stillwater,
As far as prescription GABA -A agonist medications, everything from the barbituates and drugs like meprobamate, to the modern day benzodiazepines are highly effective. I butt heads with a lot of the psychiatrists that I work with and their prescribing habits on occassion, since they tend to like to prescribe SSRI's (Selective Serotonin Reuptake Inhibitors), or anti-psychotic dopamine antagonist drugs like thorazine to deal with Panic Attack Disorder. First off, PAD is a VERY different condition than Generalized Anxiety Disorder or Agoraphobia (Social Anxiety Disorder), as these disorders tend be be modulated by serotonin, and go hand-in-hand with Serotonin-Mediated-Depression. Whereas Generalized Anxiety Disorder is a mental condition, where individuals lay awake at night wondering how they are going to pay their car insurance bills, etc.,Panic Attack Disorder is not a typical mental disorder, and is more physical than anything - causing pain and/or tightness in the chest and/or head, causing severe sweats, and flooding the brain with the "flight or flight" panic sensation that leads people to believe that they are having heart attacks and/or dying. Panic Attack Disorder is caused by an imbalance in two neurotransmitters - a deficiency in GABA, and an over-abundance in norepinephrine (or "nor-adrenalin").
True Panic Attack Disorder has nothing directly to do with serotonin biosynthesis, release, reuptake, or metabolism. Even more ridiculous than expecting an SSRI drug to effectively combat Panic Attack Disorder is using a dopamine antagonist anti-psychotic drug. Panic Attack Disorder has literally nothing to do with synaptic or neuronal dopamine levels. These drugs simply antagonize the dopamine receptors so much that a person is literally rendered a zombie, and just doesn't notice the panic attacks as pronounced. (Think of the schizophrenic patients in mental wards who sit and look out of the window while drooling on themselves, unable to even think normally). So, just because the dopamine antagonist drugs "zombify" you enough that you don't necessarily notice the panic attacks as much, does not mean that it's an appropriate treatment. Using a good GABA -A Receptor agonist like a benzodiazepine tends to be the most effective prescription treatment. Some Selective Serotonin Reuptake Inhibitors used alongside of a benzodiazepine can benefit panic attacks indirectly. Ideally, a good norepinephrine (adrenergic) antagonist drug would be a great development to combat the "flight or flight" panic reflex that is the cause of the panic attacks in the first place. Myself and my colleagues at our institution are working on several prototype drugs of this class currently.
As far as over-the-counter nootropic or herbal supplements, the kavalactone alkaloids found in the Kava Kava plant can be beneficial, and the brand Yogi now makes a kava stress-relief tea. Some of the flavonoids in Chamomile can be helpful in taking the edge off of panic attacks as well, and I highly recommend name brand Celestial Seasonings Sleepytime Tea. You can also look into the herb Withania somnifera (Ashwagandha), as it possesses some alkaloids that modulate neuronal GABA transmission. However, in my experience, Phenibut is far more effective than any other supplemental or nootropic substance, and if it is combined the correct way with a prescription drug regimen, it can significantly improve one's quality of life. Also, unlike many GABA -A Receptor agonists (like benzodizepines), tolerance to Phenibut does not occur nearly to the same degree. The intial sedating effects will become less prevalent over time, but the anxiolytic properties remain intact at right around the same dose. I have been at the same dosage for years, and have even been able to cut my dose down a bit more recently, and still maintain great control over anxiety.
Sarif,
There are two major forms of Phenibut that can be purchased by supplement suppliers - Phenibut in it’s free-amino-acid form (“Phenibut FAA”), and the hydrochloride salt of Phenibut (Phenibut hydrochloride, or “Phenibut HCL”). Both have their advantages. Generally water-soluble salts of different drugs are more easily absorbed by the gastrointestinal tract, however since Phenibut is a water-soluble amino acid in it’s pure form, Phenibut Free-Animo-Acid is still absorbed fairly well. (Phenibut is subject to extremely degradable first-pass metabolism in the stomach and GI tract, and so large doses of either form have to be used, as a large majority of the oral dose will be destroyed in the stomach). Phenibut Free-Amino-Acid has the advantage of not being so horribly sour in the mouth compared to Phenibut hydrochloride, and so it can be taken sublingually (dumped under the tongue to dissolve, and be absorbed by the veins under the tongue).
Whether taking Phenibut in free-amino-acid form or as Phenibut hydrochloride, most people dose once to twice daily. Personally, I have always only ever needed to dose once in the morn ing, as I feel the anxiolytic effects last a good twenty-or-so hours. Since the Phenibut in free-amino acid form, is it’s pure form, and does not contain the hydrochloride portion of the molecule on it, like Phenibut hydrochloride does, it is about 18% more potent, milligram for milligram than Phenibut hydrochloride. Either way, typical starting doses are 500mg to 1000mg, and after you titrate up to your ideal dosage, doses of 4000mg are not all that uncommon. (I’ll have to weight my usualy daily dosage tomorrow morning, as I take what most people consider to be an enormous dose). Most Phenibut supplement suppliers recommend only taking Phenibut twice per week to avoid the development of the mild dependence that Phenibut can cause, but that really isn’t realistic if you are using Phenibut for a legitimate therapeutic purpose. I have dosed every day for years, and as long as you gradually wane your dose down before discontinuing use, you should avoid the withdrawal syndrome, and the rebound anxiety. - That is the difference between addiction and dependence. You certainly can become mildly dependent on Phenibut, but is anybody really “addicted” to Phenibut? I’ve never heard of anybody gathering up their buddies to get together and get f#cked up on Phenibut. There are many people who are dependent on blood-pressure medications like lisinopril or beta-blocker like metoprolol, but are they “addicted” to these drugs? Of course not.
As I mentioned above, unlike GABA -A Receptor agonist drugs like benzodiazepines, tolerance to Phenibut does not occur to a very noteworthy degree. The initial sedating effects will become somewhat less apparent over time, but the anxiolytic properties are generally maintained by a steady, effective dose. I have taken the same dose for years, and I have even cut that dose down a bit recently, and I still retain very good anxiety control from my usual dose. If Baclofen sedates you, than yes, Phenibut is going to sedate you to some degree as well, as they function almost identically pharmacologically. (With Phenibut possessing a few unique properties, that I will touch on below). As far as brand name manufacturers, I suggest Liftmode.com. I have bought off them for years, and even ran analyses on some of their products, when they were still selling through Amazon, before the creation of their website. Their prices are great, and the quality is unsurpassed - the best that you will find.
medievil,
You are correct in some regards, and I touched briefly on the Ca+ neuro-transmission in my original post. Myself and my colleagues have both confirmed and measured the binding affinities of Phenibut, Baclofen, and over a dozen other GABA-chain esters and derivatives that I’ve developed, at the GABA -B Receptor, using in-vitro cloned GABA -B Receptors, and in-vitro Electrocondusive-Magnetic Resonance Imaging and Crystalline X-Ray Fluoroscopy. We have also confirmed the GABA -B binding and agonist activity on the overall effects of Phenibut on anxiety, by using the selective GABA -B Receptor antagonist Saclofen (and additionally using Phaclofen), which effectively cancelled out the majority of the anxiolytic effect of Phenibut in both in-vivo animal and human models. Both Phenibut and Baclofen have comparable binding affinity for the GABA -B Recetor, and both function as full agonists at this receptor, Baclofen’s agonist action is somewhat greater.
In addition, Phenibut antagonizes the TAAR1 (Trace Amine Associated Receptor), blocking the binding of endogenous B-phenethylamine in the brain. Also, you are correct that one of the pharmacological mechanisms-of-action that Phenibut possesses is as a gabapentinoid (such as gabapentin and pregabalin), which acts of as a preferential blocker of a2o subunit-containing Voltage-Gated-Calcium channels of the GABA protein ligands, which is responsible for Phenibut’s in-direct modulation of synaptic dopamine release, and at which site Baclofen has no appreciable binding affinity for. (This effect of the Ca+ a2o-subunit likely additionally adds more sedating property, and anticonvulsant potential than pure GABA -B agonists typically do. Knowing this, in addition to classifying Phenibut as a GABA -B Receptor agonist, we can also classify it as a GABA -B Receptor Positive Allosteric Modulator.
It is incredible that the simple addition of a single chloride atom on the phenyl ring of Baclofen could cause such dramatic pharmacological actions. It is also amazing how much the simple addition of a cyclic phenyl ring on both of these compounds can change the simple action of GABA so much, and effect the compounds’ selectivity so much.
-John Gona
Psychopharmacologist,
Psychotropic / Nootropic Treatment Specialist
Oracle Laboratories
NeuroPsych Institute
