Abstract (as presented by the authors of the scientific work):
"Salvia divinorum is a hallucinogen sold over the internet in several forms. Perhaps the most common method of use is smoking the dried leaf material. The sole presumed active constituent, salvinorin A, is a selective kappa-opioid receptor agonist. Upon smoking of the dried leaf material, some of the salvinorin A is destroyed or converted to other materials, leaving in question the actual amount of salvinorin A delivered that leads to the psychotomimetic effect. On average, 133 μg of salvinorin A was delivered in the smoke from an 830 mg per cigarette, which contained ∼2.7 mg of salvinorin A. Hence, only ∼5% of the salvinorin A available in the dried plant material was delivered in the smoke. Upon smoking, hydrolysis of salvinorin A to salvinorin B, an inactive and minor component of the leaf material, also occurs as evidenced by a higher delivered amount of salvinorin B vs salvinorin A (217 vs 133 μg per cigarette). Since smoking is an effective means of achieving the hallucinogenic effect and salvinorin A is the presumed sole active ingredient in the plant, the estimated effective dose of salvinorin A by inhalation is <133 μg per person. Considering the reported rapid metabolism of salvinorin A in vivo, the dose reaching the brain would be substantially less."
Results and discussion (as presented by the authors of the scientific work):
"The average values of chemical analytes found in the smoke of a tobacco and an S. divinorum cigarette are listed in Table I. Excluding the psychoactive constituents of the respective plants, most of the analytes were found in similar amounts in the two plants. The S. divinorum plant material used in this study demonstrated some variation even within the small sampling of the leaf material used for the smoking studies. The three samples analyzed for 2.20 ± 0.30, 3.82 ± 0.65 and 3.69 ± 0.04 mg salvinorin A per gram of plant material (n = 4 for each determination). The grand average of these determinations is 3.24 mg salvinorin A per gram of plant material or 0.324% of the dried plant material, which is near the average 0.245% salvinorin A content reported by Siebert (3). An 830 mg cigarette would then have ∼2.7 mg salvinorin A present. In the smoke, 133 μg of salvinorin A was delivered (∼5% yield) indicating significant conversion of salvinorin A to other components during combustion. Some evidence for this was seen by the presence of 217 μg of salvinorin B, which is a non-psychoactive hydrolysis product of salvinorin A. Additionally, the presence of small amounts (18 μg) of related salvinorin D or E was detected as indicated by their MW. Since salvinorins D and E can interconvert, the observed material is likely a mixture of D & E (9). Additionally, salvinorins D and E are partial hydrolysis products of salvinorin C, which is present in the plant (3); therefore, the salvinorin D or E observed here are likely combinations of amounts present in the plant and products of the combustion process in a manner comparable to the conversion of salvinorin B from salvinorin A.Considering that smoking S. divinorum as a cigarette is an effective method of achieving a psychoactive effect and salvinorin A is considered to be the sole active ingredient in the plant accounting for the effects (1), then the 133 μg of salvinorin A represents a high estimate of the minimal dosage needed to obtain a psychoactive effect from the drug. The actual amount of salvinorin A that needs to reach the brain would be significantly less due to the rapid metabolism of salvinorin A in vivo (10).
These results are in good agreement to the findings of the vaporization studies of Johnson et al. (4), where they determined that 210–420 μg using a vaporizer as the minimally effective dose in a 70 kg. It should be noted that this was the dose applied to the vaporizer and that the amount actually delivered to the subject was not determined. The vaporization method used (heating of salvinorin A in a glass vessel) might be expected to lead to less degradation of the salvinorin A than pyrolysis in a cigarette. Hence, our finding of 133 μg delivered the S. divinorum cigarette smoke compares well. Caveats to these studies are that first a single sample of S. divinorum was used and that amounts of salvinorin A can vary significantly in the plant (3) and second, the mode of simulated inhalation in the smoking apparatus may not fully replicate the inhalation pattern utilized by individuals smoking the plant material to achieve an effect. Therefore, while the numbers reported cannot be said to precisely define the average dose of salvinorin A delivered by the smoking route, it does present a value that should be within the range of delivered doses by this route."
Prof. Atanas G. Atanasov (Dr. habil., PhD)