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Panic/anxiety - GABA/Serotonin/Adrenaline/Dopamine? :)

panic anxiety gaba agonist antagonism serotonin dopamine stress acute social anxiety

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#1 birthdaysuit

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Posted 28 October 2015 - 04:47 AM


I’m 21 years of age and suffer from OCD, SAD, acute panic disorder. 

 

I exercise daily and have a routine, however, heavy weight lifting seems to increase my anxiety. Lactic acid produced in the muscles when glucose is broken down during strenuous muscular activity. Oddly enough, lactic acid has been implicated as a trigger for increased anxiety and panic in those with panic disorder. On the weekends I like to weight train and upon cessation I’m completely out of it and feel depersonalized and disconnected from others around me. These feeling occur hours after lifting and fade away during the night. I’ve only recently started to lift weights to get my upper body ready for mountain biking. 

 

​I’m also into meditating. I practice mindfulness, zen and Vipassana meditation. Some days I’m able to close eye meditate up to two hours, other days my anxiety and panic prevent me from meditating past five minutes. The anxiety locates itself in my lower chest area, near my heart as well as the upper left side of my head. The sensation in my chest feels like my heart is expanding. I’m able to cope with this by placing my hand over my heart. Meditation will exasperate this sensation.

 

The head sensation resembles a black hole, void like feeling. I often have to pull at my hair or have something touching this area for me to fall asleep. Meditation will exasperate this sensation.  

 

In the past I’ve taken picamilon for no longer than a few months, which when taken orally is presumably suppose to cross the BBB and then hydrolyze into GABA and niacin. The released GABA in theory would activate GABA receptors. GABA is said to promote relaxation and better mood, but when I take picamilon I become lackadaisical and this often feeds the onset of panic because my volubility and verbal fluency decline. I feel quite dumbed down and unintelligent. However, I am more in control of these panicky feelings and I never feel like I’m going to depersonalize or lose control. Picamilon is a GABA receptor agonist that affects the GABA-A receptor, similar to phenibut. I felt a sedative effect in dosages of 200-250mg. It doesn’t hyperpolarize the cell like alcohol does but it still has a depressant like effect. 

 

 

The problem was that I never cycled picamilon so in theory this would cause receptor down regulation and upon cessation my panic and anxiety came back in full force. 

 

I’ve tried ashwagandha as well, which has many great benefits but upon cessation my anxiety had increased 2-fold. Ashwagandha mechanism of action is agonist of GABA receptors, so that’s probably why. it posses many adaptogen and nootropic properties. It also improves stress-related memory problems by acting as a AChE inhibitor, and has the ability to prevent cognitive degeneration and even reconstruct neuronal networks. Ashwagandha also Increases testosterone and reduces prolactin levels in humans. However, one study illustrated that when male rats were given 3,000 mg/kg of the root extract for 7 days, a marked impairment in libido, sexual performance, sexual vigour and penile function was seen. Apparently there was an increase in prolactin. Note, however, that the dose used here was much higher than in the other rodent studies.

 

 

So I have learned that reduced production of GABA-A sends false information to the amygdala which regulates the body's "fight or flight response" mechanism and in return, produces the physiological symptoms that lead to panic disorder. Thus, GABA suppresses neural firing, inhibiting or regulating other neurotransmitters including serotonin, norepinephrine, and dopamine. It accomplishes this by decreasing their turnover in limbic areas - the amygdala as well as the locus ceruleus and raphe nuclei. 

 

The potential cues for triggering the anxiety response include psychological threat, novelty, social or performance situations, cognitive mechanisms, and conditioned associative memories. Thus, in panic attacks, the fear is of imminent death; in social phobia, the concern is with embarrassment; in PTSD, the emotional memory of the trauma; in OCD, the intrusive obsessional ideas; and in GAD, anxiety, there are not conditioned specific triggers (considered free-floating).

 

The large available data base on the physiology and pathophysiology of anxiety has led to the development of several neuroanatomic models of anxiety disorders. One of the most well known models was proposed by Gray, who postulated the presence of several distinct neuroanatomic circuits modulating different aspects of the anxiety reaction. In this model, anticipatory anxiety is proposed to be analogous to the state of behavioral inhibition seen in animals who are presented with a threat. In this state, the animal stops what it is doing and becomes vigilant for any sign of danger. He summarized data from animal studies to conclude that this state is activated in the presence of stimuli associated with punishment or non-reward or in the presence of novel stimuli. The actual experience of punishment or non-reward activates a different system, he called the "fight or flight" system, in which the animal responds with species-specific defensive reactions such as biting, striking, hissing, or attempting escape. This system is proposed to be most similar to the panic reaction. Evidence was presented from animal studies suggesting that the primary anatomic elements of this system include the septohippocampal areas, the locus coeruleus, and the median raphe nucleus. The theory was that the primary function of the septohippocampal formation is to act as a comparator, which assesses stimuli for the presence of danger. This comparator function is continually working at a low level when the organism is not in the presence of threat, but when threat is detected the septohippocampal system will activate the behavioral inhibition circuit, which reciprocally will cause increased monitoring of sensory stimuli for evidence of threat as well as inhibition of ongoing behavioral programs. Activation of the raphe nucleus would, in part, initiate enhanced serotonergic inputs to the hippocampus that allows an increase flow of information through this system.

The hippocampus has the densest concentration of GABA receptors and it is speculated that this may be the site of anxiolytic action for the benzodiazepines in general anxiety states. Anxiolytic drugs that affect the behavioral inhibition system might then act by either reducing the serotonergic inputs into the hippocampal septal formation. This action would have the effect of lowering hippocampal activation.

 

serotonin in anxiety is supported by its modulatory effects on the locus coeruleus and its dense projections to the amygdala. Decreased serotonin activity is associated with depression, and the most effective antidepressants have been shown to enhance the functioning of serotonin. Low activity of serotonin may permit the dysregulation of other neurotransmitters, including norepinephrine. These two systems are linked so closely that notable changes in one are reflected in the other; interactions between these systems appear to be reciprocal. The precise nature of the reciprocal interaction can vary, and the activity of norepinephrine at presynaptic serotonergic terminals may lead to a decreased release of serotonin, whereas its activity at postsynaptic adrenoreceptors may lead to an increase in the release of serotonin.

 

Someone like to translate this^^

 

The “fight or flight response” is something I struggle with in social situations such as when I’m situated in a classroom, this is accompanied by increased sweating, piercing sounds, muscle tension/rapid muscle movement and intrusive thoughts. This is very different than the anxiety I feel when I’m alone. I’m also unable to look others in the eyes. I feel apprehension and impending doom/dread. I certainly do not want to feel terror again! My brain feels as though it's trapped in a pressurized vise and my head wobbles. This has also caused me to be unable to look people in the eyes. If I do my neck will tense up and I’ll start to spasm out. I try to control my spasms by never looking up or making eye contact and resting my head on my hands. If I’m in class, I’ll distract myself by scribbling or taking notes, however if I cease doing this my symptoms will appear. If I let these symptoms continue, I’ll start to clench and sweat. Moreover, I am unable to talk long periods of time to people because my brain feels like it stops working. I’ll forget what I am saying mid sentence and an uncomfortable, overwhelming feeling will take over me. That being said it is very annoying and I want it to stop so bad! This never happened before I started smoking cannabis! I was the complete opposite of who I am today. I can’t even look at my parents in the eyes, nor my friends. Others have told me this is a time of transition from adolescence to adulthood and, like all transitions, is often accompanied by a degree of doubt and worry.

 

I guess you could explain my anxiety in terms of unwarranted or inappropriate fear. 

 

All of these sensations started to occur after my cannabis induced panic attack. All throughout me teenage years, until about a year ago I was an extrovert. Very outgoing, with lots of charisma. However, I am now the complete opposite of that following my cannabis induced panic attack. I have not felt the same since and have become extremely introspective.  

 

I quit cold turkey and went to the doctors because I felt depersonalized and derealized. My brain was in a fog, I could not concentrate, my eyesight was blurry and dull almost like I was looking through a film of grey, sounds were earsplitting, I had a full prickly rash all over my body, I had tingling in the fingers and an odd sensation in my left front-upper side of my head that resembled a void/black hole, these are supposedly symptoms of decreased GABA. Lyme disease was ruled out, although blood tests can oftentimes come back false negative, and as a child I was tested for lyme and one test came back false positive. So i’m not sure. 

 

Moreover, smoking marijuana over winter prior to my panic attack had a very positive effect on my social abilities. However, these were strains high in CBD and low in THC. Studies have shown cannabidiol decreases activity of the limbic system and decreases social isolation induced by THC. Cannabidiol has also been shown to reduce anxiety in social anxiety disorder. I would love to get my hands on a high CBD strain but they are ridiculously expensive. 

 

CBD also has anti-psychotic effects and may counteract the potential psychotomimetic effects of THC on individuals with latent schizophrenia some reports show it to be an alternative treatment for schizophrenia that is safe and well-tolerated. 

 

 

Now, THC inhibits GABA, and boosts dopamine, malfunctioning in GABA signaling is associated with movement disorders (rapid muscle movement) as well as anxiety, schizophrenia, and addiction. This inhibition of GABA may be the reason cannabis consumption affects memory and movement and is therapeutic in cases such as Fibromyalgia. Smoking strains high in THC, caused paranoia, social inhibition and panic attacks. Strains low in THC and high in CBD’s relieved the burden of anxiety and created a spontaneous, social, witty me. 

 

Fear and motivation with no confidence is felt as anxiety->paranoia, these are feeling accompanied when smoking high THC-strains of cannabis. Dopamine increase and a motivation felt as paranoia. This does not include when I smoke strains low in THC and high in CBD. Pure fear with absence of any other emotions is felt as impending doom - a fear without a consciously known origin, these are feelings I struggle with in social situations and so badly want them to stop. 

 

Fear is invoked each time certainty of action and reaction is doubted, engages the learning/challenge mode to learn the new context and remove threats, learn most effortless/painless use of reality. Learning certainty provides reward until 100% certainty is achieved after which there is no reward – this is in fact the mechanism that causes drug tolerance. After certainty is learned one can only feel fear when certainty of use comes in question. The drugs cause the user to learn more certainty than possible in reality, which causes fear-doubt depression in withdrawal. It also explains the PARANOIA created by dopaminergic drugs.

 

Moreover, a conditioned fear is often measured with freezing (a period of watchful immobility) or fear potentiated startle (the augmentation of the startle reflex by a fearful stimulus). Changes in heart rate, breathing and muscle responses via electromyography can also be used to measure conditioned fear. 

 

Inositol is a simple polyol precursor in a second messenger system important in brain myo-insitol, the natural isomer, which has been found to be therapeutically effective in depression, PANIC disorder, obsessive-compulsive disorder in double blind controlled trials and psoriasis. Now before I started taking this I panicked around people and had difficulty in situations were I was stuck on the phone for long periods of time. In general I was very uncomfortable in situations were I felt I could not escape. Inositol made it much easier for me to go with the flow; however, it also caused brain fog and short-term memory loss. Why is this? And what is the mechanism of action? 

 

Inositol 'disruption' may be linked to depression, but that's surely when inositol gets too low, but because “myo-inostiol lowers testosterone levels” Zero concept of risk/reward process, motivational issues, sleeping beautifully, can't kick into gear on waking, can sleep whenever regardless of sleep had. So this could be a problem. 

 

Caffeine seems to trigger my panic disorder and I become overly stimulated, apparently caffeine inhibits GABA but upon cessation up regulation of GABA receptors.

 

TLDR: I suffer from SAD, Acute panic disorder and OCD. I never experienced any of these sensations prior to a cannabis induced panic attack. THC makes symptoms worse, CBD helps to ease my anxiety as well as inositol. Aerobic exercise helps a lot, weight training makes me panic more. Meditation helps if I’m not already in panic mode. Ashwagandha helps but upon cessation increases anxiety, same with picamilon. 

 

My daily stack consists of:

 

Daily Stack

 

Hemp Hearts/Protein:    30g/15g

Sencha Tea:                     5g/3x Upregulates GABA receptors, also L-theanine modulates GABA.

 

Rhodiola Rosea:              250mg/2weeks on/1week off Really helps but why?

Turmeric:                         5g Not sure yet?

1:1 Chlorella/Spirulina:  3g 

Myo-inositol:                   2g/2x Helps me to control my panic, not sure specifically why?

---------------

Vitamin D

Zinc 

Magnesium L-Threonate

 

 

Weekly Stack

 

Ginger:                             2g/2x testosterone

Fish Oil:                           1250mg/4x Brain fog and inflammation 

Withania:                         200mg/2x If I’m going out and need to calm down.

Rieshi Tea:                       5g/1x Probably will stop

L-theanine:                      100mg/2x        

 

What about magnesium??

 

Its a NMDA antagonist. Magnesium seems to attenuate chronic activation of NMDA receptors, which exerts neurotoxic effects via Calcium - dependent mechanisms. 

 

Magnesium injections in rats (higher than practical supplementation) attenuated the increase of adrenaline in electrically shocked rate by 92.6%. Hence, supplementation could help with fight or flight in some way, I’m not really sure though. 

 

​I’m only asking for some input on what would be a safe and effective say to cope with my anxieties, without going the pharmaceutical route. 

 



#2 UniqueNewYork

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Posted 21 November 2015 - 02:25 AM

I have had a similar issue. I had social anxiety at age 16 that lasted for about two years. Then later GAD in my late twenties. It's funny how it get's triggered every 10 years or so.

I have always been looking to fine tune my brain and modify it for balance. It's funny because a lot of people see me as confident and outgoing and I often have to appear in front of large groups of people. Those times I feel alright. It's small intimate setting with groups of 10-30 people where I can still have occasional trouble.

Also, with the GAD, that's always temporary but it can really upset my plans and screw with my life in general.

 

What I've been doing lately is taking 400mg kava at night before bed. In the morning I drink water, eat something like a banana and take p5p then a b complex. Later I take a full spectrum amino acid supplement. Then between lunch and dinner I take a probiotic. One of the strains I take is the Longum Helveticus mix used in this study - http://www.ncbi.nlm....pubmed/20974015. Taking probiotics at night before sleeping is probably best, I just never got into the habit.

 

That's all I can tell you, it seems to work for me. Anxiety is a complex issue. Part philosophical, emotional, biological/genetic and bacterial.

 

I really like the idea of fecal transplant. There's some indication it can change a person's mental outlook and emotional stability. In effect taking someone else's brain and trying that on instead. As long as you get to keep the best parts of your own personality and just getting that extra support frame.

I think a person's mental outlook or basic philosophy is important and it too is largely based in your genetics, upbringing/past experiences AND your gut microbiota.

 

To give you an example of how strong an influence the gut plays in all of this, I had a stomach virus approx 2 years ago that caused daily bouts of watery diarrhea for months ( I lost 10 lbs ) while also waking me up in the middle of the night with a paranoid feeling that something was absolutely wrong and I was in grave danger. Seems crazy I know but it happened all throughout that time while I was fighting this 'bug'. I could not sleep for more than 4 hrs. Then it was time to walk and haunt the house completely wide awake. I never rested well during that time or felt healthy and mentally I was a wreck. It was constant anxiety but more a feeling of intense dread. It actually caused some other neurological problems that lingered for months afterward. I felt like my neurotransmitters were scrambled and mostly missing. I felt inhuman for a time unable to relate to things properly. Although I continued to function and no one really knew. I was so adept at socializing, performing my duties, doing my job etc. that I could still keep up appearances. Yet there was an emotional component to the experience that struck me as odd. I felt I was buying into the feelings that were being produced in the gut. It was impossible to ignore it. The gut had my brain 'by the balls'. However I knew that it was something outside myself ( or bug inside that wasn't me ) that was causing this to happen. The reason was that it was so unlike me in so many ways. It was a jarring departure from my basic personality which was normal positive and upbeat, while maybe just being a tad high strung which contributed to my past anxiety. I had never felt this sense of dread, paranoia and despair that seemed to visit on me overnight out of nowhere and seemingly for no reason, for the first time in my life. It wasn't depression and you couldn't draw a straight line to it from my past. This gloom wasn't my own genetic weakness or predisposition at all. It was like a bomb went off inside me unexpectedly and now I was dealing with this weird event. I looked at life completely differently in the matter of a few short days. It was the way this particular virus could act upon the host to change their mental status almost completely. Here I was in my 40's and my past never involved anything remotely like this.

Anyway, it really made me realize that this gut/brain connection was extremely powerful. It was only when I started to treat the gut issues that normalcy returned.

 

I think healing involves building the body and brain up in a holistic and complete way without leaning to much in one direction and not overdoing something and creating a possible deficiency or imbalance of some other kind. We can fiddle around with all kinds nootropics and meds we don't fully understand and try and find quick fixes that end up costing us more in the end when homeostasis returns at some point.

 

Therapy is a great tool combined with building up health, repairing the gut and helping the underlying genetic weakness. Along with a few vitamins or herbs here or there.

I've used so many things save for meds and found that magnesium is a great one as well.

I would stay away from Theanine. Also cut back on the zinc to about 10mg.

The spirulina/Chlorella I don't understand for anxiety ( Metal toxicity cleansing? Iodine? ).

Turmeric definitely.

Rhodiolia I haven't tried.

Ashwagandha helped somewhat but only to a point.

I haven't looked into the sencha tea but I definitely will.

I would get the CBD extract as well and will be trying it myself soon.

I would recommend the kava as it helped me and the do the gut repair ( or fecal transplant ) , which is a lot more complicated than I explained here.

 

 



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#3 Blackkzeus

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Posted 22 November 2015 - 09:53 PM

Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.
Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.
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#4 PalmAnita

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Posted 23 November 2015 - 07:57 AM

Magnesium isn't really a NMDA antagonist, it's part of the normal biological functioning of that receptor and there it has an antagonising effect, yes, but it isn't an actual antagonist like the pharmaceutical ones e.g. memantine, ketamine. Supplementing magnesium is generally no bad thing as latent deficiency seems to be somewhat more common than thought, but it won't do much if you're not deficient either. And most of the commonly sold forms of Mg are more of laxatives than supplements because they have such poor bioavailabilities (<20% for oxide, <30% for citrate if I'm right). Only the amino acid chelated forms like bisglycinate etc. are well absorbed but unfortunately tend to be expensive. I don't tolerate the non-chelated versions, they induce diarrhoea.

 

But for anxiety supplements - I'm fighting with that too, especially social anxiety but also general (non-specific, depression related probably) anxiety and thus have tried a wide range of things already, and well as usual, the majority didn't work. It really sucks how bad Big Pharma is performing, and quite some doctors have no idea either. 

 

Because of that, I'll just list what worked, at least for me - everybody is different, but there seems to be a general tendency for many:

 

- Tiagabine, the only GABA reuptake inhibitor available by prescription. It's an anti-epileptic that is off-label for anxiety, but it works, has some studies done (here and here). It's comparable overall to a non-sedating benzodiazepine if you ask me, but there is solid evidence that the GABA RIs don't induce tolerance and dependence - didn't believe this at first, but after reading about another compound called deramciclane that unfortunately failed in the trials but also didn't have tolerance issues, it might well be true. Needs to be tapered nevertheless and the dosage can vary greatly between individuals, for me it began to work at 5mg with a stronger effect at 10mg while others get relief from just 1-3 mg. Could be a long-term solution if it works as it promises.

 

- Memantine, the NMDA antagonist. Great in taking the edge off intensive feelings, overall tension and anxiety and can even be a bit nootropic. Comes with the price of initial mild brain fog before the brain adjusts to the effects (1-3 weeks maybe), taper slowly. It tends to make me a bit lethargic, but it's a good basic thing and others don't get the lethargy. Also combines well with psychostimulants where there's even good evidence for that the combo leads to less tolerance development to e.g. methylphenidate. Add in emoxypine and you get much less rebound effects overall. For me, low dosages (5mg per dose or so) of stimulants are anxiolytic sometimes too, with that RC derivate isopropylphenidate being the best with the least peripheral effects.

 

Selank (and semax, but that was too strong for me) - blatantly ignored by the western docs, it's a decent anxiolytic that seems to work through inhibition of endorphin / enkephalin metabolism. Must be applied intranasally because it has no oral bioavailability and the molecule is a bit fragile.

 

Mebicar (and fabomotizole), two more Russian anxiolytics that seem to work but they are just too expensive when bought online. One box of each one costs seemingly around 500 rubles, that's maybe 5$ or so and they sell it for 40$ ...

 

- Kava. Seems to work, but it's an 'intoxicant' and tolerance could be an issue. Didn't try it long enough.

 

- Phenibut. There are too many reports of tolerance and intense withdrawal to ignore them, but most seem not to taper correctly and recent evidence makes the pharmacology of it look much like pregabalin and gabapentin and unlike even it's close cousin baclofen (that doesn't seem to have tolerance issues btw, but that could be because it's more used medicinally and thus with better tapering schemes). If it is like pregabalin, then it could work well and one would just need to avoid cold turkey. Pregabalin tolerance isn't like benzos, at least for me, but requires a few weeks to build down slowly, then it doesn't induce much discomfort.

 

Probably I forgot some, but that's what I remember currently.


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#5 TheOpimizer

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Posted 24 November 2015 - 04:43 AM

I've always been so interested to try Phenibut, but I'm always scared off by the fact that its apparently very addictive and brings on brutal withdrawal. 

 

Does anyone just use it sporadically to "get drunk" per se as I've heard it's pretty potent.

 

Could I just keep some on hand to use if I don't feel like drinking but still want to go out and mingle?

 

Next obviously question is...does it cause any hangover like symptoms?


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#6 birthdaysuit

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Posted 24 November 2015 - 06:08 AM

Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.
Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.

Gotu Kola is a GABA agonist. I would like something that I can use in the longterm without down-regulation of GABA receptors. Ashwaganda I take rarely due to this fact. 

 

Does it feel sedative in anyway? 



#7 birthdaysuit

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Posted 24 November 2015 - 06:14 AM

Therapy is a great tool combined with building up health, repairing the gut and helping the underlying genetic weakness. Along with a few vitamins or herbs here or there.

I've used so many things save for meds and found that magnesium is a great one as well.

I would stay away from Theanine. Also cut back on the zinc to about 10mg.

The spirulina/Chlorella I don't understand for anxiety ( Metal toxicity cleansing? Iodine? ).

Turmeric definitely.

Rhodiolia I haven't tried.

Ashwagandha helped somewhat but only to a point.

I haven't looked into the sencha tea but I definitely will.

I would get the CBD extract as well and will be trying it myself soon.

I would recommend the kava as it helped me and the do the gut repair ( or fecal transplant ) , which is a lot more complicated than I explained here.

Meditation really helps to calm my mind but can at times make me introspective and quiet during social gatherings. I still love the feeling it gives me, though it isn’t a cure for social anxiety and panic. Why would you not recommend L-theanine, just wondering? It is a basic component of Sencha tea, which I love but can’t tolerate in social situations because of caffein content. Caffeine really puts me over the edge. 

 

I take the spirulina/chlorella for b12 and overall health, it also gives me marked increased energy. Message me when you try the CBD extract. I hate THC and would love to get a 20:1 CBD/THC strain. 

 

Thanks for all the information! 



#8 PalmAnita

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Posted 24 November 2015 - 07:15 AM

I've always been so interested to try Phenibut, but I'm always scared off by the fact that its apparently very addictive and brings on brutal withdrawal. 

Could I just keep some on hand to use if I don't feel like drinking but still want to go out and mingle?

Next obviously question is...does it cause any hangover like symptoms?

 

Well ... the same scared me off phenibut too, but now after reading up about the pharmacology and such, there is really no reason for it to be any more addictive than pregabalin. It acts basically like that with some minor baclofen-like GABA-B agonism (the Cl of baclofen likely makes the difference) but as baclofen doesn't seem to be that addictive, this can be ignored and we're left with a gabapentinoid (this term seems to be actually used).

 

They are alpha-2-delta calcium channel blockers and as such anti excitatory agents as well as there's some speculation about inducing an enzyme that converts glutamate into GABA and thus ultimately leading to more GABA -> the combination of both mechanisms makes a nasty withdrawal syndrome easily imaginable. But as it is the case with pregabalin, this could be more of a plateau / tapering issue, that one just needs to get slowly off the phenibut over the course of a few weeks or so. I'm not sure yet, but if you read the reports closely, almost all seem to go off cold-turkey and not with a good taper scheme. So maybe phenibut is better than it's reputation?

 

Pregabalin addiction seems to be a hard fact too, I've heard some horror stories about that from docs here in Germany and the opioid users seem to like it, but that's a different thing. I think there is strong evidence for the gabapentinoids to have a different and probably more favourable tolerance / dependence scheme than the benzodiazepines in regards of long-term use.

 

--

 

Last but not least, if it's available in your country, tiagabine is really worth a try! 



#9 Blackkzeus

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Posted 25 November 2015 - 07:52 PM

 

Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.
Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.

Gotu Kola is a GABA agonist. I would like something that I can use in the longterm without down-regulation of GABA receptors. Ashwaganda I take rarely due to this fact. 

 

Does it feel sedative in anyway? 

 

 it is definitely calming but does not negatively impact mental clarity - if anything , it improves overall clarity and is good for focus and consistency. It has some Pro-Intellectual properties but is not hard-ground for this and most of it's benefits come it's ability to counter-act stress states.



#10 birthdaysuit

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Posted 25 November 2015 - 09:59 PM

 

 

Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.
Try out Gotu Kola. Really helped lower my anxiety, seems much stronger than Ashwaganda to me.

Gotu Kola is a GABA agonist. I would like something that I can use in the longterm without down-regulation of GABA receptors. Ashwaganda I take rarely due to this fact. 

 

Does it feel sedative in anyway? 

 

 it is definitely calming but does not negatively impact mental clarity - if anything , it improves overall clarity and is good for focus and consistency. It has some Pro-Intellectual properties but is not hard-ground for this and most of it's benefits come it's ability to counter-act stress states.

 

I’ll have to give it a try.

 

What do you think of Holy Basil (Tulsi)?

 

I’ve been taking a constant dosage for the past week and I have felt a lot calmer. I’m not sure of its mechanism of action. 



#11 birthdaysuit

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Posted 26 November 2015 - 12:07 AM

I also take anywhere from 5000 to 20000mg of creatine five to six times a week and I feel a marked increase in clearheadedness and sociability. 

 

Creatine is is possibly a 5-HT1A autoreceptor antagonist. It would modulate serotonin, increase testosterone, lower cortisol and prolactin as well. WHAT does one think of mixing mho-inositol with Creatine?

 

 

 

 

 



#12 UniqueNewYork

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Posted 17 December 2015 - 11:36 PM

I've been looking at a lot of research concerning the vagus nerve lately and the related chronic conditions associated with it. Namely CFS, fibromylagia, Epilepsy, Adrenal fatigue, depression, anxiety/panic disorder, neurocardiogenic disorders, MS, PD, Lyme disease, etc, etc.

 

It appears that the vagus nerve is an on switch for the immune system, detoxification, digestion, circadian rhythm, bacterial/viral/fungul regulation. It is also interrupted in almost all these disorders and thereby increases inflammation in the nervous system and ultimately the brain.

 

This goes further into the gut/brain axis theory of many chronic diseases. Metals and toxins will accumulate also in this condition. It's nothing but bad for the body.

 

This is most easily seen in something called Roemheld syndrome where gas overstimulates the vagus nerve which initially causes a parasympathetic reaction that lasts for a millisecond ( usually unnoticeable ) followed by sympathetic response and an elevated heart rate until gas is expelled from the gut and the nerve relaxes again. It seems to be working in opposite but there is a complex relationship between the parasympathetic and sympathetic nervous system response. In this condition the vagus nerve is inflamed and easily overstimulated which leads to a lack of variability in response. It becomes 'stuck' in certain positions for certain lengths of time. The gut won't digest or release contents ( Gastroparesis ), the lack of hydrochloric acid and enzymes invites bacteria to overgrow and induces inflammation which inevitably travels up to the brain and creates problems with neurotransmitters. The gas from undigested food causing blocks of tachycardia are just a sign that there is inflammation in the vagus nerve. This can also cause an imbalance between gastric fluids and allow an increase in a gastric hormone called CKK-4 secreted in the duodenum. This has a marked effect on feelings of anxiety and is actually used in clinical trials to induce anxiety in subjects when testing anti-anxiety medications.

 

What causes this in the first place is not understood clearly but is suspected to be a virus like HHV-6 or cocksackie and/or certain strains of bacteria or fungus. An inflamed vagus nerve can really mess with your ability to relax and function normally. A tremendous amount of stress ( self caused or otherwise ) , lack of exercise, poor diet, extended illness, can reactivate a dormant virus or bacteria towards a low level immune response and create inflammation in two areas. The gut and brain. Both start to react to each other. The only way to break the loop of signals is to strengthen the vagal tone so that it is not  inflamed and continually overstimulated in one direction but has more resilience and fluidity. This can be done by electrical stimulation or even done manually through dunking the face into freezing water, taking a cold shower, stimulating digestion, valsalva maneuver, and a myriad of other weird activities. Meditation also helps. Being in control of the situation by reducing both gut and brain inflammation is important. Manage the inflammation and work out the vagus nerve. The important thing is to allow the body to do what it needs to do. It knows what it needs to do, so don't freak out when it does his, allow it to happen.

 

I think something like CBD has an effect on the vagus nerve indirectly.

 

It could be something as simple as a switch stuck in the 'on' position for the nervous system leading to so many diffuse and complex problems. All the psychotropics people use are trying to manage the cascade of inflammation coming from the vagus nerve.

 

Here's an interesting article about this. it talks a lot about CFS but it's all very closely tied to autoimmunity, depression, anxiety, seizures and more.

 

http://simmaronresea...syndrome-mecfs/

 

 


Edited by UniqueNewYork, 17 December 2015 - 11:38 PM.

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#13 UniqueNewYork

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Posted 01 February 2016 - 01:05 PM

I've been looking at some more recent research involving schizophrenia, OCD, anxiety, Lyme disease and depression being treated as a bacterial infection linked to Spirochaetes/borellia and treated with tetracyclines like Doxycycline. The trouble is, with the rise of antibiotic resistant strains of bacteria, is this new revelation going to become irrelevant almost as soon as these diseases have become treatable?

 

There was a website I was on where a biologist was treating his Lyme disease with tetracyclines combined with apple seeds to increase Amygdalin in the killing of the borellia . It might seem foolhardy to increase cyanide levels but the amount needed to be toxic to your own body would be extremely high. Much more than you can get from eating just a handful of apple seeds per day. 

 

I'm partial to the theory that some bacteria are involved in producing a chronic, low level stress response in the host which weakens the immune system and thus protects the pathogen from detection and attack. Higher corticosterone levels are often seen in people with chronic infection, anxiety and depression.


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#14 birthdaysuit

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Posted 28 February 2016 - 02:50 AM

I've been looking at some more recent research involving schizophrenia, OCD, anxiety, Lyme disease and depression being treated as a bacterial infection linked to Spirochaetes/borellia and treated with tetracyclines like Doxycycline. The trouble is, with the rise of antibiotic resistant strains of bacteria, is this new revelation going to become irrelevant almost as soon as these diseases have become treatable?

 

There was a website I was on where a biologist was treating his Lyme disease with tetracyclines combined with apple seeds to increase Amygdalin in the killing of the borellia . It might seem foolhardy to increase cyanide levels but the amount needed to be toxic to your own body would be extremely high. Much more than you can get from eating just a handful of apple seeds per day. 

 

I'm partial to the theory that some bacteria are involved in producing a chronic, low level stress response in the host which weakens the immune system and thus protects the pathogen from detection and attack. Higher corticosterone levels are often seen in people with chronic infection, anxiety and depression.

I was diagnosed with obsessive compulsive disorder as a child, however it got better over my high school years. It only recently redeveloped in the form of intrusive thoughts, anxiety and especially hypervigilance. Currently, I might have some sort of comorbid attention-deficit disorder/hyperactivity disorder. Everything always seems to drain my energy, especially in social situations. I have a difficult time suppressing irrelevant stimuli, so everything is overstimulating this is especially true when I have to go into grocery stores. The words, the colors, the choices, everything is too much to handle and I end up having to leave. 

 

Inattention, impaired executive function, short-term memory loss could in fact be an epiphenomenon of OCD rather than ADHD. I think it comes down to me trying to control my thoughts and behaviors in social situations which ultimately leads to a flooding of the executive system. That being said inhibitory control is impaired in ADHD and maybe even more so OCD. Short term low doses of Adderall could help, I just don’t want to ruin my dopaminergic system. Plus, I’m not even sure how I would respond to it, it might even worsen my anxiety and panic. Meditation is another method that can and does improve inhibitory control. I practice Zen meditation almost everyday and it sort of helps.  

 

I’ve tried Rhodiola Rosea, took 150g 3% Rosavins during an event that I knew would spike my anxiety. It sure didn’t help and instead worsened the situation. Felt like I was in fight or flight for three straight hours, I even almost went into a depersonalization episode. I stopped taking it for a few months before starting it again in the fall. I took 150mg once a day for two weeks. My anxiety started to deminish, however this could of been because Rhodiola gave me the motivation to get out of bed and exercise everyday. I started to feel great. After taking a day off of my anxiety increased 10-fold. Worse than it was before taking Rhodiola. I decided not to take rhodiola rosea again. I know it increase serotonin, ACTH, and lowers cortisol not sure if it has any affinity on dopamine receptors. Generally speaking though, if corticosterone levels are too high someone would display small 5-HT responses at the 1A level. I know Rhodiola Rosea has affinity at the 5ht1a receptor, agonists like CBD are said to help with sociability but Rhodiola is also said to be a COMT-inhibitor, so it would increase catecholamines.

Green tea's polyphenols are COMT-inhibitors and they increase my anxiety to such an extent that I just want to end my life. Maybe I need a COMT inducer? Not sure if they exist.  

 

I’ve also tried myo-inostiol in large dosages and it thwarts my panic and anxiety but causes major brain fog and short-term memory loss. I know myo-inositol supplementation can upregulate D2 receptors. 

 

The only supplements that seem to work synergistically were 5g of creatine everyday and vitamin D 2000IU. Seems to improve my mood, helps with fatigue and gives me a clear, social mindset. Not sure creatine’s mechanism of action but it really makes me feel great!

 

I sent my blood tests to California to get checked for latent lyme disease. I hope I do not have Lyme but I have had dozens of deer ticks on me over the years. One of my Lyme blood tests I took a few years back had a false positive! 

 

That’s my update!  Also, I’ll be looking more into the vagus nerve because it’s so interesting and sorry for the thousands of grammatical errors. 


Edited by birthdaysuit, 28 February 2016 - 02:53 AM.


#15 medievil

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Posted 28 February 2016 - 07:33 PM

I have had a similar issue. I had social anxiety at age 16 that lasted for about two years. Then later GAD in my late twenties. It's funny how it get's triggered every 10 years or so.

I have always been looking to fine tune my brain and modify it for balance. It's funny because a lot of people see me as confident and outgoing and I often have to appear in front of large groups of people. Those times I feel alright. It's small intimate setting with groups of 10-30 people where I can still have occasional trouble.

Also, with the GAD, that's always temporary but it can really upset my plans and screw with my life in general.

 

What I've been doing lately is taking 400mg kava at night before bed. In the morning I drink water, eat something like a banana and take p5p then a b complex. Later I take a full spectrum amino acid supplement. Then between lunch and dinner I take a probiotic. One of the strains I take is the Longum Helveticus mix used in this study - http://www.ncbi.nlm....pubmed/20974015. Taking probiotics at night before sleeping is probably best, I just never got into the habit.

 

That's all I can tell you, it seems to work for me. Anxiety is a complex issue. Part philosophical, emotional, biological/genetic and bacterial.

 

I really like the idea of fecal transplant. There's some indication it can change a person's mental outlook and emotional stability. In effect taking someone else's brain and trying that on instead. As long as you get to keep the best parts of your own personality and just getting that extra support frame.

I think a person's mental outlook or basic philosophy is important and it too is largely based in your genetics, upbringing/past experiences AND your gut microbiota.

 

To give you an example of how strong an influence the gut plays in all of this, I had a stomach virus approx 2 years ago that caused daily bouts of watery diarrhea for months ( I lost 10 lbs ) while also waking me up in the middle of the night with a paranoid feeling that something was absolutely wrong and I was in grave danger. Seems crazy I know but it happened all throughout that time while I was fighting this 'bug'. I could not sleep for more than 4 hrs. Then it was time to walk and haunt the house completely wide awake. I never rested well during that time or felt healthy and mentally I was a wreck. It was constant anxiety but more a feeling of intense dread. It actually caused some other neurological problems that lingered for months afterward. I felt like my neurotransmitters were scrambled and mostly missing. I felt inhuman for a time unable to relate to things properly. Although I continued to function and no one really knew. I was so adept at socializing, performing my duties, doing my job etc. that I could still keep up appearances. Yet there was an emotional component to the experience that struck me as odd. I felt I was buying into the feelings that were being produced in the gut. It was impossible to ignore it. The gut had my brain 'by the balls'. However I knew that it was something outside myself ( or bug inside that wasn't me ) that was causing this to happen. The reason was that it was so unlike me in so many ways. It was a jarring departure from my basic personality which was normal positive and upbeat, while maybe just being a tad high strung which contributed to my past anxiety. I had never felt this sense of dread, paranoia and despair that seemed to visit on me overnight out of nowhere and seemingly for no reason, for the first time in my life. It wasn't depression and you couldn't draw a straight line to it from my past. This gloom wasn't my own genetic weakness or predisposition at all. It was like a bomb went off inside me unexpectedly and now I was dealing with this weird event. I looked at life completely differently in the matter of a few short days. It was the way this particular virus could act upon the host to change their mental status almost completely. Here I was in my 40's and my past never involved anything remotely like this.

Anyway, it really made me realize that this gut/brain connection was extremely powerful. It was only when I started to treat the gut issues that normalcy returned.

 

I think healing involves building the body and brain up in a holistic and complete way without leaning to much in one direction and not overdoing something and creating a possible deficiency or imbalance of some other kind. We can fiddle around with all kinds nootropics and meds we don't fully understand and try and find quick fixes that end up costing us more in the end when homeostasis returns at some point.

 

Therapy is a great tool combined with building up health, repairing the gut and helping the underlying genetic weakness. Along with a few vitamins or herbs here or there.

I've used so many things save for meds and found that magnesium is a great one as well.

I would stay away from Theanine. Also cut back on the zinc to about 10mg.

The spirulina/Chlorella I don't understand for anxiety ( Metal toxicity cleansing? Iodine? ).

Turmeric definitely.

Rhodiolia I haven't tried.

Ashwagandha helped somewhat but only to a point.

I haven't looked into the sencha tea but I definitely will.

I would get the CBD extract as well and will be trying it myself soon.

I would recommend the kava as it helped me and the do the gut repair ( or fecal transplant ) , which is a lot more complicated than I explained here.

Alot of people with social anxiety get complete remission with amphetamine, youd need memantine for tolerance tough, but this relates to the AVPD subtype but most ppl dont know what that is ant call is social anxiety.

 

I used to be extremely socially anxious when i was young while i wanted to be extroverted and felt like i wasnt the person i wanted to be, well stimulants take away my anxiety and im the extrovert i allways wanted to be and feel like is my real personality.

 

When treating anxiety dont just focus on weak supplements, i beleive ppl with mental issues should aim for complete remission and not just mild improvement, even if it takes benzos, why live with issues when you can be like others without mental illness



#16 medievil

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Posted 28 February 2016 - 07:46 PM

Stimulants abolish not only my social anxiety but also compltely abolished my ocd back when i suffered from very severe ocd, to the point of not understanding my own ocd, in contrast with things that improve it.

 

Stimulants wont ruin your dopamine system if you take a nmda antagonist like memantine, also downregulation with stims does not ruin anything and upregulation occurs, which can be accelerated with memantine.



#17 medievil

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Posted 28 February 2016 - 08:00 PM

 

I've always been so interested to try Phenibut, but I'm always scared off by the fact that its apparently very addictive and brings on brutal withdrawal. 

Could I just keep some on hand to use if I don't feel like drinking but still want to go out and mingle?

Next obviously question is...does it cause any hangover like symptoms?

 

Well ... the same scared me off phenibut too, but now after reading up about the pharmacology and such, there is really no reason for it to be any more addictive than pregabalin. It acts basically like that with some minor baclofen-like GABA-B agonism (the Cl of baclofen likely makes the difference) but as baclofen doesn't seem to be that addictive, this can be ignored and we're left with a gabapentinoid (this term seems to be actually used).

 

They are alpha-2-delta calcium channel blockers and as such anti excitatory agents as well as there's some speculation about inducing an enzyme that converts glutamate into GABA and thus ultimately leading to more GABA -> the combination of both mechanisms makes a nasty withdrawal syndrome easily imaginable. But as it is the case with pregabalin, this could be more of a plateau / tapering issue, that one just needs to get slowly off the phenibut over the course of a few weeks or so. I'm not sure yet, but if you read the reports closely, almost all seem to go off cold-turkey and not with a good taper scheme. So maybe phenibut is better than it's reputation?

 

Pregabalin addiction seems to be a hard fact too, I've heard some horror stories about that from docs here in Germany and the opioid users seem to like it, but that's a different thing. I think there is strong evidence for the gabapentinoids to have a different and probably more favourable tolerance / dependence scheme than the benzodiazepines in regards of long-term use.

 

--

 

Last but not least, if it's available in your country, tiagabine is really worth a try! 

 

A week of diazepam and clonazepam and you wont notice any phenibut withdrawals at all, after that your completely withdrawal free, phenibut withdrawal is no issue to be concerned about as long you stock up on some diazepam



#18 medievil

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Posted 28 February 2016 - 08:04 PM

Oh god, i shouldnt delay making that thread proving you can take gotu kola and ashwaganda long term even to.ugh they act on gaba, this bullshit spread around by scienceguy is keeping alot of people from working treatments, this also refers to benzos which ppl are in absolute need off, hes advice is dangerous and leads to ppl staying having issues in their life.

 

What works is a thread leaving all treatment options open with in debt information about the risk and potential solutions leaving ppl able to make a benefit risk analysis, rather then pushing personal opinions on people such as you should never take benzos


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#19 birthdaysuit

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Posted 29 February 2016 - 07:30 PM

Oh god, i shouldnt delay making that thread proving you can take gotu kola and ashwaganda long term even to.ugh they act on gaba, this bullshit spread around by scienceguy is keeping alot of people from working treatments, this also refers to benzos which ppl are in absolute need off, hes advice is dangerous and leads to ppl staying having issues in their life.
 
What works is a thread leaving all treatment options open with in debt information about the risk and potential solutions leaving ppl able to make a benefit risk analysis, rather then pushing personal opinions on people such as you should never take benzos

Agreed! A thread leaving all treatment options for anxiety related issues with potential side effects would be of more benefit for this community. Maybe similar to something like examine.com but pertains to more specific disorders like social anxiety.
 
I’m continuing creatine, vitamin D3, exercise and meditation. I’m feeling a little better, my doctor said I most likely have Postural Orthostatic Tachycardia Syndrome (POTS), which screws up the parasympathetic nervous system. She didn’t really explain the physiology behind it but she said I most likely had it and this is coming from the neurologist. When I stand from sitting I get a little nauseous, spacey and my heart pounds faster. She even said my eyes dilated. I’ve experienced numbness, impaired vision, etc. Even symptoms of fainting. The noticeable symptom is extreme fatigue and the inability for me to carry out mundane activities. Such as walking up a flight of stairs and keep in mind I’m healthy person. I eat well and work out everyday. 

 


Edited by birthdaysuit, 29 February 2016 - 07:32 PM.


#20 birthdaysuit

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Posted 01 March 2016 - 07:32 PM

Anyone ever deal with POTS? There’s a host of debilitating symptoms. 



#21 birthdaysuit

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Posted 03 March 2016 - 11:04 PM

Well boys and girls my doctor called and I have Lyme disease. I took the iGeneX test which tests for Burgdorferi, Western Blot, etc. I got two results back both apparently for western blot. 

 

LYME IgG Western Blot

------------------------------------------

Bands 31- IND

Everything else negative, except for 

Band 41 ++

Band 58 +

 

 

 

LYME IgM Western Blot

-----------------------------------------

Bands 18 +

Bands 31+

Band 39 IND

Band 41 ++

Bands 83-93 IND

 

Both result came back as negative so I was very happy, the doctor said my pending B. Burgdorferi test will rarely come back positive if both tests previously are negative. Well I got the call and they said it was positive. Haven’t seen the results paper yet, my other doctor said not to get treated yet and to do one more test. 



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#22 medievil

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Posted 04 March 2016 - 05:48 PM

 

 

 
Agreed! A thread leaving all treatment options for anxiety related issues with potential side effects would be of more benefit for this community. 

Sarcasm?  i beleive all options should be listed and iff there are risks there should be in debt information about those risks, for example benzos with links to anecdotes of ppl that went to the withdrawal, as some ppl just need more risky stuff.







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