showed me how I was a tiny spec, on a tiny speck of a planet, in an infinitely large universe, cold and unfeeling and uncaring, loved only in a tiny way by only a couple of other tiny specs, all of whom would die in a brief instant, cosmically speaking. it was like Carl Sagan showed up to tell me how meaningless my existence was. also, unbearable sensory overload as the panic attack worsened, seconds took minutes to pass, and my kidneys felt like they were failing (they were fine though.) the ego death was more or less permanent. my "self" never recovered, I had to build a new one. uncanny experiences of feeling like I wasn't my parents' real daughter, that my phone was a dead person's. I wasn't the same person. but this person is better than she was. so.. worth it in the (years-)long run, but hardly sunshine and roses! bad trips are scary. 2C-E is known for being cold and analytical, but I'm sure you can have similar experiences on acid.
- Schroedingersat 4y agoUnless the thing that makes the trees dance and shine rather than loom and glow ominously is the same thing that has the anti depressant effect. I personally think pearl clutching about the idea someone might have fun whilst benefiting from medicine is stupid and there's no reason psychedelics should not be available to anyone who is screened for potential contraindications, but there's no reason to assert that all of the different effects are inexorably linked.
- tpm 4y agoI am also doubtful, but the new molecules look quite a bit different to both LSD-like and tryptamine psychedelics, so it will be interesting to see what will the test subjects say, if it gets that far.
- dqpb 4y agoMaybe the only reason you associate positively with the trip is that it's paired with anti depressant effects.
- deleted 4y ago[deleted]
- ipnon 4y agoThere are also primarily dopaminergic psychedelics like ibogaine that have even more potent therapeutic benefits. This suggests it is not sertonergic effects that are the primary therapy.
- heavyset_go 4y agoI agree with this. There are novel tryptamines that exist that bind to 5HT2A but don't cause a trip. I've tried a couple of them. They do have effects upon mood, generally positive, but they are distinctly different than the effects on mood from an actual trip. I think the difference comes from the meaning and significance that come from the experience of the trip itself. The meaning is logically and emotionally interwoven with your perspective, effectively changing it. I believe experience is required for that profound perspective shift, and non-psychedelic 5HT2A agonists don't provide that experience.
- ipnon 4y agoThis is the million dollar question in psychedelic research today: Are the serotonergic effects of the psychedelic tryptamines primarily responsible for the therapeutic effects, or is the profound religious-mystical component indistinguishable from the positive changes observed? It is a profoundly expensive question. If pharmaceutical companies can deliver a pill that cures depression and gives life meaning without forcing users to face their angels and demons, then the FDA would give approval before the ink on the submission form had dried. As it stands, it would seem the predominant opinion in the community of psychedelic researchers is that the religious-mystical effects are the primary therapeutic vector. It is very difficult to meet God and walk away cynical and melancholy.
- bowsamic 4y ago[deleted]
- PraetorianGourd 4y agoI am confident the OP meant “meet God” as short-hand for “a spiritual and transcendental experience wherein the ego is destroyed and rebuilt anew with a profoundly different perspective”. I don’t think anyone would earnestly claim that there is zero risk to any hallucinogenic experience. One of my hopes is that through study we can better understand the ingredients that lead to profoundly positive experiences vs. profoundly traumatizing experiences. And anyone who claims we know that today is acting in bad faith.
- ipnon 4y agoRoland Griffiths’ foundational psilocybin study did not have any adverse outcomes. They used a simple protocol: no patient or patient family history of schizophrenia or bipolar, patients underwent cognitive behavioral therapy before and after the trial, patients were made to develop a warm and trusting rapport with the physicians before administration, and a physician was on hand for the duration of the psilocybin administration to coach the patient through unforeseen disturbances and administer anxiolytics in the case of panic attacks. With this simple protocol they reported no adverse affects, although they also did not report a 100% rate of efficacy. Griffiths wrote an entire separate study on this protocol, it is self-recommending.
- swayvil 4y agoCommon cardboard tube generates all the joys of astronomy without magnifying any heavenly bodies.
- isoprophlex 4y agoCombining common cardbord tube - astronomy with real LSD might eventually get you what you need wrt. inspection of heavenly bodies. (Picturing people lying on a lawn taking turns looking through a cardboard telescope)
- taylorius 4y agoVery good! :D The whole endeavour does have a rather an air of "keep the worker drones functional and content".
- isoprophlex 4y agoAs someone with a background in organic chemistry, I have a silly nit to pick with the phrasing "LSD-like molecules" These molecules look nothing like LSD! Structurally they are as different from eachother as a dog is to a flying squirrel. Of course they act like LSD by binding to 5HT2a. This is absolutely terribly pedantic and probably only applies to the mind of someone who wants to see the molecules first, and the rest of the research later, but I would have preferred "Molecules that act like LSD can counter depression without the trip"
- tpm 4y agoOr even "Molecules that act like LSD in regards to 5ht2a can counter depression without the trip". Because LSD is also active at other targets, and presumably those new molecules too.
- ithkuil 4y agoOr perhaps they don't, that's why you get some effects and not others (as desired)?
- tpm 4y agoThe probably strongest and most selective currently known 5ht2a agonist, 25I-NBOMe, is a psychedelic, and also (unlike LSD, which is less strong and less selective), much much more toxic and user reports say that the effects, both on body and mind, are much worse. So this is a complicated topic and I look forward to reading user reports from these new molecules, if they decide to test them.
- gavinray 4y agoEh, I wouldn't call the mental effects of NBOMe's objectively worse than say LSD -- just different Now, the body load/vasoconstriction + other physical effects, definitely. You can always tell the NBOMe is kicking in when you get shuttery cold from vasoconstriction and have a weird motor rigidity. Also FWIW, there are more potent agonists than NBOMe. I know of at least one discovered by Nichols' lab that they refused to publish for fear of use as an aerosolized bio-weapon.
- neuroma 4y agoMaddening paywalled article; https://doi.org/10.1038/s41586-022-05258-z https://doi.org/10.1038/s41586-022-05258-z Honestly why bother doing the science for public good on public money if the information can't be disseminated freely.
- simonebrunozzi 4y agoTypo in the title: depession -> depRession
- jokowueu 4y agoI have tried most of these non psychadelic analogs They don't do anything such as iso-dmt for example
- acchow 4y agoUhhh, why would you do this? You can learn so much during a trip to solve some of the fundamental issues/trauma behind your depression.
- fsloth 4y agoPerhaps a depression drug that does not induce a psychedelic experience is psychiatrically safer than one that would? One would need some background in psychiatry and/or pharmacology to answer this I think. I'm guessing such talent is present on this site :)
- comboy 4y agoIt may be that somebody depressed does not feeling like exploring unknowns, or brave enough to lose himself and experience something completely different. Also, I don't think it's necessary wise to suggest somebody depressed go on such trip. It can take you different places. Sure, it may be fine 9 out of 10 times, but if somebody gets stuck in some negative positive feedback loop (heh) he may end up with a trauma.
- bananamerica 4y agoI don't do recreational drugs, but don't LSD trips make you pretty useless for a while? If my morning psych medication required me to be non-productive for 4 hours, it would be hard to find a place for it in my daily routine.
- yieldcrv 4y ago4, thats cute
- tsukurimashou 4y agoLSD isn't for daily routine unless you microdose (and even then you don't take it everyday) a trip is more like 8-12h
- bananamerica 4y agoI understand. Maybe a "no trip" LSD can be useful for people who require larger doses of the substance for therapeutic effect.
- ianbutler 4y agoSomeone who isn’t me had long lasting, maybe permanent, positive impacts with regards to depression the one time they did LSD. They did it in a very safe environment with very close friends, but hopefully we can understand the mechanism and isolate how to better help people without the stigma attached.
- classified 4y agoI'd much prefer it _with_ the trip, but then that's only possible if you don't have to work the next day, let alone the same day.
- mizaru 4y ago*in mice
- yellow_lead 4y agoCan anyone tell me the standard for determining if a mouse is depressed? Or anxious? Just curious
- Synaesthesia 4y agoOr tripping? I think that we can ascertain some things from their physiological responses, eg fear, anxiety and being content. Obviously there’s a lot we don’t know about their internal state. Psychedelics really need to be tested on humans.
- krispyfi 4y agohttps://en.m.wikipedia.org/wiki/Head-twitch_response https://en.m.wikipedia.org/wiki/Head-twitch_response
- YorkshireSeason 4y agoWhat scientifically credible, i.e. at least stably reproducible, connection does the head twitch response in mice have to do with depression in humans?
- heavyset_go 4y agoThe head twitch test is used to determine whether a substance activates 5HT2A in the same way psychedelics do. The forced swim test is used in animal models of depression: https://en.m.wikipedia.org/wiki/Behavioural_despair_test https://en.m.wikipedia.org/wiki/Behavioural_despair_test I'm a layman, I don't know what the scientific basis is for using the test to model depression. I personally find it pretty cruel.
- YorkshireSeason 4y ago
- enviclash 4y agoWhat food types contain something like that? Anything healthy?
- puchatek 4y agoThose molecules were engineered IIUC. They don't exist in nature
- heap_perms 4y agoThat's just missing the point completly.
- macrolime 4y agoIt could perhaps also be that it would work without the trip for some people, for example if the depression was more like metabolic/chemical or something in nature, while for other people the depression was caused by their life situation or other issues and working through it through a trip would help. So basically like antidepressants and psychotherapy, both work but some people get more out of one or the other.
- benevol 4y agoThis sounds like "Nutella - without the chocolate flavor". But making big pharma insanely rich - once again.
- avidiax 4y agoYes. Let's work around the moral panic that some people might enjoy tripping for a few hours under medical recommendation and supervision by not even investigating whether existing psychedelics are a viable treatment, and instead assuming that the trip needs to be removed. It would be one thing if psychedelic treatment for mental health were widespread and the time off from work or the experience was distressing to patients. But we've skipped step one there, and it has absolutely nothing to do with how unprofitable effective psilocybin, ketamine or LSD treatments would be.
- westmeal 4y agoI just saw an episode of the Simpsons where Lisa finds a flower that makes scorpions in the desert docile, so she makes an extract of the flower to test that theory for her school science fair only to find that it makes old people bearable to be around. Long story short, a pharmaceutical company finds out and before long they synthesize a pill that does the same - with the side effect of the patients eyeballs popping out of their sockets.
- kayodelycaon 4y agoInteresting. It has the opposite effect of antipsychotics and antidepressants that act the same receptors. Makes me wonder if studying LSD could help with the treatment of schizophrenia and bipolar disorder. My personal experience is the brain becomes very plastic during manic episodes, especially when they border on or cross into psychosis. In a way similar to stories I’ve read about LSD.
- wise0wl 4y agoThat was one of the original purposes for LSD---it was billed as a "psychomemetic", in that it mimicked the state of psychosis and made it so therapists could better study and treat the disease in isolation.
- SamoyedFurFluff 4y agoGenerally schizophrenia and schizophrenia spectrum disorders are an instant no-go for hallucinogenic drugs like LSD. It’s been known to trigger psychotic episodes and mental health crisis. Schizophrenia and manic episodes aren’t necessarily the same or behave similarly, and where they overlap is via schizoaffective disorder.
- Synaesthesia 4y agoYes my friend who had a psychotic break told me it was "just like an acid trip", that didn't end. I've had all kinds of delusions on LSD, it's interesting because afterwards you can reflect on the odd thoughts you just had (if you don't take them too seriously!) It sure can be insightful, in the right space.
- c7DJTLrn 4y agoPharma really will do anything to find a depression drug they can sell for huge markup when LSD, ketamine, and psilocybin are already known to work effectively.
- jasonhansel 4y agoI can imagine someone saying the same thing about aspirin. "Pharma will do anything to sell you aspirin pills, when you can just get salicylates the natural way from willow bark." No. Standardization, rigorous testing, and FDA approval are good things.
- mmsnberbar66 4y agoI would like to hear why this person is being downvoted
- 5co 4y ago
- zwkrt 4y agoit would be nice if the standardization could come from using the substances that we already have, even if just as a sensible start. I can understand mushrooms being iffy because they comlpex and vary (even between mushrooms of the same species), but LSD is a single molecule already! I would love to see a future where I can get a government-standardized tab of acid. Of course this will never happen. The reason they are investigating how to get the 'good' effects without the 'bad/uncontrollable' effects is because of who is deciding what 'good' and 'bad' are. 'Good' = Allows people to continue functioning at a high level with the current power structures in place. Put in other words, it is only worthwhile to cure someone's depression if you can do it without the cure involving that person realizing that their current government isn't working for them.
- chevman 4y agoThat's literally what they did. Started with their knowledge of LSD and went from there using a similar chemical.
- danielunited 4y agoDon’t mushrooms treat depression as well?
- mmsnberbar66 4y agoThe key thing in the title is "without the trip"
- knodi 4y agoDoes this worry anyone that this drug will be abused? Doesn't everyone like to feel good no matter the day. What if your employee gives this to you because you hate your work?
- pfkurtz 4y agoLSD: Multiple times I did it with others and profoundly deepened my relationship with those individuals. Another time I did it by myself and saw the face of evil and I've never been so terrified, but I survived and wouldn't change a thing. I don't think any of that can be captured by whatever neuro-binding effect is being mimicked by these designed molecules. I also took antidepressants for awhile once and it was diet and exercise and commitment to changing my life and talking to a therapist that was what helped; but I know others who need to take pills every day or things go bad. I wish there was a short treatment for people who need that.
- teawrecks 4y ago> I don't think any of that can be captured by whatever neuro-binding effect is being mimicked by these designed molecules Agreed, it sound like they do not cause any hallucinations, so you would likely not "see the face of evil". > it was diet and exercise and commitment to changing my life and talking to a therapist that was what helped; Speaking from my armchair, from what I understand about clinical depression, these are the things that someone who is not depressed can do because they "crave" them. For people who are depressed, there is a (possibly intermittent) neurological imbalance that is preventing them from craving these things which would otherwise keep them functioning normally. While it may be possible to power through the depression, and do these things until the imbalance is resolved, I would argue that this is only due to a temporary break or recession of their depressive symptoms, something that an effective antidepressant should aim to do. I'm not claiming my view is true, I'm looking for feedback on how correct/incorrect my view is.
- logicchains 4y agohttps://www.nature.com/articles/s41380-022-01661-0 https://www.nature.com/articles/s41380-022-01661-0 this paper was published recently, shows there's actually a lot less evidence for the "depression is caused by a neurotransmitter imbalance" hypothesis than people tend to believe.
- teawrecks 4y ago
- captainmuon 4y agoOK, now make a molecule which gives you a trip without the psychological effects. It would be cool to have a sober mind and at the same time see completely realized halucinations (not pressing-on-the-eyebulb I see weird colors, but fully formed people and things undistinguishable from reality, like when you are dreaming). I'm not sure that's even possible. But I think you could invent a lot of interesting recreational drugs in theory, alas nobody is developing them because there is no incentive and they would be illegal. Soma? Cigarettes that are safe? Aphrodisiacs? Drugs that let you tweek your personality?
- Synaesthesia 4y agoI think there's a limit to what can be achieved with drugs, still a lot awaits to be discovered out there. Did you ever read Shulgin's PIKHAL and TIKHAL? LSD doesn't so much give you those kind of hallucinations (seeing people that aren't there etc), in fact it's effects are pretty hard to nail down, all kinds of things can happen on a trip. But the closest analogy is still a "model psychosis", in other words you will experience what people have when they have psychosis, for about 8-10 hours.
- armatav 4y agoCan’t possibly let people go on any sort of subjective journey, can we?
- akimball 4y agoExtraordinary claims require extraordinary evidence.