Effects of psychedelics on neurogenesis and brain plasticity: A systematic review

Abstract

In the mammalian brain, new neurons continue to be generated throughout life in a process known as adult neurogenesis. The role of adult-generated neurons has been broadly studied across laboratories, and mounting evidence suggests a strong link to the HPA axis and concomitant malfunction in patients diagnosed with mood disorders. Psychedelic compounds, such as phenethylamines, tryptamines, cannabinoids, and a variety of ever-growing chemical categories, emerge as therapeutic options for neuropsychiatric disorders, while numerous reports link their effects to increased adult neurogenesis. In this systematic review, we examine studies assessing neurogenesis after psychedelics interventions and aim to provide a comprehensive picture of how this vast category of compounds regulates the generation of new neurons. Following PRISMA guidelines, we conducted a literature search on PubMed and Science Direct databases considering all articles published until January 31, 2022. We selected studies containing both the words "neurogenesis" and "psychedelics", using either in vivo or in vitro models, and employing classical or atypical psychedelics at all ontogenetic windows. Of a total of 205 articles, 68 met all the necessary conditions for further review. Our findings were divided into five main categories of psychedelics: CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens. We then described the outcomes of neurogenesis assessments and investigated related results on the effects of psychedelics on brain plasticity and behavior within our sample. In summary, this review presents an extensive study into how different psychedelics may affect the birth of new neurons and other brain-related processes. Such knowledge may be valuable for future research on novel therapeutic strategies for neuropsychiatric disorders.