POPULAR DRUG GAINS RESPECT
Study led by UC San Francisco researcher shows MDMA could help millions suffering from the psychiatric disorder
Retired Army Sgt. Jonathan Lubecky couldn’t get the year he spent in Iraq out of his head.
Loud noises and people wearing backpacks triggered flashbacks, and he regularly woke up from nightmares in a cold sweat. He tried to take his own life five times between 2006 and 2013.
Afraid that his next suicide attempt would succeed, Lubecky signed up to participate in a clinical research study investigating whether MDMA, commonly known as Molly or Ecstasy, could help tame the symptoms of posttraumatic stress disorder.
“I thought it’d be fun to do and it might help for a month or two,” said Lubecky, 45. “I was wrong. It’s a f—— miracle.”
The successful treatment of PTSD patients such as Lubecky is catapulting MDMA and other psychedelics into the medical spotlight as promising therapeutic tools. Long stigmatized, MDMA is proving to be effective in easing PTSD in rigorous clinical trials conducted at UC San Francisco and other respected medical centers around the globe.
Although some scientists remain skeptical, a growing number of researchers say the treatment could potentially help the more than 300 million people worldwide who suffer from the psychiatric disorder.
“MDMA allows you to access these really deep traumatic memories in a way that is not anxiety-provoking,” said Jennifer Mitchell, a UCSF neuroscientist who recently led a groundbreaking study on MDMA-assisted therapy.
Developed in 1912 by the pharmaceutical company Merck as a precursor to a blood-clotting agent, MDMA was readily available as an experimental psychotherapeutic tool in the decades that followed.
But in the 1980s, growing recreational use of the drug, particularly at allnight rave parties, led the U.S. Drug Enforcement Administration to classify it as a Schedule I controlled substance — a drug determined to have no accepted medical use and a high potential of being abused. The reclassification in 1985 immediately drove legitimate studies into the chemical’s therapeutic value underground.
In an effort to prove that the drug had clear benefits, supporters established MAPS, the Multidisciplinary Association for Psychedelic Studies, in Santa Cruz the following year. The association has since expanded its
research into other drugs, including LSD and marijuana, and recently relocated to San Jose.
Currently, the only approved medications for PTSD are Zoloft and Paxil. But the response rates of PTSD patients to the two widely prescribed antidepressants rarely exceed 60%, and less than 20-30% of patients become free of the diagnosis, according to a 2008 review of studies evaluating the effectiveness of the two drugs in treating PTSD.
New status
The psychiatric disorder, however, may have met its match. In 2017, the U.S. Food and Drug Administration granted “breakthrough” status to MDMAassisted therapy as a PTSD treatment. The new status fosters a speedier FDA review process because it joins a class of drugs that the agency has determined “demonstrate substantial improvement over available therapy.”
On Nov. 22, 2014, eight years to the day after Lubecky returned from Iraq, he entered a therapy room as part of a clinical trial at the Medical University of South Carolina.
For years, Lubecky, who lives in Washington, D.C., had taken a generic version of Zoloft with no success. And he was initially skeptical of MDMA’s ability to relieve his symptoms. As a child, he saw his eldest brother abuse drugs, so Lubecky shunned psychedelics. He also feared that a bad experience would precipitate flashbacks and cause him to turn violent.
Despite the trepidation, he nervously swallowed a pill containing 125 milligrams of MDMA. After almost an hour, the drug kicked in.
“I felt a universal pressure all over my body,” Lubecky said. “It was very much like wearing a wetsuit in warm water.”
Two therapists then guided him in conversation about his time in Iraq, starting with simple questions like, “How was the weather?” As the session progressed, the therapists asked harder questions, focusing on the details and emotions that accompanied his traumatic experiences.
He cycled between chatting with the therapists and listening to soothing music for the next six and a half hours, breaking only for a booster dose of 68 milligrams of MDMA two hours into the session.
Before enrolling in the clinical trial, Lubecky said, his previous 50-minute therapy sessions were too short to delve into meaningful topics — and he would become either too upset to talk or block out the emotions completely.
In contrast, he added, MDMA stabilized his emotions and helped him to trust his therapists. “My body didn’t go haywire when I was talking about these things,” he said.
He repeated the MDMAassisted therapy session twice in the following winter and spring, accompanied by ongoing traditional therapy. After completing the clinical trial, Lubecky’s suicidal thoughts, depression, panic attacks and inability to trust people gradually dissipated. And he’s been resilient in the years since.
Studies continue
UCSF’s Mitchell is now building on the success of the Phase 2 study that Lubecky and 25 other patients participated in. She recently led a Phase 3 trial that involved 90 patients at 15 research sites in the U.S., Canada and Israel. It’s the first psychedelic-assisted therapy to make it this far in the FDA’s regulatory pipeline.
Mitchell and her colleagues found that after two months of treatment, 67% of those who received MDMA with therapy were no longer diagnosed with PTSD, compared with 32% in the group that received the therapy and a placebo.
The study, funded by the Multidisciplinary Association for Psychedelic Studies, was published last May in the prestigious journal Nature Medicine. And if the researchers are able to replicate that finding, the treatment could gain FDA approval as early as next year.
“It’s been a long time coming, and we’ve been studying PTSD as a group for many, many years,” Mitchell said. “So it’s nice to think that perhaps we’ve identified a therapeutic that actually has some relevance.”
MDMA works by reducing activity in the amygdala, the brain’s fear-processing center, and increasing activity in the prefrontal cortex, according to Rick Doblin, the founder and executive director of MAPS.
Doblin, a co-author of the Phase 3 study, said the drug allows a patient to think more logically without feeling afraid. Additionally, he said, the drug enhances connectivity between the amygdala and hippocampus, which helps patients process their traumatic memories and put them into the past.
“MDMA has a variety of effects in the brain,” Doblin said. “You could say that it changes the brain in the opposite way that PTSD changes the brain.”
The drug also triggers the release of the hormones serotonin, dopamine, norepinephrine and oxytocin. Serotonin, in particular, fosters feelings of social connection, empathy and trust. In a therapy setting, this may help strengthen the patient-therapist relationship, said Dr. Boris Heifets, an anesthesiologist at the Stanford University School of Medicine who studies the effects of psychedelics in rodent models.
The setting also influences MDMA’s effects, according to Heifets. If taken at a rave, for example, “it’s almost not even the same drug as when you’re taking it in the context of therapy,” he said.
The treatment could be especially helpful for veterans and those with complex trauma, such as the patients in the Phase 3 study. The therapy could also aid survivors of sexual assault, who Lubecky says make up the vast majority of research participants in MAPS studies but receive little media attention.
“Veterans have a voice to speak about PTSD in a way that others cannot,” he said.
Concerns raised
Still, the research renaissance surrounding MDMA, especially the study Mitchell led, concerns some academics and clinicians.
“I’m a bit skeptical of how they present their results and, essentially, the hype surrounding MDMAassisted therapy,” said Joar Øveraas Halvorsen, a clinical psychologist at the Norwegian University of Science and Technology in Trondheim, Norway.
Halvorsen and some of his colleagues argue that MDMA-assisted therapy hasn’t been compared to existing PTSD treatments or tested in enough people to adequately measure the drug’s potential adverse effects, including cardiac anomalies, abuse potential and increased suicidal thoughts. The Norwegian scientists also contend that the therapy may be working simply because the sessions are so much longer than traditional sessions.
MDMA research, meanwhile, is expanding beyond its effects on PTSD sufferers.
Scientists are also investigating its therapeutic value for eating disorders, alcohol abuse, social anxiety in adults on the autism spectrum, anxiety associated with life-threatening illnesses and other hardto-treat disorders.
In regard to fears that PTSD sufferers would abuse the drug, Lubecky said that having completed the MDMA-assisted treatment he would never turn to MDMA for a fun night out.
“It wasn’t a fun experience — it was a lot of very, very difficult and hard work,” he said. “I went through all the worst things I’ve ever experienced in my entire life.”
Today, Lubecky said, he loves his work as a political strategist and a MAPS veterans liaison. He also enjoys providing pro bono advice to veterans with PTSD seeking help.
Without MDMA-assisted therapy, he said, his teenage stepson would have lost a father.
“I have a great life,” Lubecky said. “I wouldn’t even be alive right now if it weren’t for this.”