Is a new psychedelic revolution upon us with MDMA?

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The 1960s and 1970s painted a mixed and controversial view of psychedelics, but their truly transformative nature may lie in their potential to heal. New research indicates that MDMA, also known as Ecstasy or Molly, could hold significant therapeutic potential. 

KCRW’s Jonathan Bastian talks with Matthew Johnson, Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University and one of the world’s most published scientists on the human effects of psychedelics. Johnson has spent years researching the extraordinary benefits of MDMA in controlled treatment settings with hundreds of participants.

“MDMA releases a profound amount of serotonin into the synapses, the spaces in between neurons, so that it can affect other neurons. It does that not only with serotonin, but to a degree with other neurotransmitters, [such as] norepinephrine and dopamine,” says Matthew Johnson. Photo Seth Jacobson.

KCRW:Where did MDMA come from? 

Matthew Johnson: “MDMA was first synthesized by Merck in the very early 20th century, so it's not an ancient drug. As far as we know, it doesn't occur in any plants or animals or fungi, but for a synthetic psychedelic-type drug, it's actually one of the oldest ones. It wasn't known to be psychoactive back in 1912. … [So in early tests] they don't see anything they find interesting, and so they'll shelve it. It wasn't until [Alexander] Shulgin was manipulating various structures of psychedelics during his career — he was a chemist that created dozens and dozens of novel psychedelic compounds — [and] someone brought to his attention this older compound, MDMA. He resynthesized it, and as far as we know, this is what brought our attention to the psychoactive properties of MDMA.

He introduced it to a friend who was a psychedelic therapist in California. And this was in the years after the other psychedelics, primarily LSD, had been outlawed. And so these people who a decade earlier had been conducting legal therapy with LSD and seeing incredible results, that work was now illegal. Some of them continued that work underground or illegally. Others quit altogether. 

… These therapists were finding incredible potential for MDMA and used [it] in therapy. And so that's where it took off amongst hundreds of psychotherapists starting in California, but then spread beyond that. And then only a few years later, it became popular in the nightclub scene in Texas. … That's what in the early 80s sort of instigated the recognition of MDMA as more of a drug of abuse or one that's associated with nightlife or partying, particularly a supplement to dancing. The substance was subsequently made illegal by the DEA.”

What is MDMA composed of? And what does it do to the brain? 

“Well, it's different than the classic psychedelics like psilocybin, which is in magic mushrooms, and LSD and DMT and mescaline. Those are all classic psychedelics and they work by activating a certain subtype of serotonin receptor: the serotonin 2A receptor. MDMA is different in that it releases serotonin rather than mimicking the effects of serotonin. ... MDMA releases a profound amount of serotonin into the synapses, the spaces in between neurons, so that it can affect other neurons. It does that not only with serotonin, but to a degree with other neurotransmitters, [such as] norepinephrine and dopamine. And for this reason, its psychoactive properties are somewhat in between that of a classic psychedelic and one of the prototypical psychomotor stimulants like amphetamine or methamphetamine. 

It's actually chemically a derivative of methamphetamine. It's methylenedioxymethamphetamine. Compared to other psychedelics, people will typically describe it as being much more gentle. The propensity for a so-called bad trip is lower. It more reliably leads one to a reaction of emotional openness, without the profound reality-altering effects of other psychedelics. You're less likely to get, for example, the complete dissolution of the self. This feeling of merging into the oneness of the universe.That's more likely to happen with something like LSD or psilocybin. With MDMA, it's more of this very warm emotional tone with increased reported insight into one's own feelings and motivation. And that's the source of the potential psychotherapeutic potential.”

There have been a lot of rumors about this drug for years. I remember hearing that it burns holes in your brain and it can have these really dangerous long-term impacts. Is any of that true?

“So there's a kernel of truth. But the way you just said it about the burning holes in the brain — that is so far beyond removed from the kernel of truth that it's complete hogwash. Interesting story: The whole ‘burning holes in your brain’ really took off from Oprah Winfrey's show, in either the late 80s or early 90s, based on brain imaging. There were so many problems with this research. It resulted in the comparison of individuals who had used a bunch of times, and those who had not, sort of control participants. The results were really just a product of the gain on the monitor. So if you turn the dial to the right [and it messes] with your video settings, like the contrast. The holes where you're not seeing activity are just a complete product of the relative gain of the visualization algorithm. But then there were also just some real problems with the research underlying those images from the first place. 

The kernel of truth is that in animals, such as rats, when you give a very high dose [of MDMA] and give it repeatedly, it's very clear there is damage to the serotonin system: long-term changes that are either very long lasting and possibly permanent. [There is] some evidence that there's some reversal but also a chance for irreversible changes. In humans, there are some changes in terms of serotonin receptor availability and in some subtle cognitive functions. When you compare people who have used street MDMA, which is often not MDMA, but so-called Ecstasy, compare those to normal folks, when people have used hundreds of times, it does look like there are some changes. And that would be consistent with the animal data. 

So it is likely that at a certain dose and certain frequency, there can be some long-term changes to the serotonin system. But a huge caveat here is that we know when using at night where one is going to be sleep deprived, using in a hot environment, using even independent of temperature in a crowded environment, all exacerbate that type of damage. And on top of that ... with a surprisingly high frequency, it's often not MDMA. Oftentimes there's other things in it, such as methamphetamine and other cathinones-based compounds, many of which are also known sometimes with a stronger base of evidence to have the potential to cause neuronal damage.

I don't think there's any scientific support for concern about this type of damage from the therapeutic models that are used when people are receiving [MDMA] two or three times in a therapeutic context.”

Walk me through how MDMA clinical trials have worked. The results appear quite promising.

“This works differently than other psychiatric medications. And the same model is essentially at play with psilocybin, where I've conducted dozens of studies with hundreds of participants. It's basically the same model of so-called psychedelic therapy. You screen people because there's certain contraindications that you can readily screen out, such as severe heart disease or susceptibility to disorders like schizophrenia. After that, people are prepared for the experience. They meet with guides or therapists that will be with them. Eventually, when they do have the drug session, they build a therapeutic relationship. A huge part of this is coming to trust those people to be emotionally vulnerable with them — to really go on this inner journey with them as your shepherds and to trust, let go, and be open with their presence. 

After these preparation meetings, which span a number of hours, one is [then] ready for their session day. [In] recent MDMA work folks have likely read about for PTSD treatment, they've used three sessions. In each of these sessions, a person will come in and they're going to spend the whole day there. They come in early in the morning, and the drug effects are going to last [for an entire] work day. It's gonna start to wear off in the late afternoon. The person lays on a couch or a comfortable-looking bed. The environment is not one that looks like a hospital room or a clinical setting, even if there's a small amount of medical equipment like blood pressure equipment. It’s artfully kind of tucked away to not be prominent. The general vibe is, ‘Hey, this is a comfortable living room.’ 

The person wears eye shades, so masks over their eyes, and they wear headphones. ... Music is played during the experience. This is a pre-selected playlist of music to support the experience. The whole point of laying down and wearing eye shades, [and] listening to the music is to create an inward experience to not really become too focused on the outside environment. It's really thought that you get … the most therapeutic experience when [they] really look at themselves and not at the rest of the world. And so a good amount of the time is spent introspecting. 

Compared to the classic psychedelics like psilocybin, a little more time is spent talking with the therapist through the treatment. So when trauma comes up, and it reliably does so when you have that context to treat PTSD, the trauma will come up and the person will talk about it with the therapist. ... They encourage the person to explore. They're not there to judge or provide any easy explanations. They're here to support that person. If the person has any anxiety, they can address it by reassuring them that they're in a safe environment, and they're not going to leave them alone, and that they're going to stay with them. And then eventually, the drug wears off. 

There's discussion about the experience following the drug administration day, and the person really processes these things. It's very consistent with our best, most advanced scientific understanding of trauma, and really just the general way that memory itself works. The idea that you access these traumatic memories — you pull them out of long-term memory and now you're experiencing them. You're thinking about them. You're contemplating them in a vastly different context. The drug has some really amazing changes where for example, it tamps down the fight or flight response of the amygdala. There's an oxytocin response that might have some role in the effects that increase those feelings of safety and bonding with the therapist. The signature of the drug effect is one that sort of creates a very different valence and people often say that they have a much richer understanding of their own emotion in and of themselves. 

So often with trauma, someone will look at it through new lenses and have an essence of self-love to pervade those memories of ‘Oh my gosh, I survived this and I didn't ask for this. This wasn't my fault.’ And to have compassion for themselves for having gone through that self blame, and the panic and the hatred towards the world that can pervade these experiences. [It’s all] radically changed and that can be so profoundly moving to people. Those memories last and we know that's consistent with the way memory works. … When they store those memories, the memories themselves change. This kind of hair trigger emotional panic reaction that normally was tied one to one with those memories is no longer there. Those feelings of self love and understanding and this broader context are now what's tied to the experience. They're not forgetting that traumatic experience, but when they do think of it, now it has this completely different emotional tone. So in short, they learn from this experience, they radically re-process. They learn to have a completely different cognitive and emotional reaction to these memories.”




Andrea Brody