A handful of healthy senior citizens are about to trip on psilocybin—to see if the psychedelic protects aging brains.
Psilocybin, the active ingredient in magic mushrooms, is best known for its ties to 1960s counterculture. But now it may also herald a new genre of mental health treatment. From severe depression to post-traumatic stress disorder, studies have highlighted psychedelic drugs’ ability to reshape brain networks and relieve debilitating symptoms.
Most of these studies have focused on younger people with mental health conditions that don’t respond to standard treatment. The field’s success is prompting scientists to ask if psychedelics could also help healthy brains age better.
A team from the UC Berkeley Center for the Science of Psychedelics is about to find out. In a first-of-its-kind study focused on adults between the ages of 60 and 85, they’ll investigate how psilocybin affects perception, emotion, and memory using a battery of psychological tests.
Multiple scans before and after dosing will track changes in the brain. And detailed surveys will gauge broader shifts in well-being: Do participants feel more “in tune” with their emotions, feel less isolated, or experience a renewed sense of wonder about the world?
“What really excites me is that we’re focused on healthy older adults,” said Tyler Toueg, who co-led the study’s design, in a press release. “Most clinical trials with older adults are focused on people who already have a diagnosis. We’re asking whether we can actually promote positive outcomes in older adults who are healthy.”
Called PLASTICITY, the trial could also open a rare window into how a psychedelic experience reshapes healthy brain networks. And because the drug alters our sense of self, psilocybin could help researchers probe the ways in which the brain constructs reality.
“I’m very interested in psilocybin as a potential mental health treatment, but I’m also interested in it as a way to shed light on these central mysteries in neuroscience and psychology,” said study designer Michael Silver.
Chasing the White Rabbit
Psychedelic research was highly restricted for decades. But advocates, including the non-profit Multidisciplinary Association for Psychedelic Studies, have steadily pushed to reopen the field, arguing that these drugs might keep mental health symptoms at bay.
Early results helped usher psychedelics into the mainstream. In 2023, a randomized, placebo-controlled trial found that a single dose of psilocybin, paired with therapy, eased depression. Oregon later approved supervised psilocybin therapy—though the drug remains federally illegal in the US—and Australia became the first country to greenlight it for depression and post-traumatic stress disorder. More recently, two late-stage studies reported strong effects in severe depression, potentially paving the way for FDA approval.
Scientists still don’t fully understand how psilocybin works in the brain. But there are hints. The drug appears to rapidly reorganize the connections between brain cells, particularly in the hippocampus, a region of the brain central to learning, memory, and navigation.
Neurons constantly change their connections in a process called plasticity that encodes experiences into neural networks, allowing the brain to process information, learn, and lock in memories. In youth, these connections are flexible and expansive. But with age and in conditions like depression, the brain’s flexibility wanes.
The birth of new neurons, or neurogenesis, also contributes to plasticity. Neurogenesis only occurs in two brain regions, one of which is the hippocampus. Although whether it actually takes place in humans is controversial, it is strongly linked to learning, memory, and emotion, and it declines in both psychiatric disorders and aging.
Psilocybin may reset brain plasticity to a more youthful state.
In rats modeling depression, for example, a study showed the drug shifted dark moods into behavior that was more exploratory and engaging. Where traditional antidepressants, like Prozac, tend to blunt symptoms, psilocybin seems to overwrite entrenched negative patterns. This suggests deeper circuit-level changes.
In another study, the drug reopened a critical window for learning in mice. During adolescence, the brain is highly plastic, but it begins to stiffen in adulthood. Psilocybin temporarily restored malleability and changed the mice’s social behavior. In some brain regions, the drug increased sensitivity to oxytocin, the so-called “love hormone.” The authors suggested the drug induced a state called metaplasticity, in which neurons are more likely to respond to oxytocin and other regulators to rewire, form new connections, and grow their branches.
Psilocybin’s effects may extend beyond the brain. Depression, chronic stress, and the immune system are tightly linked. In a third study, researchers identified a brain-spleen connection that drives fear and anxiety. Psilocybin suppressed inflammatory immune cells associated with brain inflammation and dampened anxiety-like behavior in stressed mice, even under threat.
Both effects—dialing up plasticity and lowering inflammation—make psilocybin an intriguing way to potentially counter changes in the aging brain.
“We know that with age, we lose synaptic connections, especially in certain brain regions like the hippocampus and prefrontal cortex,” said Toueg. “There’s a lot of overlap between the mental states that psychedelics influence and those associated with successful aging.”
Tomorrow Never Knows
The PLASTICITY trial is designed to test whether psilocybin can produce lasting changes in neuroplasticity in healthy adults aged 60 to 85. Participants will first undergo assessments of cognition, visual perception, and brain structure using advanced MRI techniques.
Diffusion MRI scans will focus on the hippocampus to capture microscopic changes in its structure. Functional MRI will focus on brain activity as participants perform learning and memory tasks, offering a dynamic view of how activity shifts after dosing.
The study will also see if psilocybin increases vagus nerve activity, which has been linked to better stress recovery. Participants will complete detailed surveys about the experience ranging from emotional responses, like wonder, to potential shifts in outlook and social cognition.
“Things like depression, anxiety, stress and rumination are all associated with worse aging outcomes,” said Toueg. “Things like having purpose in life, emotional regulation, and awe are all associated with more successful aging.”
The trial began enrolling participants in November last year. Two volunteers have already completed the tests, and the team aims to dose 20 people by the end of 2026.
Although psilocybin trials are now widespread, older adults remain underrepresented. One estimate suggests just 1.4 percent of participants are 65 or older, despite potentially being among those most likely to benefit from interventions that enhance plasticity.
“This study allows us to directly test whether the promising findings from animal models translate to older humans and to generate data that will inform future research on aging, cognition, and mental health,” said Silver.
Toueg agrees. “I think that no matter what we find, this study will have implications for how we think about intervening in the aging brain,” he said.
