My psychiatrist is still recommending Buspar or Lyrica to control the anxiety. Lyrica I am afraid of cause of the memory and withdrawal effects. Buspar I am afraid of due to any potential negative sexual effects like premature ejaculation. or any low libido/PSSD effects although I read its actually been used to treat PSSD?
I'm not seeing anything about sexual side effects from Busprione, and I'm under the impression that the sexual side effects from SSRIs are actually that it makes it harder to orgasm, and hence SSRIs are used in treating premature ejaculation.
I have read it is a 5HT-1A agonist and I want to know if stimulating this receptor can potentially resolve this LTC syndrome cause the doctor said my biology just needs a nudge in the right direction and this could give it that slight nudge.
So im interested in it but still just scared of meds after my experience with SSRIs albeit that was at the beginning of the LTC and if I knew what I knew now I'd have waited rather than knee jerk reaction going to the doctor desperately back then trying to get a pill to solve things.
Busprione seems like really untested waters, I can't recall anybody here trying it. So as usual, it could go either way :/
Also--an interesting post regarding HIGH serotonin vs LOW serotonin. Even too much serotonergic activity can cause anxiety/OCD etc.
https://area1255.blogspot.com/2016/11/the-definite-role-of-serotonin-excess.html
And it says SSRIs work due to downregulation of certain serotonin receptors and effects on other things like allopregnenolone/GABA.
Could it be that MDMA has shifted the balance to having too much serotonin activity and too little GABA/allopregnenolone--particularly given the response to benzos?
I think its very important to consider that a high serotonin phenotype could be having problems specifically because they had too much serotonin
during a developmental stage. So for example, having a short form of the 5-HTTLPR gene is associated with increased risk of adverse effects to MDMA and dietary tryptophan depletion, and the short form is associated with lower expression of the serotonin transporter. This leads to decreased serotonin turnover and increased serotonin signaling
at first. Same thing with animal models genetically engineered to hypo-express serotonin transporters.
You would think since SSRIs are used to treat mental illness, that these people/animals with less serotonin reuptake (because they express fewer reuptake transporters) would be more resilient to mental illness, but its really quite the opposite. That's probably because there are compensations to excess serotonin signaling that can occur when the brain is developing (but the brain works very differently as far as homeostatic compensations when the brain is matured).
So the matter isn't clear cut unfortunately. You could have multiple scenarios. For example
1. Increased expression of MAO-A leads to increased serotonin (and other neurotransmitter) breakdown, and when detecting metabolites of serotonin in spinal fluid, it looks like the patients have increased serotonin when they actually just have increased serotonin metabolism (and hence less serotonin in the brain).
2. Patients have increased serotonin in the brain but that's not their actual issue - the actual issue is that they had increased serotonin during a developmental stage, while having more serotonin in the present may not be that bad for them.
The upstream portion of SSRI efficacy is thought to involve desensitization of autoreceptors that control serotonin cell firing (and the downstream, signaling that occurs after serotonin is allowed to increase). 5-HT1A receptors are expressed as both autoreceptors (presynaptic) and heteroreceptors (postsynaptic/downstream). There could be issues with 5-HT1A autoreceptors/heteroreceptors when it comes to these serotonin transporter hypoexpressing phenotypes like the short form of 5-HTTLPR.
The interesting thing is that MDMA and other drugs work very, very differently from ie SSRIs because they completely bypass the autoreceptors (MDMA doesn't depend upon natural serotonin cell firing to release serotonin and cause downstream signaling).
But as far as the different theories of downstream SSRI efficacy, I think the theories like modulation of endogenous neurosteroids and a normalizing effect on cannabinoid CB1 receptors need more investigation. CB1 receptors are actually extremely widespread and fundamental to the brain, and I do think its interesting to note that most LTC people have pretty bad reactions to weed.
I should also just nitpick the article you linked linked, for example this is its first citation
http://www.medicaldaily.com/social-...-rethink-ssris-and-other-anxiety-drugs-338608
Essentially it says that too much serotonin has been found in the amygdala of people with anxiety. But serotonin also controls the oscillatory communication between the PFC and amygdala, with people that have a short form of 5-HTTLPR having increased coherence between the mPFC and amygdala.
Serotonin function is thought to differ in the amygdala because the amygdala isn't thought to utilize "non-synaptic volume transmission", essentially meaning that serotonin normally communicates largely by diffusing of out the synapses and binding onto other adjacent synapses/cells. Serotonin reuptake transporters modulate this process.
Serotonin cells in the amygdala are weird when it comes to volume transmission, so it could be that SSRIs could still cause a net decrease in the activity of the amygdala by causing a change in other regions/networks that outweighs whatever influence the SSRIs are directly having on the amygdala.
In other words, its not as simple as "People with anxiety have increased serotonin in the amygdala, SSRIs increase serotonin in the amygdala, therefore SSRIs worsen anxiety" which is what some people may be gleaning from such an article.
The other thing to consider is phasic vs. tonic release of serotonin. For example
"Similar to the theory of dopamine advanced by Grace and colleagues [70, 71], tonic levels of 5-HT may regulate the gain of phasic signaling, with high tonic levels decreasing the effectiveness of phasic release by receptor desensitization and internalization as well as stimulation of autoreceptors on neurons participating in the phasic signal.
~
dysfunctional serotonergic signaling could lead to user anxiety and fear
(high phasic signaling), or relief and calmness (high tonic levels). This suggests that
drugs like MDA and MDMA, which release 5-HT by a mechanism independent of cell
firing and dramatically increase tonic 5-HT, should decrease this hypothesized phasic 5-
HT signal."
Its possible that serotonergic drugs could help normalize issues with phasic vs. tonic signaling.