Lysergic acid diethylamide: In search of the wonder drug

Lysergic acid diethylamide (LSD) is a potent perception-altering chemical that has been both revered and demonized since its discovery. Before its ban in the late 1960s, it was used to model aspects of psychosis and treat alcohol addiction and anxiety. Recent clinical trials show LSD can be administered safely in clinical settings to healthy volunteers and clinical groups. Small studies suggest potential therapeutic uses for anxiety. LSD's perception-altering effects involve agonism at the 5-HT2A receptor. Neuroimaging reveals LSD enhances signal diversity and complexity, decreases resting-state connectivity within intrinsic brain networks, and increases between-network connectivity, including thalamocortical connectivity.

Study at a glance

Abstract

Abstract Lysergic acid diethylamide (LSD) is a potent perception-altering chemical. Since the discovery of its effects almost eighty years ago, LSD has been revered and demonized. Before its ban in the late 1960s, LSD was used to model aspects of psychosis and treat distinct mental disorders such as alcohol addiction and anxiety. The new wave of research on psychedelics as potential treatments for mental disorders has revived interest in LSD. Recent clinical trials have demonstrated that LSD can be administered safely in a clinical context in healthy volunteers and various clinical groups. While research continues, small studies have identified potential therapeutic uses for LSD in tackling anxiety. LSD has a complex mechanism of action, affecting several neurotransmitter systems, but evidence indicates that its perception-altering effects are elicited via agonism at the 5-hydroxytryptamine 2A receptor (5-HT2A). Modern neuroimaging studies have revealed that LSD enhances signal diversity and complexity in the human brain. Functional magnetic resonance imaging (fMRI) studies have shown that LSD decreases the resting-state fMRI connectivity within several intrinsic brain networks while simultaneously increasing between-network connectivity, including aspects of thalamocortical connectivity. Recent evidence indicates that moderate to high doses of LSD have no long-lasting negative effects in healthy volunteers when administered in a clinical setting. Moreover, long-lasting positive outcomes have been reported for healthy volunteers. Whether LSD is a potential wonder drug to be used in treating various mental disorders is yet to be determined. Current studies are exploring putative therapeutic effects in several clinical populations, ranging from anxiety disorders and depression to cluster headaches.