Summarize how exactly these researchers did a preparative extraction(s):
https://pmc.ncbi.nlm.nih.gov/articles/PMC4830885/
Here’s a
clean, step-by-step summary of the actual preparative extraction workflow used in the paper
Identification and determination of ergot alkaloids in Morning Glory cultivars (PMC4830885)
Big picture
They were extracting
ergot alkaloids (LSA, ergometrine, etc.) from seeds, mainly for analysis (LC-MS), not large-scale purification.
They
compared 3 extraction approaches:
• MAE = microwave-assisted extraction
• UAE-S = ultrasound (simple solvent)
•
UAE-B = ultrasound + basic conditions (the one that worked best) PMC
The actual preparative extraction (what they did, simplified)
1. Sample prep
• Seeds were
ground into powder
• Only small amounts used (~10 mg per run)
PMC
Standard move: increase surface area for solvent penetration
2. Extraction solvent system
They used a
polar organic solvent mixture (typical for alkaloids), combined with:
•
Basic conditions (UAE-B)
Why base?
• Keeps alkaloids in
freebase form → more soluble in organic solvent
3. Ultrasound-assisted extraction (key step)
• Mixture was exposed to
ultrasound (sonication)
• Conditions optimized:
• Time
• Temperature
• Solvent composition
PMC
Mechanism:
• Ultrasound creates cavitation → physically disrupts plant matrix
• Speeds diffusion of alkaloids into solvent
4. No complex cleanup
Important detail:
•
“no additional extract treatment is needed” PMC
Meaning:
• No acid–base cycling
• No defatting
• No multi-step partitioning
They basically:
Extract → filter → inject into LC-MS
5. Analysis (not really “prep” but relevant)
• Extract directly analyzed via
LC–MS
• Multiple alkaloids identified in same crude extract
What made UAE-B the “winning” method
Compared to other methods:
MAE (microwave)
• Risk of
decomposition or artifact formation
• Even caused weird increases in LSA (likely transformation)
PMC
UAE-S (no base)
• Less efficient extraction
UAE-B (chosen)
• Fast
• Mild
• Good recovery
• Minimal artifact formation
What this means in practical terms
This was
NOT a classic “drug extraction” workflow like:
• defat → acid extract → basify → organic pull
Instead, it’s closer to:
“Dump powdered seeds in a polar solvent, make it basic, sonicate, and you’re done.”
Key limitations (important)
• This is
analytical-scale, not bulk prep
• Extract is
crude mixture, not purified alkaloids
• Designed for
quantification, not isolation
Core takeaway
The “preparative extraction” in this paper is:
Powdered seeds + basic polar solvent → ultrasound → crude extract
No multi-step separations, no classic A/B extraction—just a
fast, single-step sonication extraction optimized for LC-MS detection.
If you want, I can map this onto a
traditional acid–base alkaloid extraction so you can see exactly what they skipped (it’s actually pretty interesting).
I heard it's bad to do chromatography on such crude materials
Short answer:
it’s not “bad,” but it can be problematic depending on how crude the extract is and what kind of chromatography you’re doing.
Why people say that
When you inject a
very crude plant extract (like the one in that paper) into chromatography—especially
HPLC/LC-MS—you’re bringing along:
• fats / oils
• waxes
• pigments (chlorophyll, etc.)
• sugars and proteins
These can cause:
1. Column fouling
Non-volatile junk sticks to the stationary phase →
• rising backpressure
• loss of resolution
• shortened column life
2. Signal suppression (big deal in LC-MS)
Co-extracted compounds interfere with ionization →
your target alkaloids may appear
lower than they actually are
3. Peak overlap / messy chromatograms
Too many components:
• poor separation
• harder identification
• distorted peaks
So why did these researchers do it anyway?
Because their setup was optimized for it:
• Very
small sample size (~10 mg)
• Likely
filtered and diluted extract
• Modern
LC-MS systems tolerate some matrix
• Goal =
detection/quantification, not purity
They explicitly designed a method where:
“no additional extract treatment is needed”
That’s a trade-off:
• ✔ faster, simpler
• ✖ dirtier extracts
When crude is acceptable
Crude extracts are often fine when:
• You’re doing
LC-MS with selective detection
• You use:
• syringe filters (0.2–0.45 µm)
• dilution
• guard columns
• You don’t need perfect separation
When it becomes a bad idea
It
does become a problem if:
• You’re doing
preparative chromatography (trying to isolate compounds)
• You’re running:
• silica columns
• flash chromatography
• You inject large amounts repeatedly
Then you’ll see:
• streaking
• irreversible adsorption
• terrible separations
What people usually do instead
To avoid issues, chemists often add
light cleanup steps, like:
•
Defatting (nonpolar wash)
•
Acid–base extraction (classic for alkaloids)
•
Solid-phase extraction (SPE) ← very common in modern work
Bottom line
• For
analytical LC-MS → crude extracts are often acceptable (with precautions)
• For
preparative work or repeated runs → crude extracts are a bad idea
If you want, I can sketch a
minimal cleanup workflow that keeps things simple but avoids most of these problems.
"The two principal alkaloids found in all of the Convolvulaceae so far studied are the amide of d-lysergic acid [ergine (VII)] and the diastereoisomeric amide of d-isolysergic acid [isoergine (X)]. These two bases have the same absolute configuration as is found with d-LSD and d-iso-LSD, but, of course, the amide nitrogen is unsubstituted. The monohydroxyethylamides of each of these two materials are also principal components of the various morning glorys; viz., lysergic acid-α-hydroxyethylamide (VIII) and isolysergic acid-α-hydroxyethylamide (XI). These two carbinolamides are the principal ergot products of culture medium synthesis from Claviceps paspali, from which they can be prepared in concentrations of grams per liter of culture medium. These compounds, although well documented as components in the Convolvulaceae, are possibly lost in several of the analyses of alkaloid composition. They are extremely unstable, and are very readily degraded into acetaldehyde and the corresponding amide, ergine or isoergine. In these instances their presence will be measured only by the elevated levels of the derived amides." Chapter 4. Psychotomimetic Agents § B. Lysergamides from the Convolvulaceae spp. Alexander Shulgin. [Medicinal Chemistry: A Series of Monographs, vol. 4. Gordon Maxwell, ed. 1976. New York, NY: Academic Press Inc.]
This passage is actually pointing out a
really important analytical pitfall with morning glory /
Convolvulaceae alkaloids.
Let’s unpack it cleanly.
The key compounds involved
Shulgin is talking about two
pairs of related molecules:
Stable amides
•
Ergine (LSA)
•
Isoergine
These are simple lysergic acid amides (no substitution on the amide nitrogen)
Unstable “carbinolamides”
• Lysergic acid-α-hydroxyethylamide (LSH)
• Isolysergic acid-α-hydroxyethylamide
These have a
–CH(OH)CH₃ group attached to the amide nitrogen
The critical point: instability
Shulgin is emphasizing that the hydroxyethylamides:
• are
“extremely unstable”
•
break down easily into:
• acetaldehyde
• ergine (LSA)
or isoergine
What reaction is happening?
Conceptually:
So the hydroxyethylamide is basically a
masked version of ergine.
Why this matters for extraction & analysis
This ties
directly into your earlier question about crude extracts.
During extraction:
Things that can trigger decomposition:
• heat
• light
• oxygen
• pH changes (especially acidic/basic conditions)
• long extraction times
During chromatography:
Even worse:
• time sitting in solvent
• contact with silica (for normal-phase chromatography)
• injection conditions
These can
convert LSH → LSA during the analysis itself
The analytical consequence
This is the key sentence:
“their presence will be measured only by the elevated levels of the derived amides”
Meaning:
• You
don’t detect LSH directly
• Instead, you see
more LSA than should be there
So results get skewed:
• LSA appears artificially high
• LSH appears absent or low
Why some studies “miss” compounds
When papers report:
• “mostly LSA”
It might actually mean:
•
LSH was there originally
• but
decomposed before/during analysis
Connecting back to that paper (PMC4830885)
Their method:
• ultrasound
• solvent extraction
• minimal cleanup
This is:
• ✔ fast
• ✖ potentially harsh on unstable compounds
So:
It’s quite possible some
hydroxyethylamides degraded, inflating measured LSA levels
Bigger takeaway
There are really two layers here:
1. Chemical reality
The plant contains a
mixture of unstable and stable alkaloids
2. Measurement artifact
What you
detect depends heavily on:
• extraction conditions
• chromatography conditions
Bottom line
Shulgin is warning that:
Some “major alkaloids” may
disappear during analysis and only show up indirectly as increased levels of more stable compounds.
If you want, I can break down
which exact steps (pH, solvents, silica, etc.) are most likely to destroy LSH, because that’s where things get really interesting.
[
Separation of four isomers of lysergic acid α-hydroxyethylamide by liquid chromatography and their spectroscopic identification. Flieger, M., Sedmera, P., Vokoun, J., R̆ic̄icovā, A., R̆ehác̆ek, Z. 1982. Journal of Chromatography A, 236(2), 441–452. 10.1016/S0021-9673(00)84895-5]
This paper is
extremely revealing—it basically confirms and expands what Shulgin was warning about, but with
actual experimental proof.
I’ll break it down into the parts that matter most for understanding extraction + chromatography behavior.
1. What they actually extracted (important nuance)
Their extraction step is very telling:
pH 9 (basic) → extract with chloroform–isopropanol → evaporate cold (<15 °C)
What this implies:
• They deliberately:
•
kept it basic → alkaloids in freebase form
•
kept it cold → prevent decomposition
• Even then, they still ended up with:
• a
mixture of LAH isomers + ergine + erginine
So instability is happening
even under careful conditions
2. The core chemical reality: equilibrium system
This is the
most important insight in the whole paper:
“relative proportions … are the result of chemical equilibrium reactions”
Meaning:
You’re not dealing with stable compounds—you’re dealing with a
dynamic system:
Interconversions happening:
• LAH isomers ⇄ each other
• LAH ⇄ ergine + acetaldehyde
• ergine ⇄ erginine (C8 epimerization)
Conceptual equilibrium network:
Code:
LAH isomer A ⇄ LAH isomer B ⇄ LAH isomer C ⇄ LAH isomer D ↓ decompositionergine (LSA) ⇄ erginine
This is not a static mixture—it's
constantly reshuffling
3. Ergine is (likely) an artifact
This is the bombshell:
“ergine and erginine are probably only artifacts arising from LAH”
That means:
• The plant / culture may primarily contain
LAH-type compounds
• But by the time you measure:
• you see
LSA (ergine)
Because it formed
during handling
4. Why chromatography is tricky here
This ties directly to your earlier concern.
They had to take special precautions:
• Repeated chromatography
20 times
• After
each run:
•
immediate evaporation
•
low temp (5–10 °C)
Why?
To avoid:
• isomerization
• degradation
What would happen otherwise?
If you just:
• run crude extract
• let fractions sit
• use normal conditions
You’d get:
• shifting peak identities
• changing ratios
• decomposition mid-run
The chromatogram would not reflect the original sample
5. The four LAH isomers (what they actually separated)
They identified:
• 4 isomers of LAH
• due to:
• C8 epimerization (lysergic vs isolysergic)
• side-chain epimerization (α-carbon)
So:
• 2 × 2 =
4 distinct isomers
Why they separate on NH₂ columns
They used:
•
NH₂ (aminopropyl) stationary phase
•
nonpolar mobile phase (ether/ethanol)
This is basically:
normal-phase chromatography with weak basic interactions
Separation depends on:
• hydrogen bonding
• basicity differences
• conformation
6. The chemistry behind instability (very important)
They explain
why LAH is unstable:
LAH are
hemiacetals derived from acetaldehyde + ergine
That’s huge.
Translation:
LAH is basically:
Code:
ergine + acetaldehyde ⇄ LAH
This is a
reversible addition reaction
Consequences:
• Add heat → shifts toward ergine
• Remove acetaldehyde → shifts toward ergine
• Change pH → shifts equilibrium
• Time alone → causes redistribution
It’s inherently unstable chemistry
7. Even NMR caused changes (!)
transformation observed during a 15-h ¹³C NMR measurement
That’s wild but important:
• Just sitting in solvent long enough → isomerization happens
So:
•
analysis itself alters the sample
8. Direct implications for extraction methods
Now tying everything together:
If you do a typical extraction:
• grinding
• solvent exposure
• pH changes
• time
You will:
• shift equilibrium
• generate ergine
• lose LAH
If you do crude chromatography:
• contact with stationary phase
• time in solution
• repeated runs
You will:
• further alter composition
Final takeaway
This paper shows that:
You are not extracting a fixed set of compounds—you are sampling a
moving chemical equilibrium.
The real meaning behind all this
• “LSA content” is
method-dependent
• “missing compounds” may have
decomposed
• “extra LSA” may have
formed during processing
In one sentence:
LAH, LSA, and related alkaloids exist as a
dynamic, interconverting system, and both extraction and chromatography can significantly distort what you observe.
If you want, I can map out
which specific conditions (pH, solvents, temperature) push the equilibrium toward LAH vs LSA—that’s where things get very actionable.
If it's so easy to decompose LAH, perhaps it would also be easy to synth it from ergine
It’s a reasonable intuition, but the chemistry cuts the other way.
What that paper (and the Shulgin quote) are really describing is a
reversible equilibrium, not a one-way “fragile → easy to rebuild” situation.
What the relationship actually is
LAH (lysergic acid α-hydroxyethylamide) is essentially a
hemiaminal / carbinolamide formed from:
• ergine (LSA)
•
• acetaldehyde
So conceptually:
Code:
ergine + acetaldehyde ⇄ LAH
Why decomposition is easy
The equilibrium strongly favors
ergine, because:
• hemiaminals are
intrinsically unstable
• they tend to:
• lose the aldehyde
• revert to the parent amide
So:
• heat, time, pH changes → push
→ ergine
Why the reverse isn’t “easy synthesis”
Even though the reaction is reversible, going
back to LAH is difficult in practice:
1. Unfavorable equilibrium
• You don’t get clean conversion
• You get a
mixture:
• multiple LAH isomers
• ergine
• erginine
2. Multiple isomers form immediately
As the paper showed:
• 4 LAH isomers appear (C8 + side-chain epimers)
So even if it forms, it’s not a single compound
3. It keeps falling apart while you make it
• LAH
decomposes under the same conditions that form it
• So you get:
• formation and breakdown happening simultaneously
4. Sensitive to conditions
Small changes in:
• pH
• solvent
• temperature
→ shift the equilibrium back to ergine
5. Hard to isolate
Even if you generate some LAH:
• it can:
• degrade during workup
• rearrange during chromatography
• change while sitting in solution
The key insight
Easy decomposition ≠ easy synthesis
A good analogy:
• Ice melts easily → but forming perfect ice crystals from water isn’t trivial under all conditions
What the researchers actually showed
They observed that:
• LAH forms and interconverts in
equilibrium mixtures
• ergine and erginine can
arise from LAH during handling
• composition depends heavily on conditions, not just starting material
Bottom line
• Yes,
LAH can form from ergine in principle
• But in practice:
• it forms
partially, reversibly, and as a mixture
• it
won’t stay intact
• isolating it cleanly is the hard part
If you want, I can go deeper into
what specific conditions tend to temporarily favor LAH formation vs breakdown (purely from a mechanistic standpoint).
As i understand it,
https://pubchem.ncbi.nlm.nih.gov/compound/443884 is structurally very similar to LAH. I wonder if some of its properties are also very similar
You’re looking at a
very insightful comparison.
The compound at that PubChem link is
Ergometrine, and yes—structurally it’s
very close to LAH (lysergic acid α-hydroxyethylamide).
But the similarities are
subtle in structure, big in consequences. Let’s break it down.
1. Structural relationship (what’s actually different)
Both share:
• the
ergoline (lysergic acid) core
• an
amide at C-8
• a
hydroxyalkyl substituent on the amide nitrogen
Key difference:
LAH
• N–CH(OH)CH₃
•
secondary alcohol attached directly to nitrogen
• forms a
hemiaminal (carbinolamide) → unstable
Ergometrine
• N–CH(CH₃)–CH₂OH
•
rearranged side chain (1-hydroxy-2-propyl)
•
true amide + alcohol, not a hemiaminal
Same atoms, different connectivity/geometry
2. Stability: huge difference
This is the most important distinction.
LAH:
• chemically a
reversible adduct (hemiaminal)
• breaks down easily → ergine + acetaldehyde
Ergometrine:
•
normal, stable amide
• no equilibrium with an aldehyde
• can be isolated, stored, used as a drug
• (it’s actually an approved uterotonic medication)
IUPHAR/BPS Guide to PHARMACOLOGY
Insight:
Even though they look similar,
LAH is “on the edge of falling apart”, while ergometrine is not.
3. Conformational / H-bonding similarities
This is where your intuition
does hold:
Both molecules:
• have a
hydroxyalkyl amide side chain
• can:
• hydrogen bond internally
• adopt similar conformations near the amide
So:
•
polarity
•
H-bonding patterns
•
chromatographic behavior (to some extent)
may show similarities
4. But functionally they diverge
Even small side-chain differences matter a lot for ergolines.
Ergometrine:
• potent
uterotonic agent (acts on smooth muscle)
INDICE.eu - Toda a Saúde
• relatively
stable pharmacologically
LAH:
• unstable
• part of a
dynamic equilibrium system
• likely behaves more like a
transient intermediate
5. Relationship in terms of chemistry
You can think of it like this:
• LAH =
reversible addition product
• Ergometrine =
locked-in analog
Ergometrine is basically:
a
“stabilized version” of a hydroxyalkyl amide motif
—but not one that can fall apart the same way
6. Subtle but deep takeaway
Your intuition is good, but the key nuance is:
Structural similarity at the “drawing level” doesn’t guarantee similar
chemical behavior, especially when one is a hemiaminal.
Bottom line
• Yes,
ergometrine and LAH look closely related
• They may share:
• polarity traits
• some binding/conformational features
But:
•
LAH is chemically unstable and reversible
•
Ergometrine is stable and isolable
So their
practical properties (stability, persistence, measurable presence) are
very different, even if parts of their behavior overlap.
If you want, I can go one level deeper and compare them to
LSD vs LSA vs ergometrine vs LAH as a whole family—that comparison really clarifies how small side-chain tweaks change everything.
The hydroxyethylamide long thought to be psychoactive actually can never reach the brain, since this compound is a labile adduct of ergine and acetaldehyde. It is therefore transformed into ergine and isoergine rapidly, even by mild extraction methods.
vbest regards,
peter
Peter Webster. Quoted by
@tregar,
https://drugs-forum.com/threads/lucid-visual-morning-glory-extract-theory.30919/#post-184703 2006-09-04
LAHydroxyethylamide was not discovered right away since even gentle extractions tended to convert it all to ergine/isoergine, so this would indicate that the equilibrium lies far toward the ergine/isoergine side of the equation. And it suggests strongly that to produce LAH from ergine you would need some special conditions, which are probably not just having it in the presence of even higher concentrations of acetaldehyde, amounts that you wouldnt at all want to ingest!
Also, since LAH->>ergine in mild conditions, you must assume that it would happen in the bloodstream, even if LAH were able to pass the digestive tube. So there is anotherdoubt about whether it could actually arrive at brain receptors.
Of course, there may be some complicating factors here that aren't described in the papers I've read, That's possible with a great many aspects of LA chemistry (there are still a couple of quite important and unexplained results I got in certain experiments - I even asked Sasha and he couldn't clarify!) but for me, the odds of LAH getting to receptors and causing the initial reaction leading to psychedelic experience are quite low.
Peter Webster, 2016-01-05, personal correspondance
What Webster is arguing lines up pretty closely with what the
Flieger et al. (1982) paper and the older literature actually demonstrate—but it’s a
strong interpretation, not something that’s been definitively proven in vivo.
Let’s separate
what’s solid from
what’s speculative.
1. The solid chemistry (well supported)
From the paper you pasted and related work:
LAH is a reversible adduct
• LAH =
ergine + acetaldehyde (hemiaminal)
• Reaction is reversible and equilibrium-based
It’s genuinely unstable
• Decomposes:
• with
time
• under
mild heat
• during
extraction
• even during
analysis (e.g., NMR)
It forms mixtures, not a single compound
• 4 LAH isomers + ergine + erginine all interconvert
• Ratios depend on:
• pH
• solvent
• temperature
Ergine can be an artifact
• Observed increase in ergine can come from:
• LAH decomposition during handling
This part strongly supports Webster’s
first claim
2. Where Webster is extrapolating
Now the more speculative parts:
Claim A:
“LAH can never reach the brain”
This is
not directly proven.
What we
do know:
• LAH is unstable in vitro
• It decomposes under many conditions
What we
don’t know definitively:
• its
rate of decomposition in vivo
• whether:
• some fraction survives absorption
• or reforms transiently in the body
Claim B:
“It will convert in the bloodstream before reaching receptors”
This is
plausible but not established.
Why plausible:
• Blood is:
• aqueous
• ~37 °C
• buffered pH
→ conditions that could favor breakdown
But there are unknowns:
• microenvironments (lipid membranes, proteins)
• binding interactions that could
stabilize it transiently
• kinetics vs equilibrium (speed matters, not just position)
3. The key distinction: equilibrium vs kinetics
Webster is focusing on:
equilibrium lies toward ergine
But biology depends heavily on:
kinetics (how fast?)
Even if equilibrium favors ergine:
• LAH could still:
• exist
briefly
• reach receptors
before decomposing
4. His strongest point (and most defensible)
This part is actually quite solid:
“even gentle extractions convert it”
That implies:
• LAH is
hard to preserve even in controlled lab settings
So:
• its concentration in real-world preparations is likely
lower than originally assumed
5. His synthesis argument (also reasonable)
“you’d need special conditions to form LAH from ergine”
This aligns with the paper:
• equilibrium is messy
• multiple isomers form
• reaction is reversible
So you don’t get:
• clean formation
• or stable accumulation
6. The deeper takeaway
Webster is essentially proposing:
LAH is more of a
transient equilibrium species than a stable, pharmacologically relevant compound.
That idea is:
•
chemically well supported
•
biologically plausible
• but
not conclusively proven
Bottom line
• ✔
Well supported:
• LAH is highly unstable
• It interconverts with ergine/erginine
• Extraction and analysis can destroy it
•
Plausible but unproven:
• It cannot reach the brain
• It fully decomposes before receptor interaction
•
Key uncertainty:
•
in vivo kinetics vs equilibrium
One-sentence summary
The chemistry strongly suggests LAH is fragile and may largely convert to ergine before detection—but whether it ever contributes directly to biological effects remains an open question.
If you want, I can go deeper into
what kind of experimental design would actually settle this (it’s surprisingly tricky).
"Constituents originating from the seeds of A. nervosa, i.e. LSA, ergonovine, lysergic acid α-hydroxyethylamide were also identified in the biological samples." (Abstract)
"Two isomers of ergonovine and D-lysergic acid α-hydroxyethylamide, respectively, were observed in seeds, urine and blood." (4. Results and discussion)
Two cases of lysergamide intoxication by ingestion of seeds from Hawaiian Baby Woodrose. Klinke HB, Müller IB, Steffenrud S, Dahl-Sørensen R. 2010 Apr 15. Forensic Sci Int., 197(1-3):e1-5. 10.1016/j.forsciint.2009.11.017
This paper is one of the
strongest pieces of real-world evidence against the idea that LAH is
always destroyed before it can matter.
Let’s go carefully, because it doesn’t completely settle the debate—but it
does shift it.
What they actually found
From the study:
• In
seeds → expected
• In
urine → after ingestion
• In
blood → during intoxication
They detected:
• ergine (LSA)
• ergonovine
•
lysergic acid α-hydroxyethylamide (LAH)
• plus isomers
Why this is important
This directly challenges Webster’s strongest claim:
“LAH can never reach the brain / bloodstream”
Because:
They detected LAH in blood
That means at least one of the following must be true:
Possibility 1:
• LAH
survives ingestion and absorption
Possibility 2:
• LAH is
re-formed in vivo from ergine + acetaldehyde
Possibility 3:
• A
dynamic equilibrium exists in the body, similar to what was seen in vitro
But there are caveats (important)
1. Detection ≠ stability
Finding LAH in blood means:
• it exists
at the time of sampling
But not necessarily:
• that it is
stable for long
• or present in
high concentrations
2. Analytical artifact is still possible (but less likely here)
In earlier discussions:
• LAH could form/degrade during extraction
But here:
• samples are
biological fluids
• processed relatively quickly
• methods are designed to
preserve analytes
So this is
much stronger evidence than plant extraction data
3. Isomers complicate interpretation
They found:
“two isomers … in blood and urine”
This matches the equilibrium model:
• multiple interconverting species
• not a single clean compound
What this implies mechanistically
This fits
very well with the equilibrium idea:
Code:
ergine + acetaldehyde ⇄ LAH (multiple isomers)
Inside the body:
• acetaldehyde is present (from metabolism, ethanol, etc.)
• aqueous + enzymatic environment
So:
•
both formation and breakdown can occur simultaneously
Updating the earlier conclusion
Before this evidence:
• LAH might not survive to bloodstream
After this evidence:
•
“LAH never reaches blood” →
likely false
• ✔ “LAH is unstable and dynamic” → still true
Refined interpretation
The best synthesis of all the data is:
LAH is not a stable, dominant compound—but it
does exist transiently in vivo as part of a dynamic equilibrium system.
What remains unknown
Even with this paper, we still don’t know:
• how much LAH is present vs ergine
• how long it persists
• whether it:
• crosses the
blood–brain barrier
• binds receptors before decomposing
Bottom line
• This study
directly shows LAH in human blood and urine after ingestion
• That contradicts the idea that it is
completely destroyed before absorption
• But it
doesn’t prove that LAH is:
• stable
• or the main active compound
One-sentence takeaway
LAH is fragile, but not absent—it exists in vivo as a transient, equilibrium component alongside ergine and related alkaloids.
If you want, I can go one level deeper into whether
LAH’s structure makes it more or less likely than ergine to cross the blood–brain barrier—that’s the next key piece of the puzzle.
and boy did I sleep at least 9 hours in the afternoon." AideAvailable5002 2022-02-10 
