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Valproic Acid changes gene expression to negate Amphetamine addiction.


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The entire amphetamine cascade is so complex it makes sense why it’s one of the most addictive drugs there is. After spending countless hours on wiki and selfdecode I pretty much got nowhere as the majority of things that help are changing gene expression. From what I’ve gathered you want to decrease expression of deltafosB while increasing expression of deltaJunD and the histone methyltransferase enzyme (EHMT2)(G9a) plus many other changes in gene expression.

 

Of course that can’t be simple as it states:

 

“Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).”

 

 I spent 20 minutes looking up viral vectors and got nowhere lol

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*TAAR1 activation is supposed to be beneficial and of course there’s no practical TAAR1 agonists. 


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881156/

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Although I will say the one substance that I’ve seen over and over on selfdecode that seem to properly increase and decrease expression in the genes you want and decrease expression in correct genes for counteracting amph’s addictive cascade is Depakote {Valproic Acid} (VA)

I mean it seems like the closest thing you can get what are your thoughts about it? Side effects don’t outweigh the pros? My appointment with my new psychiatrist is tomorrow so I wanted to go over options.
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Links with VA and AMPH used together:

 

*Reduced distractibility-
https://www.ncbi.nlm.nih.gov/pubmed/9264079/

 

*Reduced Hyper Locomotion-
https://www.sciencedirect.com/science/article/abs/pii/S030439400701261

 

*This is interesting. VA ameliorates AMPH induced cognitive impairment:


https://www.researchgate.net/publication/51983635_Early_life_stress_exacerbates_cognitive_dysfunction_induced_by_D-amphetamine_Amelioration_by_valproic_acid

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This is in meth but it links VA to craving reduction 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025910/

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More pro’s of VA as a means to reduce AMPH tolerance and sensitization-

 

*HDAC Inhibitor

 

*NMDA antagonist

 

*GABA agonist- don’t remember the article but it found a strong linkage to depleted Gaba induced by amphetamine which is often dismissed as primary focus is mainly on DA/NE/SERT

 

*MAO-A and MAO-B inhibitor:


https://www.ncbi.nlm.nih.gov/m/pubmed/21775495/

 

https://www.hindawi.com/journals/bmri/2017/8124501/

 

*Increased expression of Tyrosine Hydroxylase and Tryptophan Hydroxylase:


https://www.ncbi.nlm.nih.gov/pubmed/26512932/

 

*Increases expression of deltaJunD 


https://www.ncbi.nlm.nih.gov/pubmed/21427059/

 

*Increases expression of JUN (Jun proto-oncogene, AP-1 transcription factor subunit) 


https://www.ncbi.nlm.nih.gov/pubmed/27188386/
Same article for decreased expression of GSK3B

 

*For FOS VA increases expression but decreases reaction not really sure if thats good or bad:


https://www.ncbi.nlm.nih.gov/pubmed/8719796/

 

*Increases expression of G9a-EHMT2(Euchromatic histone lysine methyltransferase 2)


https://www.ncbi.nlm.nih.gov/pubmed/17183730/
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The following links were from selfdecode.

 

AMPH decreases PTN expression potentially inducing neurotoxicity but Valproic Acid increases PTN expression. 4 of the 13 phosphoproteins in the PTN are linked to Parkinson’s 

 

1.) ANXA7 (Annexin A7) decreases expression by amph but increased expression by Valproic Acid
https://www.ncbi.nlm.nih.gov/pubmed/23459167/

 

2.) ALDH1A1 (Aldehyde dehydrogenase 1 family member A1) decreases expression by amph but increased expression by Valproic Acid.


https://www.ncbi.nlm.nih.gov/pubmed/23179753/

 

The other 2 I didn’t find-COP9 signalosome subunit 5 (COPS5), and creatine kinase U-type (CKMT1).

 

*Amphetamine decreases NYP (Neuropeptide Y)Valproic Acid increases NYP expression 


https://www.ncbi.nlm.nih.gov/pubmed/27188386/


And same article for decreases expression of 
CREBBP (CREB binding protein) 4.19 which I think is good since wiki stated:

 

“Chronic use of amphetamine at excessive doses causes alterations in gene expression in the mesocorticolimbic projection, which arise through transcriptional and epigenetic mechanisms. The most important transcription factors that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), cAMP response element binding protein (CREB), and nuclear factor-kappa B (NF-κB).[117] ΔFosB is the most significant VA and AMPH used together:

 

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*I believe VA is a protein kinase C activator which should make response to amph better by increased extracellular dopamine release so maybe just to be good or bad depending on if you don’t abuse it? It doesn’t increase all Calcium dependent proteins but it does increase expression in:

 

VA INCREASES expression in-

 

*CAMK2N2 (Calcium/calmodulin dependent protein kinase II inhibitor 2)


*PINK1 (PTEN induced putative kinase 1)


*PRKCE (Protein kinase C epsilon) 


*PRKCA (Protein kinase C alpha) 


*No expression under(PRKCG or CAMK1G)

 

https://www.ncbi.nlm.nih.gov/pubmed/23179753/


https://www.ncbi.nlm.nih.gov/pubmed/24935251/


https://www.ncbi.nlm.nih.gov/pubmed/27188386/

 

VA DECREASES expression in-

 

 

*Calcium-Dependent Protein Kinase Regulator Activity under gene-
HMGB1 (High mobility group box 1)

 

*CAMK2B (Calcium/calmodulin dependent protein kinase II beta)

 

*CAMK4 (Calcium/calmodulin dependent protein kinase IV)


https://www.ncbi.nlm.nih.gov/pubmed/15901671/
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•Valproate increases expression of DRD4 and DRD1


https://www.ncbi.nlm.nih.gov/pubmed/17183730/

 

https://www.ncbi.nlm.nih.gov/pubmed/23665938/
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