Tony Macie pictured in 2012 during MDMA-assisted therapy for his chronic PTSD. Macie said the treatment helped him process trauma in a different and positive way after other treatments failed.

SAN ANTONIO — The Iraqi interpreter wanted a ride in the Humvee after a long mission outside Baghdad in April 2007. Already crowded with armor-clad soldiers, Army Spc. Tony Macie told him he’d have to wait for more vehicles to return to Patrol Base Dog to pick him up.

No Humvees arrived, but a dump truck weighed down with explosives did. The detonation reduced the base to a pile of bricks. Survivors radioed: “broken arrow,” a distress signal for units in danger of being overrun by the enemy.

A mushroom cloud plumed overhead. Macie’s unit sped back to pull the dead and wounded out of the rubble. It took days. Two U.S. troops were killed, along with two interpreters — including the one Macie told to wait.

Did Macie kill him?

The question surged through Macie’s brain circuitry in the twin, almond-shaped amygdalae, which regulate emotions, memories and fear. His mind braced for an imminent attack as adrenaline flooded neural receptors nearly every day during his 14-month tour, and continued once he returned home.

“My brain wasn’t able to shut off. It was going a million miles a minute. You need it on a deployment. But it’s not normal at home,” said Macie, whose job as a forward observer for artillery strikes meant his mind would never stop processing where he and fellow soldiers were at all times.

Macie, now 29, was diagnosed with post-traumatic stress disorder by the Army when he left in 2008 with a medical discharge following back injuries he sustained in Iraq. He was anxious and depressed and had trouble sleeping.

Macie tried to drown those feelings with alcohol and a cocktail of painkillers and antidepressants prescribed by the Department of Veterans Affairs. He received disability compensation for PTSD, along with numerous modes of therapy offered by the agency.

Nothing helped. But there was one long shot: MDMA, known more broadly as the illegal party drug Ecstasy.

In late November, the Food and Drug Administration approved a large-scale Phase 3 trial to evaluate the use of MDMA in treatment of PTSD, which is the final step before possible approval as a prescription drug. The second phase of the drug trials, which started in 2000, began to include veterans in 2010.

Like the other veterans involved in the study, Macie was selected because of his chronic, treatment-resistant PTSD, which is severe enough that treatments fail to reduce symptoms.

The results have excited advocates searching for new ways to treat mental health injuries.

Two-thirds of the 107 participants in Phase 2 of the trial no longer meet the criteria for having PTSD a year after they completed therapy, according to researchers who analyzed data a year after patients finished the trial.

Some of the 27 veterans involved in the trial describe MDMA-assisted psychotherapy as a cure, not a treatment.

War transformed Macie’s brain. But four years ago, Macie took a single dose of MDMA and felt his PTSD symptoms begin to lift as he went through eight hours of difficult psychotherapy, where the deepest traumas of his deployment rose to the surface.

Most of the patients in Phase 2 opted for the standard three treatments. Macie said what he needed came sooner.

“I didn’t need more than one dose,” Macie said. “I got the message.”

Unlikely advocate

As a former acid-dropping Vietnam draft resister, Rick Doblin is an unlikely veterans advocate. But if the FDA grants approval for clinicians to use MDMA alongside psychotherapy – and if the drug maintains its potential – he could be among the most impactful in decades.

Doblin was exposed to war trauma early in life. As a Jewish child of the 1950s, Doblin’s brain was shaped by stories of relatives imprisoned and killed in the 1930s and 1940s during the Holocaust.

Doblin, now 63, refused the draft during the war in Vietnam and opted to study psychology to deal with what he described as worldwide irrational prejudice. He later encountered studies of LSD treatments for Dutch Jewish survivors of World War II concentration camps.

The drug helped them process long-buried trauma, Doblin said, but it did not do enough to quell their deep fear and anxiety later in life. MDMA looked to be different, Doblin said.

He followed the development of MDMA for use in treating PTSD for more than 30 years. He founded his nonprofit — Multidisciplinary Association for Psychedelic Studies — to drive clinical research on the medicinal use of MDMA, LSD and marijuana and to remove legal and social barriers that have made MDMA illegal since 1985.

MDMA accesses parts of the brain altered by PTSD and floods them with serotonin — a natural chemical associated with feelings of trust, bonding and well-being. That allows patients to think about their experiences in a more positive way, Doblin said.

Researchers have cautioned against viewing MDMA as a simple solution. Dr. Charles R. Marmar, the head of psychiatry at New York University’s Langone School of Medicine, told the New York Times that MDMA is a “feel-good drug, and we know people are prone to abuse it,” adding that prolonged use has been linked to brain damage.

Doblin’s group was responsible for gathering and training several pairs of psychiatrists across the world to guide patients throughout Phase 2 of the FDA trials, he said, and to evaluate data submitted to the FDA.

Nearly all the U.S. veterans in those trials were seen by a husband and wife team of clinicians and MAPS consultants Annie and Michael Mithoefer, who guided patients through three months of psychotherapy sessions, including a dose of MDMA paired with an eight-hour psychotherapy session each month. The patients wore eye masks and listened to soothing music as they unspooled their deepest traumas.

The pairing of MDMA and discussion of painful moments contradicts the popular idea of taking the drug in a party setting. It’s much more demanding, Doblin said.

“I’ve heard from a lot of veterans who say, ‘I don’t know why they call it Ecstasy. It’s painful and difficult,’” Doblin said. “It takes a lot of courage to do this healing.”

Macie’s first and only MDMA session is where he came to terms with the ruins of Patrol Base Dog and other difficult moments of his deployment. He described the drug’s effect as creating a new viewpoint.

“My mind switched and I felt at peace. I realized I didn’t know how to accept death and move on,” Macie said. “I understood I did everything the best I could have.”

The war on drugs in the 1980s fueled a public taboo of psychedelic treatment, Doblin said, bolstered by a 1985 ban on the drug from the Drug Enforcement Administration. The ruling pushed Doblin to seek out legitimacy in other ways, and he later received a doctorate in public policy from Harvard University to construct a path to social acceptance.

He said the FDA approval for Phase 3 MDMA testing is vindication, moving from the minor leagues to the major leagues in the field of pharmaceutical development. Most drugs fail to move out of Phase 2, when high standards can’t be met or the data does not support findings.

VA’s role

Doblin knew the Pentagon would be a big obstacle as long as the DEA classified MDMA as an illegal drug, and he looked to VA for assistance.

He has seen some success, Doblin said. Some clinicians interested in using MDMA-assisted therapy are affiliated with VA facilities but do not work directly for the agency.

The potential impact of MDMA as a legal prescription drug could be big, Doblin said, for veterans and a VA system overtaxed by providing care and running a compensation system flooded with disability claims.

However, MDMA-assisted psychotherapy is time-consuming and would be difficult to integrate on a large scale because of the VA’s vast bureaucracy, Doblin said. Contracting treatment through outside clinicians could solve logistics issues.

More than 1.4 million veterans receive VA compensation for service-connected mental health issues, according to VA data. While not all would be suitable for MDMA-assisted therapy, participants in Phase 2 of the FDA trial experienced a 54 percent reduction, on average, in PTSD symptoms, according to MAPS statisticians.

Public affairs officials at VA would not provide an interview with a mental health expert. Instead, a department spokeswoman sent a list of internally produced questions and answers on MDMA treatment highlighting agency skepticism of research efforts by pointing to concerns of addiction and side effects.

“We are quite concerned that clinically prescribed MDMA might contribute to the risk for MDMA addiction,” said Dr. John H. Krystal, the clinical neuroscience division director at VA’s National Center for PTSD.

“We believe that the magnitude of the clinical benefit associated with MDMA prescribed for the treatment of PTSD remains to be determined,” he said.

Doblin said participants in Phase 2 trials reported the opposite of the VA’s concern of addiction, with 92 percent of those who completed long-term followups reported that they did not attempt to find illegal MDMA after treatment. The risk of addiction will be a focus of Phase 3 testing, Doblin said.

Concerns about veterans addicted to VA-prescribed medication have grown since waves of injured troops returned from Iraq and Afghanistan. About 650,000 veterans were treated with opiates in 2014, according to an NPR report. The Pentagon and VA launched opiate safety programs in recent years to combat alarming levels of addiction and overmedication.

VA could not produce numbers of how many veterans it believes are addicted to VA-prescribed medications. Painkillers, for instance, can be abused as veterans with PTSD look for ways to self-medicate.

Macie said he used to be one of those veterans. “I’d go into VA with a complaint and leave with five other medications,” he said.

He took between four and 12 medications daily during his treatment at VA, including painkillers for wear and tear and the back injury he sustained going over a wall face-first during a raid in Iraq. He became addicted to them in an effort to quell his PTSD symptoms of anxiety, depression, insomnia and hypervigilance, he said.

VA could help bolster research of MDMA-assisted therapy by awarding grants for testing, which would help legitimize the drug, Doblin said.

“Just imagine the delays and suicides since 1990,” Doblin said, referring to the first time a VA facility declined to consider research for MDMA-assisted therapy.

On the day of the meeting with the FDA to discuss the results of the Phase 2 trials, Doblin brought in a folded-up newspaper featuring a story on veterans suicide.

“This is what’s happening every day,” Doblin told the agency, showing the grim headline to everyone present.

He believes the gesture worked to help move the trials ahead to the last phase. But he still thinks the victory has come too late.

“What would the world look like now if the resistance wasn’t so strong?” Doblin said.

Macie believes MDMA therapy will help save people’s lives. “It gave me my life back,” he said.

Still, he is cautious to use the word “cure” like some others have when describing MDMA only because he does not want to paint a picture of an easy road for veterans. Confronting trauma during the therapy session was difficult, he said, as is all the work that comes afterward.

Before the treatment, he said he suffered from anxiety, depression, hypervigilance and abuse of alcohol and painkillers. Nearly all of that has been stripped away since he participated in the trials four years ago, Macie said. He is still struggling with insomnia.

Macie has lived in Cambodia for the past two years, working with his nonprofit to enlist veterans for humanitarian projects throughout southeast Asia. He believes other veterans would benefit from traveling and living in another country. Travel in itself, Macie said, was like MDMA in a pure, worldly form.

“You have to open up and surrender yourself,” he said.

horton.alex@stripes.com

Twitter: @AlexHortonTX