MDMA for PTSD? How Ecstasy Ingredient Works in the Brain

The active ingredient in the drug ecstasy is set to be studied in large-scale clinical trials as a treatment for people with post-traumatic stress disorder, the New York Times reported on Nov. 29.

The ingredient, MDMA, has been shown to be effective in treating people with PTSD in smaller studies, which were sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit organization that advocates for medical research on psychedelic substances.

But how does MDMA (3,4-methylenedioxy-N-methylamphetamine) work in the brain? And how could its effects help those with PTSD? [6 Party Drugs That May Have Health Benefits]

MDMA has several effects on the brain that appear to make the process of talking through past traumas a more effective way of dealing with them, said Dr. Michael Mithoefer, a psychiatrist in private practice in South Carolina and a clinical researcher who has worked on earlier studies of the drug.

Currently, psychotherapy, or talk therapy, is the "definitive treatment" for people with PTSD, Mithoefer told Live Science. There are drugs approved to treat PTSD, but they only target the symptoms, he added.

Still, in a large percentage of people, psychotherapy doesn't work well to treat the condition, Mithoefer said. Researchers think that MDMA could help people with PTSD by improving how they respond when they undergo psychotherapy, he said.

The effects of the drug seem to act as a catalyst for patients, helping them talk through and process their trauma, Mithoefer said. In other words, it's not the specific actions of MDMA in the brain that appear to treat PTSD, but rather that it seems to make psychotherapy more effective, he said.

Your brain on MDMA

MDMA causes a big increase in the levels of several neurotransmitters in the brain, the most predominant of which is serotonin, Mithoefer said. Serotonin is thought to contribute to feelings of well-being and happiness.

The drug also increases levels of certain hormones, including oxytocin and prolactin, Mithoefer said.

Oxytocin, which is sometimes referred to as the "love hormone," is known to increase "affiliative behavior," Mithoefer said. Increased levels of oxytocin make people more inclined to connect with others, he said.

Oxytocin has also been shown to affect how people respond to certain facial expressions, Mithoefer said. For example, research has shown that people given oxytocin are less likely to interpret certain facial expressions as being angry or threatening, he said. This can be helpful in therapy, particularly for people with PTSD, who tend to be hypervigilant and looking for threats, Mithoefer said. An increase in oxytocin may allow someone to be more trusting. [11 Interesting Effects of Oxytocin]

The other hormone, prolactin, can cause a "post-orgasmic state," Mithoefer said. The hormone makes people feel more relaxed and increases their sense of satisfaction, he said.

Ultimately, MDMA seems to put patients in what researchers call the "optimal arousal zone," Mithoefer said. If people are "hyperaroused" and flooded with anxiety and emotions, therapy doesn't tend to be effective, he said. Similarly, when a person is "hypoaroused," effective therapy is difficult to achieve, he said.

But MDMA can give people several hours in the optimal arousal zone. "It's kind of the sweet spot where therapeutic change can happen," Mithoefer said.

The drug has also been shown to decrease activity in the amygdala, an area of the brain associated with fear, and increase activity in the prefrontal cortex, which is where information processing takes place, Mithoefer said. People with PTSD have been shown to have increased activity levels in the amygdala, he said.

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Mithoefer and his colleagues have done brain-imaging studies on a small group of people with PTSD, comparing their brains before and after they took MDMA, but the results are still being analyzed, he said. The drug appears to have some effects in the brain that are opposite those linked to PTSD, he said.

Therapy in a controlled setting

People with PTSD are not likely going to feel "blissed out" when they take MDMA, Mithoefer said. In the trial that he conducted, patients did have positive experiences, but did not feel euphoric, he said.

The patients are processing the trauma that they went through, and even when they take MDMA, it is difficult and painful to do that, he said. But the drug seems to help them feel like they can go through the process without feeling overwhelmed, he said.

If the drug does eventually win approval from the FDA, researchers aren't expecting it to be something patients simply go pick up at the pharmacy, Mithoefer said. Rather, it would be given at specialized clinics under direct supervision.

For example, in Mithoefer's trial, patients underwent several preparatory psychotherapy sessions before they were given the drug. When they took MDMA, they did it under the supervision of therapists, who spent 8 hours with the patients. The patients then spent the night at the clinic, and were in touch with the therapists every day for the following week. And before their next MDMA session, the therapists met with the patients several more times.

"Like any deep therapy, [the experience] can stir things up, so it's important to have proper support to process what comes up," Mithoefer said. 

And MDMA does have negative side effects, Mithoefer said. In the short term, the drug can cause such symptoms as jaw-clenching and decreased appetite, he said. More serious side effects include increased blood pressure and pulse, he said.

MDMA increases blood pressure and pulse significantly, similar to fairly vigorous exercise, Mithoefer said. Because of this effect, people with heart disease were not included in previous studies, he said.

In addition, the researchers made sure to use pure MDMA in the studies. "On the street, you never know what you're getting," Mithoefer said. While substances sold on the street under the names "ecstasy" and "molly" may contain MDMA, they frequently also contain unknown and/or dangerous adulterants, MAPS says.

Editor's Note: This article was updated on Dec. 6 to clarify that the researchers who worked with Mithoefer were not all psychiatrists, and that Mithoefer and his colleagues are analyzing brain-imaging studies on PTSD and MDMA.

Originally published on Live Science.