Neuroplasticity, Neurogenesis, and Psychedelics

Hype vs. Hope – What the Science Shows

Go to almost any psychedelic conference and you will hear the mantra: “psychedelics grow new brain cells.” You hear it in podcasts and out of the mouths of people who should know better. It is two claims fused into one, and only one of them has much evidence behind it.

First, Dear Reader, I believe definitions are in order.

Neuroplasticity is the brain’s capacity to change its existing wiring. Synapses strengthen or weaken and dendrites, the branching input structures of a neuron, sprout new spines or lose them. Whole networks reorganize their patterns of communication. Nothing new is born. What exists is remodeled. This happens constantly, in everyone, all the time. Learning a phone number is neuroplasticity.

Neurogenesis is the birth of genuinely new neurons from neural stem cells. In adult mammals it has been reliably documented in two places: the olfactory system and the dentate gyrus of the hippocampus. It is a far narrower phenomenon, and in humans it has been the subject of a twenty-year debate over whether it happens at all after childhood. That fight has only recently begun to settle

So, before we ask whether psychedelics cause neurogenesis in humans, we should notice that the field is still arguing about the baseline.

What the animal work actually shows

The plasticity findings are real, and they are largely about remodeling, not birth.

David Olson’s lab established the core result: serotonergic psychedelics like LSD, DMT, and psilocin increase dendritic spine density and synapse number in cortical neurons, in culture and in rodents, in a matter of hours. Alex Kwan’s group then watched it happen in living animals. Using two-photon imaging through cranial windows in mice, they found psilocybin produced roughly a 10% increase in dendritic spine density in the medial frontal cortex within 24 hours, and the new spines were still there a month later.

Olson’s lab later supplied a mechanism with real explanatory power. The 5-HT2A receptor sits not only on the cell surface but inside the neuron. Psychedelics cross the cell membrane while serotonin does not. Activating the intracellular pool is what drives the growth, which is why the brain’s own serotonin, flooding the same receptors from outside, does not produce the same structural effect.

The most interesting framing may be Gül Dölen’s. In mice, a single dose of a psychedelic reopened the closed developmental “critical period” for social reward learning and the length of the reopened window scaled with the drug’s duration. The period lasted from about 48 hours for ketamine to roughly three weeks for LSD. That is metaplasticity, not a change in the wiring so much as a change in how readily the wiring can change.

Thanks to the 50-year War on Drugs this data does not come from humans, but from rodents or petri dishes.

Where neurogenesis evidence is thin

The neurogenesis literature is smaller and messier than the plasticity literature, and it points in more than one direction.

The most-cited psilocybin study found that low doses tended to increase hippocampal neurogenesis in mice and accelerated extinction of conditioned fear, while higher doses produced significant dose-dependent decreases in newborn neurons (Catlow et al., 2013). That information rarely survives the trip into a wellness brochure. Single-dose 5-MeO-DMT increased proliferation and survival in the mouse ventral dentate gyrus (Lima da Cruz et al., 2018), and the harmala alkaloids in ayahuasca, not the DMT, regulate neurogenesis in vitro and in vivo (Morales-García et al., 2020).

A 2024 systematic review of sixty-eight experimental articles covering psychedelics and neurogenesis found effects that varied by compound, by dose, and by developmental stage. The review flagged widespread failures of randomization and blinding in the animal work. In the six human studies, five measured blood brain-derived neurotrophic factor (BDNF) as a proxy rather than assessing neurogenesis at all (Lima da Cruz, Leão & Moulin, 2024).

There is no direct human evidence, and there cannot easily be any. You cannot count newborn neurons in a living person. As of now, the measurement requires postmortem tissue.

The human data problem

This is where the story gets uncomfortable for the marketing copy.

The standard human proxy has been peripheral BDNF, a neurotrophic protein assumed to track plasticity. In 2025, Calder, Hase and Hasler pooled twenty-nine studies and 104 effect sizes across ketamine, esketamine, LSD, psilocybin, ayahuasca, DMT and MDMA. They found no evidence that any of them elevate blood BDNF in humans, and that better-controlled studies reported smaller effects. Either peripheral BDNF is a useless readout, they concluded, or the preclinical plasticity findings are not translating.

What has replicated in humans is functional, not structural. Siegel and colleagues scanned seven adults roughly eighteen times each and found psilocybin massively desynchronizes cortical activity, with reduced hippocampal–cortical connectivity persisting for weeks (Siegel et al., 2024). That is a network changing its behavior. It is not a neuron being born, and the two should not be spoken of in the same breath.

And microdosing?

Here the plasticity claim is weakest of all because sub-perceptual dosing is where expectancy has the most room to work.

Two findings frame it. Szigeti’s self-blinding citizen-science study put 191 participants through a design where they blinded themselves at home. Microdosers improved, and so did the placebo group, by about the same amount. What predicted benefit was what people believed they had taken (Szigeti et al., 2021). Cavanna’s double-blind trial found no support for enhanced wellbeing, creativity, or cognition.

To be fair to the other side: Polito and Liknaitzky reviewed nineteen placebo-controlled studies and concluded that a purely placebo interpretation is not well supported either, there are dose-dependent physiological and neural signals. But they counted only ten independent experiments across six labs, averaging thirty-one participants, almost entirely in healthy and psychedelic-experienced volunteers (Polito & Liknaitzky, 2024).

That is not an evidence base capable of supporting a claim about growing neurons. It is a promising set of pilot signals.

Why the distinction matters

There is a clean test coming. If plasticity is the therapeutic mechanism, then non-hallucinogenic analogs designed to trigger it without the subjective experience should work. Several have now reached Phase 1 human trials. If they succeed, the mystical experience was scaffolding. If they fail, plasticity was never the whole story.

Until then, the honest current conclusion is this: psychedelics reliably remodel synapses in rodents, possibly do something similar in humans, and may modestly influence hippocampal neurogenesis in animals. To date they have never been shown to generate new neurons in a human being.

That sentence will not sell a retreat. It has the advantage of being true, and the field’s credibility over the next decade will rest on how many of us are willing to say it.

References

Calder, A. E., Hase, A., & Hasler, G. (2025). Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis. Molecular Psychiatry, 30(2), 763–776. https://doi.org/10.1038/s41380-024-02830-z

Catlow, B. J., Song, S., Paredes, D. A., Kirstein, C. L., & Sanchez-Ramos, J. (2013). Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Experimental Brain Research, 228(4), 481–491. https://doi.org/10.1007/s00221-013-3579-0

Cavanna, F., Muller, S., de la Fuente, L. A., et al. (2022). Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study. Translational Psychiatry, 12, 307. https://doi.org/10.1038/s41398-022-02039-0

Dumitru, I., Paterlini, M., et al., & Frisén, J. (2025). Identification of proliferating neural progenitors in the adult human hippocampus. Science. https://doi.org/10.1126/science.adu9575

Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L., & Leão, R. N. (2018). A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mice ventral dentate gyrus. Frontiers in Molecular Neuroscience, 11, 312. https://doi.org/10.3389/fnmol.2018.00312

Lima da Cruz, R. V., Leão, R. N., & Moulin, T. C. (2024). Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review. Molecular Medicine, 30, 244. https://doi.org/10.1186/s10020-024-01013-4

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Morales-García, J. A., Calleja-Conde, J., Lopez-Moreno, J. A., et al. (2020). N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo. Translational Psychiatry, 10, 331. https://doi.org/10.1038/s41398-020-01011-0

Nardou, R., Sawyer, E., Song, Y. J., et al. (2023). Psychedelics reopen the social reward learning critical period. Nature, 618, 790–798. https://doi.org/10.1038/s41586-023-06204-3

Polito, V., & Liknaitzky, P. (2024). Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research. Journal of Psychopharmacology, 38(8), 701–711. https://doi.org/10.1177/02698811241254831

Shao, L.-X., Liao, C., Gregg, I., et al. (2021). Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron, 109(16), 2535–2544.e4. https://doi.org/10.1016/j.neuron.2021.06.008

Siegel, J. S., Subramanian, S., Perry, D., et al. (2024). Psilocybin desynchronizes the human brain. Nature, 632, 131–138. https://doi.org/10.1038/s41586-024-07624-5

Szigeti, B., Kartner, L., Blemings, A., et al. (2021). Self-blinding citizen science to explore psychedelic microdosing. eLife, 10, e62878. https://doi.org/10.7554/eLife.62878

Vargas, M. V., Meyer, R., Avanes, A. A., et al., & Olson, D. E. (2023). Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Science, 379(6633), 700–706. https://doi.org/10.1126/science.adf0435

AI disclosure: AI (Claude Cowork) was used to facilitate access to research and scientific data, assist with drafting and organizing text, and provide error checking. The author generated the underlying intellectual ideas and research questions, interpreted the scientific literature, formulated the essay’s conclusions, verified all sources, and made all other decisions about intellectual content.