LSD-like, non-psychedelic compounds may have antidepressant effect - Medical News Today

In a recent study published in Nature, scientists identified two compounds that activate the same receptor in the brain as lysergic acid diethylamide (LSD) but do not produce hallucinogenic effects.

In the present study, the researchers used a computational approach to identify compounds that may have therapeutic effects similar to psychedelic drugs.

The antidepressant and anti-anxiety effects of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin have been attributed to their ability to activate the serotonin 5-HT2A receptors on the surface of brain cells.

However, psychedelic drugs can produce hallucinogenic side effects by activating the 5-HT2A receptor.

Thus, it is possible that compounds that activate the 5-HT2A receptor without activating the β-arrestin-2 pathway could help treat depression without causing unwanted hallucinogenic adverse effects.

Such compounds could offer numerous advantages over psychedelic drugs in treating depression and other psychiatric disorders.

The researchers first screened the virtual library for THP derivatives that could bind a model of the 5-HT2A receptor.

They initially synthesized 17 candidates with high docking scores and tested the ability of these compounds to activate the 5-HT2A receptor in laboratory cultured cells.

After testing these compounds, the researchers found four molecules that weakly activated the 5-HT2A receptor.

These results suggest that the two novel compounds selectively activated the 5-HT2A receptor, with limited activation of the signaling pathway that could mediate the hallucinogenic effects of psychedelic substances.

In subsequent experiments, the researchers examined the behavioral effects of these compounds in mouse models.

Psychedelic drugs like LSD produce hallucinogenic symptoms such as head twitches and increased locomotor activity in mice.

Significantly, these novel compounds produced antidepressant and anti-anxiety effects in mouse models.