Greetings All,

I have read various posts on the possible reverse tolerance of salvia, but most are in reference to smoking it. Is there anyone who has experienced the reverse tolerance of salvia using the quidding method? If so, what dosage of quid was used and how often was it taken to cause someone to have reverse tolerance?

I have no direct experience, but the ROA should make too much of a difference. Tolerance is (usually) the result of activity of the active compound at the target receptor. As long as the Salvinorin A is hitting the KOR's, the effect should be the same.

The subjective differences between methods are the result of different pharmacokinetics, not pharmacodynamics.

Blessings
~ND

Thank you Nathanial.Dread for your reply (though I honestly did not fully undestand your answer)



I am not sure I understand what you mean. I get the get the impression that you equate tolerance to be where there is no change in stimulus produced from a active compound at the target receptor. My understanding of tolerance in a pharmacological context is that the neurological response to the stimulus lessen with each use, hence the effect should not be the same but less even though there are active compounds at the target receptor sites. My question is that there are people who state that they have experienced a reverse tolerance effect, that is an increase response/sensitivity to the same amount of active compound. Is that specific to salvia, what did they do, how did it happen to them, and what was their view of the experience?




Sorry, but I do not know what you mean by pharmacokinetics and pharmacodynamics. What are they?

Whether you are utilizing dry(and extract) or fresh leaf material, one is obtaining the same compound.. salvinorin alpha. Alongside other unexplored salvinorins such as B, C, D etc. I have no experience with chewing salvia but this ROA lasts longer and has a different feeling and overall experience than if one were to smoke dry leaf or extract. Either way, it is the same exact compound with similar tolerance effects. Otherwise known as reverse tolerance. This makes salvia unique due to its profound terpenoid-diterpinoid structure. Rendering it a non-alkanoid. Salvia has never been shown to produce toxicity to organs even from very high levels of this compound. So if one were to keep chewing or smoking, the experience will unfold stranger and stronger through each experience. I'd recommend some experimentation.

Let us know how it goes!

Reverse tolerance is definitely a thing (you can wiki it, it's mostly studied in the context of amphetamine and related drugs), although the exact mechanism of action is unclear. I haven't seen any controlled studies related to Salvinorin A reverse tolerance, most of the evidence seems to be anecdotal, which means there are a couple of possibilities.

Tolerance can be the result of many different neurological processes, including increases in enzymes that metabolize the drug, down-regulation of target receptors, depletion of endogenous neurotransmitters associated with the effects of the drug (such as with cocaine), or receptor desensitization (i.e. there is one theory that suggests that opioid tolerance develops because MORs become phosphorylated, which changes the protein conformation, making them less responsive to agonists like heroin).

Presumably some of these mechanisms could work in reverse.


Pharmacokinetics: "The calculus of drugs," it is the rates at which drugs defuse into different compartments, bind to receptors, are metabolized, and excreted.

Pharmacodynamics: The activity of the drug at specific receptors (is it an agonist, antagonist, which receptors does it bind to, how selective is it, etc)

Blessings
~ND

Honestly the reverse tolerance is not something you have to worry about.
After dozens of experiences, smoked and sublingual, I really never could make this clear.
You can dose without freaking out the same dose will be too strong because it won't be anything that dramatic.

Enjoy Salvia quidding !

n_k, Indeed the "reverse tolerance" nature of repeated SD exposures is real. Experience has shown that following an initial smoked extract breakthrough, subsequent exposures to even mild doses of the more subtle quidding or tincture methods can be very impressive. While scary, the initiatory breakthrough reliably obtained with the POTENT smoked extract introduces one to the VERY bizarre "salvia space". Once visited, this space seems to be easily accessed with gentler and WAY more integratable ingestion methods(quid, tincture). With a little respectful practice, in a quiet and safe setting, just a few thoroughly chewed and swallowed SD leaves can allow one "entry". As a relationship is established, and one learns personal sensitivities to different techniques, the Shepherdess becomes an ally who can be coaxed from the matrix with very little substance exposure. Rather unique it seems amongst the plant sacraments. Be safe!

Got a citation for that? I'm not trying to be nasty, I'm genuinely interested: I've spent a lot of time reaching the neurochemistry of salvinorin A (it has interesting implications for the function of the claustrum), and I can't find anything about it's tolerance or it's effects of KOR expression.

Fun fact: Salvia is an effective treatment for colitus.

Blessings
~ND

I definitely seem to have reverse tolerance with it, however I don't have enough experience with quidding to comment. I don't see why it would be any different though.

N.D, Short answer, no. You'll note I put term reverse tolerance in quotations. My sense is that this phenomenon as it relates to salvinorin a, is not a true pharmacologic tolerance(reverse tolerance). It is unlikely that the kappa opioid receptors are up regulated or down regulated. Typical use of SD is sporadic and not anywhere close to the chronicity of exposure to typical opioids(several times daily for weeks/months) that is required for actual receptor populations to be decreased(tolerance) or increased(reverse tolerance). While likely impossible to establish empirically/mechanistically/pharmacologically, the effect of vanishingly small doses of compound(SD) being capable of inducing strong, subjective, psychologic responses in "sensitized" individuals appears to be reproducible in many cases. The fascinating aspect of this reality is that it is not rational, or demonstrable on the biomolecular level. Purely speculative, however, likely related to a persons familiarity with particular profound yet relatively "shallow" trance state induced/entered on exposure to subthreshold doses of SD, AFTER an acquaintance with the deep SD trance has been established, typically by use of the dramatically, disconcertingly potent smoked/vaped extracts. I realize this explanation is not satisfying for the reductionist/materialist students of pharmacology/physiology, including myself(an anesthesiologist of 25 years), but pretty neat for us consciousness explorers. Super dialogue!

N.D, Thanks for the impetus to inquire, claustrum. An anatomic substructure that underlies and interconnects cortical, and subcortical neo-mammalian brain regions(hind/fore, left/right, superficial/deep). Indeed, the claustrum, offers consideration as a material structure(neuro-anatomic) that may assist in explanation of the holistic function of the brain as a "generator" of consciousness. I shan't attempt to refute the "emergent" concept of consciousness. As I age, and become less wedded to socio-cultural descriptions of "self and other", my psychedelic sensibilities inform me, consciousness may well be, in fact, likely is, NON-LOCAL. That said, we might still suggest research that would expose an animal model to doses of SD likely to alter CNS(central nervous system)KOR populations grossly enough to lend themselves to highly sensitive regional brain receptor quantitative analysis. In reality, if receptor population alteration, via exposure to atypical/supra-typical levels of salvinorin- a is a pharmacologic/physiologic phenom, brain KOR quantitative micro assay may/should reveal such. Let's keep looking!

Last year I did a dieta with salvia - I made a cold-pressed tea from a Mazatec recipe and drank that before bed 7 days in a row while I also restricted my diet. I also dieted Nettle root this week - apparently the nettle makes the salvia stronger actually!

Anyways - I cannot tell you measurements, but I did experience my journeys getting stronger even though I could drink a little less tea each day. I made one batch of tea that lasted me all week, so I know the tea was the same strength throughout - I just didnt have to drink as large of a cup. (you dont really drink it - you swish and gargle it, then drink it, so that it can absorb in your mouth and throat still)