JAN 27, 2017 5:48 PM PST

LSD Potently Locks Into its Receptor

WRITTEN BY: Carmen Leitch

The hallucinogenic effects of LSD, lysergic acid diethylamide, are very long lasting; a dose of the drug can act for over 12 hours. Reporting in the journal Cell, researchers have now revealed that the nature of the physical interaction between LSD and its receptor underlies this lengthy impact. Crystallography images showed the investigators that the drug gets wedged into the binding region of the serotonin receptor in an unexpected way. The receptor also ends up bending over in a way that locks the LSD inside of it.

This image is an artistic representation of the chemical structure of LSD -- highlighted in yellow -- interlocking into a red-orange ribbon diagram of the serotonin receptor. / Credit: Annie Spikes

"Once LSD gets in the receptor, a lid comes over the LSD, so it's basically trapped in the receptor and can't get out," explained one of the senior authors of the work, Bryan Roth (@zenbrainest), a Professor of Pharmacology at University of North Carolina. "LSD takes a really long time to get on the receptor, and then once it gets on, it doesn't get off.

"When I was younger, and The Grateful Dead was still around, I would occasionally go to Grateful Dead concerts. A lot of people took LSD and similar drugs during concerts, and it would be interesting to be in the parking lot hearing people wondering when their LSD experience was going to end," said Roth. "A lot of people who take the drug are not aware of just how long it lasts."

LSD seems to be experiencing a bit of a resurgence of late. Some researchers have been trying out hallucinogens in therapy for some medical conditions. It has some potential for psychiatric treatments, or at least might inform the development of new drugs. Many of these therapies use only a very small amount of LSD; this new study sheds light on why users experience the effects for an entire day.

Roth’s team also wanted to know more about LSD micro-dosing, and looked at living cells that had been exposed to very small amounts of the drug. Micro-dose levels of LSD did alter receptor signaling on the cells. That does not show however, how that works in living cells inside of people, but it does suggest that those low levels could in fact be exerting a real influence in people.

This image shows an artistic representation of LSD (in blue) fitting into a serotonin receptor (the white ribbon). / Credit: Bryan Roth

The team also saw that if the LSD receptors were mutated so they did not lock the drug inside very well, the LSD popped out of the binding pocket more quickly. That also resulted in a truncation in receptor changes.

"I think it's important for the pharmaceutical industry to understand that even if you modify just one tiny aspect of any compound, you may affect the way the entire compound sits in the receptor, and that affects the compound's performance," said the first author of the work, Daniel Wacker, a postdoctoral fellow at UNC.

You can see a talk from David E. Nichols, PhD on the neuroscience of LSD in the video above, or watch a shorter below video that gives an overview of LSD and its history.

 

Sources: AAAS/Eurekalert! via Cell Press News, Assay and Drug Development TechnologiesCell

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JAN 27, 2020
Microbiology
JAN 27, 2020
Microbes in Household Dust May Be Spreading Antibiotic Resistance
Bacteria live in household dust, and sometimes a few of those microbes are pathogenic or carry genes that confer resistance to antibiotics....
FEB 10, 2020
Cell & Molecular Biology
FEB 10, 2020
Lighting a Path to an Alzheimer's Disease Treatment
Alzheimer's impacts millions of people around the world; globally, it is thought to cost $605 billion a year, and there is still no way to treat it....
MAR 01, 2020
Cell & Molecular Biology
MAR 01, 2020
A Strain of a Common Gut Microbe Can Promote Colorectal Cancer
The microbes in our gastrointestinal tract carry their own genomes and can produce and secrete molecules that have an effect on our health....
MAR 04, 2020
Genetics & Genomics
MAR 04, 2020
DNA Fragments and Cartilage Recovered From 75-Million-Year-Old Dinosaur Bones
An international team of researchers has analyzed cartilage from a baby duckbilled dinosaur, and they have identified bits of preserved proteins and what seems to be chromosomes....
MAR 03, 2020
Cancer
MAR 03, 2020
New technique maps tissue development and tumors
Research published recently in the Proceedings of the National Academy of Sciences details the development of a new technique that is capable of mappi...
MAR 15, 2020
Microbiology
MAR 15, 2020
A Second Person Has Been Cured of HIV
New research has suggested that after long-term follow-up, HIV is no longer detectable in a patient that was previously HIV-positive....
Loading Comments...