how dmt works

[endlessness]

We should remember that 'biggest affinity' for a ligand to a receptor does not necessarily equate with maximum actions being exerted through this receptor; an example which is not tryptamine-related but illustrates the principal is the ability of buprenorphine to displace the more potent mu-ligand methadone from the mu receptor but the mu-mediated effects from bupe are less than that of methadone.In this case specifically buprenorphine whilst binding strongly to the mu receptor exerts a partial agonist and partial ANTAGONIST effect.

These bloody receptors we have are fascinating but they are incredibly complex when we consider them in totality; the interplay between them is the crux of the matter.Plus, its not inconceivable that exposure to other agents (via diet, the air etc) can have effects on receptor density which as a consequence muddles it all further.

Yes, fascinating!

When you give this example, are you implying that you think the same happens in the case of psychedelics and 5ht2a ?

It seems most likely that we don't know a whole lot more than we know (undiscovered receptors), and there may be a variety of different mechanisms leading to "psychedelic" effects.

Yes I agree with both of you it seems to me consciousness/brain interaction works in a highly complex and interdependent way where many different variables play a part. But if blocking one specific neuroreceptor site blocks the whole of the psychedelic effects, while this doesnt say all effects are caused in that specific pathway, but at least it tells that 5ht2a is at the very least like a "light switch" which mediates or conditions all other effects with the classic serotoninergic psychedelics, right? And then once it's through, the other pathways and effects can play their unique role everywhere else

 

[corpus callosum]

Endlessness, I dunno what the exact story is with the traditional psychedelics and 5HT2a receptors for sue and I dont think anyone does.My points just highlight that the only thing we do know is that we really dont know!! Neurotransmitters, their receptors and how they can all interact in a variety of ways is what interests me.

I also wonder if the differences between pharma doses required between individuals could reflect such heterogeneity in receptor function and corresponding interactions between the various neurotransmitter systems.

 

[joedirt]

Interesting joedirt! That source would be very nice!

I do remember reading something about other receptors in small amounts but I thought that still the biggest affinity was for 5ht2a receptors, and considering that when taking an antagonist like ketanserin, the psychedelic effects are completely blocked, it has to be the most essential to it, no?

No it doesn't have to be the most essential, but it certainly does implicate it... I just don' believe it's that simple. For one I'd like to see ketanserin run through a assay profile similar to the below paper. It is selective, but how selective? Even if it has the greatest affinity for 5HT2 it could still block compound form say 5HT3 if it's affinity is greater or close to the compound of interest. Also most of this work around 5HT2a was done back in the 70's when not a lot was known about brain chemistry.... We've come along way since then and I'd certainly like to see more recent work, such as the below paper below, before I hang my hat on the single receptor argument. Many of the psyhcs have greater affinities for other receptors...in fact I think all of the ones we talk about do.

Here's the source. Psychedelics and the Human Receptorome

I've got some files on my computer were I generated Excel spreadsheets and graphs that better show the relationship between pyshcs of interest and brain receptors of interest...but all the data is in the original paper, yet kinda hard to to in a direct fashion.

here is an example of the kind of plot I'm talking about , but this only shows psilocin, dmt, and 5-methoxy.... I need to finish flushing out this graph. BTW higher numbers show more affinity. The author came up with a great way or normalizing the numbers...check the paper.

Headed out for the day...I'll try and regenerate these plots later...It's actually been on my mind to have a full post about his anyway! It will make some really good discussions for nexus...


Peace