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.
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.
Sigal Samuel
You’ve become known for researching something called a critical period in the brain. What is that?
Gul Dolen
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.
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.
Sigal Samuel
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?
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?
Gul Dolen
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.
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.
Sigal Samuel
So you basically dosed some octopuses with MDMA, and ... what did you see?
So you basically dosed some octopuses with MDMA, and ... what did you see?
Gul Dolen
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.
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.
Sigal Samuel
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?
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?
Gul Dolen
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.
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.
Sigal Samuel
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?
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?
Gul Dolen
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.
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.
Sigal Samuel
And at first you thought that was because MDMA makes us super social, but that was kind of a red herring, right?
And at first you thought that was because MDMA makes us super social, but that was kind of a red herring, right?
Gul Dolen
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.
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.
Sigal Samuel
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.
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.
Gul Dolen
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.
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.
by Sigal Samuel, Vox | Read more:
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