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Psychedelic Drugs to Treat Depression, PTSD?

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Sept. 18, 2018 -- Jon Lubecky was running out of options when he checked into a small house-turned-clinic outside Charleston, SC.

The onetime Army artillery sergeant had been struggling with post-traumatic stress since he got home from Iraq, where his post had been shelled so often it was nicknamed “Mortaritaville.” In 2006, near the height of the insurgency and religious violence that followed the U.S. invasion, one of those shells sent shrapnel tearing through the outhouse where he was sitting in the middle of the night.

The shrapnel missed, but the shock of the blast knocked Lubecky out and left him with a traumatic brain injury. When he came home that fall, he found his wife had left him. He made the first of what would be five suicide attempts that Christmas.

 “My life was a country song,” Lubecky says.

By the time he got to the clinic door in November 2014, doctors at a Veterans Affairs hospital had him taking half a dozen medications to treat his PTSD, and it wasn’t working. So Lubecky signed up for an experimental treatment he hoped would help: MDMA, a psychedelic drug commonly known as ecstasy or Molly -- a compound that’s been banned for decades.

“And that’s when everything went weird,” he says. “Good, but weird.”

After years underground, psychedelic drugs are getting attention as a potential treatment for depression and posttraumatic stress disorder (PTSD).

MDMA, also known as ecstasy, has shown promise in studies of combat veterans. Psilocybin, the compound in “magic mushrooms” that gets you high, has been tested as a potential boost for people struggling to quit smoking. Researchers in Europe are conducting a survey of how “microdoses” of LSD or other drugs affect mental activity without altering perception. And the American Psychological Association held a symposium in early August on the potential uses of psychedelics.

“This is a very interesting, intriguing moment in psychiatric drug development,” says John Krystal, MD, chairman of the psychiatry department at the Yale University School of Medicine.

Lubecky was part of a trial conducted with the government’s blessing. He went to the house-turned-clinic three times, taking a dose of MDMA in combination with an extensive psychotherapy session. The drug is a form of amphetamine known for producing a sense of openness and emotional warmth, and Lubecky said it helped him discuss his experiences without producing the kind of intense physical responses of PTSD.

“The adrenaline kick didn’t happen. The hair didn’t stand up on my neck,” he says. “It’s like doing therapy while being hugged by everyone who loves you in a bathtub full of puppies licking your face.” The therapy sessions lasted up to six hours, “but it’s not traumatic at all.”

“There was no ‘A-ha’ moment,” he says. “It was an incremental change over time, with jumps after each therapy session.”

Doctors have been reluctant to explore the potential uses of psychedelics since the 1960s, Krystal says. Not only did the federal government classify them as having no acceptable medical uses and a high potential for abuse, but many researchers believed they were too powerful to use therapeutically. But the mental health field is facing “a moment of great need” that’s prompted some rethinking, he says.

“Our appreciation of the seriousness of psychiatric disorders is much more mature than it was then,” Krystal says. “We have a much better understanding about how common, how disabling -- and in some cases, with the rising suicide rate, how lethal these disorders are.”

Over the last 50 years, researchers have made “transformative” advances in understanding how the brain works. But there haven’t been corresponding breakthroughs in psychiatric drugs, he says. And there have been some promising results so far.

A phase III clinical trial of the use of MDMA to treat PTSD is moving ahead after it won FDA designation as a potential “breakthrough therapy” last summer. That status holds out the prospect of speedy review by the agency and “catapulted” fundraising for the trial’s backers, says Brad Burge, spokesman for the California-based Multidisciplinary Association for Psychedelic Studies (MAPS).

“That breakthrough therapy designation communicates to funders and to the rest of the world that this is a very serious treatment and the FDA is taking it very seriously. That’s huge,” Burge says.

The new study is a follow-up to the one involving Lubecky and another 25 veterans, police and firefighters who took MDMA combined with psychotherapy. After three doses in controlled settings, nearly all participants saw some improvement in their symptoms -- and about two-thirds “simply didn’t have PTSD anymore,” Burge said.

The results were published in May. Researchers checked in with participants 2 months after treatment, then a year later. "On average, those results actually kept getting better,” Burge says.

In Lubecky’s case, he says his PTSD symptoms are diminished by about 50% on the scale doctors use to assess the condition. Depressive symptoms are down 70%, and he no longer has suicidal thoughts. He’s now an advocate for MDMA therapy and works on veterans issues for MAPS, which he said “saved my life.”

“I was in such a place where I figured my stepson was going to be handed a folded flag off my casket at the age of 14,” he says.

“I know what an impact it’s had on my life,” he adds. “I have close friends of mine who are suffering right now. Anything I can do to grease the skids on that and the get the guys I served with, my guys, the help they need, I’ll do.”

“And now, I get to watch him grow up, drop him off at high school, watch him fall in love, watch him get his heart broke, watch him go to prom and go off to college … then when he’s old, and I’m really old, he’ll get the flag off my casket. And that’s the way it should be.”

There were no serious side effects, but the researchers did find one surprising result: Lower doses of MDMA were less helpful than not being given the drug.

“What we think might be happening there is it could be bringing up emotions or memories in people with PTSD without giving them the additional resources to deal with it in a productive way in therapy,” Burge says.

The FDA last month approved a study testing psilocybin to treat depression. British company COMPASS Pathways plans to begin the phase II trial immediately.

Depression is the leading cause of ill-health and disability worldwide, and treatment-resistant depression affects more than 100 million people,” George Goldsmith, chairman of COMPASS Pathways, says in a statement. “It is a huge unmet need, and the trial will teach us more about how this new approach might address it."

Meanwhile, researchers at Johns Hopkins University have been studying the use of psilocybin to help people quit smoking. In follow-up interviews, 15 participants reported “a number of persisting positive effects beyond smoking cessation,” says Matthew Johnson, PhD, associate professor of psychiatry at Johns Hopkins.

“We found generally people claimed vivid insights into their self-identity in psilocybin sessions -- insights into the reasons they smoked,” he says. For most participants, withdrawal symptoms “really took a back seat to their fascination with their unfolding contemplation of these psychedelic sessions.

“I had one pilot participant who said, ‘It’s kind of like I’m in The Matrix and everything’s in slow motion. Here’s a craving that’s coming … instead of that sort of automatic response where my hand goes into my pocket, grabbing a cigarette and it ends up in my mouth, it’s more of a slow, deliberative mindful response.’”

Other participants described increased appreciation or a re-emergence of interest in music and art or poetry.

Earlier research by Johnson and others at Johns Hopkins found psilocybin can produce “clinically significant” improvements in depression and anxiety in patients with life-threatening cancer. The drug may be able to provide hope where conventional antidepressant drugs have had little effect, he says.

But though imaging technology has given researchers the ability to view your brain on drugs, how psychedelic drugs work is still something of a mystery, Burge says.

“Even with MDMA, we have some strong theories about how it might be working to reduce PTSD symptoms in the long run, but we don’t know exactly why,” he says.

More brain-imaging studies might help to determine the mechanism of action of these drugs, Burge says, but they’re not needed to get federal approval of a treatment. The FDA only wants to know whether a drug is effective and that the benefits outweigh the risks.

Krystal, who also leads the clinical neuroscience division at the National Center for PTSD at the Department of Veterans Affairs, has warned that the lack of effective drugs to treat posttraumatic stress disorder is a “crisis.” Recent advances in neuroscience may provide a way to reopen the door for psychedelics or drugs like ketamine, which is also being tested as a treatment for depression, but he says that door should be pushed open cautiously.

“I think the central question at the moment is to determine exactly how much of the excitement over the potential therapeutic value of hallucinogenic drugs is hype and how much of it is real benefit,” Krystal says. “I’m afraid our current research base is so shallow that we have to approach these drugs in a very cautious and exploratory manner.”

WebMD Article Reviewed by Brunilda Nazario, MD on September 18, 2018

Sources

Journal of Psychopharmacology: “Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts.”

Compasspathways.com: “COMPASS Pathways Receives FDA Approval for Psilocybin Therapy Clinical Trial for Treatment-resistant Depression.”

Science: “All clear for the decisive trial of ecstasy in PTSD patients.”

Nordic Studies on Alcohol and Drugs: “Powerful substances in tiny amounts -- an interview study of psychedelic microdosing.”

News release, American Psychological Association: “Can Psychedelic Drugs Heal?”

John Krystal, MD, Yale University School of Medicine.

FDA fact sheet: “Breakthrough Therapies.”

The Lancet Psychiatry: “3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.”

Brad Burge, spokesman, Multidisciplinary Association for Psychedelic Studies.

Matthew Johnson, PhD, Johns Hopkins University.

Proceedings of the National Academy of Sciences: “Neural correlates of the LSD experience revealed by multimodal neuroimaging.”

Biological Psychiatry: “It Is Time to Address the Crisis in the Pharmacotherapy of Posttraumatic Stress Disorder.”

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