SYNTHESIS: A solution of 5.8 g of homosyringonitrile (see under E for its synthesis), 100 mg decyltriethylammonium iodide, and 10 g n-propyl bromide in 50 mL anhydrous acetone was treated with 6.9 g finely powdered anhydrous K2CO3 and held at reflux for 10 h. An additional 5 g of n-propyl bromide was added to the mixture, and the refluxing continued for another 48 h. The mixture was filtered, the solids washed with acetone, and the combined filtrate and washes stripped of solvent under vacuum. The residue was suspended in acidified H2O, and extracted 3×175 mL CH2Cl2. The pooled extracts were washed with 2×50 mL 5% NaOH, once with dilute HCl (which lightened the color of the extract) and then stripped of solvent under vacuum giving 9.0 g of a deep yellow oil. This was distilled at 132–142 °C at 0.3 mm/Hg to yield 4.8 g of 3,5-dimethoxy-4-n-propoxyphenylacetonitrile as a clear yellow oil. Anal. (C13H17NO3) C H N.
A solution of 4.7 g 3,5-dimethoxy-4-n-propoxyphenylacetonitrile in 20 mL THF was treated with 2.4 g powdered sodium borohydride. To this well-stirred suspension there was added, dropwise, 1.5 mL trifluoroacetic acid. There was a vigorous gas evolution from the exothermic reaction. Stirring was continued for 1 h, then all was poured into 300 mL H2O. This was acidified cautiously with dilute H2SO4, and washed with 2×75 mL CH2Cl2. The aqueous phase was made basic with dilute NaOH, extracted with 2×75 mL CH2Cl2, the extracts pooled, and the solvent removed under vacuum. The residue was distilled at 115–125 °C at 0.3 mm/Hg to give 1.5 mL of a colorless oil which upon dissolving in 5 mL IPA, neutralizing with 27 drops concentrated HCl, and dilution with 25 mL anhydrous Et2O yielded 1.5 g 3,5-dimethoxy-4-n-propoxyphenethylamine hydrochloride (P) as spectacular white crystals. The catalytic hydrogenation process for reducing the nitrile (see under E) also succeeded with this material. The mp was 170–172 °C. Anal. (C13H22ClNO3) C,H,N.
DOSAGE: 30–60 mg.
DURATION: 8–12 h.
QUALITATIVE COMMENTS: (with 30 mg) “Proscaline dulled my sense of pain and made the other senses really sharp. Everything felt really soft, and clean and clear. I could feel every hair my hand was touching. I felt so relaxed and at ease. I know that under the appropriate circumstances, this material would lead to uninhibited eroticism.”
(with 35 mg) “The whole experiment was very quiet. There was no nystagmus, no anorexia, and insignificant visuals with the eyes closed. I was restless with a bit of tremor for the first couple of hours, and then became drowsy. Would I do this again? Probably not. It doesn’t seem to offer anything except speculation about the nature of the high. The high was pleasant, but quite uneventful.”
(with 40 mg) “For me there was a deep feeling of peace and contentment. The euphoria grows in intensity for several hours and remains for the rest of the day making this one of the most enjoyable experiences I have ever had. It was marvelous talking and joking with the others. However, I was a little disappointed that there was no enhanced clarity and no deep realizations. There was not a problem to be found. There were no motivations to discuss anything serious. If I had any objection, it would be with the name, not the pharmacology.”
(with 60 mg) “The development of the intoxication was complete in a couple of hours. I feel that there is more physical effect than mental, in that there is considerable irritability. This should probably be the maximum dose. Despite feeling quite drunk, my thinking seems straight. The effects were already waning by the fifth hour, but sleep was not possible until after the twelth hour. There was no hangover the next day.”
EXTENSIONS AND COMMENTARY: There is a very early report describing the human use of proscaline tucked away in the Czechoslovakian literature that describes experiments at up to 80 milligrams. At these dosages, there were reported some difficulty with dreams, and the residual effects were still apparent even after 12 hours.
The amphetamine homologue of proscaline, 3,5-dimethoxy-4-n-propoxyamphetamine is an unexplored compound. Its synthesis could not be achieved in parallel to the description given for P. Rather, the propylation of syringaldehyde to give 3,5-dimethoxy-4-n-propoxybenzaldehyde, followed by coupling with nitroethane and the reduction of the formed nitrostyrene with lithium aluminum hydride would be the logical process. Following the reasoning given under E, the initials for this base would be 3C-P, and I would guess it would be active, and a psychedelic, in the 20 to 40 milligram range.
Nichols, DE; Dyer, DC. Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues. J. Med. Chem., 1 Jan 1977, 20 (2), 299–301. 409 kB. doi:10.1021/jm00212a022
Nichols, DE; Shulgin, AT; Dyer, DC. Directional lipophilic character in a series of psychotomimetic phenethylamine derivatives. Life Sci., 1 Jan 1977, 21 (4), 569–576. 320 kB.
Glennon, RA; Kier, LB; Shulgin, AT. Molecular connectivity analysis of hallucinogenic mescaline analogs. J. Pharm. Sci., 1 Jan 1979, 68 (7), 906–907. 252 kB. doi:10.1002/jps.2600680733
Jacob, P; Shulgin, AT. Sulfur analogues of psychotomimetic agents. 3. Ethyl homologues of mescaline and their monothioanalogues. J. Med. Chem., 1 Jan 1984, 27 (7), 881–887. 1213 kB. doi:10.1021/jm00373a013
Altun, A; Golcuk, K; Kumru, M; Jalbout, AF. Electron-conformation study for the structure-hallucinogenic activity relationships of phenylalkylamines. Bioorg. Med. Chem., 1 Dec 2003, 11 (24), 3861–3868. 577 kB. doi:10.1016/S0968-0896(03)00437-1
Meyers-Riggs, B. Leminger’s scalines. countyourculture: rational exploration of the underground, 4 May 2012.
This version of Book II of PiHKAL is based on the Erowid online version, originally transcribed by Simson Garfinkle and converted into HTML by Lamont Granquist. I drew also on “Tyrone Slothrop’s” (Unfinished) Review of PIHKAL to enumerate the many analogues mentioned in PiHKAL but not described at length. Still others remain to be added.
I have tried here to expunge any artifacts introduced by the earlier transcriptions and restore most of the typographic niceties found in the printed edition. I’ve also made minor changes to some chemical names in line with current nomenclature practice, and in the hope of aligning with more readers’ searches. Typically the change is little more than expanding a prefix and setting it in italics. The errata and changes page has further details.
“At the present time, restrictive laws are in force in the United States and it is very difficult for researchers to abide by the regulations which govern efforts to obtain legal approval to do work with these compounds in human beings.
“No one who is lacking legal authorization should attempt the synthesis of any of the compounds described in these files, with the intent to give them to man. To do so is to risk legal action which might lead to the tragic ruination of a life. It should also be noted that any person anywhere who experiments on himself, or on another human being, with any of the drugs described herein, without being familiar with that drug’s action and aware of the physical and/or mental disturbance or harm it might cause, is acting irresponsibly and immorally, whether or not he is doing so within the bounds of the law.”
Alexander T. Shulgin
The copyright for Book I of PiHKAL has been reserved in all forms and it may not be distributed. Book II of PiHKAL may be distributed for non-commercial reproduction provided that the introductory information, copyright notice, cautionary notice and ordering information remain attached.
PiHKAL is the extraordinary record of the authors’ years exploring the chemistry and transformational power of phenethylamines. This book belongs in the library of anyone seeking a rational, enlightened and candid perspective on psychedelic drugs.
Although Sasha and Ann have put Book II of PiHKAL in the public domain, available to anyone, I strongly encourage you to buy a copy. We owe them—and there’s still nothing quite like holding a real book in your hands.
PiHKAL (ISBN 0-9630096-0-5) is available for US$24.50 (plus $10 domestic first-class shipping) from Transform Press.Transform Press,