Mannitol psilocin potentiation?

[Loveall]

This 2015 online free article (second attachment) observes increased effects of mushroom extract vs pure psilocin and proposes mannitol as one of the possible contributors to this:

"This similar effectiveness of the interacting hallucinogenic components of tested extracts with 5-HT2A receptors may be correlated with the occurrence of mannitol (present in the tissues of psychotropic mushrooms) that enables a more efficient transportation of the active substances (hallucinogens) into the brain and thus enhanced their total activity [27]."

Reference [27] refers to a muscaria article. Note that mannitol is an antioxidant and may also protect psilocibin in the body (this last bit is just my speculation).

Mannitol seems to be available online, but I'm not sure it would be wise to order it as it is in erowid's watched chemical list according to this post, an extensive list that also contains other seemingly innocuous things such as Vitamin E (?).

Interestingly, mannitol is found in celery (1.8% to 0.9% in fresh leaves and stems respectively if I understand the first attachment please double check me). Also seems to be present in brown algae up to 20% by dry weight, see third attachment. Since it is in brown algae, kelp (available as a supplement) could also be a source, but I'm not sure.

Does anyone have more info on this? What about easy access to mannitol for their own bioassay? Idea would be to test psilocin potentiation. Mannitol is a sugar alcohol that is used by diabetics but it is poorly absorbed by the intestines (but perhaps absorption is non 0 and could cause potentiation effects). As a medicine mannitol can be injected to lower increased intracranial pressure and effects last for 8 hours.

An easy test would be throwing in some celery stems/leaves when making a mushroom tea (a la Bloody Mary ). Or try some kelp supplements beforehand. Worth a try I think.

 

[Loveall]

So mannitol absorption has been studied. In this study 0.56% mannitol oral water solution showed absorption in the intestines with 30% of the ingested mannitol being excreted in the urine (if I understand the study).

Also, it seems like mannitol is now a days easily available as a sweetener despite what I said in the previous post.

Finally, looking more into it, mannitol does seem to increase the liquid permeability through the brain which I think is why it came be used therapeutically to relieve craneal pressure (also used for glaucoma). I'm not a professional and am just speculation here based on what I read.

So it could be possible that using a health food supplement we may be able to help our favorite molecules cross the brain as indicated by the rats with the twitching heads.

Seems like this is worth a test. Starting with low doses and carefully. Mannitol LD50 in Rats is ~15g/kg and therapeutic doses in humans intravenously is ~1g/kg (no one should start this high, this is just an FYI reference).

 

[downwardsfromzero]

Will this also apply to similar polyols such as xylitol, sorbitol or erythritol?

It is most definitely worth a test - it might be possible to turbocharge the Lemontek that little bit more :shock:

Thanks for the information!

 

[Loveall]

Will this also apply to similar polyols such as xylitol, sorbitol or erythritol?

It is most definitely worth a test - it might be possible to turbocharge the Lemontek that little bit more :shock:

Thanks for the information!

Good question. Sorbitol does have osmotherapy applications so it may work too if mannitol does. Not sure about the others.

Also, interestingly, mannitol presence is maximum in fruit bodies before the sporulation stage in both portobello and oyster mushrooms (reference). Cubensis may follow the same trend (?). If we do find mannitol helps psilocin cross the blood-brain barrier, the mannitol mushroom cycle may be part of the reason that picking mushrooms before the caps open is important (suggesting that a way to compensate for picking mushrooms late is to add synthetic mannitol: there may be no effect if mushrooms are picked at the right time since enough mannitol is already naturally present).

Although P. ostreatus and A. bisporus generate mannitol in different ways, trends of accumulation of the polyol in both the mushrooms were similar. Mannitol concentration in P. ostreatus was low in mycelia, optimum in non-sporulating fruit bodies and minimum at the sporulating phase of growth

 

[antares]

Mannitol is an extremely potent osmotic diuretic. Intravenous mannitol is used to treat swelling of the brain in head injuries.

One possible mechanism of action might be simple diuresis leading to reduced plasma water and hence a higher concentration of psilocybin / psilocyin in the blood stream and increased transfer to the brain down this concentration gradient.

The problem is that the diuresis will wreck havoc on your fluid and electrolyte balance and might needlessly put you at risk of a whole load of different problems.

IMHO the best way to potentiate the effect would be the use of a MAOI. The risks are understood and fairly well contained with adequate preparation and caution.

 

[downwardsfromzero]

Mannitol is an extremely potent osmotic diuretic.

This may go some way towards explaining the astonishing diuretic effect I've had from Psilocybe cyanescens sometimes, if that mushroom is capable of producing significant quantities of mannitol. And that was one of the more intense trips I've experienced.

 

[Loveall]

It is most definitely worth a test - it might be possible to turbocharge the Lemontek that little bit more :shock:

Do we know why the lemon Tek works so well? I guess we can say that the acidic environment favors dephosphorilated psilocybin (producing psilocin). Since psilocybin gets metabolized into psilocin by the enzyme alkaline phosphate (link), we could speculate that the lemon tek is more intense since it has already done some of this work for us. On top of that, I guess we could also propose the possibility that Mannitol dehydrogenase enzyme reactions (or simple reduction) may convert mannose into mannitol in the presence of acidic lemon juice (link).

D-mannitol + NAD+ <-> D-mannose + NADH + H+ (lemon tek pushes this to the left?)

I have no idea if this last reaction would happen or not, but thought it may be worth pointing out here.

In short, we are bringing up the possibility that the lemon tek simultaneously produces readily bioavailable psilocin (by phosphorilazing psilocybin for us) and mannitol (by reducing mannose) in solution. Both these end products could work together to very quickly produce effects (that would be a lot of work for a humble lemon!).

I have no evidence for any of this, so it is only speculation. We can try to do some work with TLC to see if we can discard or support any of this. Seems interesting enough to get some experiments going.

It could also be that after a certain amount of mannitol, psilocin entry into the brain is not enhanced further (saturation point). If so, adding mannitol to the already excellent lemon tek may not do much. On the other hand if we are not near that saturation point...

 

[antares]

That is a great idea for a simple psychedelic research project:thumb_up:. You could do a case/control study using a fixed dose of mushrooms (from a single homogenised batch). The case would be lemon tek 30 min, analyse the sample for psilocyin / psilocybin concentrations and then after consumption, take blood samples at 15 min intervals for blood concentrations. Keep a subjective trip record.

The same subject would be his/her own control for the study a few weeks later using mushrooms soaked in plain water for 30 min and similar observations and tests done. This would take variations in metabolism largely out of the equation and verify and quantify the effectiveness of lemon tek.

 

[Loveall]

Attaching a paper that observed an 8x boost to mannitol absorption with lemon juice. This was tested on Caco2 cells (which morphologically and functionally resemble the absorptive cells lining the small intestine).

So if mannitol does help psilocin cross the brain blood barrier as a possibility suggested by the paper from post #1, improved mannitol absorption may be a possible mechanism to explain the reports of more intense trips with the lemon tek.

Any thoughts on this?

At this point I have a big bag of pure mannitol on hand (sold as a sweetener in some health food stores). Will report on any results when I do some tests. Right now it seems that making a glass of lemon juice with mannitol would be a way to address the mannitol absorption concerns mentioned before.

 

[Loveall]

I have not done any test yets, the mannitol supplement remains in the pantry quietly waiting. However, for anyone interested in this topic, this book talks about improving drug blood brain barrier transport using mannitol.

 

[antares]

Thanks for posting that link. Inspired by the snippet of information in the free pages of the book, I did a google search and found a few papers on the subject which have clarified my understanding of how it actually works in enhancing the effect site concentration of the drug. Very interesting but quite obvious in retrospect. Makes me wonder how many more obvious things I am completely missing everyday.

 

[downwardsfromzero]

Thanks for the research - as ever! - Loveall. That's an unexpected (lemon) twist in the tale

 

[Loveall]

Thanks guys. Other than the rat study and the a. muscaria article mention in the first post I have not found other mentions of mannitol possibly helping in the blood brain barrier transport of our favorite molecules. Seems like something we could maybe investigate as a team.

At the very least the sugar alcohol can make the citrus-teks sweeter.