Unexpected Development: A Connection Between Acetylcholine, Menthol, and St. John's Wort?
Here's something for you guys to mull over in the old noggins.
As I mentioned at the end of my last post, St. John's wort gets a lot of its diverse pharmacological effects from action of TRPC6, which is related to the receptors that capsaicin and menthol activate to cause sensations of hot and cold, respectively. I've known about this for some time now, but I had learned of it back before I was really that interested in this set of receptors, since before I started researching them for menthol purposes. Since the recent discussion here had St. John's wort on my mind again, I decided to look more into it and see if I could apply some of my newer knowledge to it.
So, you guys remember that enzyme phospholipase C which is involved in the biosynthesis of endocannabinoids and is activated by both kappa-opioid and muscarinic acetylcholine receptors? It was the basis for me theorizing that there could be a synergy between menthol and cholinergic supplements. Well, as I mentioned... somewhere not too ago in this thread... the way the enzyme works directly is by cleaving phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol. I've looked into some interesting stuff about inositol 1,4,5-trisphosphate before, but I never really knew all that much about diacylglycerol. Today I learned something just oh so nifty. In addition to some other related receptors, diacylglycerol activates TRPC6. So let me reiterate what exactly this means. Acetylcholine enhances imagination and hallucinations, which are a product of dopaminergic activity in the hippocampus. Up until now I didn't really have any ideas about how this worked, at least not directly. But the muscarinic acetylcholine receptors which are known to have these effects activate phospholipase C. Diacylglycerol is released as an end product, and potentially it should activate TRPC6 receptors which are present in the hippocampus. These receptors inhibit the reuptake of dopamine. Ergo, dopaminergic neurotransmission is increased and visualizations/hallucinations/dreams are enhanced. In addition to this, TRPC6 enhances the release of endocannabinoids as well and negatively modulates NMDA receptors, each of which could understandably add to the bizarreness of a dream and increase it's psychedelic-like qualities, while also making the environment more vivid and solid and accounting for the dramatic increase in hypnagogia.
Kappa-opioid receptors are known to lower dopamine levels in high doses, but obviously at the doses we're taking menthol and possibly due to its other mechanisms of action, this effect doesn't come into play. It would be obvious if it were too, because a dysphoric effect would be experienced. As a result, the activation of phospholipase C by menthol could theoretically lead to this exact same enhancement of dopaminergic neurotransmission seen with acetylcholine. This is all just a theory of course, but it seems very logical to me. The tie-in with St. John's wort also becomes very clear at this point. If phospholipase C activation is responsible for even just some of the dream-enhancing effects of menthol and cholinergic supplements, then St. John's wort would actually be working through this exact same pathway, just in a more direct way that's further downstream. Maybe that's part of how it can be such an interesting dream enhancer as well? It would also support the idea of a further synergy between these supplements.
The brain is so fascinating. 
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 Originally Posted by Highlander
Yeah that would be cool. No problem BTW.
Wed May 8th 2013
Dose: Menthodex cough drops (x5) = 74 mg (approx) taken during WBTB
Side Effects: Gripey stomach
Sleep Duration: Before = 5.75 – 6.5 hrs (WBTB 55 min) After = 3.5 hrs (approx) Total = 9.25 – 10 hrs
Cognitive: My overall recall seemed better? I experienced HI/a dream quite easily whilst resting, post WBTB.
Sexual: Yes, a bare-chested (Ex) GF in a bedroom scene.
Atmosphere: A general mixture of themes. A couple of famous people featured also. Nothing really emotional, etc.
Other Comments: The sexual type dream seems a recurrent one where I experience some ‘delay’ or ‘interruption’, or lack of privacy. It is not exclusive to Menthol usage.
There was a varied storyline to the (non-lucid) dreams in general where they seemed to blend together, although nothing really stood out as such.
Before taking the Menthol, pre-WBTB, It was a bit of a warm evening, inc. in bed initially which may have influenced my sleeping pattern.
I have had better results when taking a much lower dose of Menthol, especially when coupled with a low dose of Vitamin B6 (10 mg) which I often combine during WBTB.
T.O.T.P. The radio. CPR demo, etc - Dream Journals - Lucid Dreaming - Dream Views
Hooray, the new format! I think it looks good enough for now. 
Since you mentioned it, and especially since we know about menthol and menthone directly stimulating dopamine release now, taking a lower dose and combining it with B6, which is used in dopamine biosynthesis, makes sense that it would provide better results. Keep in mind that there's probably a dosage curve where when the kappa-opioid receptor activity gets too strong the dopamine levels will probably start to drop back down, so now that we know more about it it's probably best to really start figuring out the perfect dose to go with!
 Originally Posted by NyxCC
All right, my first menthol experiment got a bit scrambled.  I planned to do a WBTB and then take the p.oil tablets, but I took melatonin pre bed and got lucid before the WBTB alarm then woke up. Took the peppermint oil nevertheless but had a hard time falling asleep. Anyways here is the report:
Date: 7th of May
Dose: 2x200mg peppermint oil tablets
Side Effects: mild heartburn
Sleep Duration: 7 hrs
Cognitive: I had some sense of urgency during the dream which incorporated in the scenario where we were looking for a space conference. Overall vivid, had some trouble navigating the flying machine.
Sexual: I did not feel sexual attraction to Justin Bieber! But maybe the alarm clock interfered before any menthol thoughts managed to kick in?
Atmosphere: Dynamic, transitioned to happy
Other Comments: Here is the entry from yesterday, dream3 is after taking the peppermint oil tablets.
Cheetah, flying DILD, Justin Bieber
Oh my, a menthol dream with Justin Bieber in it? It would have been interesting to see what happened if you did get the libido effect. 
If you try again and you still have trouble sleeping, you may want to think about mixing it with another supplement like L-theanine to combat insomnia. It should help boost dopamine levels, too!
 Originally Posted by PeterF
Damn Alyzarin, you'r the doc of the thread 
well i got my update:
btw i'm taking Temazepam (major insomniac) so who knows how it's affecting my sleep
5-8-13
Dose: Halls menthol drops (x4) = 21.6mg right before bed (no method as i passed out right away classes,work, etc...)
Side Effects: None
Sleep Duration: Right about 7 1/2 hours, woke up a few times each less than 2 min.
Cognitive: Overall everything was calm but my recall stayed the same
Sexual: In my main dream i was at the movie theater with a sex buddy of mine & we were getting it on
(I became near lucid when i figured out that she'll never do anything like that in public lol)
Atmosphere: Pretty general, everybody was enjoying themselves
Other Comments: I had a chain of FA (3) don't really remember them but just 2:
1.I was in the middle of a dream when i began to notice all my teeth were falling off & blood everywhere, when i found my self not giving a F i said to my self i'm dreaming then immediately i wake up twice in some random places before i really wake up...
2. when i finally wake up i'm in sleep paralysis i use it as my chance to try & become lucid but while doing this i find the boogieman from Gorillaz  trying to pull apart my dream body? (i'm pretty desensitized from SP also) i become semi-lucid & end up in my childhood home in my bed still paralyzed with the boogie man still there.
Anyways this was the first time using menthol so hopefully i'll better experiences in a few more days!
Hehe, well I have to look after my baby, I can't just start it and then drop the whole thing. 
That sleep paralysis experience sounds awesome. It's a good first go, but I would definitely recommend going with a WBTB next time if you can. I got the menthol effects from taking it at bed myself, but WBTB really does seem to be the better way to go if that's your thing. Just a thought!
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Also, I don't think I said this formally, so welcome to the experiment, you two. I look forward to seeing more of your results!
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