Can benzo's or alcohol use flick on a normally dormant gene?

Can benzo's or alcohol use flick on a normally dormant gene in the brain like a switch?

Could a sensitive gaba gene on chromosome #15 that contains several genes involved in the movement of a of GABA between neurons called gene's GABRG3 and Gabrb1  -  They can test for those gene's now. 

There definitely may be something to it. On the other hand, the environmental stressors may play a huge role as well. Every human being has a breaking point, so technically, whether there's a gene sequence mutation or not, if you pile on enough stress on anyone, there's a chance that they may slip into alcohol or benzo use that could become habitual over time. Alcohol does seem to be more of a social thing, while benzodiazepines tend to be more of an anti-social, introverted sport, if you will. There is no hanging around with your buddies in a circle, with everyone having an ativan at the same time. I suppose drinking may become an anti-social, isolated activity too, but its roots usually originate in peer pressure and/or social gatherings. Unless we are taking about a bunch of high schoolers, trying to outdo each others in how many Xanax bars they can take, I'd think that most benzo use usually gets triggered by some sort of anxiety or panic disorder. Even the benzo use for insomnia and muscle relaxation may actually have a background anxiety/panic component to it.

Another interesting thing about the two is that alcohol seems to be a drug of defiance, and of basically challenging the status quo, but doing it in a way that is not exactly the most constructive.

Benzos, on the other hand are drugs of compliance, and it's basically a sign of not honoring our natural personality and sensitivities and trying to fit into some kind of an arbitrary mold of a perfectly functioning human being who's in absolute control of his/her emotions (NOT!).

There definitely may be something to it. On the other hand, the environmental stressors may play a huge role as well. Every human being has a breaking point, so technically, whether there's a gene sequence mutation or not, if you pile on enough stress on anyone, there's a chance that they may slip into alcohol or benzo use that could become habitual over time. Alcohol does seem to be more of a social thing, while benzodiazepines tend to be more of an anti-social, introverted sport, if you will. There is no hanging around with your buddies in a circle, with everyone having an ativan at the same time. I suppose drinking may become an anti-social, isolated activity too, but its roots usually originate in peer pressure and/or social gatherings. Unless we are taking about a bunch of high schoolers, trying to outdo each others in how many Xanax bars they can take, I'd think that most benzo use usually gets triggered by some sort of anxiety or panic disorder. Even the benzo use for insomnia and muscle relaxation may actually have a background anxiety/panic component to it.

 

Another interesting thing about the two is that alcohol seems to be a drug of defiance, and of basically challenging the status quo, but doing it in a way that is not exactly the most constructive.

 

Benzos, on the other hand are drugs of compliance, and it's basically a sign of not honoring our natural personality and sensitivities and trying to fit into some kind of an arbitrary mold of a perfectly functioning human being who's in absolute control of his/her emotions (NOT!).

That's an interesting take on it.  I think it is Dopamine release that makes alcohol different.  Both alcohol and Benzo's hits GABAA receptors but alcohol opens the dopamine centers too which is an upper like Cocaine or Meth but it only lasts for the first 2 hours and then when they shut down the lack of dopamine makes you tranquilized.

  With alcohol most fights and aggression start in the first two hours of drinking as dopamine revs people up. After that point everybody is hugging and bonding

The next day the hang over hits and by late afternoon its all over with. 

I wonder if the dopamine surge keeps the gabaA receptors from down regulating?  I read a few articles on it but these researchers do not know how to apply it yet.

I wonder which dopamine receptors get targeted by each. I wonder if alcohol basically washes over the entire chain of dopamine receptors with no specific affinity to any of them, where the benzos may be more targeted, where they will bind more tightly to a specific set of dopamine receptors that play a role in, as well as reinforce the avoidance behavior. At least the benzos for me always played into and/or reinforced the patterns of avoidance. Whether it was grief/trauma, panic attacks, work stress, health anxiety. It was always avoidance, avoidance, and avoidance. Is there a genetic basis for avoidance, or is it the blessing/curse of having a very good long-term memory that is very selective towards events of more significant value i.e. "emotional imprint" or "brain burn" so to speak?

I am not sure if there are people whose brains are more wired towards "flight" as opposed to "fight", and wonder if the dopamine receptor chains and the transporters work a bit different from a general population in these types of cases. A benzo will raise the GABA threshold temporarily in a situation where "flight" is a natural response, but it doesn't seem to be a feasible long term solution, especially in this day and age where benzos are so maligned and vilified and treated the way heroin was treated in the 70's. "Get off those darn pills", says someone who has never ever been on them. If it were that easy, why would so many people spend all this time carefully getting off of them?

I mean, if a cold turkey benzodiazepine withdrawal can cause a psychotic reaction, there is no doubt in my mind that benzos definitely have anti-psychotic qualities to them, which goes back to dopamine.

I wonder which dopamine receptors get targeted by each. I wonder if alcohol basically washes over the entire chain of dopamine receptors with no specific affinity to any of them, where the benzos may be more targeted, where they will bind more tightly to a specific set of dopamine receptors that play a role in, as well as reinforce the avoidance behavior. At least the benzos for me always played into and/or reinforced the patterns of avoidance. Whether it was grief/trauma, panic attacks, work stress, health anxiety. It was always avoidance, avoidance, and avoidance. Is there a genetic basis for avoidance, or is it the blessing/curse of having a very good long-term memory that is very selective towards events of more significant value i.e. "emotional imprint" or "brain burn" so to speak?

 

I am not sure if there are people whose brains are more wired towards "flight" as opposed to "fight", and wonder if the dopamine receptor chains and the transporters work a bit different from a general population in these types of cases. A benzo will raise the GABA threshold temporarily in a situation where "flight" is a natural response, but it doesn't seem to be a feasible long term solution, especially in this day and age where benzos are so maligned and vilified and treated the way heroin was treated in the 70's. "Get off those darn pills", says someone who has never ever been on them. If it were that easy, why would so many people spend all this time carefully getting off of them?

 

I mean, if a cold turkey benzodiazepine withdrawal can cause a psychotic reaction, there is no doubt in my mind that benzos definitely have anti-psychotic qualities to them, which goes back to dopamine.

Good logic

I wonder if the dopamine surge keeps the gabaA receptors from down regulating?  I read a few articles on it but these researchers do not know how to apply it yet.

This is something I kept pondering about. I wonder if the gabaA receptors are in the process of being upregulated, but since the dopamine surges can be quite strong, there may be a feeling that there is no progress taking place. I wonder if the gabaA receptors are the first to heal, and if the problem is that the overdriven glutamate receptors need a much longer time to settle down. It seems that the glutamate upregulation is the bigger problem here, and it's that part of the brain along with the amygdala that seems to take much longer to settle down.

Which brings me to a conclusion that how one tapers off of these meds is probably 100 times more important than how the person has taken them. And there may be situations where the main goal should be not to be completely med free, but to reduce the benzodiazepine liability to a reasonable level where a person can function and have a meaningful existence. Unless we are talking about situations where people are being involuntarily cut off form their medication or being forcibly medicated in an inpatient setting, it should really be up to the individual to decide what they want to do, and what their goal is.

I found this article yesterday when searching for info about GABA. It's called "Neurobiology of Alcohol Dependence and Implications on Treatment", and I think it might be useful for this discussion. It looks at dopamine, GABA, glutamate and serotonin, among other things.

http://www.turkpsikiyatri.com/en/default.aspx?modul=article&id=1064 

Thanks Lapis for a very good article you've provided.

And there was the term I saw for the first time - allostasis. I particularly like this paragraph

The above-mentioned effects of ethanol on the neurotransmitter, neuropeptide, and neuroendocrine systems not only account for its acute physiological and euphoric/ reinforcing effects but also seem to be responsible for the development of neuroadaptation (allostasis), which is considered as the main factor in dependence, tolerance, and withdrawal symptoms. Indeed, it is the neuroadaptive process which is mainly responsible for the tolerance phenomenon, an attempt to reduce the acute effects of the substance and to restore brain homeostasis (Eþel 2001, 2005, Koob 2013).

It may be kind of superfluous to even mention it, but most doctors who bill themselves as allopathic will, by the virtue of their approach, believe that allopathic medicine (regular and psychiatric medication) is actually very effective. I would not be surprised if the allopathic doctors who worked 100+ years ago, considered alcohol or opium as appropriate allopathic remedies for their ailing patients, regardless of whether the ailment was physical or psychological in nature.

All in all, it's a great read. Now, I also wonder if certain AD's that have a higher affinity to alter the NET channels in the brain may actually increase the norepinephrine levels, which would eventually result in a person needing some kind of a calming agent (alcohol, benzos, another, psych med, natural remedy, etc.) to deal with that problem, which hasn't existed before.

http://www.neuropharmacologie.u-psud.fr/News/Entrees/2012/4/25_Escitalopram%2C_a_selective_SSRI%2C_also_increase_norepinephrine_levels_by_inhibiting_the_NET.html

Glad you liked the article, LF. My big question is "How similar are benzos to alcohol when it comes to the neurobiology as described here?" I'd appreciate seeing a similar article on benzos.

Believe me, I'd appreciate to see one, as well, and have been scouring the web for a long time to find one. Hopefully, I'll find something. It is kind of unfortunate that we need to dig into these alcohol studies to really understand what has happened to us, but some of the mechanisms of action seem to be very similar. I am curious what is the X factor that applies to benzos that doesn't apply to alcohol. With the benzos, it may as well be that the receptors and neurotransmitters are being flicked on/off more often, which creates even less predictable results and outcomes, but again, it'd be good to find a study that goes that far.

It is also important because, while  there may be an overlap between alcohol and benzos, there is a sizeable population that drinks alcohol and will not go near a benzodiazepine, just as there is a sizeable population that will take benzodiazepines and not go near alcohol. Are these just learned preferences, or is there something more going on at play?

There's much talk about "cravings" when it comes to alcohol, but I'm not sure the same can be said of benzos. I never "craved" a benzo. Having been off them for a fair amount of time, I've never had the desire to go back on. I haven't read about other BBs who "crave" benzos. But alcoholics talk about the ever-present desire, and apparently, those sorts of feelings can be around for many years after an alcoholic stops drinking. Is that the dopamine issue? There's pleasure associated with drinking, but again, I don't think the same thing can be said of benzos.

In this article, the word "permanent" is used a number of times with regards to neurotransmitter changes. I'd like to know more about that. Have those things been tested? Can they say "permanent" with certainty?

I wasn't a drinker before all of this, but I will not be drinking alcohol again. It's too dicey. It was never that interesting or pleasurable to me, so I won't miss it. But it seems that other BBs who recuperate from all of this are, indeed, able to have some drinks and be fine.

Ah, so many questions remain! Thanks for the thoughtful input, LF!

The only "cravings" I got with benzos was when I started experiencing interdose withdrawal with ativan. But it was more of a feeling that I was going to collapse on the floor and drop dead from a heart attack if I did not take it, so there was definitely not a whole lot of "pleasure" in taking it. Something in my brain was telling me I was a goner if I didn't take it....

As far as alcohol goes, I've inherited my mother's physical intolerance to it. My father drank, but I started getting some GI issues in early age, and was always freaking out about getting an ulcer, so alcohol scared me, and even if I had one beer, I'd start sweating and feeling very odd. So, I just didn't drink. I did rely on chamomile tea, though, and that is a mild GABA agonist.

I always had tons of health anxiety and this fear of death, and read in my younger years about benzodiazepines and their protective effects and how they help with gastric and cardiac issues. Some of the literature I read from the old medical encyclopedias and prescription sheets certainly got me fooled.

Even in my 20's i used to suffer from stomach cramping and what I called "chest seizures", where I'd get this awful tightening feeling in my chest. I had some tests done, and nothing wrong was found with either my heart or my stomach back then....

The Dr. at the time said it was depression, and that depression can cause physical pain. I left confused thinking that depression was emotionial and was dumbfounded why I had all these physical symptoms.

I think the word craving may take a different meaning depending on the context. Driving down the street, and going by your favorite food place/restaurant may trigger craving for food even if you're not really hungry.

On the other hand, finding any kind of hole in the wall restaurant after driving for a lot of miles on a road where there is not much to find, there may also be craving for food because you're hungry and exhausted.

Typically, the word craving in everyday's language and conversations often refers to the first paragraph, only, which makes me wonder if the word is appropriate for the second kind of scenario when either alcohol or benzos are involved. Perhaps, a different word can be used. In the 2nd case scenario, it seems like it's more of a sort of a medically-induced maintenance.....

To me, a benzo taper is a form of maintenance, having the eventual goal of being off of them, while at the same time, maintaining a dose that is needed to remain functional on some level that is tolerable (even sometimes barely) to a person.

Typically, the word craving in everyday's language and conversations often refers to the first paragraph, only, which makes me wonder if the word is appropriate for the second kind of scenario when either alcohol or benzos are involved. Perhaps, a different word can be used. In the 2nd case scenario, it seems like it's more of a sort of a medically-induced maintenance.....

I can only speak from my own personal experience but for me alcohol and benzos were night and day different as far as cravings go. Benzos were a routine, I usually took clonazepam only before bed and I never had a conscious desire to take it. It was all "utility".

Alcohol was completely different. I could feel my body craving it. Not to the point where it overrode my ability to control myself and maintain safety for myself and others around me, but it created a distinct craving. Part of it might have been that it was just a habit to have some drinks at night but there was more to it than that and it was enough that I could extrapolate how someone who experiences stronger cravings could drink themselves to death or do any number of other stupid or dangerous things.

The way I was brought up, I always thought of benzodiazepines as anxiolytics, and something that would be used for highly stressful situations/panic attacks, etc. Usually, the daytime anxiety has always been the highest for me. The morning anxiety being the worst of it all. It never really occurred to me that people took benzodiazepiens for sleep, muscle relaxations or other causes. I did have an intuitive understanding that taking these meds every day would not be good and that I should stick to low-dose, sporadic use, but was uninformed about kindling and tapering. I've always thought that the dependence on these pills is psychological, but knew very little about the physical aspect of it. So, as I started to take the ativan here and there, I was ok, because the 0.5mg doses provided very good anxiety relief, without making me feel too sedated. But then, I also never really liked taking these pills, mostly due to the stigma and silence surrounding them, so I'd just not take them when not needed. But what I see now, and didn't see then is that I was having pretty unpleasant rebounds even from the sporadic 0.5mg dosing, and I'd experience mild feelings of DP/DR, slight agoraphobia, occasional dizziness, and feelings like my heart was going to give out. I started getting back pain and a lot of vague little aches and pains that I contributed to getting older and just being stressed out (which i really was).

Looking back I never really took ativan because it was fun to take. It just made me feel sort of ok, thinking that this is how the majority of the population with average anxiety levels usually feel. I think if my baseline anxiety was lower, I'd probably feel much more sedated on those pills, but I didn't. I did manage some nice periods without them, and unfortunately, failed to realize that those were my chances to walk away from them.

The biggest blind spot in my knowledge was kindling and not knowing these meds had to be tapered. I had this idea that they could jiust be stretched out and that I could just start taking longer breaks until I eventually no longer needed them. but my knowledge of the exact mechanism of action and the lack of knowledge about kindling is what got me.

I think ativan was a poor choice for me (not that benzos are great choices), because it binds to those GABA subunits pretty tightly, and my brain was very slow to recover from those GABA boosts.