syberdelic
Rising Star
I am starting a new thread on this topic in the science section as previous attempts to understand this thing have not really led anywhere constructive.
If you want to pan over previous discussions, go here.
Is DMT a 5-HT3 agonist
But I intend to start this conversation fresh, so don't bother reading this long and redundant thread unless you just really want to.
I would love to be able to eliminate the purge as it makes the whole experience completely untenable for me, but that is not the purpose of this. I intend to understand the mechanism/s behind what specifically causes the nausea and vomiting with Ayahuasca and pharmahuasca. Once the mechanism/s are understood, then we can consider whether the purge can be eliminated but again, that is not the intention of this query.
First, I am going to take off the table things other than DMT and harmalas. I know from first hand experience that tannins, terpins, and other plant materials contribute to the nausea and upset digestive tract, but the mechanisms behind this are fairly straight forward and don't need revisited. Fairly pure pharmahuasca seems to invoke La Purga just fine and in the same way, I would like to distill this discussion to the most basic components: DMT and harmalas.
Second, I am taking off the table things like spiritual purging and intensity. Maybe there is some validity to it, but these are roads that lead to nowhere in this quest for knowledge. And as an example, my partner has had Ayahuasca six times and purged every time. The purge seems to come on at 25-35 minutes, but she feels no other effects until around one hour. This tells me that the purge is something separate from the psychedelic experience. I'm sure that for most of us, the anxiety that can come along with a strong trip will exacerbate this nausea, but I'm considering this a separate entity as it will only serve to complicate the issue.
Third and finally, I would like to take off the table the notion that harmalas are 100% responsible for the nausea and vomiting. They are no doubt a contributor and probably a major one. Yes, if enough is taken, it will make one extremely nauseous and purge their guts out but this is not the scenario that we are examining here. We are talking about a moderate dosage that is adequate to inhibit MAO, say for instance 150-200mg of pure harmine HCl. This dosage does not seem capable of causing La Purga in most individuals, but rather just mild nausea/vertigo and maybe a mild upset stomach. BUT, by adding DMT into the gut, at least one purge is almost guaranteed and for those like myself, it lasts the duration of the trip.
So, to start things out, I will offer a couple of theories:
1) DMT, being a tryptamine makes it a likely candidate as a 5-HT3 agonist. Many things however contradict this including my own experience of mixing pharmahuasca with a large dose of 5-HT3 antagonist. This theory would require that DMT is a very weak agonist or binds very weakly to the receptor. But there may be some synergistic action when harmalas are introduced that cause DMT to bind more strongly to 5-HT3 or cause it to have a greater effect at opening the ion-gate. We have some data (need more) that by using moclomebide in place of harmalas as the MAOI, there is no discernible nausea. This implies that DMT on it's own is incapable of producing any significant nausea even when it is unimpeded by MAO. But others report nausea/vomiting from inhaling freebase DMT. Maybe some of it enters the esophagus/stomach? This is where we need more data of pharmahuasca use with moclomebide as the RIMA.
2) DMT is a strong agonist of the sigma-1 receptors. This receptor does not seem to do a whole lot on it's own, but rather it modulates and "amplifies" other receptors including acetylcholine and serotonin receptors which outside the central nervous system can cause nausea. Harmalas inhibit enzymes that break down acetylcholine as well as serotonin. Moclomebide inhibits only the enzymes that break down serotonin, so our limited data would suggest that elevated levels of serotonin in the gut have little or no effect on nausea. But the elevated levels of acetylcholine alone or with elevated serotonin could be modulated by overactive sigma-1 receptors via DMT to create La Purga.
If you want to pan over previous discussions, go here.
Is DMT a 5-HT3 agonist
But I intend to start this conversation fresh, so don't bother reading this long and redundant thread unless you just really want to.
I would love to be able to eliminate the purge as it makes the whole experience completely untenable for me, but that is not the purpose of this. I intend to understand the mechanism/s behind what specifically causes the nausea and vomiting with Ayahuasca and pharmahuasca. Once the mechanism/s are understood, then we can consider whether the purge can be eliminated but again, that is not the intention of this query.
First, I am going to take off the table things other than DMT and harmalas. I know from first hand experience that tannins, terpins, and other plant materials contribute to the nausea and upset digestive tract, but the mechanisms behind this are fairly straight forward and don't need revisited. Fairly pure pharmahuasca seems to invoke La Purga just fine and in the same way, I would like to distill this discussion to the most basic components: DMT and harmalas.
Second, I am taking off the table things like spiritual purging and intensity. Maybe there is some validity to it, but these are roads that lead to nowhere in this quest for knowledge. And as an example, my partner has had Ayahuasca six times and purged every time. The purge seems to come on at 25-35 minutes, but she feels no other effects until around one hour. This tells me that the purge is something separate from the psychedelic experience. I'm sure that for most of us, the anxiety that can come along with a strong trip will exacerbate this nausea, but I'm considering this a separate entity as it will only serve to complicate the issue.
Third and finally, I would like to take off the table the notion that harmalas are 100% responsible for the nausea and vomiting. They are no doubt a contributor and probably a major one. Yes, if enough is taken, it will make one extremely nauseous and purge their guts out but this is not the scenario that we are examining here. We are talking about a moderate dosage that is adequate to inhibit MAO, say for instance 150-200mg of pure harmine HCl. This dosage does not seem capable of causing La Purga in most individuals, but rather just mild nausea/vertigo and maybe a mild upset stomach. BUT, by adding DMT into the gut, at least one purge is almost guaranteed and for those like myself, it lasts the duration of the trip.
So, to start things out, I will offer a couple of theories:
1) DMT, being a tryptamine makes it a likely candidate as a 5-HT3 agonist. Many things however contradict this including my own experience of mixing pharmahuasca with a large dose of 5-HT3 antagonist. This theory would require that DMT is a very weak agonist or binds very weakly to the receptor. But there may be some synergistic action when harmalas are introduced that cause DMT to bind more strongly to 5-HT3 or cause it to have a greater effect at opening the ion-gate. We have some data (need more) that by using moclomebide in place of harmalas as the MAOI, there is no discernible nausea. This implies that DMT on it's own is incapable of producing any significant nausea even when it is unimpeded by MAO. But others report nausea/vomiting from inhaling freebase DMT. Maybe some of it enters the esophagus/stomach? This is where we need more data of pharmahuasca use with moclomebide as the RIMA.
2) DMT is a strong agonist of the sigma-1 receptors. This receptor does not seem to do a whole lot on it's own, but rather it modulates and "amplifies" other receptors including acetylcholine and serotonin receptors which outside the central nervous system can cause nausea. Harmalas inhibit enzymes that break down acetylcholine as well as serotonin. Moclomebide inhibits only the enzymes that break down serotonin, so our limited data would suggest that elevated levels of serotonin in the gut have little or no effect on nausea. But the elevated levels of acetylcholine alone or with elevated serotonin could be modulated by overactive sigma-1 receptors via DMT to create La Purga.