I’m struggling with post formats bare with me, I’ll add sources and constantly update this post. If anyone has any useful properly sourced information please post it and. I’ll update.

HWBR seeds contain several psychoactive compounds (ergot alkaloids), I will list them below. Nausea is caused via agonisation of the 5-HT3A (serotonin subtype), D2 (dopamine subtype), M3 (muscarinic subtype), and H1 (histamine subtype) receptors. A handful of these compounds are polar and agonise these nausea causing receptors, thus doing non-polar washes does not clean the HBWR seeds of poisons, it just purifies the LSA by removing non-polar alkaloids (that agonise nausea related receptors), polystarchins, and proteins, leading to reduced nausea. Note: without different advanced chromatography techniques or pressure distillation you cannot have pure LSA like most believe, but pure polar full spectrum ergot alkaloids.

** VERY IMPORTANT: AS WE INHIBIT UNWANTED RECEPTORS WE FREE UP MORE ERGOT ALKALOIDS TO ACT ON PSYCHEDELIC RECEPTORS, THUS MAKING THE HBWR STRONGER. **

Below are the ergot alkaloids that have 5-HT3A and/or D2 affinity and their respective 5-HT2A (the psychedelic receptor) pKi. Note: values are depicted in pKi. pKi is a biochemical constant that represents ligand (in our case ergot alkaloids) activity at a receptor site. A pKi < 5 is inactive, pKi = 5-6 is threshold, pKi = 6-7 is moderate activity, pKi = 7-8 is strong activity, pKi > 8 is potent. pKi is different from the Ki value you might come across if you’re browsing scientific journals. pKi is a constant while Ki is a measure of molar activity. pKi values taken from here.

Alkaloid | 5-HT3A | D2 | 5-HT2A
LSA | 6.89 | 7.38 | 7.56
iso-LSA | 6.89 | 7.38 | 6.25
Agroclavine | < 5 | 6.61 | 7.62
Chancoclavine I | < 5 | 6 | 7.74
Chancoclavine II | < 5 | 6 | 7.74
Elymoclavine | < 5 | 7.25 | 7.76
Festuclavine | < 5 | 6.61 | 7.61
Ergometrine | 7.34 | 6.70 | 6.60
Ergometrinine | 7.34 | 6.70 | 6.60
Setoclavine | < 5 | 7.04 | 7.26
Isosetoclavine | < 5 | 7.04 | 7.26
Penniclavine | < 5 | 6.59 | 7.10
Lysergol | < 5 | 7.03 | 6.46
Isolysergol | < 5 | 7.03 | 6.46
compared to LSD
LSD | 0 | 6.05 | 9.06

As we can see LSD has no 5-HT3A activity, threshold D2 activity, and extremely potent 5-HT2A activity.

To stop serotonin and dopamine related nausea we must inhibit the respective receptors with antagonists.

Studied natural 5-HT3A antagonists are:
β-pinene
Boldine
l-menthol
Gingerol

Lemon essential oil contains:
6.6% β-pinene

Peppermint essential oil contains:
35-50% l-menthol
0.55% β-pinene
Boldine (can’t find the %, if anyone knows please share it with the source)

Ginger essential oil contains:
1-2.5% gingerol
0.55% β-pinene

Make yourself a brew with 10 drops off both lemon and ginger essential oil and 5 drops of peppermint essential oil. Drink this 30min before your journey to give the phytochemicals time to work.

** I cannot find a reliable source for natural D2 antagonists, help would be greatly appreciated. **

Next I want to introduce andrenergic receptors. These are split into 5 main types (we won’t get into the subtypes). These are α1, α2, β1, β2, and β3. Ergot alkaloids agonise some of these receptors leading to the unwanted side effects. I will explain each receptor type, then show the pKi for all of the ergot alkaloids. Note: the andrenergic receptors are involved in the sympathetic nervous system, the ‘flight or fight’ response.

α1 - responsible for vasoconstriction.
α2 - responsible for (nor)epinephrine inhibition, leading to lethargy.
β1 - responsible for increased heart rate (HR) and blood pressure (BP).
β2 - responsible for bronchodilation and vasodilation.
β3 - responsible for bladder relaxation, leading to less frequent urination.

* These are not the total responses, just the relevant ones.

Alkaloid | α1 | α2 | β1 | β2
LSA | 6.04 | 7.21 | 6.46 | 5.50
iso-LSA | 8.02 | 6.01 | 6.46 | 5.50
Agroclavine | 6.95 | < 5 | 6.45 | 5.49
Chancoclavine I | 6.76 | 6.24 | < 5 | 6.12
Chancoclavine II | 6.76 | 6.24 | < 5 | 6.12
Elymoclavine | < 5 | < 5 | < 5 | < 5
Festuclavine | 6.94 | < 5 | < 5 | 6.01
Ergometrine | 7.45 | 7.32 | 7.06 | 7.37
Ergometrinine | 7.45 | 7.32 | 7.06 | 7.37
Setoclavine | 6.50 | 5.58 | 7.29 | 5.91
Isosetoclavine | 6.50 | 5.58 | 7.29 | 5.91
Penniclavine | 6.61 | 7.51 | 7.14 | 7.79
Lysergol | 6.86 | 6.14 | 6.93 | 6.16
Isolysergol | 6.86 | 6.14 | 6.93 | 6.16
compared to LSD
LSD | 0 | 0 | 6.85 | 6.13

As we can see LSD has no α1 or α2 affinity, hence no vasoconstriction or lethargy.

We want to inhibit α1 and α2 with antagonists, while agonising β1.

Caffeine’s primary action is as an antagonist of α1 and α2. Fun fact: caffeine is methyltheobromine.

Both caffeine and theobromine act competitively against the neurotransmitter adenosine as adenosine receptor antagonists. Although this isn’t via andrenergic receptors this does cause stimulation and vasodilation.

Because theobromine acts as a phosphodiesterase inhibitor it will indirectly agonise β receptors through signalling cAMP causing more epinephrine to bind to β receptors resulting in vasodilation.

Make yourself a brew with 2 tsp of coffee and 3 tbsp of cacao powder, or alternatively just use kola nut extract. Drink this 20min before the journey so the caffeine and theobromine have time to work. SWIM makes naturopathic tinctures with 400mg of kola nut 10:1 extract dissolved in 8mL of absinthe and adds 40 drops (2mL) of coffea arabica bean essential oil, and uses 5 drops of this.

Last but not least are the muscarinic receptors M1, M2, M3, M4, and M5. As you can probably guess from the name these are the primary receptors muscimol activates (the main psychoactive in Amanita Muscaria).

These receptors are involved in motor function, locomotion, short-term memory, vasodilation, emesis (vomiting), amongst other things.

M3 is involved heavily in emesis. The ergot alkaloids that agonise M3 have a mean pKi of approximately 7. This makes them moderate agonisers. To inhibit muscarinic receptors tropane alkaloids are used in microdoses (ie. scopolamine and hyoscyamine from datura spp.).

Just chew 3 datura stramonium or metel seeds straight after the coffee/cacao brew to allow them to work. This will also free up more ergot alkaloids for psychedelic effects. Note: this is nowhere near the required dose for a psychoactive effect. This will only inhibit muscarinic receptors.

There is very little (but some) histamine receptor agonisation on H1, H2, H3, and H4. I will write about this later when I have time.

Post deleted by writer>>was rude!

Peace

Very useful info thanks for sharing = )

I only had problems with this from time to time and not permanently ... but I am really sure that it would be interesting to try it out. Gonna check out lemon essential oil at first.

And I thought the bad nausea was not from Ergots but from *real* Plant toxins?

Because I was thinking that extracting the Ergot Alks would grant a product free of ill feelings

Maybe I also need to try this, but what I can say is that eating 10+ whole seeds is never a good option for the stomach ...

No lol not under influence just very busy and wrote this in a rush. I’m an accredited naturopath and homeopath with certifications in biochemistry and medicinal chemistry. Just putting research together and SWIM has tried this taking HBWR seeds soaked in room temperature absinthe, drinking the absinthe then having yopo seeds orally with zero nausea. Not too mention Syrian rue extract 30min beforehand. This does work.

Nausea is caused by the influx of serotonin on the 5-HT3A caused by ergot alkaloids, etc. Toxins are a common misconception, but SWIM does a soak in a absinthe for 3 days anyway and drinks that.

Good to know!

So in that other thread you say that you got 10 drops of your lemon essential oil and then you ate 5 COMPLETE (ok no outer shell) seeds of Yopo.

And you did not get ANY (or at least not big) nausea?

Maybe gonna try this out ...

So as far as I understood you say 5 seeds was a moderate dose (combined with 350 mg MAOI) and 10 drops of Lemon Essential oil reduced the nausea to a worthy level?

Gonna try this if it really is that way. But I am having colubrina instead of peregrina, but I guess this should not make a huge difference.

THXX

SWIM also chewed 3 datura metel seeds. Scopolamine microdoses are used as heavy anti-nausea medication. This will provide 78-205μg of scopolamine. This is considering 3 seeds weigh 39mg at reported tropane alkaloid levels of 0.2-0.5%. Source here.

And not 350mg of MAOI, 350mg of Syrian rue extract. I can’t give any recommendations here.

Yo ok, 350 mg Harmalas would be quite high then, so 250 should definetly also be good. And yes you also had those Tropanes, but everything else which I said, is this somehow correct?

5 Yopo Seeds is a quite moderate dose when eaten directly?

Yes for SWM this was subjectively. I cannot speak for others. 5 seeds without the shell correct. SWIM also had 200mg of blue lotus 200:1 extract.

Very nice work of you!

But I wouldn't rely too strongly on the simulated values from Paulke, but more take them as a rough guidance. And an absence of a simulated value does not mean, it is 0, but that they didn't calculate this value.

Therefore e.g. some indicated values by your are not correct:



E.g. if we look up the Ki (not pKi, pKi = –log Ki) values of Alpha1 Alpha2 Beta1 Beta2 from the ki database we get values for LSD of:

Alpha1: 220-380 nM -> pKi of 6.42-6.66
Alpha2: 220-270 nM -> pKi of 6.57-6.66
Beta1: 140 nM -> pKi of 6.85
Beta2: 740 nM -> pKi of 6.13

But already in Paulke's work they do indicate measured in-vitro receptor pKi values for LSD, so I'm a bit puzzled, you sometimes did take them (e.g. for 5HT2) and other times not (like for Alphas). Additionally one shouldn't compare the generalized values for 5HT2 with the specific values for 5HT2A. The LSD pKi for 5HT2A is around 8.6.
But this already stems from Paulke's work, likely as no specific 5HT2A values for ergine were available.




I do not know why they got such sky high values for alphas compared to previous works. So to me at least their values seem not very trustworthy.

Unfortunately Paulke did not simulate LSH, which is often the dominant alkaloid in fresh seeds, and IMHO likely mainly responsible for the typical psychedelic effects.

Also a total alkaloid extraction usually already delivers quite a small amount of nausea, especially if seeds are fresh, as LSA is nauseating in higher dosages itself, and as it seems LSH not so much.




This cannot be mentioned often enough, as there are still many people believing e.g. Kash's tek would deliver pure LSA, and therefore people get the completely wrong impression of the effects LSA has.

Great info - elymoclavine looks promising from the figures, and I've always thought that some members of the clavine group of alkaloids looked promising. Maybe LSA was just us barking up the wrong tree all along.


You won't find boldine in any essential oils as it's a benzylisoquinoline alkaloid.

Named after the Boldo plant, Peumus boldus, a possible source might be the sweet bay tree, Laurus nobilis (J. Nat. Prod. 1982, 45, 5, 560-563), although you'd have to check which plant part, if any, contains a usable amount. (Incidentally, I've found L. nobilis stem bark to be... interesting.)

Well Isbell tested Elymoclavine, but came to the conclusion (Isbell H, Gorodetzky CW. Effect of alkaloids of ololiuqui in man. Psychopharmacologia (1965)).



Maybe Elymoclavine is similar to LSA: So stimulating in very low doses, but sedating in higher doses. Or maybe vice-versa? Unfortunately Isbell did not publish this Elymoclavine study, so we have no idea what dosages were tested.

Also in a synthetic mixture with all the alkaloids as measured in the plant (without LSH) it looked similar (same work):



IMHO either the sedative properties of LSA counteract the other ergolines, or it is really mainly the LSH responsible for the effects most people are looking for.

BTW: In this work are in-vitro measured values for some clavines (Pertz H. - Naturally Occurring Clavines - Antagonism--Partial Agonism at 5-HT 2A Receptors and Antagonism at α 1 -Adrenoceptors in Blood Vessels, 1996 ):



Interestingly this work ("On the pharmacology of the ergot alkaloid elymoclavine", 1984) came to the conclusion that the effects of Elymoclavine are very similar to Bromocriptine.

IMHO a few interesting findings in this study:



So I could guess it works the other way around as LSA. So low dosages are rather sedating, while higher ones are activating. But I really find it interesting that it has such a strong effect to lower blood pressure.




I thought this as basically already busted. I mean every human study on LSA so far clearly showed that it is mainly a non-visual sedativum, getting you into a dreamy state. OK, if you like that, but if you like the typical psychedelic effects, then not what you actually wanna have. But the seeds can be quite visual. As I wrote in my rumblings thread, I'm pretty convinced this is mainly due to LSH. As the difference in visual aspect between unripe seeds and old ones is pretty obvious.