Psychedelic activities

COMMENT I am not sure the serotonin is inhibitory and dopamine excitatory is all that naive. There were clinical studies published where they showed that serotonin agonists could completely suppress the CNS stimulant effects of amphetamine clinically in humans. So you may be seeing the same thing. I am not sure that it has to be a psychedelic activity superimposed. It may simply be some kind of a synergistic attenuation. 

There is evidence for Cannabis use as early as 5,000 B.C. in Central Europe and there are probable references to it in the earliest writings of China and Egypt. The frozen tombs of the inhabitants of Siberia in about 500 B.C. have yielded quantities of seeds along with a variety of devices for burning them. A very hot, dry climate appears necessary for producing grass with high psychedelic activity, which may account for the failure to use Cannabis as an intoxicant in Northwestern Europe. ... 

Convert indole to indolyl-3-methyl-ketone (I) by treating indolyl-Mg-Br (preparation already described) with acetyl-Cl, by treating indole in POCl3 with dimethylacetamide (Vilsmeier reaction), or by reacting indole with diketene (ACS 22,1064(1968)). 15.9 g (1) in 50 ml methanol cool, stir and add dropwise 16 g Br2. Reflux 1 Vi hours on water bath cool, filter, wash with ether and recrystallize-methanol to get 18 g indolyl-3-Br-methyl-ketone (II). Dissolve 11.9 g (II) in 60 ml warm isopropanol and add 11 g 3 8% aqueous DMA (or equimoiar amount other amine) reflux one hour on water bath. Filter (recrystallize-ethanol) to get 8.5 g indolyl-3-dimethylamino-methyl ketone (III). Add 4.6 g (0.02 M) (III) in 30 ml tetrahydrofuran to 2.3 g lithium aluminum hydride in 50 ml tetrahydrofuran, stir one-half hour at room temperature and reflux two hours. Add a little water dropwise and extract the precipitate with acetone. Dry, evaporate in vacuum the combined organic phases to get an oil which will precipitate with ether-petroleum ether to give DMT. (Ill) should be tested for psychedelic activity. Dialkyltryptamines BCSJ 11,221 (1936), BSC 2291 (1966)... 

The various cocaine precursors and analogs seem not to have been tested for psychedelic activity. Cogentin (benzo-tropane) is hallucinogenic at a dose of about 4 mg. Synthetic compounds which may have activity are -pseudo-cocaine, tropacocaine, eccaine,... 

EXTENSIONS AND COMMENTARY The two aromatic ring positions that are associated with human psychedelic activity are the 4-position (of psilocybin fame) and the 5-position (of 5-methoxy-this-and-that fame). Here is a compound with both positions oxygen-substituted (with the methylenedioxy ring that is so effective in the phenethylamine world) and it has not been looked at in man, to my knowledge. I snooped around in the literature associated with this kind of DMT substitution, and the world of di-oxygen substitution to be found at these two potent focal points is almost unknown. Aside from the 4,5-methylenedioxy-diisopropyltryptamine,... 

Hofmann and his co-workers had made several tests of the psychedelic activity of their own extracts, both as broad spectrum mixtures and also of the separated alkaloids, but their self-administered dosages had not reliably produced much more than minor effects. Our first goal would therefore be to obtain an extract which, when taken in a dose roughly equivalent to that used in native ceremonies, produced some effects of significance. We based our extraction procedures both on published analytical work, on generally accepted... 

Test for psychedelic activity. Dissolve 4 g (VII) and 2.5 g KOH in 12 ml ethanol and reflux eight hours. Dissolve in 20 ml water, acidify with dilute HCI and evaporate to dryness. Dissolve residue in hot ethanol and evaporate to get 3 g 5-aminomethyl-3-methoxy-isoxazole (Vlll). Test for activity. 1 g (VIII) in 10 ml glacial acetic acid and 4.5 g HBr and reflux one hour. Evaporate in vacuum to get muscimole. 

S) Sub-threshold psychedelic activity has not been demonstrated, however. 

X) Toxic signs of toxicity appear at dosage levels below which psychedelic activity appears. 

O) Other than psychedelic activity other than psychedelic activity has been demonstrated. These "other" activities include such things as anti-depressant, analgesic, anorexic, adrenergic bronchodilator, stimulant and antitussive. 

X signs of toxicity below active level P physical more than mental 0 other, non-psychedelic activity F synthesis not finished... 

Myristicin is reported to have psychedelic activities as well as toxic properties (see nutmeg), and apiole is reported to have antipyretic properties (merck). 

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