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MDMA Therapy for Loneliness? Researchers Say It Could Work

Marta Zaraska

Some call the drug "ecstasy" or "molly." Researchers are calling it a potential tool to help treat loneliness.

As public health experts sound the alarm on a rising loneliness epidemic in the United States and across the globe, early research is finding that MDMA could increase social connectedness and reduce defensiveness in some people — effects that some say could, in combination with therapy, help combat loneliness. 

In the latest study, MDMA "led to a robust increase in feelings of connection" among people socializing in a controlled setting. Participants were dosed with either MDMA or a placebo and asked to chat with a stranger. Afterward, those who took MDMA said their companion was more responsive and attentive, and that they had plenty in common. The drug also "increased participants' ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful." 

The study was small — just 18 participants — but its results "have implications for MDMA-assisted therapy," the authors wrote. "This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration." 

MDMA "really does seem to make people want to interact more with other people," says Harriet de Wit, PhD, a neuropharmacologist at the University of Chicago and one of the study's authors. The results echo those of earlier research using psychedelics like LSD or psilocybin. 

It's important to note that any intervention involving MDMA or psychedelics would be a drug-assisted therapy — that is, used in conjunction with the appropriate therapy and in a therapeutic setting. MDMA-assisted therapy has already drawn popular and scientific attention, as it recently cleared clinical trials for treating posttraumatic stress disorder (PTSD) and may be nearing approval by the US Food and Drug Administration (FDA). 

According to Friederike Holze, PhD, psychopharmacologist at the University of Basel, in Switzerland, "there could be a place" for MDMA and psychedelics in treating chronic loneliness, but only under professional supervision. 

There would have to be clear guidelines too, says Joshua Woolley, MD, PhD, a psychiatrist at the University of California, San Francisco. 

MDMA and psychedelics "induce this plastic state, a state where people can change. They feel open, they feel like things are possible," Woolley says. Then, with therapy, "you can help them change."

Loneliness Can Impact Our Health

On top of the mental health ramifications, the physiologic effects of loneliness could have grave consequences over time. In observational studies, loneliness has been linked to higher risks for cancer and heart disease, and shorter lifespan. One third of Americans over 45 say they are chronically lonely. 

Chronic loneliness changes how we think and behave, research shows. It makes us fear contact with others and see them in a more negative light, as more threatening and less trustworthy. Lonely people prefer to stand farther apart from strangers and avoid touch

This is where MDMA-assisted therapies could potentially help, by easing these defensive tendencies, according to Woolley.

MDMA, Psychedelics, and Social Behavior

MDMA, or 3,4-methylenedioxymethamphetamine, is a hybrid between a stimulant and a psychedelic. In de Wit's earlier experiments, volunteers given MDMA engaged more in communal activities, chatting, and playing games. They used more positive words during social encounters than those who had received a placebo. And after MDMA, people felt less rejected if they were slighted in Cyberball — a virtual ball-tossing game commonly used to measure the effects of social exclusion.

MDMA has been shown to reduce people's response to other's negative emotions, diminishing activation of the amygdala (the brain's fear center) while looking at pictures of angry faces

This could be helpful. "If you perceive a person's natural expression as being a little bit angry, if that disappears, then you might be more inclined to interact," de Wit says. 

However, there may be downsides, too. If a drug makes people more trusting and willing to connect, they could be taken advantage of. This is why, Woolley says, "psychedelics have been used in cults." 

MDMA may also make the experience of touch more pleasant. In a series of experiments in 2019, researchers gently stroked volunteers' arms with a goat-hair brush, mimicking the comforting gestures one may receive from a loved one. At the same time, the scientists monitored the volunteers' facial muscles. People on MDMA perceived gentle touch as more pleasant than those on placebo, and their smile muscles activated more.

MDMA and psychedelics boost social behaviors in animals, too — suggesting that their effects on relationships have a biological basis. Rats on MDMA are more likely to lie next to each other, and mice become more resilient to social stress. Even octopuses become more outgoing after a dose of MDMA, choosing to spend more time with other octopuses instead of a new toy. Classic psychedelics show similar effects — LSD, for example, makes mice more social. 

Psychedelics can induce a sense of a "dissolution of the self-other boundary," Woolley says. People who take them often say it's "helped them feel more connected to themselves and other people." LSD, first synthesized in 1938, may help increase empathy in some people. 

Psilocybin, a compound found in over 200 species of mushrooms and used for centuries in Mesoamerican rituals, also seems to boost empathy, with effects persisting for at least seven days. In Cyberball, the online ball-throwing game, people who took psilocybin felt less socially rejected, an outcome reflected in their brain activation patterns in one study — the areas responsible for social-pain processing appeared to dim after a dose. 

Making It Legal and Putting It to Use

In 2020, Oregon became the first state to establish a regulatory framework for psilocybin for therapeutic use, and Colorado followed suit in 2022. Such therapeutic applications of psilocybin could help fight loneliness as well, Woolley believes, because a "common symptom of depression is that people feel socially withdrawn and lack motivation," he says. As mentioned above, MDMA-assisted therapy is also nearing FDA approval for PTSD. 

What remain unclear are the exact mechanisms at play. 

"MDMA releases oxytocin, and it does that through serotonin receptors," de Wit says. Serotonin activates 5-HT1A receptors in the hypothalamus, releasing oxytocin into the bloodstream. In de Wit's recent experiments, the more people felt connected after taking MDMA, the more oxytocin was found circulating in their bodies. (Another drug, methamphetamine, also upped the levels of oxytocin but did not increase feelings of connectedness.) 

"It's likely that both something in the serotonin system independent of oxytocin, and oxytocin itself, contribute," de Wit says. Dopamine, a neurotransmitter responsible for motivation, appears to increase as well. 

The empathy-boosting effects of LSD also seem to be at least partly driven by oxytocin, experiments published in 2021 revealed. Studies in mice, meanwhile, suggest that glutamate, a chemical messenger in the brain, may be behind some of LSD's prosocial effects. 

Scientists are fairly certain which receptors these drugs bind to and which neurotransmitters they affect. "How that gets translated into these higher-order things like empathy and feeling connected to the world, we don't totally understand," Woolley says.

Challenges and the Future

Although MDMA and psychedelics are largely considered safe when taken in a legal, medically controlled setting, there is reason to be cautious.

"They have relatively low impact on the body, like heart rate increase or blood pressure increase. But they might leave some disturbing psychological effects," says Holze. Scientists routinely screen experiment volunteers for their risk for psychiatric disorders. 

Although risk for addiction is low with both MDMA and psychedelics, there is always some risk for misuse. MDMA "can produce feelings of well-being, and then people might use it repeatedly," de Wit says. "That doesn't seem to be a problem for really a lot of people, but it could easily happen." 

Still, possibilities remain for MDMA in the fight against loneliness. 

"[People] feel open, they feel like things are possible, they feel like they're unstuck," Woolley says. "You can harness that in psychotherapy."

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