Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics
This review (2018) describes psychedelics, ketamine, and a range of other substances as psychoplastogens (i.e., substances that help the brain increase its plasticity and thereby enable therapeutic change).
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.
Research Summary of 'Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics'
Introduction
Neural plasticity—the capacity of the brain to change its structure and function in response to experience—is central to healthy cognition and behaviour, and its dysregulation underlies many neuropsychiatric conditions. Olson frames several mood, anxiety and substance use disorders as disorders of maladaptive circuit strength: circuits promoting harmful responses are potentiated while those that support adaptive behaviour are weakened. The prefrontal cortex (PFC) and hippocampus are highlighted because structural atrophy in these regions, including dendritic retraction and spine loss, is a hallmark of depression and is thought to disrupt mood-regulating circuits. While protein trophic factors such as brain-derived neurotrophic factor (BDNF) can reverse these changes experimentally, their pharmacokinetic limitations motivate a search for small molecules that cross the blood–brain barrier and promote plasticity. This paper introduces and motivates the concept of "psychoplastogens," a proposed class of small-molecule, fast-acting therapeutics that rapidly induce measurable structural and functional plasticity and produce relatively long-lasting behavioural effects after a single administration. Olson sets out to describe this class, distinguish it from slower-acting plasticity-promoting drugs, and review evidence that certain agents—including ketamine, scopolamine, GLYX-13 (rapastinel), and serotonergic psychedelics—meet the proposed criteria and hold therapeutic promise for disorders such as depression, PTSD and substance use disorders. The paper also highlights mechanistic hypotheses and translational opportunities and cautions about potential risks of this approach.
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Olson, D. E. (2018). Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics. Journal of Experimental Neuroscience, 12. https://doi.org/10.1177/1179069518800508
References (4)
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