Tripping on acid can make the bland and ordinary seem vivid and magical. The Beatles song, “Lucy in the Sky with Diamonds” — believed to be a nod to the drug LSD based on the song's letters — featured lyrics about “tangerine trees and marmalade skies." These colorful pictures describe a trip that can linger for 12 hours or more, but up until now, we've never understood why the hallucinogenic effects of the drug last so long.

Researchers at the University of North Carolina (UNC) found LSD binds to the serotonin receptor in the brain at an unexpected angle. Furthermore, this part of the serotonin receptor folds over the LSD molecule like a “lid," which seals the drug inside. This process explains why the effects of acid trips take hours to disappear.

Read More: The Truth About Where LSD Trips Take Your Mind And Body

"LSD takes a really long time to get on the receptor, and then once it gets on, it doesn't get off," said Bryan Roth, a professor of pharmacology at University of North Carolina and a senior co-author on the study, in a statement.

How LSD Interacts With Serotonin

In the study, published in Cell, Roth and his research team took images of how the LSD binds to various serotonin receptors. LSD has a unique property that actually holds onto the lid, while for many other compounds like serotonin, the lid remains rather flexible. Since LSD latches on, the effects last a really long time.

The drug's ability to fit in and let the receptor's "lid" close over it depends on the chemical structures of both the drug and the receptor. For example, when Roth's research team exposed cells with mutant receptors that had floppier lids to LSD, the LSD binded more quickly, and also left the receptor much faster. In other words, short LSD binding led to different signaling patterns than the longer binding events.

LSD Effects

Many of the effects of LSD are primarily due to how the drug interacts with serotonin. In a recent study, published in Current Biology, researchers asked volunteers to bring in clips of music they felt a strong emotional tie to, and were then divided into three groups: people who took 100 micrograms of LSD (typical dose for acid trip), people who took a placebo, and people who took the LSD along with ketanserin, an acid-cancelling drug. The participants listened to their own music, and then some free jazz while in a brain scanner, to rate how meaningful the snippets were.

The reason why acid trips last 12 hours or more is linked to how LSD binds to receptors in the brain. Photo courtesy of Alejandro Alvarez, Public Domain

People who took LSD found jazz more meaningful than people in either of the groups. Meanwhile, the third group of people took LSD and ketanserin — a drug that blocks the ability of LSD to interact with a chemical called serotonin. This means ketanserin blocked the effects of LSD, which numbed them to the typical hallucinations.

Read More: Scientists Observe LSD Effects On The Brain

How LSD Wears Off

The drug's psychedelic effects begin to wear off as the lid moves around and frees some of the LSD molecules from the receptors, according to the researchers. The molecules are cleared from the bloodstream in a couple of hours, but the acid trip continues. The brain responds to the remaining molecules by drawing the receptors and LSD inside the cells, where they are broken down. Researchers believe this is the moment when the effects disappear.

LSD And Mental Health

Understanding what drives LSD's potent and long-lasting effects may help drug developers design psychiatric drugs that can target a variety of mental health conditions, with fewer side effects. LSD is also a semisynthetic member of a larger class of chemical compounds that are recognized as therapeutics for conditions, including migraine headaches, postpartum hemorrhage, and Parkinson's disease.

LSD treatment for medical conditions like anxiety and PTSD could potentially be useful.

In a 2014 study, published in the Journal of Nervous and Mental Disease, researchers found LSD can promote statistically significant reductions in anxiety for people who were coming to terms with their end of life. They tracked 12 people who were near the end of life as they attended LSD-assisted psychotherapy sessions. Overall, the patient’s anxiety "went down and stayed down."

The drug is also suspected to help with treatments for depression and alcoholism. A 2015 study conducted at Cardiff University found people who took the drug were "somehow psychologically refreshed" afterwards. The participants, who had previous experience with LSD, were injected with a “moderate” (75 mcg) dose of the drug before having the activity of their brains monitored using functional magnetic resonance imaging (fMRI). The dose produced “quite profound effects” in terms of brain activity and the mood and mental state of the participants.

The participants didn’t have a “bad trip,” although three suffered some anxiety and temporary paranoia. Early results from the trial, involving 20 people, are said to be “very promising” and add evidence that psychoactive drugs could help reverse patterns of addictive or negative thinking. The researchers believe these drugs offer a great opportunity in mental health.

Research on LSD has led many to believe it has potential in a variety of medical applications, but more information is needed to understand its course of action, and how it can be modified in the brain.

Source: Wacker D, Wang S, McCorvy JD et al. Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell. 2017.

See Also:

Tripping On Acid Alters Time Perception, Could Someday Treat Depression

LSD Triggers Strong Activation Of Mind’s Semantic Networks, Study Finds