New research shows MDMA and psilocybin may restore neural flexibility in people with PTSD, thereby helping the brain unlearn fear and relearn safety.
For researcher Lynnette Averill, the quest to find a treatment for post-traumatic stress disorder (PTSD) is deeply personal. Averill’s father served as an enlisted infantryman with the U.S. Marine Corps in Vietnam and struggled to cope with his war experiences when he returned home. After years of ineffective treatments, he died by suicide when Averill was three.
Driven by a mission to support veterans’ mental health, Averill trained as a psychologist and began working with people with PTSD — a condition that affects more than 12 million Americans in any given year. Victims of violence, abuse and accidents can experience post-traumatic symptoms such as persistent flashbacks, hypervigilance, and entrenched negative beliefs about themselves and their environment.
“People can be very stuck in black-and-white thinking, such as, ‘I’m a bad person,’ ‘I deserve this,’ ‘the world is dangerous,” Averill, a clinical research psychologist at the Baylor College of Medicine in Texas, said during a panel discussion at the Psychedelic Science conference in Denver in June 2025.
The root of these symptoms lie in how trauma shapes changes in the brain in the weeks and months after a frightening event. The brain’s fear center — the amygdala — becomes hyperactive, constantly signaling danger, while the brain regions responsible for contextualizing memories and managing emotional responses become less active and less able to counterbalance those fear signals. Traditional therapies, such as antidepressant medications and trauma-focused psychotherapies, help only a fraction of patients and can take months to be effective.
“For many people with PTSD, they simply aren’t enough, ” Averill told Live Science.
Consequently, Averill is one of a group of researchers who are exploring a new potential avenue for treating PTSD: psychedelics. Psychedelic-assisted psychotherapy, using MDMA or psilocybin, may act on the brain systems disrupted in PTSD, rather than simply treating the symptoms.
“There’s potential for people to feel that the needle has moved in hours,” Averill said. “And that is just quite literally lifesaving.”
How trauma changes the brain
PTSD shares symptoms with depression and anxiety. Yet it is characterized by a response to a single trauma or set of traumatic events. Such experiences spark fear and often challenge an individual’s core beliefs that the world is a just, safe and predictable place. People with PTSD can feel helpless and without agency.
It’s normal for people who have endured traumatic events to experience these symptoms for a short time, and for most people, they resolve within a week or two, clinical psychologist Gregory Fonzo, a co-director of the Charmaine and Gordon McGill Center for Psychedelic Research and Therapy at the University of Texas at Austin’s Dell Medical School, told Live Science. But a subset of people get stuck.
“PTSD is essentially a disorder of nonrecovery,” Fonzo said.
During the instigating event, trauma activates the brain’s fear alarm system, including the amygdala, and signals a rapid release of stress hormones and neurotransmitters, such as norepinephrine (noradrenaline). The higher levels of norepinephrine increase arousal and the physiological “fight or flight” response. The interaction of norepinephrine and corticotropin-releasing hormone modulates increases activity between the amygdala and hippocampus, reinforcing the synaptic connections that help store fear and vivid details of the event.
For the majority of people who recover quickly, this powerful fear response is successfully extinguished. The prefrontal cortex, the brain’s regulatory control system, and the hippocampus, the brain’s center for memory, exert top-down control and file the event as a past memory and no longer dangerous, which restores normal signaling in the amygdala.
For people who develop PTSD, however, the trauma creates more persistent changes in the brain, Dr. Jerrold Rosenbaum, a psychiatrist and director of the Center for Neuroscience of Psychedelics at Massachusetts General Hospital, told Live Science.
In PTSD, the amygdala remains stuck in an overactive state, causing symptoms like hyperarousal, irritability and being easily startled. At the same time, the prefrontal cortex, which normally calms those alarms, becomes underactive, leaving the amygdala’s overreactive fear response unchecked.
Neuroimaging has shown that PTSD is associated with a reduced volume of the hippocampus, which is the brain region that processes the context — the where, when and circumstances — of an event. In normal circumstances the hippocampus can discriminate between real and perceived danger. For example, it will categorize the sound of a car backfiring in an everyday environment differently than the blast of gunshot, which occurred specifically in a war zone. But a diminished hippocampuscould make it harder for patients to distinguish between the two.
There’s also evidence that PTSD is associated with changes in the connectivity of the default mode network (DMN), a set of interconnected brain regions that are highly active when a person is resting, their mind is wandering, or they are engaged in thinking about themselves or their memories rather than the outside world.
Dave
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I find that medical cannabis treats my PTSD just fine. I don’t need a psychedelic crap.
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