Now I'm sure you're thinking... "wtf? CITE!". Well, here you go:









I think Ram Dass would approve.

Caveats:

1. Rat studies
2. Kappa agonist other than salvia

Cue "Lipan Conjuring" by Tool.

If my little theory is at all valid, you gotta wonder what other drugs the South American shaman had that could have therapeutic applications today.

So I started wondering what would naturally raise kappa opioid ligand levels, not that I would want to stop anyone from being a psychonaut!









Ok, I'm too tired to go any further with this tonight, but I think this might lead to some nice prejudiced statement about modern American lifestyles being bad in even more ways.

imo, tying this together... (and I could be horribly wrong)

Novelty / reward / overstimulation / palatable food / euphoria all raise dynorphin levels, in an attempt by the body to regulate addiction and the pursuit of hedonism. This manifests in a reduction of pre- and postsynaptic dopamine D2 receptors in the straitum and nAC, as does treatment of ADHD with methylphenidate. Perhaps it represents the neurological correlate of the temporary nature of hedonism.

And this is why obese people have the seemingly contradictory fact of low numbers of D2 receptors. They have been downregulated by constant hyperphagia and hedonism from food, resulting in dynorphin increases leading to D2 receptor decreases. But this is not effect to completely blunt the gluttony-- and the global increase of the "self-stimulation" bar makes them seek the most rewarding, the most hedonistic things quite ironically as neuroplastic changes here have blunted the normal response to things.

In ADHD, the problem is too many D2 receptors; the excess of DATs here from genetic mutations (and whatever else) removes the DA and prevents any significant reward or hedonism from occurring in the first place. So, by the use of euphoric stimulants (which in turn increase dynorphin levels), or Strattera, whose main metabolite directly agonizes the kappa receptors as dynorphin does, result in normalization of the striatal D2 receptor densities. But, the base problem-- which led to an overpopulation of D2 receptors-- has to be corrected, or this neuroplasticity will reversed in time.

Exercise and food restriction, as shown in the above studies, decrease dynorphin levels and thus effectively lower the self-stimulation threshold... sensitizing and increasing D2 receptor densities.

The chronic treatment of kappa opioid agonists such as salvia divinorum results in not only the acute D2 reduction during treatment (which is a transient effect), but also a tolerance to the exogenous agnoist and endogenous dynorphin. As a result, the removal of reinforcement from self-stimulating behaviors results in less dynorphin getting released in the first place, and the baseline levels having less of an effect on suppressing the D2 receptors. Thus, neuroplastic "rebound" results in an unregulation of D2 receptors.

This allows the hyperphagic rat to obtain normal stimulation from regular food, resetting the threshold. But if they start eating that palpable food once again, the cycle will repeat. The same thing applies to libido- it "resets" the sensitivity to erotic stimuli.

This allows the reduction of impulsivity in ADHD by diminishing the maximum amount that things are novel by. This makes selection of non-novel things more likely. But, the person must still find a way to get reward and satisfaction from them.

So, I think that maybe, just maybe, kOR agonists can give people a chance to reset and correct poor behavioral choices and the pursuit of hedonism, reward, and materialism more quickly than behavioral changes alone, wherein they would have to force themselves to do something that does not at all appeal to them (and quit doing the shit that does appeal to them) for quite a while for this system to naturally rebalance itself. But even after the reset button is pushed, the opportunity to do it right is also the opportunity to fuck things up all over again, to start the cycle of suffering anew, and not learn from the last.

Maybe my theory is wrong, but I like it, dammit.

"Constant over stimulation numbs me
and I wouldn't have it any other way.

It's not enough, I need more.
Nothing seems to satisfy.
I don't want it, I just need it.
To feel, to breathe, to know I'm alive.
...
Something kinda sad about
the way that things have come to be.
Desensitized to everything.
What became of subtlety?

How can it mean anything to me
If I really don't feel anything at all?"
-Tool, "Stinkfist"

Frangi, I really like your way of thinking.

So to sum this theory up - when we use dopaminergics or better yet are just plain hedonistic our body reduces or increases the number of d2 receptors to deal with the higher levels? Or does that even matter?

Something about your theory speaks to me personally and I want to try and get some kind of reset on my dopamine system, even if it's minor. I tried some salvia last night, smoked it, 5x extract. First time ever, went easy on it. Still, even though I took it slow, my whole brain turned inside out. The whole room swirled into, well, swirlies. I didn't go too deep but I didnt just graze the surface either. About ten minutes later I was just a little fuzzy headed. After that I wanted to crash out. I woke up this morning and feel somewhat less phuzzy than I usually do - a little glow about me. I dont want to take that as proof though, it could easily be expectations.

I will be trying salvia a few more nights just to see what may come of it. I will be trying to cut my dose even lower. I just don't enjoy having the room spinning like that. Perhaps I should not smoke it but put some in my cheek??

The reason I'm really interested, frangible, in this theory of yours is that time and time again I hear about people having an afterglow from using salvia, sometimes lasting a few days. Then you mentioned this d2 receptor deal and I think it makes perfect sense actually.

That afterglow lasted a few days with me as well, but I didn't just touch the surface when I used salvia (the 10x, a long while back now). Something about my reality being torn to shreds really changed my perspective on things...temporarily.

I think part of that perspective also has to do with the d2 receptor changes.

But yeah, it's crazy go nuts shit. I've just never had a real high tolerance for hallucinogens. My unconscious mind has for some reason decided that they are dangerous, so I get really uncomfortable with the whole experience. My ego must be interfering...

Makes sense...



Many are uncomfortable with it. I wouldn't say it was the most pleasant experience for me either though.

To me, Salvia 20x just felt like NO "laughing gas"... as I tried it, I laughed my ass off for about 30 secs, then for the next 2 mins weird body sensations (sensation of gravity fucked up), but that was all. But as I remind myself, on LSD, I laughed my ass off for HOURS... Salvia, thus, being a 30sec LSD-like experience. I didn't feel any after-glow on salvia, probably because of the whole bunch of cannabis smoked afterwards.

I know Inositol has some effects on d2 receptor.

But is an increase in striatal d2 receptor density what we looking for (to relieve ADD)?

Finally the inositol d2 study surfaces (I was looking for that).

But YEAH-what he asked, is dopamine receptor density something we want to increase? Doesn't the body make more dopamine receptors when it feels it's being overstimulated or is it the other way around?

According to the studies I posted above, too many straital D2 receptors are linked to ADHD, and stimulant treatment decreases them. My interpretation of that is other problems with ADHD (too little dopamine, too many DATs, poor executive and goal completion behavior, etc) lead to upregulation/sensitization of them from lack of use, and that increasing their numbers may correspond with aggravated hyperactivity/impulsivity symptoms..

Good question.

Consider that an overactive PAM (prefrontal-amygdala-medial dorsal thalamic) circuit is related to depression symptoms.
The PAM circuit is inhibited by the ASPM (amygdala-striatal-pallidal-medial dorsal thalamic) circuit. An underactive ASPM disinhibits PAM, which is not fun. You need a balance of DA, 5HT, glutaminergic receptors to keep these circuits operating normally.

Also, overactivity of the prefrontal cortex and the caudate nucleus loop is related to OCD and attentional disregulation. Attention and distractibility are modulated by orbital cortex, striatum and thalamic centers. To oversimplify, dopamine is inhibitory.

Dopaminergic inputs to the striatum can inhibit it. Since the striatum inhibits thalamic output, excess dopaminergic activity in the striatal circuits disinhibit the thalamus, which then allows too much information to flood the cortex. This is one theory of schizophrenia.
(Abarbanel's classic paper -- see figure 5c)
To sum up: heck, I don't know.

I dont think I know either.

Click to view attachment

Whoa. Bottom-line this for me willya? So how do I orgasm faster?

so is the original question too simplified?

If I do too much coke all the time what does my brain do to counteract the overstimulation of dopaminergic pathways? Does it hide receptors or does it make new ones to try and keep a balance?

Let's say hypothetically that I've done too much ritalin over the past few years and my dopamine system is fried. Would increasing dopamine receptor density help or harm the problem? Would taking salvia, which blocks dopamine receptors, which would in turn let dopamine receptors go back to normal to try and fix the low dopamine, help at all?

Use Salvia for 3-4 days in a row, perhaps. At least the data looks fairly promising for rat studies there! So if you catch yourself mounting a female rat, it worked. (if nothing else, salvia in low doses is a pretty potent libido stimulant)



Too much DA -> Dynorphin -> Kappa receptor agonism -> D2 receptor population decrease
Too little DA -> Less dynorphin baseline -> D2 receptor upregulation / sensitization** (yeah, the data's pretty shaky on that one But we know diet/exercise do this, and hedonism does the opposite...)



Human studies have shown that kappa opioid agonists decrease stimulant craving and lessen withdrawal. This has been reported many times with salvia anecdotally, and I can confirm this through personal experience.

Free full text: http://www.aapsj.org/view.asp?art=aapsj070361

It is indeed very complex, and the location of the D2 receptor and whether it's pre- or postsynaptic controls its function, which is of course in the larger context of that particular circuit or region in the brain.

Which begs the question, "So isn't talking about D2 receptors globally oversimplifying things?" Well, you can blame the kappa opioid system for that one-- it has global effects and hits both pre- and postsynaptic receptors.

This is awesome stuff, and a good read there on the page about stimulant abuse and salvinorin. Frangible I want to make a little clone of you and keep him in my pocket for when I need to learn something else.


I must admit that over a period of a few years now I've had off and on access to a number of stimulants(mostly ritalin). I haven't gone on binges that lasted several days or anything like you see in meth addicts but I can definitely tell my adventures with ritalin have left me rather anhedonic lately and I've been wondering if there might be something I can do about it. Going out and socializing feels like work lately and even going out to get smashed makes me feel only ill, instead of euphoric and jolly as it used to be.

I was a bit frightened last night with taking too much salvia so I only took one hit. I felt the whole trip start to happen but then it left too quickly. Tonight I will suck it up and go further and report on the mood shifts...

I have also slightly abused stimulants in my youth (well I'm still young but anyway... a few years ago). Dirty speed pills with whatever they put in it (mostly methamphetamine) and ecstasy. It probably did damage and still have some impact. I'm now on dexedrine thought (sometimes methylphenidate), for my ADD, but I try the best to keep the dose the lowest and the least often.

For me going out and socializing isn't very hard since I have the same friends since a few years, and cannabis is very friendly!!

But I wish I could "regenerate" my probably damaged dopaminergic system. Seroquel seems promising for this, but unavailability and possible risks (type II diabetes...) makes me away from it. On the other side, salvia is readily avalaible, cheap, and has very little risks!

Would it be better to take oral salvia much like a supplement or smoke extracts? Many ppl eat salvia instead of smoking to allow less intense longer trips. Has anyone tried it?

I found a really neat recipe to make blotter paper out of salvia leaf. You can use the stuff orally but it takes a lot and it takes a bit of chewing(unless you use a tincture or blotter paper). I will look into getting some leaf myself to try out...

I have this funny feeling that says the longer you can extend the experience the longer the afterglow will work.

There are quite a few people who use this stuff purely for it's antidepressant activity it seems after googling for a while...

I would think the "afterglow" would help with burnout / anhedonia etc. As far as oral forms, I've only used the oral tincture (alcohol-based; I lose at attempting to smoke things) but it really, really fucking burns. Not pleasant (well, at least until the salvia kicks in). OTOH, at least you don't have the risk of falling into ego death and dropping something burning onto something flammable.

Personally I'd love to see salvorin A in a transdermal carrier.

I don't know if inhalation vs. oral would have more therapeutic potential. I think from the duration of the "afterglow" described, it doesn't seem so much related to the length of effects, so at least part of it is independent.

Oh, and I once did use salvia as an antidepressant-- I was really emo'ing out. A pretty massive dose reversed the depressive state, with about zero other effects.

Strattera/atomoxetine might be another option-- apparently its major metabolite is a kappa agonist. (I used it for a month, it basically made me narcoleptic)

I didn't like statera. I thought it was cool the first time I took it, like a super charged cup of coffee, but then it just fell flat...

Here's the instructions on how to make blotter paper which sound like just about the best way to take salvia.

http://www.totse.com/en/drugs/psychedelics...lott170441.html

Hmm, interesting if it works... I dunno if it'd be absorbed well enough without the alcohol in the mouth.

I'll let you know, as I'm always down with trying something like this. I may prerinse with mouthwash like some do.

I've used salvia sublingual before, which works very well (also not as chaotic), but you must go with the regular leaves...not the extracts. And use a ton of it

Another random kappa opioid factoid:

I just took a (low) dose. After perceiving the effects with and without meditating, my impression is that salvia sort of turns up the volume in terms of perceptible effects on things that are always there, but difficult to perceive because of the amount of other crap going on in our brains. I still think if I was better at meditation and took the drug enough times, I could get to the point where I could recreate the effects it has by will alone, just in noticing how it consistently shifts my perception and feeling of consciousness in the same direction, to the same point, every time.

humans are being bombarded CONSTANTLY by all outside energy, and our brains do a fantastic job at filtering what we receive into something we can relate to, removing all the weird shit. Psychedelics decrease some of the filtering

I'm ordering some right away!!

where can i buy bulk salvia?

I have finally gotten to the point where I can handle the salvia trip and I have to say the afterglow is the best. Four or five days of being completely in a state of contentment. It's quite nice.

One of the things that's helped a lot is to have something very pleasing to listen to whilst diving. If you don't it seems like any external noise turns into a living being that distracts and sometimes even brings me down. Also, the internal dialogue can take off and interupt the experience. A good 10-15 minutes of ambient music really does the trick to pull you into a blissful and meditative state.

I've smoked some 20x extract a few weeks ago and never touched again. I think I could try a smaller dose. I also have some 20x "tincture". I wonder what would be a good dose to not get the full "ego-death"...

Was the dose one, or several? And oral or smoked? And, (last question) can you be more specific about what the "massive dose" was?

Yeah since for me, a single puff of 20x extract got me into full-blown "ego-death"... Really freaky... But amazing... (I could easily write a whole book describing this 5 minute experience)

What is weird is that when coming back to reality you feel extremely confused and really baaaaad (absolute dysphoria). Once reality becomes clearer the dysphoria dissapears and a feeling of "afterglow", incredible antidepressant effect, takes place.

No kidding.. I figured the 20x was going to be strong so I took a real light hit (water pipe). I was in another world for 5 minutes. And when I got back, I didn't know who's house I was in.

for about a week after no less. I feel great and troubles seem to mean so little.

The great part is that it's not because it's artificially raising levels of stuff that will crash after it's over. It's reseting things which feels much more productive in the long run.

Music is essential to the experience. Any external noise like fans I found have a haunting effect on the trip.

I found any sensory stimulation (light, music, etc.) to be disturbing while into the trip. Anything making me go back to reality was really disturbing (like re-learning everything from the beginning but way too fast).

Anyway I won't go into details since as I said, I could easily write a book about my single experience with it.

I like some music, but one time I took a huge rip of 20x extract from a water bong while a Chili Peppers song was playing. Then fucking Linkin' Park started their shit on my radio, and I swear that snapped me back to reality just long enough to change to another station.

I go\et really, really happy after hitting Salvia and am very resolute and focused. It is my favorite psychedelic by far. I don't mind the ego death really...

Bump for more experiences and Darksanitys new book I would like to read more about your experience actually.

I'm sure it would be a bit more enlightening than the reports from totse. I just found this site...It's quite funny in a way, their forum was down so I couldn't go further. Here were a few front pages things I found.

http://www.totse.com/en/drugs/otc/badtripoffbena.html - Complex issues addressed complete with references!

http://www.totse.com/en/drugs/otc/.html - Apparently we have been using it the wrong way!

http://www.totse.com/en/drugs/otc/.html - Love the saying "baked out of my gourd"

http://www.totse.com/en/drugs/otc/dontmakethesam.html

"i looked through my house for a bottle of robotussin i had found on 2/3 empty it didnt really work so a few times later i tried taking whole bottles of the shit. it was a pretty good high i later found out it was the oppisite of speed it slows down your system.after i knew alot about it and tried it a couple times i decided to go 'robotrippin' with a friend we bought 2 bottle of dm robotussin i drank a bottle and a half and he drank about half a bottle. wow i felt good until my brother came home and saw my friend was acting strange he was usually very outgoing but now his system had slowed down a little so my friend told my brother what had happened and he took matters into his own hands and told my mom. then my mom was furious she offered us this stuff to through up i didnt take it but my friend did which made him feel horrible. i couldnt find a drug that worked for me yet so far my brother had ruined dxm whic i liked the search was on i even tried taking 6 benadryls in school once which led to delirium. then it hit me wtf was i wasting all my time on OTC (over the counter drugs) so i tried the obvious solution WEED"

Tkardde, can we organise an M&M article from one of these writers please

What type of music would you recommend? During my last experience, a ticking clock had an effect on my trip. It set the beat for some chanting, rhythmic "song" that all the little oompa-loompa like people were marching to. Crazy stuff.

Comptine D'Un Autre: L'Apres Midid -Yann Tiersen ('Amelie' sound track)

http://www.youtube.com/watch?v=4Z2ljWwIaHs

Don't mind the silly video...

I remember reading somewhere chronic salvia use makes you suicidal... Ill have to look up a refrence.

searching government sites or sites with the word "parent" would probably be the best way to find that...

http://www.albinoblacksheep.com/flash/flashback

I think this could be similar to a salvia trip, although I've never been that deep personally. It reminds me of dxm trips Ive had though

Hey guys,
I was really surprised to run across this thread. I registered on this forum years ago and was doing reading on salvia for specifically the same reasons as mentioned on this thread.
I found myself reading through it and going... "Wow. People like me. People who love to learn, and love science."

Kudos and all that.

My experience with salvia has been the same as much on here... Overall I find I enjoy smoking the LEAVES the best (it's more mild and less scary... less overwhelming) which can be bought pretty affordably off of ebay. It's a good clearheaded buzz but tends to be anti-addictive... which means you have to really activate that masochisitic bodybuilding hit-the-iron mechanism to reap the benefits of it.... but the afterbuzz is very pleasant.

And where have you been the past 4 years Mr?

"It's a good clearheaded buzz but tends to be anti-addictive... which means you have to really activate that masochisitic bodybuilding hit-the-iron mechanism to reap the benefits of it"

What do you mean?

Hahah... Me and my five posts have you beat on the registration date by two months. ;-)

Basically, I used to be really into bodybuilding. I kept lifting up but slacked, lost my passion for it, and god knows didn't feel like chatting online about it... I never knew about this forum before though, and neuroscience is my current passion. (Actually I've recently been getting hardcore back into lifting -- but mostly because of the effects it has on the brain.)

In other words, kappa opioid agonists are literally used to treat coke addiction. It reduces dopamine levels in a certain addiction-related area of the brain and because of this tends to make you not want to smoke it again. That's the reason for salvia's initial dysphoria (pre-the afterglow).

Yeah, I'd probably be using this stuff a lot more often to reset my mind. After about six small experiments I've gotten to the point where the trip just kinda sucks and the discomfort that follows is a drag. I might hit it up again soon but for now I might look into getting the leaves and chewing them or something so that it's not as "hit over the head" strong.

I smoke salvia a few times back in H.S., probably around 2001. I definitely noticed the messed up gravity effects. I was like a 5 minute (at the most) weird and weak acid trip. Overall, I liked it but didn't care to use it all the time. It was just an experimental thing. I always like acid but hated shrooms with a passion! lol



I will probably be starting focalin here within a week.

Do you think salvia would be good to use every other day to help off-set the long-term negative dopaminergic effects from long-term methylphenidate use?

I also have an addicting personality but only want to use the medication as prescribed so I can actually finish my degree. Would the salvia help me not to want to crush up a pill and snort it like I did with ritalin years back?

I don't think Salvia would change anything about that but... Have you ever wondered about taking Concerta?

Yeah, I think so, if one "reason" you want to do that is boredom/anergic depression. Taking the ritalin as prescribed will help to not do that too.

Also note that the evidence with inositol & ADHD are mixed or negative. So maybe depression and ADHD have different conditions here, or it could depend on the subtypes of these. But inositol could have multiple mechanisms.

Its also worth noting that reverse tolerance is commonly noted with salvia (for psychedelic effects).

can we say, to simplify, that mu signal = DO THIS AGAIN
and the kappa signal = get rid of the eurphoric aspects, without affecting the reinforcement/desire part (ie, it says 'this activity is good, and its expected/status quo from now on)

from the cocaine addiction studies, it seems like pretreatment with KOR agonists 'unmakes' the reward path that was created by following the euphoria.

and thus has antidepressant effects by encouraging the smoker to find new reward paths instead of the stunted ones exhibited in ahedonia?

Some possibly relevant studies i can't figure out how to relate.



(DA is higher in the NA during depression)



There are theories of depression that it is a chronic state of pain, thus the reduced sensitivity to normal pains in the depressed.

This indicates KOR has feedback from vassopressin & oxytocin release. - interesting especially since the effect of extremely high dose salvia is no memory of the trip, and large doses have trips that are hard to remember. Oxytocin could be related to the 'heat' sensation many people experience after taking a hit of salvia, although i don't know how oxytocin affects temperature regualtion, just that it is involved somehow. I wonder if there is a rebound effect?



Also, if comparing dynorphin activity to KOR activity, keep in mind dynorphins have other effects, whereas i think salvinorin A is highly selective for the KOR.




plus reference to "dynorphin A" as DA confuse me to no end.

I'm still trying to see if there is some connection between the relationship between KOR and novelty, and the psychedelic effects of salvia.

Also interesting strattera is used for ADHD, but was ineffective for depression.