Serotonin psilocybine

Stijve, T. (1985). Een chemische verkenning van het geslacht Panaeolus. Coolia, 28, 81-89. Stijve, T. (1987). Vorkommen von Serotonin, Psilocybin and Hamstoff in Panaeoloideae. Beitrdge zur Kenntnis der Pilze Mitteleuropas, 3, 229-234. 

Stijve, T. 1987. Vbrkommen von Serotonin, Psilocybin und HarnscofF in Panaeoloi-d.fs.E Beitragezur Kenntnisder Pike Mit-teleuropas 3 229—234. 

This method, although described for indoles, probably also worlds with 5-OH-tryptamine (serotonin), and 5-OH-DMT (bufotenin) with compounds of the latter type, orally active psilocybin analogs will be obtained in one step. Dissolve 5 g 5-OH-indole (or analog) in 25 ml ethanol. Add 5.5 g 33% aqueous dimethylamine (or other amine, e.g., piperidine) and add slowly dropwise with stirring 3.5 g 38% aqueous formaldehyde. Two minutes after the end of the addition shake with water and CHCI3 dry and evaporate in vacuum the CHClj phase to get 5 g oily 4-dimethyl-aminomethyl-5-OH-indole (1) (can chromatograph on 100 g alumina and elute with ethyl acetate). It has been claimed that this method does not work. 

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. 

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... 

Magic mushrooms belong to the genus Psilocybe, and include Psilocybe mexicana and hougshagenii, traditionally considered to be most important, and also Stropharia cubensis and Panaeolus sphinctrinus. These contain psilocybine and psilocine which mimic the action of serotonin. The Mazatec shaman, Maria Sabina, described the effects of the mushrooms as follows This is a world beyond ours, a world that is far away, nearby and invisible. And this is where God lives, where the dead live, the spirits and the saints, a world where... 

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. 

Serotonin (5HT) affects sleep, temperature, sexual behavior, sensory perception, appetite, and mood. There are many serotonin receptors, and activation of each brings about different effects. LSD and psilocybin activate serotonin receptors. 

Mescaline-containing buttons on top of the peyote cactus can be chewed or used to make a tea, or ground into a powder. Mescaline is absorbed rapidly, and effects begin between one-half and two hours after ingestion. Its half-life is six hours. Much of mescaline is excreted unchanged in urine as soon as one hour after use and for up to four days. In animal studies, there is evidence that mescaline passes into the fetus and can induce malformations. Mescaline, LSD, psilocybin, and DMT all activate the same serotonin receptor subtype in the brain. 

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. 

Fig. 2. Representative hallucinogenic drugs which hear structural similarities to some of the monoamine transmitters. It has been hypothesized that these similarities may cause the hallucinogens 10 mimic natural transmitters at synaptic receptors in the brain. Note presence of benzene-ring structure in these substances, a structure that is present in four out of the live monoamines previously shown. Also note presence of indole ring in psilocybin and lyseigic acid diethylamide, a structure that is also present in the monoamines serotonin and histamine...

Psilocybin, a chemically similar naturally occurring molecule, is much less potent than LSD but likely shares aspects of its actions on serotonin neurons once the body converts it into psilocin. Our ancestors probably discovered its source, Psilocybe Mexicana, P. semilanceata, an P. cyanescens, by accident when foraging for edible mushrooms. One can only imagine how unexpected the experience must have been for the first person who inadvertently prepared one of these mushrooms for consumption, bringing new meaning to the phrase dinner and a show. ... 

The complex sensory experience known as hallucinations can, however, occur from other sources besides drugs like LSD or psilocybin, and this fact may shed some light on the nature of the hallucinatory experience, drug-induced or otherwise, and its connection to serotonin. Consider, for example, the following hypothetical scenario ... 

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. 

Psilocybin is a neurotoxin that targets the central nervous system and serotonin receptors in the brain when it is ingested. It is believed that the mushroom produces this bitter toxin as an insecticide to protect itself from predators. 

Though psilocybin is known as a natural hallucinogen and has a reputation of being gentler than LSD, it is still known to cause panic attacks, bad trips, and to precipitate mental illness in some people. In 1998, a study at the Psychiatric University Hospital in Zurich, Switzerland, demonstrated that psilocybin produces a psychosis-like syndrome in healthy humans that is similar to early schizophrenia. The study showed that psilocybin-induced psychosis was due to serotonin-2A receptor activation and was not dependent on dopamine stimulation. 

Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Babler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. NeuroReport 1998 9 3897-3902. 

The psilocybin and psilocin molecular grouping bears a close resemblance to chemicals appearing in the brain. One of the psilocybian analogues is, in fact, one of the closest known compounds to the neurotransmitter serotonin, differing only with respect to the rare substitution just mentioned it is 4- rather than 5-hydroxytryptamine. Psilocin, interestingly, is the nearest relative to bufotenine, once thought a psychoactive compound,... 

In addition to the action of tryptamines on serotonin receptors, there may be indirect effects of psilocybin on dopamine receptors as well. Some people speculate that dopamine is the neurotransmitter most involved in the experience of pleasure—for example, the rush of a cocaine high. The interaction with dopamine may account for some of the intense erotic-ecstatic sensations and feelings that can be part of the psilocybe mushroom effect. 

Tryptophan (fig. 8) is one of the twenty amino acids used by all of life on Earth to build proteins. Although plants, fungi, bacteria, and some other organisms can biosynthesize tryptophan from smaller carbon molecules, humans cannot and must ingest tryptophan as part of their diet. That is, tryptophan is one of the essential amino acids. In fungi and plants, tryptophan is the chemical precursor for the biosynthesis of tryptamines such as DMT and psilocybin. In humans and other animals, tryptophan is the precursor for the synthesis of the neurotransmitter serotonin, 5-hydroxytryptamine (5-HT fig. 9). 

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