Ok, I thought we could discuss the role of MAOIís, in combination with DMT and other psychedelics such as psilocin.
Main article by Jonathan Ott.
The general idea is that because of MAO inhibition, levels of endogenous neurotransmitters are increased and could therefore compete with the drug for receptors, thus rendering the exogenous compound less effective.
The benefit is apparently only for oral DMT, in its action of allowing free passage into the brain from the gut.
Other than increasing the absorption of another compound such as psilocin in a similar fashion, use of an MAOI as a potentiator seems counterproductive.
However...The author commented that the "high 5-HT [serotonin] level" produced by the MAOI blocked the effect of DMT, thought to owe its psychoactivity to serotonin antagonism - with higher background levels of serotonin, higher doses of DMT would be required to produce equivalent effects absent MAOI.
We have seen that MAOI hardly can be said to potentiate DMT; if anything, the reverse obtains, with serotonin antagonism/blockade...
It thus follows that the ayahuasca effect is due to MAO inhibition in the digestive system or blood stream, protecting DMT from metabolism en route to the brain, where the MAOI paradoxically attenuate the DMT effect.
He also goes on to comment on potentiation (or lack thereof) of psilocybin mushrooms by MAOIsOral or intramuscularly-injected methysergide (a 5-HT receptor antagonist) was shown to exert a very strong potentiating effect on intramuscularly-injected DMT...
This is consistent with the hypothesis of DMT psychoactivity as a result of serotonin antagonism - MAOI, which elevate brain serotonin, inhibit the DMT effect, and the serotonin antagonist methysergide and serotonin receptor blocker pindolol enhance it.
So, such a 5-HT receptor blockade resulting from inhibition of enzymatic degradation could possibly decrease the binding potential for exogenous psychoactives. However, this also depends on the relative affinity of the receptors and their subtypes for different ligands and also the extent of the increase in serotonin, which is proportionate to MAO inhibition and individual neurochemistry.To be sure, I have heard considerable anecdotal evidence, to the effect that pre-treatment by Syrian rue seeds, B-carboline-rich seeds of Peganum harmala L. used in anahuasca,(5) can potentiate the effects of psilocybian mushrooms, pursuant to this general notion of B-carbolines as all-purpose potentiators of visionary drugs. However, nobody has proffered hard evidence of this, even with the most rudimentary controls. All the anecdotal evidence I have heard concerns vague bioassays involving psilocybian mushrooms as the psilocybin source, sometimes not even weighed doses, but counted, by pairs! Since potency of psilocybian mushrooms is notoriously variable, even in commercially-cultivated Psilocybe cubensis (in commercial-style Mason jar cultures, there was up to a four-fold variation in potency of individual mushrooms from a given jar, even up to nearly three-fold variation in psilocybin content between caps and stems of the same mushroom). Given this gross variation in psilocybin potency, even of cultivated mushrooms, and the fact that, as we have seen, MAOI weaken, rather than potentiate, DMT and LSD, we will need controlled human bioassays with pure B-carbolines and psilocybin in pharmahuasca capsules to establish whether or not MAOI can truly potentiate psilocybin.
If it is shown that MAOIs do in fact potentiate psilocinís action in the brain, then the increase in activity is due to:
a) A synergism with the abundant serotonin.
b) An increase in absorption from the digestive tract, leading to more psilocin reaching the brain, in quantities that overwhelm the abundance of competing neurotransmitters.
c) The receptors to which psilocin and other similar psychedelics bind have a higher affinity for such compounds than serotonin.
I find this last option interesting.
If Psilocin is shown to have a higher binding potential than serotonin on specific receptor subtypes, I would think it holds some intriguing possibilities for psilocinís role in understanding structure/effect relationships in regards to the coding of information through biochemical means.
It would also give credence to T. Mckennaís stoned ape theory, in that perhaps serotonin emulates psilocin, and that plants shape the human organism, if not all animal life, more than such organisms shape themselves.
What are your thoughts?