Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics

Abstract

Neural plasticity-the ability to change and adapt in response to stimuli-is an essential aspect of healthy brain function and, in principle, can be harnessed to promote recovery from a wide variety of brain disorders. Many neuropsychiatric diseases including mood, anxiety, and substance use disorders arise from an inability to weaken and/or strengthen pathologic and beneficial circuits, respectively, ultimately leading to maladaptive behavioral responses. Thus, compounds capable of facilitating the structural and functional reorganization of neural circuits to produce positive behavioral effects have broad therapeutic potential. Several known drugs and experimental therapeutics have been shown to promote plasticity, but most rely on indirect mechanisms and are slow-acting. Here, I describe psychoplastogens-a relatively new class of fast-acting therapeutics, capable of rapidly promoting structural and functional neural plasticity. Psychoplastogenic compounds include psychedelics, ketamine, and several other recently discovered fast-acting antidepressants. Their use in psychiatry represents a paradigm shift in our approach to treating brain disorders as we focus less on rectifying "chemical imbalances" and place more emphasis on achieving selective modulation of neural circuits.

Keywords: DMT; LSD; MDMA; PTSD; Psychoplastogen; depression; induced plasticity; ketamine; neural plasticity; psychedelic.

Figure 1.

Ketamine is the prototypical psychoplastogen. (A) Immature cultured cortical neurons (DIV6) treated with ketamine display increased dendritic branching compared to vehicle-treated neurons. (B) Mature cultured cortical neurons (DIV20) treated with ketamine display increased synapse formation relative to vehicle-treated neurons. VEH, vehicle; KET, ketamine; magenta, MAP2 staining; green, synapses determined by colocalization of pre- (VGLUT1) and postsynaptic (PSD-95) puncta.