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Can Ecstasy be repurposed to catalyze the patient/psychotherapist bond?

Stanford researchers have teased apart the addictive and pro-social effects of MDMA -- suggesting the possibliity of a non-addictive therapy.

The street drug Ecstasy or Molly -- more formally known as 3,4-methylenedioxy-methamphetamine or just by the acronym MDMA -- has a split personality.

Especially popular as a party drug, MDMA gives people who take it a sense of well-being and makes them extremely sociable -- even instilling feelings of unguarded empathy for strangers. That makes MDMA a natural fit for raves, dance parties featuring lots of densely packed, sweaty bodies and unfamiliar faces. It may also may make MDMA a good medicine for psychiatry.

But MDMA harbors some abuse potential -- and some dark and potentially serious side effects.

So a couple of Stanford researchers set out to separate the drug's benefits from its risks. In a study published in Science Translational Medicine, they appear to have succeeded, by conceptually separating the brain pathway responsible for MDMA's therapeutic bond-enhancing properties from the one behind its addictive potential.

Boris Heifets, MD, PhD, is a surgical anesthesiologist whose clinical practice has fueled his interest in the study of drugs that powerfully transform patients' mental state. Rob Malenka, MD, PhD, is a neuroscientist whose research has produced deep insights into the biology of addiction. Heifets and Malenka have teamed up before to advocate the co-optation of banned drugs such as MDMA, ketamine and psilocybin for carefully regulated therapeutic purposes and as scientific probes for investigating the neurophysiological underpinnings of social behavior.

MDMA's abuse potential stems from its capacity to stimulate the brain's reward circuitry. From my news release about the study, where Malenka describes:

The brain's reward circuitry tells us something is good for our survival and propagation... It evolved to tell us food is good when we're hungry, water is good when we're thirsty, and warmth is good when we're cold. For most of us, hanging out with friends is fun, because over the course of our evolution it's promoted our survival.

Addictive drugs trick our brain by triggering the release of a particular chemical from a particular set of neurons in the reward circuitry, as I wrote in a Stanford Medicine magazine article about the neurobiology of addiction several years ago.

In an experiment in mice, Heifets, Malenka and their colleagues proved that MDMA's phenomenal "pro-social" effect operatives through the release of a different chemical from a different set of neurons that feed into the reward circuitry.

MDMA is far less addictive than nicotine, heroin, cocaine or methamphetamine. But in a therapeutic scenario in which millions of people were taking microdoses of it daily to counter the social deficits of depression, autism spectrum disorder or schizophrenia, even a low addictive potential could have public-health consequences.

The new findings show it may be possible to develop drugs that, like MDMA, foster intense feelings of empathy and trust but lack MDMA's abuse potential.

"Some 25 million people in the United States who suffer from PTSD could benefit from a drug capable of establishing, with a single dose in a therapist's office, a trust level that typically takes months or years to achieve," Heifets told me.

MDMA is now in late-stage clinical trials as an adjunct to psychotherapy for post-traumatic stress disorder. In this limited, carefully managed therapeutic setting, Heifets thinks it's safe.

In the mouse study, one experiment testing MDMA's ability to encourage sociability consisted of finding out whether an "explorer" mouse given a relatively low dose of MDMA or, alternatively, a saline solution would rather spend time in a chamber holding another mouse under an upside-down mesh cup (to keep that mouse from moving about), or instead hang out in an otherwise identical chamber with a cup but no mouse. As it turned out, saline-treated explorer mice consistently get bored after 10 minutes with another mouse. But explorer mice given MDMA sustained their social curiosity for at least 30 minutes. 

"Giving MDMA to both mice enhanced the effect even further," Heifets said. "It makes you wonder if maybe the therapist should also be taking MDMA."

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