Mind

Here's Why LSD Trips Last So Long

New analysis shows how the drug LSD locks onto a brain cell's serotonin receptor, producing a psychedelic experience that goes on for many hours.

After taking a dose of the drug lysergic acid diethylamide (LSD), a user typically undergoes a hallucinogenic experience that can last half a day or more, depending on dosage and drug tolerance.

Researchers at the University of North Carolina School of Medicine may have come closer to explaining why LSD trips last so long. They discovered the reason after learning what the drug looks like when attached to the serotonin receptor of a brain cell.

"There are different levels of understanding for how drugs like LSD work," Bryan L. Roth of the UNC School of Medicine said in a statement. "The most fundamental level is to find out how the drug binds to a receptor on a cell."

Using a technique called X-ray crystallography, the researchers captured an image of LSD in its active state within a brain cell. A single molecule of LSD binds to the cell's serotonin receptor. But that's not all. The receptor itself locks the molecule into place by covering over it, almost like a lid.

"LSD takes a long time to get onto the receptor, and then once it's on, it doesn't come off. And the reason is this lid," Roth explained.

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As the psychedelic trip winds down, some molecules detach from their receptors while others are pulled into the cell along with the serotonin receptor itself, where they degrade over time. The researchers just published their findings in the journal Cell.

So why does figuring out why an illegal drug like LSD produces such an enduring experience matter to researchers, or anyone else for that matter? The reason is that LSD and other hallucinogenic substances are increasingly being studied for their potential therapeutic uses.

The researchers of the current study are clear that they do not advocate the use of LSD, citing its dangers, but also make note of potential benefits, some of which have been known to the scientific community for decades.

In 2015, a national survey of 190,000 U.S. adults found a reduced likelihood of psychological distress and suicidal thoughts among those who had experience using one or more psychedelics, including LSD or psilocybin, also known as "magic mushrooms," over the course of their lifetimes.

"Growing evidence including the present research suggests that classic psychedelics may have the potential to alleviate human suffering associated with mental illness," the researchers concluded. The study, a joint effort by Johns Hopkins and the University of Alabama at Birmingham scientists, appeared in the Journal of Psychopharmacology.

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Two years earlier, in 2013, a study by the Norwegian University of Science and Technology found that the use of psychedelics such as LSD, magic mushrooms or peyote was not linked with mental health problems. In a meta-analysis of information gathered from 130,152 randomly chosen people, including 21,967 participants who had used psychedelics at least once, the researchers found that users of these drugs tended to have fewer issues related to mental health. The study was published in the journal PLOS One.

Even if psychoactive drugs like LSD are typically associated with illicit, recreational use, studying how these substances could open new avenues for mental health treatment through the development of new psychiatric drugs with fewer side effects.

Photo: A molecule of LSD bound to a serotonin receptor. The orange bar in the this illustration is the "lid" that locks in the LSD molecule. Credit: Lab of Bryan Roth, UNC School of Medicine WATCH: Is LSD Really That Dangerous?