Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis
This pre-registered systematic review and meta-analysis of 29 studies found no evidence that psychoplastogens (e.g. ketamine, psychedelics, MDMA, scopolamine) acutely increase peripheral BDNF in humans (SMD = 0.024, p = 0.64), with results unchanged by drug, dose, blood fraction, age or diagnosis. The authors conclude peripheral BDNF is unlikely to be a useful marker of rapid neuroplasticity in humans and recommend more precise neuroimaging and stimulation-based measures for future translation.
Authors
- Gregor Hasler
- Abigail Calder
Published
Abstract
Background
Peripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test whether the rapid upregulation of neuroplasticity seen in preclinical studies is detectable using peripheral BDNF in humans.
Methods
This analysis was pre-registered (PROSPERO ID: CRD42022333096) and funded by the University of Fribourg. We systematically searched PubMed, Web of Science, and PsycINFO to meta-analyze the effects of all available psychoplastogens on peripheral BDNF levels in humans, including ketamine, esketamine, LSD, psilocybin, ayahuasca, DMT, MDMA, scopolamine, and rapastinel. Risk of bias was assessed using Cochrane Risk of Bias Tools. Using meta-regressions and mixed effects models, we additionally analyzed the impact of several potential moderators.
Results
We included 29 studies and found no evidence that psychoplastogens elevate peripheral BDNF levels in humans (SMD = 0.024, p = 0.64). This result was not affected by drug, dose, blood fraction, participant age, or psychiatric diagnoses. In general, studies with better-controlled designs and fewer missing values reported smaller effect sizes. Later measurement timepoints showed minimally larger effects on BDNF.
Conclusion
These data suggest that peripheral BDNF levels do not change after psychoplastogen administration in humans. It is possible that peripheral BDNF is not an informative marker of rapid changes in neuroplasticity, or that preclinical findings on psychoplastogens and neuroplasticity may not translate to human subjects. Limitations of this analysis include the reliability and validity of BDNF measurement and low variation in some potential moderators. More precise methods of measuring rapid changes in neuroplasticity, including neuroimaging and stimulation-based methods, are recommended for future studies attempting to translate preclinical findings to humans.
Research Summary of 'Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis'
Introduction
Preclinical work established that several fast-acting compounds — including ketamine and classic psychedelics — promote structural and functional neuroplasticity in cortical circuits and have rapid antidepressant or therapeutic effects in animals. This group of molecules, often termed psychoplastogens, has been associated in animal models with dendritogenesis, synaptogenesis and increased neurotrophic signalling, notably involving brain-derived neurotrophic factor (BDNF). In humans, peripheral measures of BDNF (serum or plasma) are frequently used as an accessible proxy for brain neuroplasticity, but peripheral BDNF is biologically noisy and prior human studies of psychoplastogens have produced mixed results. Calder and colleagues set out to test whether the rapid upregulation of neuroplasticity reported in preclinical studies is detectable in humans using peripheral BDNF. They conducted a preregistered systematic review and meta-analysis across a broad set of psychoplastogens (ketamine, esketamine, LSD, psilocybin, ayahuasca/DMT, MDMA, scopolamine, rapastinel and related compounds), examined multiple timepoints, and planned moderator analyses to investigate factors such as blood fraction (plasma versus serum), timing of measurement, dose, assay specificity, study design and risk of bias.
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Study Details
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- APA Citation
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
References (31)
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Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Dos Santos, R. G., Osório, F. L., Crippa, J. A. et al. · Therapeutic Advances in Psychopharmacology (2016)
Ly, C., Greb, A. C., Cameron, L. P. et al. · Cell Reports (2018)
Moliner, R., Girych, M., Brunello, C. A. et al. · Nature Neuroscience (2023)
Vargas, M. V., Dunlap, L. E., Dong, C. et al. · Science (2023)
Olson, D. E. · Biochemistry (2022)
Calder, A. E., Hasler, G. · Neuropsychopharmacology (2022)
Olson, J. A. · Neuroscience Insights (2018)
Shao, L-X,, Liao, C., Gregg, I. et al. · Neuron (2021)
Greb, A. C., Vargas, M. V., Duim, W. C. et al. · ACS Pharmacology and Translational Science (2020)
Show all 31 referencesShow fewer
Cameron, L. P., Patel, S. D., Vargas, M. V. et al. · ACS Chemical Neuroscience (2023)
Nardou, R., Sawyer, E., Song, Y. J. et al. · Nature (2023)
Medeiros, G. C., Gould, T. D., Prueitt, W. L. et al. · Molecular Psychiatry (2022)
Holze, F., Vizeli, P., Müller, F. et al. · Neuropsychopharmacology (2019)
Straumann, I., Ley, L., Holze, F. et al. · Neuropsychopharmacology (2023)
Hutten, N. R. P. W., Mason, N. L., Dolder, P. C. et al. · ACS Pharmacology and Translational Science (2020)
Abdallah, C. G., Jackowski, A., Salas, R. et al. · Neuropsychopharmacology (2017)
Kopelman, J., Keller, T. A., Panny, B. et al. · Translational Psychiatry (2023)
Barrett, F. S., Doss, M. K., Sepeda, N. D. et al. · Scientific Reports (2020)
McCulloch, D. E-W., Madsen, M. K., Stenbæk, D. S. et al. · Journal of Psychopharmacology (2021)
Sampedro, F., de la Fuente Revenga, M., Valle, M. et al. · International Journal of Neuropsychopharmacology (2017)
Skosnik, P. D., Sloshower, J., Safi-Aghdam, H. et al. · Journal of Psychopharmacology (2023)
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
Grunebaum, M. F., Galfalvy, H. C., Choo, T. H. et al. · American Journal of Psychiatry (2018)
Grunebaum, M. F., Ellis, S. P., Keilp, J. G. et al. · Bipolar Disorders (2017)
Holze, F., Vizeli, P., Ley, L. et al. · Neuropsychopharmacology (2020)
Holze, F., Ley, L., Müller, F. et al. · Neuropsychopharmacology (2022)
Ley, L., Holze, F., Arikci, D. et al. · Neuropsychopharmacology (2023)
Rocha, J. M., Rossi, G. N., de Lima Osório, F. et al. · Journal of Clinical Psychopharmacology (2021)
Vogt, S. B., Ley, L., Erne, L. et al. · Translational Psychiatry (2023)
Zheng, W., Zhou, Y. L., Wang, C. Y. et al. · PeerJ (2021)
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