Editor's Note: What follows is a verbatim transcript of part of an address by Robert Keil, Ph.D. at an Albert Hofmann Foundation seminar on Dec. 6, 1997.

"Psychedelic Chemistry and Urban Myth"

by Robert Keil, Ph.D.

What's in that piece of paper?

 As an organic chemist, I often get asked questions about psychedelics and related compounds. Often these questions are simple ones about the nature of molecules, often times they reflect a deep philosophical difference between the questioner and myself, a "hard" scientist. The most obvious example of this is in the debate over the purity in LSD samples. Everyone has an opinion about the strength of LSD: that it is weaker than in the '70s, that some LSD creates certain mental states, that some LSD is probably adulterated with speed. What can analytical science tell us about these questions? Unfortunately, not as much as you might like!

 Before we explore this, let's look at the chemistry and packaging of typical "street" LSD and think about what else it could contain. I'm going to be considering mostly LSD-impregnated blotter paper, which seems to be the most common form. Other forms are far more amenable to being adulterated with other drugs. The typical active dose of LSD is about 100 mcg [micrograms]. Just how much is that? Well, if you take a grain of salt, that's typically 500 mcg. LSD is truly amazing in its potency. But how much of something else could be in there, lurking on the paper? Well, a typical piece of thick paper might weigh about 10-50 mg. By testing this amount of chemical that the paper can absorb (e.g. by using caffeine as a model), you might be able to get up to, say, 5 mg on a typical piece of blotter paper. You can prove this to yourself with some paper, caffeine (No-Doz), and a good balance.

 So we've established that a piece of blotter can hold about 5 mg of total compound (any more and the excess falls off the sheet.) Can't that 5 mg be something like speed, or ecstasy (MDMA)? Simply put, no. Neither speed nor MDMA is going to have much effect at that dosage. Amphetamine might have some "kick," but this is below the dosage usually used. What about strychnine? This question probably came from a listing in the Merck Index (a standard reference text) that indicates as one of the symptoms of strychnine poisoning heightened visual acuity. You will also note that strychnine is extremely bitter and can be tasted in concentrations of 1 part in 700,000. It would seem unlikely that enough strychnine could be present to cause physical effects, yet not have any bitter taste when rolled over the tongue. Although it is hard to find the lethal dose of strychnine from the literature, it appears to be over [recording blurred].

 OK, so maybe there is no poison or amphetamine on blotter, but what about the purity of the actual LSD? Perhaps there is a potent isomer that colors the experience? Here is where things get tricky. LSD is a difficult molecule to produce. You need to start with a complex natural product called ergotamine, and perform several manipulations on it. The final product is sensitive to light and oxygen and there are several by-products that can be made along the way. Perhaps, the theory goes, these trace by-products act to catalyze or potentiate the LSD effects in some way, even though they are present in very small amounts. For the chemist, this theory is nearly impossible to disprove.

 Hofmann and many workers have looked at many of the isomers, by-products, and close chemical cousins of LSD, and LSD is by far the most potent of them all. None of these "minors" have anywhere near the strength of LSD itself. So can we exclude their effects? No, because of a dirty secret of chemists. Practically speaking, it is nearly impossible to make truly pure compounds. Even simple compounds such as aspirin and Prozac contain very small amounts of impurities. In fact, there are analytical chemists whose job it is to look at generic copies of their company's drugs and see if they are made using the original procedures. Even the most purified drug will contain very, very small amounts of characteristic impurities that give away a compound's origin.

 So no matter how pure LSD is made, with the best starting materials and techniques, a skeptic could always say, "But wait, maybe there is still some impurity left that catalyses the experience in some way. Maybe it's just in such small amounts that you can't see it, but it's there." There can be no way to disprove this statement. The best a chemist can say is that it is extremely unlikely, given what we know about neurochemistry and the way other drugs behave. But I can't say it cannot happen.

 Which brings me to the "Jaegermeister effect." Jaegermeister is a brown liquor from Germany that's become popular in the last few years, especially among college students. Invariably, if you bring up the subject of Jaegermeister, you'll hear someone claim that the high from Jaegermeister is different from that of other drinks (often it's claimed that it contains morphine, opium, shoe polish ...) It's easy for a "rational" scientist to discount these claims and chalk it up to a placebo effect. This attitude frankly disturbs me, because it discounts the human factor in what after all is a discussion about consciousness. If someone claims to have a certain feeling, can anyone really say that the claim is invalid?

 Both sides in this discussion seem to be missing each other's crucial point. The "rational" scientist ignores the input of subjects and focuses only on the molecules. The "humanist" claims that the experience is paramount. Of critical importance is to remember that the psychedelic experience is influenced by mind-set, physical setting, and dosage taken. Over and over, the psychedelic literature has stressed the variability of the experience, when the compounds were legal and dosages were known. In today's climate of prohibition, a fourth variable, identity of the psychedelic agent is added.

 Generally, statements about psychedelics are made from one person's viewpoint, yet that person will try to generalize the statement, saying, for example, that a particular drug is qualitatively different now than it was a decade ago. How can you test this statement? By finding someone who has undergone no personal growth or change in his mind for years? (Besides, Pat Buchanan probably wouldn't volunteer!) I find it odd that very often we find it easier to say that a drug is different than to say that we have changed internally.

 The opposite problem bedevils modern neuroscience. The ability to clone and measure receptors has led to the seductive idea that all moods and mental states can be traced to the states of the synapses. Yet the variability of response to mood-altering drugs implies that this cannot be so simple. Even such well-understood drugs as Prozac can have widely different effects on different people -- read "Listening to Prozac." When a vastly more complex drug like LSD enters the body, merely knowing how it binds to which subset of receptors is not going to answer the question, "What happened to me, to my mind and consciousness?"

 The inability of research to properly study the mind with these substances for legal reasons perpetuates this problem. "Recreational" users are unable to verify what they are taking, and scientists are unable to ask how people react to these compounds. Perhaps in the future we can look forward to a blending of these viewpoints, to a science that allows for human experience and a public that attributes changes in mental states to many subtle, sometimes non-material factors.

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