Cracking the Code: Can Your Biology Predict Your Response to Psychedelic Therapy?

This article answers the question: What biological markers are emerging from scientific research that could help predict who will respond best to psychedelic-assisted therapies?

Synopsis 

As psychedelic therapy is about to become mainstream, a crucial question is being asked: why does it perform miracles for some and nothing for others? The answer may lie in our biology. A systematic review of nine studies recently identified several promising "biomarkers"—measurable markers in our blood and brain—that are associated with positive responses to ayahuasca and psilocybin therapies. These include proteins in the blood that are involved in inflammation and neuroplasticity, and some patterns of brain activity and connectivity. Although the research is still in its early stages, these findings are paving the way to a future of tailored psychedelic medicine, where therapies can be crafted based on a person's unique biological makeup.

The Quest for Personalized Psychedelic Medicine

Psychedelic-assisted therapy is showing tremendous promise for the treatment of various mental illnesses, ranging from treatment-resistant depression to PTSD. Yet, as with any medication, individual responses can be extremely diverse. For someone who is considering this therapeutic path, one of the largest questions is whether it will be effective for them personally. That is where the science of biomarkers comes in. A biomarker is a biological signpost—a quantifiable element in the body that can mirror a particular disease state or predict a response to treatment. Identifying these markers for psychedelic therapy could help move the field from one-size-fits-all to a highly personalized level.

Clues in the Blood

Recent research has pointed to several promising biomarkers that can be evaluated with a simple blood test. A 2025 systematic review in Therapeutic Advances in Psychopharmacology found two significant proteins in the blood that are linked to treatment outcome [1]. The first is Brain-Derived Neurotrophic Factor (BDNF), a protein vital to the growth and survival of neurons. Studies have found that increased levels of BDNF after ayahuasca treatment are linked to a significant reduction in depressive symptoms. This supports the leading theory that psychedelics work, in part, by promoting neuroplasticity—the brain's ability to reorganize and form new neural connections [2, 3].

The second blood-based marker is C-reactive protein (CRP), a marker for inflammation in the body. The review found that CRP levels were also associated with treatment response, suggesting that there could be a link between the body's inflammatory state and the therapeutic effects of psychedelics. These findings are particularly interesting since they suggest that relatively non-invasive blood tests could one day be used to help clinicians determine if a patient is a suitable candidate for psychedelic therapy.

Whispers from the Brain

Beyond blood tests, neuroimaging techniques like fMRI are also revealing how brain activity can predict treatment response. The review identified several patterns of interest. For example, reduced blood flow in the amygdala, the emotional processing center of the brain, after a psilocybin session was strongly associated with a reduction in depressive symptoms [1]. This suggests that deactivating this typically overactive region is one way in which psilocybin has its antidepressant effect.

The other important area is the Default Mode Network (DMN), a network in the brain that is very active when we are engaged in self-referential thinking or mind-wandering. In depression, the DMN can become rigid and overactive, locking individuals into patterns of rumination and negative self-talk. The review also confirmed that one of the main actions of psychedelics is that they decrease activity in the DMN and increase connectivity between the DMN and other networks in the brain [1, 4]. It is this "resetting" of the DMN that is thought to allow for the breaking of rigid thought patterns and the establishment of new, healthier ones. The extent of this DMN modularity decrease was predictive of long-term depression improvement. 

A Common Path to Recovery

Interestingly, some of the biomarkers found to be linked to psychedelic therapy, such as BDNF and changes in amygdala activity, are also implicated in response to traditional antidepressants. This suggests that these different forms of treatment are likely tapping into an identical neurobiological mechanism to cure. By understanding these mechanisms in shared, scientists can make both traditional and psychedelic treatments more efficacious.

To skeptics of psychedelic therapy, this research should be reassuring. It demonstrates a clear, measurable biological substrate for the profound psychological changes these drugs can usher in. It suggests that the experiences people report are not just "in their heads" but are reflected in tangible changes in their brains and bodies. While the science is still in its earliest stages, it is also propelling us quickly toward a day when mental health care can be precisely tailored to the individual.

The Future is Personal

The discovery of these biomarkers is an important step toward individualizing psychedelic medicine. One day, a simple blood test or baseline brain scan may assist a clinician in knowing not only whether a patient is an ideal candidate for psychedelic therapy but also which drug and dose could work best for that individual. This would be a significant advance over the present trial-and-error method of mental illness treatment.

Even though we are not there yet, the path ahead is increasingly clear. The convergence of neuroimaging, molecular biology, and clinical research is unlocking the code of the psychedelic experience. For individuals afflicted with mental illness, research offers more than hope; it offers the possibility of a future where healing is not a matter of chance, but an anticipated and personalized science.

References

1.Wong, S., et al. (2025). Biological markers of treatment response to serotonergic psychedelic therapies: a systematic review. Therapeutic Advances in Psychopharmacology. https://doi.org/10.1177/20451253251384513

2.Moliner, R., et al. (2023). Psychedelics promote plasticity by directly binding to BDNF receptors. Nature Neuroscience, 26(6), 1032–1041. https://doi.org/10.1038/s41593-023-01316-5

3.Constantino, J. L., et al. (2025). A systematic review of blood biomarkers associated with the acute and sustained antidepressant effects of psilocybin. Journal of Affective Disorders, 374, 463-472. https://doi.org/10.1016/j.jad.2025.01.005

4.Vohryzek, J., et al. (2024). Brain dynamics predictive of response to psilocybin for treatment-resistant depression. Nature Medicine, 30(3), 823-831. #https://pubmed.ncbi.nlm.nih.gov/38515439/

5.Palhano-Fontes, F., et al. (2019). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine, 49(4), 655-663. #https://pubmed.ncbi.nlm.nih.gov/29903051/

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.