Enlisting Marijuana and MDMA to Fight PTSD

After deploying to Iraq for a seven-month tour of duty in 2004, Nigel McCourry recalls, "I was engaged in a fight every day, whether it was gunshots or bombs blowing up next to me or land mines. It was the most intense experience of my life."

That experience did not end when McCourry, a U.S. Marine, returned to the United States. "It didn't matter if it was a year or four years or six years after coming back from Iraq," he says. "There was no sense of separation of time. The experience was so fresh that I was constantly reliving it. I was alive in it."

Separation was also elusive for Roberto Pickering, another Marine, who arrived in Iraq a year before McCourry and served nine months there. "We saw a lot of heavy combat during the initial invasion of Iraq," he says, and "I lost a few very close friends who were in my unit." After he got back to the U.S., he "lost another couple of friends in further deployments of the unit."

Finding it impossible to achieve emotional distance from their experiences in Iraq, both men struggled to make new connections or renew old ones. Even getting a decent night's sleep was a challenge.

"I ended up drinking a lot, basically as a way of forcing myself to pass out at night," McCourry says. Pickering was "self-medicating heavily with alcohol and severely suffering a depression."

Years of anxiety and alienation left McCourry despondent. "I had this war inside of me that would flare up without warning," he says. "I couldn't live with it anymore. I got to the point where the thought of living day in and day out like that for the rest of my life was so miserable I wanted absolutely nothing to do with it."

Pickering could not hold a job. "I was incapacitated," he says. "I was a zombie."

For both men, the journey back to the land of the living began with illegal drugs.

McCourry enrolled in a study of MDMA-assisted psychotherapy and was amazed by how quickly it made a difference. After years of insomnia and nightmares, he was suddenly able to sleep through the night. Within two years he felt like this "huge healing event had taken place," because he finally "had this sense of separation from the experiences of Marine combat."

Pickering used marijuana to replace alcohol and the "kamikaze cocktail" of prescription drugs—sleeping pills, anti-anxiety meds, mood stabilizers—that had previously left him foggy. "It got my head back on straight," he says. "I still struggle sometimes, but I'm leaps and bounds beyond where I was."

Psychiatrists call the problems Pickering and McCourry encountered after serving in Iraq post-traumatic stress disorder (PTSD). People who qualify for that diagnosis find themselves re-experiencing a traumatic event (through nightmares or flashbacks, for example); avoiding trauma-related thoughts, feelings, or reminders; and experiencing negative emotions that may include depression, isolation, and excessive guilt or blame. They are also prone to "fight or flight" symptoms such as hypervigilance, a heightened startle reaction, irritability, and difficulty sleeping or concentrating.

Research suggests about 30 percent of Vietnam War veterans experience PTSD at some point in their lives. In the late 1980s, the National Vietnam Veterans Readjustment Study found that 15 percent were at that point diagnosed with the disorder. Annual rates for veterans of the Gulf War and the wars in Iraq and Afghanistan seem to be in the same ballpark: somewhere between 11 percent and 20 percent, according to studies cited by the Department of Veterans Affairs (V.A.). By comparison, the annual incidence of PTSD among adults in the general population is about 3 percent. Nearly 1 million veterans are receiving compensation for disabilities that are at least partly due to PTSD, according to V.A. records.

The age-adjusted suicide rate is also higher among veterans than in the general population: about a fifth higher for men and more than twice as high for women. The upshot is that hundreds of thousands of veterans with PTSD, including at least some of the 20 or so who kill themselves every day, might be interested in trying the substances that Pickering and McCourry credit with helping them reclaim their lives.

The main obstacle they face is the federal government's pharmacological taboos, which impede access to those drugs and scientific validation of their benefits. But thanks to the work of a plucky and persistent organization founded three decades ago, MDMA and marijuana could be available as doctor-prescribed medicines sooner than you might think.

'Solid Inner Strength' Although methylenedioxymethamphetamine (MDMA) was first synthesized in 1912, its unusual effects were not noted until the 1970s, when the psychonautical chemist Alexander Shulgin reported that the drug reduced inhibitions without clouding consciousness. To the contrary, he wrote, MDMA produced "clarity" and a "marvelous feeling of solid inner strength." Because MDMA seemed to promote empathy and self-reflection, psychotherapists found it useful in their work. Many of them objected when the Drug Enforcement Administration (DEA) banned MDMA (a.k.a. "ecstasy" or, more recently, "molly") as a dangerous party drug in 1985.

The following year, Rick Doblin, an activist who had helped organize opposition to the MDMA ban, founded the Multidisciplinary Association for Psychedelic Studies (MAPS), which aimed to win government sanction for medical use of various proscribed substances. The group is now close to achieving that goal with MDMA. Last fall, the Food and Drug Administration (FDA) gave MAPS the go-ahead to proceed with Phase III studies of MDMA-assisted psychotherapy as a treatment for PTSD, the final stage before approval of a new medicine. Doblin hopes MDMA will be available as an FDA-approved prescription drug within four years.

Given the substance's reputation for reducing fear and enhancing trust, it made sense that MDMA might help people overcome PTSD. Confronting the trauma and teasing out its lingering effects are crucial to PTSD therapy but may be challenging, to say the least, for someone who habitually avoids trauma-related thoughts and panics when they come up, especially if he views his therapist with suspicion. "One reason for treatment resistance is that PTSD sufferers are often so overwhelmed by the negative memories of their trauma that they cannot engage in a therapy that focuses on it," notes British psychiatrist Ben Sessa in a 2016 review of MDMA research in Neuroscience Letters. "A drug that temporarily reduces the fear response whilst increasing trust and empathy in the therapeutic relationship could be a useful adjunct to psychotherapy."

MAPS-sponsored research supports that hypothesis. In a Phase II study conducted by Charleston, South Carolina, psychiatrist Michael Mithoefer and his wife, Annie, a psychiatric nurse, 83 percent of the subjects who received MDMA in conjunction with psychotherapy showed a clinical response, meaning they saw reductions greater than 30 percent in the severity of their PTSD, as measured by the Clinician-Administered PTSD Scale (CAPS). The mean CAPS score in this group fell from about 80 to less than 30. Ten of the 12 subjects, all of whom began with CAPS scores indicating severe PTSD, no longer qualified for the diagnosis. By comparison, 25 percent of the subjects who received placebos saw improvements of more than 30 percent. Seven of the eight subjects in the control group subsequently chose to take MDMA, and all of them showed a clinical response.

That study, published by the Journal of Psychopharmacology in 2011, had a small sample, and blinding probably was less than fully effective, since subjects may have surmised they were getting the real thing based on the effects they perceived. But follow-up evaluations conducted 17 to 74 months after the last treatment found that the improvements experienced by the subjects who received MDMA generally persisted. While two of the 16 subjects who completed all of the evaluations relapsed, the average CAPS score was essentially unchanged.

The subjects in that study were crime victims, mostly women who had been raped or sexually abused. A subsequent MAPS-sponsored study involved 21 Iraq and Afghanistan veterans, plus three firefighters and one police officer. The results, which have been shared with the FDA but have not been published yet, were similarly impressive.

Instead of using an inactive placebo, this study randomly assigned subjects to receive 30, 75, or 125 milligrams of MDMA, followed by supplementary doses equal to half the original upon request. Summarizing the results at a MAPS conference last April, Mithoefer said there was "not much improvement" in the 30-milligram group but "quite a lot of improvement with the other doses." Mean CAPS scores, which ranged from 80 to 90 at the beginning, fell to between 70 and 80 in the low-dose group, to less than 50 in the high-dose group, and to less than 30 in the medium-dose group.

So far, Mithoefer said, MAPS has sponsored six MDMA studies with a total of 107 subjects. "Pooled data shows a large effect size," he said. "At 12 months, we have a very big reduction in CAPS [scores] across all six studies."

Mithoefer emphasizes that the improvements are not necessarily easy. "Several people in our studies," he noted, "have said this: 'I don't know why they call this ecstasy!' It's not just that people get blissed out and everything's fine. It's often difficult."

'I Killed Two Small Girls' Nigel McCourry was one of the subjects in the veteran study. Beginning in May 2012, he did five sessions, spaced one month apart. "I had huge breakthroughs that ended up resulting in my sleep issues completely going away after that very first session," he says. That represented an enormous improvement for someone who typically could not fall asleep until 5 or 6 a.m. and often had "really intense nightmares."

In one of them, McCourry would be shot by a sniper while on patrol in the desert. "I would jolt out of my sleep with a pain in my arm where I'd been shot in the dream," he recalls, "and then for the entire day I would be really disturbed by that dream, and I would still have a pain in my arm where the bullet hit me in my dream."

The breakthrough that allowed McCourry to sleep normally again involved a horrifying and heartbreaking incident in Iraq. "I killed two small girls," he says. "They were in a truck that was coming through the desert behind us in a firefight. I noticed this truck coming at us, and I signaled to it to stop. It kept coming, so finally it got close enough and I just started opening fire on the vehicle. Eventually the truck stopped, and it ended up it was a father and his two girls." Although "I understand now that I did the best thing that I could've done given the situation and what my options were," McCourry says, "before the MDMA therapy, I really had this sense of self-hatred for these two girls having died, and I held myself responsible in a way I shouldn't have."

The MDMA-assisted psychotherapy that McCourry underwent is mainly self-directed. The subject sits or reclines on a futon or couch, eyes closed or covered by shades, and listens to music that is "initially relaxing and later emotionally evocative." The co-therapists, one male and one female, are mostly there to encourage introspection and keep the subject on track.

"I would focus on any sensations that would come up, especially uncomfortable sensations." McCourry says, "because at that point, I'd been running from pain and uncomfortable thoughts for so many years that I was very good at running away from these things." In the therapy sessions, by contrast, "when something really challenging or really painful came up," he would "go back inside and use that process of inward awareness and focus to be able to understand the nature of whatever that situation was."

Some effects of that process, such as the ability to sleep through the night, "were instantaneous," while other issues were "a little bit more complicated" and "took time to kind of fade away or heal or work themselves out." But McCourry's psychotherapist and psychiatrist both noticed a dramatic change in him after the MDMA sessions. The psychiatrist in particular was "blown away," he says. "He said, 'This is remarkable. I can't begin to tell you the difference between who I see now in front of me vs. who came in to see me a year or two ago.' He said, 'I'm discharging you from my care. Come back and see me if you ever need anything, but I've got no reason to treat you at this point.'"

The American Legion, the country's largest veterans group, says marijuana could "help cut the amount of veteran suicides." But in a frequently noted Catch-22, the drug's Schedule I classification discourages the research that would be necessary to change its classification.

Today McCourry, who earned a master's degree in chemistry from the University of North Carolina in 2014 and works for a company in Portland, Oregon, that distributes lab equipment, is eager to share his "story of healing" with fellow veterans. Every day in America, he says, "veterans are committing suicide because they can't stand living with PTSD, and I think we could save a lot of these people if we just got this medicine available."

MAPS is working on that. In August the FDA deemed MDMA a "breakthrough therapy." That designation, which means a drug "may demonstrate substantial improvement over existing therapies," streamlines the approval process. MAPS says it has raised half of the $25 million it needs to pay for its Phase III studies, the first of which will begin enrolling subjects in the spring. Assuming all goes as planned, says Doblin, the group's founder and executive director, "we should have MDMA as a medicine in 2021."

Cannabis Catch-22 Progress with marijuana has been decidedly slower.

Twenty-four of the 29 states that allow medical use of marijuana explicitly recognize it as a treatment for PTSD, while three more give doctors enough leeway that they can recommend it for that purpose. "If you had said to me seven years ago that we were going to pass over 20 laws in seven years, I would've said you're crazy," says Michael Krawitz, executive director of Veterans for Medical Cannabis Access. "But that's exactly what we did, and now it's seen very clearly as a veterans' issue." The federal government, however, still classifies marijuana as a Schedule I drug, meaning it has no recognized medical value. That classification creates problems for veterans who receive medical treatment from the Veterans Health Administration (VHA).

Back in 2010, Krawitz got that agency to clarify that "patients participating in state marijuana programs must not be denied VHA services." That statement grew out of a battle between Krawitz and a VHA doctor who tried to make him sign a pain treatment contract that included a ban on illegal drug use. "The medical ethics are very clear," he says. "You're never to be denied treatment as punishment." But Krawitz says doctors who do not understand the VHA's policy still sometimes insist that their patients abstain from marijuana.

Even VHA physicians who have no problem with medical marijuana are not allowed to recommend it. In 2002, the U.S. Court of Appeals for the 9th Circuit ruled that such communications are protected by the First Amendment, Krawitz notes, and "outside the V.A., doctors feel very comfortable writing recommendations for cannabis." But the 9th Circuit's conclusion was never confirmed by the Supreme Court, and the VHA takes the position that marijuana recommendations remain legally perilous. That means veterans in medical marijuana states who find the drug useful for PTSD, pain, or other conditions have to see (and pay) another doctor if they want to obtain it legally.

Marijuana's Schedule I status also impedes attempts to verify its medical utility, because the listing triggers special regulatory requirements for researchers and may deter their employers and funding sources from backing studies of the plant's benefits. In a frequently noted Catch-22, marijuana's classification is one of the factors that discourages the research that the DEA says would be necessary to change its classification.

The American Legion, the country's largest veterans group, supports the rescheduling of marijuana to facilitate medical research, arguing that it could "help cut the amount of veteran suicides." But the plant's classification is not the only barrier. Even compared to other Schedule I drugs, marijuana is especially hard for scientists to study, unless they are investigating its hazards rather than its benefits.

The history of the first U.S. study to test marijuana as a treatment for PTSD, which finally got under way early this year, illustrates the obstacles. Sue Sisley, a Phoenix psychiatrist, approached Doblin about the possibility of conducting such a study in November 2009, having been intrigued by reports from her patients.

"None of them are claiming it's a cure," Sisley says. "They report that the cannabis helps them initiate sleep and then, in turn, will suppress a lot of the nightmares and flashbacks that make their sleep erratic. There are all these dark thoughts rolling through their heads, especially at night. So they're up at night, and then their anxiety is worse in the day because they're chronically sleep deprived, and then they're dealing with the worst anxiety in the day and they have that hypervigilance, that startle reflex, that's constantly plaguing them. Those are the kind of things that they said the cannabis seems to quell."

'The FDA Was a Joy to Work With' The experiences with marijuana reported by Sisley's patients seem to be common. In New Mexico, which in 2009 became the first state to recognize cannabis as a treatment for PTSD, it is the most frequent qualifying condition in the medical marijuana program, reported by 19,032 registered patients as of July, compared to 13,205 with severe chronic pain. A 2014 study, reported in the Journal of Psychoactive Drugs, looked at before-and-after CAPS scores of about 80 New Mexico patients and found that marijuana use was associated with an average reduction of 75 percent.

That result, while impressive, has to be interpreted with caution. As the researchers noted, the sample was "a highly select group of pre-screened patients who had already found that cannabis reduced their PTSD symptoms" and may have had an incentive to exaggerate their initial problems to qualify for the state's medical marijuana program. Furthermore, there was no control group of otherwise similar patients who did not use marijuana. An unpublished Israeli study that found large CAPS reductions in 29 combat veterans after they smoked marijuana had the same weakness.

To test promising findings like these, Sisley and the folks at MAPS designed a controlled, triple-blind study in which veterans with PTSD would be randomly assigned to use four different kinds of marijuana: one high in THC, marijuana's main psychoactive ingredient, and high in cannabidiol (CBD), which does not make you high but may help relieve anxiety; one high in THC and low in CBD; one high in CBD and low in THC; and one low in both. MAPS submitted the study protocol to the FDA in November 2010 and, after some modifications, received the agency's approval in April 2011.

"The FDA was a joy to work with," Sisley says, because the agency is legally required to reply within a month after receiving protocols, revisions, and questions. "It's all those other agencies that come afterwards that don't have any required timeline. They can take years to respond to your inquiries, and that's how the cannabis research has been systematically impeded by the government. These are layers of government red tape that no other Schedule I drug has to deal with. Only cannabis is required to go through all these additional layers of scrutiny."

Among other requirements, the MAPS study had to get approval from the U.S. Public Health Service (PHS) in order to obtain cannabis from the National Institute on Drug Abuse (NIDA), the only entity in the United States that is legally permitted to produce it for research. While other Schedule I drugs are available from a variety of DEA-licensed sources, researchers have to get marijuana from NIDA, which pays a single contractor at the University of Mississippi to grow it. MAPS fought a nine-year legal battle to break up NIDA's marijuana monopoly, arguing that competition would improve quality, increase variety, and facilitate medical research. The DEA was unpersuaded.

Four and a half months after the FDA approved the MAPS marijuana study, Doblin got word that the panel reviewing it for the PHS had unanimously rejected it. Two months after that, the institutional review board at the University of Arizona, where Sisley planned to conduct the study, approved the very same protocol. MAPS had the approval of the two entities whose permission would ordinarily be required to proceed with a drug trial, but it was stymied by an agency that had veto power only because the research involved marijuana.

The PHS reviewers' objections were puzzling and inconsistent, Doblin says, but he did his best to address them. The delay consumed almost two years, and in the end the protocol was approved unchanged. "Veterans are a highly sympathetic patient population," Doblin notes. "I think that made all the difference in getting the study approved [by the PHS]. From a political perspective, that element made it very difficult to say no."

'We Have to Be Activists' That was not the end of the study's travails. In April 2014, NIDA informed MAPS, contrary to what it had indicated in 2011, that it did not have the varieties of marijuana required for the study and would have to grow a new crop. A couple of months later, the University of Arizona fired Sisley from her part-time position as director of interprofessional education in the telemedicine program. As detailed in a 2014 story by Ray Stern in Phoenix New Times, the decision, which left Sisley scrambling to find a new research site, seemed to grow out of the controversy over her marijuana research, which drew objections from conservative state legislators even though it was perfectly legal under both state and federal law.

The last major blow to the study before it finally got started was again related to NIDA's marijuana monopoly. When the research material finally arrived in August 2016, laboratory tests found that the THC and CBD concentrations were not quite what NIDA had promised, which already was not quite what the researchers had wanted. Tests also found relatively high levels of mold, which the researchers ultimately decided did not pose a threat to the subjects. But the negative press coverage generated last March by Sisley's criticism of NIDA's marijuana apparently helped precipitate the departure of Johns Hopkins University psychologist Ryan Vandrey, a cannabis expert who had agreed to conduct part of the study in Baltimore.

Vandrey's departure meant that all 76 subjects for the study had to be enrolled in Arizona. "It's always been one obstacle after another," Sisley says, "and we've always managed to hurdle all of these barriers, so we will get to 76 no matter what." She figures the study should be completed within two years.

Future marijuana researchers will face fewer barriers. In June 2015, four years after MAPS ran into a brick wall at the PHS, the Obama administration eliminated that layer of review. A year later, the DEA finally announced that it is willing to license additional suppliers of marijuana for research, although it's not clear if and when that will actually happen. "We do not know how long the process takes, because this is the first time this has been done," DEA spokesman Melvin Patterson says. As of August, the DEA had received 25 applications, but a "senior DEA official" told The Washington Post the agency was facing resistance from the Justice Department.

The issue is crucial not just because additional suppliers will make research easier but because NIDA marijuana cannot be used in Phase III clinical trials. The material tested at that stage has to be the same as the material that will be made available to patients should the drug be approved by the FDA.

MAPS is backing one of the would-be marijuana producers, University of Massachusetts at Amherst plant scientist Lyle Craker, who also was involved in the organization's earlier attempt to break the NIDA monopoly.

"The nature of our work requires that we strive to change laws that are blocking this kind of research," Sisley says. "We have to be activists. We want to be scientists. We want to just do the work. But unfortunately, the way the system's structured, we have to continually point out these barriers that are preventing the work from happening."