How Psychedelics Rewire the Brain to Treat Depression

Scientists are beginning to recognize psychedelics as more than a party drug. A push to decriminalize psychedelic medicine recently renewed research interest in the health benefits of hallucinogenic substances. And the push paid off.

Psychedelics have transformed how doctors treat depression with most of the spotlight on psilocybin. It’s been found that a single trip can improve depressive symptoms, including those whose depression has been labeled as treatment-resistant. What’s more, ongoing studies show one mystical experience is enough to keep depression away for up to a year. The drug’s effects boil down to how it revamps the brain.

“Our default mode of thinking typically blocks us from exploring the possibility of change. Psychedelics temporarily bring down our defenses to let us truly feel and process our past and present experiences in new ways,” says David Merrill, MD, PhD, a psychiatrist and the director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica. 

Having your brain altered might sound terrifying and it’s one reason psychedelics were taboo for so long. Still, with the proper supervision, micro-dosing on psilocybin and other drugs could help in strengthening our brains and making them more resilient against depression and other health conditions.

You might have heard from anyone who has taken psychedelics that the drug opened up their minds to change. This figure of speech is actually quite literal, says Merrill, since psychedelics are psychologically reorganizing the brain on a neural and cellular level. 

The psychedelic experience shakes up the human mind like a snow globe, explains Robin Carhart-Harris, PhD, a psychiatrist and head of the Center for Psychedelic Research at Imperial College London told PBS. Left alone, the snow is laying at the bottom but jiggling it causes things to move around, creating a flurry of randomness. Similarly, psychedelics disrupt your brain and stir up the neural patterns you have cemented in your life. 

People feel this shake-up in their minds by experiencing an altered sense of reality. This is likely because hallucinogens target an area involved in creating our conscious experience called the claustrum. The claustrum acts as a communication conductor for the brain, deciding who talks to who. Psychedelics like psilocybin decrease 15 to 30 percent of activity in the claustrum, allowing brain regions to expand their networks to other areas they may not have talked to as much. For example, a single dose of psilocybin strengthened the connections between the prefrontal cortex and brain areas in charge of positive emotions. At the same time, the connections between the prefrontal cortex involved in anxiety and other negative emotions decreased. 

This mental effort of metabolizing what we’ve lived through allows for new perspectives to be formed. “This can be transformative even after only 1 or 2 psychedelic experiences,” adds Merrill.

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