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

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.

Comments

Re: Too long was always my gripe

[tylersoze]

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.

Re: People who use elicit drugs...

[tylersoze]

Well no shit dumbass, so can "licit" drugs like alcohol, the legality of the substance has no bearing on the issue. If I want to take mushrooms or LSD in the comfort of my own home in a controlled setting (look up set and setting) and have a great time that's my business. Heck I don't even drink and really drunk people are the ones that disgust me.

Re:Placebo?

[budgenator]

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.

Re: People who use elicit drugs...

[The-Ixian]

Dude, how about operating machinery while sick with the stomach flu? I mean really, distraction is distraction.

Obviously the problem is not the drugs it is the choices that people make while on drugs. There's a difference. Just like you can't blame a gun for killing people. People kill people. Why don't we outlaw guns?

Why does everybody feel it's ok to blame the drugs? oooo the drugs made me do it... how about no, the drugs enabled you to do it... they didn't make you anything.

Re: Too long was always my gripe

[Ellis D. Tripp]

Pretty much. Some people are just too "tightly wrapped" for psychedelics. Rather than surrendering to the experience, they try to fight it and end up having a really bad time.

Control freak personalities in particular are prone to this. I can only imagine the scene if somebody dosed the White House water cooler these days....