Psychedelics induce fast and long-lasting antidepressant effects and neuronal plasticity, but their hallucinogenic effects limit their use. We show that, in mice, psychedelics bind directly to TrkB (the brain-derived neurotrophic factor (BDNF) receptor) with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding.
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References
Goodwin, G. M. et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N. Engl. J. Med. 387, 1637–1648 (2022). Phase 2 double-blinded trial with psilocybin for the treatment of major depressive disorder.
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Casarotto, P. C. et al. Antidepressant drugs act by directly binding to Trkb neurotrophin receptors. Cell 184, 1299–1313.e19 (2021). Original finding that conventional and rapid-acting antidepressants bind to TrkB.
Cameron, L. P. et al. A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 589, 474–479 (2021). A paper discussing potentially non-hallucinogenic psychedelic analogues that retain plasticity-inducing and antidepressant-like effects.
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This is a summary of: Moliner, R. et al. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat. Neurosci. https://doi.org/10.1038/s41593-023-01316-5 (2023).
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Psychedelics bind to TrkB to induce neuroplasticity and antidepressant-like effects. Nat Neurosci 26, 926–927 (2023). https://doi.org/10.1038/s41593-023-01317-4
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DOI: https://doi.org/10.1038/s41593-023-01317-4
