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ARCHIVE:  January 9, 2002

Salvia divinorum and Salvinorin- A Receptor Sites

Dear Dr. Shulgin:

I was wondering if they had found any neurotransmitter sites for Salvinorin-A, B or C. They are compounds of such high potency that I wonder if they might actually mutate receptor sites into new sites specific for salvia. Is this possible?

-- Whistler

Dear Whistler:

Addendum added Oct. 2002; salvia receptors discovered

Salvinorin-A is the active component of the plant Salvia divinorum, also known as Ska Pastora, hojas de la Pastora, or leaves of the shepardess by the Mazatec in northern Oaxaca. The extremely high potency and the complex chemistry of Salvinorin-A definitely places it in a unique category. The pure compound is fully active in man at a dosage of less than a milligram and it has a monstrous molecular structure containing some 23 carbon atoms, three more than LSD. And since seven of them are asymmetric, there are a total of 128 isomers that can exist. The total synthesis of it would be a most challenging task and I am not aware of anyone who as made a start in this direction.  

As to its neuroreceptor sites of action, I have no ghost of an idea as to what or where it might be. One study has been made with a commercial company screening salvinorin-A within a collection of about a dozen neuroreceptors (including dopamine, serotonin, GABA and muscarinic receptors) and nothing of interest was found. And there have been no clinical studies performed, so the human pharmacokinetics and metabolism are also unknown.

For a long time I have been intrigued by a parallel between salvinorin-A and delta-1-tetrahydrocannabinol, or THC. This active factor of Cannabis sativa (Marijuana) has 21 carbon atoms and, like salvinorin-A, contains no nitrogen atom and thus is not a base. It has only been in the last few years that a receptor site for THC has been found, with a natural endogenous agonist named anandamide. This is a 22-carbon non-basic amide. I nurtured a fantasy that that all these twentyish carbon things might be somehow interrelated -- maybe sharing in some way a common receptor site. This was masterfully shot down when my dear friend Raphe Mechoulam, in Israel, tested salvinorin-A against the THC receptor site a couple of years ago and found it not to be active.

I am without any ideas as to why salvinorin-A is active. Any hypothesis must account for the fact that the simple deacetylation product, salvinorin-B, is not active. And I am not familiar with salvinorin-C at all.

-- Dr. Shulgin

See the Salvia Divinorum Action Center for latest info on S.divinorum's legal status.

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