More than a party drug: MDMA could help ‘extinguish’ traumatic memories

Post-traumatic stress disorder is one of the most common mental health conditions in the world, with an estimated six out of every 100 people in the United States alone experiencing PTSD at some point in their lives — a figure that doesn’t account for people who live with complex trauma.

Yet despite its pervasiveness, available treatments for PTSD don’t work for at least a third of people with the condition. There are no pharmaceutical drugs approved for treating the particularities of PTSD, only the depression and anxiety that very often comes with it.

For the second week of our three-part series on psychedelics, we’ll be looking at a drug that has the potential to move the needle of PTSD treatment: MDMA.

MDMA, popularly known as molly or ecstasy, could be approved by the U.S. Food and Drug Administration as a treatment for PTSD as soon as 2024. If you trace the drug’s rambling journey over the past century, including the DARE-fueled 1990s myth that taking ecstasy makes your brain look like Swiss cheese, this development — pardon my technical language here — is a big deal.

I spoke with Jennifer Mitchell, director of UC San Francisco’s Institute for Translational Neuroscience and lead author of the phase III MDMA trial published in 2021, about how MDMA is thought to work in the treatment of trauma and potentially many other disorders, how it differs from psilocybin-assisted therapy, and the barriers that remain to MDMA therapy being accessible to those who could benefit from it the most.

But first, a trip — pun intended — down MDMA’s proverbial memory lane.

The history of MDMA

MDMA, short for the mouthful that is 3,4-methylenedioxy-N-methylamphetamine, was invented in 1912 by a German pharmaceutical company. The compound was originally developed for medications that control bleeding. But MDMA was more or less forgotten until the 1970s, when Bay Area psychedelic chemist Alexander Shulgin synthesized MDMA and took it himself.

Two years later, he published a paper that described the experience as “an easily controlled altered state of consciousness with emotional and sensual overtones,” comparing the high to a mixture of cannabis, the stimulant MDA, and psilocybin without the hallucinations. Shulgin thought it could be used therapeutically to reduce anxiety and other emotional problems. By the mid-’80s, hundreds of psychotherapists were using MDMA in their practices, without FDA approval.

This was around the time that club-goers began using MDMA recreationally and it was given its apt nickname, Ecstasy. The Drug Enforcement Administration criminalized MDMA as a Schedule I substance in 1985, labeling it as having no known medical use and a “high potential for abuse.”

A few people kept pushing for MDMA research, in spite of inaccurate claims of inevitable brain damage that kept the drug in the academic shadows for two decades. (MDMA produces no neurotoxic effects at the doses administered in clinical trials, and studies show that harmful long-term effects of the compound are probably caused by very high doses that most people don’t take). Leading the effort for decades has been Rick Doblin, a researcher who in 1986 founded the nonprofit advocacy group Multidisciplinary Assn. for Psychedelic Studies (MAPS). Against all odds, the FDA recognized the drug’s therapeutic potential in 2017 by granting MDMA “breakthrough therapy” status.

Results of a phase III trial sponsored by MAPS published in 2021 were encouraging. In follow-ups two months after their final MDMA-assisted therapy session, two-thirds of the study’s 90 participants no longer met the diagnostic criteria for PTSD. Another 21% of participants saw a meaningful reduction of symptoms. “That leaves 12% who didn’t respond,” Mitchell said. “We have to figure out why that is.”

If these results were to be reproduced on a larger scale, it would be a huge deal for those with treatment-resistant PTSD. As I mentioned, the only pharmaceuticals prescribed for PTSD are antidepressants, which treat just the depressive symptoms of the condition and don’t work for about a third of people who take them.

Beyond PTSD, “our belief is that MDMA probably holds promise for disorders of mood or emotion — things like depression, anxiety, eating disorders, and alcohol and drug use disorder,” Mitchell said. A separate set of clinical trials will need to be held for those conditions before MDMA therapy can be approved to treat them.

I asked Mitchell why PTSD is the first condition to go through the FDA’s approval process for MDMA. She explained that in the ‘70s and ‘80s, when hundreds of therapists were still using the drug in their practices, it appeared that MDMA may be effective for couples therapy. “It could help people get to those underlying issues that were harder to communicate,” she told me. “For that reason, it was thought that MDMA could also help people process trauma that was hard to communicate, hard to let go of, that was still being carried with them.”

Coupled with the fact that there’s no pharmaceutical treatment specifically for PTSD, and that the condition is one that “blossoms and flourish over time if left untreated,” Mitchell said, it was easiest to make a case to the FDA that this treatment is sorely needed.

The science of MDMA

Most of what’s known at this point about how MDMA works has been gleaned from studies on animals, and thus caution is needed in interpreting that research.

On a neuroscientific level, the compound seems to help extinguish memories of fearful experiences in the amygdala, the part of the brain that regulates emotions and ties emotional meaning to our memories, Mitchell explained. When someone takes MDMA, “they’re able to access trauma-related memories in a way that doesn’t make them feel uncomfortable or embarrassed,” Mitchell said. When trying to access their memories during a traditional therapy session, someone with PTSD usually dissociates quickly from these memories, causing them to shut down during psychotherapy.

“With MDMA, they don’t,” Mitchell said. “They can really dive into the traumatic memory, process it and release it. The memory of it still exists, but it’s not as emotionally laden, and therefore doesn’t impact every day of your life.”

MDMA also elevates levels of oxytocin, dopamine and other chemical messengers, producing feelings of empathy, trust, self-compassion, and closeness with others (hence its other nickname, the “love drug”). My favorite MDMA factoid might be that the notoriously solitary octopus wants more hugs after being dosed with the compound.

Limitations of MDMA and the path forward

As is the case for psilocybin-assisted therapy, which I wrote about last week, the therapy aspect of this treatment is thought to be essential to its efficacy.

“Some people come to us and say, ‘I’ve done these drugs four times, and it didn’t do anything for my trauma,’” Mitchell said. For one, MDMA on the black market is often laced with speed, meth, cocaine or other adulterants.

And “set and setting” — that is, a person’s mind-set when they trip (the “set”) and their environment (the “setting”) — seem to play a crucial role for clinical trial participants who’ve seen the most progress, as well as working with a therapist to process what came up in the MDMA session.

“I’m not a proponent of people putting this in their Vitamin Water, microdosing or doing it in your living room every Friday night in high doses with your friends,” Mitchell said. “I do feel that these are very powerful tools. But like any sword, it depends who’s wielding it and what they’re aiming at. I hope people will take this walk with us slowly.”

The long-term effects of MDMA-assisted therapy on PTSD are being studied. For now, this type of treatment isn’t intended for ongoing use. Participants in the phase III trial took part in just three sessions.

Though MDMA therapy could be approved as a treatment for PTSD relatively soon, it could be a long time before it’s accessible to people with fewer resources. It’s hard to assess at this point how costly treatments will be, but advocates fear that, as seen in many other treatment modalities, the hype around the treatment’s promise will inflate prices.

“To do psychedelic therapy, you need a special environment, a psychiatrist, two psychedelic facilitators — a whole staff monitoring this process. What will that look like in clinical care? How do you scale it up in an affordable, sustainable way?” Mitchell said.

“I don’t want this to be solely the panacea of the upper-middle class, people who have money and the time and wherewithal to find it.”

. . .

Next week, I’ll be writing about ketamine, the only psychedelic that is readily available as a treatment for depression — if you have the money.

Until then,

Laura

If what you learned today from these experts spoke to you or you’d like to tell us about your own experiences, please email us and let us know if it is OK to share your thoughts with the larger Group Therapy community. The email GroupTherapy@latimes.com gets right to our team. As always, find us on Instagram at @latimesforyourmind, where we’ll continue this conversation.

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More perspectives on today’s topic & other resources

MDMA therapy is almost legal — but who will have access? In this piece by DoubleBlind Mag, writer Jose Guzman looks into who will qualify for MDMA therapy, what it might cost, and whether historically marginalized communities who are often neglected by the healthcare system will be able to benefit from it.

For some couples on the brink of divorce, taking MDMA was a last resort — but it ended up being the only thing that worked. Drawn to the drug’s ability to produce feelings of empathy, trust and compassion, couples are using unregulated MDMA on their own in an effort to help them reconnect, improve communication and have better sex.

Like MDMA therapy, EMDR (Eye Movement Desensitization and Reprocessing) represents great promise in the treatment of trauma, and has already helped countless people. My friend and writer Tiffany Gibson dives into the similarities and differences between these therapies.

What’s it like to take a $249 drug-free psychedelic trip? My colleague Adam Tschorn visited a Santa Monica-based startup called the Reality Center that’s been trying to expand the mind and aid in healing the body via digital psychedelics — a proprietary combination of pulsing lights, sounds and vibrations — instead of consuming drugs.

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