Salvia as antidepressant

[Dondante]

So it seems there is some evidence that salvia may have this property. I'm looking for others that have experienced antidepressant effects. I'm also trying to figure out how salvia does this, and why the hell its hallucinogenic.

What I've gathered is that salvinorin A is a potent KOR agonist. KORs are found on dopaminergic neurons projecting from the ventral tagmental area to GABAergic neurons in the nucleus accumbens. Dopamine release activates G-alpha S resulting in cAMP production, subsequent CREB activation, which causes transcription of dynorphin. Dynorphin is the body's KOR ligand so I suppose salvia has a similar effect ... it activates the presynaptic KORs, which decreases dopamine release in the nucleus accumbens.

So the short term effect of salvia is decreased dopamine release. If salvia has antidepressant effects, it must be through modulation of the mesolimbic reward pathway discussed above. So my guess is that salvinorin A causes downregulation of the KOR, which results in increased dopamine transmission in the nucleus accumbens, and a lasting decreased response to dynorphin. For this too happen, though, wouldn't salvia have to cause tolerance? Another option would be that salvia's immediate effect has more lasting inhibitory effects on CREB activation and dynorphin transcription. Maybe lower levels of dynorphin persist after the short, but significant drop in dopamine transmission.

Also, I'm curious how this pathway relates to salvia's intense hallucinogenic action. "... GABAergic medium spiny neurons of the NAc shell receive a significant glutamatergic input from the PFC, amygdala, and hippocampus. Kappa-receptors are present on the presynaptic terminals of presumed excitatory synapses as well as on the dendrites of the medium spiny neurons." So it could be through modulation of glutamatergic transmission in the PFC if I read that right, but I assume it must be very different from the effect of serotonergic psychedelics.

http://jn.physiology.org/cgi/reprint/85/3/1153

Anyway, I found a few examples of salvia as an antidepressant, but I'm interested to hear more. Does it work better with the quid method instead? How long does the relief last? Thanks for any input.

Most psychedelics make me feel a refreshed appreciation for life. Salvia, however, seems to be extremely anti-depressant for me. Even smoking very small amounts (far below breakthrough) seems to lift a great weight off my shoulders. If I am out of pot and really aching for a toke, a bowl of salvia--plain leaf even--can make that all melt away!

There's a link on Erowid to a paper by an Aussie psychiatrist detailing a woman who experienced antidepressant effects from low dose salvia. What's even more noteworthy is that the woman hadn't responded to any of the normal antidepressants. I found that low sublingual doses had an antidepressant effects that were noticable from the very first dose.

No doubt somebody, somewhere will be looking at kappa agonists as potentially novel drugs for depression (they'd have to minimize the trippy feelings for clinical use though!)

 

[Smyth]

Kappa antagonists are being looked at in the context of treating depression:

"Stress causes a cyclic AMP-responsive-element (CRE)-binding protein (CREB)-mediated induction of the opioid peptide dynorphin in the nucleus accumbens. Dynorphin induction in this region causes certain depression-like behaviors (for example anhedonia). Accordingly, administration of κ receptor antagonists, which block dynorphin action, either systematically or into the nucleus accumbens, has been shown to decrease depression-like behaviors in rodents"

Reference Located Here.

 

[Dondante]

Antagonists make much more sense, but somehow there are still people that report depression relief from salvia as well.

 

[rainz3d]

Salvia produces a very nice 3-day anti-depressent quality for me, as well as many others. some people have taken advantage of this and used sub-hallucinogenic doses daily or tri-daily for the AD effects, which are obviously apparent using recreational doses also. I can't help but half-heartedly attribute this effect to 'salvia's mystical healing powers'.

 

[toxide]

Salvia would be a good antidepressant once the experience is over and you realize yer not goingto die and the god awful pain it produces is over and you realize life isn't as painful as a salvia experience, other than that I think salvia is as far from antidepressant as a drug can get

 

[nuke]

Salvia chills me the fuck out, after the really confusing part.

 

[Dondante]

I've never really noticed any antidepressant effect, but the fact that it is reported makes me wonder. I've never been terribly depressed either, but with something like ketamine, I can feel a "mood lift" that lasts a few days. I can't guarantee it's not placebo, but it seems real enough. The whole idea of salvia being an antidepressant seems counterintuitive considering its action.

 

[Aidan of TCC]

You've brought up a question that's been fascinating me for some time now. To sum it up in one brief sentence, KOR agonists AND DOR antagonists both show significant anti-depressant properties. Salvinorin a is likely to be the jumping off point for a whole new class of anti-psychotics and anti-depressants in the next decade or two. Right now the chemical framework of salvinorin a is just in the infancy of its exploration, and from what I've read, the potential derivitive psychoactives with potential pharmaceutical value are extensive.

If you want to read more, I've got a whole collection of recent journal articles on the topic that I've got hosted somewhere and can dig up.

 

[fastandbulbous]

Something about salvia use is weirdly mood stabilizing rasther than mood elevating; it's more like it might also reduce manic behaviour afterwards. Totally different to the antidepressant effect after AMT which is noticably mood elevationg for anything up to a week after use

 

[Aidan of TCC]

Something about salvia use is weirdly mood stabilizing rasther than mood elevating; it's more like it might also reduce manic behaviour afterwards. Totally different to the antidepressant effect after AMT which is noticably mood elevationg for anything up to a week after use

You might find the paper titled "Salvinorin a: From Natural Product to Human Therapuetic" of interest, I found it on my webspace here: http://www.unc.edu/~dlinz/KappaDeltaOpioidPapers/

 

[aanallein]

Salvia single handedly cured me of chronic life threatening depression which had been a problem for me for over 4 years.

Its been 5 years since that experience and I still haven't fallen back to where I was before. It was literally like somebody flipped a switch in my brain. No other way to describe the complete transformation I went through in under a minute.

 

[Dondante]

You might find the paper titled "Salvinorin a: From Natural Product to Human Therapuetic" of interest, I found it on my webspace here: http://www.unc.edu/~dlinz/KappaDeltaOpioidPapers/

I thought you'd be familiar with Roth. Yeah, I've read that paper ... it very interesting, but doesn't really say much for why salvia would have antidepressant properties. It talks about antinocioceptive effects and diarreah relief, but that's about it. I don't think anyone is going to want salvinorin A for pain relief.

There is considerable evidence supporting a role for the
KOR:dynorphinergic signaling complex in the regulation of mood
disorders (9, 38, 39). Indeed, KOR agonists induce depressivelike
behaviors in animal models, whereas KOR antagonists have
antidepressant-like effects in vivo (40).

Salvia is an agonist ... which is the reason for my confusion.

 

[Aidan of TCC]

I thought you'd be familiar with Roth. Yeah, I've read that paper ... it very interesting, but doesn't really say much for why salvia would have antidepressant properties. It talks about antinocioceptive effects and diarreah relief, but that's about it. I don't think anyone is going to want salvinorin A for pain relief.



Salvia is an agonist ... which is the reason for my confusion.

I wonder if it doesn't have some secondary delta agonist action?

I can't say I fully understand the opiate receptors, they're incredibly complex. There's all sorts of weird kappa/delta interactions that I doubt anyone has a firm grasp on the true workings of.

P.S. DonDante, I just registered today so I can't reply to private messages I"m afraid.

 

[Aidan of TCC]

I thought you'd be familiar with Roth. Yeah, I've read that paper ... it very interesting, but doesn't really say much for why salvia would have antidepressant properties. It talks about antinocioceptive effects and diarreah relief, but that's about it. I don't think anyone is going to want salvinorin A for pain relief.

Salvia is an agonist ... which is the reason for my confusion.

Well for some reason I still can't reply to the pms, there must be a timer as well as a post count restriction. If you want to get in touch, and if you're on facebook, look in the local groups for psychopharmacology anonymous. There's only 3 members at the moment. Otherwise I believe my aim is in my profile.

 

[Dondante]

I wonder if it doesn't have some secondary delta agonist action?

It has absolutely no affinity (Ki >5,000 nM) for any receptors except kappa-opioid. Ki for kappa is ~ 5 nM... it an incredibly selective ligand.

And I think I might be on Facebook, but I don't know how to use it. My girlfriend put me on there a few years ago, but I've never tried to access it. I'll see if I can figure it out.

 

[Doktah]

I know this is a dead thread, but I felt this was worth adding to it for those who come across it...

It seems that Kappa Antagonists work as anti-depressants by constantly antagonising the KOR... With Salvia, it is an agonist, but it only acts as such for a short period of time...

Theoretically, both approaches should have similar effect; by constantly antagonizing the KOR, you are decreasing activity at those receptors, whereas by periodically agonizing the KOR, you're likely down-regulating (albeit to a slight degree) the KOR, which would also decrease net activity.

Both have advantages and disadvantages:

- With the salvia approach, you must first agonize the KOR before you get therapeutic effects... you are more likely to experience some negative effects while the KOR is activated (which doesn't last too long anyway), but in essence, the therapeutic effect is essentially a withdrawal effect from the main effects of the drug.
- With constant antagonism, you would likely experience greater therapeutic effect (and more consistent), but it is also likely that you'll upregulate the KOR, and you've likely to experience a sort of withdrawal effect consisting of increased KOR activity for a period of time dependent on the half-life of the drug. This would probably be an unpleasent experience. *This would only become apparent obviously after you stop taking the drug*

This is purely my own theory, but I would expect to see results fall inline with this reasoning. I have been very interested in JDTic (fully selective permanent Kappa antagonist) as of late, I would be very worried about possible rebound effects following cessation of the drug. For this reason, I am thinking that a dose of salvia (or other Kappa agonist) before bed would likely be superior in terms of mitigating negative side effects while still garnering decent therapeutic effects.

 

[dingophone]

I know this is a dead thread, but I felt this was worth adding to it for those who come across it...

It seems that Kappa Antagonists work as anti-depressants by constantly antagonising the KOR... With Salvia, it is an agonist, but it only acts as such for a short period of time...

Theoretically, both approaches should have similar effect; by constantly antagonizing the KOR, you are decreasing activity at those receptors, whereas by periodically agonizing the KOR, you're likely down-regulating (albeit to a slight degree) the KOR, which would also decrease net activity.

Both have advantages and disadvantages:

- With the salvia approach, you must first agonize the KOR before you get therapeutic effects... you are more likely to experience some negative effects while the KOR is activated (which doesn't last too long anyway), but in essence, the therapeutic effect is essentially a withdrawal effect from the main effects of the drug.
- With constant antagonism, you would likely experience greater therapeutic effect (and more consistent), but it is also likely that you'll upregulate the KOR, and you've likely to experience a sort of withdrawal effect consisting of increased KOR activity for a period of time dependent on the half-life of the drug. This would probably be an unpleasent experience. *This would only become apparent obviously after you stop taking the drug*

This is purely my own theory, but I would expect to see results fall inline with this reasoning. I have been very interested in JDTic (fully selective permanent Kappa antagonist) as of late, I would be very worried about possible rebound effects following cessation of the drug. For this reason, I am thinking that a dose of salvia (or other Kappa agonist) before bed would likely be superior in terms of mitigating negative side effects while still garnering decent therapeutic effects.

I've theorized this as well, yeah a full K agonist like salvinorin A would likely cause a good bit of downregulation, which would create an antidepressant effect. I think one of the reasons it's thought that buprenorphine works well for depression is that it's known to be a Kappa agonist as well as a Mu agonist. JDTic does seem really interesting, but I can't find much on human use of it.

 

[Fortheloveofnod]

For me, Salvia unlocked a severe psychological depression

 

[flat-line]

I could see Salvia giving people a "I am alive" after glow, if you can get past the confusion of it all.

I think Salvia has a lot of potential as a modified compound, as salvinorin A is alone it is just such a bizarre confusing experience.