Effects of psychedelics on neurogenesis: A systematic review of pre-clinical studies
This systematic review of 68 pre-clinical (and related human) studies categorised psychedelics into five classes—CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines and entactogens—and synthesised their reported effects on adult neurogenesis and related brain plasticity. The authors conclude that diverse psychedelic compounds can modulate the birth of new neurons and neural plasticity, supporting further investigation into their therapeutic potential for neuropsychiatric disorders.
Authors
- Lima da Cruz, R. V.
- Leão, R. N.
- Moulin, T. C.
Published
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 malfunctions 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 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 terms "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. 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 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.
Research Summary of 'Effects of psychedelics on neurogenesis: A systematic review of pre-clinical studies'
Introduction
Major Depressive Disorder (MDD) is a leading cause of global disability and current pharmacotherapies such as benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) fail to produce adequate benefit in around 50–60% of patients, a situation often labelled treatment-resistant depression (TRD). Earlier antidepressant research led to the monoamine hypothesis, but this has been reframed by some investigators as the neurogenic hypothesis, which links improvements after chronic antidepressant treatment to restoration of adult neurogenesis, the ongoing generation of new neurons in restricted brain zones such as the dentate gyrus. Psychedelic compounds—spanning cannabinoids, NMDA antagonists, harmala alkaloids, tryptamines and entactogens—have re-emerged as candidate therapeutics for neuropsychiatric disorders and are reported to modulate brain plasticity, including neurotrophic signalling, neuritogenesis and synaptic remodelling. Vitor Lima da Cruz and colleagues set out to systematically review preclinical and available human experimental studies that assess the effects of psychedelics on neurogenesis and related plasticity measures. Following PRISMA guidance, the investigators searched PubMed and ScienceDirect for articles combining the terms “psychedelics” and “neurogenesis” (including MeSH terms), screened titles and abstracts, extracted experimental details and outcomes, and classified findings by chemical group to provide an integrated picture of how diverse psychedelics influence the birth, survival and maturation of new neurons as well as associated molecular and behavioural endpoints. The review emphasises differences by dose, developmental window and experimental model and aims to highlight gaps relevant to therapeutic development.
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Lima da Cruz, R. V., Leao, R. N., & Moulin, T. C. (2023). Effects of psychedelics on neurogenesis: A systematic review of pre-clinical studies. https://doi.org/10.1101/2023.07.19.549676
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