Researchers Finally Solve the Puzzle Behind LSD’s Long-lasting Effects

A team of researchers discovered the mechanisms behind LSD’s long-lasting effects. LSD is cleared from the bloodstream quickly yet the effects linger for half a day or even longer. The team found that LSD molecules were getting trapped because the receptor had a molecular “lid.” The details are in a paper that was just published in the journal Cell.

Lysergic acid diethylamide, also called LSD or acid, is a psychedelic drug. LSD, which is odorless and colorless when pure, causes visual hallucinations, illusions, euphoria, an altered sense of time, and wakefulness. Negative side effects include nausea, anxiety, intrusive thoughts, panic attacks, and agitation. People with mental illnesses are more prone to adverse effects and “bad trips.” Although the drug is generally associated with illegal recreational use, there is growing research to suggest that LSD may have clinical applications. LSD has been used in psychotherapy for treating alcoholism and PTSD. It can also be used to reduce anxiety in terminally ill patients. Scientists still don’t understand all of the mechanisms behind LSD, however. The drug’s effects last for 12 or more hours even though LSD is rapidly removed from the bloodstream.

Scientists from Roth Lab in The University of North Carolina at Chapel Hill used crystallography to study LSD’s effects on serotonin receptors. The researchers found that the drug attached to the receptor’s binding site at an odd angle, helping the molecule wedge in. Unexpectedly, the receptor also formed a “lid” over the LSD molecule. This trapped the drug, explaining the long-lasting effects. To confirm their findings, the team exposed modified receptors to LSD. The receptors had nonfunctional “lids” and as expected, the drug was released early. The researchers also exposed human cells to microdoses of LSD. The LSD molecules still ended up trapped in the receptors, showing that even tiny doses of the drug could potentially have long-lasting effects.

The team’s findings provide new insights into the molecular mechanisms behind LSD’s effects. Their research also confirms that microdoses of LSD can have long-lasting effects, though the exact effects are currently unknown.

REFERENCE

Wacker et al. Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell (2017).

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