The Fascinating Evolution of a Club Drug: Could Ecstasy Cure PTSD?

“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.”

In his book PiHKAL: A Chemical Love Story (PiHKAL stands for “Phenethylamines I Have Known and Loved”), published in 1992, Dr. Shulgin said of his experience with MDMA:

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.

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