It’s no secret that being on acid — also known as LSD, or lysergic acid diethylamide — can make the mundane seem full of meaning, but now we may know why. And not only that, scientists may have figured out why trips last so long. Two studies on LSD provide glimpses of how the drug works in the brain.
In one study, published in Current Biology, researchers took brain scans from volunteers who listened to both personally meaningful songs and meaningless songs while either tripping, on a placebo, or on acid and another drug. The scans let us see just how the drug makes it suddenly seem like everything is so profound. In a separate study published in Cell, scientists captured images of how LSD interacts with certain receptors in the brain. It turns out that LSD has a structural feature that makes it bind with the receptor for a long time and keeps the trip going for hours.
LSD has been around since 1938, when it was synthesized by the chemist Albert Hofmann. It’s a potent psychedelic that played a big role in ‘60s counterculture. But starting in the 1970s, LSD (along with mushrooms and MDMA) was designated a tightly controlled substance as part of the war on drugs. As a result, there has been very little research on any of these substances. Now that the war on drugs is subsiding, scientists are cautiously starting to do more studies, and there’s even interest from the Food and Drug Administration, which approved a large-scale study of ecstasy to treat PTSD. Another psychedelic drug, psilocybin, is being studied to help ease fears of death in cancer patients.
Given this new interest, having a better grasp of the structure of LSD can help us develop better drugs for a variety of conditions. And knowing how the brain creates meaning can be useful for understanding the neurological basis of mental illnesses like schizophrenia. Many schizophrenics see meaning where there is none, almost like they’re on a constant acid trip — so studying what acid does may lead to breakthroughs for the disease. What’s more, research from the 1950s and 1960s indicates acid itself may have therapeutic uses under the right circumstances; Cary Grant was an early adopter of LSD therapy. More recent research has suggested both psilocybin and LSD may help with cluster headaches, sometimes called suicide headaches because they are so severe that people who experience them often kill themselves.
In the Current Biology study, researchers led by neuroscientist Katrin Preller at the Zürich University Hospital for Psychiatry asked volunteers to bring in snippets of music that they felt a strong emotional tie to — examples include Simon and Garfunkel’s “Sounds of Silence,” songs by Radiohead and Muse, and classical music by Hungarian composer Franz Lizst. The volunteers were divided into three groups: people who took 100 micrograms of LSD (a typical dose for people who want to trip), people who took a placebo, and people who took the LSD along with an acid-canceling drug called ketanserin. (More on the this last group later.)
The volunteers listened to their own music and then some free jazz — which wasn’t unpleasant but had no personal connection for the participants — while in a brain scanner. After that, they rated how meaningful the snippets were.
There were two interesting findings. The people who took LSD found the jazz more meaningful than the people in either of the other groups. The people who had a proper trip suddenly seemed to appreciate the new music more.
This makes sense for the people who took LSD versus a placebo. But what about the third group of people who took LSD and ketanserin? Ketanserin is a drug that blocks the ability of LSD to interact with a chemical called serotonin. Preller’s team found that the people taking both LSD and ketanserin had the same results as those who took the placebo. They didn’t find the jazz any more meaningful. “It blocked all the effects of LSD, so it was like if people didn’t take any drugs,” says Preller. “All the typical symptoms — hallucinations, everything — were gone when we pre-treated people with ketanserin.”
So, we know that ketanserin blocks serotonin, and that taking ketanserin blocked the effects of acid. This proves that many effects of LSD are caused by how the drug interacts with serotonin, according to Adam Halberstadt, a professor of psychiatry at the University of California at San Diego who was not involved in the study. We didn’t know this before because most studies of LSD are in animals, adds Preller. Earlier animal studies suggested that a different brain receptor, one that affects dopamine, might be responsible for LSD effects.
And don’t forget that Preller’s team took brain scans of all the participants. Their scans showed which parts of the brain “light up,” or are active, when people listen to things they find meaningful. In this case, the active area was a set of structures called the cortical midline structures. This makes sense, because we already knew that this area plays a role in creating identity and a sense of self. Next, Preller wants to study whether we can get the same effect when people are experiencing meaningful images or touch instead of sound.
So we know how LSD creates meaning. But why do the trips last so long? In a second study published in Cell, scientists led by John McCorvy and Daniel Wacker at the University of North Carolina at Chapel Hill decided to investigate this question. They took images of how the LSD binds to various serotonin receptors — including the receptor in the Preller study. “What we saw is that the receptor is shaped a little bit like a vase, and it has a space in the middle where the LSD binds and there’s a lid above it,” says Wacker. “LSD has this unique property that it actually holds onto the lid. For many other compounds like serotonin, the lid remains rather flexible. Because LSD holds onto it, it really stays in there.” Because the LSD latches on, the effects last for a long time.
The team also tested a mutated version of LSD that didn’t attach to the lid as carefully. “The hypothesis was that this lid keeps the LSD in there for a long period of time, and for a mutation we found that LSD comes on faster but it also leaves faster,” says McCorvy. So this mutated LSD still binds, but the trip probably both starts and ends more quickly. Wacker and McCorvy note that they’re not personally advocating people take LSD, but are both interested in how more research on the drug can be helpful. “For example, LSD has spurred interest in serotonin for mental health reasons over the past decades,” says McCorvy. “By using it as a compound, we can actually generate new compounds in the future, and it all starts with something that was discovered and used recreationally.”