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 billion 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.
The rehabilitation of psilocybin as a medical treatment raises some concerns. Some scientists worry about the drug, which can induce psychosis in some people, becoming widely available outside of clinical settings. And they are loath to see a repeat of the 1960s embrace of recreational LSD, which caused much harm and set research into psychedelics back decades.
But many scientists in the mental health profession believe that the risks pale against the potential benefits, which include not only effective treatments for depression but also a new understanding of the neural basis of many mental health disorders. “We’re convinced that the effects of these drugs are pretty profound and that there is a story that will be relevant to understanding new approaches to brain disease,” says Jerrold Rosenbaum, a Harvard Medical School professor, former psychiatrist-in-chief at Massachusetts General hospital and leader of its new Center for the Neuroscience of Psychedelics.
A New Renaissance
Although psychedelic drugs have been used by indigenous populations for millennia, they only entered the western medical mindset in 1943, when Albert Hoffman, a chemist at the Swiss pharmaceutical giant Sandoz, accidentally ingested a compound called lysergic acid diethylamide, or LSD. He promptly entered “a dreamlike state” and hallucinated “an uninterrupted stream of fantastic pictures, extraordinary shapes with intense kaleidoscopic play of colors.” Hoffman became convinced LSD might have some use in medicine and psychiatry.
Not long after, a Manhattan banker named R. Gordon Wasson took a trip to Oaxaca, Mexico, sampled psilocybin mushrooms, and published a 15-page account of his psychedelic experience in Life magazine, introducing the American public to the power of the plants.
Psychiatrists were soon reporting therapeutic benefits. By the 1960s they had dosed more than 700 alcoholics, half of whom subsequently stayed sober for at least a couple months. Other researchers discovered that the drugs were helpful for anxiety, depression, the existential angst of terminal cancer patients, and other mental health disorders—provided they were administered under supervision.
Psychedelic drugs lost their legitimacy soon after the counter-culture embraced them for recreation, triggering a spate of suicides, mental breakdowns and bad trips. Federal research funding dried up. Over the years, however, a few groups in the U.S. and abroad continued to conduct experiments on mice and map out the strange molecular-level gymnastics that give psilocybin its ability to so profoundly alter human perception.
Key to the action of the drug is its ability to bind to a special class of tiny proteins that protrude from the surface of many brain cells and detect passing chemical signals—in this case the neurotransmitter serotonin. What made the active molecules in LSD and psilocybin so powerful was a quirk in their geometry that caused the chemicals to get stuck in these proteins—known as serotonin 5H 2A receptors—and linger for hours, rather than quickly washing out as normal neurotransmitters would. Once the chemical was wedged inside a the receptors, it began to wreak havoc on the cell’s internal signaling, causing some neurons that normally wouldn’t fire to pop off like firecrackers, and prompting others to go dark.
These insights didn’t come close to explaining the deep questions scientists had about the drugs— why, for instance, they elicit deep spiritual experiences?—which could only come with human trials. In the early 1990s, after a campaign of lawsuits and lobbying by psychedelic advocates, the FDA re-evaluated psychedelic drugs and other “drugs of abuse” and indicated it would be open to applications to study them.
Clinical trials on mystical experiences, terminally ill cancer patients and addiction came in the mid-2000s from such prestigious institutions as New York University, UCLA and Johns Hopkins. Meanwhile, brain-scanning tools helped document the remarkable effects of the drugs on the brain. In recent years, a clearer picture of how these drugs work their magic—and why they might work as a therapy for mental disorders— has begun to emerge.
The Mystical Brain
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