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Scientists May Have Found Exactly How LSD Treats Depression

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This could lead to trip-free treatments for millions of Americans with the mental disorder.

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Photo Illustration by Kelly Caminero / The Daily Beast / Getty

We’ve known that psychedelic drugs like psilocybin mushrooms and LSD show a lot of promise in addressing some of the world’s most widespread mental disorders for a while now. Not only can they treat things like treatment resistant depression and PTSD, but they can even help terminally ill patients with their end-of-life anxiety.

What scientists don’t know, though, is why exactly psychedelics are so effective at treating these disorders. Luckily, some new research by an international team of neuroscientists sheds light on this trippy mystery.

The researchers published a study on Monday in the journal Nature Neuroscience that showed that LSD and psilocin (the primary molecule in magic mushrooms) bind to a specific receptor in the brains of laboratory mice—causing an antidepressant effect as a result. Since the mechanism specifically works to reduce depression, the study’s authors believe that it could lead to the development of drugs to treat depression in humans without hallucinations.

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“The hallucinogenic effects of psychedelics limit their widespread clinical application, as their administration is restricted to clinical settings that often require intensive monitoring,” the study’s authors wrote. They added that their research suggests “that the antidepressant and plasticity-promoting effects of psychedelics may be dissociable from their hallucinogenic effects.”

Today, more than 17 million U.S. adults and 2 million children suffer from clinical depression. Roughly 10 to 30 percent of those patients don’t respond to traditional antidepressant medication either—resulting in treatment resistant disorders.

Enter psychedelics. In recent years, drugs like ketamine, LSD, magic mushrooms, and MDMA have shown a lot of promise in treating disorders like depression and PTSD. However, one major hurdle with these drugs is the fact that they often cause hallucinations. That means that patients undergoing psychedelic treatments need to be supervised by doctors in a highly-regulated medical setting.

That poses a huge barrier for the vast majority of patients. However, if the drug was as easy as popping a pill at home without the worry of tripping out, then it could open the doors to treating millions of people.

Broadly, scientists know that psychedelics encourage two processes that benefit mental health: neuroplasticity, which is when new neural connections are made in the brain; and neurogenesis, which is the formation of brain cells. Both of these processes are likely caused by the activation of specific receptors.

The study’s authors found that LSD and psilocin bind well to a receptor called TrkB in petri dishes. The binding resulted in an increase in neuroplastic activity. To study this mechanism further, the authors gave a single dose of LSD to mice with chronic stress. The team found that the drug resulted in an antidepressant effect due to the drug binding to TrkB.

Moreover, the researchers found that the effect on TrkB was independent from the drug’s effect on the brain’s serotonin receptors, which are believed to be responsible for psychedelic hallucinations. This suggests that the antidepressant effects can be caused independently from the hallucinatory effects.

“In conclusion, our findings support TrkB as the key target for psychedelic drug-induced plasticity,” the authors wrote. “These data confirm TrkB as a common binding target for antidepressants … but potentially devoid of hallucinogenic-like activity.”

So, in the future, we could have the feel-good benefits of LSD or magic mushrooms without the psychedelic trip. While that might be a little less fun than just taking the drug, it will be a huge boon to the millions of people in the U.S. who suffer from depression every day—and that’s something to feel groovy about.

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