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OfflineChemiker
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findings on vitamin C and psilocin pharmacokinetics
    #6357427 - 12/11/06 01:24 PM (14 years, 11 months ago)

IV administration of 1 mg psilocybin led to psychological effects, "within two minutes." The authors state that nausea, vertigo and fatigue were felt within the first 2 to 5 minutes. 3 mg of IV psilocybin additonally led to vomiting, cardiovascular side effects, and dissociative phenomena reported as frightening (intense derealization and depersonalization). After 10 minutes these effects were vanishing and complete recovery was observed after 40 minutes. Peak psilocin levels were reached in plasma within 2 minutes (1.9 +/- 1.0 min).

Clearly, my assertion that psiloc(yb)in does not need to still be present in the brain for the effects to be felt is seriously challenged by these findings and therefore I rescind that statement. My source was: Stafford, P. Psychedelics Encyclopedia (3rd edition). Ronin Pubslishing, Berkeley, 1992.. p. 69. I should have known better than to trust such a shitty source. I think this is also repeated (or was) and cited in the LSD FAQ online. How many of you can honestly say that you wouldn't have trusted that reference?

Upon IV administration, psilocybin is rapidly dephosphorylated and peak psilocin levels were reached within 2 minutes as noted. [note that this this should not be taken to imply that I agree with the hypothesis that mushroom tea should still result in a significantly shorter trip that is more intense - I still do not believe that this is the case - the difference in absorbtion and half-life would most likely not be that different].

The authors stated that they were going to report detailed information on the correlation between psychological effects and plasma concentrations. I will summarize the findings if I can find the article (if they indeed published it). They also said that they wanted to do positron emission tomography studies to correlate neural activity with the action of the drug. If I can find such a study, I will summarize the findings.

The authors of the study did not test plasma for psilocybin and warn that whether or not psilocybin is completely converted to psilocin is unknown at the time of the study (but the conversion is extremely rapid and the bulk of the evidence suggests that the conversion is complete). I think it is interesting to note that IV psilocybin was associated with negative physical (and in one person at a higher dose: frightening psychological) effects.

As far as the authors know, this was the first study involving the intravenous administration of psilocybin to humans in a controlled setting.

I also happened to stumble across what may be evidence supporting claims that vitamin C enhances a mushroom trip. Ascorbic acid (vitamin C) is known to stabilize psilocin from autooxidation (the mechanism is not clear, though it is speculated metal ions in solution may be acting as catalysts). The authors studied the degradation of psilocin in water and in the presence light. 10 nM (aqeous) psilocin exposed to light displayed about 7% degradation after 30 mins and about 14% after one hour. The authors note that psilocin degradation was "strongly" dependent on concentration, but since they don't make the kinetics clear, whether or not the % degradation would be affected also isn't clear (though I suspect that it would not if this is a [pseudo]first-order process). For comparison, an equimolar concentration of psilocin in 25 nM ascorbic acid in aqeous sln. exposed degraded by about 4% after one hour.

For those in support of the "tea makes a faster, more intense trip" ["T"] hypothesis, you should take note of this: The authors don't report the temperature, so it was probably 20 Celsius (or 25). Around this temperature, an increase of 10 degrees results in reactions occuring about twice as quickly. Using that as a guideline, if mushrooms steep in tea at 80 Celsius for 5 minutes, the reaction would go about 2^6 times faster than at 20 Celsius (2^6 = 2*2*2*2*2*2 = 64, the equivalent of 320 minutes at room temp). After 320 minutes in water and exposed to light, 50% (!!!!) of the psilocin sample had degraded. I consider it exceedingly unlikely that making mushroom tea could possibly help enhance the experiences.

For those who are still interested in making mushroom tea, then I suggest you add vitamin C. Psilocin under the same conditions but with 25 nM (as previously mentioned) ascorbic acid had only degraded by about 7% after 320 minutes. If the T hypothesis is correct, however, then making mushroom tea with vitamin C added to the water should blow your fucking mind.

I am not aware of how this would affect the kinetics of metabolism, degradation or elimination of psilocin in plasma or in the gastrointestinal tract. Bear in mind that these studies were simply done in water, with light used to speed up the oxidation process.

Source:

Hasler, F. et al. Determination of psilocin and 4-hyroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharmaceutica Acta Helvetiae. 72, pp. 175 - 184. (1997)

----------------------------

Another study demonstrated that oral psilocybin administration resulted in plasma levels consistent with psychological effects, up to 8 hours (or more) after 0.2 mg psilocybin / mg bodyweight (roughtly equivalent to a 65 kg adult taking somewhere between 1 to 3 grams of P. cubensis). The previous study stated peak plasma concentrations occur at 105 +/- 37 minutes after oral ingestion. This study found that peak concentrations of psilocin were found to occur 70 to 90 min after oral ingestion of psilocybin.

Source:

Lindenblatt, H. et al. Quantitation of psilocin in human plasma by high-performance liquid chromatography and electrochemical detection: comparison of liquid-liquid extraction with on-line solid phase extraction. Journal of Chromatography B. 709, pp. 255 - 263. (1998)

===========================

So, one of the things I said was wrong and I was really arrogant about it and I was a real fucking asshole about it. I apologize for that. At least I can not only admit to being wrong (and anyway, I think most of you would have taken my source as indisputable), but I'm the one who actually looked into it, found my error and announced it. I will try to improve my attitude in the future.


Edited by Chemiker (12/11/06 02:30 PM)


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OfflineChemiker
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Re: findings on vitamin C and psilocin pharmacokinetics [Re: Chemiker]
    #6357659 - 12/11/06 02:58 PM (14 years, 11 months ago)

A follow up study involving psilocin and PET does not seem to have been done, nor can I find a study documenting plasma concentrations of psilocin and correlations of altered states of consciousness by these authors. One of their later studies states that they didn't monitor psilocin serum levels while investigating altered states experienced by those under the influence due to the cost.

Apparently the pharmacology of psilocybin is reviewed in:

Passie, T. The pharmacology of psilocybin. Addiction Biology. 7, pp. 357 - 364. (2002).

My library doesn't seem to subscribe to this journal, so I don't have access to the article.

BTW, raw data from one of the two studies can be provided. The psilocin % vs. time curve in the autooxidation study may be of use to some.


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OfflineGNB
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Re: findings on vitamin C and psilocin pharmacokinetics [Re: Chemiker]
    #8485620 - 06/04/08 11:52 PM (13 years, 5 months ago)
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I realize this is an extremely old thread, but I think some users might like to read the journal article.


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