Salvia's mechanism of action

[BristolRob]

I know it's a Kappa agonist but anyone have any ideas what that actually does...

It's a mystery to me 8(

 

[qwe]

it shreds your soul to pieces

that's its physical mechanism of action!

 

[BristolRob]

My friend is resolute that anything that's legal can't be any good

Seems he's guna be in for a shock

-- anyone any idea about the pharmacological/biochemical/neurophysiological mechanism of action?

 

[Dondante]

What I've gathered is that salvinorin A is a potent kappa opoid receptor agonist. KORs are found on dopaminergic neurons projecting from the ventral tagmental area to GABAergic neurons in the nucleus accumbens. Dopamine release causes transcription of dynorphin. Dynorphin is the body's KOR ligand so I suppose salvia has a somewhat similar effect in this region ... it activates the presynaptic KORs, which decreases dopamine release in the nucleus accumbens ... not really sure what this means, but it is counterintuitive considered salvia is reported to have some antidepressant properties.

So that's probably not the answer you were looking for. Hallucinogen action ... I pretty much have no clue. The KOR is expressed pretty heavily in the prefrontal cortex, so that could be a good candidate for alteration of consciousness, but I'm no expert. It seems somehow cortical glutamate transmission gets out of whack with any mind altering drug, but I'm not sure what the connection is. If anyone knows mouse brains (I don't), then take a look at this:

http://www.ncbi.nlm.nih.gov/entrez/...056,57923,57057,60089,60090,59710,59711,59712

I'm assuming that neurophysiology is probably as meaningless to you as it is to me. It doesn't really explain much. I find systems explanations much more intersting, not to mention understandable. Redgreenvines is the expert on this. Here's an amazing thread (jump down to post #4):

http://www.entheogen.com/forum/showthread.php?t=8187

 

[Dondante]

it shreds your soul to pieces

that's its physical mechanism of action!

I enjoyed reading you recent salvia reports ... reminded me of my first trials with it. Yikes!

 

[BristolRob]

Thanks for that Dondante, it was useful. I didn't know kappa receptors could be found on DA cells. Interesting, the mesolimbic DA system seems to be the tail end of so much. The tryptamines and the dissociatives all seem to end up being linked to DA. The nucleus accumbens seems tgo be a vital relay station, receiving afferents from the prefrontal cortex and limbic regions and sending efferents out to the mesolimbic DA system. I've read an interesting hypothesis that the positive symptoms of schizophrenia can be understood as limbic afferents to the NAC dominating matters relative to PFC afferents.. It's quite a well regarded hypothesis I think. Anthony Grace

I'm assuming that neurophysiology is probably as meaningless to you as it is to me. It doesn't really explain much

On the contrary, I think neurophys is vitally important. Especially the rare data recorded from intracranial electrodes. What is the mind if not the manifestation of electrical energies. Of course neurochemistry is important but at the end of the day, all these different neurotransmitter/receptor effects are influencing these energies - so it is the energies that are primary really

 

[jasoncrest]

Does Buprenorphine, which is a kappa antagonist, block all the effects of Salvia?

 

[Aidan of TCC]

To give a completely unscientific response, it's my belief that the experience of a high-dose salvia trip results from a complete loss of contact with the cognitive framework each of us uses to make sense of the world.

From the day we're born we learn to cope with...existence by categorizing elements of our environment into schemas. When we're hungry, we think, "I need some food", food being a schema into which anything that provides nutrition falls under. If we all didn't have a schema for food, we'd instead think "I'm hungry, I need an apple or some beef or a carrot or some popcorn or toast or.........................." Life would be very overwhelming if we didn't simplify our environment like this.

By about the time we're teenagers, we very rarely encounter something in our environment that a pre-existing schema can't tell us how to handle. We have schemas for everything from the newly-acquired "attractive member of the opposite sex", which tell us how to behave appropriately in social situations, to the very fundemental "animate" and "inanimate" schemas that prevent (most of) us from striking up conversations with furniture.

It's my personal theory, at least, that salvinorin a disassociates us from the ingrained schemas we rely on to interpret our world correctly, casting us back to the level of a newborn still struggling to understand why the ground pulls us towards it or whether or not we're something that is alive.

I hope that makes a little bit of sense.

Does Buprenorphine, which is a kappa antagonist, block all the effects of Salvia?

Yes, KOR antagonists do block the action of salvia, though I've not read anything that used Buprenorphine specifically.

 

[Dondante]

On the contrary, I think neurophys is vitally important.

I wasn't discounting it's importance. Actually I'm very interested in neurophysiology and psychopharmacology. I was just making the observation that since so little known, it is hard to make connections between physical brain activity and the psychedelic mental state. The recent paper on 5-HT2A receptors in Layer V pyrimidal neurons was quite interesting though ... and intuitive, since the huge dendritic trees play a vital gating function for conscious processes. The mesolimbic system is a very primitive system ... can't be responsible for hallucinogenic action, but changes can certainly add a flavor to ones experience.

I hope redgreenvines doesn't mind me quoting him, but I found this thread so interesting that I had to make sure more people read it. It fits in nicely with the idea of a breakdown in schema representation.

... the signals enter the cortex and spread circular fashion similar to waves around raindrops.

interference patterns form to create the basis of engrams of gestalt moments. ( to be associated with similar ones from before )
the engrams are fixed into memory by multiaxxoned cells forming connections with the active signal transducers on exciteation with peak interference events (where waves cross over)

the whole field creates a memory for any moment whether there is an enhanced mental state or not.
this includes bits of touching the floor, some sensing the couch, glances of seeing the couch, seeing the body, fragments of hearing the breath or music, etc. nothing is separated or formed into objects until later.

the moment is experienced as fragments of all things together in a holographic field of waves from incoming signals (and memory activity).

it becomes sustained longer due to the psychedelic, some object recognition begins but it spreads through this hologram as a minor note due to the fullness of the extended resonance of the moment full of partial object presence.

the motion into the couch is like the gravity effect, combine that with the persisting sense of being bits of the whole room at once, and you pretty much have a good model for what is being experienced.

One might ask why we dont feel like that all the time, i.e. part of the totality around us. In reality we do get the same feed of signals from all senses, but, when they are sustained longer (fade mroe slowly) and flood the resonance field of cortex then the little perception waves (memory actions) can be overcome, resulting in less sense of separate objects, less mental completion of shapes and more partial sensed objects become joined where there are gaps in signal as if an open or unified field of undefined mental energy which is our actual resting state subsumes everything that is not yet separated.

again we don't normally see this as we hop from perception to perception and mostly just ignore any but the most specific sensations, and none of it is for extended duration without emotional disturbance, meditation or psychedelic.

The psychedelic state is unlocked from timebase, things are extended and overlapped and space itself is expanded - things stay fresh longer, and are smoothed into eachother like a dream.
The quotidian state is locked down to timebase, things expire quickly, space is confined as experience becomes smoothed into a movie of one thing after another.

It brings to mind the CCritical section that some programmers may be familiar with when working with multi threaded processes.
if one thread needs to share data with another thread (each normally proceeds without waiting for completion of steps by the other) then they need to Lock a critical section before the read or write, and unlock it afterwards.
these critical sections become the turnstyles of the manic potential crowds of computer processes.
Psychedelic states seem to let threads flow without critical sections while quotidian states are marshalled in lock steps, with carefully timed and measured signals. Unlike the garden of eden, all expiring quickly instead of staying fresh and hanging around.

 

[krazycrow]

It unplugs your heart, your soul and 97% of your brain until you are a nothing.

 

[fastandbulbous]

Neurophysiology/neuroanatomy etc tend to make my head hurt if I spend a lot of time on them. Interesting, but I'm happiest with things on a molecular scale!

It seems to be a very unusual effect on cognition from KOR agonists. Pentazocine is something you'd think of should be recognizable to anyone experienced with salvia, but it is quite a different (but just as weird) beast. The only drug thats ever caused me to become lost by just turning around (in my house as well!). More difference that any mu activity could account for

 

[UnfortunateSquid]

I know it's a Kappa agonist but anyone have any ideas what that actually does...

Shouts abuse at kids in trackies until they pummel you into a psychedelic delerium :D

Sorry.