Study hints at modulating influence of secondary compounds in mushrooms vs pure psilocybin

[Bancopuma]

An interesting study I'd not seen before now.

Study:

Matshushima, Y., Shirota, O., Kikura-Hanajiri, R., Gosa, Y. & Eguchi, F. et al. (2009) Effects of Psilocybe argentipes on Marble-Burying Behaviour in Mice. Bioscience, Biotechnology, and Biochemistry, 73,8: 1866-8.

https://pdfs.semanticscholar.org/27db/ba7610194971742f8adf5a8dde8e3b06addb.pdf?fbclid=IwAR2ld6CQCuz3ax1mDPe4qO8sstDrMyrrS92AUiUy6eN4u7tEmIX0r5mvkBQ

Abstract

Psilocybe argentipes is a hallucinogenic mushroom. The present study examined the effects of P. argentipes on marble-burying behavior, which is considered an animal model of obsessive-compulsive disorder. P. argentipes significantly inhibited marble-burying behavior without affecting locomotor activity as compared with the same dose of authentic psilocybin. These findings suggest that P. argentipes would be efficient in clinical obsessive-compulsive disorder therapy.

...we obviously need to be cautious when attempting to extrapolate and infer from animal model studies (in this case an animal model of OCD), but I thought this was quite an interesting finding:

"In the experiments, when mice consumed P. subcaerulipes, it significantly inhibited their marble-burying behavior, but, unlike an equivalent dose of purified psilocybin, did not affect locomotor activity. Further, the mushroom was more effective than purified psilocybin in inhibiting the behavior, and lower doses were required. Based on these results, the authors suggest that the mushroom has the potential "to be efficient in clinical obsessive-compulsive disorder therapy".

This is at the very least suggestive that there could be secondary compounds in the mushroom that modulate or synergise with the psilocybin in mushrooms to some degree, beneficially in this case (even if it is the presence of psilocybin/serotonin precursors in the mushroom) and these compounds may be lacking when ingesting pure synthetic psilocybin. Much of the psilocybin mushroom potency data is out of date, and more research on the potential modulating influence of secondary compounds found in mushrooms (such as baeocystin/norbaeocystin and others) is certainly warranted.

 

[Loveall]

Thanks for posting this. Looks like they used freeze dried mycelium dissolved in water to dose the rats. I can't find their HPLS results, did I miss it?

I have noticed fresh mushrooms seem different vs. dry.

There is probably a lot of stuff going on which we don't understand. This study is puzzling. An interesting mistery to look into.

 

[fathomlessness]

so the ocd mice are less prone to losing their marbles? :d

has any study conclusively looked at the alkaloids within Psilocybe argentipes?

 

[endlessness]

Interesting, thanks for sharing bancopuma!

so the ocd mice are less prone to losing their marbles? :d

:lol:

has any study conclusively looked at the alkaloids within Psilocybe argentipes?

This paper says they have found, appart from psilocybin, another substance in Psilocybe argentipes which the author thought might be baeocystin but hasnt confirmed the id. They also found 3 other non-psychoactive substances: ergosterol, ergosterol peroxide and a,a,-trehalose.


As for the original study posted in this thread, and in relation to the difference between psilocybin vs full mushroom, it seems dosage is significant... At the lowest dose of mushroom studied, which is 0.05g/kg (equivalent of 3.5g mushrooms for a 70kg human), there is a reduction from around 20 marbles to 15 marbles buried, but the equivalent 0.025mg/kg of pure psilocybin also reduced the same.

The difference is only really significant at higher doses, but from the data presented its hard to know what is the exact the dosage that the difference appears significant in marble-burying, because the mushroom dosage graph shows data for increases from 0.05 to 0.1 (or equivalent from 3.5g to 7g in humans), but the psilocybin dosage graph increases from 0.025mg/kg to 5x that amount, 0.125mg/kg, or in humans equivalent to 3.5g to 17.5g). That's a large gap. Would be nice to have more data on intermediate dosages for pure psilocybin.

Another interesting thing that the original paper claims is that the effect is probably not related to the hallucinogenic effects because it is not exactly dose-dependent (or at least it is only dose-dependant up to a certain dosage, then it stops reducing the marble-burying numbers), so they think it is not 5-HT2a mediated.

I might be nitpicking but one thing I found a bit of a stretch is that they say

"Hallucinogenic mushrooms pro-duce a wide variety of tryptamine derivatives other than psilocybin. Some of these, such as psilocin, baeocystin, norbaeocystin, bufotenin, and aerginascin, have psychoactive effects, although many hallucinogeni cmushrooms produce smaller amounts of them than psilocybin. These findings suggest that inhibition of marble-burying behavior by P. argentipesis due to the involvement of a variety of psychoactive substances"

. I think it is not correct to assume "a variety of substances" just because some (other) species of mushrooms show a variety of substances. Those mentioned substances have certainly not all been found in all psilocybin-containing mushrooms. Taken that together with the fact the analysis paper I linked earlier only shown one extra psychoactive substance, potentially baeocystin, I think a more honest assessment imo would say "these findings suggest ...... due to the involvement of one or more psychoactivesubstances". The next step for this research should be to include baeocystin in tests with psilocybin, as well as further analyse the mushrooms they have with LC-MS or similar, to find what other compounds are there.

What do we know anything about baeocystin pharmacology?

 

[dragonrider]

I already suggested in one of the NMT threads, that the fact that the presence of NMT in acacia can alter and enhance the effects of DMT, could be explained by receptor modulation.

I even started a thread about this very topic of receptor modulation once.

The problem is that it is quite a complicated mechanism, and it is difficult to do an experiment to confirm this hypothesis. You would have to have a substance that does nothing other than modulating one or more receptors a psychedelic is active on.

The reason i'm so interested in receptor modulation, is that i am convinced that i have experienced the effects of it on a few occasions. And on two such instances the effects where quite powerfull. In one case even extremely powerfull.

The only reason why i haven't done more experiments with the receptor modulating mechanism i experienced, is that i found the effects too unpredictable. However, i am currently growing morning glories (wich i believe contain very powerfull modulators, but only when they're fresh), and if they produce seeds at the end of this summer, i intent to do some of these experiments again. The modulating effects of some lysergamines may even be more powerfull than those of NMT and NMT derived compounds like baeocystin.

 

[Legarto Rey]

Indeed whole plant(fungus) "potions" often contain myriad related bio-active compounds that may synergize or antagonize(psychedelic effects) in ways that are complex. Most would agree that subtle, or not so subtle subjective effects are obvious when compared to isolated compounds.

Receptor binding site affinities are just the start. Consider agonistic/antagonistic allosteric effects at the entire receptor complex, in which dynamic conformational changes to the receptor complex may inhibit/activate across a spectrum. Similar allosteric dynamism is at play within enzymatic systems that are separate from, but intimately related to what is transpiring at particular receptors. The complexity is astounding. And fun to investigate via "bio-assay"!

Peace

 

[dragonrider]

Indeed whole plant(fungus) "potions" often contain myriad related bio-active compounds that may synergize or antagonize(psychedelic effects) in ways that are complex. Most would agree that subtle, or not so subtle subjective effects are obvious when compared to isolated compounds.

Receptor binding site affinities are just the start. Consider agonistic/antagonistic allosteric effects at the entire receptor complex, in which dynamic conformational changes to the receptor complex may inhibit/activate across a spectrum. Similar allosteric dynamism is at play within enzymatic systems that are separate from, but intimately related to what is transpiring at particular receptors. The complexity is astounding. And fun to investigate via "bio-assay"!

Peace

I once took 1P-LSD with some fresh morning glory seeds. The trip started normally, but after one and a half hours, i suddenly, wooosh, was catapulted out of my body. Visuals became weirder, brighter, more complex and more colourfull, and i started to hear loud, flanging jet-engine noises.

As these effects came very suddenly, and more than an hour after the 1P-LSD had kicked in, i think these effects cannot be attributed to anything other than the seeds. But the amount of seeds (somewhere around 30 morning glory seeds) by itself was by far not enough, to generate such effects.

So these effects had to be the result of the synergy between the 1P-LSD and the seeds, i think.

But how to explain this weird synergy? I think allosteric modulation of some of the receptors LSD is active on, is the most plausible explanation.
This effect could also explain the synergy between DMT and NMT, as NMT does not even seem to be active enough by itself, though it seems to be less dramatic there.