Stanislav Grof, a Czech psychiatrist and one of the first to research therapeutic uses of LSD, believed that the West had lost touch with the healing potential of non-ordinary states of consciousness. When psychedelic drugs became illegal in the United States, Grof created an alternative called holotropic breathwork. The idea was that hyperventilation, combined with music and a ritualistic setting, could foster an altered consciousness, through which patients could be guided into insight and problem resolution. Mithoefer went to California to train with Grof, then began to use breathwork in his own practice. And though he says it is often effective, he wondered how much more could be accomplished using MDMA. In 2000, Mithoefer approached Doblin to ask if he knew of a country in which a study of MDMA-assisted therapy might be permitted.
"You can do it here," Doblin said. "And we'll help."
Doblin says his optimism was based on a change in leadership and culture in the federal bureaucracy. When he first founded MAPS, Doblin says, "the FDA was refusing to permit all the studies we proposed," even one attempting to use MDMA therapy to ease the fears of a dying cancer patient who had found solace using the drug before it was banned. "The FDA said, 'No, we have to protect him from brain damage,'" Doblin says.
Then in 1992, after six years of refusals, the FDA approved a MAPS-funded human safety study. Safety studies are required before any drug can move on to Phase II -- studies of a specific medical application. In MDMA's case, this was particularly important because many believed the drug to be so toxic. Even talking about the possibility of therapeutic benefits would only make more people want to try it, some believed, and that would inevitably lead to more emergency room visits. And deaths.
More than 200 fatalities involving ecstasy use in the United States were reported to the Substance Abuse and Mental Health Services Administration from 1994 to 2001. Many of these deaths were related to traffic accidents and the use of other drugs and alcohol or other incidental causes. Of deaths directly related to ecstasy, most were caused by heatstroke. MDMA exerts a stress on the body similar to strenuous exercise and increases core body temperature, so dancing all night in a hot, crowded bar can quickly go from fun to deadly. More rarely, some ravers, paranoid about hyperthermia, have reportedly consumed so much water, many gallons, that the water itself became toxic and killed them.
Perhaps of even greater concern was the possibility that MDMA could cause permanent brain damage. Though research is ongoing and hotly debated, it's clear that test animals injected with high doses experienced lasting deformation of serotonin receptors in the brain.
There were worrisome human studies as well: In some, long-term recreational users of ecstasy performed more poorly on tests for short-term memory and some other cognitive functions than control groups, though the meaning of these results is complicated by the fact that most long-term ecstasy users also use other dangerous drugs.
The new safety study was not testing the dangers of MDMA under the conditions of illegal use. Eighteen people were given dosages similar to those that would be used in psychotherapy sessions, and the settings were comparable to the calm of a psychiatrist's office. The gist of the findings: MDMA given under those circumstances produced no acute harm or evidence of brain impairment. These results were bolstered by a Swiss study in which people who had never before taken MDMA were given brain scans before and after being given a single therapeutic-range dose of the drug. Comparison of the before and after scans showed no damage.
Given those results, Doblin figured the time was right for persuading regulators to approve Mithoefer's proposal, a placebo-controlled, double-blind study (meaning that neither doctor nor patient would be told who got the real drug). The safety study, and others done elsewhere, had made the case: Many valuable medicines have been developed from far more problematic drugs.
Doblin and the Mithoefers spent 18 months developing an elaborate protocol for the study: Research subjects would be limited to people who'd struggled with the disorder for years, and whom conventional treatments hadn't helped. The cases would be relatively severe, as scored on the standard diagnostic test, and subjects would be required to undergo multiple non-drug therapy sessions with the Mithoefers before and after the two MDMA sessions to prepare them for the experience and to help them process it afterward. The protocol dealt with such details as what kind of touching would be permitted (supportive, non-sexual), and what kind music would be played on earphones (soothing).
Submitted to the FDA in October 2001, it was approved a month later.
Then, in September 2002, the institutional review board engaged to guarantee the study's ethics -- de rigueur for human medical research -- abruptly withdrew its support. A study published in Science magazine found that relatively small doses of MDMA had created severe damage to the dopamine system in the brains of squirrel monkeys and orangutans. Dopamine damage could put human users at risk of developing Parkinson's disease, among other problems. In the case of the primate test subjects, the Science article said, the drug was so toxic that two of 10 animals died, and two more were in such bad shape that the researchers didn't give them a planned third injection.
After 2 1/2 years of work, the PTSD study appeared to be doomed.
A year later, Science printed a retraction: The vials containing the drugs that so damaged the monkeys' brains had been mislabeled. It wasn't MDMA after all, but methamphetamine. A new review board quickly signed on to support Mithoefer's study, but the irony of the wasted year wasn't lost on him: The misidentified drug that had been deemed too toxic to evaluate for medical use, the drug that was far more toxic than MDMA, was already a prescription drug.
Meanwhile, in the four years the MDMA study lingered between concept and reality, Donna Kilgore had been driven to the brink. She took "every anti-depressant you can name," tried a dozen therapists and an almost equal number of therapeutic approaches. But nothing made that numbness, panic and rage recede.
"I was getting to the point," she recalls, "where it was either go sit on a mountaintop or go dive off a cliff."
That's when a therapist told her about the Mithoefers' experiment. She applied, and became patient No. 1.
DONNA SPENDS A LOT OF HER TIME ON THE CROOKED COUCH holding the Mithoefers' hands, one on each side. She needs that reassurance now, recalling the rape.
"I was backed into a corner, nowhere to go, desperate. I kept telling him I wouldn't tell anybody," she says.
Can she feel that desperation now?
"A little bit, yeah."
Minutes pass. On the tape, you can hear the blood pressure cuff whir to life as the amplified beat of her heart thumps faintly in the background.
Finally she speaks, her voice rising with conviction.
"I feel protected. I do. I feel completely protected. I don't feel like I'm hanging out there anymore . . . It feels good to be loved. It feels good to be protected."
Minutes pass. She is lost in a vision, she will say later. She can see herself standing on a ridge, high above a valley shrouded in mist. Down in the valley, she knows, is a battlefield, containing all kinds of terrors. Her terrors. She knows they are there, but can't see their shape through the fog. Now the fog is lifting. Now she can begin to see.
"You're right," she says, as if in response to an assertion that hasn't been made. "I am angry. I'm angry at myself. It changed from being afraid to being mad at myself, that I allowed it to happen . . .
"And not just that," she says. There's a sudden, involuntary intake of breath. "I think that a lot of this baggage I'm carrying around is really stuff that I put in there myself. I stacked the luggage. Either in disappointment in myself or self-blame. Don't get me wrong. Under no circumstances do I think that I deserved it or I asked for it or that I did something to bring that on. I don't feel that way at all . . . It's like you take your base line [which is] fear, and you throw some self-doubt on top of that, and then you throw some desperation on top of that, and, before you know it, you got a seven-layer burrito going there. I mean I can feel every one of them. I don't know how to express it, but I can feel them . . . just one right on top of the other, and maybe I've done that for so long, that when the rape happened, that was maybe the straw that broke the camel's back, and my mind said, 'Okay, that's enough, you're cut off, no more.' There's no more room on the pile."
The Mithoefers murmur sympathetic words as Donna continues unburdening herself.
"It's not just about the rape. It's not just about any one thing. It's so many different things . . . All I can remember feeling, as far as I can remember, is fear. Heart-stopping, gut-dropping fear . . . I've kept all this inside for so long, and it feels so heavy . . . these emotions -- it's like I've been trained to be this way as long as I can remember -- to be seen and not heard. Just from that point on, I've tried to make myself as small and inconspicuous as possible. And then the rape happened, and you're headline news . . . I was ashamed."
The study protocol calls for the therapists to periodically ask the subjects to rate their level of distress on a scale of zero to 10.
"Zero," Donna says quickly. Another pause. "No, that's not entirely true. That's a lie. I would say about a two. It's a disturbing revelation, I guess you could say."
Once again, she pauses.
"I feel calmer, a whole lot calmer," she says. "Kind of putting it all together, rather than just throwing it all in a box."
"OH, MAN, I'M IMPRESSED," SAYS MARK WAGNER, a clinical psychologist on faculty at the Medical University of South Carolina in Charleston, an expert in psychological testing and an independent evaluator conducting the before and after PTSD assessments in Mithoefer's study. "I didn't know much about the clinical use of MDMA before this," Wagner says, "But I've seen each and every one of these patients, and, just as a clinical psychologist, it is impressive to see the degree of treatment response these folks have had. There are a couple of areas in medicine, like hip replacement, where one day you are bedridden, and the next you're out playing tennis. Or with Lasik surgery, you're blind, and then you can see. Nothing in psychology is like that. But this was dramatic."
Lilienfeld, the Emory psychologist, is less enthusiastic. "These subjects knew if they got the drug or the placebo," he says. "Particularly when you have a very dramatic and powerful intervention, people may change but not in a longstanding way."
Wagner points out that two subjects who got the placebo were convinced they had gotten MDMA, and others who did get it weren't sure. The people who wrongly believed they'd gotten the drug initially showed improvement, but quickly relapsed. "The chance that a placebo effect would last for three months is very slight," Wagner says. "And for it to last for a year or more, which anecdotally we believe might be the case here, would be extremely remote."
But if MDMA does work, the question remains, why? "Patients in our study had a fear of the fear," Wagner says. "Something about the MDMA made it possible for them to approach the feared thought, the feared 'place' in their mind -- and when they got there, it wasn't as terrible as they thought. A lot of these people, the light bulb went off, they had the insight, but there's still a lot of work to do. They've had this for years, it's shaped their lives, and now they have to rebuild them."
In Mithoefer's Psychedelic Medicine article, he theorizes that the breakthroughs came from having the psychic calm -- the feeling Donna had of being protected -- that allowed subjects to meaningfully reexperience and reassess the events that traumatized them, and at the same time be able to feel a powerful new connection to positive aspects of their lives. In Donna's case it was the love of her husband and children. Another patient told Mithoefer: "I had never before felt what I felt today in terms of loving connection. I'm not sure I can reach it again without MDMA, but I'm not without hope that it's possible. Maybe it's like having an aerial map, so now I know there's a trail."
For some subjects, the most significant part of the experience seemed to be a physical release of mental anguish. In Mithoefer's article, he says one subject exclaimed: "I can relax! Forty-three years of fear and not being able to feel my body. Now I can feel my body without pain."
Another subject, a 50-year-old woman named Elizabeth, had one of the more dramatic physical releases. "I thought it was supposed to be talk therapy, that I was supposed to talk about things, but it doesn't have to be," she says. "The drug itself will do the work."
Her trauma centered on a stepfather who viciously abused her and her brother from an early age. She describes him as "a truck driver, ignorant, uneducated, Southern, moonshine-drinking, swearing, wife-beating idiot. He thought kids were there for his entertainment, amusement and personal use."
From an early age, Elizabeth was stuck in a grim survival mode. "Doesn't matter what you do to me, you will never touch me," is how she described it. "It was a feeling, all self-defense, all self-protection, nobody gets in."
Her whole life evolved, pathologically, from that premise. Running away as an adolescent from the horrors at home, she was raped, twice, by men who picked her up as she hitchhiked. With no real concept of love and nurture, she got involved in a series of physically and emotionally abusive relationships. When something triggered memories of her abuse, she froze in a nearly catatonic state, caught between fight and flight, unable to do either.
During her MDMA session, Elizabeth says, she remembered that after her mother divorced her stepfather, she'd confided to Elizabeth that he had been the best lover she'd ever had.
As she talked about how that made her feel, Elizabeth recalls, Mithoefer "was pushing me verbally. I was mad, and he was pushing me, provoking me to feel it. I just kept getting madder and madder, hitting the bed. Then the drug just took me and slammed me down. I was sitting one second, then down on my back in the next. I became very rigid, the tension was so powerful. I remember lying on the bed where I slammed down, looking at Dr. Mithoefer . . . like I'm mad at him for putting me through this, and this wave of energy just slammed through me, and it was just a release of a tremendous amount of this negative energy. It was powerful, and it was explosive. I felt like I'd been through something significant . . . My mother traded my childhood for sex!"
In the weeks following the therapy sessions, Elizabeth says, she would be standing in the kitchen, or just sitting in a chair at work, and without warning that powerful release would move through her body. Afterward, she says, "I felt at ease, a level of ease I was not familiar with, just being comfortable within myself, within my body."
That feeling of ease has given her a new relationship with her life, she says. Difficulties continue, but "I'm not having as much problem with the puzzle. I'm able to just keep slugging away. I don't feel so much like going to bed and sucking my thumb."
The problems don't disappear, Mithoefer says, they just become something that can be managed.
"All subjects have told us they found MDMA helpful," Mithoefer says in his article. "Some have felt the effect . . . was dramatic and even lifesaving: however, others have reported disappointment that MDMA was not a "magic bullet" to remove all their symptoms, or have said it would have been helpful to have one or a few additional sessions."
Parrott, the MDMA critic from Britain, worries that in some cases MDMA magnifies negative feelings instead of positive ones, and can bring up difficult memories that may be overwhelming. It's problematic, he says, that the outcome of therapy sessions can be so dependent on the skill of the therapist.
Mithoefer acknowledges that this is an issue and says that's precisely why he believes that, if MDMA is ever prescribed, it should be administered only in licensed clinics by specially trained therapists.
Still a problem, says Parrott. "Those patients who had good experiences on the drug would often want further-on MDMA sessions (just like many novice recreational users)," he writes in an e-mail. "This scenario is very worrying for many obvious reasons: reducing efficacy but increasingly adverse effects following repeated usage; drug seeking elsewhere when it stopped being forthcoming from the clinic etc; regular use leading to a variety of psycho-biological problems."
Wagner, who questioned all of Mithoefer's subjects in detail about their post-therapy attitudes, thinks Parrott is way off mark. "I didn't see a single individual who thought: 'Oh, yeah, this is great fun. I'm going to try to go out and use this for recreational use.' All of them took this very seriously and therapeutically. They saw it as hard, but important, work."
Amy, a woman in her 40s, is a case in point. She remembers being psychologically and physically abused by her father "from birth," culminating one winter when he locked her in the basement for three weeks. She had a reaction to MDMA very different from Donna's instant giggles. When the drug started to take effect, she says, "It just hit me, and it wasn't pleasant. I felt like I was going to throw up. So I said, Okay, when's this happy, lovey feeling going to happen? I went to lie down on the couch and waited to go higher, but the drug took me down instead. [Mithoefer] was taking notes. I felt like he was drawing circles around me, but he showed me his notes, and they were just notes. That's when I saw that my internal world and external world didn't match up, and I connected with that. I saw myself as a baby wrapped in a white blanket, my family members standing there, and I realized, It wasn't my fault . . . I was flooded with feelings of peace and safety. 'It wasn't my fault. I didn't do anything,' I kept saying. 'I was a little girl. I was a baby.'
"After the first session, I felt exhausted, like I had a really bad hangover. But everything continued to unfold. I started to make connections. Like going into the grocery store, I used to feel very alienated. I couldn't connect with the other shoppers. But after the first session, I realized I could look at the people, and I wasn't afraid, like they were going to hurt me. I made the connection between the way I was always sizing up my environment, the alienation and the numbness that I felt, and the abuse.
"It felt weird at first, but kind of nice, that I could look at someone, and they would look back, and we'd smile at each other."
But like several other of the test subjects, Amy also confronted difficult new terrain. "Sometimes to go forward you have to go backwards," she says. "I knew that, but it wasn't comfortable to go there, back into the basement, into the abuse, into the beatings. I was apprehensive. I had already started feeling more grounded, but I'd functioned so long on autopilot that feeling things was difficult."
Difficult, but also better. "So many things happened," she says. "Before, I never wore a seat belt. I would look at it but not wear it. It was self-sabotage. But after therapy, without even thinking about it, I just automatically started putting it on."
FOR A YEAR AFTER HER TWO MDMA SESSIONS, Donna Kilgore says now, she was symptom-free.
"To me, the biggest breakthrough -- it meant the world to me to be able to look at the fear, to look at the shame. I didn't know I was ashamed. It was like I'd been wearing the scarlet letter. It was so heavy. When I got out of that session, I felt a hundred pounds lighter.
"Before, I knew the path was through the battlefield, but I just could not get through it. [But during the MDMA therapy] I knew I could walk through it, and I wasn't afraid. The drug gave me the ability not to fear fear." Otherwise, she says, "I would have not been able to do it."
Donna's sense that she'd had a breakthrough was supported when she retook the evaluation test on which she'd rated as an extreme case just weeks earlier. Her score had declined dramatically -- Mithoefer says that he can't give an exact number before publication of results -- but if she had been taking the test for the first time, she would not have been considered to have PTSD at all.
It's now been more than three years since her MDMA sessions. Donna is "still extremely grateful for the experience," she says. But problems are starting to crop up again.
"I've had a lot of stressors recently," she says. Her husband got laid off from a good job; they had to move; she had a difficult job at a dental practice for children.
Donna was doing paperwork in the office. "It wasn't in the best part of town," she says, "and I started to have catastrophic thinking again." It was the resurgence of the paralyzing, unreasonable fears characteristic of PTSD that she'd had before the MDMA sessions. "I just started being convinced that someone was going to come in with a gun and start shooting. And then I just couldn't listen to the children screaming in the next room . . ."
She says she had to quit the job. She begins to cry.
"I know I can work through it," she says, her voice breaking a little. "I know what I'm fighting now, and I can fight it."
Does she think it would help if she could have another MDMA therapy session?
"Yes," she says quickly. "But I can't. It's illegal."
Tom Shroder is editor of the Magazine. He can be reached at email@example.com. He will be fielding questions and comments about this article Monday at noon at washingtonpost.com/liveonline.