It sounds too good to be true, but there’s serious science behind the hypothesis.
Sigal Samuel is a senior reporter for Vox’s Future Perfect and co-host of the Future Perfect podcast. She writes primarily about the future of consciousness, tracking advances in artificial intelligence and neuroscience and their staggering ethical implications. Before joining Vox, Sigal was the religion editor at the Atlantic.
If I told you psychedelics might help people with everything from depression to blindness to anorexia to autism to stroke, you might think that’s just pure hype.
Fair enough. The claim does sound hyperbolic.
Yet there’s scientific evidence pointing in that direction.
For the past few years, Johns Hopkins neuroscientist Gul Dolen has been busy experimenting with psychedelics. She’s dosed octopuses with MDMA. She’s given mice LSD. And her groundbreaking research has found that all psychedelics have something special in common: They can hit a “reset” button in the brain, temporarily bringing it back to a childlike state, where the mind is super malleable and good at learning new things.
So she wondered: What can psychedelics do for human brains? Can they help people relearn all sorts of things they’ve lost the ability to do because of a health condition? For example — can they help stroke patients move or walk again, even if the stroke occurred years earlier?
Dolen is now testing just that. If she’s right that psychedelics are the “master key” that can unlock all kinds of healing, they could change life for millions of people — which is why Dolen was recently named one of our Future Perfect 50, Vox’s annual list of trailblazers working on solutions to some of the world’s biggest problems.
I invited Dolen onto The Gray Area to discuss what she learned from octopuses and mice, how she’s currently using psychedelics to try to help humans, and how she thinks psychedelic-assisted therapy will change in the coming years. Below is an excerpt of our conversation, edited for length and clarity.
You’ve become known for researching something called a critical period in the brain. What is that?
A critical period is this window of time where you’re really, really sensitive to the environment around you, and what you learn during that time period kind of becomes locked in for the lifetime. It’s a really strong period of learning and sensitivity to your environment.
I want to talk about your lab’s research on using psychedelics to reopen these critical periods. And I want to start with the octopuses. What was going on in your octopus experiments?
Octopuses are not social. They are actually viciously asocial. Outside of brief periods when they’re mating, they will attack another octopus that’s in the same tank with them. But every other cephalopod that we know of is social. So it occurred to us that maybe they have the neural circuitry for social behavior, but that under normal circumstances, for whatever adaptive evolutionary reason, they’ve suppressed that sociality — and that maybe a drug like MDMA could bring that back.
That was the hypothesis we were testing. And remarkably, that’s exactly what happened.
So you basically dosed some octopuses with MDMA, and … what did you see?
We were measuring how much time they spent in one of three chambers, one a center neutral chamber, another chamber that had a little Star Wars figurine in it, and then the other side had another octopus in it. And before they got the MDMA, they spent all their time with the Star Wars toy, not because it was so interesting but because it was maximally far away from the other octopus.
After MDMA, they basically spent most of their time right up against the flower pot where the other octopus was, and they completely changed their body posture and became relaxed and almost draping all eight arms over the the flower pot that had the other octopus in it. Almost like a hug. We saw them doing a lot of play behavior. One was doing backflips. Another one looked like it was dancing like a ballerina.
But you weren’t satisfied with just the octopus. You also went on to do some experiments with giving psychedelics to mice. And you published a groundbreaking paper about this mouse experiment. Can you tell me what you did there?
What we were measuring was how well the animals are able to learn an association between one type of social condition and one bedding and a different social condition and a different bedding. So it’s like, here’s two new types of bedding that you’ve never been on before. And then we’re going to pair one of them with hanging out with your buddies. And then the other one we’re going to pair with hanging out by yourself.
In juvenile animals, they learn that association really well. They really love hanging out with their friends, and they will spend significantly more time in the bedding that they associate with hanging out with their friends compared to the bedding where they spend time by themselves. But as they get older, they don’t do that anymore. They spend equal amounts of time in both bedding.
So, in your experiment, you gave the mice MDMA and what did you see? How could you tell that a critical period had been reopened?
In the animals that were treated with MDMA, they were able to learn that association just like they were a teenager again. So we returned them to their teenage levels of learning after we gave them the MDMA.
And at first you thought that was because MDMA makes us super social, but that was kind of a red herring, right?
Yes. It turned out when we tried all the other psychedelics we had in our in our pocket, like LSD and ketamine and ibogaine and psilocybin, they all opened this critical period as well — even though they don’t have these pro-social properties. That was our first clue that it wasn’t about the social. It was about the opening of critical periods and that what generalizes across psychedelics is the ability to reopen a critical period.
If we’re right about that, then it might be the case that just by changing the context, we can reopen a different critical period. So if we want to reopen a social critical period, we give a social context. But if we want to change it to, say, a motor critical period or visual critical period, then we give a motor or a visual context.
This seems really related to what’s called, in the psychedelic world, “set and setting”: “set” being your mental state or your intentions and expectations going into a trip, and “setting” being your physical environment.
Looking at your results initially, I might have just thought, oh, the mechanism that makes psychedelics open critical periods is just a neurochemical one — like, presto, it’ll happen automatically [after taking the drug]. But it sounds like the opening of a critical period is maybe just as susceptible to set and setting as the rest of a trip.
Exactly. It’s just like how MDMA-assisted psychotherapy requires psychotherapy as the context to get the cure. It’s not that you’re taking MDMA and just going to a rave and getting cured for PTSD. The context really matters for the therapeutic effects.
This is the way that psychedelics are disrupting all of neuropsychiatric treatment approaches right now, because up until psychedelics came on the scene, the dominant model for how drugs work with the brain was the biochemical one. We had this model for the last 50 years or so that depression is just a biochemical imbalance in serotonin and all we have to do to cure depression is to restore that biochemical imbalance.
But what our results are suggesting is that, no, if you want to cure these neuropsychiatric diseases like PTSD, what you need is the learning model [which focuses on unlearning behaviors built around trauma that are no longer adaptive, and learning more adaptive behaviors]. I really think that the psychedelics are telling us that it’s the learning model that is responsible for these remarkable therapeutic effects that last for years and years after just one, two, three doses.
So rather than the biochemical imbalance model, which essentially medicalizes these people for life — you have to take a pill for as long as your depression symptoms last, and all it’s doing is treating the symptoms — the critical period reopening explanation is saying, no, what we’re doing is restoring the ability to learn, and that is what’s going to give you the durable therapy that’s going to last potentially forever.
Your research also found that, depending on which psychedelic you take, the critical period might stay open for days, weeks, or even a month. if someone might be in this super-malleable state for that long after they come down from the initial trip, should therapists be making more use of that time?
I definitely think so. The clinical trials have been hyper-focused on the trip itself, but we need to be paying more attention to what happens after the trip, because that’s the window of time when learning is happening.
If we’re not, then the best-case scenario is just that we’re not taking that opportunity to maximize learning, but the worst-case scenario is that we put people in this vulnerable, open state and they are going to go back to their traumatic lifestyle, their life that’s full of all kinds of anxieties, and we’re going to do damage while they’re in this in this open state.
We’ve talked about reopening a critical period for social learning. There’s also a critical period for vision, and I know there’s already been research showing that ketamine can enable mice to recover from lazy eye by reopening that critical period.
My understanding is that you were so excited about this that you started a new project called PHATHOM (Psychedelic Healing: Adjunct Therapy Harnessing Opened Malleability) to explore the implications for people dealing with other kinds of stuff, like stroke patients.
The critical period for motor learning, just like other critical periods, closes as you get older. But it reopens for about two months right after you have a stroke, as the brain is trying to adapt to its new situation. Then it closes again. So if you don’t get the right kind of physical therapy within two months after having a stroke, the extra physical therapy isn’t really going to give you much more improvement after that.
I said, look, even for those people whose critical period closed a year ago, I think we can use these drugs to reopen them and then give them physical therapy as the paired adjunct to the psychedelic, and then we’ll be able to restore this ability to learn. So we pulled in the head of the stroke training program at Johns Hopkins, and we are mostly collaborating with him now. And we’re simultaneously raising money. We need about $1 million to do a phase one safety trial to make sure that people who’ve had a stroke are going to tolerate psychedelics well and that they’re not going to have any other medical issues. While we do that phase one trial, we’re hoping to get some preliminary data as well, to give us insight as to whether we’re right that we can get some motor learning if we pair it with psychedelics.
So let’s say I’m a stroke patient and I had my stroke 30 years ago. How hopeful are you that I might be able to regain my movement?
Look, this is a theory, and we could be wrong. The devil is in the details. But I can tell you, 10 years ago people said, “Some of these people with PTSD, they had their trauma 30 years ago, they’re old dogs and you can’t teach them new tricks” — and yet look at where we are right now. I actually think that if we’re right about this critical period explanation, then there’s no reason why we wouldn’t be able to achieve those same victories in stroke patients.