OK,

So the other day, yesterday to be precise, I was discussing how my dissertaion was based on drug drug interactions.
In reaction to this, one of my collegues asked me if I had therefore covered grapefruit in the disseration.
I was all like ..."what?"
He went on to explain how there is something in grapefruits which can inhibit certain memebrs of the cytochrome p450 family and hence can effect the metabolism of certain drugs.
Intrigued by this information which i had never come across, i went on to do some further research and came across this page from wiki...

http://en.wikipedia.org/.../Grapefruit_juice_effect

Scrolling through the list of drugs affected, my attention was imediately drawn to psilocybin!!!!

Now, im not an expert in this field and I dont claim to know a great deal on the topic, and thus have brought it up here in order to bring it to the attention of the people in the know, but from my understanding of this, does this not mean that if you were to wash down some of your fungal friends with some grapefruit juice, then the juice would give similar effects to a MAOI i.e potenation and increased duration?

Is Cytochrome P450 3A4 a monoamineoxidase enzyme?
What would happen if you were to eat some shrooms and take a MAOI aswell as some grapefruit juice. Would that result in a super long/potent trip?

Also, the other question which came to mind is, if this works for psilocybin, would it work for other tryptamines too?

Sorry if this has been covered before, but this is something i have never come across!!

Hmm interesting, not heard of this before. Its interesitng as I've heard its very good to wash down cactus with grapefruit juice as it cancels out some of the bitterness...

Also I've read quite a few reports of people that SWEAR that washing down mushrooms with lemon or blackcurrant juice make the resulting trip much stronger...I assumed this was down to the fruit acids converting the psilocybin to psilcybin so it hits you faster and stronger...well with grapefruit you would get these fruit acids and possibly this extra benefit...

Certainly interesting...I think experiments should be conducted!

My thioughts exactly.

Although, if it was the case that it had some kind of MAOI like effects, I find it hard to believe that it isn't already common knowledge in these sorts of sub-cultures?!!

Wow thats interesting stuff. I think I might down a glass of grapefruit juice next time I have shrooms.

Peace,

Macre.

It has not been demonstrated (either in vivo or in vitro) whether Cytochrome P450 3A4 (or CYP3A4) somehow metabolises psilocybin or psilocin. For more information on this enzyme look here. But in a nutshell, this enzyme is not a MAO.

The wikipedia article does not give any reference for the psiloc(yb)in-CYP3A4 interaction, implying that it is hypothetical. Of course, it is worth trying the grapefruit-mushi combo since they may interact in some sort of way.

Thanks for bringing this up!

The Cytochrome P450 A series of enzymes is involved in N-demethylation of various tryptamines. Inhibitors of these enzymes can reduce the ability of your body to metabolize certain tryptamine compounds such as ergot alkaloid used in migraine therapy. Some are also involved in the metabolism of harmaloids although the D kinds are more involved.

Although drinking grapefruit juice with shrooms is most likely harmless purposely trying to inhibit enzymes that are meant to break down drugs and toxins is dangerous for your liver and brain if not done correctly. Strong cytrochrome p450 inhibitors is definitely not recommended. Grapefruit juice again is harmless in this regard.

always been under the impression that it wasn't specifically something in grapefruit, but that all acids potentiate substances, with bases doing the opposite(millk for shrooms). perplexed has FOAFS who suck on lemons/limes while on LSD to give them an extra boost, does it have something to do with it breaking it down faster? *interested*

Not positive, and don't quote me on this. THIS COULD HAVE VERY WELL BEEN PLACEBO..BUT

Some time ago when SWIM was growing mushrooms he had stumbled across this on a number of websites including the shroomery..myth vs. fact at the time.

Anyways afew nights out of the month SWIM tried 3.5g of his Koh Sam's with & without grapefruit juice (around 12oz of juice was consumed while chomping on SWIMs litle friends).

Out of the many times SWIM has done mushrooms the effects have always started within a time window of roughly 30-40 minutes, and afew other times the effects started around 25 minutes or so.

But the one night SWIM consumed the mushrooms with grapefruit juice and the initial effects came on in about 10 mintues. No joke. And not just "ahhhh starting to feel the slight body load, etc" but ..."wow this is hitting SWIM fairly decent for ten minutes!" SWIM was pretty surprised to say the least.

Mushrooms have never hit SWIM in 10 minutes. And around the 15-20 minute mark it was intensifyiny very fast.

All in all interesting.

PEACE

This talk about grapefruit reminded me - so this may be relevant -

There are threads posted on the Shroomery about the use of Black Currant Juice mixed with mushrooms for pontentiating the effects, also reports of mixing in limes and/or lemons. I haven't had the chance to try the combinations myself although, some members have reported anywhere from 2x - 4x potentiation.

I knew a guy who would always grind his shrooms and mix them with orange juice. He said the acidic juice helped break down the shrooms and extracted the alkaloids, so the trip came on sooner and with less nausea.

Could be, it's definitely interesting. Whatever is going on definitely seems to work hehe

SWIM had heard that ascorbic acid seems to convert oxidized psilocin back into an active (the experiment he's thinking of apparently involved an inactive blue brew of psilocybe that seemed to become active with addition of ascorbic acid), or at least help prevent the oxidization of psilocin. SWIM's also heard that certain acids seem to serve as catalysts for the enzymatic processes that convert psilocybin to psilocin. He doesn't have any sources for this, unfortunately.

For DXM, grapefruit seems to work similarly to an SSRI, but SWIM doesn't know just how accurate this common assessment really is. SWIM also recalls that some drug interactions with the compounds found in greapefruit juice can be dangerous, so proceed with caution. Very interesting topic, though.

yes I have found over and over that both ascorbic acid and grapefruit juice taken with mushrooms enhance the trip..it comes on faster and the visuals/visions are stronger..I even made a tea with a bit of apple cider vinegar added once and it seemed to really enhance the trip.

no real chem knowledge here - but grapefruit juice seems to do the trick with mu - that or lime juice - both seem to do something orange juice doesnt.
speed of onset and increase of fx.

This is due to Blackcurrant acting as a MAOI. The MAOI activity is not much to speak of compared to the Harmala-alkaloids, but it still have a definitive effect if taken in the right dosages. Blackcurrant has been demonstrated to inhibit MAO-A 37 % and MAO-B 60 % in vitro, and 70 % to 90 % MAO-B inhibition was found in three human subjects [Merz & Co GMBH, 1991]. The same study concludes that maximum inhibition is obtained 60 minutes after application, and that 20 grams Blackcurrant is the optimum dosage.

The MAO-A inhibiting is what you want, as that is the enzymes that break down tryptamines. MAO-B inhibiting is certainly not needed, and can potentially give unwanted interactions. Blackcurrant mainly acts as inhibitors for MAO-B. Thus, Harmala-alkaloids is a much better option, as they are selective MAO-A-inhibitors.


Acidic environments will dephosphorylate Psilocybin, i.e convert it into Psilocin. This will give a stronger effect for a shorter duration of time, as the body will not need to do the time consuming conversion. I often make mushroom tea with a good dose of lemon juice, that works well. Anything that make the tea acidic will do the trick, including orange juice and vinegar.


Wow, interesting! This would be very important knowledge if it turns out to be correct. I would love to hear more about this, if anyone has any information.

As for the Grapefruit theory, this is indeed interesting stuff! Thank you for bringing that to the community's attention. I look forward to see how this thread turns out.

Hmmm what an interesting thread.

It seems then that there could potentially be two mechanisms at work with grapefruit then. Both the acidic environment and the enzyme inhibition.
I guess the only way to test this would be to try similar doses..one time with just oj and another time with grapefruit.

Theres alot of talk of people doin this oj, but not many people seem to have tried the grapefruit route.

IMHO, it just slows down the metabolization of certain chemicals at lowest steps (kidney).
it's certainly not a maoi

Unfortunately, this is secondhand information or worse. It may have been mentioned previously on the nexus. SWIM's always noticed differences from honey and/or any source of ascorbic acid, however, so it's likely that this info is somehow valid.

Are you sure the noticed difference is not only from the brew containing no or almost no Psilocybin? Even honey will dephosphorylate Psilocybin into Psilocin, yielding a brew that works much faster and with what seems a higher potency, but are shorter in duration.

i have always noticed that keeping the stomach empty, with acidic environment keeps the trip going, although i had no real basis other than my own experience so it was rather subjective. even back in the day, like 16+ yrs ago, we would eat vitamin c pills, and chug orange juice before/during lsd trips because it seemed to enhance it somehow. now with mushrooms, my fav combination is with fresh blueberries, chewed together. makes the mushroom much more palatable, and seems to synergize very well. i would imagine the same would be true for blackcurrent. interesting that blackcurrent can act as maoi.
i would give grapefruit a try.