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Alexis Madrigal: Welcome to Forum. I’m Alexis Madrigal. About fifteen years ago at a Holiday Inn by the San Jose airport, I got a glimpse into the future. Back then, there were only a few people advocating for psychedelic medicine to be mainstreamed, and many of them were at that hotel for a convening of the Multidisciplinary Association for Psychedelic Studies.
I got to hear from advocates who claimed that the whole path psychiatry had taken might be wrong — and that MDMA, psilocybin, and other drugs offered a potential new pathway to treat severe depression, PTSD, and other mental health problems that had resisted treatment by conventional means.
At the time, it really did seem on the fringes of mainstream medicine, but within a decade there was a huge Michael Pollan book, tons of new studies and papers, and it seemed as if people in this country would soon have access to these medicines. But here we are, and that hasn’t happened quite yet.
Today, we’ll talk about why — and what could change in this Trump administration.
Joining us, we’ve got Michael Silver, director of UC Berkeley’s Center for the Science of Psychedelics and professor in the School of Optometry and the Department of Neuroscience. Welcome.
Michael Silver: Thank you. Thank you for having us.
Alexis Madrigal: We also have Berra Yazar-Klosinski, founder and CEO of Yazar Lab, former chief scientific officer of Lykos Therapeutics, and former deputy director of the Multidisciplinary Association for Psychedelic Studies. Welcome.
Berra Yazar-Klosinski: Hi.
Alexis Madrigal: We’ve also got Marlena Robbins, an Indigenous public health and policy consultant and doctoral student at UC Berkeley’s School of Public Health. Welcome.
Marlena Robbins: Good morning. Thank you.
Alexis Madrigal: Thanks for joining us.
Michael, let’s just start with some of the basic science — this is what you’re focused on, these biological mechanisms of psychedelics. Do we understand anything about how they work, or do we understand a lot?
Michael Silver: It kind of depends on the level of analysis and understanding. I would say we know quite a bit about the chemical structures of different psychedelic compounds. We know a lot about which receptors in the brain they interact with. We know a lot about where those receptors are expressed in the brain.
But there’s still a huge gap between that level of knowledge and the psychedelic experience.
Alexis Madrigal: The phenomenal experience of it.
Michael Silver: Yeah. That we know almost nothing about. And the field has really been stunted by the lack of psychedelics research for decades, going back to the passage of the Controlled Substances Act. So there’s a lot of catching up to do.
During that time, there’s been incredible advancement in neuroscience tools and other ways of measuring experience and brain correlates — but it’s just been so difficult for researchers to be able to do that work with psychedelics.
Alexis Madrigal: What’s different about psychedelics versus other classes of drugs in terms of what they allow you to study inside the brain?
Michael Silver: Studies have shown that having a psychedelic experience — even in the context of an experimental laboratory — can produce the most profound, meaningful, spiritual experiences of people’s lives, on par with the birth of a child or the death of a parent.
Most drugs don’t do that, and that’s a fascinating neuroscience question. Why should compounds reliably elicit these transcendent states and deep experiences of awe?
And then, of course, their potential as mental health treatments is quite unique as well. They offer a very different model for treating mental health than most of the psychiatric drugs currently used, which are more about symptom management. This is more about psychological insight and possibly permanent — or at least very enduring — change in people’s mental health.
Alexis Madrigal: You’ve also worked on visual systems, so they also allow you to probe those in new ways?
Michael Silver: Yeah. That’s my own area of expertise, and that’s a big focus at our psychedelic center at Berkeley.
To understand how the brain generates visual experience from patterns of light hitting our eyes — that’s a miraculous feat. Having compounds that perturb or change that process in the brain in a way that we do understand at the physical level is a really powerful tool for understanding the relationships between mind, brain, and consciousness.
Alexis Madrigal: Marlena, maybe I’ll come to you next. You’re a doctoral student with Indigenous roots who came into this field. Obviously, these medicines — these plants and compounds — have been used by Indigenous people for a long time. How do you see the intersection of the current field of psychedelic medicine with Indigenous knowledge frameworks?
Marlena Robbins: I see a legacy of biopiracy and bioprospecting — going into Indigenous communities and extracting ceremony, medicine, knowledge systems, stories, songs — and then bringing it back to the market for mass consumption.
They play with the molecules, create new recipes. We’ve seen that with coca, tobacco, and alcohol, and we’re starting to see that with these medicines.
So how do we safeguard them? How do we put power back into sovereign Indigenous nations, where they have a say over how these medicines are utilized and cultivated?
Take mushrooms as an example — when they’re cultivated, who’s cultivating them? Where are they coming from? Why are they being grown? Because these medicines have their own consciousness, and we see them as holy beings who we consult with. They’re the doctors, the counselors, the teachers — and we’re asking them for their help.
Alexis Madrigal: It seems difficult in the current medical environment — I’m thinking about the distance between that and, say, a phase three clinical trial and the FDA. Do you see your role as bridging those things, or is it more of a protective role — to keep out that more clinical view of things?
Marlena Robbins: I think back to Mi’kmaq Elder, the “Two-Eyed Seeing” approach — where we’re seeing science from an Indigenous worldview and from a Western worldview, and those two systems should work in tandem.
Not one overpowering the other, but actively learning from and teaching each other. But that comes from a space of humility.
Alexis Madrigal: Mhmm. Mhmm. Thank you for that. We’ll come back to some of these issues, but for both of you, I want to bring Berra into the conversation.
You’ve been on the treatment side of this — both working with MAPS and with a company trying to bring one of these medicines into the clinic. Give me your sense of where the field is now, relative to a few years ago or even twenty years ago.
Berra Yazar-Klosinski: The field, relative to a couple of years ago, has really started to mature in terms of understanding the value of working in tandem with Indigenous knowledge — and combining that into how we better characterize data from clinical trials.
There’s largely been a rift between those two factions, so I’m very sympathetic to that cause as well.
Twenty years ago, before I started doing this work, it was pretty much impossible to convince universities to take on these types of clinical trials. A big part of what I had to do when I first started at MAPS was help universities understand that this wasn’t some fringe effort — that we were really trying to conduct rigorous research on the potential risks and benefits of these treatments.
Of course, there are all sorts of factors that go into whether a university decides to take on a project, but it was pretty fringe. Over that time, we conducted seventeen different clinical trials at MAPS. Many others have also conducted rigorous trials for a variety of these substances.
Alexis Madrigal: What were you trying to treat, and with what substances?
Berra Yazar-Klosinski: Our flagship program was MDMA in combination with psychotherapy for the treatment of post-traumatic stress disorder, primarily focusing on moderate to severe symptoms. Initially, we started with treatment-resistant participants — most had tried psychotherapy, which is the first-line recommended treatment for PTSD. About a quarter had also tried medications approved for PTSD, which are two SSRIs: Paxil and Zoloft.
Alexis Madrigal: Go ahead, keep going.
Berra Yazar-Klosinski: From our pilot studies — later reproduced in large, multisite phase three clinical trials — we found that about ninety percent of participants had a clinically meaningful reduction in PTSD symptom severity, and about two-thirds no longer met diagnostic criteria.
Those results required three sessions with MDMA and a course of psychotherapy, both during and between dosing visits.
Alexis Madrigal: These seem like really strong results, just from the outside — but the FDA didn’t see it that way, right? They ultimately didn’t approve the treatment.
Berra Yazar-Klosinski: Right. These studies were conducted under a breakthrough therapy designation. MDMA for PTSD has that designation, as do psilocybin — a synthetically produced compound also found in mushrooms — and DMT.
That means the FDA provides extra attention and access for meetings to figure out how best to conduct these studies. There was a lot of collaboration with regulatory agencies, including the FDA, to design these clinical trials.
However, it takes such a long time to conduct clinical development for a new chemical entity — up to twenty years — and these programs aren’t necessarily accelerated in terms of reducing the standard for demonstrating efficacy and safety. The bar is the same.
So it still takes twenty years — but the reality is, these drugs have been studied for over forty.
Alexis Madrigal: They’re in kind of a different place.
Berra Yazar-Klosinski: They’re in a different place in terms of how we understand their safety and efficacy, and some of the reasons—
Alexis Madrigal: Berra, I need to cut in, sorry. We’re going to have to take a break. We’ll come right back to this.
We’ve got Berra Yazar-Klosinski, founder and CEO of Yazar Lab. We’ll be back to talk more about the trials for MDMA — right after this break.
