Discovery May Lead to LSD-Based Treatments for Depression, Phobias

The mechanisms underlying how LSD alters the brain to change perception could be used to create treatments for patients with psychiatric disorders, according to a new study published by Current Biology.

In psychiatric disorders, such as depression, phobias, or substance use disorders, perception is significantly altered, compared with individuals who do not have a mental illness.

Patients with substance use disorders have a different perception of illicit drugs, compared with individuals without the disorder, who may view the drug as dangerous. Patients with phobias may perceive certain harmless things alternatively compared with others, while patients with depression may perceive themselves more negatively than others without depression.

The way individuals perceive things is developed in the brain, and the mechanisms behind the formation of perception has been largely unknown. The researchers discovered that serotonin 2A receptors are involved with altered perception in brains under the influence of LSD, according to the authors.

In the study, participants were asked to categorize 30 pieces of music in terms of importance. Interestingly, the administration of LSD changed the meaning of each piece of music.

"Pieces of music previously classified as meaningless suddenly became personally meaningful under the influence of LSD," said researcher Katrin Preller, PhD.

Excessive or exaggerated attributions of meaning to things is common among multiple psychiatric disorders. A coherent self requires a functioning cortical mid-brain structure, which is thought to be altered in certain disorders, according to the study.

"LSD now seems to affect this very network and influence the experience of meaning," Dr Preller said.

Through functional magnetic resonance imaging , the researchers were able to observe that irrelevant stimuli became important to patients after they were administered LSD. However, if the serotonin 2A receptors were inhibited before taking LSD, psychological changes triggered by the drug were normalized, according to the study.

"This was very surprising," Dr Preller said. "After all, studies on animals revealed that LSD also stimulates other receptors, such as the dopamine D2 system."

It was previously assumed that the activation of certain receptors was the cause of euphoria experienced from taking LSD. These current findings suggest that serotonin 2A plays a significant role in the subjective experience under the influence of LSD and changes to the brain.

The researchers said this study demonstrates how LSD affects the brain neuropharmacologically, and how perception is formed. Although the serotonin 2A receptor was observed to generate new meaning, dopamine receptors may regulate the relevance of important stimuli.

These findings may prove to be important for creating novel drug therapies for patients with psychiatric disorders that are characterized by altered perception, such as depression, phobias, and substance use disorders, the study concluded.