Psychedelic drugs are promising treatments for many mental illnesses, but researchers don't fully understand why they have such powerful therapeutic effects. Now, a study in mice suggests that psychedelics all work in the same way: They reset the brain to a youthful state where it can easily absorb new information and form crucial connections between neurons.
Findings show that psychedelic drugs can enable long-term changes in many types of behavioral, learning and sensory systems that are disrupted in mental illness. But scientists caution that more research needs to be done to determine how the drugs remodel brain connections.
Psychedelic drugs such as MDMA (also known as ecstasy), ketamine and psilocybin – the active ingredient in magic mushrooms – are known for producing mind-altering effects, including hallucinations in some cases. But each compound affects a different biochemical pathway in the brain during the short "trip," leading scientists to wonder why so many of these drugs share the ability to relieve depression, addiction and other hard-to-treat conditions in the long run.
Gül Dölen, a neuroscientist at Johns Hopkins University in Baltimore, Maryland, and her colleagues sought answers by studying how psychedelics influence social behavior in mice. Mice can learn to associate socialization with positive feelings, but only during a "critical period" for adolescents, which ends when they reach adulthood.
The scientists trained mice to associate one "bedroom" in their enclosure with mice friends and another room with solitude. They could then examine how psychedelics affected the rodents' room choices — a measure of whether the drug affects the critical period.
Dölen's team had previously found that giving adult mice MDMA in the company of other mice reopened the critical period, making the MDMA-treated animals more likely to sleep in the social room than untreated mice. This was not surprising: MDMA is known for promoting bonding in some animals and in humans.
Mice didn't prefer the social space if they were given enough ketamine to render them unconscious and thus oblivious to the other mice. This suggests that the drugs only open the socially critical period when taken in a social context. Each drug opened the critical period for a different length of time, ranging from a week for ketamine to more than four weeks for ibogaine.
New connections through psychedelic drugs
Next, the team looked at the animals' brains. They discovered that neurons in certain brain regions had become more sensitive to the 'love hormone' oxytocin. Dölen suspects that the drugs confer a state called metaplasticity on the neurons that makes the cells more responsive to a stimulus such as oxytocin. This condition makes them more likely to rewire and form new connections.
Dölen argues that psychedelic drugs function as a master key that can unlock many kinds of critical periods—not just one for sociability—by imparting metaplasticity to neurons. The end result depends on the context in which the drugs are taken: the level of social involvement in this case. The results indicate, she says, "that there is a mechanistic relationship between the onset of the critical period and that altered state of consciousness shared by all psychedelics."
Takao Hensch, a neurologist at Harvard University in Cambridge, Massachusetts, says the paper is groundbreaking in finding biological mechanisms for how psychedelic drugs work. “It gives hope that critical periods are not irreversible and a very careful cellular understanding of psychedelic drugs could be the key to reopening brain plasticity,” he says. He adds that social behavior is very complex and the effects of the drugs in other brain regions need to be studied.
David Olson, a biochemist at the University of California, Davis, is skeptical. The drugs, he says, could change physical connections between neurons in certain areas of the brain, rather than inducing metaplasticity that makes the neurons more open to being influenced by environmental stimuli. Dölen is now testing whether the psychedelic drugs can reopen other types of critical periods, including those for the motor system. Reopening, she says, could extend the amount of time that people who've had a stroke can benefit from physical therapy, which currently only works in the first few months after a stroke.
Source: nature.com (EN)