Brain inflammation a key role in addiction?

[Neuroprotection]

More research is now being published that shows that addiction to a wide range of drugs of abuse including amphetamines, alcohol and opioids May not be simply a result of chemical imbalance is and personality disorders. Rather the immune system particularly microglia through the release of highly toxic pro inflammatory cytokines may induce induce and maintain drug dependence and tolerance in the long term possibly on a scale of years or decades. Anti inflammatory compounds that block sytokines can reduce craving and depressing mood.
What do you all think of this research, sorry I can't post links because of my vision but hopefully you can find this on Google.

 

[Cotcha Yankinov]

I think microglia are mediating a lot of tolerance to opoids. Blocking activation of microglia with dextro-naltrexone (blocks Toll Like Receptor 4 and so forth) can probably help shut down microglia and mitigate tolerance development, as well as mitigate other negative effects of microglia like induction of pain amplification states.

Low dose naltrexone might still work okay (it's been shown to amplify morphine analgesia) but the dextro-naltrexone isomer lacks the opoid affinity while maintaining the toll like receptor blockade, so it would be ideal, in a perfect world. But toll like receptors are up regulated on activated microglia so even low/ultra low dose naltrexone might be worth it.

Opoids bind to toll like receptors and activate the microglia on the other hand. I hope you're doing well neuro

 

[Neuroprotection]

I think microglia are mediating a lot of tolerance to opoids. Blocking activation of microglia with dextro-naltrexone (blocks Toll Like Receptor 4 and so forth) can probably help shut down microglia and mitigate tolerance development, as well as mitigate other negative effects of microglia like induction of pain amplification states.

Low dose naltrexone might still work okay (it's been shown to amplify morphine analgesia) but the dextro-naltrexone isomer lacks the opoid affinity while maintaining the toll like receptor blockade, so it would be ideal, in a perfect world. But toll like receptors are up regulated on activated microglia so even low/ultra low dose naltrexone might be worth it.

Opoids bind to toll like receptors and activate the microglia on the other hand. I hope you're doing well neuro

Do you Think that Microglyol activation contributes to benzodiazepine tolerance, and if so how much?
Yes I am great hope you're well too.

 

[Cotcha Yankinov]

I don't know about benzodiazepines, but with a similarly glutamate decreasing medication Gabapentin, downregulation of astrocyte's Glutamate transporters was found to play some role. Depakote (an HDAC inhibitor) was found to help reverse that glutamate transporter down regulation.

 

[asecin]

what anti inflammatory compounds that block cytokines can you suggest?

 

[AlphaMethylPhenyl]

Just FYI while astrocytes also participate in cleaning up apoptosis/necrosis, microglia are essential in this respect. They metabolize waste so that it doesn't do all kinds of nasty things.

Inflammation is definitely linked to mental disorders (mostly depression iirc), but to addiction?

If it's true that benzos can lead to damage of organic brain matter (temazepam most likely), microglia will be working overtime to contain and dispose of the significantly affected cells. Microglia are otherwise really important. They are agents of hygiene, like brushing and flossing and showering and washing your hair.

 

[Cotcha Yankinov]

Excellent points, someone was speaking a while ago of wanting something that wiped out all microglia by blocking some colony stimulating factor type thing that's necessary for microglial survival - that sounds like a horrible idea.

At least it's possible that when targeting toll like receptors you might get some specificity for the troublesome microglia.

 

[Limpet_Chicken]

Why temazepam over other benzodiazepines?

 

[Cotcha Yankinov]

^I'm curious as well. Short half life = more kindling and Glutamate excitotoxicity that activates microglia?

 

[AlphaMethylPhenyl]

It's the only one that I recall a definitive study on. It also has a particular hazard in its high abuse potential relative to other benzos. Abusing any psychiatric drug theoretically could cause brain damage. But just to clear the air a bit, "brain damage" is far from a well-defined concept.

All benzos have this permanent damage potential.

Funnily enough, on http://www.benzo.org.uk/adv.htm we read that it leads to increased cortisol levels. Stress hormones are not good for those under enough stress to be prescribed a benzo.

 

[Limpet_Chicken]

I must be odd in respect of temazepam then. Because its one of the least useful benzos of the lot to me. Very little euphoriant effects compared to most. Only chlordiazepoxide, diazepam, nordiazepam and oxazepam are crappier, maybe lorazepam. Best I've had being nitrazepam, loprazolam, flubromazepam and flubromazolam.