SYNTHESIS : A solution of 0.323 g of lysergic acid diethylamide
(LSD) in 10 mL CHCl3 was diluted with 70 mL
CCl4 and added over the course of 1 h to a refluxing solution of 0.44
g BrCN in 30 mL CCl4 in a nitrogen environment and protected from
direct illumination. After the addition was complete, the reaction was
held at reflux for an additional 6 h, allowed to cool, and washed with
an aqueous solution of tartaric acid. The organic solvents were
removed under vacuum, and the residue dissolved in 70 mL CH2Cl2 and
washed with 50 mL additional tartaric acid solution. The CH2Cl2 phase
was dried with anhydrous Na2SO4, and after removal of the drying agent
by filtration, the solvent was removed under vacuum. The residue was
cleaned up by passage through 5 g of neutral alumina being eluted with
a 9:1 CH2Cl2/MeOH mixture. Centrifugal chromatography with alumina and
CH2Cl2, under a nitrogen atmosphere containing ammonia, provided a
solid product. After recrystallization from IPA or EtOAc, there was
obtained 0.24 g (71%) 6-cyano-nor-LSD
(9,10-didehydro-N,N-diethyl-6-cyanoergoline-8b-carboxamide) with a mp
of 190-191 °C.
To a solution of 0.33 g 6-cyano-nor-LSD in a mixture of 3 mL acetic
acid and 0.6 mL H2O, under a nitrogen atmosphere, there was added 0.6
g powdered zinc and the stirred mixture was heated for 4 h with an
external oil bath maintained at 130 °C. The reaction mixture was
cooled to ice-bath temperature, diluted with an additional 3 mL H2O,
and brought to an alkaline pH with the addition of concentrated
NH4OH. This suspension was extracted with CH2Cl2 (5x10 mL), the pooled
extracts dried with anhydrous Na2SO4, and the solvent removed (after
filtration) under vacuum providing a tan solid. Centrifugal
chromatography (with alumina and a 9:1 CHCl3/MeOH elution solvent
under an ammonia vapor environment), followed by the removal of the
solvent under vacuum, yielded a solid product which was recrystallized
from EtOAc / hexanes. There was thus obtained 0.19 g (61%) of tan
crystals of nor-LSD
(9,10-didehydro-N,N-diethylergoline-8b-carboxamide) with a mp of
196-198 °C (dec.).
To a solution of 66 mg nor-LSD in 2 mL freshly distilled DMF under a
nitrogen atmosphere, there was added 48 mg anhydrous K2CO3 and 38 mg
ethyl iodide. When TLC analysis indicated that the nor-LSD had been
consumed (4 h) all volatiles were removed under a hard vacuum. The
residue was solubilized in CHCl3 (5x5 mL) and the pooled extracts
dried over anhydrous Na2SO4, cleared by filtration, and the solvent
removed under vacuum. The residue was separated into two components by
centrifugal chromatography (alumina, CH2Cl2, nitrogen and ammonia
atmosphere) the first of which was the major product. After removal of
the solvent, this was dissolved in hot benzene, filtered and
cooled. The addition of hexane prompted crystallization of
N-ethyl-nor-LSD (9,10-didehydro-N,N,6-triethylergoline-8b-carboxamide)
as a white crystalline product which weighed 66 mg (61%) after
drying. It had a mp of 108-110 °C and an [a]D + 40.5 (c 0.46,
EtOH).
DOSAGE : 40 to 150 micrograms, orally
DURATION : 8 - 12 hrs
QUALITATIVE COMMENTS : (with 20 µgs, orally) "This has a very
real effect at this level, whereas I have no response at all from LSD
at 20 mikes."
(with 50 µgs, orally) "This is already coming on in fifteen minutes,
and is completely developed in another hour. Very few visual changes
or distortions but easy eyes-closed imagery. Pretty much out after ten
hours; it was a good, repeatable experiment."
(with 60 µgs, orally) "In about an hour or so, gentle movements of the
house plants were noted. The walkway of the painting above the
fireplace changed as if the sunny spots were moving ahead. The visual
aspects became more LSD-like after a couple more hours, though in a
very gentle way. The spider windowpane looked three-dimensional: at
first I thought the windows were double-paned, but they were
not. Stones, rocks and glass had a magical look to them, but tree bark
looked like tree bark. Occasionally, a dark streak (spot) would go
through the visual field and a page of a book would move sharply
without effort. These aspects were very pleasant to me."
(with 75 µgs, orally) "I am up to a ++ within the hour and am feeling
lazy. It is very diuretic and certainly not anorexic. Have been
dieting strenuously for the past 4 days, but could definitely be
interested in food. Also a decongestant. Body feels balanced. Thinking
easy. Concepts easy to follow through. Mind and feelings together as
should be. Definitely a plus two, no further. I wonder if it would be
possible, at any level, to attain that blurring of boundaries that is
the plus three at its best? My mind was at all times capable of
realistic and down-to-earth thought, this is not a material that will
allow you to float two inches off of the floor."
(with 100 µgs, orally) "It sort of sneaks up on you. Certainly not the
push of LSD and, sadly, not the sparkle either. Possible time
slowing. Easy sleep and no price to pay the next day."
(with 150 µgs, orally) "Extraordinary experience, none of the demands
of LSD, just a completely together trip. There were hints of tummy
discomfort and some chills early in the trial, but they were trivial
and quickly passed. Fine music, and fine sex."
EXTENSIONS AND COMMENTARY : What a remarkable compound. It is a
little more potent than LSD, but much less
aggressive in the nature of its action. There appears to be little if
any of the push, the taking control nature, of LSD and a greatly
modified degree of visual distortion. The warmth and humor appears to
be there, but all seems more allowing rather than demanding.
I suspect that this material is rather unstable in solution, even as
the tartrate in dilute saline, although I cannot guess why that should
be. A few months in the dark, at zero degrees and in the absence of
air, led to a very real drop in potency, measured by a control assay
of a freshly made solution of the same nominal concentration.
What a difference a single atom makes, an ethyl rather than a methyl
group at the ring-D nitrogen atom. The absence of any group there (a
hydrogen atom rather than the methyl group of LSD or the ethyl group
of ETH-LAD) is nor-LSD, the synthetic intermediate mentioned in the
preparation recipe above. It has no activity at all even at a half a
milligram. The allyl group at this location gives AL-LAD and the propyl group is PRO-LAD, and both of these are active and
have their own individual entries.
