Tonic: MDMA Mimics a Genetic Disorder Called ‘Cocktail Party Syndrome’

Summary: Tonic explores MAPS-sponsored study of MDMA-assisted therapy for social anxiety in autistic adults. Tonic also speaks to Brad Burge of MAPS about MAPS’ clinical trials of MDMA-assisted psychotherapy as a potential treatment for PTSD. “The best thing about this potential treatment, in my view, is the fact that it only needs to be done a few times. Why is that? We’re not addressing symptoms: We’re addressing the underlying root cause of PTSD—the trauma at its core,” explains Burge. “MDMA has the ability to make you more open and compassionate and trusting. That’s a great idea if you’re dealing with PTSD in a therapeutic setting.”

Originally appearing here.

For introverts, New Englanders, and other taciturn types, opening up to new people, or even our oldest friends, can be a challenge. But people with a genetic disorder called Williams syndrome have no problem opening up—that is the problem. The disorder, which affects one in 10,000 people, or roughly 30,000 Americans, inspires a feeling of kinship and closeness with everyone they encounter. They might hug strangers at the grocery store, tell checkout clerks they love them, and invite everyone in the parking lot over for a slumber party.

It’s terrifying for their parents, who fear the risk of exploitation that comes with unconditional love and indiscriminate trust. But people with Williams syndrome radiate joy. When one young man with Williams attempted to describe his condition, he was momentarily at a loss for words. “It’s…” he said thoughtfully, then smiled broadly. “It’s like a party!”

He wasn’t entirely wrong. Williams is sometimes called “cocktail party syndrome” because of its tendency to make people extremely outgoing and irrepressibly friendly.

In the mid-1990s, when scientists identified the 26 missing genes that cause Williams, some researchers hoped it would lead to a better understanding of the genetic roots of human behavior—especially attachment and bonding. In 2009, a team of researchers discovered that one gene in particular might help explain why people with Williams seem to love and trust everyone they meet. The gene, called GTF2I, plays a part in regulating the brain’s production of oxytocin, a hormone involved in intimate moments from parent-child bonding to romantic encounters. It’s been called both the “love hormone” and the “trust hormone.”

One of the hormone’s effects is to relax the amygdala, the brain’s fear center. Essentially, oxytocin allows the amygdala to let its guard down so we can develop the feeling of closeness to others that is essential to attachment. Ordinarily, oxytocin is released by the pituitary gland in controlled, strategically timed doses—for example, when a new mother nurses her baby. But for people missing a copy of the GTF2I gene, the trickle becomes a flood. And the floodgates are open all the time.

This can indeed make life like a party. The openness, empathy, and selflessness it engenders can also make life with Williams seem like a more enlightened way of being. Either way, the experience seems like something the rest of us could benefit from trying—at least for a little while.

As it turns out, there’s another way to open the oxytocin flood gates, short of removing the GTF2I gene: Taking MDMA has a similar effect on the brain. It’s how the drug, best known for being the key ingredient in ecstasy and Molly, fosters feelings of connection and intimacy that earned it the label of “empathogen,” and made it a popular tool in 1970s couples counseling, helping partners drop their defenses and communicate freely.

MDMA also increases production of the antidepressant hormone serotonin, which helps explain the drug’s mood-boosting effects and its ability to heighten feelings of awareness and alertness. But serotonin doesn’t seem to explain the feeling of universal kinship that many recreational ecstasy users have described. Evidence in favor of oxytocin’s role comes from lab rats: given a dose of MDMA, they behave in unusually friendly ways, such as “lying next to each other and cuddling,” according to Discover magazine. When they’re given an oxytocin blocker along with the MDMA, however, the cuddling stops.

Likewise, Williams researchers who removed the mouse equivalent of the GTF2I gene raised mice who were similarly cuddly and lacking in social inhibitions. Instead of scurrying into corners to avoid detection by predators, as mice normally do, these mice sauntered out into the open as if looking for a party. When a new mouse was introduced into their cage, they greeted the new guy much more eagerly than unmodified mice did.

For people with Williams syndrome, the ability to bond quickly with strangers is part benefit and part handicap, since they typically can’t turn this tendency off, even when they encounter strangers the rest of us would deem a threat. They also struggle with the concept that different types of relationships entail different levels of intimacy. They treat everyone, from the bus driver to their grandmother, with the same intense and unconditional love. This makes them exceptionally vulnerable to being abused or taken advantage of.

Of course, MDMA’s ability to produce instant attachment is part of its appeal for recreational users. The difference is that, unlike in Williams syndrome, its effects wear off in a matter of hours, and the ability to discriminate in whom to befriend returns. But while it lasts, it can be a powerful way to deepen personal bonds and forge new ones. And as researchers are learning, that can be an especially valuable tool in psychotherapy, where trust and openness are the keys to successful treatment for a variety of psychological disorders.

Although MDMA was made illegal in the US in 1985, after gaining a reputation as a party drug, it has reemerged recently in clinical trials for a variety of conditions, particularly post-traumatic stress disorder. Recent studies have shown that people suffering from severe PTSD whose symptoms hadn’t improved with other treatments found significant relief from MDMA in combination with psychotherapy. Late last year, the US Food and Drug Administration gave the green light to phase-three trials for MDMA as a PTSD treatment: the final stage before drug approval, which could happen as early as 2021 if the trials succeed.

Researchers think the drug helps PTSD patients partly because it mimics one of the effects of Williams syndrome: It makes the amygdala less sensitive to threatening facial expressions. Fleeting, unintended expressions of anger or disapproval from a therapist often trigger a strong amygdala reaction in people with PTSD. When patients took MDMA, however, their fearful reactions diminished and they responded more strongly to positive facial expressions—as people with Williams also do. Being able to trust and open up to a therapist seemed to be what made the difference for PTSD patients who’d gotten no relief from previous treatments.

“What MDMA therapy does is it provides a chance for effective psychotherapy, and that allows a patient to come to terms with trauma,” said Ben Sessa, a British psychiatrist who advocates for MDMA as a treatment aid. “Of course, many, if not almost all, psychiatric disorders have some degree of trauma at their core, whether it’s depression, anxiety disorder, OCD, and especially addictions. I think it could be applied a lot more widely than just PTSD.”

Sessa is currently involved with a study to test whether MDMA can help treat people with alcoholism, operating on the principle that trauma underlies addiction. But he believes the drug could also be helpful fo
r the general population.

“At the moment, most of the research is based around clinical tools for people with psychiatric disorders,” he said. “But there’s a school of thought that says that healthy people can use these drugs to explore their own psyche and to gain greater understanding of self and connectivity with others.”

Williams syndrome, with its hallmark gregariousness, is often called the opposite of autism. So it’s perhaps no surprise that researchers also believe MDMA could help people on the autism spectrum overcome their social anxiety. Although treatments for social anxiety already exist for the general population, they rarely work well for people with autism. But people on the autism spectrum who’d taken ecstasy recreationally told researchers that it had helped them connect socially in ways they hadn’t been able to before. Of more than a hundred autistic people surveyed, 72 percent said that recreational ecstasy use made them more comfortable in social settings and 77 percent said the drug made it easier to talk to people, while 78 percent reported “feeling at ease in my own body.”

In 2014, the FDA approved the first-ever trial for MDMA, combined with therapy, for social anxiety in autism. Researchers with the Multidisciplinary Association for Psychedelic Studies (MAPS), which is conducting the trial, presented findings in April suggesting the treatment had yielded significant improvements—and that its effects had lasted long after the sessions ended.

Similarly long-lasting effects were reported by participants in the PTSD study, also sponsored by MAPS, which found that after three psychotherapy sessions in combination with MDMA, 83 percent of participants no longer met the criteria for a PTSD diagnosis. Those effects lasted during follow-up assessments over the course of several years.

“The best thing about this potential treatment, in my view, is the fact that it only needs to be done a few times,” said MAPS spokesman Brad Burge. “Why is that? We’re not addressing symptoms: We’re addressing the underlying root cause of PTSD—the trauma at its core.”

By elevating oxytocin levels, MDMA helps with more than just cementing the patient-therapist bond, Burge said. People under the influence of MDMA are also better able to direct their increased compassion inward.

“Often a hallmark of PTSD is a lot of self-blame,” he said. “People blame themselves for having had this experience or for having had such a difficult reaction to it. One of the goals of psychotherapy is to help relieve some of that guilt, so people can look at what happened to them not as something that happened because they’re a bad person, but because bad things happen to everyone.”

MDMA has its limitations, like all drugs. It’s an amphetamine, so it increases heart rate and blood pressure, although only about as much as vigorous exercise. Still, Burge says, anyone with a history of serious heart, liver, or kidney disease shouldn’t take it. And he warns that while MDMA can be helpful in a clinical setting, taking ecstasy or Molly at a club is dangerous, since the dosage and chemical composition aren’t controlled.

And of course, like Williams syndrome, MDMA makes people vulnerable, which can be good or bad, depending on the situation.

“MDMA has the ability to make you more open and compassionate and trusting. That’s a great idea if you’re dealing with PTSD in a therapeutic setting,” Burge said. “It’s not a great idea if you’re not genuinely in a safe place. You don’t want to trust the wrong people.”