Ketamine can temporarily produce psychosis-like symptoms

Transcript

Transcribed by machine (Whisper) from the episode’s audio, so a word may be off here and there.

1. 1:30:55

   Tell us about the relationship between ketamine and schizophrenia. Okay. Because I think a lot of people, and maybe you could define schizophrenia, even though most people think about people hearing voices and psychosis, there's a bit more to it that maybe we just, you know, can't bring out. Okay, so one of the things now that we know, see, the problem is that if you look at the endpoint, that doesn't tell you what started the problem.

2. 1:31:19

   It started early in development. You know, schizophrenia is something that appears when, you know, late adolescence, early adulthood, but it actually is already a problem, a genetic problem from the get-go. So what is the concordance in identical twins? Meaning if you have one identical twin, if you have identical twins in the womb and one is destined to be full-blown schizophrenic, what's the probability the other would be?

3. 1:31:46

   So here's the experiment. Okay, this is very, very, it's been replicated many, many times in mice, I should say. Oh, no, actually, okay, let me start with the human. Okay, so ketamine is for a long time, Long time, and it still is a party drug, Special K. I've never taken it, but this is what I hear. I haven't either. It's a dissociative anesthetic, right? But I'll tell you what happens, because I've talked to these people who have done this.

4. 1:32:13

   You take ketamine, sub-anesthetic. By the way, it's an anesthetic. It's given to children. It's a pretty good anesthetic, and it's also used in veterinary medicine. But in any case, you give it to... You take young adults. Here's what they experience. They experience out-of-body experience. You know, they have this wonderful feeling of energy. And they're very, you know, it's a high, but it's a very unusual high.

5. 1:32:44

   Now, you know, if they just go and have one experience, but if they have two, like they party two days in a row, a lot of them come into the emergency room. And here's what the symptoms are. full-blown psychosis, full-blown. We're talking about indistinguishable from a schizophrenic break. So auditory hallucinations. Yeah, auditory hallucinations, paranoia, very, very advanced. You'd say that, my God, this person here has become a schizophrenic.

6. 1:33:22

   And this is really, like you say, the symptoms are the same. However, if you isolate them for a couple days, they'll come back, right? So it means that schizophrenia can induce, I mean, sorry, ketamine can induce a form of schizophrenia, psychosis, temporarily, not permanently, fortunately. Okay, so what does it attack? Okay, and there's another literature on this. It turns out that it binds to a form of receptor, a glutamate receptor called NMDA receptors, which are very important, by the way, for learning and memory.

7. 1:33:56

   But we know the target, and we also know what the acute outcome is, that it reduces the strength of the inhibitory circuit, the interneurons that use inhibitory transmitters. The enzyme that creates the inhibitory transmitter is downregulated. And what does that do? It means that there's more excitation. And what does that mean when there's more excitation? It means that there's more activity in the cortex and there's actually much more vigor and you start becoming crazy, right, if it's too much activity.

8. 1:34:31

   So this is interesting. So this is telling us, I think, that we should be thinking about, and now there's a whole field now in psychiatry that has to do with the glutamate hypothesis for the first, where the actual imbalance first occurs. It's an imbalance between the excitatory inhibitory systems that are in the cortex keep you in balance. And NMDA and methyl deaspartate receptors are glutamate receptors.

9. 1:35:03

   Yes, they are glutamate. They're one class of blood. That's one class. That's right. Okay. So now here is a hypothesis for why ketamine might be good for depression. People are taking it now who are depressed, right? So here you have a drug that causes over-excitation. And here you have a person who is under-excited. depression is associated with lower excitatory activity in some parts of the cortex well if you titrate it you can come back into balance right so you what you do is you fight depression with schizophrenia a touch of schizophrenia now you you know you have to keep giving i think once every three weeks they have to have a you know a new dose of ketamine but it's helped an enormous number of people with very very severe you know clinical depression So as we learn more about the mechanisms underlying some of these...