“It’s basically like years of therapy in two or three hours. You can’t understand it unless you’ve experienced it.”
– former Army Ranger and MDMA-assisted psychotherapy study participant
“This therapy made it possible for me to live.”
– Anonymous participant in MDMA-assisted psychotherapy for PTSD study
MDMA (3,4-methylenedioxy-methamphetamine), popularly known as Ecstasy, X, E, and Molly, is a synthetic, psychoactive drug that has similarities to both the stimulant amphetamine and the hallucinogen mescaline.
It produces feelings of increased energy, euphoria, compassion, trust, and empathy toward others, and distortions in sensory and time perception.
Long associated with underground parties, raves, music festivals, and house parties, the drug and its variations have gained a reputation for being a dangerous substance with no positive attributes or therapeutic benefits.
But that’s far from the truth.
A One Hundred-Year Journey
MDMA was developed in 1912 by German pharmaceutical company Merck during attempts to develop a drug to control bleeding. Merck patented MDMA in 1914, but the company did not conduct studies on the compound at the time.
The Merck archive reveals that the company revived its interest in MDMA (then known as methylsafrylaminin) in 1927, when the first tests were carried out on animals. Details are sparse, but records suggest that Merck chemist Max Oberlin stumbled on the original patent and thought MDMA might mimic adrenaline because it had a similar structure. A search of Merck’s records also found references to MDMA in 1952 and 1959, but again, details about any research done are lacking.
The U.S. Government is said to have carried out secret tests of MDMA and other drugs in the early 1950s at the Army’s chemical center. The experiments are often described as a search for a truth serum, but they were carried out on animals, and it is more likely the military was searching for new chemical weapons.
Despite those small, sporadic research efforts, MDMA was largely unknown until the mid-1970s.
Independently predicting that MDMA might be psychoactive, a biochemist and pharmacologist named Dr. Alexander Shulgin stumbled upon the compound in 1965 while working at Dow Chemical, but he did not try the substance at that time.
Shulgin ended his career with Dow in the mid-1960s to pursue independent research on new drugs, primarily phenethylamines and tryptamines. With a small group of friends, he built a body of objective and subjective reports for hundreds of psychoactive chemical compounds.
In 1976, a graduate student told Shulgin about her positive emotional experience with MDMA, which led him to develop a relatively easy way to synthesize it. Shulgin tried the drug himself that year.
Shulgin and a colleague published a report on MDMA in 1978, in which they described the drug as inducing “an easily controlled altered state of consciousness with emotional and sensual overtones” comparable “to marijuana, to psilocybin devoid of the hallucinatory component, or to low levels of MDA.” Believing MDMA allowed users to strip away habits and perceive the world clearly, Shulgin called the drug “window.”
I feel absolutely clean inside, and there is nothing but pure euphoria. I have never felt so great, or believed this to be possible. I am overcome by the profundity of the experience.
Shulgin was impressed with the drug’s disinhibiting effects and believed it could be useful in psychotherapy. He personally used MDMA on occasion for relaxation, referring to it as “my low-calorie martini,” and gave the drug to his friends, researchers, and others he thought could benefit from it.
One of those people was Leo Zeff, a psychotherapist who had been known to use psychedelics in his practice. When he tried Shulgin’s sample of MDMA in 1977, Zeff was so impressed with the effects of the drug that he cancelled his plans to retire so he could promote its use in psychotherapy. Over the following years, Zeff traveled around the U.S. and occasionally to Europe, eventually training an estimated 4,000 psychotherapists in the therapeutic use of MDMA. Zeff called the drug “Adam,” believing it put users in “a state of primordial innocence.”
From Clinic to Criminalization
By the late 1970s and early eighties, the use of “Adam” had spread through personal networks of therapists and users of psychedelics. In hopes that MDMA would avoid the same fate as LSD and mescaline (criminalization), therapists and experimenters tried to limit the spread of information.
But a recreational market developed, and MDMA became popular in the nightclub scene. In 1983, small group of chemists known as the Boston Group dominated production of the drug, and Michael Clegg, their southwest distributor, saw a money-making opportunity. He called the drug Ecstasy and began openly selling it in Texas – even marketing the drug using pyramid sales structures and toll-free numbers for orders. Clegg’s “Texas Group” advertised Ecstasy parties at nightclubs and bars, promoting MDMA as a “fun drug” that was “good to dance to.”
Upon learning of the Texas Group parties and pyramid scheme, the U.S. Drug Enforcement Agency (DEA) announced an emergency Schedule I classification (the most restricted class of drugs) of Ecstasy in May of 1985. The federal government considers Schedule I drugs to be among the “most dangerous,” with no known medical benefits and the potential for “severe psychological or physical dependence.”
Possession of a ”trace” of a Schedule 1 drug by a first-time offender can result in 15 years in prison and a $125,000 fine.
Expert witnesses testified that the drug had valid medical uses, and a presiding judge recommended that MDMA be classified as Schedule III, which would have allowed doctors to continue using it in therapy. DEA administrator John C. Lawn overruled, and classified the drug as Schedule I. A Harvard psychiatrist sued the DEA over the ruling, stating that the agency had ignored the therapeutic uses of MDMA. The federal court agreed with the psychiatrist, but even after reviewing the expert testimony of several psychiatrists citing over 200 cases where MDMA had been used in a therapeutic context with positive results, Lawn reclassified the drug as Schedule I again. His reason? He said the evidence for beneficial use of the drug could be dismissed because it wasn’t published in medical journals and it hadn’t been reviewed or approved by the FDA.
Making MDMA illegal backfired: it did not significantly reduce recreational use, and it increased demand. And unfortunately, the classification of MDMA as Schedule I brought most research and therapeutic use to a halt, although some therapists continued to recommend the drug illegally.
In 1986, Dr. Rick Doblin, one of Dr. Zeff’s students, founded the non-profit research organization Multidisciplinary Association for Psychedelic Studies (MAPS), with the goal of funding clinical trials on MDMA and making it an FDA-approved prescription medication by the year 2021.
Shulgin obtained a DEA Schedule I license for an analytical laboratory, allowing him to possess and synthesize scheduled substances. On occasion, he conducted research for law enforcement, and received several awards from the DEA.
But in 1994, two years after the publication of PiHKAL, the DEA raided Shulgin’s lab. In the 15 years preceding the publication of PiHKAL, two announced and scheduled reviews had failed to find any irregularities. Despite this, the agency fined Shulgin $25,000 for for violating the terms of his DEA license by running analytical tests on street samples of potentially controlled substances that were not part of a pending legal case. Rather than having unreasonable restrictions placed onto his work by the government, Shulgin decided to turn in his DEA license and stopped working with scheduled substances.
Today, MAPS continues its research into MDMA-assisted psychotherapy, and so far, the results are promising. Most of the organization’s research is on MDMA use for post-traumatic stress disorder (PTSD), but studies on the drug’s use in treating social anxiety in autistic adults and anxiety associated with life-threatening illness are being conducted as well.
Therapeutic MDMA: Not Your Dealer’s Drug
Experts are quick to emphasize that recreational and pharmaceutical MDMA are not the same drug; in fact, they barely resemble each other. While the terms MDMA, Ecstasy, and Molly are used interchangeably, Molly or Ecstasy bought on the street is often fake or has been cut with dangerous adulterants like methamphetamine, and rarely contains actual MDMA.
The DEA reported that only 13% of Molly seized in New York from 2009-2013 contained any MDMA whatsoever, and even then it often was mixed with other drugs. When DEA labs test seized drugs marketed as Molly, they usually find other synthetic drugs, particularly methylone, an ingredient often found in the drug called bath salts. The biggest risk associated with buying the drug on the street is that you don’t know what you are really getting.
In therapy, pure MDMA is used, and it is not prescribed as a medication for regular use, as antidepressants are. It is used during psychotherapy, under close guidance, for a limited number of sessions.
To date, no studies have shown that clinical usage (taking pure MDMA in moderate doses under medical supervision a limited number of times) leads to long-term cognitive damage, according to Matthew Johnson, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine. MDMA has been given to more than 1,113 subjects in recent studies, with only one report of a serious, drug-related adverse event, which ended once the drug wore off (a participant was admitted to the hospital with an irregular heartbeat and was released the next day).
While MDMA can increase heart rate, blood pressure, and body temperature, when used in a controlled setting the drug doesn’t present any real danger as long as the patient is moderately healthy, experts say.
MDMA acts by increasing the activity of three neurotransmitters (the chemical messengers of brain cells): serotonin, dopamine, and norepinephrine. MDMA causes these neurotransmitters to be released from their storage sites in neurons, resulting in increased neurotransmitter activity.
Serotonin plays an important role in the regulation of mood, sleep, pain, appetite, and other behaviors. The excess release of serotonin by MDMA likely causes the mood elevating effects experienced by users.
Serotonin also triggers the release of the hormones oxytocin and vasopressin, which play important roles in love, trust, sexual arousal, and other social experiences. This may account for the characteristic feelings of emotional closeness and empathy produced by the drug; studies in both rats and humans have shown that MDMA raises the levels of these hormones.
However, by releasing large amounts of serotonin, MDMA causes the brain to become significantly depleted of this important neurotransmitter, contributing to the negative behavioral after-effects – including confusion, depression, sleep problems, drug craving, and anxiety – that users can experience for several days after taking MDMA.
Penicillin for the Soul
Depression, PTSD, substance abuse, relationship problems, premenstrual syndrome, and autism are among several psychiatric disorders MDMA-assisted therapy has been reported to treat with great success. MDMA eliminates the typical fear response and increases communication. MDMA is often referred to as an “empathogen or an “entactogen,” or “penicillin for the soul” for these reasons.
A paper titled MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults published in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry, which outlines the evidence for using MDMA, cites the following benefits of using the drug in therapy:
Most of the therapeutic effects of MDMA result from changes in affect, cognition and social interaction. Vollenweider et al., (1998) reported that MDMA produced acute “increased responsiveness to emotions, a heightened openness, and a sense of closeness to other people.” When combined with psychotherapy that supports one or more of these effects, MDMA permits individuals to confront and consider emotionally intense memories, thoughts or feelings and perhaps through changes in mood and perception increases empathy and compassion for others and one’s self.
A Paradigm Shift and Promise for PTSD
In 2010, a small MAPS-sponsored study of MDMA-assisted psychotherapy in the treatment of PTSD found that 83 percent of those who had been treated no longer showed symptoms of PTSD. A follow-up study, published in 2012, found that most of those subjects remained symptom-free and that none of them reported harm from the use of MDMA. The researchers said those results support their claim that MDMA-assisted psychotherapy can have lasting effects after just a handful of treatments. Dr. Michael Mithoefer, the study’s principal investigator, said:
With such encouraging data, including evidence of long-term effectiveness after only two or three MDMA-assisted psychotherapy sessions, there is now no doubt that this research should be expanded to larger clinical trials.
The participants in that study included survivors of sexual assault, abuse, and one military veteran. None of them had responded adequately to existing psychotherapies and drug treatments for PTSD, and had suffered from PTSD for an average of over 19 years.
After his 2004-2005 tour in Afghanistan and Iraq with the National Guard, Virgil Huston suffered from PTSD. He worked with a therapist for six years and took “every antidepressant known to man,” but saw no improvement. Huston, who participated in Dr. Mithoefer’s study, told USA Today that after three day-long MDMA-assisted psychotherapy sessions, he no longer exhibits symptoms of PTSD:
I’m not perfect. But I know this: If there is a silver bullet for curing PTSD, then this could be it.
In a recent article titled Is Ecstasy the Key to Treating Women with PTSD? writer Kelley McMillan shared stories of female MDMA study participants.
One told McMillan she was in “a fight for her life” and MDMA opened up a world of new emotions for her:
I was able to feel. I think that’s the biggest takeaway. While on the MDMA, I had access to feelings that I hadn’t ever had access to before. I spent 35 years suicidal, and I’m not anymore, because of the MDMA and two really skilled therapists.
Another participant said of her MDMA-assisted psychotherapy experience:
Instead of feeling hyperaroused or overstimulated, I felt a tremendous calm and had reduced anxiety. I felt really empowered, like I could direct my mind where I needed to.
I felt as if I was literally reprogramming my brain and confronting all of the fixed thought patterns and belief structures that were keeping the PTSD in place, that were making me relive the past over and over again. I was able to file those memories in the past.
Psychiatrist Dr. Julie Holland, author of Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA, explained why the drug is so useful in therapy:
Patients are awake, alert, connected. They want to talk. They want to explore. They feel calm enough and their fear is extinguished enough that they can actually process the trauma. You basically couldn’t design a molecule that is better for therapy than MDMA.
It’s almost like anesthesia for surgery. It allows you to dig and get to the malignant thing that needs to be pulled out and examined. It takes years in psychotherapy to dig around the trauma and start to get to it. This is a way for people to process the core issue in order to move forward.
Andrew Feldmár, a psychologist who is working on a Vancouver study into MDMA-assisted psychotherapy, said, “I have worked with people who have been for years on major tranquilizers or major antipsychotics who after one or two MDMA sessions never had to take the ordinary standard pharmaceutical drugs again.”
In early 2015, both the FDA and the DEA approved studies of MDMA, which appears to be a sign of positive changes to come, as Brad Burge, communications director for MAPS, told The Huffington Post:
The smooth process of regulatory approval for this study indicates that stigma is no longer standing in the way of regulatory approval for research into the therapeutic uses of MDMA and other psychedelics.
And – also in early 2015 – Dr. Philip Wolfson, a longtime advocate of MDMA-assisted psychotherapy, was given permission by the FDA to conduct a MAPS-sponsored study on MDMA use in patients with life-threatening illnesses, and was also granted a license from the DEA to give the drug to patients.
Dr. Thomas Insel, director of the National Institute of Mental Health, told SF Gate that his agency is following several privately funded studies that are using psychedelic drugs in conjunction with psychotherapy to treat a variety of mental disorders:
It’s a really interesting and a very powerful new approach. It’s not just taking MDMA. It’s taking it in the context of a treatment that involves improved insight and increased skills and using this in the broader context of psychotherapy.
The National Center for PTSD (in the Department of Veterans Affairs) has been consulting with MAPS about an upcoming study on MDMA-assisted couples therapy involving veterans and top VA-affiliated psychologists that will begin at the end of this year.
One of the biggest obstacles standing in the way of developing MDMA into an FDA-approved medication is funding. The process is a $20 million endeavor and one that relies completely on the fundraising efforts of MAPS, partly because pharmaceutical companies have little interest in developing a drug administered only a few times. In 2016, MAPS will move MDMA-assisted psychotherapy one step closer to legalization when it begins phase-three clinical trials, which will involve more than 400 participants and last five years. If those trials are successful, psychiatrists may be prescribing the treatment by 2021.
Dr. Evan Wood, a psychiatric researcher at the University of British Columbia, recently told Newsweek that drugs like MDMA can help people have profound realizations that permanently change their behaviors. He explained that with mental health conditions like anxiety and depression, the existing paradigm is to frame these as chronic, lifelong diseases that require long-term use of medication.
Treatment with psychedelics and compounds like MDMA represent “a total paradigm shift in the way that mental illness is treated,” Dr. Wood said.
“The re-emerging paradigm of psychedelic medicine may open clinical doors and therapeutic doors long closed. This is an area that could potentially bring about major changes in people, without a sort of chronic-disease model where people would be forever on an expensive [pharmaceutical] medication. It’s a totally different model: it’s not one pill every day, it’s one experience and we’re going to try to heal you.”