12 replies to this topic

[kurdishfella]

hi, I have tried various drugs SSRI,SNRI & MAOI for my SA that have not worked. I'm not sure what is left to try, I mean there are antipsychotics but I don't think  I should be on those.  And also TCA's like Clomipramine(sister drug to imipramine) which I am on right now.

I looked into other drugs which might be used off-label for anxiety and found mood stabilizers. Valproate and Carbamazepine interest me the most, has anyone been on either of those for social anxiety or  the likes?

Tiagabine and Pivagabine also intrest me but they are not prescribed were I live.

[John250]

hi, I have tried various drugs SSRI,SNRI & MAOI for my SA that have not worked. I'm not sure what is left to try, I mean there are antipsychotics but I don't think I should be on those. And also TCA's like Clomipramine(sister drug to imipramine) which I am on right now.
I looked into other drugs which might be used off-label for anxiety and found mood stabilizers. Valproate and Carbamazepine interest me the most, has anyone been on either of those for social anxiety or the likes?
Tiagabine and Pivagabine also intrest me but they are not prescribed were I live.

I’ve used both and what I noticed was a dulling of emotions. Lexapro at only 10mg works great for me for anxiety but the other 2 just made me tired with mild anhedonia. My mood was a bit more stable but that could’ve been from just being tired.

[Junipersun]

Also tried both, they are shit. Don't do much for anxiety and come with nasty side effects. 

[jack black]

I agree too. However, try Lamictal and/or Lithium, they are mostly side effects free and work quite well.

However, the the best thing for SA is lowly propranolol. I try not to take everyday, as it can cause depression and sexual dysfunction.

[kurdishfella]

I have tried beta blockers they are useless including propranolol.

 

the reason I choose valproate and carbamazepine is becuase they both inhibit CRH , lithium and lamictal does not.

 

I think I will go with valproate becuase of how many areas of CRH it affects :

 

 

Valproic acid decreased CRF concentrations in the median eminence and raphe nuclei. Moreover, CRF mRNA expression was decreased in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) of the hypothalamus.

Valproate decreased CRH release in rats.

Valproate significantly diminished the cortisol response to hypoglycemic stress.

Furthermore, repeated administration of VPA has been reported to decrease receptor binding of CRH/CRF1 in the amygdala and CRH/CRF2A mRNA in the paraventricular nucleus of the hypothalamus.

Valproic acid is a powerful HDAC inhibitor.

The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells.

CRF1 receptor binding was decreased in both the basolateral amygdala and cortex by Valproic acid.

Valproate altered glutamate metabolism in the hippocampus.

Valproic acid is also able to stimulate the extracellular signal- regulated kinase (ERK) pathway in the rat hippocampus and frontal cortex, and it has been suggested that this effect might mediate the antimanic action of the drug. We can speculate that one or more of the pathways listed here could be involved in mediating the effects of valproic acid on CRF mRNA expression.

Sodium valproate significantly elevated GABA and taurine in most regions. Aspartate and glutamate were less affected.

Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors.

Pharmacological inhibition of fatty acid amide hydrolase (FAAH) attenuates social behavioural deficits in male rats prenatally exposed to valproic acid.

Valproic acid thought to possess anticonvulsant activity because it inhibit voltage-gated sodium channels, which prevent NRHypo neurotoxicity (glutamate excitatory).

 

[Junipersun]

Consider that Valporate is an anti-androgen, which might in itself contribute to anxiety and depression. It is also harder to built muscle mass while on valporate. 

[kurdishfella]

is there any special dose when it becomes an antagonist on androgen? Like if I stay under 500mg I could be Ok and avoid the anti-androgen action?

Edited by farshad, 18 October 2018 - 04:48 PM.

[John250]

If you’re looking for anti-anxiety I would think it would almost be safer to responsibly use benzodiazepines over something like Valproate and Carbamazepine. Who knows what kind of long-term side effects they can have. Plus Valproate is hard on the liver. When I was using 1000mg Depakote my liver enzymes were higher than when I used oral anabolic steroids. Lamical is pretty side effect friendly but also maybe try Emoxypine and Selank first. They are anxiolytic and have a lot of health benefits.

[kurdishfella]

I'm just looking for things that target CRH-CRHR1 system which are what Helps my Anxiety. 

I have tried 2 Benzodiazepines klonopin and valium, the former didn't work and the latter was meh.. something strong like valproate that targets  many corticotropin-releasing hormone and its receptor 1  places, I  believe could be of much benefit to me.

Carbamazepine is not as effective as valproate on CRH from what I can tell , I only found 1 study which says ''Carbamazepine inhibit hypothalamic CRH''

There is also a blood pressure medication by the name of Verapamil which inhibits hypothalamic CRH .

Edited by farshad, 18 October 2018 - 05:51 PM.

[John250]

What about a CRH-CRHR1 antagonist?

Also always good info here:

https://www.selfhack...he-role-of-crh/

Edited by John250, 18 October 2018 - 09:28 PM.

[John250]

Substances to decrease CHRH1

Substances Interaction Organism Category
CP 154526 Decreases activity ® Substances of Biological Interest
Morphine Decreases reaction ® Substances of Biological Interest, Synthetic Toxin, Drugs
Naloxone Decreases reaction ® Substances of Biological Interest
Norepinephrine Decreases activity , Decreases reaction ® , ® Important Natural Compounds, Substances of Biological Interest
Pentobarbital Decreases activity , Decreases reaction ® , ® Substances of Biological Interest, Synthetic Toxin, Drugs
Methamphetamine Decreases activity , Decreases response to substance ® , ® Substances of Biological Interest, Synthetic Toxin, Drugs, Common/Popular Medications
Corticotropin-Releasing Hormone Decreases activity ® Substances of Biological Interest
Antalarmin Decreases activity ® Substances of Biological Interest
R 121919 Decreases activity ® Substances of Biological Interest
Astressin Decreases activity ® Substances of Biological Interest
Phenylalanyl corticotropin-releasing factor (12-41) Decreases activity ® Obscure Chemicals
2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine Decreases activity ® Obscure Chemicals
Hydrogen Peroxide Decreases expression ® Beneficial Substances, Important Natural Compounds, Substances of Biological Interest, GRAS
Methimazole Decreases expression ® Substances of Biological Interest
N-(1-ethylpropyl)-(3-methoxy-5-(2-methoxy-4-trifluoromethoxyphenyl)-6-methyl-pyrazin-2-yl)amine Decreases activity ® Obscure Chemicals
NBI 77860 Decreases activity ® Substances of Biological Interest
Plant Extracts Decreases expression ® Important Natural Compounds, Substances of Biological Interest
Propylthiouracil Decreases expression ® Substances of Biological Interest, Synthetic Toxin, Drugs
Rifampin Decreases expression ® Substances of Biological Interest, Synthetic Toxin, Drugs
Triazoles Decreases activity ® Substances of Biological Interest
Vehicle Emissions Decreases methylation ® Substances of Biological Interest, Toxins, Airborne Pollutant
Astressin B Decreases activity (R R) Substances of Biological Interest
Corticotropin releasing hormone (9-41) Decreases activity ® Obscure Chemicals
Lipopolysaccharide, E coli O55-B5 Decreases expression ® Obscure Chemicals
Perchlorate Decreases expression ® Substances of Biological Interest
Pexacerfont Decreases activity (R R R R R) Substances of Biological Interest
2',3,3',4',5-pentachloro-4-hydroxybiphenyl Decreases expression ® Obscure Chemicals
Propionaldehyde Decreases expression ® Substances of Biological Interest
4-(1-ethylpropoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridine Decreases activity ® Obscure Chemicals
4-(2-chloro-4-methoxy-5-methylphenyl)-N(2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl)-5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine Decreases activity (R R) Obscure Chemicals
4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)pyrimidine Decreases activity (R R) Obscure Chemicals
4-(bis(2-methoxyethyl)amino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)-1,3,5-triazine Decreases activity ® Obscure Chemicals
Arsenic Decreases expression ® Substances of Biological Interest, Airborne Pollutant, Cigarette Toxin, Food Toxin, Household Toxin, Natural Toxin, Pesticide, Pollutant
BMS-764459 Decreases activity ® Substances of Biological Interest
CRA1000 Decreases activity ® Substances of Biological Interest
Corticosterone Decreases expression ® Potential Recommendations, Possibly Consumable Substances, Substances of Biological Interest
Dibutyl Phthalate Decreases expression ® Substances of Biological Interest, Airborne Pollutant, Food Toxin, Household Toxin, Industrial/Workplace Toxin, Natural Toxin, Pollutant, Synthetic Toxin
Dietary Fats Decreases expression ® Potential Recommendations, Possibly Consumable Substances, Food, Fats and oils, Beneficial Substances, Important Natural Compounds, Substances of Biological Interest, GRAS
GW 876008 Decreases activity ® Substances of Biological Interest

Substances to decrease CHRH2

Substances Interaction Organism Category
Pirinixic acid Decreases expression ® Substances of Biological Interest
Astressin Decreases activity ® Substances of Biological Interest
Astressin B Decreases activity ® Substances of Biological Interest
2,4,5,2',5'-pentachlorobiphenyl Decreases expression ® Obscure Chemicals, Airborne Pollutant, Industrial/Workplace Toxin, Pollutant, Polychlorinated Biphenyl, Synthetic Toxin
2,5,2',5'-tetrachlorobiphenyl Decreases expression ® Obscure Chemicals, Airborne Pollutant, Industrial/Workplace Toxin, Pollutant, Polychlorinated Biphenyl, Synthetic Toxin
Cadmium Chloride Decreases expression ® Substances of Biological Interest, Airborne Pollutant, Food Toxin, Household Toxin, Industrial/Workplace Toxin, Pesticide, Pollutant, Synthetic Toxin
Dibutyl Phthalate Decreases expression ® Substances of Biological Interest, Airborne Pollutant, Food Toxin, Household Toxin, Industrial/Workplace Toxin, Natural Toxin, Pollutant, Synthetic Toxin
N-Methyl-3,4-methylenedioxyamphetamine Decreases expression ® Obscure Chemicals
Nanotubes, Carbon Decreases expression ® Substances of Biological Interest
PCB 180 Decreases expression ® Substances of Biological Interest, Airborne Pollutant, Industrial/Workplace Toxin, Pollutant, Polychlorinated Biphenyl, Synthetic Toxin
Plant Extracts Decreases expression ® Important Natural Compounds, Substances of Biological Interest
Propylthiouracil Decreases expression ® Substances of Biological Interest, Synthetic Toxin, Drugs
Thyroxine Decreases expression ® Possibly Consumable Substances, Beneficial Substances, Important Natural Compounds, Substances of Biological Interest, Common/Popular Medications
Vehicle Emissions Decreases methylation ® Substances of Biological Interest, Toxins, Airborne Pollutant
Astressin-2B Decreases activity (R R R R R R R) Substances of Biological Interest
Bisphenol A Decreases expression ® Substances of Biological Interest, Toxins
Phenylalanyl corticotropin-releasing factor (12-41) Decreases activity ® Obscure Chemicals
Procymidone Decreases expression ® Substances of Biological Interest
Sauvagine Decreases activity (R R) Substances of Biological Interest
Titanium dioxide Decreases expression ® Substances of Biological Interest
2,2',3',4,4',5-hexachlorobiphenyl Decreases expression ® Obscure Chemicals, Airborne Pollutant, Industrial/Workplace Toxin, Pollutant, Polychlorinated Biphenyl, Synthetic Toxin
Vinclozolin Decreases expression ® Substances of Biological Interest, Pesticide, Synthetic Toxin
2,4,4'-trichlorobiphenyl Decreases expression ® Obscure Chemicals, Airborne Pollutant, Industrial/Workplace Toxin, Pollutant, Polychlorinated Biphenyl, Synthetic Toxin
2,4,5,2',4',5'-hexachlorobiphenyl Decreases expression ® Obscure Chemicals, Airborne Pollutant, Industrial/Workplace Toxin, Pollutant, Polychlorinated Biphenyl, Synthetic Toxin

Edited by John250, 18 October 2018 - 09:33 PM.

[kurdishfella]

 

 

Substances to decrease CHRH1

do any of them seem practical to even use? not for me 

Edited by farshad, 19 October 2018 - 01:15 AM.

[John250]

Maybe kratom?

https://books.google...tom crh&f=false

https://corpina.com/...ls-brains-sake/

Edited by John250, 20 October 2018 - 12:28 AM.