Role of Diazepam in Epigenetics:From the Molecular Level to Clinical Implication

"The Role of Diazepam in Epigenetics: From the Molecular Level to Clinical Implications"

 

https://pubmed.ncbi.nlm.nih.gov/33513583/

 

 

Abstract

 

There is growing evidence linking epigenetic mutations to neurologic disorders such as epilepsy. The effect of the medications primarily used to treat neurologic disorders has recently been studied, including research on epilepsy and the epigenetic process. The impact of the widely used medication diazepam on epigenomics, microRNA levels, the ensuing genetic exposure and potential clinical effects was reviewed. The action of diazepam, particularly in altering the synthesis of enzyme 5' adenosine monophosphate activated protein kinase (AMPK) was found to affect many enzymes, which changes or modifies the epigenetics. Epigenetic enzymes such as histone acetyltransferases (HATs), class II histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) are mainly activated by AMPKs, including the phosphorylate substrates, which often lead to their inhibition, although HAT1 activity may be improved. It has been reported that diazepam can reduce histone methyltransferase expression exposure, may increase class III histone deacetylases activity and may decrease the effect of DNA methyltransferases inhibitors. Diazepam has been found to contribute to mutations of the epigenome and genetic expression, and may protect against neurologic disorders, aging, dementia and several brain diseases. It has also been found that microRNA expression can be influenced by diazepam treatment and may have neurologic effects. Although the reported effects of diazepam on epigenetic enzymes of are equally effective in both amplifying and reducing acetylation of histone, histone and DNA methylation and gene expression, the effect of diazepam on the epigenome, genetic expression, and subsequent effects in all healthy diazepam users is unclear.

Read this abstract (can't find a link to the actual article) and while the authors seem to be viewing diazepam as a treatment for neurological disorders such as epilepsy all I can think is the reason we are all suffering is because the benzo causes epigenetic damage to a healthy brain!  Am I way off in thinking that?!

I was thinking the same thing, Deanna! The last line of the abstract is important:

 

"Although the reported effects of diazepam on epigenetic enzymes of are equally effective in both amplifying and reducing acetylation of histone, histone and DNA methylation and gene expression, the effect of diazepam on the epigenome, genetic expression, and subsequent effects in all healthy diazepam users is unclear."

This is all just speculation. Epigenetics is a trendy topic nowadays so people write about it a lot. Truth is we don't know much if anything.

Seems like it would be difficult to study in human beings. Wouldn't they need to eliminate confounding factors?

I was thinking the same thing, Deanna! The last line of the abstract is important:

 

"Although the reported effects of diazepam on epigenetic enzymes of are equally effective in both amplifying and reducing acetylation of histone, histone and DNA methylation and gene expression, the effect of diazepam on the epigenome, genetic expression, and subsequent effects in all healthy diazepam users is unclear."

 

Been thinking about this alot.  If you look at the disparity we have in the length and severity of withdrawal in the exposed population, this is the one theory I've heard that explains why.  We are all so genetically diverse, and if benzos impact gene expression, this explains why the road back to ourselves is so long and hard.  And I'm thinking this also explains why some long-haulers seem to never really get better, because other confounding factors like neuroplasticity, other health issues and the trauma of the experience can alter our thoughts/actions which leave their own epigenetic marks.  In a way I can see how we are never really the same because epigenetics explains that we are never really the same over time without benzos either.

 

However I choose to think positively because all of the above also means we can be our best selves going forward with all the right choices: nutrition, exercise, lifestyle changes, meditation, gratitude and kindness 

I was thinking the same thing, Deanna! The last line of the abstract is important:

 

"Although the reported effects of diazepam on epigenetic enzymes of are equally effective in both amplifying and reducing acetylation of histone, histone and DNA methylation and gene expression, the effect of diazepam on the epigenome, genetic expression, and subsequent effects in all healthy diazepam users is unclear."

 

Been thinking about this alot.  If you look at the disparity we have in the length and severity of withdrawal in the exposed population, this is the one theory I've heard that explains why.  We are all so genetically diverse, and if benzos impact gene expression, this explains why the road back to ourselves is so long and hard.  And I'm thinking this also explains why some long-haulers seem to never really get better, because other confounding factors like neuroplasticity, other health issues and the trauma of the experience can alter our thoughts/actions which leave their own epigenetic marks.  In a way I can see how we are never really the same because epigenetics explains that we are never really the same over time without benzos either.

 

However I choose to think positively because all of the above also means we can be our best selves going forward with all the right choices: nutrition, exercise, lifestyle changes, meditation, gratitude and kindness 

 

I have no doubt that genetics and other factors play huge roles in how things for each of us. So many variables involved. And neuroplasticity can work both ways, i.e. in both a positive and a negative direction. But I agree that it makes sense to work on the things that we do have control over.