'Rebooting a computer'
Not surprisingly, there are skeptics. Dr. Edna Foa, who developed a widely used treatment for PTSD called prolonged exposure therapy, or PE, met with Mithoefer to review audiotapes of MDMA-assisted therapy. She walked away shaking her head.
"I was completely confused," Foa said. "They were all over the place. They didn't use evidence-based therapy, which would be CBT (cognitive behavioral therapy), PE or EMDR (eye movement desensitization and reprocessing). They were just kind of going with feeling. I don't know the rationale."
She was also jolted by the frequent hugs the Mithoefers gave patients at difficult points in the session. "It's very unusual," Foa chuckled. Foa said she never touches a patient "unless they ask for it. And then I hold their hand."
Mithoefer said the key feature of his approach is that it's "nondirective," in that what happens during the session is determined primarily by the individual's own process and needs. He said he often includes elements of other types of therapy -- including PE and CBT -- but that it depends on the patient's response.
Even those who see promise in MDMA-assisted treatment aren't sure how it works. "It's not well understood by any means," said Mithoefer. "We think it gives people this window of time in which they can process things without being overwhelmed by emotion, but also not being numbed up."
He said brain imaging studies, while crude, support the theory that MDMA alters hard-wired connections between conscious thought and emotional reactions -- or overreactions.
"We do know that MDMA decreases activity in the left amygdala, and increases it in the prefrontal cortex" -- brain areas associated with emotion and higher thinking, respectively, he said.
David Nichols, a professor of pharmacology at Purdue University, said no one really knows why MDMA, as well as drugs like LSD and psilocybin, have such a profound effect on the brain.
"I liken it to rebooting a computer," he said. "But when it comes to things that change the fundamental structure of personality and consciousness, and changes who you are, we don't really understand that."
Nichols warned against a simple explanation. "You could talk about neurotransmitters, but that's really superficial. (MDMA) releases serotonin, dopamine, norepinephrine. It activates other hormones. But what does that all mean?"
'Why do we need this MDMA?'
Uncertainty is easier to take if you think there's no other option, and Foa argued it's a misperception that existing treatments are ineffective.
A recent study by psychiatrists at the National Center for PTSD tracked 171 patients who received either PE or CBT therapy. After 10 years, fully 80% still enjoyed milder symptoms. However, about one in four of those treated could not be found for followup.
"With PE, you get about 40-50% (cured) of PTSD, and you get about 80% getting improvement," said Foa. "So we have good treatments, that have no side effects. The question is, why? Why do we need this MDMA?"
Foa also cites concerns about neurotoxicity, although a 2011 study by Harvard psychiatrist Dr. John Halpern found that occasional MDMA use produced no cognitive damage.
Dr. Julie Holland, a psychiatrist who is overseeing the safety of an MDMA study Mithoefer is now conducting on veterans, said most risk is eliminated by the controlled nature of the experience.
For casual Ecstasy users, said Holland, "The biggest risk is not knowing what they're taking." Apart from being illegal, the street drug is often contaminated with other substances. Holland added that, "The next big one (risk) is heatstroke, if you get out and dance for six hours."
"The third biggest risk is overhydration," she explained. People are taught to stay hydrated, but MDMA causes the body to retain water. Combined with the drug's disorienting effects, this can lead users to overdrink, to a condition known as hyponatremia, a dangerously low concentration of sodium in the blood. "This is the main reason MDMA users die," said Holland, "from drinking too much water."
In a controlled setting, said Holland, "You get an incrementally higher heart rate, higher blood pressure and body temperature, but there isn't real danger as long as you're moderately healthy."

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