The Salvia divinorum Research and Information Center - Shroomery

Ps94amay99
CHEMICAL INVESTIGATIONS OF SALVIA DIVINORUM
After discovering the active principles of the morning glories (lysergic acid amide derivatives) and mushrooms (psilocybin and
psilocin), Hofmann turned to the study of S. divinorum. However, his chemical and pharmacological investigations were
unsuccessful and he stated that the active principle was apparently unstable (Hofmann 1964, 1980; Schultes & Hofmann
1980). Díaz and colleagues studied the mint extensively, but had limited success in the chemical aspects of their research (Díaz
1979, 1975). In 1980, a bioassay-directed investigation of the plant was undertaken. The assay was based on the behavior of
mice in the open field, which has been employed to test compounds for psychotropic activity (Brimblecombe & Greene 1962).
This study used rats in the open field, which was modified for mice in the S. divinorum study. An aqueous infusion of the fresh
leaves was prepared, using the open field to test the various fractions and extracts for activity. Eventually, an impure active
compound was isolated via preparative thin-layer chromatography (TLC). Obtaining it from the infusion was extremely
inefficient and it was found that lyophilizing (freeze-drying) the leaves and extracting them as explained below gave much
better yields. The active compound turned out to be a new furanolactone neoclerodane diterpene which was named divinorin A
(1); its inactive desacetyl derivative, divinorin B (2), was also isolated (Valdés et al. 1984; Valdés 1983). As the results were
being prepared for publication, Ortega, Blount & Marchand (1982) reported the isolation of a compound (no biological activity
was mentioned in their paper) they called salvinorin, which turned out to be identical to divinorin A. Therefore, divinorins A
and B should be known as salvinorins A (1) and B (2), respectively (see Figure 1).
Testing of salvinorin A in the open field indicated it had activity and potency similar to that of mescaline. Originally both
compounds appeared to exhibit sedative activity in the modified open field (Valdés et al. 1987; Valdés et al. 1984; Valdés
1983). However, further testing and comparison of the two compounds to amphetamine, secobarbital, forskolin, and cannabis
extract has allowed a different interpretation of the experimental results: amphetamine stimulated the mice; secobarbital,
forskolin and the cannabis extract had strong sedating effects, and, at higher doses, the animals lost their righting reflex (the
ability to right themselves if turned on their side or upside down). Mescaline, salvinorin A and isosalvinorin A - the 8-epimer
of salvinorin A (Valdés et al. 1984) - interrupted (decreased) animal activity without an accompanying true sedation, as the
mice could be readily stimulated to move rapidly for short periods by sharp noises or light touching. They maintained their
righting reflex at all dose levels of the three compounds (from 3.2 to 100 mg/kg). Loliolide (Valdés 1986) was isolated from S.
divinorum and the absolute stereochemistry of the salvinorins was unambiguously determined using the non-empirical exciton
chirality circular dichroism method on their 1,2-diol dibenzoate tetrahydrofuran derivative (Koreeda, Brown & Valdés 1990).
SALVIA DIVINORUM AND SALVINORIN A AS POTENTIAL DRUGS OF ABUSE
Until recently, S. divinorum was considered to be a plant with low abuse potential. The large number of fresh leaves needed
and the bitterness of the prepared infusion tend to discourage all but the most intrepid users. The effects of the potion have
been reported to be from mild to nearly nonexistent, but field observations in Oaxaca demonstrated that intense and longlasting
visions do occur (Valdés 1983; Valdés, Díaz & Paul 1983). Some Mazatecs, as well as non-native experimenters, chew
a coca-like "quid" of the fresh leaves which induces strong and persistent visions (Siebert In press; Blosser 1993; Ott 1993).
Although the Mazatecs use only fresh leaves for visionary experiences, the dried leaves retain activity and are smoked by
marijuana users and others in Mexico and the U.S. The effect has been reported to be either like that of marijuana or of taking
the infusion (Ott 1993; Díaz 1975). The plant has been described as the entheogen (hallucinogen) par excellence (Ott 1993).
There are two inaccuracies about S. divinorum that are fixed in the literature. It was identified by Wasson (1963) as possibly
being the ancient Aztec narcotic plant pipiltzintzintli and this has been perpetuated until the present (Ott 1993; Foster 1984;
Anon. 1973). It has been demonstrated that either marijuana or one of various species of morning glories are better candidates
for being the unknown Aztec plant. From the descriptions quoted by Aguirre Beltrán (1973) it is obvious that pipiltzintzintli
cannot be S. divinorum and even Wasson, himself, later doubted his own hypothesis (Valdés 1987; Díaz 1979). When Wasson
and Hofmann first acquired S. divinorum, it was brought to them by a curandera, and they were not allowed to go to the
location where it actually grew. From early statements made by Wasson (1963; 1962), it has been surmised that the plant is a
cultigen which exists only in a few Mazatec gardens, and the Mazatecs consider the plant to be foreign to their region (Ott
1993). Don Alejandro informed us that the plant grows wild in the fairly inaccessible highlands of the Sierra Mazateca. It is
brought by Mazatec shamans to the lower mountain regions, planted, and left to "grow wild" near the villages where they live.
During field-collecting expeditions, it was seen growing freely over a huge area for a couple hundred meters along the side of a
http://www.sagewisdom.org/valdes94.html (3 of 9) [04.09.01 10:21:51]