Psychedelics For Treating Depression: New Research Finds Key In BDNF Receptor

In response to the question of how psychedelics can prove effective in treating mental health conditions like depression, an international neuroscience team seems to have found a new answer.

Published in the Nature Neuroscience journal, results from the preclinical research show that LSD and psilocin (psilocybin’s metabolite) bind directly and effectively to a specific receptor in the brains of mice and that itself produces a reduction in depression -without involving hallucinations.

“Essentially all antidepressant drugs, including psychedelics, promote neuroplasticity, which is considered a critical component of their therapeutic effect,” the paper starts off. “Brain-Derived Neurotrophic Factor (BDNF) and its receptor TrkB are central mediators of plasticity and the therapeutic action of antidepressants.” 

Recent findings show that antidepressants, including fluoxetine, imipramine and ketamine directly bind to TrkB and potentiate BDNF signaling. Further, BDNF and TrkB “have also been implicated in the action of psychedelics as downstream effectors of 5-HT2A activation.” 

Because psychedelics “produce robust spinogenesis and dendritogenesis, and these effects are known to require intact TrkB signaling,” the team explains they set out to explore whether direct binding to TrkB might mediate psychedelics’ neuroplastic effects.

What they found is that psychedelics produce similar therapeutic effects “at least as effective as those of currently used antidepressants,” by binding to “distinct but partially overlapping sites” in the brain.

Specifically, LSD and psilocin’s binding to a receptor called TrkB showed increased neuroplastic activity when tested in-vitro. 

Following suit, researchers gave a single LSD dose to chronically stressed mice, resulting in an antidepressant-like behavior. 

The compound’s effect on endogenous BDNF-signaling promotor TrkB was found to be independent of activation of the serotonin 2A receptor (5-HT2A), the latter believed to be responsible for the psychedelic experience (mice’s head-twitching.)

This discovery, the study’s authors say, could lead to the development of effective antidepressant drugs that do not hold hallucinogenic effects, something that limits psychedelics’ widespread clinical application in view of the intensive monitoring these effects require as well as the concern of potential appearance of Hallucinogen Persisting Perception Disorder (HPPD,) among other unwanted consequences.

The findings “support TrkB as the key target for psychedelic drug-induced plasticity” and confirm “TrkB as a common primary target for antidepressants,” while suggesting that their “high affinity” with TrkB modulators without producing 5-HT2A activity “may retain the antidepressant potential of psychedelics without hallucinogenic effects,” the team concluded.

Photo: Benzinga edit with photo by Olia Danilevich on Pexels.