|Ask Dr. Shulgin Online
ARCHIVE: June 12, 2002
Dear Dr. Shulgin:
Where in the future are you or other researchers looking for the next generation entheogens, psychedelics or maybe a class not yet defined? Is there something that exists (at least theoretically) that will produce a response in humans unlike anything we've seen presently? It seems to me that there are great similarities between many different substances. I've found Salvia to be close to LSD (not in duration but effect), yet they are so different in chemical structure. I'm wondering if there is another level or plateau that needs to be explored with futuristic compounds. Thank you for all the work you've done in our community.
-- Mr. Yuk
Dear Mr. Yuk:
I am very optimistic about what the future has in store for us. Of course, exact details are impossible to know otherwise these new things would be here in the present. But some hand-waving generalities as to where these might come from are pretty obvious.
A major source, and a continuing source, will be the result of chemical modification. You mentioned both LSD and Salvia. There has been many chemical modifications made of LSD. Most of these have dropped potency or even eliminated any activity at all, but some have led to compounds that are of equal or greater potency. But consider the structure of Salvinorin A, the active component of Salvia divinorum. It presents a treasure house of sites just begging to be chemically modified. There is an acetic acid ester that has been removed by hydrolysis and successfully replaced. What about other esters such as a formate or a propionate? There is a carboxylic acid methyl ester there. Maybe the ethyl or the propyl ester homologues might be interesting. Remember that the parent compound is active in man at less than a milligram total dose -- these minor modifications might very well change both the potency as well as the nature of its effects.
Another continuing source of new things will be from our plant teachers in nature. We are continuously being made aware of new, active plants about which we know very little. My present pursuits are the psychoactive cacti. A good example is a relatively unexplored columnar giant called Pachycereus pringlei. In the published literature, there have been five compounds reported as being present. I have seen four of these, and have obtained mass spectra of 18 additional compounds. Some of these new components I have already identified, but none of these is known to be active in man. And yet I know that the cactus is active as I have actually eaten it and have gotten real effects. Could this be an example of a plant that contains two compounds that are active in combination whereas neither one is active as an isolated chemical? Such things are known in nature.
All of this brings up a most important point. The synthesis of new compounds or the isolating of new natural components in the future is the relatively easy part of this exploration. They have to be tasted to determine if they have activity and just what the nature of that activity might be. The laboratory part of this quest requires considerable skill and patience. The human experimentation part requires great caution. As you have mentioned, the new activities that might be found in the future may be of quite a different nature, and could potentially be harmful. All things new are, by definition, unknown.
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