Psychedelic-inspired drugs without hallucinogenic effects could effectively treat depression
A new paper recently published in Nature Neuroscience, co-authored by senior postdoc Caroline Biojone from Sâmia Joca Lab. The study shows that animal experiments identify separate mechanisms behind psychedelics' antidepressant and hallucinogenic effects and provide a target for future drug development.
Recent scientific evidence has indicated that psychedelic substances, such as psilocybin, can also improve the mood of depressed patients. However, hallucinations can be risky and make it difficult to use these substances for depression treatment. Researchers have now discovered a way to separate the mood-enhancing effects from the hallucinations. They found that compounds such as LSD and psilocybin (found in magic mushrooms) can induce antidepressant-like effects in animal models through a new mechanism that does not involve hallucinations. Psychedelic substances interact with multiple parts of the brain, making their effects complex.
New research led by Eero Castren (Univ Helsinki), in collaboration with many researchers, including Caroline Biojone (Biomedicine, Aarhus University), shows that psychedelic substances bind more strongly to TrkB, a neurotrophin involved with neuroplasticity, than traditional antidepressant drugs. They also increase the number of connections between brain cells in mice, which is believed to be important for rapidly improving mood.
This is effect is crucial for the antidepressant effect of psychedelics and other antidepressants, but it is not involved in the hallucinogenic effect. On the other hand, by blocking another protein to which the psychedelics also bind, the 5-HT2A receptor, the researchers observed that psychedelics still had an antidepressant effect without causing hallucinations.
These striking results open up the possibility of developing new drugs that can treat depression without causing hallucinations. Although these results are promising, it will take time to develop drugs that specifically target TrkB and conduct thorough tests to ensure their effectiveness and safety for people with depression. It will require further research and time before these medications can be available for use in humans.