Science now knows why acid trips last so long

Long trip.
Long trip.
Image: Manel Torralba via Flickr/CC by 2.0
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For over 50 years, LSD has fascinated both users and scientists with its often transcending, sometimes dazzling, widely varied hallucinogenic effects.

As with other drugs (including alcohol), the body can filter out lysergic acid diethylamide from the bloodstream in a matter of hours. But LSD lasts much longer than an alcohol buzz: people have reported acid trips lasting eight, 12, and 16 hours, and sometimes for days on end. For the first time, scientists have figured out why: advanced atomic imaging shows that acid bonds with brain receptors and then changes their structure, so that they keep the drug trapped in the brain till long after it’s been flushed from the blood.

The brain picks up LSD with receptors that normally grab the neurotransmitter serotonin, which affects mood. But when these receptors latch onto acid instead, they change shape to prevent the drug from easily escaping—not unlike a venus flytrap clamping down on a meal.

“You can think of it as a hole in the ground. LSD jumps into it and then pulls a lid down over the top,” Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill, told Wired.

As Roth and his co-authors explain in a paper published Jan. 26, it’s not a permanent trap—eventually, the molecular lid moves enough to let the drug loose—but the additional binding would explain why acid trips last way longer than other psychotropic drugs like psilocybin mushrooms. It also sheds light on why microdosing, (taking around 10-20 micrograms of LSD, or about a tenth of a typical dose) actually works. Despite the tiny doses, the mild effects—users report productivity boosts and improved relationships—can last all day long.

The researchers didn’t use human subjects to study the LSD binding process. Instead, they synthesized these receptors from a line of lab cells, doused them with the drug, and then froze them in action so that they formed crystals. The team then used X-rays to take highly magnified pictures of these crystals to look at how the different atoms in these molecules were arranged, a practice called crystallography, and were able to distinguish the LSD within the serotonin receptors.

Roth thinks that if he and his team can figure out how serotonin receptors envelop the drug, they can figure out how to design psychiatric drugs, like antidepressants, that will last longer, so users can take them at lower doses less frequently. Less medication, in general, is good for patients: it’s one less thing for them to remember, and can have lessen side effects.

LSD is illegal in the US, but pharmacologists and psychiatrists are still increasingly researching its therapeutic potential. This particular study was funded in part by the National Institutes of Health and used lab equipment from the Department of Energy. In the past, though, research on LSD had to be crowdfunded.