Effects of psychedelics on neurogenesis and broader neuroplasticity: 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 dysregulations in patients diagnosed with mood disorders. Psychedelic compounds, such as phenethylamines, tryptamines, cannabinoids, and a variety of ever-growing chemical categories, have emerged 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 or other neurogenesis-associated brain plasticity after psychedelic interventions and aim to provide a comprehensive picture of how this vast category of compounds regulates the generation of new neurons. We conducted a literature search on PubMed and Science Direct databases, considering all articles published until January 31, 2023, and selected articles containing both the words "neurogenesis" and "psychedelics". We analyzed experimental studies using either in vivo or in vitro models, employing classical or atypical psychedelics at all ontogenetic windows, as well as human studies referring to neurogenesis-associated plasticity. Our findings were divided into five main categories of psychedelics: CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens. We 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.

Keywords: Dentate gyrus; Hallucinogens; Major depression; Neurogenesis; Plasticity; Psychedelics.

Fig. 1

Flowchart of article selection following PRISMA guidelines. A total of 205 articles were initially identified from PubMed and Science Direct databases. After assessing abstracts, and conducting full-text analysis, 68 experimental articles were included in the final sample

Fig. 2

(A) Publication trend as cumulative (dark red) or absolute (light red) number for original articles and reviews identified by our search. (B) Localization of laboratories, identified by the affiliation of the correspondent author, which published original articles investigating the relationship between psychedelics and neurogenesis or neurogenesis-related plasticity (darker colours represent a higher number of publications, grey locations denote no publication record in our sample)

Fig. 3

Results of OHAT Risk of Bias quality assessment of studies using human subjects. Percentages of studies within a risk of bias level are represented in the x-axis for each risk of bias item. Low risk of bias (blue, purple), unclear risk of bias (yellow), and high risk of bias (pink, red)

Fig. 4

Results of SYRCLE Risk of Bias Quality assessment for the studies with animal experiments. Percentages of studies within a risk of bias assessment (Yes/No/Unclear) are represented in the x-axis for each risk of bias item