MAPS: Special Digest: Salvia Divinorum ... a new frontier for research

[maps-forum@xxxxxxxx]

Contributions from Walter Mandell, Seth Lee Cabe, Thomas Seay,
C6H10N2O2@xxxxxxx, and Tore M. Schanke

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From: Walter Mandell <wmandell@xxxxxxxxxxxxxx>
Subject: Re: MAPS: Salvia Divinorum ... a new frontier for research

Ian Soutar wrote:
> 
> Maps Forum,
> I know people in Canada growing and enjoying Salvia Divinorum.  It is a
> remarkable psychedelic because it is easy to grow and contains the most
> powerful natural psychedelic known.  The effective dose is only about
> 500 micrograms which puts in league with LSD.

WM: Salvia divinorum contains salvinorin A, which is the psychoactive
substance. it is a neoclerodane diterpenoid (it is not an alkaloid).
While salvinorin A (usually known just as salvinorin) is active in doses
above 200 mcg.., it is present in relatively low concentration in Salvia
leaf. 1 G of dried Salvia divinorum leaf contains about 2.5 mg of
salvinorin. Thus salvia leaf (which is effective if chewed as a quid, or
if smoked more or less as cannabis is) is not nearly as potent on a
weight basis as is LSD.
> 
> Maps could benefit by encouraging the use of this herb in research and
> getting some real scientific results without wasting too much energy
> fighting the tough U.S. drug laws.
<snip>
> 3/ It has been used for 1000 years or so in Central America.  Its
> methods of use are well known.

WM: The duration of use of Salvia divinorum is unknown. It may, or may
not, have been used by the Aztecs (this is controversial). Its known
native use is among the Mazatecs in the Oaxaca region of Mexico and to a
lesser extent among neighboring tribes. It was unknown to the west
until this century. Post Spanish conquest references to pilpiltzintli
(which I've probably misspelled) may actually refer to the rapidly
spreading use of cannabis (introduced by the Spanish) rather than to S.
divinorum. There is no evidence that its use goes back 1000 years or so.
It is not a Central American herb but rather an herb that grows in the
Sierra Mazateca in Mexico. Mexico is a North american nation, not a
Central American nation.

> 4/ The active ingredient can be easily extracted, making the dose
> predictable for research.
WM: While it is easy to make crude extracts, refining pure salvinorin is
more difficult. However there are several published procedures for this.

> 5/ IT IS ABSOLUTELY LEGAL AND AVAILABLE IN MANY GREENHOUSES!

WM: So far no one has been prosecuted for using or growing Salvia
divinorum. Legal status may vary from country to country, and may change
rapidly. For example it may be illegal under general laws forbidding
intoxicants in some Scandinavian countries.

> 6/ The effect only lasts at full strength for 10 minutes when smoked.
WM: This is variable. Smoking may produce strong effects lasting over
1/2 hour. 

> Yet it lasts for an hour when the leaves are chewed.

WM: Chewing may produce strong effects lasting over one and 1/2 hours.
Drinking the water based infusion (a Mazatec custom reported on by
Valdes) may produce effects lasting several hours.

>7/ Its mode of action is as yet unknown ... thus a major break though in
> pharmacology has yet to be made in this area.

WM: True. If it is researched more. As of now a lot of receptor sites
are known at which it does not act!
> 
> As a Quaker I am interested in experimenting with this visionary
> substance for enhancing silent meditation.  A small group of us have
> discussed having a Salvia/Meditation study group.

WM: Salvia has definite potential as an 'entheogen'. It is used in a
sacred/healing/ritual context by the Mazatecs, and can bring about
states that are best described as 'pharmacologically induced mysticism'
- characteristics of such states vary with dose, set, and setting but
can include oceanic feelings of union with God, gods, spirits, or with
the universe as a whole. At high dose individual selfhood may be lost
without loss of awareness. Characteristic of the Salvia state are
non-Euclidean perception of space and non-sequential perception of time.
One may experience being everyone, and everywhere, now and then
simultaneously. 
> 
> In the U.S. this type of study group associated with some religious
> group could establish Salvia as a sacramental substance ... and make use
> of U.S. laws protecting religious freedom to protect the status of
> Salvia Divinorum.

WM: Probably not. Do not underestimate the forces of religious bigotry
in the US. Salvia will be seen as a threat by religious conservatives if
it is promoted as a sacrament. It will then be made illegal for
ostensibly non-religious reasons. A recent post on MAPS detailed
persecution of members of the Native American Church despite the
supposedly protected status of their religious use of peyote.
> 
> Maps could help both popularize its use in Scientific circles and also
> make people aware of the dangers associated with the abuse of Salvia
> Divinorum.  Excessive dosage may be hazardous because the visions are so
> overpowering.

WM: While there is absolutely no evidence that S. divinorum is habit
forming, and while no fatalities from its use have been reported, the
possibility of injury (burns, falls, fires etc.) occurring when it is
taken demands that a sitter be present whenever it is used by neophytes
and whenever high dosage or very strong preparations are used (extracts;
vaporization of leaf, or extract; any use of pure salvinorin). During
the Salvia intoxication orientation, perception, memory, judgment and
coordination may all be impaired.

WM: Those wishing to learn more about Salvia should go to Daniel
Siebert's Salvia site at 
http://salvia.lycaeum.org/ and check out the entire site including the
Salvia divinorum FAQ at http://salvia.lycaeum.org/faq.html
A bibliography on Salvia divinorum is given at http://salvia.lycaeum.org/biblio.html
A recent monograph of Salvia divinorum is Salvia Divinorum and
Salvinorin A available as ER Monograph series # 2, David Aardvark,
Editor; published by The Entheogen Review, 564 Mission Street, Box 808,
San Francisco, CA 94105-2918. There is a very active Salvia divinorum
e-mail list that can joined through Daniel Siebert's site.

-------------------------
From: "Seth Lee Cabe Iii" <cabes@xxxxxxx>
Message-Id: <990114160539.ZM19853@xxxxxxxxxxxxxxxxxxxxxx>

	While I am not aware of any studies concerned with the
psychopharmacology of Salvinorin A, it seems similar to DMT in it's effects.
 The duration and intensity seem to be approx. the same.  Also, like DMT,
there is a threshold amount that must be absorbed quickly in order to get
maximum effects.  I have heard that if this threshold is reached a mental
state can be reached that is more powerful than LSD, psilocybin/cin, etc.,
but only for a very short duration.  This seems to match up with what I have
heard about DMT.

-Seth
-------------------------
From: Thomas Seay <hippy@xxxxxxxxxxxxxxxxxxxxx>
Subject: Re: MAPS: Salvia Divinorum ... a new frontier for research

Has anyone studied the possible negative side effects of taking Salvia 
Divinorumm?

-Thomas Seay
-------------------------
From: C6H10N2O2@xxxxxxx
Subject: Salvinorin A Pharmacology

Hi All,

Back a while ago there was some speculation that Salvinorin A had a mechanism
of action that involved activation of adenylate cyclase. Salvinorin A has a
structure similar to that of Forskolin (a selective and potent activator of
adenylate cyclase). Has there been any confirmation or refutation of this
original hypothesis? I have heard some anecdotes that indicate that Forskolin
at high doses can produce visual hypnogogic like geometric patterns.

Also, it has been reported that Salvinorin A has an active dose of around 250
micrograms, is this for oral administration? Being a diterpene it is likely
that it undergoes extensive first pass catabolism through the portal system. I
have also read an account of someone smoking it and achieving an effect that
was so much more intense that it could only be described as qualitatively
different. If this is so it is very likely that the ED50 for Salvinorin A is
far below the 250 microgram amount, it is just that oral administration is a
relatively ineffective means.

Also, if this later hypothesis is true, we should be aware that the abuse and
mishap potential of Salvinorin A is probably higher than experience thus far
has led people to believe. The extract when administered by other means could
potentially produce dangerously severe intoxication. It is unclear whether or
not Salvinorin A has reward effects strong enough to encourage the use of
abusively high doses. cAMP is known to agonize reward systems such as
dopamine, so this possibility should be investigated.

All these possibilities should be considered before Salvia Divinorum becomes
popularized as a legal and safe psychedelic.


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From: "Tore M. Schanke" <tore.schanke@xxxxxxxxxxxxxxxxxxx>
Subject: Re: MAPS: Salvia Divinorum ... a new frontier for research

The best source for information on Salvia divinorum is Daniel Siebert's Salvia
pages, at:
               < http://salvia.lycaeum.org>

Salvia divinorum is a plant that is rapidly spreading among those interested in
ethnobotanical psychotropics. They've become quite common, and a bit
'fashionable', far outside of their native habitat, the Mazatec country of
Sierra Madre. You now can find them cultivated almost anywhere in the americas
and europe...
It is available on the net as live plants, dried leaves and 5X fortified
'incense'. It can be smoked or taken as a 'quid'.

S. divinorum is a 'new world' Salvia (Calosphace), like the very common Salvia
splendens, which also seems to have interesting pharmacology, -and is not much
related to S. officinalis etc.
It contains about 1-3 mg/g dried leaves of the psychoactive neoclerodan
diterpenoid, salvinorin A, and a lesser amount of salvinorin B, which doesn't
seem to be active.

Salvinorin A, is active from about 100 µg in a human being. Doses above 1 mg
are generally considered too much, ('scaring' or anesthetic). Physiological
toxicity is still unknown, but the acutely toxic dose must be rather high.
It is not a psychedelic like LSD, psilocybin etc. But is a strong 'vision'
inducer, and can take you into a totally different 'universe' of experience.
Dissociative phenomena are very common. (It often feels like the plant
completely takes you over, mind and body).
There are some similarities to phencyclidine and ketamine (and gas
anesthetics), though it has a very 'unique' quality to it. S. divinorum itself,
is not nearly as unpleasant and dangerous as these drugs, however, (but is in
my opinion a bit too short-acting).
The use of this plant requires good knowledge about its effect. At higher doses
and for 'novices' a 'sitter' should always be present. (You often no longer
knows what your body is doing).
On the other hand, you're rather soon 'back' after the experience, usually in
5-15 minutes if smoking or 20-30 minutes if chewing.
Often one gets no effects the first times, but it can be very active from the
start. It just needs quite and safe surroundings, and little light. This is
definitely not a party drug.
I find the effects very interesting, but never very 'gentle'.

The 'mechanism of action' is not studied very much. A 'NovaScreen' test was
done for many possible 'receptors' and 'sites of action', but this only rules
out these...
I'm planning to focus some of my work the coming years, on finding and
identifying the salvinorin 'site of action'... I hope I can find something, but
I hope to find coworkers, as I'm not certified to do work like radio-labeling
salvinorin A. (But, - am allowed to use labeled compounds in binding studies).
I have the plans for the steps that are probably needed, but not the necessary
'backing' totally cleared out, -so if anyone have any ideas...

I think a lot can be gained by neurochemical studies on the salvinorins, a new
receptor or not, the quest will none the less be interesting...

Yours,
- Tore


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