THE BOTANY OF SALVIA DIVINORUM
In the past two decades, most
research concerning S. divinorum has focused on the psychoactive chemical
compounds and its pharmacologic potential. S. divinorum has proven to be unique
not only in its botanical significance and ethnopharmacological tradition, but
also in its biochemical characteristics. Like many other members of the genus
Salvia, S. divinorumcontains unusual terpenoid compounds (Ott 2001).
In 1962, Gordon Wasson and Albert Hofmann collected S. divinorum juice from a
leaves given to them in San Jose Tenango from the same flowering plants used as
identification by Epling and Jativa.. The juice was preserved in alcohol to be
studied, but chemical investigation at the time was unsuccessful. Hofmann
concluded that the psychoactive principle must be unstable (Hofmann 1979).
Diaz et al. also studied the mint, but were also had limited success in studying
the chemical properties of the plant (Valdes 1994) . S. divinorum’s
hallucinogenic components were isolated in 1982 by the research group of Alfredo
Ortega, who had also isolated the new compounds salviarin and splendidin from S.
splendens (Ott 2001). Ortega et al. isolated a novel trans-neoclerodane
diterpene from S. divinorum and determined its structure using X-ray
crystallography, but did not study biological activity, or extend the research
to investigate the pharmacological applications of the compound. The new
compound was named salvinorin (Ortega 1982).
L.J. Valdes has produced a large body of work regarding S. divinorum, both in
ethnobotany and chemistry, and was also the first to test salvinorin as a
psychoactive principle. In 1984, Valdes et al. isolated the same compound as
Ortega et. al. Unaware that the compound had already been characterized and
named, the group referred to active compound as divinorumA, and its inactive
desacetyl derivative was called divinorum B. The two terms (salvinorin and
divinorin) are now applied interchangeably, although salvinorin A and salvinorin
B are, officially, the correct names for these molecules (Valdes 1987, 1984).
Valdes et. al. tested the biological effects of salvinorin A in mice, and noted
that salvinorin had similar effects to mescaline, dramatically reducing animal
activity in a manner similar to sedation, but without true sedation since the
mice were able to move rapidly for short periods of time. The absolute
stereochemistry of the salvinorins was also determined (Koreeda et al. 1990).
While Valdes, Diaz, and Paul had personally tested Salvia divinorum leaves
during Mazatec cermonies while conducting ethnobotanical research, Valdes et.
al. did not conduct psychonautic human bioassays to determine whether salvinorin
A was, in actuality, the visionary principle active in S. divinorum (Ott 1996).
“Basement shamans” (apparently Daniel Siebert and friends) in California were
the next group to isolate and test salvinorin as a psychoactive principle (Ott
1996). Siebert soon tested various methods of leaf and salvinorin intake by
volunteers to determine site of absorption, effects, and dosage. Siebert found
that extended exposure (10 minutes) to the oral mucosa produced psychoactive
effects in all volunteers, while quick swallowing and rinsing of leaves produced
no effects at all, leading Siebert to conclude that the gastrointestinal system
breaks down the psychoactive compound and that leaves must be chewed or held in
the mouth to produce hallucinations. Siebert isolated salvinorin A by the same
method used by Valdes et al. (1984).
20 volunteers were given capsules of salvinorin A, which produced no effects,
reinforcing the hypothesis that salvinorin is inactivated by gastrointestinal
absorption. Because salvinorin A is not water soluble, injection was not tested.
Inhalation of the vaporized salvinorin A was tested, however, and proved to be
the most efficient and dramatic method of salvinorin A intake to produce
hallucinations. Threshold effects were usually noted at 200-500 Φg, and
hallucinations occurred within 30 seconds, rather than the 10-15 minutes
required by oral ingestion (Siebert 1994). With activity apparent at the 200 Φg
level, salvinorin A is now the most potent entheogen known thus far, and one of
the most potent natural compounds discovered (Valdes 2001, Ott 1996).
Samples of salvinorin A were also submitted to Novascreen for receptor site
screening, and was shown not to affect any brain receptor sites affected by most
other hallucinogens, suggesting that a unique pathway and receptor site may be
present for salvinorin A (Siebert 1994).
Salvinorin A is the first diterpene to be identified as a hallucinogen in humans
(Valdes et al 2001). Siebert has also determined and compared levels of
salvinorin A found in leaves from several plants grown throughout the United
States and Mexico, concluding that leaves may contain a range of .89-3.70 mg/g
salvinorin A in dry weight (Siebert 1999). Valdes et al. have further studied
the bioactive compounds of Salvia divinorum, and discovered that a third
compound exists, salvinorin C, which comprises only about 10% of the bioactive
compounds in S. divinorum, but may be even more potent per unit of measure than
salvinorin A (Valdes et al 2001).
Salvinorin A, salvinorin B, and salvinorin C bear close resemblance to other
neoclerodane diterpenes from Latin American Salvia species, such as salviarin
and splendidin. The salvinorins have been the only neoclerodane diterpenes
tested for hallucinogenic properties thus far, however, and other similar Salvia
compounds should be tested for pychotropic activities (Valdes et al 2001). Great
research potential exists in the biochemistry and application of the salvinorin
compounds, and related molecules, as hallucinogens, antibiotics, and to discover
new neurological pathways and receptor sites.