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“We have to design treatments that are fully biological, psychological, and sociological at their core. Psychedelics represent that, and psychiatry has started to take notice.”

In this episode of the Mindspace podcast, Dr. Joe speaks with Dr. Kyle Greenway. Dr. Greenway is a senior resident in psychiatry at McGill University. He runs a clinic in Montreal where he and his team treats patients using ketamine-assisted psychotherapy.

His work centres around the intersection of biology, psychology, and sociology for the treatment of his patients. And he has a deep understanding of why psychedelics are so effective in the treatment of many mental illnesses.

Dr. Greenway and Dr. Joe spoke about:

  • How psychedelics differ from other psychiatric treatments and why they appear to be so effective
  • The role of psychotherapy in psychedelic treatments
  • The potential mechanisms in the therapeutic actions of psychedelic treatments
  • The importance of integration therapy after a psychedelic experience
  • How ketamine-assisted psychotherapy actually works

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Here are some highlights from their conversation:

What do we know right now about the neurobiological and psychological mechanisms of psychedelics? Why are these drugs so effective? What are you betting on in terms of the best theories here?

My favourite theory and this is something I’ll call state-dependent learning.

Even in rats or mice, if you set them loose in a maze, you get their performance. You do it again with them being administered anything ranging from a barbiturate to cannabis to cocaine, you’re going to see differences in performances. When you do it again with them in a sober state, you’ll see that they have learned a lot less from their non-sober learning experience.

For example, if they did it on a barbiturate, then you do it again without a barbiturate in the system, you find out–a reasonable explanation of what’s going on is, ‘okay. They really just didn’t learn as much.’

The fascinating thing is if you re-administer that barbiturate, in fact, they actually regain a lot of the performance you thought they lost. So those memories were not just faultily encoded. They were encoded in the context of what was going on in the brain. In that case, a drug, but the same thing is true of your environment.

So if you study in a very particular environment, for example, with a particular smell, then you go to do a test, and you don’t have access to that smell, you’re going to have less access to those memories that were formed with that particular environment. This is called state-dependent learning. And this is a phenomenon we see all over neuroscience and psychology.

I would say one reason that antidepressants work, again, is because they change that state. So they kind of lessen all of the learnings that you have about who you are, who the world is, how you should react, how you should feel. All of that stuff is kind of lessened.

With a psychedelic, we’re talking about a radically different state. So you have a completely disorganized access to your current environment and your past memories. Things are not so orderly as, ‘Okay. This state is associated with that feeling, that memory, whatever.’

So what we see in the brain–there are many ways of describing it, and you mentioned a couple. The Entropic Brain Hypothesis is essentially describing that the brain has a lot less order to it. Entropy being kind of the lack of order. So when there’s less order, information is not being channelled along its old circuits. Your brain is not clearly saying, ‘Okay. This belongs in the auditory cortex. This belongs in the visual cortex.’ Information kind of bleeds through the different pathways. And this is one way you get hallucinations. If auditory information is kind of channeled into the visual cortex, suddenly you get a little bit of synesthesia, as if you’re seeing sound.

If you do neuroimaging, you find that indeed there are connections being made between networks to a much greater extent than normally would be the case. That definitely involves more entropy in the brain. You can measure that in a variety of ways.

Either the cause of that or a co-artifact of that is that this default mode network is disrupted. The default mode network is the way your brain organizes itself habitually. Maybe the closest thing we have in the brain as a correlate to the ego, your sense of self, who you are, etcetera. So whether it’s a disruption of the default mode network, the orchestrator of the brain–whether it’s a disruption of that that produces this greater entropy or it’s the reverse or they’re kind of parallel processes is not so clear.

But the psychedelic state is absolutely characterized by novel pathways being formed in your brain where information is travelling in different ways. And that kind of ties into the idea that this creates space for growth. You’re not just stuck in the same sort of rut, new things can happen to a much greater extent.