Misc Lethality Danger of Barbiturate/Non-Barbs in Comparison to Physical Dependancy Dangers of Benzo's/gaba-aR PAM's

[Phenpsycho]

I'm just wondering how some of the older tranquilizers compare to benzodiazpines/Gaba-aR PAMS when it comes down to physical dependency only, namely barbiturates, and non-barbiturates that act at the same site(aka clomethiazole, carisoprodol/meprobamate). I recently acquired some phenobarbital, and carisoprodol(Soma), and am aware of the increased risk of lethal overdose. I'm also aware that they're considered highly psychologically addicting like benzos, yet I never hear about their actual physical dependence liability in comparison to the BZD's/PAM's.

Is it common to develop physical dependence to and withdrawal from barbiturates or similar tranquilizers as quickly as with the newer anxiolytics? I know some tranquilizers like carisoprodol are claimed to be able to mimick gaba without the endogenous neurotransmitter present in quantifiable amounts in animal experiments. Does this mean Soma functions more like psychedelics do on serotonin transporters, like merely mimicking some aspects of what serotonin does to the body, while not quickly re-structuring the input/output of GABA itself?
If so, I would think that while benzo's and similar anxiolytics are safer physically, your body would become reliant on them much faster as a trade off.

I may be misunderstanding this wrong, which is why I'm asking here. I'm confused about this subject. I don't know if it's only Soma and Clomethiazole that mimic GABA's dampening of neuronal firing, or all barbiturates. I know this subject is complex, so don't hold back, I'm really interested in learning about this.

I used to think barbiturates/Soma/clomethiazole needed GABA to have an effect, but I've been reading conflicting information. Benzo's act more like SSRI's only in the sense that they make GABA available through modulation of the rate at which it's released, and is then re-uptaken; however, SSRI's and BZD/PAM's always need endogenous neurotransmitters to have an effect, is this correct?

The more I think about it the more I'm unsure of this subject :/

 

[Flynnal]

Is it common to develop physical dependence to and withdrawal from barbiturates or similar tranquilizers as quickly as with the newer anxiolytics?

As quickly? I would say about the same. No matter what drug it is, if it affects a specific receptor by activating it, then that receptor will be desensitised to the normal ligands and activators of that receptor. This is why withdrawal happens. If it were not for the body/brain adapting to long-term use of a specific drug, withdrawal would never happen. But it does, and unfortunately it can even be fatal where sedative-hypnotics or tranquilisers are used long term.

I used to think barbiturates/Soma/clomethiazole needed GABA to have an effect, but I've been reading conflicting information.

Barbiturates can emulate the function of GABA even without the presence of GABA itself. That is, they not only modulate GABA post-allosterically but can also directly act as GABA and essentially replace the function of it.

 

[Phenpsycho]

Thanks for the clarification on the subject. It was insightful for me.

What isn't true across the board that I'm aware of is receptor desensitization to endogenous ligands in repeated response to the consumption of exogenous ones that interact with a specific receptor, using psychedelics as an example. I'm not sure about all psychedelics, but I thought they don't cause a depletion in serotonin from using them in general(this is a gross over generalization as I'm sure some must have a dirty pharmacology) I could be wrong about that I will research the subject further, and await more replies from you or other members. From my understanding currently though, psychedelics can interact with the serotonin transporter without causing desensitization of it. They cause some effects that mimic serotonin on the body, but also obviously
quite different effects like hallucinatory experiences. I'm unsure if this is due to the fact that tolerance to trip doses of psychedelics develop tolerance so rapidly, thus generally being consumed less, or because it's just their pharmacology at play. Microdosing them daily might cause desensitization to serotonin, at least I would think so.

I'm severely sleep deprived and running on stimulants, nutrient shakes, and vitamins at the moment. I've been sleeping for a few hours with the help of marijuana, but not enough each night to think clearly. I can tell there's a lot of gaps in my logic, so sorry to anyone who reads this thread, and can't make sense of my line of thinking.

I'm going to take a small dose of mirtazapine and catch up on my sleep for more than 3 hours a night. Should shove some cereal and milk down my throat, and chug some Kiefir before hitting the hay too.