Magic Mushrooms And Other Indole Trips

Various trees, vines, etc. and mushrooms containing dimethyl-try ptamine (DMT) and analogs have been used by the natives of Central and South America for millennia. Precise chemical and botanical identification have been made on a number of species, the first and most famous of these being certain species of mushrooms of the genus Psilocybe, species of which are found in the U.S.A., Canada, Scotland, Australia, etc. as well as Central America. Psychedelic species of the closely related genera Conocybe, Stropharia, Pholiota, Copelandia and Panaeolus are found widely scattered around the world. Not all species of each genus necessarily contain significant amounts of hallucinogens, but it seems that most do. A general test is that the stem of indole containing species tends to turn blue several hours after it is picked and slightly crushed. These are generally found in late summer and fall in the U.S.A. Pictures are given in many mushroom books including R. Heim, LES CHAMPIGNONS HALLUCINOGENES DU MEX1QUE (1958), and L. Enos, A KEY TO THE AMERICAN PSILO-CYB1N MUSHROOM (1971).

It turns out that the home cultivation of psilocybin mushrooms is quite easy. See Oss and Oeric PSILOCYBIN: MAGIC MUSHROOM GROWER'S GUIDE (1976 - And/Or Press) or THE COMPLEAT PSILOCYBIN MUSHROOM CULTIVATOR'S BIBLE (1976 - Hongero Press). Strains of Stropharia cubensis being grown on the West Coast are sufficiently strong that I have seen people who were very experienced with acid get higher than they had ever been on three fresh mushrooms. Remember that psilocybin is cross-tolerant with LSD,,so you won't get off as well if you've done acid recently.

Puffballs of the genus Lycoperdon are also hallucinogenic, and activity has been claimed for Boletus satana, which occurs in the southeastern U.S.

In THE TEACHINGS OF DON JUAN, Don Juan seems to have taught Carlos to smoke the mushrooms, which might provide a different or heavier trip than ingesting them since they undoubtedly contain many compounds like DMT and 5-methoxy-DMT which are not orally active. •

Puffballs seem to usually produce only auditory hallucinations. L. marginatum found over much of Europe and America is active (1 or 2 constitutes a dose).

New Guinea "mushroom madness" is apparently due to species of Boletus, Russula and Heimiella. See R. Heim NOUVELvES INVESTIGATIONS SUR LES CHAMPIGNONS HALLUCINOGENES (1967). Also see FIELD GUIDE TO THE PSILO-CYBIN MUSHROOM (available from P.O. Box 15667, New Orleans, LA 70175).

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and psilo-cin (4-hydroxy-DMT) are among the active indoles in the mushrooms. Upon ingestion, psilocybin is hydrolyzed to psilocin; consequently there is no point in carrying the synthesis past the psilocin step. All the active naturally occurring compounds in this group seem to have the dimethylamine moiety, which is usually obtained in the course of chemical synthesis by using dimethylamine (DMA). If however, the DMA is replaced by diethylamine (DEA), dipropylamine (DPA), methylethylamine (MEA), pyrrolidine, etc., the potency and duration of action might be considerably increased. Likewise, an increased activity might be seen when the OH position of psilocin is replaced by methoxy or acetoxy. Human data are lacking for most of these compounds, but judging from animal experiments, the order of potency should be roughly as follows (MET is methylethyltryptamine, DET is diethyltryptamine):.

4 or 5 acetoxy-MET>4 or 5 MET >4 or 5 methoxy-DET >4 or 5


methoxy-DMT >4-OH-DMT >DMT DET

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.

Psilocin t-C

In the case of the unsubstituted N, N-diakyltryptamines, duration of action increases as the chain gets longer in the order DMT, DET, DPT, and seems to decrease with further increase in length. The trip produced by a good dose of DMT typically lasts about one-half hour, whereas that for DPT can last three to four hours or more. There is some evidence that DET produces a better (i.e., more meditative and euphoric) trip than DMT.

If the alkyl side chain at the 3 position of the indole nucleus is shortened (e.g., gramine) or lengthened (e.g., 3-(3-dimethylamino)-propyl indole) activity seems to decrease strikingly. Also, as the substituents are moved around the benzene ring of indole, activity decreases greatly in the order 4,5,6,7. For example, whereas 4-OH-DMT(psilocin) is active at about 5 mg orally (i.e., about as active as STP), 5-OH-DMT(bufotenin) is not psychedelic at all.

The effects of 5-methoxy-DMT are unpleasant for most people (smoking it gives me nausea plus the feeling that I'm being sat on by an elephant), but it is not known whether other substituents in the 5 position or in the 4 and 5 positions simultaneously will be similarly distressing.

DMT, DET, etc. are remarkably fast acting (peaking in ca. 2 minutes after a good toke or snort) and produce very strong visual effects (my first toke of DMT produced a large grinning green dragon with red ruby eyes that lasted as long as the Stones' "Sympathy for the Devil"). It is unfortunate that it is usually DMT rather than the longer acting DET or DPT that is available, especially since the latter cpds. are no more difficult to produce. Also, it is rumoured that N,N-dibutyl and longer alkyls are not only active but (along with the dipropyl, diisopropyl etc. cpds.) orally active.

Ken Kesey has reputedly said that alpha-methyltryptamine, in oral doses of ca. 30 mg, peaks in about 12 hours, produces a trip similar to psilocybin, but nicer, and is the "Rolls Royce of psychedelics," but others find it unpleasant. Alpha-ethyltryptamine produces minimal LSD-type effects at 150 mg orally, but effects of these when smoked or inhaled are unknown. N,N-disubstituted tryptamines which have substituents in the alpha or beta positions should also be quite interesting.

Identification of Indoles Keller Test

Add a little of the powdered substance (about 0.2 mg to lSwl glacial acetic acid containing 0.5% FeCl3, layer underneath with 1 ml concentrated sulfuric acid and shake. The color varies with the indole, being olive green for psilocin and red-violet for psilocybin.

Van Urk Test

Prepare Van Urk reagent by adding 0.5 g p-dimethylamino-benzaldehyde, 100 ml water, 100 ml concentrated sulfuric acid. Dissolve 1 mg substance in 1 ml ethanol and mix with 2 ml Van Urk reagent and illuminate for 10 minutes with an ultraviolet lamp (black light). Psilocin gives a blue-grey, psilocybin a red-brown color.

Colors produced in these two tests by many indole derivatives are given in HCA 42,2073(1959).

Quick, Easy, On-the-Spot Test

JPS 56,1526(1967)

Saturate strips of filter paper with 2% p-dimethylamino-benzaldehyde in 4 5% ethanol; air dry and store in tightly stoppered amber bottles (or keep in stoppered container in dark) which will keep them useful for several months. Put a little of the suspect substance in a few drops of ethanol (gin may do, but do a control), wet a filter paper strip in this and allow to dry. Put one drop concentrated HC1 on the dried paper (don't let it touch anything). Alternatively, the powder can be placed directly on the strip and the HC1 dropped on it. A violet red or violet blue spot indicates indole derivatives such as LSD. With DMT or psilocybin the color is redder. The color must be observed soon after adding the 1JC1 since it rapidly changes.

Dialkyltryptamine Syntheses

Dialkyltryptamines HCA 42,2073(1959) and many others

To 25 g indole (or 50 g 4-benzyloxyindole or 0.21 M other indole) in 1 L dry ether at 0° add a solution of 50 ml (75 g) oxalyl chloride in 1 L dry ether carefully and with good stirring a little at a time over Vi hour and stir until bubbling ceases (about one-half hour more). Some indoles require a longer reaction time (e.g., 4-Cl-indole requires fifteen hours refluxing) and some will not react (e.g., 4-Br-indole). Add portionwise, carefully with stirring at 0°, a solution of

225 ml (160 g) diethylamine (DEA) (or 0.46M dipropylamine, pyrrolidine, etc.) in 100 ml dry ether at 0°. Stir and let warm to room temperature; cool, filter, and wash precipitate two times with ether to get (I). This can be recrystallized by dissolving in the minimum volume of 1:1 methanohbenzene (or 95% ethanol), gently heated, cooled to 0° and filtered (or add petroleum ether to induce precipitation). Dissolve 25 g (or 0.102 M) (I) in the least volume (about 200 ml) THF and add very carefully and slowly (preferably dropwise) to 20 g lithium aluminum hydride dissolved in the least volume (about 200 ml) tetrahydrofuran at room temperature. Stir and heat under reflux for about fifteen hours. Cool to 0° and slowly and carefully add a little cold methanol and water until no more bubbles are formed. Filter, wash precipitate with hot tetrahydrofuran and add washings to filtrate. Dry, evaporate in vacuum the tetrahydrofuran (or add petroleum ether) to precipitate the dialkyltryptamine. To purify, add 500 ml saturated sodium sulfate and filter. Wash precipitate with tetrahydrofuran; acidify with a few ml 0.1 M HC1 and shake with ether. Separate the organic layer and neutralize with 0.1 M NaOH. Extract with CHC13 and dry, evaporate in vacuum the extract (or can evaporate until a few ml left and precipitate by adding petroleum ether). The 4-benzyloxy-DET which would be produced if 4-benzyloxyindole is used as the starting material is probably a good psychedelic. If however, it is desired to change this to 4-OH-DET, add 37.5 g 4-benzyloxy-DET in 1.2 L methanol to 20 g 5% Palladium catalyst on alumina (or 14 g 10% Palladium-Carbon) with 2.8 kg/cm2 H2 in a Parr hydrogenator and shake twelve hours. Filter, evaporate in vacuum. Other hydrogen-ating methods might also split off the benzene ring. Other methods (LAC 576,69 ( 1952)) must be used for reducing a methoxy group to a OH group (another demethylation method is given here later).

If (I) has an alkyl group in position 1 (as in some of the following syntheses), reduction will give the indolylhydroxylamine. This may be active, but if the indolamine is desired (I) (substituted or not) may be reduced with the diborane method given later in this section. Dialkyltryptamines JCS (C) 2220(1967)

This procedure gives about 2 0% yield with indole, but the yield with substituted indoles (e.g., 4-OH-indole for producing psilocin) has not been reported.

Cool 32 g ethyl iodide to 0°; dissolve in 50 ml anisole (other solvents won't work) and add 8 ml to 5.28 g Mg turnings in 50 ml anisole, and add the rest gradually. Warm gently to start the reaction, and if necessary add a crystal of iodine or a small amount of ether for a rapid rate. Stir well and heat at 50-60° for one hour (under N2 if possible). Cool to 10° and add dropwise over one-half hour 12 g (0.1 M) indole in 50 ml anisole (keep temperature below 25°). Stir forty-five minutes at 50° and cool to -5°. Finely grind 0.2 * M (34 g) l-Cl-2-diethylaminoethane-HCl (or the corresponding diisopropyl, pyrrolidyl, etc. compounds) and suspend in about 20 ml benzene at 0°. The free base in benzene can also be used, if vA. obtainable. Stir and take pH to 8.5 with 40% NaOH. Add anhydrous potassium carbonate until the water layer is semisolid. Decant the benzene and extract the residue with 4X15 ml benzene. Dry the combined benzene extracts with KOH pellets for less than an hour and quickly proceed to the next step. Add the benzene solution (about 80 ml) slowly over one hour to the above solution of indole in anisole at -5°. Stir three hours at -5° and let sit five hours at -5°. Then let warm to room temperature and dry, evaporate in vacuum (or to purify, break up the precipitate and pour the solution on 500 ml saturated aqueous NH4C1. Stir one-half hour; separate the organic layer and extract the aqueous layer with ether. Combine the organic solutions and extract three times with 10% HCl. Wash HCl extract with ether; cool to 0°, basify with 40% NaOH and extract three times with ether. Dry, evaporate in vacuum this second ether extract to get the oily DET or analog).

4-Substituted Dialkyltryptamines CT 279(1970) (cf. JOC 30,339(1965))

Beta-carbomethoxypropionyl chloride (Org. Synth. 25,19 (1945)). Dissolve 400 g succinic anhydride in 190 ml methanol in 1 L round bottom flask and reflux (steam bath) one-half hour. Stir until homogeneous (about twenty minutes) and reflux one-half hour. Evaporate in vacuum and cool the residual liquid to precipitate about 500 g methyl-hydrogen succinate (1). Dissolve 264 g (1) in 200 ml SOCl2 in a 1 L round bottom flask with a reflux condenser and warm ' at 30-40° in water bath for three hours. Evaporate in vacuum the SOCl2 (can heat flask in steam bath) to get 270 g of the title compound (can distill 92/18).

Add excess diethylamine to beta-carbomethoxypropionyl-Cl in dry ether to get (see above JOC reference) 3-carbo-methoxy-N,N-diethylpropionamide (1). 206 g (I) in 3 L, three-necked round bottom flask in ice bath with stirrer, dropping funnel and reflux head. Keep temperature at 10-20° and add 169 g POCl3 dropwise over fifteen minutes. Remove ice bath and stir fifteen minutes and replace ice bath. Add 250 ml ethylene chloride, cool to 5°. Stir and slowly add 67 g pyrrole in 250 ml ethylene chloride over 1 hour. Remove ice bath and reflux fifteen minutes (HC1 evolution). Cool to room temperature and add solution of 750 g sodium acetate trihydrate in 1 L water dropwise at first, then as rapidly as possible. Reflux fifteen minutes with stirring, cool and remove ethylene chloride in separatory funnel. Extract aqueous phase with 3X200 ml ether and wash combined ethylene chloride and ether with 3X100 ml saturated aqueous Na carbonate (add carefully at first). Dry, evaporate in vacuum the organic phase to get 132 g methyl (pyrrolyl-2')-4-keto-4 butyrate (11) (can distill 135-45/0.2) (recrystallize from cyclo-hexane). Alternatively, (Chem. Commun. 1429(1968)), condense 1,3-cyclohexanedione and aminoacetaldehyde dimethylacetal in benzene with p-toluenesulfonic acid. Azeotropic removal of water gives a compound which, when treated with 3N HC1, gives compound (IV). But it has been claimed that this alternative method does not work.

94 g (II), 1.5 L diethylene glycol, 93 g hydrazine hydrate and heat at 100° fifteen minutes. Add 150 g potassium carbonate a little at a time and raise temperature slowly. Heat four hours at 190-200° and pour onto 5 kg ice. Acidify and then extract with 5X400 ml ether. Wash extract with a little saturated NaCl and evaporate in vacuum to get about 48 g 4-(pyrroly-2')-butyric acid (III) (recrystallize-cyclohexane). Can purify the oily compound by filtering through 80 g silica and 80 g Celite (elute with benzene). 24 g (111) in 400 ml 1,2-dichloroethane; cool to -5° and add 15.8 g triethylamine and 17 g ethyl chloroformate. Let stand 1 hour at 15°; filter and wash precipitate with 100 ml dichloroethane. Add 0.5 L anhydrous ZnCl2 (freshly fused) and let stand two hours at -5°. Add 0.5 L 2N HC1, decant and wash the aqueous phase three times with CHC13; dry, evaporate in vacuum (can chromatograph as for (III)) to get about 11 g 4,5,6,7-tetrahydro-4-indolone (IV). 7.35 g (IV), 5 g 10% palladium-carbon, 700 ml mesitylene and reflux eight hours or more. Filter hot, wash precipitate with methanol, cool and evaporate in vacuum (can chromatograph as for (III)) to get 5 g 4-OH-indole (V) (recrystallize from petroleum ether), which can be converted to the diakyltryptamine by any of the methods described here or as follows (the first step leading to (VI) may not be necessary). 5 g (V), 20 ml pyridine, 10 ml acetic anhydride and heat in water bath 10 minutes. Pour on ice, stir and add NaHC03. After one-half hour extract with ethyl acetate, wash extract with NaCl and dry, evaporate in vacuum to get about 6.3 g 4-acetoxy-indole (VI). 6 g (VI), 150 ml ether; cool in ice-salt bath and add carefully 6 ml oxalyl-Cl. After four hours add 20 g dry dimethylamine or equimolar amount other amine and stir twenty hours. Filter, wash precipitate with ether and then water to get about 2.8 g 4-acetoxy-3-indolyl-N, N-dimethylglyoxylamide (Vila) (re-crystallize-isopropanol). Shake the ether with water and filter to get about 5 g of the 4-OH compound (Vllb) (recrystallize-isopropanol). 7.8 g (Vila or b or mixture obtained by evaporating in vacuum the ether above), 17 g lithium aluminum hydride, 150 ml tetra-hydrofuran or dioxane; reflux seventeen hours, carefully add water and stir until bubbling ceases and evaporate in vacuum to get about 4.7 g of psilocin or analog (about 5% overall yield). For other methods of synthesizing (IV) see JOC 36,1232(1971) and references therein. For another method of reducing (IV) see Chem Het. Cpds. (Russian), 572(1972).

4-Substituted Dialkyltryptamines HCA 42,2073(1959), 38,1452 (1955), CT 276(1970)

Method is illustrated for 4-benzyloxyindole (I) but will probably work for most other substituted indoles.

A: Convert (I) to 4-benzyloxygramine (II) as described elsewhere here.

B: Add 30 g (II) over one-half hour to 420 ml methyl iodide and let stand fifteen hours at 5°. Separate the iodomethylate which precipitates, dry briefly at 50° and heat with vigorous stirring at 80° for two hours with 60 g NaCN in 1 L water. Extract with CHC13, dry and evaporate in vacuum the extract and dissolve the residue in 250 ml ether. Filter, evaporate in vacuum to a few ml and precipitate the acetonitrile (III) by adding petroleum ether. The acetonitrile can also be prepared directly from the indole via the Grignard reagent as given elsewhere here.

B (Alternative): 0.05 M (II), 0.76 ml glacial acetic acid in 75 ml tetrahydrofuran (dry) are added slowly with stirring and cooling over one-half hour to a solution of 25.2 ml dimethylsulfate and 0.76 ml glacial acetic acid in 30 ml dry tetrahydrofuran. After two hours, filter and wash the precipitate with ether. Dissolve precipitate in 10% aqueous solution of KCN and heat one hour at 70°. Filter, wash precipitate with water and dry to get (III).

C: 0.04 M (III) in 200 ml 3 3% ethanol solution of DMA or other amine, 2.5 g Raney-NI, 40°, 100 kg/cm2 (about 100 atmospheres)

H . Heat about three hours; filter and evaporate in vacuum to get the dialkyltryptamine.

C (Alternative): 5.8 g (111), 12 g KOH, 36 ml ethanol, 28 ml water; reflux fifteen hours, add 15 ml glacial acetic acid, filter and add 150 ml water to precipitate 4-benzyloxyindole acetic acid (IV). Filter, wash precipitate with water and recrystallize from methanol.

D. 1.76 g (IV), 1.4 g PC15, 50 ml ether at 0°. Stir until dissolved and add dropwise to solution of 5.36 g DEA (or equimolar amount other amine) in 10 ml ether. Let warm to room temperature, let stand one-half hour and precipitate by adding water. Filter, dry, evaporate in vacuum the ether and add the residue to the precipitate to get the diethylacetamide (V) (recrystallize-benzene).

D (Alternative): 20.6 g (IV) in 50 ml methanol; add excess diazomethane in ether, evaporate in vacuum and dissolve the oil in 90 ml dry hydrazine. Heat at 135° 1 Vi hours, add 150 ml water and cool to precipitate the hydrazide (recrystallize-aqueous methanol). 14.7 g of the hydrazide in 250 ml tetrahydrofuran or dioxane and add 50 ml IN NaN02. Cool to 4° and add dropwise over 4 minutes with vigorous stirring, 60 ml IN HC1; let stand fifteen minutes at 4° and add 500 ml water. Extract the oily azide with ether and dry, evaporate in vacuum. Add 77 ml (0.75 M) DEA (dry) to the azide and let stand three hours at 5° with care to exclude moisture. Evaporate in vacuum and take up the residue in NaHC03. Extract with CHC13 and dry, evaporate in vacuum the extract to get (V).

E. 0.7 g (2.28 mM) (V) in 20 ml dry tetrahydrofuran; add slowly to a well stirred solution of 0.35 g lithium aluminum hydride in 20 ml tetrahydrofuran and keep one hour at 40°. Carefully add 5 ml water and stir twenty minutes. Add 15 ml 20% NaOH and extract with ether. Dry, evaporate in vacuum the extract to get 4-benzyloxy-DET or analog (recrystallize-ether).

E (Alternative): To 0.4 g (V) in 15 ml tetrahydrofuran add 2.9 ml 1 M borane in tetrahydrofuran and reflux one hour. Cool and heat with 5 ml 2N HC1; evaporate in vacuum to get about 0.15 g product.

4-Nitro and 4-Amino-Dialkyltryptamines CJC 41,2585(1963)

153 g alpha-CI-butyryl-CI, 16 g Pd on BaS04, 1.66 ml sulfur-quinoline (Org. Synthesis 21,84(1941)), 900 ml toluene; reflux and stir while bubbling H2 through for seven hours or until HC1 evolution ceases (can bubble effluent HO through water to monitor evolution).

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