Researching ecstasy's effects on the human brain

Scientists call for experiments with MDMA to explore the drug’s potential therapeutic benefits.

MDMA, more commonly known as ecstasy, promotes empathy and social closeness in its users. It’s still not clear exactly how it works in humans, what regions of the brain it targets, or which molecular pathways it affects. Two Stanford researchers want to change that, and are calling for more experiments on the illicit drug to explore its potential to help treat disorders like autism and PTSD. We speak with Boris Heifets about why he’s raising the issue in the latest edition of Cell.

ResearchGate: What motivated you to write this commentary?

Boris Heifets: I had done some clinical work with MDMA before coming to Stanford, and I was aware of the remarkable—if preliminary—clinical trial data emerging about its use in psychiatric disorders. However, I had basically shelved the idea of pursuing any mechanistic studies. As a young investigator, it seemed a bit risky to spend much time studying a Schedule 1 substance (i.e. “no accepted medical use”).  When I joined Dr. Malenka’s lab a few years ago, I was surprised to find out he had an interest in studying this drug as well, following on a recent study he published with Gul Dolen looking at social reward in mice. We started work on it, and got some very positive feedback on our preliminary data. As a research tool, I think it has tremendous value. We wrote this Commentary to encourage the broader scientific community to take a more nuanced view of this drug, that despite its legal status it may have importance to science and medicine.

RG: What can we learn from research on MDMA and its effects?

Heifets: I’ve heard psychiatrists say “the relationship is the treatment.” This is a fundamental part of successful psychotherapy, forging a productive bond between therapist and patient. In people, controlled clinical trials (and a large collection of anecdotal data) all show that MDMA consistently enhances feeling of empathy, openness to others, and a certain self-awareness—these subjective effects are probably what make it effective, with just one or two doses, as an adjunct to psychotherapy in patients with PTSD. In several ways, this is a radical departure from the standard model of therapy (e.g. long-term SSRI treatment), and begs a number of questions: foremost in my mind, how does it reinforce positive social interactions? How does a social bond help recovery? Can a single dose of a drug modify the course of a long standing psychiatric condition?

“It is difficult to understate the social and economic impact of psychiatric disease worldwide.”

RG: What have studies with other illicit drugs taught us about how the brain works?

Heifets: This a broad topic that I can barely do justice to in a few lines—but suffice it to say, we have learned a tremendous amount about the neural circuits and molecular mechanisms of addiction using tools like cocaine and morphine. Studying rodent behavior has limits in what it can tell us about the human condition, but remarkably, reward and addictive behaviors transcend species.

RG: Which patients would benefit most from the knowledge studies with MDMA could produce?

Heifets: It is difficult to understate the social and economic impact of psychiatric disease worldwide, and at the same time as the efficacy of psychiatric drugs is being questioned, many large pharmaceutical companies have withdrawn from or scaled back their R&D for psychiatric drugs. Clearly, safer, novel drugs based on the biology of MDMA would represent an entirely new therapeutic class. Another way I can imagine MDMA research helping a wide swath of patients is by renewing interest in the value of “talk therapy,” perhaps spurring efforts to improve patients’ access to therapists and training more therapists.

RG: You’re an anesthesiologist. Are there particular ways that field would benefit from MDMA research?

Heifets: It’s funny you should ask that, because it’s the same question I got from the National Institute of Mental Health after my last grant submission!  It’s easy to forget that anesthesiologists routinely give profoundly mind-altering drugs on a daily basis. As an example, anesthesiologists have been giving patients ketamine since the 1960’s, but it was the psychiatric community, over the last decade or so, that recognized ketamine’s potential a rapid-acting antidepressant. To put it briefly, I want to understand how rapid-acting treatments for psychiatric disease work. This class of therapies is quite small right now: ketamine is one example, MDMA is another. Both almost certainly involve rapid induction of synaptic changes. Understanding how rapid-onset therapy works, using MDMA as an exemplar, has broad application to other scenarios where targeted synaptic modification with psychoactive drugs could have tremendous benefit, for example as an adjunct to Deep Brain Stimulation for psychiatric disorders. This emerging field in perioperative medicine is well within anesthesiology’s scope of clinical practice.

“It’s easy to forget that anesthesiologists routinely give profoundly mind-altering drugs on a daily basis.”

RG: Is it difficult for researchers to get access to MDMA for use in studies?

Heifets: It’s not easy. One needs to have a Schedule 1 license from the Drug Enforcement Administration (DEA), among other state and local regulatory approvals. Our local branch of the DEA worked with us to implement all the necessary safeguards, and overall has been very helpful to us. That said, it still took a year from the time we started the approval process until we could start experiments.

RG: Would there be potential for MDMA studies with human subjects?

Heifets: Several small studies have already been completed, some showing very promising preliminary results using MDMA-assisted psychotherapy to treat Post Traumatic Stress Disorder in patients who have failed all the standard treatments. All though I am not affiliated with any clinical trials, I understand that several more human MDMA studies are underway in the US and abroad.

RG: Beyond learning from MDMA to develop new drugs, there’s been talk of reclassifying MDMA itself for use in conjunction with psychotherapy. How would additional research fit into that effort?

Heifets: Re-scheduling MDMA and approving its use for a specific indication should only happen after a thorough assessment of all the risks and potential benefits to a patient population. Like any drug, MDMA can have adverse reactions, some of them severe. At this point, well controlled clinical studies are the best way to address the legal status of MDMA.

Featured image courtesy of Tanjila Ahmed.