Why LSD Trips Last So Long and Connect Us to the Universe

By Nathaniel Scharping | January 26, 2017 3:08 pm
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LSD (in blue) fitting into a serotonin receptor (white ribbon). (Credit: Bryan Roth)

Two studies looking at one crucial receptor in our brains give different insights into the psychedelic effects of LSD.

Two separate teams of researchers publishing papers today in Cell examined how LSD binds to serotonin receptors in our brains and what the consequences of those reactions are. Their results offer an explanation for two hallmarks of LSD use: Its long-lasting effects and apparent ability to give users a sense of deep connection to previously mundane items and ideas.

Look Into the Crystal Molecule

The first study comes from researchers at the University of North Carolina at Chapel Hill, who used a highly precise imaging technique to look at how LSD attaches to neurons in the brain. They used X-ray crystallography, a process that involves shining an X-ray beam at crystallized molecules of interest and noting the ray’s diffraction pattern as it passes through. In this way, researchers can build an image of the internal atomic structure of a molecule. Applying the crystallography technique to neurons entangled with molecules of LSD gave them an unprecedented view into the mechanics of the drug’s interaction with our bodies.

To our brains, LSD looks confusingly similar to the neurotransmitter serotonin, which allows it to attach to receptors in place of the hormone. Once there, it stimulates our brains in unfamiliar ways, leading to the hallucinations and rapturous experiences reported by users. LSD attaches most readily to members of the 5-HT class of serotonin receptors, and these are thought to be responsible for many of its psychedelic effects.

Peering into their crystallized versions of these receptors, the researchers saw that once LSD gets into a receptor, it seems to be held there by what they call a “lid” — a part of the receptor folds over the molecule and holds it in place. Instead of eventually disentangling itself from the receptor, as with most other molecules, LSD sticks around until it gets absorbed by the cell and broken down. This explains why LSD trips can last as long as 12 hours, even though the drug itself disappears from the bloodstream after only about 4 hours.

The researchers also studied what happens to our neurons when they exposed to tiny doses of LSD. The concept of microdosing has gained popularity recently as a means of enhancing creativity and treating depression, while avoiding the psychedelic effects of the drug. However, no clinical evidence in favor of microdosing yet exists.

Finding Meaning Where There Was None

Not only are the 5-HT2A receptors particularly good at holding on to LSD molecules, they also appear to be responsible for many of the psychedelic effects of the drug, as confirmed by a separate study from the University Hospital for Psychiatry Zurich.

They first had participants listen to different pieces of music and pick songs which affected them the most and least. But after giving them LSD, researchers noticed patients reported feeling moved by more pieces of music than before, or, as researchers say, they found “meaning” in music that they were previously unable to connect to. This wasn’t surprising, as LSD users often associate “trips” with a sense of connectedness to things that had gone unnoticed before. The effect has even been suggested as a means of treating depression.

They also tested this effect in patients who first received a drug that specifically blocks the 5-HT2A receptors in the brain, while leaving other receptors affected by LSD untouched. In these people, the effect vanished. They didn’t discover meaning in the songs as when they weren’t under the effects of LSD. The 5-HT2A receptor, the researchers conclude, is responsible for modulating how we attach meaning to objects, people and concepts in or lives. A distorted ability to attribute meaning to experience is a common hallmark of some mental diseases, and establishing a defined pathway by which this happens could offer new routes for treatment.

Taken together, these two studies highlight the key role that 5-HT2A receptors play in mediating our reactions to LSD. By illuminating both the physical process that brings LSD molecules into contact with our neurons and the behavioral effects of that interaction, researchers are better able to understand how LSD could play a role in treating mental illnesses, in addition to developing similar drugs that may bring about the same results, but without the trippy side-effects.

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  • Jean

    I would like to volunteer for the first clinical trials.

  • Erik Bosma

    Pot is much the same. I brought a copy of Bitches Brew by Miles Davis to a friend’s house one night when we had some killer weed to smoke. Now these people did not listen to jazz or anything except Top 40 pop music and a little country and would normally have kicked this album off the turntable after a few seconds. Well, they listened so intently, no one even spoke for the whole time. Every one was “like Wow, man!”… afterwards. On top of that, this is a double album and if you’ve ever given it a listen it ain’t really even jazz. So my question has always been, do psychedelics make crappy music sound really good to anyone or does it allow people with crappy musical tastes to enjoy complex music that they would never enjoy normally? Hmmmm….

    • John C

      You focus more without other mental distraction as other areas of the brain generating internal chatter are subdued.

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      • Erik Bosma

        Yes, but it also can make really terrible music sound as if it was written by a musical genius. We tried that once. We listened to some very crappy (by everyone’s standards) music while on acid. Then the following day we re-listened to the same stuff. Never laughed so hard in my life. It was even embarrassing thinking that this crap, for one night, actually sounded like fine music to us when it was definitely crap. Wish I could remember the songs but that was the Sixties….. Man.

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        • RockaRolla7

          Too funny. I experienced the same thing on pot myself. At a party the music was awesome. I went back the next day and borrowed the album. I’ve never been a Pink Floyd enthusiast–except for that one night. I didn’t like it the next day either…

          • Erik Bosma

            I’ll bet you were listening to Ummagumma. That was probably their wildest album before they became mainstream when Sid was still with them. Then he went insane. Many people hadn’t really heard about them until after that album. I loved it by the way. But big mean old Roger Waters kicked him out and then they went top 40. Poor Sid. He was a genius rest his soul. I don’t like them now. Maybe a whole whack of pot might help but I doubt it.

          • Connie

            This could totally explain the whole Dylan thing…

          • Erik Bosma

            I mean big mean old David Gilmour.

    • Rudolf Penner

      Bitches Brew is a hot album in and of itself…I don’t think anybody would need anything to appreciate it…

  • Andy Anderson

    I think the study worked well because different genres of music can create certain reactions, feeling, and emotional standards that people may not experience from their daily life. Music like LSD can allow a person to escape for a few moments to another place. Of course, LSD may take you further than music can but listening to certain genres or a certain song can take you away for a few minutes. With the study playing different types of genres, defiantly made the study interesting and helped understand the influence LSD can have in your selection of music. When participants listened to music while on LSD certain genres that they typically did not like become enjoyable while ones they tend to listen to really was not the same. The influence of the LSD does seem like it played a role in what people found enjoyable in music. I think this study shows that when we have these experiences we can lose ourselves in a different way whether it is drug-induced happiness or that one song that draws you away from it all, music and LSD seems like you can get lost, one way or another.

    • Kathryn

      When smoking pot some years ago, I could hear what I was seeing, and see what I was hearing. I don’t know what if any music was playing, but I do recall the most beautiful colors that are not describable or even comparable to any thing I’ve seen in life. It seemed as though I had an understanding of life itself. It was impossible to decide what world was reality,
      because in reality they were both real at the time.

      • Portefoi

        Apparently they don’t grow/make drugs like they used to… just saying. Never experienced anything of the sort. No colors, no hallucinations of any kind while on drugs, anyways. I had some fantastic hallucinations when I had a really high fever for a few days when I was a young teen, though. I often wondered about the “purity” of the drugs of my generation (graduated in the 90’s) as compared to the 60’s and 70’s.

        • non name

          It is true, they don’t do drugs today as it was at the very beginning, for the simple sake of profit. They put fillers on drugs to make volume, and then, get more profit for each gram sold.
          Some times, what they use as filler only make it worst (heavy and bad side-effects) than when it is pure.

    • Erik Bosma

      I had to firmly quit acid when I was about 19 in 1972 because the highs were so intense they either scared the hell out of me or they were SOOOO… intense that I just went with it not caring if I lived or died because I was pretty sure it was all over for me anyways. However, no matter how all the reality melted like magma or Satan followed me around for hours laughing his fool head off at me, I always came back with a big grin on my face although vowing to never ever do it again. But is was pretty potent then cause I have done it since, for old times sake, and it was basically very mellow; barely like a pot or hash stone.

  • rhansing

    Once with a notebook, I wrote the incredible creative piece… when I read it later, it was gibberish… and stupid. REALLY STUPID. I always wondered why art and music that has no questionable value in the “survival of the fittest” benefit in evolutionary biology… Hmmmm… maybe it does… Yep, I select my music to fall asleep… Absolutely no Hard Rock… And sometimes… I have to change the type I listen to, to fall asleep… Basically if one type fails… I will switch and switch until I find the right one to sleep. I also use shifting my five senses… hearing… tactile, vision etc. I stopped in taking drugs… by 1972… but I always wondered if these techniques I use are the result of by brain being rewired… My reason for quitting was that I get high on living life… but I wonder if that “high” was induced… I will never know since I can’t go back to the” befores” and conduct a controlled experience. After all I was totally smitten at nineteen with this beautiful brown eyed girl. She had this special smell that drove me crazy…That was before I took drugs.. Who knows?

  • Daliot

    I don’t know whether the researchers would find this interesting but FWIW, one night back in the early ’70s, while tripping, I convinced myself while in conversation with a fellow tripper that I should quit smoking.

    I was smoking a pack a day in those days. We discussed the pros and cons of smoking for a long time and at some point I concluded that it was an enemy of my body and good health and that it made absolutely no sense to be a smoker. From that moment on, I considered myself a non-smoker. I threw away my pack and stopped cold turkey. That was it. Over the years, I would occasionally bum a smoke from someone while having a drink but it always grossed me out. I never liked it again. Something clicked in my head that reinforced my decision to be a non-smoker. I always reasoned that my experience was somehow similar to self-hypnosis. Who knows? Anyway, I’ve remained a non-smoker ever since and have always attributed it to the decision I made that night.

    • Bruce Kopetz

      As much as I revere hallucinogens, I’m certain your underlying desire to free yourself from nicotine addiction was the true reason for your success. The insight you had while tripping merely reinforced a decision you’d taken long before–but had yet to act on.

      • Erik Bosma

        agree

  • Sandy Gibbs

    How would this work on someone who takes a Selective Seratonin Reuptake Inhibitor?

  • n0ne000

    it’s actually a subpart or ligand of the 5HT2A receptor. there’s a video of brain cells moving like tendrils and connecting and reconnecting alot, from LSD. if associating new things and concepts together is the effect of neuroplastcity, then why would there be a way to stop the effects and get the effects. is it maybe the razors edge? pot (THC) doesn’t affect the same places. one place it does effect, is the orbitalfrontal cortex, which is thought to be responsible for impulsitivity, forethought and i not very well understood supposedly. CBD effects the 5HT1A receptor which is not the same in effects as the 5HT2A recceptor, they are also coded on different chromosomes. the 5HT2A receptor is coded on the 13th chromosome.

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