It’s a familiar feeling: several hours after dropping a tab, your trip begins to peak. Then it escalates until you’re viewing the world through a Rainbow Brite aquarium, with every sound twisting and echoing from the depths of your skull. As you fall into the existential hole of your mind, things start to get real, real weird, and you might be ready to call it quits. But it’s only been four hours since you dropped – the LSD is making itself at home, right in your brain cells. Literally and figuratively.

It’s commonly known that the effects of lysergic acid diethylamide can last up to twenty hours, but until now, the reason why hasn’t been clear. Researchers at the University of North Carolina School of Medicine have published in Cell a heap of new information regarding the popular hallucinogen’s effect on the brain. The years-long experiment involved binding an LSD molecule to a human serotonin receptor, then producing the first-ever crystal structure of the exact moment they joined. The process, called x-ray crystallography, was the only way to discover this breakthrough information.


An LSD molecule binds with a human serotonin receptor. (UNC School of Medicine)

Postdoctoral researchers Daniel Wacker, PhD, and Sheng Wang, PhD, led the research, finding out that the LSD-to-receptor relationship functions much like a trash bin. The LSD molecule prompts the receptor to trap the molecule within it, closing its lid. It remains in this position for hours. There comes an end, though: once the molecules finally “pop off” the receptor, they are sucked into the cell and disassembled for recycling, finishing the acid trip.

To come to their conclusion, the researchers synthesized a human serotonin receptor, then bound the LSD molecules with it. They “froze” the exact moment that the two interacted, allowing them to produce a type of X-ray photo that eventually led to the lid theory.

Recent years have seen scientists revisit the Schedule I drug due to its potential to treat a range of mental illnesses, including depression. Wacker hopes that understanding the effects of LSD on the brain could lead to its implementation in pharmaceuticals. The scientist is an advocate of its potential usage in medicine, saying, “I think it’s important for the pharmaceutical industry to understand that if you modify just one tiny aspect of any compound, you might affect the way it sits in the receptor. And as a result, you might affect how the compound works.”

(Inverse, UNC Healthcare)