The New Promise of Psychedelics
Research on mice suggests that the long-banned drugs can have surprising therapeutic effects for humans, though risks remain
By Alison Gopnik, WSJ
July 20, 2023 2:47 pm ET
Psychologist Alison Gopnik explores new discoveries in the science of human nature. Read previous columns here.
Recently there has been a remarkable renaissance of medical research into psychedelic drugs, which were widely banned a half-century ago. The risks and dangers of these drugs still need to be better understood, but it’s becoming clear that they may have important potential benefits. New studies suggest that psychedelics, carefully administered in controlled settings with trained therapists, can help treat mental illnesses like depression, addiction and PTSD. But just how do psychedelics achieve these therapeutic effects?
A new study in the journal Nature by the neuroscientist Gul Dolen at Johns Hopkins and colleagues tackles this question. What psychedelics have in common, the study finds, is that they return the relatively rigid, developed adult brain to a more flexible, open state, more like the childhood brain. This may be key to their positive effects.
Each of the classic psychedelic drugs—MDMA (Ecstasy), LSD, psilocybin, ketamine, ibogaine—is a different kind of chemical with a different effect on the brain. MDMA leads to strong feelings of social connection; the LSD experience is more like solitary mysticism; ketamine is also an anesthetic. The effects of some last for hours, others for days. And, of course, people can have similar experiences without chemicals—the ecstasies of religious mystics or the epiphanies of Romantic poets.
The research suggests that psychedelics work by opening up the brain to new possibilities, allowing it to escape from old ruts, change and learn.
To search for what unites these drugs, Dolen’s team gave mice a variety of psychedelics and observed their effects. Mice, like people, have what are called “critical periods” for various kinds of development—times when the brain is especially open to new experiences and especially likely to learn and change. After a critical period closes, that type of learning is much harder. These specific critical periods reflect a more general phenomenon: Brains start out more “plastic,” easier to change and more sensitive to experience, and get more efficient but more rigid as people—or mice—grow older.
One critical period for mice involves social learning. Young mice do better than their elders at a task that involves learning about other mice. In the study, all the psychedelics reopened this critical period: Adult mice under their influence learned like young ones. Neither cocaine nor saline had this effect. The researchers also found that the drugs that last longer in humans led to a longer reopening of critical periods in mice.
As expected, the different drugs acted through different chemical mechanisms. But all of them ultimately activated genes that made the brain more “plastic,” more easily changed.
Other research shows that psychedelics may reopen other kinds of critical periods. For example, amblyopia, or “lazy eye,” must be treated early for the visual cortex to rewire properly. But a 2020 study published in Current Biology found that ketamine reopened the visual critical period in mice, allowing older animals to recover from amblyopia.
These results have important implications for psychedelic therapy. We know that the effects of psychedelics depend on “set and setting”—the context and the attitude of the person who takes them—and that psychedelic experiences can feel wonderful or terrible to the user. The new research suggests that psychedelics work by opening up the brain to new possibilities, allowing it to escape from old ruts, change and learn. That might give humans a chance to change addictive habits or destructive thought patterns.
But the chemicals themselves don’t determine how the brain changes or what it learns. Any transformation depends on what happens next. The potential medical benefits depend on therapists making sense of the disruptive experience, ensuring that the mind and brain settle in a better place.
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