Scientists at the University of Carolina School of Medicine have, for the first time ever, crystallized a human serotonin receptor with an LSD molecule attached to it, which has offered incredible insight into how this powerful substance effects our brains, like why it lasts so long.
Since its discovery by Swiss chemist Albert Hofmann in 1938, lysergic diethylamide (LSD) has remained arguably the most fascinating and mysterious drug in the history of drugs. The unique patterns of visual hallucinations and mind-blowing revelations seem logically impossible given the minute dose required for said effects.
Despite being one of the longest lasting psychedelic drugs available (we’ll admit, some 2C and 3C drugs have it beat on length, but not quality), virtually all of it leaves your body before you’ve even began to reflect on the sheer amazingness of the last 12 hours.
Completely contrary to the laughably untrue rumor that LSD remains in your spinal cord forever, other scientists have determined that your brain’s fluid rids itself of the drug after just four hours of taking it. For a drug that lasts at minimum eight hours, how could that be possible?
As it turns out LSD binds to serotonin receptors in a certain way that causes the receptor to close a lid over the LSD and lock it in. Receptors, like this serotonin receptor, are located on the outside of brain cells and function like little dials that respond to chemical messengers floating around between cells. Different molecules activate different receptors in a variety of ways.
At such a small scale, everything is in constant motion. Molecules constantly pop on and off of receptors and don’t always stay bound for very long. LSD is not the only molecule that interacts with this specific serotonin receptor; for one, serotonin does as well. However, LSD’s unique shape allows it to insert itself deep into the cavity and shut the door behind it.
According to the scientists’ carefully performed computer models, the serotonin receptors hold onto LSD firmly and rarely wants to give it up. Natural metabolism in the neurons eventually digests the entire LSD-bound receptors and spits them out as waste. In the meantime, the brain made up by those cells just enjoyed a transcendental psychedelic experience.
Researchers went to the painstaking work of isolating human serotonin receptors purified from genetically modified organisms designed to express the receptor. If that part wasn’t already hard enough, the next step consisted of coaxing their newly purified receptors to bind to LSD, and then forcing it to crystallize.
“To get crystals of a known compound bound to its receptor is incredibly difficult,” said Bryan L. Roth, an author on the paper.
A simple task conceptually, it can be impossible in many cases. The payoff is that a crystallized sample can be analyzed with a technique called X-ray crystallography, which takes a snapshot of what the receptor looks like with an LSD molecule bound to it—the money shot.
This research has vast implications for scientists that study the neuroscience of LSD, and means its life changing revelations are one step closer to helping those with neuropsychiatric disorders. Not only that, its unique binding pattern to the serotonin receptor could have repercussions in the world of drug discovery to make vital drugs last longer and be more effective.