Do Psychedelics Only Affect a Small Part of Your Brain?

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This article discusses the common myth that psychedelics like LSD and psilocybin only target a small set of brain cells. We will explore new evidence proving otherwise and that shows these drugs affect the brain much more strongly.

Synopsis

Researchers long thought psychedelics affected the brain mainly via one type of brain receptor, the 5-HT2A. But a groundbreaking 2025 University of Michigan study surprises us by finding that these chemicals change the behavior of way more brain cells than we thought. Most of them don't even have the 5-HT2A receptor. This research, and other research into how psychedelics change the brain, shows that perhaps such drugs can help people in more complex ways than we ever imagined. 

The Surprising Truth About How Psychedelics Change Your Brain

If you ever wondered how psychedelics can work, you might have heard that they primarily impact one specific type of brain receptor. That receptor has the name 5-HT2A. It is serotonin-sensitive, a brain chemical that affects mood and thought. That was the prevailing theory for decades. It gave us a simple explanation for the intense experiences people reported. But what if that's only half the story? Emerging research is rewriting this long-held presumption. It discloses that psychedelics may have a much greater effect on our brains than we ever imagined [1].

This new find is more than intriguing science. It has significant ramifications for mental health treatment. As psychedelic therapy becomes increasingly mainstream for the care of depression, PTSD, and addiction, we need a clear understanding of how these chemicals work. A 2025 University of Michigan study has provided us with a missing piece in this puzzle. It shows that psychedelics change the activity of a surprisingly large number of brain cells. Most of them don't even have the 5-HT2A receptor at all [2]. This new discovery opens up new ways of doing research. It may even lead to even more effective treatments.

Beyond the 5-HT2A Receptor: A New Way of Thinking

The 5-HT2A receptor has been the preeminent target for psychedelic study for decades. It's a protein on some brain cells that responds to serotonin. Serotonin is a neurotransmitter in the brain that influences mood and thinking. Psychedelics like LSD and psilocybin are similar to serotonin. They can attach to and stimulate these receptors. This is what creates the mind changes we see with psychedelic use. But this is only half the story, according to the University of Michigan study.

The researchers used a new approach to labeling and tracking brain cells stimulated by psychedelics. They found that these drugs acted on a far greater area than they had expected. They observed alterations in areas of the brain that are not dominated by very few 5-HT2A receptors. This suggests other mechanisms are involved [2]. Other research has also shown how different brain receptor systems interact. It suggests that psychedelics can affect many cell processes [3]. The experience of psychedelics is not a result of stimulating one receptor alone. It's more like many changes that ripple across the whole brain.

How Brain Plasticity Helps Psychedelics to Heal

One of the most exciting areas of research into psychedelics is neuroplasticity. This is the ability of the brain to reorganize through new associations between brain cells. Scientists think that this is one of the key reasons why psychedelics create long-term healing effects. From research, a single dose of a psychedelic is able to lead to rapid and long-term growth of new dendrites and synapses. These are the associations between brain cells [4]. This "rewiring" of the brain may help to break down rigid behaviors and modes of thinking. These are characteristic of many mental disorders.

The new discovery that psychedelics act on many varieties of brain cells, not just 5-HT2A receptor-carrying cells, adds another twist to what we knew. It provides the prospect that the brain-modifying effects of these substances may be more general than we presume. By stimulating brain plasticity to a larger degree, psychedelics are able to aid the brain in healing itself from within. This creates a more resiliant and malleable neural network. This may be why so many find that they undergo deep, lasting positive shifts in mood, worldview, and general health after a psychedelic episode. 

What This Means for Future Psychedelic Therapy

The discovery that psychedelics engage the brain much more extensively than we ever thought has enormous potential for the development of new treatments. It shows that we may be able to tailor therapies to be more specific and more effective. They may have fewer unwanted side effects. For example, by understanding the complete extent of the receptors and cellular pathways to which therapeutic action is related, we may be able to come up with new drugs. These may access the therapeutic potential of psychedelics without inducing a complete psychedelic experience [5].

As we venture deeper into the vastness and complexity of the brain, the psychedelic history is an opening-eyes reminder. So much more is yet to be found. The journey from a primitive receptor-based model to an increasingly fine-tuned understanding is proof that science is constantly evolving. With each discovery, we move closer to realizing the full potential of psychedelic medicine. We're offering new hope to the mentally ill.

References

[1] Cameron, L. P., Benetatos, J., & Lewis, V. (2023). Beyond the 5-HT2A receptor: classic and nonclassic targets in psychedelic drug action. Journal of Neuroscience, 43(45), 7472-7480. https://www.jneurosci.org/content/43/45/7472

[2] University of Michigan. (2025, October 8). Psychedelics alter far more neurons than expected. University of Michigan News. https://news.umich.edu/psychedelics-alter-far-more-neurons-than-expected/

[3] Calder, A. E., & Hasler, G. (2023). Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology, 48(2), 238-249. https://www.nature.com/articles/s41386-022-01389-z

[4] Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., ... & Olson, D. E. (2018). Psychedelics promote structural and functional neural plasticity. Cell reports, 23(11), 3170-3182. https://pmc.ncbi.nlm.nih.gov/articles/PMC6082376/

[5] Drewko, A. J., Habets, R. L. P., & Brunt, T. M. (2025). Above the threshold, beyond the trip: the role of the 5-HT2A receptor in psychedelic-induced neuroplasticity and antidepressant effects. Molecular Psychiatry. https://www.nature.com/articles/s41380-025-03169-9

Disclaimer: Psychedelic Assisted Psychotherapy has not been approved by any regulatory agencies in the United States, and the safety and efficacy are still not formally established at the time of this writing.