Cotcha Yankinov
Bluelight Crew
- Joined
- Jul 21, 2015
- Messages
- 2,952
I should clarify - I meant that maybe their serotonin signaling levels never fell below a certain threshold until the comedown, not during the comeup or during their SRA naïve days.
I'm not saying that excess serotonergic signaling has to be the primary cause of issues, it could be a decrease in serotonergic signaling on the comedown with simultaneous alterations in neurophysiology that leads to issues, and this could be worse in people with more active MAO-A.
Alternatively, with chronic neurotransmitter shortages (like with an overactive form of MAO-A) sensitization of serotonin receptor response could be homeostatically beneficial, but the homeostatic sensitization could prove not to mix well with a sudden increase in neurotransmitters from an SRA. So either way, an increase in MAO-A activity could worsen a serotonin signaling shortage and increase risk of adverse effects, or could lead to chronic upregulation/sensitization of receptors and lead to adverse effects developing from an acute excess in signaling, in line with similar depersonalization issues from 5-HT2A agonists. Not that you can't see significant downregulation of 5-HT receptor response with classic psychedelics, and potentially see issues from that.
I should note that the short form of 5-HTTLPR (which confers risk to adverse effects of MDMA) is actually associated with lower levels of expression of SERT, but yet they have increased risk of adverse effects from tryptophan depletion. It could be that the functional consequences at a circuit level are more important to consider than what is going on at the individual synapse.
The 80% more active MAO-A thing that this person was telling me about was just a random example that might not contribute much to LTCs, but what it was meant to convey is that something could previously never be a problem because of thresholds. A bridge could be fine at holding up 10,000 pounds for 20 times (although you may see stress if you examine the bridge very closely) but the 21st time at 11,000 pounds could be all it takes for the bridge to collapse (just an analogy). Of course its incredibly more complicated because we're talking about the human brain, and it could go far beyond simple receptor homeostasis and deep in to the land of actual brain function.
I'm not saying that excess serotonergic signaling has to be the primary cause of issues, it could be a decrease in serotonergic signaling on the comedown with simultaneous alterations in neurophysiology that leads to issues, and this could be worse in people with more active MAO-A.
Alternatively, with chronic neurotransmitter shortages (like with an overactive form of MAO-A) sensitization of serotonin receptor response could be homeostatically beneficial, but the homeostatic sensitization could prove not to mix well with a sudden increase in neurotransmitters from an SRA. So either way, an increase in MAO-A activity could worsen a serotonin signaling shortage and increase risk of adverse effects, or could lead to chronic upregulation/sensitization of receptors and lead to adverse effects developing from an acute excess in signaling, in line with similar depersonalization issues from 5-HT2A agonists. Not that you can't see significant downregulation of 5-HT receptor response with classic psychedelics, and potentially see issues from that.
I should note that the short form of 5-HTTLPR (which confers risk to adverse effects of MDMA) is actually associated with lower levels of expression of SERT, but yet they have increased risk of adverse effects from tryptophan depletion. It could be that the functional consequences at a circuit level are more important to consider than what is going on at the individual synapse.
The 80% more active MAO-A thing that this person was telling me about was just a random example that might not contribute much to LTCs, but what it was meant to convey is that something could previously never be a problem because of thresholds. A bridge could be fine at holding up 10,000 pounds for 20 times (although you may see stress if you examine the bridge very closely) but the 21st time at 11,000 pounds could be all it takes for the bridge to collapse (just an analogy). Of course its incredibly more complicated because we're talking about the human brain, and it could go far beyond simple receptor homeostasis and deep in to the land of actual brain function.