Some appreciation for Ghost's long studies.
Ghost wrote:Recently I’ve become quite interested in how brain histamine levels could be playing into PSSD.
Also, here are the links to the 3 sources I am using for this article. I will reference them below as well
Article 1: “NCBI Article” (A1)
http://www.ncbi.nlm.nih.gov/pubmed/11164999
Article 2: “Frontiers Article” (A2)
http://journal.frontiersin.org/Journal/10.3389/fnsys.2014.00064/full
Article 3: “Helmut Haas Article” (A3)
http://www.ehrs.org.uk/haas.pdf
Before I begin, I want to introduce quickly the 3 Histamine Receptors that I studied. I am using direct quotes to ensure that this information is correct.
Histamine H1 Receptor: (A1/A2) “Mainly postsynaptic” “High densities found in the Hypothalamus, and other limbic regions” “Cortex, Amygdala, Striatum”
Histamine H2 Receptor: (A1) “Mainly Postsynaptic” “Activation leads to mainly excitatory effects” “Mainly found in Hippocampus, Amygdala, Basal Ganglia”
Histamine H3 Receptor: (A1/A2) “Exclusively presynaptic” “inhibition of histamine release of other neurotransmitters” “ACH, DOPAMINE, SEROTONIN, GABA” “modulates GLUTAMATE NMDA receptors” “involved in many CNS functions, AROUSAL, ANXIETY”
Full intros to each of these Histamine receptors can be found in the links. I HIGHLY RECOMMEND reading/ understanding them before continuing. study study study
Why does this all matter for PSSD?
A few reasons…
1) Histamines role in neurotransmitter levels.
Because histamine H3 receptors inhibit the release of Serotonin and Dopamine, among other transmitters noted above. Although heightened serotonin levels may be detrimental to PSSD and sexual function, I believe that inhibiting the H3 receptor would possibly be able to relieve some genital anesthesia and anhedonia by rising the pleasure neurotransmitter dopamine. This may be especially helpful if coupled with the libido increasing effects of a H1 antagonist such as Loratadine. It is a very promising place to look at least...
Histamine “controls feeding behavior” and “taste perception” as well.
Also read that H3 receptors may have an affect on alcohol…Would need some more expert advice on this…But I do know that a lot of PSSD suffers are affected by alcohol after cessation of treatment.
2) The action by which Histamine H1 blocking can increase sexual function (not pleasure).
This is aimed at Gonzo, and others (myself) who have used Loratadine or other Histamine H1 blockers to get better erections.
Let me quote quick…
“H1-receptor activation causes excitation in most brain regions (brainstem, thalamus, hypothalamus, cortex, amygdala, striatum) through Gq11 protein and a direct block of a leak potassium conductance or phospholipase C, inositoltrisphosphate (IP3) and diacylglycerol (DAG) mediation. IP3 releases Ca2+ from internal stores and activates a number of Ca2+-dependent processes, including the opening of a cation channel (TRPC) or the stimulation of a Na+ -Ca2+-exchanger (NCX). Furthermore, the elevated intracellular Ca2+ can stimulate NO-synthase”
I believe that Cialis or Viagra eventually work by increasing NO levels. So when you add that to more NO synthesis, you’d have…one hell of an erection. They would work together symbiotically.
But...there's a catch...
"Histamine H(1)R DOES activate nitric oxide synthase, HOWEVER, it also activates PROTEIN KINASE C; which causes peripheral vasoconstriction - also , more h1 activation tends to lead to anxiety....the only way h1 blockade provides benefit for PSSD sufferers, is when h3's are also blocked - thus balancing out the anti sympathetic effects of H1 blockade." -Area
This would again support the idea of needing to add a H3 inhibitor (Pitolisant) for you to really see some benefit from Histamine approach.
3) Mental functioning/ Brain fog
A lot of people (myself included) notice these problems after taking an SSRI
Let me quote again…
“The importance of H3 receptor signaling in the brain to acquire and store short- and long- term memories has been documented extensively” (Abuhamdah et al. (2012)) (From article 2)
I will say that the H3 antagonist Pitolisant has been shown to have nootropic properties (memory enhancing). It is also being tested for the treatment of Parkinson's disease and Schizophrenia. This is another way to go about raising dopamine levels instead of jumping on a Dopamine Antagonist. This could be a very promising drug/ approach for the treatment of anhedonia/ genital anesthesia sufferers.
At this point I would need clarification from others as to how an SSRI could have decreased memory function, or if the H3 receptors are likely the cause of this at all. Just a hypothesis…I don't want to speculate anything else until I get more info.
4) Inability to Reach Orgasm
(Haven't researched this yet personally, but this is a quote from catalunya from personal experience/ research).
"higher histamine levels are associated with decreased ejaculatory latency (time taken to orgasm) and i suffered from quite long latency periods before i started taking l-histadine and b6."
I believe that this means, catalunya correct me if I'm wrong, that for you raising histamine made reaching orgasm easier? This could be another downside of the histamine lowering approach, and something that would definitely have to be monitored. Also very interesting for people who suffer from inability/difficulty to orgasm. Sonny? Maybe this is why these people may have less problems with genital anethesia, because they have histamine that is too LOW instead of too HIGH. Again, just thoughts. Input would be appreciated.
Possible antagonists
H1:
(2nd generation H1-antagonists)
Loratadine (Claritin)
Cetirizine (Zyrtec)
Mianserin (antidepressant)
(3rd Generation H1-antagonists)
Levocetirizine (Xyzal) - Prescription Only
H3: (Some are very hard to obtain)
Clobenpropit
Conessine- Found in a number of plant species. Long CNS clearance time.
Pitolisant- Available online $25 http://tht.co
Where to turn from here?
Ideally, I would be looking primarily for a Histamine H1 antagonist to be paired with a Histamine H3 antagonist in hopes to relieve sexual function and sensitivity. Fixing this dopamine problem would help with many PSSD symptoms, but would likely be ineffective with treating issues such as Low T, higher prolactin, or problems with the "love hormone" Oxytocin. Hopefully, it would at least bring back some of the pleasure and ability of sexual activity.
I will keep updating this and learning as I go…This is the first big PSSD research I have done. Collaboration on this will be key. Very Happy
