Brain-derived neurotrophic factor (BDNF) is a protein that supports the growth and connections of neurons, and TrkB is the receptor it acts on. Both come up because many antidepressants are thought to work partly through this system.
A 2023 Nature Neuroscience paper reported that LSD and psilocin bind TrkB directly, with affinities about 1,000-fold higher than other antidepressants tested. In mice, their effects on plasticity signalling and antidepressant-like behaviour depended on TrkB and were independent of 5-HT2A, while LSD’s head twitch still needed 5-HT2A (Moliner et al., 2023).
This is contested and not a human result. Another 2023 study instead tied psychedelics’ growth-promoting effects to 5-HT2A receptors inside neurons (Vargas et al., 2023). The TrkB paper did not test DMT, so claims that DMT binds the BDNF receptor go beyond it. Nobody has measured TrkB binding by psychedelics in a living human brain.
Sources
- Moliner et al., 2023, Nature Neuroscience: psychedelics bind TrkB
- Vargas et al., 2023, Science: intracellular 5-HT2A
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