Psilocin and Psilocybin

semperviva it has been demonstrated that tryptophan is a precursor of psilocybin (93a). It was simultaneously suggested that a similar oxidation of tryptophan or a tryptophan metabolite at the 4-position constitutes an important intermediate stage in the biosynthesis of the ergot alkaloids from tryptophan. 

Since the discovery of 5-hydroxytryptamine (serotonin, enteramine, thrombocytin) (VII), and the demonstration of its physiological activity and its important function as a neurohormone, the possibility of its occurrence in plants has attracted much attention. It was first shown to be present in Mucuna pruriens DC. (cowhage), and is probably responsible for the intense irritation which results when cowhage comes into contact with the skin (94). This irritation could be a mechanical effect due to the trichomes, but it is more likely to be the result of liberation of 

Several syntheses are on record which avoid the preparation of 5-benzyloxyindole in these procedures, the indole ring is usually formed after provision is made for the introduction of the ethanamine side chain. The first of these (107, 108) was an adaptation of Ewins original trypt-amine synthesis. A subsequent route (109) started from ethyl a-cyano-2,5-dimethoxycinnamate (VIII), which was prepared by condensation of 2,5-dimethoxybenzaldehyde with ethyl cyanoacetate. When this was boiled with potassium cyanide solution, addition of the elements of hydrogen cyanide was accompanied by hydrolysis of the ester function and decarboxylation, to give 2,5-dimethoxyphenylsuccinonitrile (IX). 

Hydrogenation of the latter gave the corresponding diprimary amine (X R = Me), which on demethylation gave the phenol (X R = H). Ferricyanide oxidation then gave 5-hydroxytryptamine in 25% over-all yield from 2,5-dimethoxybenzaldehyde (109). 

The synthesis developed by Abramovitch and Shapiro (110) utilizes the formation of 6-methoxy-l-keto-l, 2,3,4-tetrahydro-/3-carboline (XII) by the Fischer cyclization of the p-methoxyphenylhydrazone (XI) of 2,3-dioxopiperidine. Alkaline hydrolysis of XII and decarboxylation of the product (XIII) gave 5-methoxytryptamine (HO), demethylation of which had previously been reported (103). 

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Compounds with a low relative activity (e.g., DMT, DET, 5 methoxy-DMT) have very little activity orally and must be smoked or sniffed. Unfortunately, these compounds taste and smell like burning plastic when smoked and are harder to smoke than hash. There is, however, no evidence for the notion that they are damaging. With the exception of DMT, DET, psilocin and psilocybin, most of these compounds are probably legal in most states. 

Also known to be hallucinogenic are the indole derivatives psilocin and psilocybin found in the so-called magic mushrooms, Psilocybe species. Ingestion of these small fungi causes visual hallucinations with rapidly changing shapes and colours. Psilocybin is the phosphate of psilocin although based on 4-hydroxytryptamine, they also act on 5-HT receptors. 

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 hallucinogenic principles of magic mushrooms psilocin and psilocybin were selectively detected and quantified in mushrooms samples using HPLC ODS separation coupled with tandem mass spectrometry, reaching detection limits in the picogram range [25]. 

Most of the early syntheses of psilocin and psilocybin employ the O-benzyl ether as a protecting group. This provides more stability to the chemical intermediates, but also requires the additional step of reductive debenzylation. The flow chart of this process is conversion of 4-hydroxyindole to 4-benzyloxyindole via the sodium salt, with benzyl chloride the conversion of this with oxalyl chloride to 4-benzyloxyindole-3-glyoxylchloride the conversion of this to 4-benzyloxy-3-(N,N-dimethyl-glyoxamide with anhydrous dimethylamine the conversion of this to... 

Gordon and Valentine Wasson made the discovery of the psilocybe mushroom, from which Hofmann later isolated psilocin and psilocybin. 

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. 

Schedule 1 Ecstasy, China White, GHB, Heroin (synthetic and natural), Lysergic Acid Diethylamide (LSD), Marijuana, Mescaline, Peyote, Psilocin and Psilocybin (constituents of magic mushrooms)... 

There has been much mention of this test in the psychedelic literature, but it is by no means reliable. Some mushrooms blue only after the first "flush of the fruiting bodies (growth of the fruiting bodies recurs, usually at one-week intervals). Some authors have concluded that this "bluing occurs only in mushrooms containing both psilocin and psilocybin. 

To be aware of the use and control of psilocin- and psilocybin-containing mushrooms. 

To appreciate the methods available for identification and quantification of psilocin and psilocybin in fungal products. 

The legislative control of psilocybin-containing mushrooms is complex under the Misuse of Drugs Act, 1971. Both psilocin and psilocybin (the phosphate ester) are classified as Class A drugs. However, cultivation of the mushrooms which contain these compounds and possession of fresh mushrooms is not deemed an offence under the Act. However, if the materials are deliberately prepared , by,... 

Identification of Psilocin and Psilocybin Using Chemical Analysis... 

Such identification is not possible because the presence of psilocin and psilocybin is observed in many different species of this genus. Coupled to this, it is also not possible to use the ratios of the amounts of these drugs to identify species because such amounts will vary during the day and between days. Therefore, all that is possible with chemical analysis is to demonstrate the presence of the drugs. 

If, following presumptive testing, it is thought that psilocin and psilocybin might be present in the samples under investigation, then TLC is carried out. This allows a decision as to which samples should be further analysed by using the more expensive instrumental methods and which can be excluded at this stage. 

It is necessary to use instrumental techniques to confirm the identity of psilocin and psilocybin if these are thought to be present in the samples under investigation. Of these, GC-MS is the most commonly used method for such confirmatory studies. 

Table 8.2 GC operating conditions and parameters nsed for the GC-MS analysis of the trimethylsUyl ethers of psilocin and psilocybin [2] ...

HPLC can conveniently be used to quantify psilocin and psilocybin in drug samples. As a quantitative method, it has a number of advantages over GC-MS. For example, HPLC does not require any thermal stability of the drug and hence derivatization is not needed. This eliminates the problems associated with ensuring complete derivatization and the risk of sample contamination. Although a number of reported HPLC analytical methods can be found in the literature, we will illustrate the procedure involved by describing a relatively simple method which has been recently reported by Musshoff et al. [4]. 

By using this procedure, it was possible to quantify both psilocin and psilocybin which had been previously identified from GC-MS analysis. 

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