SYNTHESIS: To a solution of 13.6 g homosyringonitrile (see under
ESCALINE for its preparation) in 150 mL acetone containing 200 mg
decyltriethylammonium iodide and 30 g of finely powdered anhydrous
K2CO3, there was added 20 g methyl iodide. The mixture was held at
reflux for 18 h in a heating mantle with effective stirring. This was
added to 1 L H2O, acidified with concentrated HCl, and extracted with
3x75 mL CH2Cl2. The extracts were pooled, washed with 2x100 mL 5%
NaOH, once with dilute HCl, once with saturated brine, and the solvent
was removed under vacuum. The pale yellow residue was distilled at
130-150 °C at 0.3 mm/Hg to yield 12.9 g of
3,4,5-trimethoxyphenylacetonitrile as an off-white solid. Upon
crystallization from methylcyclohexane/CHCl3 it was white and had a mp
of 77-78 °C. Attempts to prepare this compound by the theoretically
appealing route from 3,4,5-trimethoxybenzaldehyde to
N,N-dimethyl-3,4,5-tri-methoxybenzylamine (reductive amination with
dimethylamine), to 3,4,5-trimethoxy-N,N,N-trimethylbenzylammonium
iodide (methylation with methyl iodide), and then to 3,4,5-
trimethoxyphenylacetonitrile (with some source of cyanide ion) gave
excellent yields in the first two steps, and no product at all in the
last step.
A solution of 20.6 g of 3,4,5-trimethoxphenylacetonitrile in 70 g
pyridine was treated with 15 mL 99+% D2O and held at reflux for 24 h.
All volatiles were stripped first under vacuum and finally with a hard
vacuum at room temperature in a Kugelrohr apparatus. The dark residue
was treated again with another 30 mL pyridine and another 15 mL 99+%
D2O. The flask was protected with a drying tube and held at reflux
for another 24 h. Again, all volatiles were stripped, and the residue
distilled at 110-130 °C at 0.25 mm/Hg to yield 16.77 g of an almost
white solid. The GCMS verified this chemical to be
3,4,5-trimethoxy-beta,beta-dideuterophenylacetonitrile, with a parent peak
at m/e 209 and no visible peak at m/e 207.
A solution of 250 mL of 1 M LAH in THF was cooled under He to 0 °C and
treated with 6.8 mL 100% H2SO4 added very slowly with vigorous
stirring. A solution of 18.23 g
3,4,5-trimethoxy-beta,beta-dideuterophenyl-acetonitrile in 200 mL anhydrous
THF was added slowly, and following the addition stirring was
continued for 20 min. The reaction mixture was brought to a reflux
for 30 min on a steam bath, cooled again to 0 °C, and the excess
hydride destroyed with 15 mL IPA. About 10 mL of 15% NaOH was
required to convert the solids to a filterable white consistency.
These were removed by filtration, the cake washed with IPA, the
filtrates and washes were combined, and the solvent removed under
vacuum leaving 17 g of a white oil as residue. This was dissolved in
2 L dilute H2SO4, washed with 3x75 mL CH2Cl2, made basic with aqueous
NaOH, and then extracted with 3x75 mL CH2Cl2. Removal of the solvent
from these extracts under vacuum yielded 10.3 g of a colorless oil
which was distilled at 120-130 °C at 0.3 mm/Hg to provide 9.2 g of a
white oil. This was dissolved in 50 ml IPA and neutralized with
concentrated HCl, producing spontaneous crystals. These were diluted
with 50 mL anhydrous Et2O, removed by filtration, washed first with
Et2O/IPA, and then with anhydrous Et2O. After air drying, the final
yield of 3,4,5-trimethoxy-beta,beta-dideuterophenethylamine hydrochloride
(beta-D) was 10.0 g of white needles.
DOSAGE: 200 - 400 mg (as the sulfate salt); 178 - 356 mg (as the
hydrochloride salt).
DURATION: 12 h.
QUALITATIVE COMMENTS: (with 200 mg) The onset was very gradual and
very gentle. At about an hour and a half I was rather out of my body
(at least I wasn't aware of my body, it felt so light). I was
listening to Berlioz Requiem, and it took me to the highest realm. I
was totally caught up in the magnificence of the music, of the genius
it took to compose it, the love it took to complete it, and the
devotion of the composer. I felt as though this music had been
written for me. What came next is hard to remember because I was so
taken with this experience which came only 1 1/2 hours after
ingestion. I wondered what time it was and how come I was having a
peak experience so soon, because this material was supposed to reach
its peak after two hours. Well, now we can revise the records, heh?
Incidentally this material is really good for interior work. It was a
magnificent experience--one of the best.
(with 275 mg) I begin to feel it in 15 minutes, stomach getting
squeamish. Looking up into the clouds, becoming absorbed in them,
watching light grow in intensity, stomach feelings disappeared.
Became totally absorbed by the music. Listening to Boito's Prologue
to Mephistopheles--exquisitely beautiful, dramatic. Lying on the
couch, the music continuing, I was suddenly filled with enormous
power. I realized that raw, male power was pouring through me as I
had never before experienced it. I was wild, totally self satisfied,
and completely oblivious of others and their needs. I wanted to
strike out, to win, to conquer. I felt what conquerers have felt in
the past, the unbridled passion to vanquish everything. I could see
how such misguided power could lead nations to war. Wanting still
more power, I was about to find out if God would grant me the power to
destroy the world if I wished it, when I felt a gentle kiss on my
brow. My wife had leaned over just in time to save the world.
(with 275 mg) Never had I had such a magnificent appreciation of God.
It was clear that if I minded my business and turned to Him to learn
as I had been doing today, then I could continue to grow and learn in
a most wonderful way. It became crystal clear to me that I didn't
have to help anybody or heal anybody, as everyone can turn directly to
the source for their needs. An earth-shaking experience.
(with 300 mg) I had extreme nausea, and vomited. This had a very
hard impact on me, and I had to retreat with a paranoia that swept
over me without warning. I lay down and let it sweep on, and through
this came several very important insights. At least they were
important to me. It was about the fourth hour before I could emerge
from my retreat, and at that time I knew that I had answered some
troublesome personal problems. It was a satisfactory day, but I
probably shall not repeat it.
(with 350 mg) Strong body awareness started within 15 minutes.
Visual activity started within half an hour. Visuals were typical
kinds, but seemed to arrive earlier. A strong experience of
pleasantness started and continued throughout the experience. I
tended to internalize to some extent. Ended on a water bed at maybe
an hour and a half, pulled covers over me, and went inward with
considerable visuals but not much insight. I felt good about where I
was. I would not mind being there again, so something was going well.
I am not sure how long this continued. The visuals decreased
somewhere around the 5th or 6th hour. After 8 or 9 hours, activity
considerably decreased. I felt quite clear and reasonably centered.
Would I do this again? The answer is yes.
(with 500 mg) I consumed the material over a period of twenty
minutes, and at the 1 hour 45 minute point, haven't had any nausea,
but I am still careful not to bounce around. Am absolutely grounded
even though I am completely into the experience. No more that state
in which it is possible to seriously consider trying to rise two
inches above the floor and skim, as I do so expertly in dreams. As a
matter of fact I haven't had those dreams for some time now. This
material doesn't allow the straddling of realities as does ordinary
mescaline. I know where my realities are, and reality is, basically,
where my center is. Thus I am grounded in the physical reality even
when the doors are open to non-physical levels.
EXTENSIONS AND COMMENTARY: The 4-D and the beta-D are two of five obvious
deuterium isomer derivatives of mescaline. The three remaining are:
(1) 3,5-D (4-methoxy-3,5-bis-trideuteromethoxyphenethylamine); (2)
2,6-D (2,6-di-deutero-3,4,5-trimethoxyphenethylamine); and (3) alpha-D
(alpha,alpha-dideutero-3,4,5-tri-methoxyphenethylamine). I fully expect both
3,5-D and 2,6-D to be indistinguishable from mescaline in effect,
since it is known that not much metabolism takes place in man at these
locations of the molecule.
The last compound, alpha-D, could be quite a different matter. The
principal metabolite of mescaline is 3,4,5-trimethoxyphenylacetic
acid, and this product requires enzymatic attack at the exact position
where the deuteriums will be located. To the extent that they are
harder to remove (come off more slowly or to a lesser degree), to that
extent the molecule will be more potent in man, and the dosage
required for effects will be less. The compound will be easily made
by the reduction of 3,4,5-trimethoxyphenylacetonitrile with lithium
aluminum deuteride. And if there is a believable difference between
alpha-D and mescaline, it will be necessary to synthesize each of the two
optically active alpha-mono-deutero analogs. That will be quite a
challenge.
Some years ago I performed a fascinating series of experiments with
another isotopically labeled mescaline derivative. This was beta-14C
labeled material, which I self-administered on three occasions, at
three different levels. One dosage was with 350 milligrams, a second
a few weeks later was with 4 milligrams, and a third was a few weeks
later yet, with about 60 micrograms. In each case, exactly the same
absolute quantity of radioactivity was administered, so the metabolic
distribution was equally visible. Only the weight dosage was
different. Urinary analysis was run for each experiment for the
presence of unchanged mescaline, and for the primary metabolite,
3,4,5-trimethoxyphenylacetic acid. The smaller the dosage, the
proportionately larger amount of mescaline was oxidized to the
inactive acetic acid, and the smaller amount was excreted in an
unchanged state. It seemed to me that there might be a finite
capacity of the body to oxidatively deaminate mescaline, and at larger
and larger dosages, this capacity became increasingly depleted.
Perhaps this is why mescaline requires such a large dosage to be
effective in man.
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