LSD and psilocin—the psychedelic compound in magic mushrooms—can produce an antidepressant response in mice through a molecular mechanism that is completely separate from the one responsible for hallucinogenic effects.
Psychedelic drugs, best known for causing hallucinations, can also lift users’ moods, preliminary results from clinical trials suggest. But the risks that come with the trip are an obstacle to using the drugs as antidepressants. Hallucinations might trigger psychosis in people with certain risk factors, and because of their unpredictable effects, clinicians have to closely monitor patients as they take the drugs.
The work is rigorous and careful, says Revathy Chottekalapanda, a neuroscientist at Weill Cornell Medicine, and the results are intriguing. But Chottekalapanda and others emphasize that the path from demonstrating these kinds of effects in basic research to developing drugs that are effective in humans could be treacherous.
In the new study, the researchers show that psychedelic drugs have a similar mechanism. First, they demonstrated that LSD and psilocin bind to TrkB in cells in a dish—and do so 1000 times more strongly than classical antidepressants. They also found the drugs spurred rat and mouse neurons to develop an increased number of neural connections, indicating increased neuroplasticity.
His team took advantage of the fact that rodents on a hallucinogenic drug normally twitch their heads as if they are shaking off a fly. Mice given LSD along with the serotonin 2A blocker did not display the head-twitch response. But they did show an improvement in the “freezing” behavior that researchers use as an analog of human depression, suggesting the drugs were still having an antidepressant effect.
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