Editor's note: This is the third installment of a three-day series on the experimental use of the drug Ecstasy to treat post-traumatic stress disorder. On Saturday, we met Rachel Hope and those studying whether the drug, also known as MDMA, is safe in a clinical setting. On Sunday, we continued Hope's story.
(CNN) -- When Rachel Hope picked up the phone in 2005 to call Dr. Michael Mithoefer, she didn't have high hopes.
"I had very low expectations," said Hope, who suffered from post-traumatic stress disorder for years before investigating whether the drug Ecstasy might be able to free her from her torment. Her PTSD was traced to a period of sexual abuse as a child and a life-threatening car accident.
In the initial 45-minute conversation, Mithoefer determined that Hope didn't have other serious psychological problems. He agreed to fly her to South Carolina to take part in his study of the experimental therapy. There, she underwent more psychological testing and a physical exam. There were standard therapy sessions, so Mithoefer could understand Hope's past and her symptoms. Finally, she was ready.
Light streamed through the skylight as Hope lay back on a futon in Mithoefer's office, in the rear of a small bungalow.
On either side sat Mithoefer and his wife, Annie, a nurse.
Annie put in a CD and music started playing. As Hope placed a capsule on her tongue, they began to talk. Thirty minutes later, she began to feel deflated. Even though she had no experience with drugs, she knew: she'd been given a placebo.
True to their protocol, the Mithoefers continued the therapy, as if Hope were under the influence of MDMA. Said Hope, "We went through the process, but by the end, I'm like, 'I'm not different.'"
A week later, Mithoefer called back. He had permission to conduct MDMA sessions with test subjects who'd previously received the placebo. Would Hope like to fly back to South Carolina?
And so once again, Hope found herself on the futon, the light streaming, the music playing, the capsule on the tongue. This time, everything changed.
"It was like my whole brain was powered up like a Christmas tree, all at once," recalled Hope.
Listening to audiotapes, it isn't obvious what's happening. The conversation is fractured. But something was going on inside Hope's brain.
"Somehow, I became aware of the hardwiring decisions that my brain had made to explain why all these traumatic things happened to me, and what they meant to me about being a woman, a child living in the world, about sex, about violence," she said. "What the medicine did, it brought everything up for question."
Mithoefer said he lets patients drive the direction of the session. Typically, they alternate between talking and stretches of pure introspection. The trauma, he said, "always seems to come up."
"It's not that people just have a blissed-out experience and feel great about the world," he cautioned. "A lot of the time it's revisiting the trauma, and it's a painful, difficult experience. But the MDMA seems to make it possible for them to do it effectively."
Hope said it certainly worked for her. She estimates that 80% of her symptoms disappeared after that first MDMA-assisted session. "It allowed me to rewire my brain," she said. Another 10% of her symptoms went away over the next few weeks, she said.
According to results published last month in the Journal of Psychopharmacology, the effect was typical. Of 19 subjects in the study, more than two-thirds still showed significant improvement more than three years later -- what Mithoefer and colleagues describe as "meaningful sustained reductions" in their symptoms.
With PTSD, a common measure of severity is the so-called CAPS score, determined by answers on a detailed questionnaire. To be part of the study, patients needed a CAPS score above 50, which generally signifies moderate to severe symptoms. Hope rated a score of 86. At long-term followup, about three years after their final MDMA-aided session, only two people in the study had scores as high as 50. The CAPS score for Hope was 14.
One patient, who chose to stay anonymous, described a sense of new freedom: "I was always too frightened to look below the sadness. The MDMA and the support allowed me to pull off the controls, and I ... knew how and what and how fast or slow I needed, to see my pain."
"The question is whether this was just a flash in the plan, where people just feel good from taking a drug," said Mithoefer. "The answer to that turns out to be no, it really wasn't just a flash in the pan for most people."
For all the promise, however, 19 people is still a tiny study.
'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."
'Real people are paying the price'
Additional studies using MDMA against PTSD either have been completed, are planned or are under way in Colorado, Canada, Spain, Switzerland, Israel, Australia and Great Britain. Meanwhile, Mithoefer is conducting a study treating military veterans and firefighters; so far 11 people have enrolled and more than 280 have called to see if they might take part.
While the military and Department of Veterans Affairs have expanded services in recent years, they struggle to keep pace with the inflow of new patients. The number of active-duty military personnel seeking treatment for PTSD rose from 10,408 in 2002 to 281,468 last year, according to Cynthia Smith, a Department of Defense spokeswoman.
One reason MDMA seems tempting is the sense that existing treatments are not enough. "It's not like we don't have effective treatments for PTSD," said Dr. Boadie Dunlop, director of the Mood and Anxiety Disorders Program at Emory University. "But there are many people for whom these therapies don't work."
Retired Brig. Gen. Loree Sutton, who headed the DOD's Centers of Excellence for Psychological Health and Traumatic Brain Injury from 2007 to 2010, said she left the Army in part because she felt existing treatments often do more harm than good.
"We invested in conventional approaches towards research, but I also knew we had to go beyond that," said Sutton. "Real people are paying the price for our failure to harness knowledge."
The National Center for PTSD, a branch of the VA, says approved treatments include a type of antidepressant known as SSRIs (selective serotonin reuptake inhibitors), along with EMDR, CBT and PE, developed by Foa. In some studies, more than three-quarters of those who complete PE therapy are "cured." But success can be hard to evaluate, in part because treatment is too emotionally painful for many patients to complete.
The DOD and VA also support a variety of research, much of it to try to fine-tune existing approaches. For example, Foa is leading a study offering more sessions in a shorter amount of time -- twice weekly -- to soldiers at Fort Hood, Texas. About 360 people are expected to enroll.
Neither the VA nor the military is part of clinical MDMA research, but Sutton said that before leaving the Army, she did call Rick Doblin to encourage his work. Doblin is the founder of MAPS, the Multidisciplinary Association for Psychedelic Studies, which wants to turn mind-altering drugs like Ecstasy into prescription medicine.
"With MDMA -- Ecstasy -- if rigorously designed studies show there's a benefit, better than existing therapies, then we should use it," Sutton said.
Doblin said he's working with the Defense Department to develop a protocol involving active-duty troops, and said he would gladly give up his status as the prime backer of MDMA research: "If there are other people who have a better idea, or want to try it with cognitive behavioral therapy, or whatever -- if there are other people trying to fund MDMA research, we think that would be great." With a laugh, he added, "We could even provide them with free MDMA. We have a lot more than we need."
Hope no longer has flashbacks or night terrors, and she no longer jumps when the phone rings. After finishing with Mithoefer, she decided to abandon her quiet life on Maui and moved to Los Angeles.
In 2008 she felt strong enough to have a second child. "That's another part of the gift of MDMA," she said recently. "Before those sessions, I just couldn't get it together, to expand my family the way I wanted to."
Crowds no longer faze her. In fact, she spent two months this fall as a full-time climate-change protester, doing street theater in a polar bear hat in front of hostile crowds at presidential debates and similar events.
"It gets pretty intense," she said. "It's something I couldn't have done, before the treatment."
Grateful as she is for Mithoefer's study, she feels as strongly as ever about avoiding recreational drug use. "I have a very, very serious respect for that medicine. You really don't want anybody to do this without professional supervision. It could open portals, in a way that could really damage you."
Chatting in his office, where books about shamanism sit side by side with standard psychology texts, Mithoefer remained cautious.
"I think at this point, what we know is that MDMA can be administered safely to people with PTSD, to the right people in the right setting with the right screening. It shows very encouraging signs of being effective, you know, but the numbers are too small to say we can definitively prove that."