Psilocin, structure

The natural prototype for the phenylalkylamines is mescaline (Structure 1), isolated from the peyote cactus (Lophophora williamsii) by Heffter in 1896 (100) and subsequently obtained synthetically by Spath in 1919 (218). Used for many centuries in the form of peyote by Indians in Mexico and the American Southwest (3), it is often referred to as one of the classic hallucinogens, along with psilocybin, psilocin, and LSD. Little structure-activity work was directed toward mescaline or its congeners until 1955, when Peretz et al. (174) reported that a-methyl mescaline (TMA) (8), which represented a hybrid of the structure... 

Gessner, P. K., Godse, D. D., Krull, A. H., and McMullan, J. M. (1968) Structure-activity relationships among 5-methoxy-N,N-dimethyltryptamine, 4-hydroxy-N,N-dimethyltryptamine (psilocin) and other substituted tryptamines. Life Sci., 7 267-277. 

The two principal hallucinogenic constituents of psilocybe mushrooms (and related genera) are psilocybin and psilocin (Schultes and Hofman 1980,1992) (figure 9.4). They are very similar, having a dimethyltryptamine structure and differing only by a phosphoric acid molecule. Psilocybin may be called 4-phosphoryl-DMT and psilocin may be called 4-hydroxy DMT. They are both approximately 1/200 as potent as LSD. Absorption is adequate through the oral route, making this a common form of consumption. 

Psilocybin (Figure 3.5a) and psilocin (Figure 3.5b) are indole derivatives substituted in position 4 by a hydroxyl group, where psilocybin is phosphory-lated. Due to its ionic properties, psilocybin is soluble in water. In addition, phosphorylation protects psilocybin from oxidative degradation. Both compounds are found to affect laboratory animals, but there is evidence that only the dephosphorylated form, psilocin, is the active species. In their structure the toxins resemble serotonine, a biogenic amine known to be a neurotransmitter. 

Psilocybin and psilocin are psychoactive hallucinogenous alkaloids synthesized from the small mushroom genus Psilocybe spp. On average, the concentration of these alkaloids is 300 g in 100 g of mushroom mass. Structurally, these alkaloids are neurotransmitters 5-HT. 

This structural group of indole alkaloids covers simple indole alkaloids (e.g., tryptamine, serotonin, psilocin and psilocybin), /3-carboline alkaloids (e.g., harmine), terpenoid indole (e.g., ajmalicine, catharanthine and tabersonine), quinoline alkaloids (e.g., quinine, quinidine and cinchonidine), pyrroloindole... 

The a for the structural development of psilocin and psilocybin is L-tryptophan and the j3 is tryptamine. Psilocin is A and psilocybin is P. A and P are the main alkaloids in hallucinogenic mushrooms belonging to the genus Psilocybe. 

The hallucinogens generally fall into two chemical classes. The indole alkylamines include LSD, psilocybin, psilocin, dimethyltryptamine (DMT), and diethyltrypta-mine (DET), all of which are structurally similar to serotonin. The other chemical subclass of hallucinogens contains phenylethylamine derivatives such as mescaline, MDMA, MDA, and DOM (dimethoxymethyl amphetamine). A related stimulatory hallucinogen, PCP, is a piperidine analogue that produces unique effects. 

Cross tolerance has been demonstrated between LSD and mescaline, psilocybin, and psilocin. There seems to be no cross tolerance between LSD and marijuana or amphetamine. These observations are indicative of the structural similarites of the compounds. 

They obtained the teonanactl plant from Mexicans whose trust they had won over enough to allow them to participate in a sacred mushroom ceremony. Roger Herr identified the teonanactl mushroom as Psilocybe Mexicana, and he asked Hofmann to do the biochemical analysis. Unable to establish a bioassay for the extracts he made from the mushrooms, Hofmann took the psilocin and psilocybin extracts himself and reported vivid subjective experiences that were similar to those of LSD. LSD, psilocin, and psilocybin were all similar to serotonin in their molecular structure. 

Psilocybin is a naturally occurring hallucinogen. It exerts neurotoxic effects similar to LSD and has a chemical structure similar to the neurotransmitter serotonin in the human brain. Psilocybin is found as an indole alkaloid (nitrogen-containing organic base) in the fungal (Protista) kingdom. Often it is accompanied by the related alkaloids, psilocin, baeocystin, and norbaeocystin. 

This compound cluster exhibits a two-ring, "open-chained, indolic chemical structure, and in contrast to other psychedelics it is all but inactive when taken orally unless accompanied by certain other compounds. Shortacting tryptamines are closely related to neurotransmitters (such as bufotenine), to MDA (a major botanical source of the snuffs belongs to the nutmeg family), to tryptophan (an essential amino acid produced in human digestion of proteins) and to psilocybin and psilocin (which are tryptamines of longer duration). DMT, the simplest member, occurs normally in the blood, brain and (in higher concentrations) in the cerebrospinal fluid. 

MSTFA and psilocin (see structure 3) react to form the following product ... 

Figure IIB. A space-filling representation of the framework drawing of psilocin depicted in Figure llA. The molecular structures depicted in the figures in this chapter are two-dimensional, line-drawing representations of the molecules that show how the atoms are connected and allow for ready comparison of similarity between molecules. Molecules actually have three-dimensional shapes in which each of the constituent atoms occupies a volume defined by its cloud of electrons. Linus Pauling and two of his colleagues, Robert Corey and Walter Koltun, first developed a form of molecular models to depict the 3-dimensional space-filling aspect of molecules in the way shown in this figure.

When R.G. Wasson, R. Heim and A. Hofmann began their interdisciplinary research program to study the Mexican species of mushrooms and their usage in Mexican mushroom cults, their efforts culminated in a 1958 landmark report that described the isolation, molecular structure and synthesis of the mushrooms active ingredients psilocybin and psilocin. Several years later, these substances were also identified in a species of mushroom in Europe, Psilocybe semilanceata, which became the first in a series of newly discovered species. Since then, psychoactive mushrooms from other genera have been reported with increasing frequency. 

There is quite a body of scientific literature that discusses the changes (increases and well as decreases) of psilocybin and psilocin content in mushrooms as a function of their nutrient diet. And, under the 4-HO-DET entry, I mentioned that the inclusion of an unnatural component into the diet just might produce an unnatural alkaloidal product, with an exploitation of the natural and available enzyme systems that are part of the mycelial structure. 

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