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Medicine Science

Why An LSD High Lasts For So Long (pbs.org) 138

Lysergic acid diethylamide (LSD) has been credited, in part, for the creation of the iPhone, the polymerase chain reaction, as well as some pretty abstract artwork. Since the drug is classified as a Schedule 1 substance in the U.S., it's been more difficult for scientists to legally study the drug and learn about how it affects the brain. Therefore, when a study (or two) is published it makes the findings all the more fascinating. Two studies were published last week (one in Current Biology, the other in Cell) that examine how LSD produces such diverse effects and why the drug takes so long to wear off. The Scientist reports the findings from for the first study: For the Current Biology study, 21 volunteers were given a placebo, a small dose of LSD alone, or the same dose of LSD but with kentaserin, a serotonin 2A antagonist. Study participants who took the kentaserin reported virtually the same experiences as those who took the placebo, and fMRI brain scans confirmed similar brain activities across participants in both groups. The serotonin 2A antagonist "blocked all the effects of LSD, so it was like if people didn't take any drugs," coauthor Katrin Preller, neuroscientist at the Zurich University Hospital in Switzerland told The Verge. "All the typical symptoms -- hallucinations, everything -- were gone." As for why an LSD high lasts for so long, Angus Chen has written an in-depth report on PBS Newshour about the findings from the study published in Cell: LSD and other psychoactive drugs work by binding to specialized proteins called receptors on the surfaces of neural cells. On the receptor protein is a sculpted "pocket," into which molecules with the right shape can fit and thus stick to the cell, where they initiate changes in the brain. But different substances can often fit into the same receptor. Many receptors that bind LSD and DMT, for example, also fit the natural chemical messenger serotonin -- which is produced in the body and helps regulate mood. Figuring out how each drug interacts with the same receptor in a different way is key to understanding why an LSD trip lasts all day whereas an experience with extracted DMT is often over in 15 minutes or less. By freezing an LSD molecule bound to a single brain cell receptor as a crystal in a lab, researchers were able to get a 3-D x-ray image of the drug and the protein locked together. The image showed Bryan Rother, a pharmacologist at the University of North Carolina at Chapel Hill and senior author on the paper, and his co-authors something strange about the way LSD fit inside this receptor. Drugs typically come and go from receptor proteins like ships pulling in and out of a port. But when an LSD molecule lands on the receptor, the molecule snags onto a portion of the protein and folds it over itself as the molecule binds to the receptor. LSD seems to stimulate the receptor for the entire time it is trapped underneath the protein "lid," Roth says. Proteins are in constant motion, so he thinks the lid eventually flops open, allowing the drug to fly out and the effects to wear off. But the team ran computer models that suggest it could take hours for that to happen. Until then, the trip goes on.
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Why An LSD High Lasts For So Long

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  • But taken orally there are no effects without an MAOI, and with one it too lasts hours (though not as long as LSD).

  • Never liked acid (Score:2, Interesting)

    by Anonymous Coward

    Never liked acid. While other drugs tend to amplify or enhance mind states that you normally experience to a lesser degree without drugs, acid always made me feel like my brain was doing shit it fundamentally shouldn't be doing at all, not really related to any normal mind state. If I had to do psychedelics again, I'd stick to mushrooms, I always found they had more euphoric effects to go with the trippy shit, generally a much more fun experience. And yeah, acid did tend to go on a bit too long.

    • by kelemvor4 ( 1980226 ) on Tuesday January 31, 2017 @01:23PM (#53775073)

      Never liked acid. While other drugs tend to amplify or enhance mind states that you normally experience to a lesser degree without drugs, acid always made me feel like my brain was doing shit it fundamentally shouldn't be doing at all, not really related to any normal mind state. If I had to do psychedelics again, I'd stick to mushrooms, I always found they had more euphoric effects to go with the trippy shit, generally a much more fun experience. And yeah, acid did tend to go on a bit too long.

      Forget that, last time I did mushrooms they grew eyes and started walking towards me. Later, I discovered that if I jumped up and smashed my head into bricks that sometimes a "good" mushroom would come out and give me the power to destroy they eyeballed mushrooms. From that point on, only falling into a bottomless pit or walking into the bad mushroom's eyes would be harmful to me. Eventually I climbed a flagpole and moved on.

  • by Dins ( 2538550 ) on Tuesday January 31, 2017 @09:20AM (#53773241)
    I know scientific method and all that, but I think it would be relatively easy to determine whether you were given the placebo or the actual LSD...
    • There were three groups; placebo , LSD, LSD+2A_antagonist. The interesting thing was that the placebo group AND the LSD+2A_antagonist group had the same outcomes. Seems serotonin antagonists are very effective at blocking the same receptors used for LSD. I'm guessing their will be more studies to see if you could give a serotonin 2A antagonist to someone to make them come down from LSD.
      • Re:Placebo? (Score:5, Interesting)

        by Opportunist ( 166417 ) on Tuesday January 31, 2017 @09:39AM (#53773319)

        5HT-2A antagonists aren't really something you should hand out like candy. Those receptors are all over your body, not just your brain, and they deal with a LOT of body functions. Particularly blood clotting.

        Using it as a "safety switch" to cancel horror trips is something I would not recommend!

        • Quetiapine is reasonably safe, & quite effective for the purposes of aborting a bad trip.
        • Try L-Theanine, 200-2,000mg+ (you can mix the pure powder into tea like peppermint tea). It's a harmless amino acid found naturally in green tea in small amounts, and aborts trips via another way besides 5ht2a antagonism. I believe it just quiets the excitation (glutamate) of the brain. I've tested it personally and with other people who all agree it works, and is the least prone to side effects of any other medication administered for such purposes. I was actually trying to test out the combination on some

      • Re:Placebo? (Score:5, Insightful)

        by budgenator ( 254554 ) on Tuesday January 31, 2017 @10:19AM (#53773535) Journal

        The article says the effect lasts so long because the receptor lock on to the LSD molecule. I doubt an antagonist would work because they generally block the receptor without activating them but in this case the sites are activated already and the LSD is locked on. The antagonist can't replace the LSD molecule. At best they can keep the LSD from activating additional receptors.

        It looks like with LSD, once you're high, you just have too ride it out.

        • by bodog ( 231448 )

          try it before you make an unfounded proposition :)

        • by Lehk228 ( 705449 )
          possibly useful for when you take some acid, then half an hour take a bunch more because "it's not working man i think it wa s a dud" then "woah oh shit there it goes"
          • Well they could try, but I still suspect that when you're at the "woah oh shit there it goes" stage, you better be planning on being there for a few hours. There is stuff that gets you tripping for a half hour or so but acid isn't one of them.

    • by GuB-42 ( 2483988 )

      It depends on the dosage.
      With very small doses the effects are not that strong. It is more about slightly altered perception than full-blown hallucinations. Colors may become more vivid, you notice small things that you haven't noticed before, etc... You can get the same effects with a placebo. Even experienced trippers can be fooled, at least to some extent.
      And the summary explicitly mentioned small doses.

      Of course, at high doses, there is no way you are going to say you had a placebo if you were given the

    • Simple. Because you didn't get the placebo or the 2A antagonist before reading the summary.

      You know it's a bad trip when the summary uses the term DMT, twicefully, but does not explanify what it means. Not that I am one of those people who would read beyond the subject line. Please don't think less of me or judge me. I'm the same person I was before this secret became generally known. There may be some kind of cure or electroshock therapy for those of us who read more than the subject title.
  • The first 4 hours were fun, but after that it just got kind of tedious.

    There were always rumors it was jacked up with speed or strychnine, but I never thought you could fit enough of either in blotter for that to be true.

    • by Dins ( 2538550 )
      DMT is nice and quick (15-30 minutes I hear). I've never done it, but wouldn't mind trying it.
      • Re: (Score:3, Interesting)

        by Anonymous Coward

        I've heard the same. I know somebody in town who's invited me to come give it a try some time when his daughter isn't home but I've yet to take him up on it. The nice things about LSD over mushrooms are price, longer trip, and (more) predictable onset. I can't think of any others. Mushrooms cost more, but aren't too tricky to grow - Plus I think growing them yourself adds something to the experience. The trip with shrooms is only 2/3 as long (or so), but coming down after that duration is usually welcome an

    • by Anonymous Coward

      Alexander Shulgin synthesized a slight variation of LSD called AL-LAD.
      https://erowid.org/library/boo... [erowid.org]

      It lasts about half as long as LSD.
      At low doses, AL-LAD is less cerebral, more visual than LSD.
      At high doses, the effects get more similar, nearly identical.

      I can fully recommend it and haven't taken any apparent damage after 20+ AL-LAD trips. ... or if you're more naturally inclined, you could just eat magic mushrooms, which also act much shorter than LSD.
      Personally I find mushrooms to be much more diffic

    • by tylersoze ( 789256 ) on Tuesday January 31, 2017 @09:57AM (#53773407)

      Yeah mushrooms are preferable for just a nice time. LSD for profound mind altering experiences that you need to plan a whole block of time for, at least it was for me. I never understand these people that have bad trips or see things that aren't there (as opposed to just simple visual effects) It really is all about set and setting as they say (and making sure you know exactly what your ingesting). You can absolutely take these drugs responsibly, like everything else it's the dumbasses that ruin it for everybody.

      • I always assumed that the "bad trip" was really about loss of control. Some people can't seem to handle that.

      • by swb ( 14022 )

        Mushrooms are lower impact, but that works against them, too, with shorter and less intense peak effects, and though shorter, they had a similar "long tail" effect where you just felt kind of hyper but without the benefits of peak effect.

        They required dedicating less time, but I never found the difference completely compelling.

        • I dunno. With acid I always ended up sick of it towards the end - the last few hours being a drag when I just wished it was over. Mushrooms on the other hand, I always preferred the time when the visuals had pretty much gone but the world still felt sparkly and nice. More euphoric. That's when me and the wife would head off into town. Maybe that's just different occasions and expectations though.

      • by Anonymous Coward
        I've done a fair bit of acid, up to 1mg a few times. My hands have turned into Julia fractals and all sorts of other crazy stuff - I love that kind of thing... Never had a bad trip though.

        I wont give my partner acid any more as he goes crazy, complete dissociation with only a couple of tabs. Had to hold him to the bed for 4 hours as he kept wanting to go outside and fight random made-up situations. Not really a bad trip though because he cant really remember what happened.

        Once I took AMT, and figured it
      • by Anonymous Coward
        Really +5 for anyone who has a bad trip is a dumbass? You guys will learn the hard way if you think that's how it works.
        • I meant dumbasses in the sense of not using these kinds of drugs in a responsible manner and then freaking out, dying or whatever giving more fuel to the anti drug crowd. I personally would never allow myself to be under the influence of anything in public or in an environment I was not comfortable in or I had to be responsible for anyone but myself.

    • > The first 4 hours were fun, but after that it just got kind of tedious.

      WRONG DRUG.

      If you experience an erection lasting more than four hours see your doctor immediately, or go to a party.
    • The first 4 hours were fun, but after that it just got kind of tedious.

      There were always rumors it was jacked up with speed or strychnine, but I never thought you could fit enough of either in blotter for that to be true.

      While the strychnine thing was a myth (which was understood by the time I was into psychedelics), there are at least a handful of other active substances that can fit on a square of blotter and produce qualitatively similar effects. Some other psychedelics are active at sub-miligram dosages and have been around for decades, and some of them are somewhat commonly available now. They may be sold surreptitiously as "acid" or more openly and correctly named. LSD experiences are notoriously variable and unpredic

  • That molecule gets trapped in there, feeding crazy signals to the brain, until it just happens to fall out.

    • Imagine if a small but statistically significant number of those molecules stay trapped in there for a very long time. And even if they come lose, they get trapped in another receptor and fold it over before being removed from the body.
      • by GuB-42 ( 2483988 )

        I think we can model this as an exponential decay.
        As in : the molecule has a 50% of coming out loose and being eliminated every 6 hours.

        They sure, some molecules will stay in for much longer than the duration of the trip but after a few days, nothing significant will be left, and after maybe 2 weeks, there won't be a single molecule left in your brain.
        There are mentions about some kind of "afterglow" lasting a couple of days after a good trip and sometimes subsequent "flashbacks". However, I think they are

    • Or until the receptor sites are hopelessly fatigued and you crash into a two day hang-over.

  • Lysergic acid diethylamide (LSD) has been credited, in part, for the creation of the iPhone, the polymerase chain reaction, as well as some pretty abstract artwork.

    Don't forget the Beatles song [google.com]. Incidentally don't talk about flower power. The substance is a fungus.

  • by MrKaos ( 858439 ) on Tuesday January 31, 2017 @09:43AM (#53773341) Journal

    Animals and insects eat psychedelic drugs in the wild - just to get wasted. Deers do it, so do some flies - and they repeat the experience, so it is not an accident.

    It says a lot for how long the psychedelic experience has been around consciousness, that it is not unique to humans.

  • I can fly! I can fly! I can fly! Splatt!

  • Maybe someone who knows more biochemistry can answer. Could you give kentaserin to someone having a bad trip to bring them back to reality? At that point, is it already too late because the LSD has already bound to the relevant receptors?
    • Could you give kentaserin to someone having a bad trip to bring them back to reality?

      There are those of us who perceive and experience reality as the bad trip.

    • by GuB-42 ( 2483988 )

      I know that antipsychotics can be used to stop a bad trip. Some of them can act as serotonin antagonists.
      Though I don't know how effective they really are compared to a placebo, and if they are, by what mechanism.

  • by Anonymous Coward

    Steve Jobs used it as a young man, and what he said was that he thought everyone should have the experience. None of Apple's inventions have been credited directly to that, that's your own flawed conclusion. He was talking about himself and the kind of person he felt he could become (incidentally, you don't need substances to access that part of yourself). Don't pass it off as fact. Bear in mind too that LSD was a very different proposition back then, it was a very different substance, initially used in a v

  • by Anonymous Coward

    LSD was also a strong influence on Bill Wilson [theguardian.com] in his search for a cure to alcoholism. The story goes that Bill Wilson eventually split with AA over AA becoming a completely anti-drug organization, and he still wanted to experiment with LSD and alcoholism.

  • Does Slashdot need to repost everything on Reddit a few days later? Mother of God. This site is increasingly obsolescent. I love it, but I think that's just nostalgia talking.

  • https://en.wikipedia.org/wiki/... [wikipedia.org]

    And STP lasted for close to 24 hours. Yes. I can personally verify that it did. And yes, this is long, long beyond the statute of limitations.

  • that you thought a long-duration psychedelic was a bad thing.

    DOI & other 4-substituted psychedelic phenylisopropylamines are where it's at, (nod to the "STP" (DOM) poster) with 36+ hour durations. You can fall asleep & wake up still in that oh-so-desirable mindspace. DOI has been shown to have health-promoting effects (via TNF-alpha (beneficial to the cardiac system)) and is not illegal. Not for everyone, but that ought to go without saying. Educated, responsible use is vital.
    • 36 hours, jeez, that's a lot of time to set aside, or a long time to be so "altered." LSD seems plenty long enough, and has a well-established safety profile when used with care. DMT might be a bit too quick, like a drag race, but I'd think an Indy 500-type duration would be enough for most people, rather than going up to a whole 24 hour endurance race like LeMans.

      Something producing a full-on LSD-like experience in say, 2-4 hours would be a huge hit, both with psychonauts and scientists. I think 8+ hour
  • "(LSD) has been credited, in part, for the creation of the iPhone, the polymerase chain reaction, as well as some pretty abstract artwork." ...and also a Baseball No-Hitter by Dock Ellis.

    Must See Video Story: https://www.youtube.com/watch?... [youtube.com]

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