Robust Methods For Quantifying Neuronal Morphology And Molecular Signaling Reveal That Psychedelics Do Not Induce Neuroplasticity
Umed Boltaev, Hyun W. Park, Keaon R. Brown, Maya Delgado, Jorryn Wu, Brianna N. Diaz-Pacheco, Maria Botero Pinzon, Keer He, Erin Ahern, Nina Goldshmid, Eleanor H. Simpson, Dalibor Sames
bioRxiv Preprint Server March 4, 2024 preprint DOI: 10.1101/2024.03.04.583022 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Primary cortical neurons |
| Topics | Neuroplasticity |
| Citations | 4 |
| Key findings | Psychedelics do not directly modulate TrkB or BDNF-TrkB signaling and do not induce morphological growth in primary cortical neurons, in contrast to BDNF. |
Abstract
Induction of neuroplasticity has become the dominant explanatory framework for the rapid and sustained therapeutic effects of classic psychedelics. Within this broad concept, examination of morphological neuronal plasticity, such as dendritic arbor growth, is widely used to assess the neuroplasticity effects of classic and novel psychedelics. At the molecular level, it has been reported that serotonergic psychedelic compounds mediate dendritogenesis via the master molecular regulator of plasticity, TrkB, either directly via BDNF/TrkB signaling potentiation or indirectly through 5-HT2A receptor. To examine these hypotheses in detail, we developed a robust multimodal screening platform for unbiased, semi-automated quantification of cellular morphology and multiplex molecular signaling in the same cortical neurons. We found that in widely used primary neuronal cultures psychedelics do not directly modulate TrkB receptor or BDNF-TrkB signaling. We also found 5HT2a receptor gene expression and functional receptor levels are low, and psychedelics do not induce morphological growth, in contrast to significant dendritogenesis elicited by BDNF. Our results challenge recently published results in the field and indicate a need for rigorous experimental methods to study morphological manifestations of neuroplasticity effects induced by clinically used and experimental therapeutics.
Comparable studies
Other experimental studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics Promote Structural and Functional Neural Plasticity Neurons in vitro and in vivo | 2018 | Laboratory study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Focused attention meditation changes the boundary and configuration of functional networks in the brain One human participant | 2020 | Single-case experimental design with intensive longitudinal data | n = 1 |
| Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation. Rat brain models | 2002 | Review with experimental data |
Citations in the library
Cited by 4
- The polypharmacology of psychedelics reveals multiple targets for potential therapeutics. Neuron July 15, 2025
- Emerging mechanisms of psilocybin-induced neuroplasticity TIPS - Trends in Pharmacological Sciences September 16, 2025
- Licit use of illicit drugs for treating depression: the pill and the process. Journal of Clinical Investigation June 17, 2024
- Not all serotonergic psychedelics are alike - they induce distinct patterns of altered metabolic activity and connectivity May 28, 2024
Cites 22
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
and 17 more in the library