For most of his adult life, Aaron Presley, age 34, felt like a husk of a person, a piece of “garbage.” He was trapped in a reality that was so excruciatingly tedious that he had trouble getting out of bed in the morning. Then, all at once, the soul-crushing, depressive fog started to lift, and the most meaningful experience of his life began.

The turning point for Presley came as he lay on a psychiatrist’s couch at Johns Hopkins University, wearing an eyeshade and listening through a pair of Bose headphones to a Russian choir singing hymns. He had consumed a large dose of psilocybin, the active ingredient in what’s more commonly known as magic mushrooms, and entered a state that could best be described as lucid dreaming. Visions of family and childhood triggered overwhelming and long-lost feelings of love, he says, “like heaven on earth.”

Presley was one of 24 volunteers taking part in a small study aimed at evaluating the effectiveness of a combination of psychotherapy and this powerful mind-altering drug to treat depression—an approach that, should it win approval, could be the biggest advance in mental health since Prozac in the 1990s.

Depression, often characterized by feelings of worthlessness, profound apathy, exhaustion and persistent sadness, affects 320 million people around the world. In a typical year in the U.S., roughly 16 million adults, or 7 percent, suffer from a depression-related illness such as major depression, bipolar disorder or dysthymia. Roughly one-third of those who seek treatment won’t respond to verbal or conventional drug therapies.

Magic-mushroom therapy is offering some hope for these hopeless cases. In the Hopkins study, published last year in JAMA Psychiatry, the therapy was four times more effective than traditional antidepressants. Two-thirds of participants showed a more-than 50-percent reduction in depression symptoms after one week; a month later, more than half were considered in remission, meaning they no longer qualified as being depressed.

Larger clinical trials underway in the United States and Europe are aimed at winning regulatory approval. Two studies that have enrolled more than 300 patients in 10 countries were given “breakthrough therapy” status in 2018 and 2019 by the U.S. Food and Drug Administration (FDA), which will now expedite its review of the results. If the trials succeed, new protocols that combine psilocybin with psychotherapy in a clinical setting for the treatment of depression could be established quickly. Treatments could appear in clinics as early as 2024.

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