A non-hallucinogenic LSD analog with therapeutic potential for mood disorders.

Hallucinations limit widespread therapeutic use of psychedelics as rapidly acting antidepressants. Here we profiled the non-hallucinogenic lysergic acid diethylamide (LSD) analog 2-bromo-LSD (2-Br-LSD) at more than 33 aminergic G protein-coupled receptors (GPCRs). 2-Br-LSD shows partial agonism at several aminergic GPCRs, including 5-HT, and does not induce the head-twitch response (HTR) in mice, supporting its classification as a non-hallucinogenic 5-HT partial agonist.

Translational control by ketamine and its implications for comorbid cognitive deficits in depressive disorders.

Ketamine has shown antidepressant effects in patients with major depressive disorder (MDD) resistant to first-line treatments and approved for use in this patient population. Ketamine induces several forms of synaptic plasticity, which are proposed to underlie its antidepressant effects. However, the molecular mechanism of action directly responsible for ketamine's antidepressant effects remains under active investigation.