Mescaline; 3,4,5-trimethoxyphenethylamine

Publication Year: 
1991

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Mescaline is one of the oldest psychedelics known to man. It is the major active component of the small dumpling cactus known as Peyote. It grows wild in the Southwestern United States and in Northern Mexico, and has been used as an intimate component of a number of religious traditions amongst the native Indians of these areas. The cactus has the botanical name Lophophora williamsii or Anhalonium lewinii and is immediately recognizable by its small round shape and the appearance of tufts of soft fuzz in place of the more conventional spines. The dried plant material has been classical used with anywhere from a few to a couple of dozen of the hard tops, called buttons, being consumed in the course of a ceremony
Throughout the more recently published record of clinical human studies with mescaline, It has been used in the form of the synthetic material, and has usually been administered as the sulfate salt. Although this form has a miserable melting point (it contains water of crystallization, and the exact melting point depends on the rate of heating of the sample) it nonetheless forms magnificent crystals from water. Long, glistening needles that are, in a sense, its signature and its mark of purity. The dosages associated with the above “qualitative comments” are given as if measurd as the sulfate, although the actual form used was usually the hydrochloride salt. The conversion factor is given under “dosage” above.
Mescaline has always been the central standard against which all other compounds are viewed. Even the United States Chemical Warfare group, in their human studies of a number of substituted phenethylamines, used mescaline as the reference material for both quantitative and qualitative comparisons. The Edgewood Arsenal code number for it was EA-1306. All psychedelics are given properties that are something like “twice the potency of mescaline” or “twice as long-lived as mescaline.” This simple drug is truly the central prototype against which everything else is measured. The earliest studies with the “psychotomimetic amphetamines” had quantitative psychological numbers attached that read as “mescaline units.” mescaline was cast in concrete as being active at the 3.75 mg/kg level. That means for a 80 kilogram person (a 170 pound person) a dose of 300 milligrams, there was a M.U. Level of 10 put into the published literature. The behavioral biologist were happy, because now they had numbers to represent psychological properties. But in truth, none of this represents the magic of this material, the nature of the experience itself. That is why, in this Book II, there is only one line given to “dosage,” but a full page given to “qualitative comments.”
Four simple N-modified mescaline analogues are of interest in that they are natural and have been explored in man.
The N-acetyl analogue has been found in the peyote plant, and it is also a major metabolite of mescaline in man. It is made by the gentle reaction of mescaline with acetic anhydride (a bit to much heat, and the product N-acetyl mescaline will cyclize to a dyhidroisoquinoline, itself is a fine white crystalline solid, mp 160-161 C) and can be recrystallized from boiling toluene. A number of human trials with this amide at levels in the 300 to 750 milligrams range have shown it to be with very little activity. At the highest levels there have been suggestions of drowsiness. Certainly there were none of the classic mescaline psychedelic effects.
If free base mescaline is brought into reaction with ethyl formate (to produce amide, N-formylmescaline) and subsequently reduced (with lithium aluminum hydride) it is converted to the N-methyl homologue. This base has also been found as a trace component in the Peyote cactus. And the effects of N-methylation of other psychedelic drugs have been commented upon elsewhere in these recipes, all with consistently negative results (with the noteworthy exception of the conversion of MDA to MDMA). Here, to, there is no obvious activity in man, although the levels assayed were only up to 25 milligrams.
N, N-Dimethylmescaline has been given the trivial name of Trichocerine as it has been found as a natural product in several cacti of the Trichocereus Genus but, interestingly, never in any Peyote variant. It is also has proven inactive in an in dosages in excess of 500 milligrams, administered parenterally. This observation, the absence of activity of a simple tertiary amine, has been exploited in the development of several iodinated radiopharmaceuticals that are mentioned elsewhere in this book.
The fourth modification is the compound with nitrogen atom oxidatively removed from the scene. This is the mescaline metabolite, 3,4,5- trimethoxyphenylacetic acid, or TMPEA. Human dosages up to 750 milligrams orally failed to produce either physiological or psychological changes.
One additional manipulation with some of these structures has been made and should be mentioned. These are the analogues with an oxygen atom instered between the aromatic ring and the aliphatic chain. They are, in essence,inoethylphenyl ethers. The first is related to mescaline itself, 2-(3,4,5-trimethoxyphenoxy)ethylamine. Human trials were conducted over the dose range of 10 to 300 milligrams and there were no effects observed. The second is related to trichocerine, N,N-dimethyl-2-(3,4,5-trimethoxyphenoxy)ethylamine. It was inactive in man over the range of 10 to 400 milligrams. Mescaline, at a dose of 420 milligrams, served as the control in these studies.

pp. 705-707 Pihkal by Alexander Shulgin and Ann Shulgin (1991)

Alexander Shulgin
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