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Gabapentinoids against anxiety. Extraordinary Phenibut

Paracelsus

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Today we will talk about a group of substances that have interesting mechanisms of action and multiple applications as a sedative, anti-anxiety and hypnotic. We will talk about gabapentinoids in general, and their unusual representative - phenibut.

Why might it be interesting for Breaking Bad users? In my opinion, anxiety is one of the problems that accompanies today not only people whose lives are associated with risk, psychoactive substances and hard work, but also almost everyone in general. We live in a time of great changes and paradigm shifts. This is a very interesting time. But it can be unpleasant for the psyche and subjective perception of life.

Usually the anxiety is silenced with tranquilizers, but in my opinion these are too drastic measures. I don't like tranquilizers because of their side effects and high, for a medical substance, addictive potential. They need to be used when other methods do not help. Therefore, I want to draw your attention to another group of drugs. They are more accessible, less addictive and, with the right approach, can help to get rid of anxiety manifestations both in everyday life and when using substances or during recovery activities.


Gabapentinoids

Gabapentinoids are a class of drugs that vaguely resemble the neurotransmitter gamma-aminobutyric acid (GABA) (i.e. GABA analogues). Although they were designed to mimic the action of GABA, more recent studies have found that they affected another target, the A2D subunit of calcium channels. Two gabapentinoids are approved by the FDA: gabapentin and pregabalin. Several more are currently being tested (imagabalin), others are being used in scientific research (atagabalin).

Gabapentin has been a universal drug since 2004. It is commonly used for seizures, nervous pains, alcoholism, drug addiction, itching, restless legs, sleep disorders and anxiety. It has an unusually wide range of doses: recommendations suggest using from 100 mg to 3600 mg per day. Most doctors use it at a low level, where it is quite inconspicuous (read: it usually doesn't work). At the highest level, it can cause sedation, confusion and addiction.


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The mechanism of action of pregabalin. It modulates hyperexcited neurons via the following mechanism:
Pregabalin binds to presynaptic neurons at the alpha2-delta (α 2-δ) subunit of voltage-gated calcium channels.
Drug binding reduces calcium influx into presynaptic terminals. Decreased calcium influx reduces excessive release
of excitatory neurotransmitters (eg, glutamate, substance P, noradrenaline).


From the point of view of the scientists who analyzed pregabalin, it definitely does the same thing as gabapentin. But in practice, it often turns out that gabapentin does not seem to work so well. Patients, even with minimal manifestations of anxiety, cannot do with gabapentin alone. While studies confirm that pregabalin is great for anxiety. At the same time, gabapentin shows itself well only in some cases, such as social phobia. It is not effective for panic or agoraphobia, and in the case of generalized anxiety disorder, it shows itself only in combination with tranquilizers. Why this happens is still unclear.

One possibility is that the dosages of these substances taken are incorrect. UpToDate recommends treating anxiety disorders with gabapentin, using an initial dose of 600 mg per day. But it recommends 300 mg of pregabalin per day. This dosage table assumes that 1 mg of pregabalin = 5 mg of gabapentin, so 300 mg of pregabalin = 1500 mg of gabapentin! Perhaps what they think of as a ”high dose" of gabapentin coincides with what we think of as a ”low dose" of pregabalin. Maybe all the doses of gabapentin are just too small? This is an open question, but not a recommendation to consume more gabapentin. Do not forget that more mgs - more risks of adverse reactions.

Another possible reason is some obscure pharmacological mechanism. In one study, we tried to compare the pharmacology of two drugs. They say that the body can easily absorb pregabalin, but has a limited ability to absorb gabapentin – the more gabapentin, the less the percentage is absorbed.

Another important difference: gabapentin is usually not a controlled substance or less controlled, but pregabalin is technically addictive, but it's not worth worrying too much about. Although it is theoretically possible to become addicted to gabapentin, if you take a really large dose and try very hard, you should be desperate even by the standards of drug addicts. There are many more cases of dependence on pregabalin, although most experts agree that this is still quite unusual. One of the likely culprits is the rate of absorption: pregabalin is absorbed in about an hour, gabapentin - in three or four. Fast-acting substances are always more addictive; they peak higher and earlier, and it is easier for the brain to associate the stimulus (taking the drug) with the reaction (feeling good).



Phenibut

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According to the Classification System of Anatomical Therapeutic Chemistry (ATC), phenibut is consistently included in the groups of analeptics, psychostimulants, ADHD medications and nootropics. Already at this stage, strange things begin. Earlier we talked explicitly about anti-anxiety, tranquilizing, and therefore sedating effects, but here we see the opposite - phenibut is referred to as a stimulant.

In most countries, phenibut is sold without a prescription. Moreover, it is often sold not as a medical drug, but as a dietary supplement in stores, not pharmacies. I do not recommend buying phenibut in stores or online in powder form or without normal medicinal packaging - it is not known what you will take inside in this scenario. It is worth buying phenibut in pharmacies or at least in packages under the licensed names Phenibut, Phenibut, Noofen, Citrocard.

It's funny that the FDA sometimes asks people to stop selling it, but they never got serious and it's still easily available on the open internet. But in some countries in recent years it has been made prescription. This applies primarily to the countries of the former Soviet Union. I had a funny thought that the availability of phenibut reflects the level of freedom in society. As long as it is freely available, you can relax. But enough jokes, let's continue.

With regard to social anxiety, prevention of panic reactions, agoraphobia, generalized anxiety, phenibut often shows very good results. In addition, it can give a hard-to-describe feeling of calm and well-being.

Early research into phenibut focused on GABA, the main inhibitory neurotransmitter. The brain has two kinds of GABA receptors, GABA-A and GABA-B. Alcohol, Xanax, Valium, Ambien, barbituates, and the other classic sedatives all hit GABA-A. There aren’t that many chemicals that hit GABA-B, and the few that are out there tend to be kind of weird – one of them fell to Earth on a meteorite. But phenibut is a GABA-B agonist. This sounds like a neat solution to the mystery: a drug with unique anti-anxiety properties affects a unique inhibitory receptor. But another GABA-B agonist, baclofen, has minimal anti-anxiety effects. It is mostly just a boring muscle relaxant (there was some excitement over a possibility that it might cure alcoholism, but the latest studies say no). So probably GABA-B on its own doesn’t explain phenibut.

As for the place of phenibut in the classification by mechanism of action, today it refers to both GABA receptor agonists and gabapentinoids. The fact that phenibut acts as a gabapentinoid has been discovered relatively recently. I found articles from 2015 that point to this. Until that time, phenibut was considered only as an agonist of the GABAB receptor. But its gabapentinoid activity is much weaker than that of gabapentin itself, so why should its effect be stronger?

Baclofen is superior to phenibut as a GABA-B agonist, and gabapentin is superior to phenibut as a gabapentinoid, but phenibut works better than either of them. Magic! Could this be a synergistic effect between two different actions? If this were true, we would expect that the combined intake of gabapentin and baclofen would have an effect similar to phenibut. But these drugs are sometimes used for the same neuromuscular diseases, and no one has ever noticed anything unusual. I'd love to see how it's being studied, but I don't expect much.

Phenibut has two enantiomers, r-phenibut and s-phenibut. Both are decent gabapentinoids, but only r-phenibut has GABA-B activity. If both worked equally well, that would suggest phenibut worked on A2D; if r-phenibut worked better, that would implicate GABA. Someone think that phenibut is probably more GABA-B agonist than gabapentinoid, but этоне объясняет explain why it’s so different from baclofen.

There is the point that baclofen has some issues with blood-brain barrier permeability. Although some of it gets through, it could build up in the plasma much faster than in the brain, giving it disproportionately peripheral effects.


Recommendations

Phenibut shows its effectiveness in anxiety, fear, obsessive states, insomnia and nightmares, dizziness. In states of abstinence from alcohol, stimulants or euphoretics. In these cases, the medicine should be taken by the course.

A single dose for adults is 20 - 750 mg. 20 mg seems to be too small a dose, in my practice I started with 65 and reached 250 mg. The optimal dose for me is 125 mg. It is better to start with a minimum. Usually the drug is taken 3 times a day: in the morning in the afternoon and in the evening. The maximum daily dose should not exceed 2.5 g (if a person is more than 8 and less than 60 years old).

It is worth taking phenibut for 2-3 weeks, you can extend the course up to 6 weeks. With prolonged use and high dosages, it is necessary to monitor liver function indicators and the biochemical picture of peripheral blood. Between courses, it is worth taking a break of 2-4 weeks. After taking the drug for a long time, it is better to stop gradually.

Needless to say, phenibut is potentially addictive and can seriously ruin your life. The conventional wisdom in the phenibut user community is that you can safely take 500 mg once a week (or maybe every two weeks). Anything that goes beyond that and you quickly develop tolerance. Increase the dose to combat tolerance, and you will start feeling worse on the days when you don't take it, using it more and more to compensate for the rebound, and eventually get withdrawal syndrome, closely related to delirium tremens, which sometimes kills recovering alcoholics.

Phenibut lengthens and enhances the effect of hypnotics, narcotic analgesics, antiepileptic, antipsychotic and antiparkinsonian drugs. Also, it should not be mixed with alcohol and exclude or at least reduce the consumption of the latter during the course of phenibut.

Phenibut should not be consumed if you have stomach problems - it has a strong irritating effect on the mucous membrane. At a minimum, it is worth reducing the dosage if you feel increased heartburn or unpleasant sensations in the stomach.

As for the use of stimulants, euphoretics, cannabis, cannabinoids, psychedelics. In general, all substances that directly or indirectly increase anxiety under certain circumstances. Phenibut can reduce these manifestations. Both for those who have them caused directly by use, and for those who experience post-effects. In these cases, it is worth taking phenibut in a single dosage for adults of 20 - 750 mg. Unfortunately, the dosage will have to be selected independently - phenibut acts quite individually and is very heterogeneous for different people. We adhere to the rule: We start with the smallest single dose. We paint up to the working dose. We do not raise it higher.

A couple cases for example:
1. A person uses cannabis, but has recently been experiencing panic reactions when using it. A break, a change of grade, set and settings do not help. Take 60-125-250 mg of phenibut 20-30 minutes before the planned smoking (here and further indicate the possible dosage ranges).

2. The person had a session with stimulants or euphoretics. Does not plan to wait out this day. He wants to go away and rest. He is afraid of phenomena characteristic of the termination of the action of these substances. Take 250-375-500 mg of phenibut once. Drink mineral water without gas in small portions. Eliminate physical exertion, strong visual, auditory and stressful stimuls.

Phenibut is recreationaly taken for its anxiolytic and euphoric properties, with tolerance and withdrawal syndromes commonly reported adverse effects. It`s taken orally at an average dose of 2.4 g - it`s huge dose, really. Case reports in the medical literature feature users who present to emergency departments heavily sedated or experiencing withdrawal. There have been no reported deaths relating to phenibut use. I recommend using it only according to the indications and in the dosages described above or after consulting with a doctor.

Be calm and understand what you are going to do with your own neurochemistry.
As always, I invite everyone interested to a discussion.
Thank you for your time.
 

HIGGS BOSSON

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Working in an underground laboratory carries legal risks. Many develop paranoia against this background, if you engage in illegal activities for a long time. Will Phenibut help get rid of the paranoia associated with the police?
 

Paracelsus

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In my opinion, phenibut can help. He does not remove paranoia, because it islogical and real in the described situation. But it (like other gabapentinoids) can help with anxiety, fear-mongering, concentration. This will allow a person to do things more efficiently, spend time outside of work more calmly and improve the quality of life. For this option, the course plan, which is described in the topic, is suitable. This is not a panacea, but an option.
 

AlexBarkat

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Thanks for sharing this information about gabapentinoids and their potential for managing anxiety. It's always good to explore alternative ways to address anxiety without relying solely on tranquilizers. Mental health is crucial, and it's great that you're shedding light on this topic. Speaking of mental health, I came across some valuable insights on https://www.mentalhealth.com/therapy/benefits-of-healthy-high-self-esteem that emphasize the importance of healthy self-esteem in maintaining overall well-being. Anxiety affects so many people in various ways, and it's essential to have open discussions about potential solutions.
 

blacky2340

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I personally am on pregabalin which was initially offered to me by a friend who is a doctor for getting better quality sleep. I take 150mg of pregabalin in the morning/day which boosts my mood and does reduce anxiety, but nothing like a cure. Before sleep 250-300mg does knock me out so bad that I can do a line of speed on it and it will still knock me out cold. First time I took it before sleep was the first time I had a dream that actually made sense to me and was meaningful as well, I'm not sure I ever had better sleep. (I have an affective mood disorder, I am able to go a week without sleep until hallucinating vividly, which is really hard on me)
Have not tried phenibut or gabapentin, but I'm sure they work in a similiar way.
 

Paracelsus

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I personally am on pregabalin which was initially offered to me by a friend who is a doctor for getting better quality sleep. I take 150mg of pregabalin in the morning/day which boosts my mood and does reduce anxiety, but nothing like a cure. Before sleep 250-300mg does knock me out so bad that I can do a line of speed on it and it will still knock me out cold. First time I took it before sleep was the first time I had a dream that actually made sense to me and was meaningful as well, I'm not sure I ever had better sleep. (I have an affective mood disorder, I am able to go a week without sleep until hallucinating vividly, which is really hard on me)
Have not tried phenibut or gabapentin, but I'm sure they work in a similiar way.
blacky2340That's right, all this substances belong to Gabapentinoids. However, their mechanisms of action may differ. This also leads to differences in effects and effectiveness. Sometimes insignificant, sometimes pronounced. However, using them on a regular basis, it is better to avoid increasing the dosage, and if the effects begin to weaken, it is worth considering the option to take break to avoid the development of tolerance and withdrawal syndrome. It can be unpleasant, but it is quite realistic to carry it at home. The situation, of course, may be complicated by the existing specificities of your neurochemistry.
 
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