Administratively:
This thread appears to be in the wrong forum. It could fit in OD but it might also do nicely in ADD (neuro/pharm discussion) since there were some points raised that were kind of advanced even if also kind of tangent. Is moving to ADD okay?
On-topic:
We don't have to look very far for a real-life example casus, do we? 2M2B (2-methyl-2-butanol, or probably more correctly 2-methylbutan-2-ol) and ECX (1-ethynylcyclohexanol) are RC alcohols that are quite potent and relatively hard for the body to metabolize since the alcohol function is sterically protected from dehydrogenase, thereby preventing conversion to side-effect or hangover producing effects like acetaldehyde does when you drink booze.
Then again, the appearance of these substances is inevitably and usually almost immediately compared to regular alcohol (ethanol), which holds a historically cultivated place in our society... so technically it is a different what-if scenario than if we consider never having discovered ethanol until just now.
Ethanol is so old that it was able to penetrate our society and our lives far before we ever became contemplative and critical beings. Even more: amongst apes it is likely for fermented fruit derived alcoholics to be alpha's in power even if somewhat out of control. Chaos can rule. Nowaways alcohol's position is hardly affected by the scrutiny imposed on most other drugs, because most importantly it concerns the interests of autorities and powerful lobbys and secondly alcohol is quite inextricable from our society and this fact is naturally used to justify and ignore the way it damages and corrupts. As the saying goes "old habits die hard", reflecting and confirming my argument.
If instead we were not conditioned to see alcohol as an easily underestimated and accepted part of the majority of cultures, and if there was no more than a feeble minority of users that had alcoholic interests at heart I believe it would be subject to the same sort of populistic incident politics we see everywhere, and that would go something like this:
At first every drug that is able to keep flying below the radar (by starting out rogue, unclassified and unregistered and claiming no casualties for a time) is ignorantly "condoned", the existence and use of the drug attract no attention but only its seekers and users'. If cultures with different values remain separated and there is very little contact there is logically also little conflict. Peaceful co-existence by default.
Then if there are incidents the sheer amount of outrage and revolt that is voiced and stirred up by the collaterally damaged, provoked and bereaved, the involved and the related... further amplified by media, that outcry can initiate inquiry. The public's conscience is taxed with controversy, misery, unacceptance and a call for justice. The cybernetic nature of the public and media also produces reverberation and resonance. Self-amplification which I think can occasionally emulate an equivalent of hysteria.
Politics when democratic are supposed to be an extension of the populus and grave injustice calls for a hero. The less internal conflict of interest there is (such as taxes and import/export business or industries such as pharmacy displeased with external involvement and regulation) and the easier it is to ignore those opposed who are interested and invested in keeping the freedom to choose themselves... the easier it is to step up and be that hero. And to promise not to let such incindents happen again, not as long as they can do anything about it, all as a way to rectify of course. To present resolution to the public's outrage and blind demand for action. Does that sound like emotions ruling? Or reason?
About GABA-ergics, some theories, info and other slight tangents:
I think Z-drugs are carcinogenic, and also while something like zolpidem may be relatively specific and effective as a hypnotic I don't think any GABAergics known are appropriate for chronic medication therapy considering abuse potential, tolerance and dependence. The symptoms would have to be even more devastating than the horror of becoming dependent on GABAergics like benzo's which I have experience with. The Z-drugs were initially thought to be safer but this may have been marketing plus wishful thinking and a lack of proper information on long-term use.
A few mild GABAergics that I do consider alright but are found to be weak or ineffective by a lot of people are valerian and it's consistuent acids or derivatives thereof, but most of all L-theanine which arrived in bulk at my doorstep not two hours ago. L-theanine (the stuff found in green tea) is a glutamine-like compound that apparently acts on the glutamate transporter and basically lowers glutamate activity that way. Glutamate is the excitatory messenger in the very system GABA is the inhibitory messenger.
I believe this indirect mechanism of action is one of the reasons it is not that effective for everyone. It is for me and this might be because I might generally have overactive glutamate as one of the factors that produces my particular form of ASD. This might be due to abnormal expression of glutamate receptors, they might be mutated and more sensitive to glutamate or they might just be more abundant.
Theanine is considered to be relatively inoccuous and self-attenuating. I understand that the GABA system / GABA receptors are special in that they have inherent activity: even when there is no GABA or agonist ligand to activate the receptors there is activity. It is hypothesized that there exists a natural equilibrium between one part of the receptors natively being in activated conformation and the other part inactivated conformation. I am not sure if the same holds true for glutamate receptors. But there is also an equilibrium between GABA and glutamate themselves since GABA can be converted into glutamate.
All this complicates our understanding of the dynamics and the influence drugs have on this system and its equilibria. I'm personally very interested in the possibilities of glutamate transporter inhibitors and if it is possible to develop more potent ones. I'd very much like to know if such compounds would be a worthwhile alternative to direct GABA agonists, and if they would retain the apparently safety profile theanine has. Also I wonder about allosterically binding (non-competitive) glutamate transporter inhibitors or ones that exhibit the umbrella binding effect which are competitive but possibly still better. Basically I hope that the complex nature of the GABA/glutamate system equilibria and especially the indirect relationships can be exploited to essentially fool the system much better than "blatant" direct GABA agonism.
By the way phenibut, a GABAB agonist, cures me of a lot of my ASD symptoms - maybe even the cleanest and selective of any drug. However, even though it might be less tricky or risky to handle for me than benzo's or other "carpet-bombing" strong depressants, it still requires cycling using it. I've been told GABAB is in particular not a receptor one should fuck with and I try to use it only rarely. Not sure if adding valerian as a GABAA modulator is smart to balance things out or if it only adds to potential problems.
I also have picamilon but I can't decide on it compared to phenibut. It has an unusual stimulating quality which makes me suspect glutamate involvement.
