So what did you come to out of out of these various models, these various tests, the results that you got?

Like what kind of conclusions were you able to you know, at least tentatively, draw with respect to the effects of providing these like, you know, chronic low doses of of psilocybin to rats.

It's it's actually interesting because one of the first clinical studies that were done in maybe we'll call it the new era of psychedelic research, right?

It was back in 2008 by a guy called Moreno and they actually did a psilocybinic clinical trial in a small subset of humans with obsessive compulsive disorder And they gave them also very low doses, and they saw an immediate effect on the compulsive actions that they had.

So what we are thinking that these microdoses could do is that they could increase the resilience to stress in animals and lower the urge to do compulsions.

This kind of um it echoes there's a a comedian performer named Adam Strauss.

I've uh I've had him on the show.

And he uh is somebody who has diagnosed uh OCD and explicitly has sort of part of one of his comedy routines, but a part of his sort of advocacy for psychedelics has been to speak to how his experience working with psilocybin seems to have sort of played a um a positive contribution in his life with respect to managing his O C D As yeah, I had tried to get his uh watch his show so many times, but it's just it seems impossible from Denmark to get to see it.

But uh yes I read about him and it uh we also have anecdotal case reports here from Denmark, uh where people have But have uh used small doses of psilocybin to to help with their obsessive compulsive disorder.

And there's also published uh cases of of this uh uh in single people uh like case studies where they also have reported uh using small low low doses for obsessive compulsive disorder.

So there is A little bit of evidence coming up, but we don't have any clinical trial that supports this yet.

Uh it could be placebo, it could be whatever, but there's a like a faint um grasp of uh of hope that it it may work So you you you might have you might have just explained this.

Um so uh you know you I might be asking you to repeat yourself based on a different angle of approach.

But in your paper you write um The present results substantiate many anecdotal and self-reported claims from psychedelic microdosing in recent years.

These results may indicate a therapeutic potential of repeated low doses of psilocybin in cases where approach and avoidance motivations are in conflict.

Can you explain what approach and mo uh avoidance motivations are and what they look like when they're in conflict?

Um that is uh also based on on the findings that we found in the brain uh of these animals so maybe if we just go back to the results where we we have actually so the one thing about rats that you can't do in humans is that you can take out the brain and we can analyze it afterwards and we can see is there's something going on in the brain of these rats.

And we could actually measure in an in a region of the brain called the thalamus, we could measure increased synaptic plasticity and we had uh more um Exonal terminals uh in in this region.

And this region is also involved in what we call approach and avoidance behavior.

Can you we just take a pause there for a second?

Yes.

You said uh exonal term terminals.

You just said can you just explain that a little bit in maybe more like layman's terms?

Do you mean as in like just like more axons?

Like as in like more synaptic density or something?

Yes.

So all the the brain is full of neurons that have uh that are connected to each other with and they have uh one connection going out that is called an axon.

So we have one connection that is going out that's called an axon.

And if you have more In the end of this exon, there's actually it spreads out and it gets into these what is called synaptic connections.

And the neuron is then connected to another neuron by touching these synaptic connections with each other.

And when we see more of these, we see more of these synaptic connections, which is also called synaptic plasticity.

If you follow the psychedelic literature, you will see that there is a talk about increasing synapsic plasticity.

And that is what we see in the thalamus of these rats.

Okay.

Well and you were about to explain how the this synaptic plasticity and this region of the brain are related to this approach and avoidance motivations being in conflict, and then explain a little bit more about.

what that means.

Yeah, so a approach and avoidance really means that y if you are a smoker or drinker, for example, you will want to have your cigarette or your drink.

But you also know that it's bad for you.

So you have this pull towards something that you want, but also a push away.

So this is the approach and then you have the avoidance is a push away that I know it's bad for me.

I I shouldn't do it.

And but you still want it.

Or the the cake at four o'clock in in the office, right?

You you really want it, but you also know maybe you shouldn't eat it.

Um so that is a an approach and avoidance behavior.

And in compulsive disorder or obsessive compulsive disorder, most of the people that have obsessive compulsive disorder knows that It's not good to act on my obsessions because with this compulsion I have, because it's going to be a repetitive pattern.

And even though I get I get relief from doing the repetitive or compulsive actions.

I get relief on the on the anxiety.

It's also a reinforcement.

So if I do it and I get relief, I will want to do it again and get relief.

And that is how we believe that these compulsions are actually starting.

So that is also an approach and avoidance conflict.

Yeah, that I want to do my repetitions, but I also know that it's bad for my for my continuing OCD to do them.

And now does that does that have to be an OCD or or do we see these same behaviors in people that You know, I I mean anyone can have a compulsion.

You mentioned picking up the phone.

For most of us, picking up the phone is a compulsion, right?

But we don't have O C No, and that so the approach avoidance behavior is seen in many uh cases, like in smokers or uh binge eaters uh or just regular people who have uh some kind of uh compulsion that uh that you have an urge to do.

Um And without having obsessive compulsive disorder, of course.

And so and in this area of the brain, you said the uh para-something thalamus?

It's called a paraventricular thalamic nucleus, but uh it's part of the what is called the thalamus.

Uh yes.

You have to pardon my uh lack lack of specificity, lack of lack of neuroscience background.

Um Now and and so it's associated with sort of this sort of area of the brain, and then w did you did some tests or s uh observations of the rats that you gave psilocybin?

Like what was the w what was your the relationship to speaking about this area of the brain and your research specifically with the rats.

Like, did you study psilocybin's effect on this area of the brain to draw conclusions with behavior?

Yeah, no, we actually we didn't look at the whole brain.

That's the first thing to say.

So there could be many areas where this is happening, but we the reason we looked at the paraventricular phalamic nucleus is that it's very rich in another receptor type that's called a serotonin-7 receptor.

And there is 14 different receptors of the serotonin class.

And you have the 5 HT or the serotonin-2 receptor, which is primarily responsible for the psychedelic actions, but then you also have the serotonin one and seven receptors that look alike.

And we looked at the the serotonin 2A and 2C receptor, they are called, and then we looked at the serotonin-1A receptor and the serotonin-7 receptors.

And one when we looked in the areas of the other receptors, we didn't really see anything.

But when we looked in the region where we have a lot of serotonin-7 receptors, we saw this uh upregulated synaptic plasticity, so more synapses in this region.

And so and and so you're like from that drawing the conclusion of like, oh, so psilocybin on the on uh there we might be seeing a biological basis for these behaviors with respect to approach and avoidance motivations being in conflict.

Yes, that that is the conclusion.

I think so, especially because we have a very low dose of a drug, we have a non-psychedelic dose of a drug uh of of psilocybin and we're seeing changes in in the behaviors that match the changes we see in the brain, uh at least on a On a regional level we we know that this brain area is involved in these compulsive actions and approach avoidance actions So we're we're trying to link the two and we but we need more studies to actually conclude that they are connected and that this is what we see.

So we are we are working on more studies uh at the moment to try and try and figure this out.

What is the effect on compulsive actions and approach avoidance?

Okay, thank you so much for tuning into this micro.

What you just heard was a clip from microdosing psilocybin effects on stress resiliency and compulsive behaviors with Dr.

Michael Pallner, episode 194.

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