From abstract:

Methods :

In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological, and endocrine effects of 0 mg, 8 mg, and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia.

Results :

SA produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin, and reduced resting electroencephalogram spectral power. The SA administration was associated with a rapid
increase of its levels in the blood. SA did not produce euphoria, cognitive deficits, or changes in vital signs. The effects were transient and not dose-related. SA administration was very well-tolerated without acute or delayed adverse effects.

How wonderful to know that even 12mg vaporised may not lead to serious biological health hazards!

Full paper attached.

Thanks for sharing.

Something doesn't add up here, though. We know that Salvinorin A can bring strong effects in the 1-2 mg range, without considering reverse tolerance.

They say they administered SA using a commercial vaporizer (text refers to Supplement 1, not available here). We know that reports of active vaporized salvia exist, even when the device used is not able to deliver extremely high temperatures, but some of the data in the paper are surprising.

Take for instance the plasma levels of SA and SB after administration. The difference in the measures between the "low dose" (8 mg SA) and "high dose" (12 mg SA) are minimal, with a peak of about 0,9 ng/ml SA in the first and 1,02 ng/ml in the second. The difference between both is not proportional at all to an increase of 50% from the 8 mg to the 12 mg dose.

So either the expression of SA in blood plasma is highly non linear for some strange reason, or there is some saturation level of SA in plasma, or the alleged 8 and 12 mg doses were not actually fully administered due to low effectiveness in the ROA. I personally do not believe they effectively administered 8-12 mg of Salvinorin A reading the subjective reports in the paper.

A somewhat interesting article, but I wonder if someone shifted a decimal point?

8mg of Salvinorin A is a low dose??!! Even 0.8mg is a moderately strong dose.

I once vaporized approx 1mg of Salvinorin A in my GVG, and it was a fairly strong experience – quite beyond some of the subjective comments in the study:



Let me tell you, if I vaporized 12mg of Salvinorin A, I’m not sure what I’d be going through, but I’m absolutely sure I wouldn’t be having a “lot of thoughts about my day”.

These are not statements consistent with 8 or 12mg vaporized doses of Salvinorin A.

Here’s another quote that sheds some light and then obfuscates:



The drug was delivered more slowly – how much more slowly? At what rate was it delivered? I didn’t read the whole paper – is the rate of administration mentioned anywhere? Everyone knows (except these researchers apparently) that a dose of Salvinorin A must be consumed within a fairly short timeframe. This is why plain leaf isn’t effective for many people – the administration is spread out over too long a time period.

Then they go on to say that a dose of12mg Salvinorin A is a dose lower than “characteristic recreational use”?

Something doesn’t add up here.

noone is gunna want to vaporize 12 mg of salvinorin.

Fair observations Vodsel, I'd like to contribute :



Personally, I do not know that. I have vaporised 3-4 mg and could only reach the pulling sensations stage. Never further. To back this up, of an 40x commercial extract that claims to be standardised, I needed more than 1/10th = 100mg of 40x = around 8-10mg Salvinorin.
I think it is completely up to the individual's system what they think "strong" effects are, and the dosage they may need.

Most of all, these claims that we "know" are mostly personal experiences, and I think you would agree that there is a fairly low amount of SA human studies studying CNS effects and biological functions.



I am no molecular biologist, so I have no idea on the linearity of plasma concentrations, the potential saturation in plasma levels, or other factors that would contribute to a non-linear SA expression. However, I would be very wary in believing that the pipe was left with more than 5mg SA and the researchers did not report this. 5mg (even 1mg) are very obvious.



Good point. But keep in mind, not only the study did not focus on qualitative data (they just took some quotes, not the whole conversation, and matched it with some factors like dissociation etc., so they would deliberatly leave the "wow!!" out), but these users were previous salvia users. I would not expect them to crap their pants out of excitement.

Generally, I agree on the weirdness that 12mg might provoke in our judgement, but personally, something was off in all the reports I read on "Don't smoke more than 1mg!! It's terrifying!", and I could never see or feel the reasoning behind it. To me, this reasoning came from Siebert with his first discovery story, and the terrifying aspect might be attributed more to the individual interpretations of salvia experiences.



Gibran, you should not confuse what we in the nexus consider recreational users, and what the scientific world does. For the most part, they consider anecdotal reports of teens and youtube uploaders etc. as the recreational users (unfortunately), and in all fairness, these people claim or show consumption of even 100x. A bowlful of 100x (let's say 100mg), has (allegedly) around 22mg SA. So in their eyes, a 12mg dose of SA is a dose lower than recreational use.

Hell, I don't know.. but at least for now, 3-4mg vaporised SA does nothing for me, so my views are more consistent with the reported findings.

Got hold of the supplementary data sheet :

Thanks for the information!


It’s not clear from your statement if the 3-4mg dose you took was pure Salvinorin A or 3-4mg in an extract. You also didn’t describe your vaporization technique, so It’s hard to say why you got minimal effects with 3-4mg.

As with DMT, many users report taking extremely large doses (100+ mg) and having only minor effects. The discrepancy is usually due to technique, and not drug-response variability. And let’s not forget that the experience reports of those recreational users who load “half a bowl” are just as often horrific as they are uneventful.

Regarding the 40X, there are no laws or regulations regarding manufacturer’s claims regarding Salvinorin A content in extracts. Salvia is often sold as “incense”, so no ingredient claims need to be substantiated. Also, there are no requirements for using any label terms, such as “standardized”. What does “standardized” mean? – Anything, nothing.

The Salvinorin A I used was purified to a high degree (98% Salvinorins: 80% Salvinorin A, 18% Salvinorin B.
See The Salvia Analysis Thread ).

I used my GVG and copper mesh. The dose took slightly longer to vaporize than DMT, but when it did, it vaporized almost instantaneously. The effects were typical of an equivalent amount of 20X extract that I prepared (approx 20mg).

When working with such small quantities, slight changes in technique can have significant effects on the quantity of substance actually inhaled.

Here’s a quote from the paper that sheds some light on their technique:



The supplementary data sheet states:



These two quotes seem to contradict each other:

“Although a vaporizer reaches the target temperature within minutes, the typical recreational
method of delivery (in which subjects apply direct heat to a glass pipe or aluminum foil containing Salvia) attains this temperature instantaneously.”

“Once the target temperature (250-300°C) was reached the subject was instructed to inhale deeply and hold his or her breath for 30 seconds. This was repeated two additional times.”

Many questions are left unanswered. A big one: I don’t know how the “VP 600” vaporizer works, but what was happening to the vapor continuing to be generated while subjects were holding their breath?

Good points!



It is a slightly off white powder from personal extraction, surely not to the purity you describe (80% SA), and it was burnt with a torch lighter in a water bong. So definitely not comparable to vaporised SA. I only mentioned my experience to show exactly your point : the variability is indeed due to method of smoking, substance purity, and technique.



Of course there are no laws, but there is meaning in standardisation, it means that any "bowlful" contains approximately similar quantity of SA as any other bowlful of the same sample (vial, tube, etc). But true, that holds no inferential power to mention that "it was standardised", but as an anecdotal report, I received consistent effects throughout the 40x vial (and many follow-ups from the same company), so I can only guess that it was somewhat standardised.



Agreed. It would be erroneous to assume complete ignorance of that fact on the part of the researchers though. I would like to assume some extent of knowledge on the subject. The measurement techniques they used (from blood analysis to EEG) are pretty expensive, and they must have used quite a large amount of their grant, which only tells me that they strived to be as accurate and technical as possible.



From what I could find out, the particular vaporiser (because of its type of enclosure), will keep the vapor circulating at the temperature input for as long as possible. I think they explained in the supplementary data sheet quite adequately what they meant by "slower". If you inhale one dosage of any amount in one breath, it should be considered "faster" than inhaling the same dosage in 3 breaths. But generally, you're right on the matter that we cannot know for sure how the technique took place, however, that fact alone does not invalidate their findings as far as my opinion is concerned.

10 people did "want" to.
That kinda invalidates your claim

11, including myself. I "want" to.

Another question:

What was their rationale for using such large doses?

It seems to me that a human drug study would have to show that intended doses are safe – where in the literature (other than reports from recreational users) does it show that a vaporized dose of 12mg is safe?

And the method of administration still doesn’t add up. Even if only 20% of the Salvinorin A was vaporized in the first inhalation, that would still be a dose of 2.4mg. From personal experience, after inhaling 2.4mg SA and holding for 30 seconds, there’s no way I’d be able to take a second inhalation, let alone a third.

One thing this study shows is that the “VP 600” vaporizer is a very inefficient device for administering Salvinorin A.


My guess is that if someone were to effectively and efficiently inhale a 12mg dose of pure Salvinorin A, the experience would be more like the “typical” horrific high-dose experience reports that are available online.

I find this very interesting for a few reasons. As we all know salvinorin is active in the micro-gram range, but does anyone know the actual dosage it takes to achieve say a strong effect? For example I can smoke 5-10mg of DMT and its most definitely active. Though 30-50mg(smoked not vaporized) is about where breakthroughs happen.

There's probably nothing wrong with the paper... Maybe just the things people are assuming are taking place aren't?

Gibran why did you grab only that quote from the paper? Sounds like it was clipped from the tail end(probably when they'd be conducting questionaires) or beginning of an experience. This quote sure sounds like a high dose to me, "I felt like I was on a different planet". Obviously all of these statements are tiny little chunks in an experience to highlight what they were looking for. Not full on experience reports focusing on the intensity of the experience...

The VP-600 probably isn't ideal for smoking Salvinorin A but at least it's more controlled then a GVG, or a pipe and a lighter with plant material. Actually some posts on other forums recommend it because it can attain high temperatures. So maybe its not bad for the job after all?

Merk says the boiling temp for salvinorin A is 238-240 C (Ortega) and 242-244 C (Valdes).(Salvinorin A)
Daniel Siebert from "The Salvia Divinorum reaserch and information center" says :-

"Based on my own experiments using an adjustable thermocouple-controlled heat gun, I found that the ideal airstream temperature for vaporizing salvinorin A from dried leaves is approximately 277°C."

Many web-sites claim the VP-600 can attain 298*C.

Also Gibran you've actually measured a dose of Salvinorin A to 2.4mg accuracy? For some reason I supremely doubt that.


Anyways,
I find it interesting that the higher dosages given reported less of an "intensity" effect then the intermediate dosages. I also find it cool how the lower dosages gave a greater concentration of Salvinorin A plasma levels for a longer time then the high dosage. Actually if you look at the blood plasma levels, it sure looks possible to take 3 hits of Salvinorin A in 2-3 minutes. Much like DMT, metabolism isn't instantaneous even if a target compound is smoked. That's the kind of fallacy that gets a lot of freshmen in college passed out on frat house floors before the end of an evening.

Looks from my perspective that this paper has all of it's information straight... Nice paper thanks for posting.

Thank you all for the info and the comments.



Either they wanted to obtain preposterous results (unlikely) or they adopted the dosages that delivered consistent, manageable experiences when assaying off the record with the chosen ROA. My bet would be this. They settle for this vaporizing device, considering the functioning method and the temperatures it can reach, and they try it, starting with lower dosages since they are obviously familiar with the salvia lore. Doses of 1 mg return nothing worth measuring, neither do 2 or 4, so they raise the stakes to 8 and 12.

What I was thinking is... The paper mentions something we have not brought up yet:



Minutes? That sounds more like quidding, or like smoking in insufficient lungfuls for an extended period of time. In both cases, the total dosage of salvinorin ingested during X minutes is certainly larger than the 1-2 mg we know to work when efficiently smoked in one go. The effects, however, can be quite milder when the administration is slow. Consider the variability in dosages quidding fresh leaves. If the difference between subjective effects depended solely on the personal metabolism of the user or synergy with other substances ingested, a double blind assay in monitored subjects, with accurately measured amounts, would return results very highly variable - from slight effects to mind-shattering rides; and this is not the case.

The most relevant data suggested by this paper seems to be, intentionally or not, related to the pharmacokinetics of salvinorin A.



Although it is not clear whether they measured blood or plasma levels (they mention both, and they are different things since we cannot be sure that red blood cells do not sequester SA) I think these "not significant differences" between doses of 8 mg and 12 mg are probably very relevant.

This might be hinting to the fact that intense effects with salvinorin A occur after some sort of flooding.

From Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans (Hooker et al. 2008):



Administering large amounts with a spaced ROA might raise a lot the overall dose needed to reach a "critical mass". Most likely this is what happened here, and it doesn't happen when a sufficient amount of SA is quickly smoked or vaporized in one toke.

Take into account that the inhale-exhale phase is to a degree longer than 40 seconds total for each one, so if they had to do 3 tokes, the total administration duration would be within ~2 mins. Now, how would they pinpoint the onset? They would probably observe something on the subject or derive that from the EEG's channel dampening. I guess that not everyone must show identical effects on the first toke, so by definition, the claim "to minutes" (if they showed onset after 1 min), would be valid.

Excellent points InMotion.

So what do you suggest happened with the dosage? What is your prediction? Less, more, inadequate?

I have no doubts their claim of minutes is valid. My point is, smoking quickly and efficiently 1 mg SA (about 40mg of proper 10x, or 20mg of 20x, etc.) has its onset in less than a minute, already counting with the 20-30 seconds of holding in the smoke. I usually have obtained strong effects in half a minute, having everything in one go. The fact they measured onsets in "minutes" hints for a slow pace of administration, which as far as we know requires substantially larger doses to achieve the same peak, salvinorin breakthrough effect.

So I think the mild effects they registered with such large loads have to do with the long delivery times, and the long delivery times are related to a low efficiency of the ROA, which requires of course a higher dosage to reach the same peak as a shot administration.

True, I see your point. So in other words, that is an even more appealing approach, since the study wanted to measure biological responses. Prolonguing the exposure may not have led to terrifying experiences, but surely covered the aims of the study. Thankfully, it was not a study regarding the psychedelic experience itself, but to form a basis on biological measures on the interaction between humans and SA. I think a recent one was with Macaque monkeys as subjects, so I can only be glad that someone conducted this one.

The study is welcome and interesting, my only warning is everyone else's - beware of correlating 8-12 mg doses of salvinorin A with the effects reported in this paper. The ROA is essential when trying to evaluate the effects of salvinorin, and their ROA seems to be inefficient.

They more or less bring this up themselves. When comparing the study with recreational use, they say



They also suggest the presence of other active compounds in Salvia leaf and bring up the variability in alkaloids concentration in salvia leaf, but we have enough consistent reports of salvinorin extracted, analyzed, ingested and clearly working in the 1 mg range, whether directly vaporized or measured and infused in leaf.

No -- I haven’t measured and vaporized 2.4mg Salvinorin A. But you misread my statement. I have vaporized roughly 1mg of mixed Salvinorins (approx. 80% SA, 18% SB), and based on the rather strong effects of that experience, I quite reasonably stated that “after inhaling 2.4mg SA and holding for 30 seconds, there’s no way I’d be able to take a second inhalation, let alone a third.”

Exactly, they even state clearly in the limitations section that these findings should not be considered generalisable to recreational uses (as with most scientific studies really).

As has already been suggested, my guess is that the rate of administration was significantly slower than us “recreational” users are used to.

On the other hand, if we assume the full dose of 12mg was vaporized and inhaled in 3 inhalations (if it wasn’t, then the amounts reported become rather meaningless), then at least one of those inhalations contained at least 4mg Salvinorin A.

A single inhalation of 4mg of Salvinorin A held for 30 seconds will produce a very intense, possibly strongly dysphoric experience.

I have no idea why the subjective effects were as they were.

Finally, my posts in this thread aren’t meant to criticize the scientific methodology of the study, but to remind people, as Vodsel has already, that a 12mg dose of Salvinorin A, either in pure form or in an extract, when administered in an efficient manner (which isn’t hard to do with extracts), is likely to produce an extremely intense and possibly deeply unpleasant experience.