Book II of PiHKAL: A Chemical Love Story. Alexander & Ann Shulgin #142: PEA
SYNTHESIS: This compound has been made industrially by a number of routes, the motant being the reduction of benzyl cyanide and the decarboxylation of phenylanaline. It is offered in the catalogs of all the major chemical supply houses for a few pennies per gram. It is a very strong base with a fishy smell, and rapidly forms a solid carbonate salt upon exposure to the air. It is a natural biochemical in both plants and animals.
DOSAGE: greater than 1600 mg.
QUALITATIVE COMMENTS: (with 200, 400, 800 and 1600 mg) “No effects.”
(with 500 mg) “No effects.”
(with 800 and 1600 mg) “No effects.”
(with 25 and 50 mg i.v.) “No effects.”
EXTENSIONS AND COMMENTARY: Here is the chemical that is central to this entire book. This is the structural point of departure for every compound that is discussed here. It is the “P” in PiHKAL. It is without activity in man! Certainly not for the lack of trying, as some of the dosage trials that are tucked away in the literature (as abstracted in the “Qualitative Comments” given above) are pretty heavy duty. Actually, I truly doubt that all of the experimenters used exactly that phrase, “No effects,” but it is patently obvious that no effects were found. It happened to be the phrase I had used in my own notes.
This, the simplest of all phenethylamines, has always been the darling of the psychopharmacologists in that it is structurally clean, it is naturally present in various human fluids and tissues, and because of its close chemical relationship to
Phenethylamine is found throughout nature, in both plants and animals. It is the end product of phenylalanine in the putrefaction of tissue. One of its most popularized occurrences has been as a major component of chocolate, and it has hit the Sunday Supplements as the love-sickness chemical. Those falling out of love are compulsive chocolate eaters, trying to replenish and repair the body’s loss of this compound—or so the myth goes. But this amine is voraciously metabolized to the apparently inactive compound phenylacetic acid, and to some
Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
To a large measure, this book has emphasized the “phenyl” end of the phenethylamine molecule, and the “what,” the “where,” and the “how many” of the substituent groups involved. There is a broad variety of chemical groups that can be attached to the benzene ring, at one or more of the five available positions, and in an unending number of combinations. And, in any given molecule, the greater the number of substituents on the benzene ring, the greater the likelihood that there will be psychedelic action rather that stimulant action.
But what can be said about the “ethylamine” end of the phenethylamine molecule? This is the veritable backbone that holds everything together, and simple changes here can produce new prototypes that can serve as starting points for the substituent game on the benzene ring. Thus, just as there is a “family” of compounds based on the foundation of phenethylamine itself, there is an equally varied and rich “families” of other compounds that might be based on some phenethylamine with a small modification to its backbone.
So, for the moment, leave the aromatic ring alone, and let us explore simple changes in the ethylamine chain itself. And the simplest structural unit of change is a single carbon atom, called the methyl group. Where can it be placed?
The adding of a methyl group adjacent to the amine produces phenylisopropylamine, or
The placement of the methyl group between the two carbons (so to speak) produces a cyclopropyl system. The simplest example is
The dropping of one carbon from the phenethylamine chain gives a benzyl amine, basically an inactive nucleus. Two families deserve mention, however. The phencylidine area, phenylcyclohexylpiperidine or PCP, is represented by a number of benzyl amines. Ketamine is also a benzyl amine. These are all analgesics and anesthetics with central properties far removed from the stimulant area, and are not really part of this book. There is a benzyl amine that is a pure stimulant, which has been closely compared to amphetamine in its action This is
What happens if you extend the chain to a third carbon? The parent system is called the phenyl-n-propylamine, and the parent chain structure, either as the primary amine or as its alpha-methyl counterpart, represents compounds that are inactive as stimulants. The
The chain that reaches out to the amine group can be tied back in again to the ring, with a second chain. There are 2-aminobenzoindanes which are phenethylamines with a one-carbon link tying the alpha-position of the chain back to the aromatic ring. And there are 2-aminotetralines which are phenethylamines which have a two-carbon link tying the alpha-position of the chain back to the aromatic ring. Both unsubstituted ring systems are known and both are fair stimulants. Both systems have been modified with the
And there is one more obvious remaining methylation pattern. What about phenethylamine or amphetamine compounds with two methyl groups on the nitrogen? The parent amphetamine example,
This is as good a place as any to discuss two or three simple compounds, phenethylamines, with only one substituent on the benzene ring. The 2-carbon analog of
About PiHKAL • info
This version of Book II of PiHKAL is based on the Erowid online version, originally transcribed by Simson Garfinkle and converted into HTML by Lamont Granquist. I drew also on “Tyrone Slothrop’s” (Unfinished) Review of PIHKAL to enumerate the many analogues mentioned in PiHKAL but not described at length. Many, many others have since been added.
I have tried here to expunge any artifacts introduced by the earlier transcriptions and restore the typographic niceties found in the printed edition. I’ve also made minor changes to some chemical names in line with current nomenclature practice. Typically the change is little more than expanding a prefix or setting it in italics. The errata and changes page has further details.
“At the present time, restrictive laws are in force in the United States and it is very difficult for researchers to abide by the regulations which govern efforts to obtain legal approval to do work with these compounds in human beings.“No one who is lacking legal authorization should attempt the synthesis of any of the compounds described in these files, with the intent to give them to man. To do so is to risk legal action which might lead to the tragic ruination of a life. It should also be noted that any person anywhere who experiments on himself, or on another human being, with any of the drugs described herein, without being familiar with that drug’s action and aware of the physical and/or mental disturbance or harm it might cause, is acting irresponsibly and immorally, whether or not he is doing so within the bounds of the law.”
The copyright for Book I of PiHKAL has been reserved in all forms and it may not be distributed. Book II of PiHKAL may be distributed for non-commercial reproduction provided that the introductory information, copyright notice, cautionary notice and ordering information remain attached.
PiHKAL is the extraordinary record of the authors’ years exploring the chemistry and transformational power of phenethylamines. This book belongs in the library of anyone seeking a rational, enlightened and candid perspective on psychedelic drugs.
Though Sasha and Ann have put Book II of PiHKAL in the public domain, available to anyone, I strongly encourage you to buy a copy. We owe them — and there’s still nothing quite like holding a real book in your hands.
PiHKAL (ISBN 0-9630096-0-5) is available for US$24.50 (plus $10 domestic first-class shipping) from Transform Press.Transform Press,
Berkeley, CA 94701
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