[HN Gopher] LSD-like molecules counter depession without the trip
___________________________________________________________________
LSD-like molecules counter depession without the trip
Author : hericium
Score : 309 points
Date : 2022-10-02 03:28 UTC (19 hours ago)
(HTM) web link (www.ucsf.edu)
(TXT) w3m dump (www.ucsf.edu)
| danielunited wrote:
| Don't mushrooms treat depression as well?
| mmsnberbar66 wrote:
| The key thing in the title is "without the trip"
| GenerocUsername wrote:
| Doubt.
|
| 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.
| tpm wrote:
| I 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.
| desro wrote:
| [citation needed]
| rippercushions wrote:
| There 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
| waffleiron wrote:
| Every 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
| rippercushions wrote:
| The 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.
| eurasiantiger wrote:
| There's also some evidence that those serotonergic
| antidepressants actually worsen depression and make it
| chronic.
| [deleted]
| GavinMcG wrote:
| "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."
| betwixthewires wrote:
| ...except sweetness isn't what all those foods have in
| common?
| namero999 wrote:
| Precisely. That's why the placebo effect is so effective.
| peanut_worm wrote:
| Not really a fair comparison. How can you compare weight gain
| to a mental illness?
| andai wrote:
| Wasn't there something about artificial sweeteners causing
| the brain to release hormones that lead to insulin
| resistance? So the brain is reacting to the "flavor" rather
| than the actual sugar (or more precisely, the neurological
| pathway that consciousness experiences as sweet taste is also
| linked to this sugar-related physiological chain reaction).
| kolinko wrote:
| I think this might've been a myth.
|
| I wore a constant glucose monitor for a while (Veri), and
| drinking soft drinks filled with all kinds of artificial
| sweeteners caused no glucose changes. If sweeteners caused
| a spike in insuline, I would see glucose levels fall.
|
| I tried finding research on the subject once, and couldn't
| find anything legit.
| naasking wrote:
| > I wore a constant glucose monitor for a while (Veri),
| and drinking soft drinks filled with all kinds of
| artificial sweeteners caused no glucose changes.
|
| It doesn't cause immediate changes, it causes long-term
| changes to glucose response by altering the gut
| microbiome. Here's a recent double-blind randomized
| controlled trial showing these effects that was discussed
| on HN a few weeks back:
|
| https://www.cell.com/cell/fulltext/S0092-8674(22)00919-9
|
| This is the first study that I think showed this pretty
| conclusively.
| Etheryte wrote:
| Yes, it was on the frontpage of HN a few weeks ago. Off the
| top of my head the results were that certain artificial
| sweeteners spike insulin and some don't.
| fuckstick wrote:
| This doesn't pass the smell test for an in vivo result.
| If they spiked insulin in a physiological meaningful way
| without actual glucose you'd expect hypoglycemia. It's
| not like insulin resistance is an acute process.
| naasking wrote:
| You should read the study:
| https://www.cell.com/cell/fulltext/S0092-8674(22)00919-9
| fuckstick wrote:
| Did you? It doesn't contradict anything I stated.
|
| I don't think the GPs informal synopsis characterizes the
| gist of that paper in any meaningful way.
| schrodinger wrote:
| I thought it was that the reduce insulin sensitivity, so
| you're affected when you DO have sugar on the future?
| sheen wrote:
| I 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 wrote:
| This is specifically true for some phobias:
|
| https://ec.europa.eu/research-and-innovation/en/horizon-
| maga...
| Sugimot0 wrote:
| Wow 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.
| jnovek wrote:
| While this is a completely fair counterpoint, the part that
| GP didn't mention is that a patient's subjective experience
| is usually ignored or minimized in psychological research,
| which prefers to focus on behavior and biological phenomena
| (because they are easier to measure).
|
| It seems to me like the "trip" aspect is at least worth some
| investigation.
| dqpb wrote:
| Maybe the only reason you associate positively with the trip is
| that it's paired with anti depressant effects.
| galaxyLogic wrote:
| Maybe 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.
| puchatek wrote:
| A trip is more than a series of visual disturbances. It's an
| emotional rollercoaster. Your perception of yourself and your
| surroundings changes drastically and you have many insights
| that you perceive as very significant. This can help take
| your attention away from irrelevant things and direct it to
| more meaningful things in your normal life.
|
| And even the hallucinations can show you that we construct
| our realities in every instant of our lives. You know this
| already of course but knowing and experiencing are two
| different things.
| Out_of_Characte wrote:
| The 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.
| sterlind wrote:
| set 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.
| peanut_worm wrote:
| What is a "cognitive hallucination"? LSD can absolutely
| change your thought patterns
| Schroedingersat wrote:
| Unless 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.
| Nursie wrote:
| > Therapeutically what matters is the increased feeling of
| well-being that lasts for weeks if not longer.
|
| But what if that is a consequence of the 'hallucinations'
| changing your perspective on things? What if the psychedelic
| break with baseline reality for a few hours is the trigger
| that changes things?
|
| It's definitely interesting to try and understand. I also
| just react poorly to people trying to create 'useful'
| versions of a drug without the 'fun' parts. I don't dabble
| any more but the experience of compounds like these was well
| worth the time invested.
|
| (I put hallucinations in quotes above because I think there's
| a difference between the psychedelic experience and something
| all-out hallucinatory, read erowid reports on belladonna,
| datura and brugmansia for the latter)
| heavyset_go wrote:
| I 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.
| [deleted]
| ipnon wrote:
| There 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.
| armatav wrote:
| Can't possibly let people go on any sort of subjective journey,
| can we?
| enviclash wrote:
| What food types contain something like that? Anything healthy?
| puchatek wrote:
| Those molecules were engineered IIUC. They don't exist in
| nature
| westmeal wrote:
| I 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.
| ianbutler wrote:
| Someone 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.
| heap_perms wrote:
| That's just missing the point completly.
| captainmuon wrote:
| OK, 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 wrote:
| I 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.
| classified wrote:
| I'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.
| macrolime wrote:
| It 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.
| neuroma wrote:
| Maddening paywalled article;
| 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.
| kayodelycaon wrote:
| Interesting. 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.
| Synaesthesia wrote:
| Yes 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.
| SamoyedFurFluff wrote:
| Generally 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.
| wise0wl wrote:
| That 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.
| ipnon wrote:
| This 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.
| sallystarace wrote:
| I am a religious person who happens to have enjoyed LSD in my
| time. I have had the most profound experiences during my many
| trips, and not a single one that was at all like the sense of
| awe I get from worship.
|
| I love the headspace that you get into during the trip. It is
| great for finally addressing issues that you have set aside.
| After the trip however, you think that all your ideas are good,
| then it wears off, so either way it is not useful just by
| itself.
| mistermann wrote:
| Note that "you" refers to you, _and some other people_ , but
| not necessarily all other people.
|
| I would even classify this realization as an exception to
| your "is not useful" rule.
| ipnon wrote:
| I made a poor choice of words. It would have been better to
| say "the experience of the ineffable and reckoning with
| intensely personal beliefs." I meant no blasphemy with my use
| of religious and Christian terms.
| bowsamic wrote:
| [deleted]
| ruined wrote:
| if i were unhappy with my life after an epiphany, i would
| simply act to change my situation
| bowsamic wrote:
| The only great impulse of change I had after my trips was
| an intense urge to kill myself
| ruined wrote:
| what, with no reason? you didn't have a why? fix the why.
| ceejayoz wrote:
| Not all whys are known, and not all known whys are
| fixable.
| bowsamic wrote:
| It didn't show me a why it just showed me that I want to
| die. Other LSD users say I should take more at a higher
| dosage but that seems like a bad idea
| ruined wrote:
| you keep looking at LSD for feelings you're having while
| sober. examine your reasons for your feelings now. if you
| can't identify your own motivations, how can you
| attribute cause like that?
| bowsamic wrote:
| I wasn't ever suicidal before, I was after, that's all I
| know
| mistermann wrote:
| A theory / thought experiment:
|
| Take "it just showed me that I want to die" and unpack
| every single word into an absurdly and "pedantically"
| complex, _comprehensively and perfectly correct_
| articulation of the(?) precise meaning in this context.
| In doing so, use various forms of articulation, not only
| paragraph /narrative form.
|
| If you are doing it right, ideally you will find yourself
| having to fight against your own mind at several points
| during the analysis.
|
| Work on the problem for a month or six, even just two or
| three minutes at a time now and then. I propose that at
| the end of this process, you will possess more knowledge
| than you did before.
|
| There are various techniques to accelerate this process,
| but I will let you figure those out on your own along the
| way. As a hint: consider various topics of discussion
| that arise on the website you are on.
|
| I should probably also note: this is not necessarily a
| risk-free undertaking, so maybe build some safeguards
| into your methodology.
| bowsamic wrote:
| I have literally no idea what the hell you are talking
| about
| chaps wrote:
| What dosage did you take? I've heard low doses can
| actually be a deeply frustrating experience.
| bowsamic wrote:
| 100ug
| andai wrote:
| Curiously, antidepressants can trigger suicide in
| suicidal people because they give them the energy to act
| on those impulses.
|
| My friend was suicidal, and psilocybin was the only thing
| that made him go back to wanting to be alive (though the
| effect only lasted ~2 weeks each time).
| parineum wrote:
| >Curiously, antidepressants can trigger suicide in
| suicidal people because they give them the energy to act
| on those impulses.
|
| As someone with somewhat first hand experience with this,
| it's not exactly "gives them the energy".
|
| The anti-depresents I started taking worked exactly as
| advertised. The "problem" was I wasn't just depressed, I
| was also just not happy with life. Anti-depresents can
| get you out of a depression but they won't make you
| happy.
|
| It was a bit enlightening to understand the difference
| between the sadness I felt and the depression but it can
| also make you feel more helpless when the depression
| lifts and you still don't really want to wake up
| tomorrow.
|
| As a result of this experience, I think it's
| irresponsible to prescribe anti-depresents without
| accompanying therapy.
| naasking wrote:
| > if i were unhappy with my life after an epiphany, i would
| simply act to change my situation
|
| It's anything but simple if you're depressed. You seem to
| think that insight drives motivation, but in depressed
| people these are often decoupled. You can have all the
| insights you want but the motivation to do anything just
| does not manifest.
| isoprophlex wrote:
| The experience is highly variable between people. I'm sorry
| you had such a rough time, and I'm hoping that things are at
| least slowly getting better for you.
|
| About the god thing, my 2 cents. "god" doesn't always mean
| Christian White Old Guy on a Cloud Looking Angrily Downwards.
| There's a less narrow interpretation.
|
| If psychedelics strip away your day-to-day preoccupations,
| and show you life with a vastly different set of mental
| filters in place, many people experience a transcendent
| feeling of belonging to something bigger than their sober
| selves. A connectedness to other humans and nature that goes
| beyond ordinary experience. The idea that death isn't so bad,
| only suffering is; and suffering is the price we must pay for
| the ability to see its opposite, beauty.
|
| Which people then conversationally condense to "yeah you meet
| god"
| bowsamic wrote:
| So they just mean a transcendent, spiritual experience?
| isoprophlex wrote:
| Yeah i guess that's a lot more accurate if you want to
| avoid the cultural baggage of the god-word
| swayvil wrote:
| _It expands your consciousness_ is a popular way of
| describing it.
|
| Imagine a chronic obsessive cellphone gazer. One day he
| lifts his nose from the screen. Sun! Clouds! Birds and
| squirrels!
|
| Except moreso.
| bowsamic wrote:
| But shouldn't God be in all things, including the
| profound, if he's really the Absolute? I doubt he'd be
| limited to our human conception of nature
| swayvil wrote:
| I prefer to observe first, theorize second.
| bowsamic wrote:
| So He is more of a Kami?
| swayvil wrote:
| That would be one of those theories.
| canadiantim wrote:
| This is a really good explanation
| Schroedingersat wrote:
| Meeting is just a way of describing a numinous experience. I
| have heard atheists, christians, pagans and sikhs alike use
| the term. Mathematicians often use it to describe especially
| profound proofs regardless of religion.
| PraetorianGourd wrote:
| I 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 wrote:
| Roland 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.
| loceng wrote:
| They're looking for a pill they can patent, and then will
| demonize and do a fear campaign on the non-patentable options.
|
| If the supposed anti-depressant effect of whatever specific
| molecule they claim doesn't induce relatively rapid nerve
| generation, opening up previously closed or blocked off
| pathways - that pruned off arguably due to trauma and lack of
| use - then they likely aren't as powerful as where the mystic
| effects come from; it's the temporary turning off, removing the
| ego mind from the algorithm of the mind/the mind's eye -
| allowing you to see reality very differently then you've been
| formed rigidly in beforehand; some tribes give Ayahuasca to
| their babies to keep them open as they develop, rather than
| letting trauma and/or natural processes lock them into more
| narrow behaviour and thinking patterns.
| [deleted]
| jokoon wrote:
| Meeting God or finding meaning in life is not on the
| requirement list for the FDA. There other ways to evaluate
| treatments for depression.
| avidiax wrote:
| I have not heard the claim that it's the mystical experience
| doing the work. I have heard some theories about the glutamate
| system in the brain, which is strongly affected by e.g.
| ketamine, psilocybin.
|
| My experience with ketamine treatment for TRD is that it was
| lots of awesome shapes and colors and sense of melting into the
| floor, but definitely no communion with "god" or "mystics", no
| special reexamination of the self or amazing new perspective.
| Despite that, I still experienced some improvement in symptoms.
|
| I would hope that pharmaceutical research can reduce the time
| and expense related to this treatment and the side effects like
| nausea, and less on the moral panic that some people use these
| drugs for fun somehow.
| Stevvo wrote:
| "I have not heard the claim that it's the mystical experience
| doing the work."
|
| This claim has been the prevailing view of almost every
| psychedelic researcher from the 60s until ~10 years ago. It
| was also a big contributor to there being almost zero human
| research into psychedelics over that time period.
|
| It's still the prevailing view today, but not talked about
| because researchers can actually get funding if they lie
| about it.
| dylan604 wrote:
| >My experience with ketamine treatment for TRD is that it was
| lots of awesome shapes and colors and sense of melting into
| the floor, but definitely no communion with "god" or
| "mystics", no special reexamination of the self or amazing
| new perspective
|
| I've heard people also make similar comments to the LSD or
| psylocibin experiences as well. In my personal experience,
| that's purely a matter of dosage. Sounds like an obvious
| thing, but not everyone knows how a particular dosage will
| affect them. Any particular dose that is just a fun time for
| one person might be 1:1 meeting with a higher power for
| someone else.
|
| This is where I hope honest legal regulation would help.
| Rather than having to think about how many stems/caps you can
| eat from SourceA vs SourceB, you can just take a capsule that
| is accurately measured at X mg. Maybe you need to take half
| or take 2, but at least it would be the same each time.
| s0berpotato wrote:
| I was introduced to the idea through a podcast of Lex Fridman
| hosting John Vervaeke. The idea is that being trained in some
| methods enables you to better re-frame ideas, reality etc.
| when under the effect of these substances and then to be able
| to integrate them to your life once you are sober. Basically
| to identify when something you identified and felt while
| under the effect is more "real" since your brain makes
| connections which don't usually happen. The training allows
| you to see these connections as something more than noise.
| hallway_monitor wrote:
| The trip you had was different than what people experience on
| LSD or psilocybin. You still had a trip. You broke out of
| your normal frame of mind and were able to comprehend things
| from a perspective that you couldn't previously conceive of.
| It seems to me like this is the important component and not
| whether you think you met God or your creator. It seems to
| make sense that the changes in yourself afterwards are due to
| the experience and not to the chemistry, and I wonder if the
| people focusing purely on the chemistry have never had a
| trip.
| galangalalgol wrote:
| It also lines up with people getting similar benefits from
| serious meditation practice or dramatic life experiences.
|
| The common theme is that all these things change
| perspective, and none of them are entirely safe.
| ohbleek wrote:
| My experience is that the majority of the people focusing
| on the chemistry have ever oriented a trip and it was the
| impetus for going into research that focuses on the
| chemistry.
| lm28469 wrote:
| > 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
|
| Instead of selling xxx tonnes of xanax&co per day worldwide and
| make absolutely outrageous profit doing so ? Doubt
| ceejayoz wrote:
| Xanax has been generic for decades. This happens to all
| medications. Pharmacy _loves_ newly patentable venues like
| this. It'd be another new, expensive pill or infusion to
| market.
| parineum wrote:
| It's almost like the patent system is meant to spur
| innovation and development of new things.
| sixQuarks wrote:
| Exactly. Very naive thinking.
| jasonhansel wrote:
| You do know that these new psychedelic-like drugs are going
| to be patented and probably quite expensive, right?
| fragmede wrote:
| That's not even hypothetical either. Ketamine was proven to
| have great anti-depressant effects so Johnson &Johnson came
| out with their own patentable formulation of it called
| Spravato.
| BurningFrog wrote:
| Not exactly.
|
| Ketamine is _well known_ to have great anti-depressant
| effects, but since it 's long out of patent, no one has
| the incentive to spend $1B to get the FDA approval for
| it.
|
| So J&J invented the chiral twin molecule (the mirrored
| version), got it approved, and it's now sold as Spravato.
|
| To me this is 100% a regulation bug rather than some
| misfeature of capitalism or corporate greed.
| feet wrote:
| They didn't invent anything, they just made a specific
| enantiomer
| heavyset_go wrote:
| J&J didn't invent esketamine, they patented the use and
| formulations of esketamine for certain conditions.
| avidiax wrote:
| I don't think it's a regulation bug to require a study to
| approve a drug for a certain use.
|
| The bug is that we don't incentivize funding expensive
| studies to discover unpatentable (i.e. cheap) treatments.
|
| The minimum "patch" would be that the governments of the
| major drug markets decide that effort and discovery of
| applications count as a basis for patents. Then a drug
| maker could fund their studies based on which drug
| candidate is the most promising, not which is the most
| promising but also novel and thus patentable.
|
| Much better, would be to have the governments presiding
| over the major drug markets get together and create a
| proportional fund to cover studies for the public's
| benefit. The economics of that would be similar to
| private companies, but at least the profits would go
| towards further research.
| [deleted]
| BurningFrog wrote:
| > _I don 't think it's a regulation bug to require a
| study to approve a drug for a certain use._
|
| That's actually not how it works.
|
| When a drug is FDA approved for a certain use, doctors
| are free to prescribe it for anything the think it's
| useful for. This is called "off label" use, and is ~20%
| of prescriptions in the US. This "loophole" cures a lot
| of people!
|
| And there are some clinics who do use regular Ketamine
| for depression. The main problem for them is that
| _insurance_ will not cover this usage.
|
| > _The bug is that we don 't incentivize funding
| expensive studies to discover unpatentable (i.e. cheap)
| treatments._
|
| This I agree with. Though I'd expect some philanthropic
| billionaire to get to that long before any governments
| would.
| Natsu wrote:
| Normal ketamine is a mix of both antiomers. Spravato is
| only s-ketamine in an inhaler.
|
| Also, while some see the trip as the point of this, I
| woke up at knife point due to psychosis caused by that.
| Yet it also really does basically cure depression, if not
| accompanying anxiety, and it is known to cause new
| psychosis.
|
| So I hope this works out and can be used on people who
| really need to avoid the psychosis caused by ketamine.
| mmsnberbar66 wrote:
| tbh never heard of ketamine psychosis
| Natsu wrote:
| It can apparently trigger them in susceptible people. I
| got to see it first hand.
| kennedywm wrote:
| $1B? Is that an exaggeration? I can't seem to find
| anything close to that number anywhere. Perhaps you're
| mistaking the low-end cost of developing a new drug
| (around a billion, but it can be three times that) with
| the cost of FDA approval.
| BurningFrog wrote:
| It's probably the full cost of getting an approved drug,
| including a lot more than the approval itself.
|
| So that number was probably 10x off. That doesn't change
| the conclusion though.
|
| I learned all this from Scott Alexander. All details
| here: https://slatestarcodex.com/2019/03/11/ketamine-now-
| by-prescr...
| yodsanklai wrote:
| Xanax is available in generic form and costs almost nothing.
| pgt wrote:
| Something Huberman said on his podcast about alcohol is that
| the anti-depressive effects of SSRIs are not due to serotonin,
| but due to neuroplasticity.
| jnovek wrote:
| Can you elaborate on this, please? I've never heard this
| hypothesis and I don't totally understand what it means.
|
| Are you saying that SSRIs trigger changes in the brain? What
| changes? Why do they trigger these changes?
|
| Genuinely curious.
| twic wrote:
| It's been decades since i studied this stuff, but i
| remember there being a very promising line of work on the
| connections of the growth factors BDNF and NGF, which
| promote neuroplasticity, to depression. Seems it's still
| being worked on:
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174655/
|
| https://pubmed.ncbi.nlm.nih.gov/30235967/
| heavyset_go wrote:
| The theory is that hippocampal neurogenesis could be a
| factor in the treatment of depression. The hypothesis is
| based on the fact that effective antidepressants trigger
| neurogenesis, and not all antidepressants have the same
| mechanisms of action.
| snek_case wrote:
| Yes, SSRIs trigger change in the brain. That's why the
| effect is not instant when you start taking the pill, the
| change needs some time to start to happen. In particular,
| it's believed that depressed people have lower levels of
| neuroplasticity. Their brains are less able to adapt to
| their current circumstances and they're stuck in negative
| thought patterns. SSRIs help increase the brain's ability
| to grow new connections and help the brain adapt, which
| helps you get out of negative thought patterns.
|
| If you're interested enough to watch a whole talk about
| this (you can jump to around 26 minutes):
| https://www.youtube.com/watch?v=k2AdebIbx5Y
| loceng wrote:
| Leading also to an increase in rate of suicide compared
| to placebo, and arguably increased homicide as well; guns
| being the misdirection narrative.
|
| Edit to add: Downvotes even though in 2015 the FDA
| required "black box" suicide warnings on SSRIs because
| what I'm saying is true?
| snek_case wrote:
| There's this narrative going around that antidepressants
| bad because medication bad, psychiatric industry evil,
| modern medicine bad, yadda yadda yadda.
|
| The problem is, everybody's brain chemistry is unique and
| different, because our genetics are different. Some
| antidepressants work for some people and not others. I've
| personally tried 5 of them. Only one of them worked on
| me, and it had some unfortunate side-effects (messed with
| my sleep). My ex-girlfriend used a different
| antidepressant (Zoloft). Personally, I've tried Zoloft
| and all it did was make me sleepy all the time, but I've
| found Lexapro was quite effective and useful for getting
| my life back on track.
|
| The way efficacy studies are done right now is, we
| measure the average effect on a group of people. That's
| doesn't really make sense when you think that everyone's
| genetics are unique and the antidepressant could be
| making some people better and some people worse, right?
| Maybe half the group feels better, but a quarter of the
| group becomes suicidal. Then on average, you see scores
| going up, you see the drug is beneficial on average... It
| would be kind of like giving everyone in a group a
| prescription for eyeglasses, all with the same
| prescription, and measuring that on average, participants
| can read better with the eyeglasses than not.
|
| In some ways, modern medicine is still very primitive.
| Flooding the whole brain with a chemical and hoping that
| it interacts with the right receptors and has a
| beneficial effect without too many side effects if you
| have the right genetics is very primitive. It's the best
| we have right now though, and antidepressants in general
| are probably more helpful than not, but yes, people
| SHOULD be aware that they might very well not work on
| them.
| heavyset_go wrote:
| I've written about this in the past a lot[1], but 5HT2C
| activation is the primary cause of suicidal ideation when
| starting SSRIs. Once 5HT2C is downregulated after a few
| weeks, the feelings and akathisia caused by 5HT2C
| activation dissipate, as does suicidal ideation.
|
| 5HT2C activation can be very, very uncomfortable, and can
| exacerbate depression, anxiety and suicidal thoughts.
| Downregulation results in an equilibrium where those
| feelings and symptoms are relieved over time, however.
|
| [1] https://hn.algolia.com/?dateRange=all&page=0&prefix=t
| rue&que...
| Silverback_VII wrote:
| What about very cheap and nonetheless effective "treatments"
| like exercise,sleep hygiene, magnesium, zinc, fish oil, onion,
| galic, saffron and even simply eating edible non psychoactive
| mushrooms? all these have been associated with a reduction in
| depressive symptoms.
|
| but obviously nobody can make a fortune with these simple
| advices.
| okaram wrote:
| 1. Most of those are not actual treatment, and the
| association is spurious.
|
| 2. Tons of depressed people are still depressed even though
| they exercise, eat well and sleep.
|
| 3. Tons of people are making fortunes peddling these and
| similar 'cures' to everything :)
| 6stringmerc wrote:
| This is true but it's modeled after behaviors in the big
| picture - you just described a lot of effort and commitment
| versus taking a pill, maybe doing therapy / counseling once a
| week or two, and just living life. I'm getting back into
| fitness routine and it takes time, effort, and money that
| typically aren't subsidized by the corporate gigs I've
| worked.
| nonrandomstring wrote:
| > you just described a lot of effort and commitment versus
| taking a pill
|
| Funny but I have come to regard the "effort and commitment"
| as part of the recovery mechanism. Causal or concomitant, I
| have no idea, let's just say 'linked'.
|
| By the same token I have come to regard "convenience" as,
| if not a great evil, some kind of joker/trickster that
| lures us down a dark path.
| j-bos wrote:
| This strikes me so much. Exercise is a proven health
| booster and yet health insurance doesn't cover gym
| memberships or exercise equipment. Why is that?
| michaelmarkell wrote:
| Treatments like exercise also have high variance -
| depending on the circumstance and how diligently you
| implement it, it may have no effect, a big effect, or
| even cause injury in the worst case.
|
| Insurance likes low variance outcomes because they're
| easier to model accurately
| msgilligan wrote:
| I'm not in the insurance industry and have no idea what
| the actual reason is.
|
| And I don't know what the statistics are, but a
| significant percentage of people with gym memberships
| rarely go to the gym. I suspect the percentage of people
| with free (i.e. payed for by insurance) insurance who
| rarely go would be much higher.
| msgilligan wrote:
| Further thought: Maybe insurance companies could pay,
| reimburse, or reduce rates for those who can reliably
| prove they are exercising.
| jan_Inkepa wrote:
| My insurance offers reduction if you pass a basic health
| check each year. It's kinda nice but also sets up a
| slightly adversarial relationship with my doctor, which I
| don't like.
| heavyset_go wrote:
| I've seen plans that subsidize gym memberships.
| parineum wrote:
| >health insurance doesn't cover gym memberships or
| exercise equipment
|
| Because neither of those things are necessary to
| exercise.
|
| I bet if you asked your GP for some body weight exercises
| you could do at home he'd happily provide some for you
| and insurance would cover the visit.
| guerrilla wrote:
| As I've argued before, if someone can diet and exercise then
| they aren't very depressed, so most of that advice is useless
| and why people work on drugs since taking a pill daily is
| much easier to accomplish for someone who can't get out of
| bed or find a reason to do anything at all.
| Silverback_VII wrote:
| Magnesium, zinc and fish oil supplements don't seem very
| hard to take. And what about a cold shower of 2 min each
| day? also easy to implement without much effort if one is
| willing to suffer a little bit.
| guerrilla wrote:
| > Magnesium, zinc and fish oil supplements don't seem
| very hard to take.
|
| Obviously people do that and it works for a handful, but
| rather ineffective in general.
|
| > willing to suffer a little bit.
|
| Yeah, no. That's definitely not something a seriously
| depressed person can do, I say as someone doing that now.
| People who suggest these things are completely out of
| touch with what depression means. You'd be lucky if they
| were taking shows _at all_.
| Silverback_VII wrote:
| >but rather ineffective in general.
|
| Study with 22 people with major depression: "Treatment
| with both omega-3s was associated with a significant
| improvement in depression, with an average 64% drop in
| symptoms for the EPA group and 71% in the DHA group."
|
| https://www.webmd.com/depression/news/20210618/fish-oil-
| supp....
| guerrilla wrote:
| > Study with 22 people
|
| i.e. worthless. DHA is being studied and has massive
| effects on inflammation but the science is definitely not
| there for depression. You need to adjust your
| epistemology if you are making decisions based on tiny
| studies like that.
| hallway_monitor wrote:
| Seems like 22 subjects is better than zero. One is better
| than zero so if it worked for one person that's probably
| worth trying for a second. I hate how people act like you
| can't try anything until it has had a study with
| thousands of people over years. Sure, that increases
| confidence but in most cases the study doesn't invent a
| treatment, it just adds trust in the effectiveness.
| guerrilla wrote:
| No, that's not how it works at all or else we should also
| recommend fairy crystals at the same time. Anyway, people
| _do_ try it. That 's the point. It's common practice and
| it's known to not work for most people with severe
| depression. It's only a matter of time that we have
| strong meta-meta studies showing that definitively. For
| now, here's a Cochrane meta-study that reviews 35 studies
| [1].
|
| 1. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651
| 858.CD...
| Silverback_VII wrote:
| >i.e. worthless
|
| Certainly not and considering the almost non-existent
| side effects, it is at least worth a try since it looks
| very promising. You are right that it is a tiny study but
| it doesn't mean that it has no value.
|
| I have to say that I know people like you very well, I
| almost can hear the "go see a therapist and take your
| meds" or better "don't try and certainly don't think you
| can solve this on your own". A positive force first and
| foremost acknowledge people's potential and doesn't put
| roadblocks everywhere.
| lm28469 wrote:
| But that's the thing, a lot, if not the majority, of people
| getting prescribed these awful drugs aren't depressed, they
| just have a shitty life, a shitty job, no hygiene, no
| nutritional education, are going through a hard place, etc.
|
| Giving pills to these people is a crime
| guerrilla wrote:
| Why do you think you know this? What do you base it on?
| heavyset_go wrote:
| It's not your place to decide if the quality of life
| improvements others experience with medication are worth
| it or not. Sometimes life gives people circumstances that
| are hard to cope with, and sometimes medication helps
| them cope.
| xen2xen1 wrote:
| I'll take it in good faith you're not just being a nasty
| troll, but that's a LOT of work for someone who is depressed,
| enough to be a non-starter. In reality drugs should probably
| be seen as a way to start better life habits. The benefits of
| hose habits are real, but getting there is a lot.
| BurningFrog wrote:
| Those things can often work, but the depressed mind is often
| 100% convinced that there is no way out. Nothing you do can
| make a difference.
|
| Intellectually you can agree that all those things are worth
| doing.
|
| But some deep calculating part of your mind will see that
| between hard work that will not help, and doing nothing which
| will also not help, the latter is the rational choice.
| feet wrote:
| There are other serotonin receptors at which psychedelics are
| active besides 2a
| swayvil wrote:
| Common cardboard tube generates all the joys of astronomy without
| magnifying any heavenly bodies.
| isoprophlex wrote:
| Combining 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 wrote:
| Very good! :D The whole endeavour does have a rather an air of
| "keep the worker drones functional and content".
| isoprophlex wrote:
| As 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"
| kaoD wrote:
| I'm curious about this and someone here might know. Why do they
| bind to the 5HT2a receptor yet not cause trips?
|
| I always assumed the difference in strength between, say, DMT
| and psilocybin was because DMT was "more agonist" (pardon the
| layman terms).
|
| Do these molecules intrinsically not cause trips, or is this
| more akin to microdosing? Would a higher dose of these
| molecules cause a trip?
| ekianjo wrote:
| Because not just one receptor is involved
| valec wrote:
| different ligands can bind to the same receptor in different
| ways and cause different signaling cascades. look up "biased
| agonism"
| tux3 wrote:
| It's fascinating how Nature effortlessly creates these
| leaky abstractions, completely opposite to how we design
| systems, and makes good use of the constant layering
| violations where we would see unmaintainable code that we
| can't wrap our heads around.
|
| When we design signaling mechanism, they deal with the
| layer below while presenting a simpler digital interface to
| the layer above. Your Ethernet PHY has to care about
| electrical details, but to the IP stack it's just a stream
| and sink of bytes. No weird side-band edge cases effects,
| like if the IP stack could affect DC balance by changing
| the mix of 1s and 0s it sends out.
|
| But those G protein-coupled receptors -- or whatever it is
| -- it seems like if you don't want to miss important side-
| band edge case signals, you really have to model them as
| this 3D structure that threads through the membrane 7
| times, that you can jiggle on one side to change the shape
| it has on the other side.
|
| The receptor-agonist abstraction makes total sense from a
| human perspective (and it's a good and useful model), but
| at the end of the day the Wikipedia lists nine different
| types (partial, super-, inverse, co-, irreversible, biased,
| ..) of agonists, multiple of which can apparently apply to
| a single ligand ("can concurrently behave as agonist _and_
| antagonists at the same receptor, depending on effector
| pathways or tissue type").
|
| Nature seems to have absolutely no preference for clean
| abstractions, and I don't know how to feel about that, but
| it's fascinating to me. Maybe my horrible code is actually
| universally optimal under a non-human optimizer =)
|
| Or maybe it's just intrinsically hard to make clean
| abstraction out of chemistry? I wonder if it _would_ be
| beneficial for a large system like the body to be built out
| of cleaner (less powerful) abstractions that don't expose
| all their internal details, but maybe stochastic DNA
| mutations with natural selection isn't a good enough
| optimizer to find that place in humanity genomespace?
|
| Death is so out of style compared to Adam and SGD.
| stackbutterflow wrote:
| I think that's called five-billion-years-of-trial-and-
| error driven development.
| heavyset_go wrote:
| I disagree. We build happy paths for our designs, but
| there are plenty of vectors for attack and modification
| outside of things like exposed APIs and other "contracts"
| we bake into systems. You see this all the time with
| viruses, jailbreaks, virtualization, and hardware
| hacking.
|
| If we had instrumentation that allowed us to poke and
| prod at microscopic integrated circuits, there would be a
| lot of attack vectors exposed there, too.
|
| After all, our abstractions are built upon implementation
| details, and if you can play with the implementation
| itself, those abstractions and contracts are up for grabs
| when it comes to modifications.
| magicalhippo wrote:
| > like if the IP stack could affect DC balance by
| changing the mix of 1s and 0s it sends out
|
| For those that don't know, avoiding DC bias due to the
| distribution of 0's and '1 in the transmitted data is a
| real concern and something that's engineered into many
| transmission protocols. A common choice is a form of
| paired disparity code[1] like 8b/10b[2], found in HDMI,
| DisplayPort and PCIe 1.0/2.0, and variations[3] like
| 128b/130b for PCIe 3.0 or 128b/132b for USB 3.x.
|
| [1]: https://en.wikipedia.org/wiki/Paired_disparity_code
|
| [2], https://en.wikipedia.org/wiki/8b/10b_encoding
|
| [3]: https://en.wikipedia.org/wiki/64b/66b_encoding#Techn
| ologies_...
| kortex wrote:
| > No weird side-band edge cases effects, like if the IP
| stack could affect DC balance by changing the mix of 1s
| and 0s it sends out.
|
| As someone who started in chemistry and moved into
| computers, this made me laugh out loud hard. It's an
| absurd and absolutely perfect analogy for the weird shit
| biology does all the time.
|
| I think it is intrinsically hard to make clean
| abstractions out of chemistry. Biochemistry even more so.
| Chemical synthesis in the lab is all about the loop of:
| react under ideal conditions, work up, extract, purify,
| repeat. Biochemistry is just...fancy soup.
|
| You get some barrier, especially for really nasty stuff,
| like peroxisomes, but there is just tons of diffusion.
| Especially with neurochem, where usually drugs have to be
| the right lipophilicity to cross the BBB but also
| specific to targets.
| nonrandomstring wrote:
| > like if the IP stack could affect DC balance by
| changing the mix of 1s and 0s it sends out.
|
| Brilliant! I'm going to steal that for a datacoms lecture
| to hammer home 'layers'.
| gpcr1949 wrote:
| (I have a background in organic chemistry as well)
|
| I somewhat disagree with this. Measuring chemical similarity is
| notoriously difficult, see these two interesting blog posts
| from a cheminformatic angle [0][1]. The molecules are not only
| pharmacologically similar but even chemically at least somewhat
| similar, perhaps in the same way a dog has much more
| similarities with a flying squirrel than with, let's say a
| church. I would argue the main active molecule [2] is
| relatively similar to LSD (compared to other well known
| psychedelics) due the presence of the tetrahydropyridine unit,
| which is also present in LSD, albeit connected to the 3
| position of the indole in a different way. Also, there is a
| pharmaco*phor*ic similarity: positively charged N and 5-6 fused
| aromatic ring oriented in the same way with some degree of
| rigidity (though you could argue this is just a roundabout way
| to bin it in a category of 5ht2a binders). So in this way, I
| feel that it has something like an LSD-based design philosophy
| to it.
|
| Quantitatively, making use of one of the most common similarity
| metrics, the Tanimoto similarity of ECFP4 fingerprints, the
| similarities to LSD, psilocin, DMT and mescaline are
| respectively 0.17,0.15,0.18 and 0.07. In other words, the
| similarity is low to all compounds and the indole derivatives
| are about equally far removed from the compound from TFA,
| although a bit closer than mescaline. The numbers probably
| rather follow your line of reasoning.
|
| Finally, I'd also like to remark that I consider the fact they
| generated quite novel chemical matter a plus: most of the
| people working on generating new 5HT2A agonists are currently
| using quite conservative classic SAR approaches, for example
| creating constrained (e.g. Lophora's azetidines) or
| deconstructed versions (e.g. Delix's ring opened LSD variants
| and ibogaine analogs) of better known compounds, or even just
| prodrugs of known compounds (Field trip's FT104 is a 4-HO-DIPT
| prodrug). This will also make it easier for them to fight
| patent challenges if this series of compounds will lead to a
| clinical candidate.
|
| [0]
| http://www.dalkescientific.com/writings/diary/archive/2020/0...
|
| [1]
| http://www.dalkescientific.com/writings/diary/archive/2020/0...
|
| [2] The SMILES string of molecule 69 from the paper, which is
| the one from the cryo EM structure:
| `C[C@@H]1C=C(c2c[nH]c3ncccc23)CNC1`
| carrychains wrote:
| Your preference is unnecessarily pedantic and logically reduces
| in specificity to the exact phrasing that peeves you.
| isoprophlex wrote:
| Definitely!
| cwkoss wrote:
| The article was written from the perspective of a 5HT2a
| receptor
| amelius wrote:
| > These molecules look nothing like LSD!
|
| Who said "look"?
|
| You're being pedantic about your own interpretation.
| 9991 wrote:
| They didn't say "LSD-shaped". There are lots of ways to be
| "-like", and one is acting in a similar manner. Your training
| is blinding your thinking.
| bfung wrote:
| Haha, I feel ya -
|
| As a computer/tech person, when business people say real-time,
| or AI (when they just want simple statistics) I get the same
| annoyance and react with the pedantism (you don't need REAL-
| time, just sub-second latency).
|
| But for the non-experts and layfolk, many KNOW what LSD does,
| but none of us know what 5H... yup. =)
| erikpukinskis wrote:
| Simple statistics can be AI. AI just stands for Artificial
| Intelligence. An if-statement can be AI.
|
| Are you thinking of machine learning?
| throw827474737 wrote:
| Being pedantic (and a smartass) the same, "real-time"
| original definition is that some calculation/reaction of the
| system is guaruanteed to be always bounded and within the
| system rqequirements (usually for it not to fail). So
| depending in the use case and application, real-time can be
| sub-second, or even seconds/minutes.
|
| E.g. if the instagram folks require likes to happen in real-
| time for all users around the world that is fine to be within
| seconds, but a safety critical application in a car must
| respond within milliseconds.. "you don't need REAL-time, just
| sub-second latency" in general does not make much sense,
| sounds more like this application real-time requirements just
| lie in the sub-second resolution region?!
| SirRuthven wrote:
| > react with the pedantism...
|
| Some pedant has to say it: shouldn't that be "pedantry"?
| bfung wrote:
| LOL - true, thx.
| xdfgh1112 wrote:
| "LSD-like" can mean "acts like" just as well as "looks like",
| so you're being hyperpedantic.
| snek_case wrote:
| Actually, I don't think he's being pedantic at all. LSD binds
| to a wide array of proteins and receptors in the brain
| (including dopamine receptors) and the binding profile of
| this substance is most likely very different from that of
| LSD. Likely to be much more specific to 5HT2a, closer to
| psilocybin than LSD. IMO they just said "LSD-like" because it
| would make a nice headline.
|
| See this diagram on wikipedia for LSD binding affinities
| (lower means more affinity): https://en.wikipedia.org/wiki/Ly
| sergic_acid_diethylamide#/me...
| realce wrote:
| Scientists are excited about a new hotdog-like food that
| prevents depression without the meat: cake!
| ekianjo wrote:
| or alternatively the headline is just super clickbaity by
| adding LSD when it was not needed.
| alehlopeh wrote:
| So using LSD in a title makes it clickbaity? Come on,
| that's ridiculous. Don't squeeze the life from that term by
| applying it to anything you don't like.
| Retric wrote:
| The comparison to LSD is sensationalized and misleading
| making it clickbait even if the link is not deceptive.
| https://en.wikipedia.org/wiki/Clickbait
| ekianjo wrote:
| > So using LSD in a title makes it clickbaity
|
| Yes alluding to something illegal makes it clickbaity.
| quietbritishjim wrote:
| I guess it's like the question of: could you say an SSD is
| "hard drive-like" even though it works totally differently? I
| would say you validly could.
| boloust wrote:
| While you could say a drug is "LSD-like" because one of the
| many receptors it targets is also targeted by LSD, that
| would be more akin to saying a keyboard is "hard-drive-
| like" because they both plug into a computer.
|
| Biology is extremely complex, and even drugs that have
| similar receptor binding profiles can have very different
| effects.
|
| Most drugs will have action across a wide range of
| receptors. There are a multitude of drugs that target the
| 5-HT2A receptor, including the most common antidepressants
| and antipsychotics, for example.
| jcynix wrote:
| Hmm, depends on the receptor, where the molecule or the
| hard drive docks to?
|
| So USB hard drives might be keyboard like (for USB
| keyboards), but hard drives which dock to the SATA
| connector aren't ...
|
| Anyway, such comparisons sometimes limp and sometimes
| don't have any legs at all.
| doctor_eval wrote:
| Well, they are both mammals, so at some level a dog actually
| _is_ squirrel-like.
| erikpukinskis wrote:
| A dog is extremely squirrel-like. Compared to a fish or a
| fungus or a sequoia a squirrel and dog are basically the
| same.
| lifeisstillgood wrote:
| "This is absolutely terribly pedantic and..."
|
| Don't worry. You're in the right place :-)
| motbus3 wrote:
| Don't worry Y in Ycombinator is for pedantic XD
| arjvik wrote:
| Actually if we're being pedantic, it's capitalized as
| YCombinator.
| kn8 wrote:
| Y Combinator ;)
| panxyh wrote:
| But Why Combinator?
| chalst wrote:
| Fixpoints are too powerful a concept to be added safely to
| any but the most pedantic minds.
| tpm wrote:
| Or 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 wrote:
| Or perhaps they don't, that's why you get some effects and
| not others (as desired)?
| tpm wrote:
| The 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 wrote:
| Eh, 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.
| mseidl wrote:
| Maybe a flying squirrel compared to a flying dog would be
| better?
| sva_ wrote:
| Where can you see these molecules?
|
| I wonder how they look like compared to serotonin and some
| tryptamines
|
| https://i0.wp.com/sitn.hms.harvard.edu/wp-content/uploads/20...
| c7DJTLrn wrote:
| Pharma 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.
| [deleted]
| jasonhansel wrote:
| I 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.
| zwkrt wrote:
| it 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 wrote:
| That's literally what they did. Started with their
| knowledge of LSD and went from there using a similar
| chemical.
| jasonhansel wrote:
| Personally, I wouldn't want to take a medication that would
| permanently change my political views.
|
| I seriously doubt there's a drug that reliably makes your
| political opinions more correct and truthful, but I'm sure
| that there are drugs that impair your judgment so much that
| you cannot tell you are impaired. So I would suspect that
| LSD falls into the latter category, not the former.
|
| If the changes are irreversible, I certainly wouldn't want
| to take that risk.
| mmsnberbar66 wrote:
| I would like to hear why this person is being downvoted
| 5co wrote:
| benevol wrote:
| This sounds like "Nutella - without the chocolate flavor".
|
| But making big pharma insanely rich - once again.
| avidiax wrote:
| Yes. 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.
| simonebrunozzi wrote:
| Typo in the title: depession -> depRession
| pfkurtz wrote:
| LSD:
|
| 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 wrote:
| > 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 wrote:
| 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.
| Synaesthesia wrote:
| The effects used to be classified as a "model psychosis" in the
| 1950's by psychiatrists. That classification was simply
| dismissed by the government as it implied LSD had useful
| research properties: allowing individuals to experience the
| effects of mental illness for 8 hours and then sobering up.
|
| The government was adamant that LSD and psychedelics had to
| have no legitimate medical or scientific value, and they had to
| be banned. To be fair they had escaped controlled use and were
| being used as "party drugs".
|
| But anyway, it sure can be a hella scary and strange
| experience, and not always pleasant. Handle with care.
| jokowueu wrote:
| I have tried most of these non psychadelic analogs
|
| They don't do anything such as iso-dmt for example
| acchow wrote:
| Uhhh, why would you do this? You can learn so much during a trip
| to solve some of the fundamental issues/trauma behind your
| depression.
| scaramanga wrote:
| As someone who has enjoyed tripping, and is generally positive
| about the benefits of the experience, there are a number of
| reasons that spring to mind.
|
| You may not have the luxury of time for that. Or even a save
| place to do it. What if you are in a vulnerable and insecure
| housing situation? Living on the streets? etc.
|
| You may not feel ready for that. For example if you feel
| anxious and avoidant about having a raw and truthful
| "conversation" with your self because of what you might find
| there, then it probably means that it isn't a great idea.
|
| Perhaps you don't have the access to talk therapy, supportive
| friends and family, and the like, to trip-sit you, or to
| discuss and process your experiences with after the trip.
|
| I don't think it would be fair to take options off the table
| because you (we) think one is better. I mean, why drink a can
| of PBR, when fine whiskey exists? Why masturbate when you can
| have sex, which is clearly superior? The fact that one
| proposition exists does not take the other one away.
|
| That said, with the way the laws are, one proposition IS taken
| away by prohibition so really it's a question of why put one of
| them through FDA approval to enter widespread usage while the
| other one sits in a weird limbo where the vast majority of
| those seeking it are forced in to an illicit drug trade which
| endangers them. But that question has a lot more to do with the
| moral and political failings of our society.
| fsloth wrote:
| Perhaps 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 wrote:
| It 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 wrote:
| I 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.
| tsukurimashou wrote:
| LSD isn't for daily routine unless you microdose (and even
| then you don't take it everyday) a trip is more like 8-12h
| yieldcrv wrote:
| 4, thats cute
| int_19h wrote:
| It's not an either-or. You can't be tripping all the time,
| either.
| yieldcrv wrote:
| Not everyone has 14 hours of trip time and another half a day
| of shock
|
| With the risk of lifelong HPPD
| jasonhansel wrote:
| Not everybody wants to hallucinate.
| mizaru wrote:
| *in mice
| yellow_lead wrote:
| Can anyone tell me the standard for determining if a mouse is
| depressed? Or anxious? Just curious
| Synaesthesia wrote:
| Or 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 wrote:
| https://en.m.wikipedia.org/wiki/Head-twitch_response
| YorkshireSeason wrote:
| What scientifically credible, i.e. at least stably
| reproducible, connection does the head twitch response in
| mice have to do with depression in humans?
| YorkshireSeason wrote:
| There is nothing credible.
|
| This research direction is an example of _" cargo-cult
| science"_ [1] as Feynman understands the term. (That does not
| mean that the hypothesis is necessarily wrong.) There is a
| reason for "in mice" being an internet meme [2].
|
| [1] https://calteches.library.caltech.edu/51/2/CargoCult.htm
|
| [2] https://nitter.eu/justsaysinmice
| knodi wrote:
| Does 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?
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