20 Jan. 2023. A small clinical trial shows psychotherapy with the psychedelic drug MDMA generates brain signals that help relieve symptoms in people with post-traumatic stress disorder. Findings from the trial conducted by the MAPS Public Benefit Corporation appear in the 12 Jan. issue of the journal Frontiers in Psychiatry.
Post-traumatic stress disorder or PTSD is a chronic debilitating psychiatric disease marked by recurring flashbacks, dreams, and fearful episodes, often resulting from first-hand experiences with traumatic or dangerous experiences, such as military combat. When people with PTSD experience these symptoms, they often engage in behaviors to avoid triggering their fears and emotions, as well as loss of sleep, broken relationships with friends and family, and negative thoughts about themselves. PTSD is treated mainly with psychotherapy, although new drugs for the condition are also being developed.
Researchers from MAPS Public Benefit Corporation, a subsidiary of Multidisciplinary Association for Psychedelic Studies, a not-for-profit organization in San Jose, California, study the therapeutic effects of so-called mind-altering drugs for treating psychiatric disorders. One of those compounds is 3,4-methylenedioxy-methamphetamine or MDMA, more commonly known as ecstacy. MDMA is a synthetic chemical similar to stimulants, known to increase production in the brain of dopamine that increases energy and activity, and serotonin affecting mood, appetite, sleep, and hormones affecting trust and sexual arousal. MDMA also boosts norepinephrine in the brain, a chemical increasing heart rate and blood pressure, making MDMA potentially dangerous for people with heart conditions.
A team from MAPS Public Benefit Corporation, Medical University of South Carolina, and other institutions sought to learn more about the workings of MDMA in the brains of people with PTSD. The researchers cite several clinical studies showing benefits from MDMA for people with PTSD as part of their therapy. But in this study the team aims to discover more precise ways MDMA works in the brains of people with PTSD to gain those benefits. The researchers hypothesized MDMA would modify recruitment of signals in parts of the brain generating hyperactive fear responses, particularly the amygdala that regulates emotions such as fear and aggression, the hippocampus controlling memory, learning, emotion, and motivation, and insula affecting a wide range of sensory, affective, and cognitive functions.
Audio scripts with neutral and fear-arousing stories
To track these brain activities, the researchers used a technique called functional MRI, a type of magnetic resonance imaging that graphically displays blood oxygen levels in the brain in real time as an indicator of brain activity. For this clinical trial, the team recruited 10 participants in a larger clinical study testing MDMA dosage levels among participants with PTSD in psychotherapy sessions. Of the original 10 individuals, nine completed the trial, of which eight were military veterans and one civilian first-responder.
Participants were assessed for PTSD symptoms at the beginning of the study, then followed their prescribed treatments that included psychotherapy both with and without MDMA. During the sessions they heard six-minute audio scripts with neutral and fear-arousing stories during which they submitted to functional MRI brain scans, including a follow-up session after two months.
Results of the functional MRI scans show increased brain activity connecting the amygdala, hippocampus, and insula indicating better ability to process fears and emotions during the fear-arousing scripts heard by participants in MDMA-assisted psychotherapy. However, the scans show this brain activity occurring more on the left side of participants’ brains, not the entire brain. The researchers also found fewer differences between fear-arousing and neutral scripts among MDMA-assisted patients in signals to the cuneus in the brain that processes visual information. And, changes in brain signal connections among the amygdala, hippocampus, and insula in MDMA-assisted patients correlated with fewer reports of PTSD symptoms.
“These data add to our understanding of the biological rationale for using MDMA combined with therapy in the treatment of PTSD,” says MAPS Public Benefit Corporation CEO Amy Emerson in a company statement. “The results suggest that treatment with MDMA-assisted therapy may help reset the dysregulation in the brain caused by PTSD and that the effects are durable even two months after treatment.”
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