What are some CRF1 antagonists?
kurdishfella 27 Feb 2019
To examine whether Lmo3 in the amygdala is important for anxiety-like behavior, we locally reduced Lmo3 expression in the BLA of wild type mice using a lentiviral vector expressing a short hairpin RNA targeting the Lmo3 transcript. Mice with Lmo3 knockdown in the BLA exhibited decreased anxiety-like behavior relative to control mice. These results suggest that Lmo3 promotes anxiety-like behavior specifically in the BLA, possibly by altering Crhr1 expression. This study is the first to support a role for Lmo3 in anxiety-like behavior.
Go figure I have a mutation in this too together with CRHR1, CRHR1-IT1 and MGC57346-CRHR1, I wonder what else controls CRHR1. ... and what decreases LMO3? Valproic acid.
Caravaggio 28 Feb 2019
Check your plasma ammonia and urinary orotic acid.
Quote from a German article about urea cycle disorders (translated):
Ammonia increases the transport of tryptophan via the blood-liquor barrier, which leads to an increased production and liberation of serotonin - a tryptophan restriction has proven favorable in patients with constat moderate hyperammonemia.
Without diagnosis you could try to take sodium benzoate, it reduces ammonia in an alternative pathway.
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kurdishfella 28 Feb 2019
Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive
https://www.ncbi.nlm...les/PMC3475726/
good read on BLA
https://www.scienced...ateral-amygdala
Edited by farshad, 28 February 2019 - 09:58 PM.
kurdishfella 18 Mar 2019
valproic acid (XR) the only thing that worked..
possibly olanzapine and lithium carbonate too
antipsychotic, anticonvulsant and benzo etc more likely to work since they hit a broad spectrum in the brain .
kurdishfella 28 Mar 2019
crhr1 makes youre more emotional
https://www.ncbi.nlm...les/PMC3297975/
olanzapine (20-60mg) + valproate(2500mg-3k) + lithium carbonate (1200-2kmg) (memantine / tianeptine etc family/progesterone oil)
kurdishfella 13 Apr 2019
either too much CRHR1 mutation in the hippocampus
or somewhere in the amygdala too much CRHR by the gene LMO3 in the basal amygdala
or..something with these two CRHR1-IT1 (CRHR1 intronic transcript 1) & MGC57346-CRHR1 etc
Edited by farshad, 13 April 2019 - 01:14 AM.
kurdishfella 11 May 2019
Edited by farshad, 11 May 2019 - 03:18 AM.
kurdishfella 13 May 2019
https://en.wikipedia...Allostatic_load
Allostatic load is "the wear and tear on the body" which accumulates as an individual is exposed to repeated or chronic stress. The term was coined by McEwen and Stellar in 1993. It represents the physiological consequences of chronic exposure to fluctuating or heightened neural or neuroendocrineresponse which results from repeated or prolonged chronic stress.
https://en.wikipedia...i/Myxedema_coma
https://en.wikipedia...i/Levothyroxine
https://en.wikipedia...riiodothyronine
Edited by farshad, 13 May 2019 - 09:40 PM.
kurdishfella 09 Jun 2019
amygdala, locus coeruleus (not issue) and hippocampus. Within the hippocampus, the CRHR1s are most abundant, residing mainly on the pyramidal cells of CA1 and CA3. Chronic activation of CRHR1s by CRH induced by early life stress has been shown to underlie memory deficits and learning impairments and anxiety in adulthood.
In CRF1 knockout mice, and mice treated with a CRF1 antagonist, there is a decrease in anxious behavior and a blunted stress response, suggesting that CRF1 mechanisms are anxiogenic.[8][12] However, the effect of CRF1appears to be regionally specific and cell-type specific, likely due to the wide variety of cascades and signaling pathways activated by the binding of CRF or CRF-agonists.[12] In the central nervous system, CRF1 activation mediates fear learning and consolidationin the extended amygdala, stress-related modulation of memory formation in the hippocampus, and brainstem regulation of arousal.[12]
Edited by farshad, 09 June 2019 - 12:51 PM.
kurdishfella 12 Jun 2019
Antidepressant-Like Effects of Shuyusan in Rats Exposed to Chronic Stress: Effects on Hypothalamic-Pituitary-Adrenal Function
Results from the present study demonstrated that Shuyusan could decrease the serum contents of CRH, ACTH, and CORT. It also could increase the expression of hippocampus GR receptor in the rat model of depression. Our results suggested that the mechanisms of action of Shuyusan were due to decreasing the serum contents level of CRH, ACTH, and CORT and increasing the expression of hippocampus GR receptor. Fluoxetine is selective serotonin reuptake inhibitors’ (SSRIs) medications, it could increase the levels of NE, 5-HT, and DA in the brain of rat and was related to downregulation of 5-HT receptor, but not decreased the serum contents level of CRH, ACTH, and CORT and increased the expression of hippocampus GR receptor.
http://www.hindawi.c...am/2012/940846/
Tables showing the reduction of CRH ACTH CORT and mRNA
http://www.hindawi.c...12/940846/fig4/
http://www.hindawi.c...12/940846/fig5/
Ingredients of Shu-Yu-San:
Albiziae Flos, Acori Tatarinowii Rhizoma, Bupleuri Radix, Curcumae Radix, Gardeniae Fructus, Menthae Herba, Polygalae Radix, Poria, and Ziziphi Spinosae Semen.
kurdishfella 13 Jun 2019
kurdishfella 13 Jul 2019
Drugs such as sumatriptan induce a significant decrease of ACTH, cortisol, and prolactin concentrations, both in patients with migraine and in controls (Rainero et al., 2001). Acute subcutaneous administration of sumatriptan activates the pituitary-adrenal axis: significant increases in β-endorphin and cortisol concentrations are reported across all subjects receiving sumatriptan (Facchinetti et al., 1994), and these would produce secondary effects.
kurdishfella 15 Sep 2019
CRH-stimulated conductance was significantly inhibited by alpha-helical CRH-(9-41), hexamethonium, bretylium, or doxantrazole. CRH-induced enhancement of HRP flux was significantly reduced by all drugs but aminoglutethimide
https://www.ncbi.nlm...pubmed/10444454
neuroplasticity crucial for overcoming anxiety and crhr1 antagonist increases that
Edited by farshad, 15 September 2019 - 12:04 AM.
kurdishfella 21 Oct 2019
Antidepressant-Like Effects of Shuyusan in Rats Exposed to Chronic Stress: Effects on Hypothalamic-Pituitary-Adrenal Function
Results from the present study demonstrated that Shuyusan could decrease the serum contents of CRH, ACTH, and CORT. It also could increase the expression of hippocampus GR receptor in the rat model of depression. Our results suggested that the mechanisms of action of Shuyusan were due to decreasing the serum contents level of CRH, ACTH, and CORT and increasing the expression of hippocampus GR receptor. Fluoxetine is selective serotonin reuptake inhibitors’ (SSRIs) medications, it could increase the levels of NE, 5-HT, and DA in the brain of rat and was related to downregulation of 5-HT receptor, but not decreased the serum contents level of CRH, ACTH, and CORT and increased the expression of hippocampus GR receptor.
http://www.hindawi.c...am/2012/940846/
Tables showing the reduction of CRH ACTH CORT and mRNA
http://www.hindawi.c...12/940846/fig4/
http://www.hindawi.c...12/940846/fig5/
Ingredients of Shu-Yu-San:
Albiziae Flos, Acori Tatarinowii Rhizoma, Bupleuri Radix, Curcumae Radix, Gardeniae Fructus, Menthae Herba, Polygalae Radix, Poria, and Ziziphi Spinosae Semen.
kurdishfella 27 Nov 2019
] It produces antidepressant-like effects in rats.[2] However, captodiamine is unique among antidepressant-like drugs in that it increases brain-derived neurotrophic factor (BDNF) levels in the hypothalamus but not in the frontal cortex or hippocampus.[2] This unique action may be related to its ability to attenuate stress-induced anhedonia and corticotropin-releasing factor (CRF) signaling in the hypothalamus.[2]
kurdishfella 01 Dec 2019
The amygdala and its cortical targets show decreased activity during a variety of task challenges in individuals engaged in Alcohol drinking.
Hip 02 Dec 2019
Kambo, a medicine used by Amazonian Indians, and which is beneficial for a number of diseases, contains a corticotropin-releasing factor (CRF) receptor agonist called sauvagine.
The Cortene Peptide (CT38) is also a CRF receptor agonist. CT38 is currently being tested as an experimental chronic fatigue syndrome treatment in a clinical trial.
2 Duckets 23 May 2020
Nobody knows of any other CRH-Inhibitors that have not been mentioned yet?
Pulsatilla chinensis - its a CRH antagonist
kurdishfella 16 Jul 2020
Have / (or has? idk) anyone experienced with any CRH1 antagonists yet?
Edited by kurdishfella, 16 July 2020 - 06:26 PM.
kurdishfella 23 Jul 2020
I message these guys about my crhr1 lmo3 mutation https://www.creative...roductions.html
im trying to find any scientists / and labs interested to study me im sure they will find some interesting things. to my knowledge there hasn't been discovered any human with this mutation and the studies was done on rats genetically engineered to have it.
kurdishfella 28 Jul 2020
Guys. it is said that twins share identical genes. but lets say twins are born and one is born with high levels of LMO3 (leading too excess lvls of crhr1) and the other has low level of LMO3(low levels of crhr1). Neither one has normal levels. Would this disprove that fact? Because i'm pretty sure I know of one and they are on youtube HodgeTwins.
One is also left handed and the other is right handed. This could also mean handedness is part genetic.
It is true that identical twins share their DNA code with each other. This is because identical twins were formed from the exact same sperm and egg from their father and mother. ... While this rarely happens, it makes it so that one identical twin may have a genetic condition, while the other twin does not.
if twins have identical genes then why do they get different dna origin results
Edited by kurdishfella, 28 July 2020 - 02:03 AM.
kurdishfella 17 Oct 2020
kurdishfella 16 Jan 2021
It is possible for your parents not to have CRHR1 mutation but then you get it, but your children not, vice versa.
Edited by kurdishfella, 16 January 2021 - 05:03 AM.
sjd88383jdjxj388 08 Jan 2022
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CarlSagan 30 May 2023
Man great thread with a lot of follow up @
Do you still take any?
I've been looking for the mechanism for restoring proper restorative sleep after a decade without it, with excessive REM sleep & fast onset.
and I found lowering CRH is a major mechanism for this
In depression / narcolepsy REM sleep latency shortens dramatically. REM sleep goes up and Slow Wave Sleep goes down. So people get exhausting overactive sleep with crazy dreaming. which further feeds into the disorder.
Well if people (without addisons) take hydrocortisone before sleep it significantly delays REM latency , lowers REM sleep, and increases slow wave sleep.
but the theory is its not the cortisol itself. its the flood dose of cortisol creating a drop in Corticotropic Releasing Hormone as a response. where CRH acts as a signalling hormone for REM sleep
https://www.nature.c...ticles/1300362
Cortisol administration resulted in a significant increase in highly synchronized EEG activity including delta and theta frequencies, according to a higher amount of slow-wave sleep. This effect predominated in the first few hours of night sleep. REM sleep was decreased, which appeared to be secondary to the lengthened first sleep cycle
&
https://pubmed.ncbi....ih.gov/7829766/
https://pubmed.ncbi....h.gov/3614616/
https://pubmed.ncbi....h.gov/1996621/
* "demonstrating that some cortisol is needed for REM sleep, with excess cortisol inhibiting REM sleep." "An alternative interpretation is that the decrease in REM sleep in normal subjects receiving exogenous glucocorticoids is caused by CRH and/or ACTH suppression" "In Addison’s patients, on the other hand, high ACTH and CRH levels are still present despite HC administration, so that CRH and/or ACTH may still signal the entry into REM sleep" "Although one study found that iv administration of CRH reduced REM sleep (23), this is probably an indirect effect of CRH, as iv administration of this hormone is unlikely to cross the blood-brain barrier."
a lot of these CRH lowering substances with significant effect are inaccessable to me unfortunately. but i have 2 leads to add to this thread and 1 with big effect
1. iron deficiency also comes with the REM sleep skew (even in iron deficiency without anemia). and in iron deficiency there's a lower cortisol release response from ACTH. which gets stimulated by CRH. so i guess CRH stays high to try make up for the lower response? creating the rem sleep skew. so fixing with heme iron may play a role in lowering it.
https://pubmed.ncbi....ih.gov/1651678/
https://www.ncbi.nlm...s/PMC3424605/
https://jcsm.aasm.or...664/jcsm.9690
2. high salt diet for 9 days had a big impact in mice here, if the same applies to humans https://pubmed.ncbi....ih.gov/8247254/ (but maybe not in the few hours leading to sleep , just overall intake for 9 days?)
" CRH mRNA levels were unchanged after 2 days salt-loading, but declined to 77% of control levels after 9 days"
which is interesting because you mentioned lithium, which is known to raise slow wave sleep and delay REM onset. and lithium has similar properties to sodium.
Not sure what amount they used here
Edited by CarlSagan, 30 May 2023 - 11:29 AM.