299 replies to this topic

[jadamgo]

Yeah, I realize that Intuniv is usually marketed for hyperactivity, but my theory is that it may help people who fit the ADD category of symptoms too. The thing is, I used to be hyperactive, as a child I was very impulsive and had lots of issues with focus and controlling myself. However, my parents and teachers stamped that out with discipline (and of course maturing with age). I wonder however if the underlying issues that caused my hyperactivity as a child are still present, but manifest themselves differently due to behavioral conditioning. Like, perhaps the constant punishment I received as a child for my impulsiveness (understandably too, since I did some stupid shit without thinking about it, like pushing people off of a stage as a joke, yeah, I know, WTF child-self :P) simply placed mental blocks in my head causing me to constantly think about everything I do before I do it, and hence from the surface it appears that motivation is my only issue.

Well, if you had ADHD-combined as a child, you don't have SCT nor ADHD-PI now. You have residual ADHD-C. SCT is a separate disorder -- you don't convert from one to the other.

It's common for executive dysfunction to remain as the only symptom set in adulthood, with improvements in overt hyperactivity, impulsivity, and in some cases, attention control. This is because some of the skills that were developmentally delayed by childhood executive dysfunction are just that -- delayed. Not impossible. You learned to control your attention just like normal people do, but it took you longer because you had a learning disability in the realm of self-control. However, the core executive dysfunction that lies at the heart of ADHD-C still remains, and can still interfere with self-regulation, especially when motivation is not intrinsically very strong.

The thing is, I think that the approach my parents and teachers took fixed the symptoms of hyperactivity, that is, they conditioned me to overthink my actions, which has had positive and negative effects. On one hand, I'm now a very careful, thoughtful person; I analyze my thoughts and feelings and hence tend to be very self-aware. However, on the other hand, I overthink social interactions and tend to feel awkward interacting with new people/giving presentations, since I obsess over what people are thinking about what I'm doing (i.e "Am I acting weird, do they notice, are they bored, etc, etc").

Conditioning kids with ADHD to "act right" is necessary, but not entirely without drawbacks. While you found it easier and easier to control yourself as you matured, and your delayed PFC gradually caught up with those of your peers, there was a period of time before that maturation where you simply couldn't control yourself enough to keep the punishments from happening.

According to decades of behavioral research, the results of uncontrollable punishment are chronic anxiety and tension, and/or learned helplessness. Most of the anxiety-related disorders are very highly comorbid with ADHD, from OCD to Panic Disorder to PTSD, and especially Generalized Anxiety and Social Anxiety. Depressive symptoms, whether clinical or not, are also highly comorbid.

Way more than half of ADD/ADHD adults deal with at least some anxiety/depression because of how fucked up their conditioning was -- we were all expected to act much older than our brains knew how to, and it usually leaves some problems with socializing, motivation, and task completion. These problems continue throughout adulthood until specifically addressed with counter-conditioning. Drugs alone won't do the trick -- you need to finish learning the social skills and self-regulation skills that were delayed.

For example, you described difficulty with emotion/thought-regulation: not knowing how to stop yourself from overanalyzing things to the point of upsetting and distracting yourself. More specifically, you described overanalyzing social interactions while (and probably before and after) they happen. You'll need to practice interacting more spontaneously, trusting your adult mental filter to catch inappropriate statements even though your childhood mental filter did not. Trust me, nobody with social anxiety ever becomes obnoxiously confident -- your problem nowadays is a filter that's too strong, even though you learned as a child that your problem was a lack of filter. The distraction and discomfort you experience when interacting with people, and perhaps some other skill deficits, are the only obstacles to enjoying other people.

Perhaps the underlying issue has always been hyperactivity; some sort of dysfunction in my Prefrontal-Cortex, the symptoms of which have simply changed over the years. On the surface, it appears that motivation is my sole problem, or more accurately, my anticipatory anhedonia (capable of feeling pleasure in the short-term such as watching a movie, but difficulty feeling pleasure with delayed-rewards, such as developing hobbies). However, I wonder if my problem is not anhedonia in the classical sense (as a result of low dopamine/expedited reuptake), but more to do with my ability to regulate and sustain my attention on tasks that don't necessarily provide constant positive feedback, such as learning to play an instrument. My theory is that a dysfunctional PFC (as a result of various causes, such as insufficient blood flow, elevated cAMP causing HCN flooding, excitotoxicity, etc) could possibly impair one's ability to feel a constant flow of sustained interest in a low-stimulus activity. You see, I fit most of the symptoms of classical ADHD (not ADD), with the exception of not having difficulty controlling my attention, at least in the usual sense. I can focus just fine when I want to, however, I have a lot of difficulty voluntarily initiating and pursuing long-term low-stimuli activities, such as learning a skill, even when I have a personal interest in the skill. I lack the feeling of joy when learning that other people feel. I like the results, but the task itself is difficult and I feel little satisfaction while doing it. I've also begun to notice an issue where I seem easily stressed, and when I become even a little stressed, my cognitive ability goes out the window. This part is the most interesting to me; stress seems to just "switch off" some aspect of my cognition. I've heard of issues with stress breaking ADHDer's focus, but for me, I can still focus when stressed, but it's like information enters my mind and immidietly trickles out. When I become frustrated when learning, I get caught in a loop of just re-reading the information I'm trying to understand, over and over again, but it doesn't sink in.

All of this is skill-deficit in self-regulation, caused by the executive function disorder at the core of ADHD. That's the underlying PFC disorder you mention -- there are things normal brains automatically do to keep themselves running smooth, that ADHD brains don't automatically do. So you need to learn both the normal emotion- and behavior-control skills that were delayed, and additional coping mechanisms to deal with the ongoing executive dysfunction.

You'll have to find ways to consciously do what other people's brains do unconsciously. That's the challenge of adult ADD/ADHD.

During my research in regards to ADHD's neuropathology, I've come to understand that the amygdala handles emotional integration of experiences (i.e fear, pleasure, aggression) and that it's function can be summarized as primarily handling quick responses to urgent situations, such as freezing when confronted with something terrifying.

Understandably and unavoidably simplified -- a full discussion of amygdalar function would require a textbook, half of which will be found incorrect over the next 50 years.

Essentially, during acute stress, the amygdala overrides the Prefrontal-Cortex (which has more to do with slow, rational thinking) and produces immediate responses to stressful situations.

As pop psychology calls it, "amygdala-hijack": those moments when emotion takes over and reasonable thinking temporarily flies out the window. Later, when calm, you may go "WTF? How did it make any sense for me to do that?!"

A dysfunction in this balance between the amygdala and the PFC seems to explain much of my issues. The amygdala is not well-suited to handle a rational process such as learning abstract concepts.

More like "is completely incapable of rational thought" because amygdala-hijack is expressly designed to prevent such a slow process from delaying action during a life-or-death emergency, and to prevent historically valuable instinctual responses from being overridden by semi-rational thought. For most of our history, we didn't have the great rational minds we have today, and our amygdalas act like we still don't have them.

And an overactive response to stress from the amygdala could explain my coinciding social issues. When I'm socializing with people, I sometimes get a sort of "tunnel vision" sensation; almost like dissociation, but yet I still feel connected to reality. After the situation is over, my memories of my time spent socializing are faded; not gone, I still remember everything that happened, but they feel faded, nowhere near as vivid as much of the rest of my memories. Also, during this time I tend to fail to absorb facts while talking with the person, so though I'm not suffering from full-blown amnesia, I may forget much of what we talked about. It's very odd, since I wouldn't call it anxiety exactly, more like tension.

It may not have a strongly felt "fear" component of what many people call anxiety, but it's still a hyperaroused fight-or-flight response triggered by the perception of possible danger. Behaviorally, it's a classic fear response; whether or not you subjectively feel afraid. Subjective feelings are partly dictated by social standards; we aren't supposed to be afraid of something so "simple" as talking to people!

Anyways, to make a long story short, I have a hunch that my PFC may be the root of my problem, not simply depressed levels of dopamine. This would explain why Adderall/Ritalin failed to produce much of a response in me (most people talk of Adderall being the holy grail of motivation, almost to the point of euphoria. It didn't seem to have any affect on my ADD/ADHD at all), why Caffeine makes my problems worse (Caffeine raises cAMP, which at pathological levels can impede PFC connection to the rest of the brain by opening hyperpolarization-activated cyclic nucleotide-gated channels, which can effectively disconnect the PFC which excessively stimulated). I'm willing to at least give Intuniv a try, at worst, it will make me sleepy. It does have positive long-term effects that may be worth the temporary sleepiness, as by lowering levels of cAMP in the PFC, it allows for stronger synaptic connections to be formed, possibly yielding better working memory, alleviating anxiety relating to the Amygdala-PFC, etc.

In most stimulant-responders, the only reason the stimulants work is by enhancing PFC function. If they don't improve your executive functions, they won't help. However, Intiniv works to improve PFC function in a different way from stimulants; it improves signal-to-noise ratio by making it easier to tune out weak signals and crank the volume up on strong signals. Subjectively, it makes known irrelevant things fade farther into the background, and it makes known important things stand out more. But accurate dosing is crucial -- mess with the PFC too much, and your skill boosts disappear. The same problem happens with stimulant overdosage: overshoot the sweet spot, and the improvements are lost.

When guanfacine is used as a behavior-controlling drug, at doses high enough to depress norepinephrine levels throughout the whole brain, it no longer improves attention. That's because the PFC itself becomes sedated, and thus can't do its job of controlling things.

Also, here's an update in regards to my supplements: I've been taking 250 mg Uridine (UMP) twice a day with 3g flax oil twice a day (switching to fish oil when I run out of flax oil) with 1.5 g yeast 3x a day for the B-Vitamins (with an additional B12 supplement once a day). I have probably noticed the most subtle, but worthwhile results from my usage of that stack. It modulates dopamine activity rather than stimulating it, which is what seems to be happening with me. I've noticed less fluctuations in my motivation, and while I still have motivation issues, I find that rather than having spikes here and there, I seem to have more frequent and longer feelings of motivation, but of lesser intensity, which is what I prefer. I tried Sulbutiamine (first 600mg, then 800 mg), and noticed nothing spectacular (took with fat and without just to see). The odd thing about this supplement is that people here universally recommend taking it as a "once in a while" kind of supplement", yet most of the studies I've seen seem to say that it actually lowers dopamine release, which in the long-term upregulation of receptors (especially D1 receptors, which are the holy grail of long-term salience, but unfortunately, sulbutiamine downregulates kainate receptors which seems to have consequences on memory). So for Sulbutiamine to work, the studies seem to indicate it's actually for long-term use so re-sensitize the dopinamergic system, and is not in fact beneficial in the short term. I wonder if the reason people seem to have remarkably fast "tolerance" to Sulbutiamine's effects is that the "effects" they felt were just placebo induced by the substance's hype. I don't see how a drug that reduces/modulates dopamine could have noticably positive short-term effects. I plan to try taking it for two weeks and then trying a double dose of ritalin against my newly upregulated receptors to see what happens.

Speaking of ritalin/ADHD meds, I've stopped taking Adderall, and have replaced my morning dose with 10 mg Ritalin instead. Amphetamines seem to build tolerance too rapidly, and of course there's the excitotoxic effects (though I was taking a fairly small dose). I plan to take it on occasion when I need a focus boost, rather than daily. Just a warning to Adderall users, even at my rather conservative dose of 20mg XR (which is roughly 10 mg active at any given time), I've noticed depressive withdrawal symptoms. Definetly manageable, but I've noticed that today and yesterday I just had a tendency to feel gloomy and tired, which suspiciously arose the same day I stopped taking it. Adderall is thought to possibly indirectly affect Seratonin a little, so I'd definitely watch out for depressive symptoms when withdrawing, just keep in mind they'll probably fade.

Cool. Is that Ritalin a sustained-release formulation? The half-life is only 2-4 hours if you're a normal metabolizer. Fast-metabolizers like me run a half-life somewhere closer to 1-2 hours. The point is, you need to either take sustained release, or you need to microdose throughout the day. Otherwise, your dopamine levels will fluctuate wildly, interfering with self-regulation. Like I always tell bipolar people, you have to get stable before you can develop good coping skills! It applies equally to people with ADHD whose improper dosing schedules destabilize their dopamine levels.

P.S. I think this post just won NaNoWriMo.

Edited by jadamgo, 07 February 2013 - 06:14 AM.

[GetOutOfBox]

Well, if you had ADHD-combined as a child, you don't have SCT nor ADHD-PI now. You have residual ADHD-C. SCT is a separate disorder -- you don't convert from one to the other.

Well that makes sense in my case, since I was a classic case of ADHD as a child, although just for the sake of other people with ADD reading this, it should be noted that SCT and ADD have pretty much the same symptoms, just different pathologies (ADD is primarily dopamine dysfunctions, though a whole bunch of other systems are implicated, while SCT could be caused by any number of issues, ranging from neurotransmitter issues to neural defects in the brain).

According to decades of behavioral research, the results of uncontrollable punishment are chronic anxiety and tension, and/or learned helplessness. Most of the anxiety-related disorders are very highly comorbid with ADHD, from OCD to Panic Disorder to PTSD, and especially Generalized Anxiety and Social Anxiety. Depressive symptoms, whether clinical or not, are also highly comorbid.

Way more than half of ADD/ADHD adults deal with at least some anxiety/depression because of how fucked up their conditioning was -- we were all expected to act much older than our brains knew how to, and it usually leaves some problems with socializing, motivation, and task completion. These problems continue throughout adulthood until specifically addressed with counter-conditioning. Drugs alone won't do the trick -- you need to finish learning the social skills and self-regulation skills that were delayed.

That's definetly part of the issue, moreso than many realize. I'd like to emphasize this to anyone reading this thread, don't dismiss the possibility that many of your problems are self-fulfilling. Just a few months ago, I had a sudden realization that much of my loneliness, low self-esteem, low productivity, were brought on by myself. You may at first dismiss this possibility, but somehow that fact escaped me, and I'm normally very self-aware. For whatever reason, the fact that I had few friends, wasn't successful in my hobbies, and just wasn't happy, was a result of me simply not making any attempts to grow, to expand my interests and meet new people by my own accord. It seems obvious now that many of my issues are self-inflicted/within my control, but for whatever reason it wasn't before.

However, nootropics have really helped me bring this realization to fruition. I'm fairly certain that the Uridine stack/Noopept are having long-term effects on me, relieving my motivation issues. I'm not magically more motivated, but I find it easier to be motivated to due to long-term rewards. For example, my old self made glacial progress in his hobbies (yes I'm referring to myself in the third person ^_^), due to the fact that actually working felt like some massive task. I had virtually no motivation to work, starting any kind of mental task was like shoving my head through mud. It just wasn't satisfying, versus how most people seem to derive some pleasure and satisfaction from working on personal hobbies, like painting. For me, programming was just as boring as doing calculus, despite my own personal interest in programming, if that makes any sense. I wanted to work, desperately, but I felt almost zero motivation to do it.

Now I find myself subtly enjoying my hobbies. It's not a miracle, I still have to sit down and say "Alright you, work!" to myself, but I find it much easier to get going and to keep working. This lines up with Uridines supposed modulation and upregulation of dopamine receptors. It's probably helped that I've reduced my reliance on stimulants such as Caffeine (used to get something like 150 mg a day from macha tea, I haven't had any for more than a day in a row for about 1.5 months) and Adderall, who have probably over time caused massive downregulation of my dopaminergic system. The Noopept has probably helped via typical racetam effects, and also by increasing BDNF/NGF. It's my theory that increasing the secretion of those compounds makes one more sensitive to learning behaviors/responses, in a neutral way. So by combining Noopept with working and achieving results (and thus being conditioned to associate my hobbies with reward), perhaps it made that conditioning more concrete, or perhaps happen at a greater rate. I guess this could go both ways, enforcing negative behavioral patterns as well, such as drug seeking. Of course, this is all just conjecture, but either way, I'm definitely feeling an improvement.

For example, you described difficulty with emotion/thought-regulation: not knowing how to stop yourself from overanalyzing things to the point of upsetting and distracting yourself. More specifically, you described overanalyzing social interactions while (and probably before and after) they happen. You'll need to practice interacting more spontaneously, trusting your adult mental filter to catch inappropriate statements even though your childhood mental filter did not. Trust me, nobody with social anxiety ever becomes obnoxiously confident -- your problem nowadays is a filter that's too strong, even though you learned as a child that your problem was a lack of filter. The distraction and discomfort you experience when interacting with people, and perhaps some other skill deficits, are the only obstacles to enjoying other people.

I've started getting out and talking to more people, going to events and such. I'm being less of a recluse. I plan to look into a therapist who practices CBT for social disorders, and/or trying something like Toastmasters. I realize that social anxiety is always mainly treated by repeatedly having positive social experiences, usually in a controlled setting, such as group sessions. Some people have physiological disorders that amplifies their fear/anxiety response, but even then, the treatment is only augmented with the appropriate medication, not replaced.

I think I have a fairly high chance of rehabilitation. You see, I'm aware and unashamed of my tension/anxiety, I feel prepared to deal with it. Also, I luckily suffer from a minor case, as I am capable of socializing, I just have to work my way over that initial bump of worrying if the person will think I'm odd. Once I have a basic grasp of who they are, I feel much more comfortable. I definetly have no problem with existing friends. So it's really just a matter of learning that most people are nice enough, and it's not so bad if they think you're a little odd. My main issue is just relaxing my "armour" and letting the person see who I really am, the fact that I let so little of my real interests/feeling out is the main reason why I have only a couple of friends. You see, I meet someone, since I'm so cautious, I never learn whether we share anything in common, and hence it remains superficial.


All of this is skill-deficit in self-regulation, caused by the executive function disorder at the core of ADHD. That's the underlying PFC disorder you mention -- there are things normal brains automatically do to keep themselves running smooth, that ADHD brains don't automatically do. So you need to learn both the normal emotion- and behavior-control skills that were delayed, and additional coping mechanisms to deal with the ongoing executive dysfunction.

You'll have to find ways to consciously do what other people's brains do unconsciously. That's the challenge of adult ADD/ADHD.

In most stimulant-responders, the only reason the stimulants work is by enhancing PFC function. If they don't improve your executive functions, they won't help. However, Intiniv works to improve PFC function in a different way from stimulants; it improves signal-to-noise ratio by making it easier to tune out weak signals and crank the volume up on strong signals. Subjectively, it makes known irrelevant things fade farther into the background, and it makes known important things stand out more. But accurate dosing is crucial -- mess with the PFC too much, and your skill boosts disappear. The same problem happens with stimulant overdosage: overshoot the sweet spot, and the improvements are lost.
When guanfacine is used as a behavior-controlling drug, at doses high enough to depress norepinephrine levels throughout the whole brain, it no longer improves attention. That's because the PFC itself becomes sedated, and thus can't do its job of controlling things.

Yeah, it's definetly something to be careful with. I'd start with the minimum dose, and work my way up. The most attractive part to me is, it's a pseudo-long term improvement, using it for a period of time allows for stronger connections between the PFC and other parts of the brain to form, as the cAMP levels are reduced to normal(ish). So some of the benefits should last after stopping use of it, though they'll probably fade again. However, it seems to be a much more proactive treatment assuming it works; stimulants are essentially doomed to fail, as they all eventually produce downregulation. Of course, the downregulation is fairly small at low doses, however most people keep pushing their dose up so as to keep getting the initial feeling of being on top of the world.

Cool. Is that Ritalin a sustained-release formulation? The half-life is only 2-4 hours if you're a normal metabolizer. Fast-metabolizers like me run a half-life somewhere closer to 1-2 hours. The point is, you need to either take sustained release, or you need to microdose throughout the day. Otherwise, your dopamine levels will fluctuate wildly, interfering with self-regulation. Like I always tell bipolar people, you have to get stable before you can develop good coping skills! It applies equally to people with ADHD whose improper dosing schedules destabilize their dopamine levels.

It's an instant release tablet. However, in me, the effects of 10mg are so subtle, I don't really feel any major fluctuations between doses. This really highlights the difference in body chemistry; I've never really reacted much to stimulants (I can remember not feeling very different when I first tried Adderall, which is supposed to be very potent), whereas a friend of mine tried ritalin, and 10 mg had him bouncing off the walls.

[jadamgo]

I've started getting out and talking to more people, going to events and such. I'm being less of a recluse. I plan to look into a therapist who practices CBT for social disorders, and/or trying something like Toastmasters. I realize that social anxiety is always mainly treated by repeatedly having positive social experiences, usually in a controlled setting, such as group sessions. Some people have physiological disorders that amplifies their fear/anxiety response, but even then, the treatment is only augmented with the appropriate medication, not replaced.

I think I have a fairly high chance of rehabilitation. You see, I'm aware and unashamed of my tension/anxiety, I feel prepared to deal with it. Also, I luckily suffer from a minor case, as I am capable of socializing, I just have to work my way over that initial bump of worrying if the person will think I'm odd. Once I have a basic grasp of who they are, I feel much more comfortable. I definetly have no problem with existing friends. So it's really just a matter of learning that most people are nice enough, and it's not so bad if they think you're a little odd. My main issue is just relaxing my "armour" and letting the person see who I really am, the fact that I let so little of my real interests/feeling out is the main reason why I have only a couple of friends. You see, I meet someone, since I'm so cautious, I never learn whether we share anything in common, and hence it remains superficial.

Yes, having controlled positive experiences can be great, but the other half of the learning process comes after you've learned the cognitive-restructuring and other emotion-regulation skills. Once you're actually equipped to handle rejection, dislike, and other such unpleasant things, the final step of the counter-conditioning process is to directly expose yourself to the possibility of rejection. And in the case where rejection does in fact happen (which, most people find, is far less common than they expected/worried), you use the emotion-regulation skills to manage your reaction to it, and find out that it isn't at all that bad.

Why, as a recovered social-anxiety/major-depressive, I found myself getting rejected several times today at work, for various reasons. Each time it was upsetting... for anywhere from 30 seconds to 2 minutes. Then, each time, I went back to normal. Now, before CBT, I would have ruminated on those negative experiences for literally days. I wish "days" were an exaggeration, but really, it's the truth. I can still remember some stupid things I said years ago in college because I ruminated on them for days afterwards, burning them into my memory. But now that I've learned those delayed emotion-regulation skills, I simply don't ruminate like that anymore. From what you've written GetOutOfBox, it seems like you've also made a lot of progress in your emotion-regulation skills. Is that right?

[GetOutOfBox]

Yes, having controlled positive experiences can be great, but the other half of the learning process comes after you've learned the cognitive-restructuring and other emotion-regulation skills. Once you're actually equipped to handle rejection, dislike, and other such unpleasant things, the final step of the counter-conditioning process is to directly expose yourself to the possibility of rejection. And in the case where rejection does in fact happen (which, most people find, is far less common than they expected/worried), you use the emotion-regulation skills to manage your reaction to it, and find out that it isn't at all that bad.

Why, as a recovered social-anxiety/major-depressive, I found myself getting rejected several times today at work, for various reasons. Each time it was upsetting... for anywhere from 30 seconds to 2 minutes. Then, each time, I went back to normal. Now, before CBT, I would have ruminated on those negative experiences for literally days. I wish "days" were an exaggeration, but really, it's the truth. I can still remember some stupid things I said years ago in college because I ruminated on them for days afterwards, burning them into my memory. But now that I've learned those delayed emotion-regulation skills, I simply don't ruminate like that anymore. From what you've written GetOutOfBox, it seems like you've also made a lot of progress in your emotion-regulation skills. Is that right?

How exactly does one learn to deal with rejection? I imagined that simply by having plenty of positive social experiences, one will be less likely to be shaken by rejection, as one's confidence would be increased by the "practice" in socializing. What exactly do they call a therapist who utilizes CBT/other well founded techniques for social disorders?

Yep, I'd say I've made a ton of progress. I sort of awakened a few months back, and realized that all along it was within my power to take control of my life, to get out and meet people, to work on my hobbies, etc. I sort of suddenly saw what I wanted to do, and clearly how to do it.

[jadamgo]

How exactly does one learn to deal with rejection? I imagined that simply by having plenty of positive social experiences, one will be less likely to be shaken by rejection, as one's confidence would be increased by the "practice" in socializing. What exactly do they call a therapist who utilizes CBT/other well founded techniques for social disorders?

It's true that after you've practiced extensively with emotion regulation and socialization, your confidence will increase and your vulnerability to other people's negativity will decrease, and it'll be mostly automatic. However, there's plenty of practice to do before you get there. You have to practice these skills consciously before they become automatic, much like with any other skill.

You start by learning ways to deal with specific negative emotions. Various systems of psychotherapy emphasize different approaches -- for mainstream CBT, there are 2 main ways to deal with distress "on the fly". There's the cognitive worksheet approach of writing down your current thoughts, attitudes, and beliefs about the upsetting situation, checking them against a list of common cognitive distortions and writing down new thoughts that aren't distorted.

The other main CBT approach is applying behavioral skills, like deep breathing, muscle relaxation training, and distracting yourself temporarily. Some of these behavioral methods are suitable for use in the middle of an upsetting situation because they don't require you to leave the situation, and they can be used without anybody noticing.

Once you've learned skills for handling negative emotions as they arise, the way to deal with rejection is that you practice using those skills right when you get rejected. For example, I made a joke that nobody laughed at about an hour ago, and noticed myself scowling, hunching forward, and feeling upset. So I relaxed my face and my posture, and surreptitiously took a few deep, slow breaths. I felt mostly better after doing that, and the remaining emotional residue wore off over the next few minutes.

Since I have a lot of practice working with troublesome emotional reactions, I automatically handled that moment of social anxiety without having to think about it. But when I was first learning it, I had to intentionally bring to mind all the steps to handling the problem: "Okay, what am I supposed to do when this happens? Oh, right, muscle relaxation and deep breathing. Okay, let me check which muscles are tense... and relax them... and now take a deep breath in, and out..."

Yep, I'd say I've made a ton of progress. I sort of awakened a few months back, and realized that all along it was within my power to take control of my life, to get out and meet people, to work on my hobbies, etc. I sort of suddenly saw what I wanted to do, and clearly how to do it.

That's the core skill of most modern psychotherapies: waking up to the fact that you can develop control over what were once uncontrollable actions and reactions. In ACT, that moment of stepping back from a situation and realizing that you've become enmeshed in overly emotional, distorted perceptions is called "de-fusion". Though CBT doesn't explicitly mention de-fusion (the closest thing being the cognitive distortion of "emotional reasoning"), it's actually crucial to CBT as well, because the very act of realizing that your perceptions may be distorted in a way that upsets you is itself an act of de-fusion.

[GetOutOfBox]

I'd just like to post an update that I've had an amazing improvement in my symptomatology; the brain fog that comes with ADD is pretty much gone (and only crops up when I don't get a good sleep), I don't feel lethargic as often and too the same degree (prior to my regimen, a frequent issue I had was often wasting days just doing simple activities, such as watching tv shows/gaming, since I just felt so incapable of actually engaging in any creative process). My mood has also improved greatly overall; not in an unnatural way, I merely feel more stable. Stress doesn't sap my "emotional energy" like it used to, I find that I can have a somewhat stressful day and still feel like working on my own things. One of the most interesting mood issues I mentioned earlier were surges of anger disproportionate to the cause (intense exercise would often make me feel surges of rage for whatever reason. I could control it, but they soured my mood), is now gone. I sometimes experience "blips" where I feel a minor rise of anger as a result of something petty, but they feel normal.

Motivation is great right now. I'm not magically more motivated to do things, but it comes easier and actually stays once I have it. I find myself progressing in my personal study of electronic music greatly each day, rather than over a period of weeks like before. In a nutshell, I feel like I now have a "normal" level of motivation.

In terms of cognition, I have noticed a minor improvement in memory, however I wouldn't say it's an improvement in my ability to memorize things; rather I feel that when I learn something, it seems better integrated into my long-term memory. It's hard to describe, but the best example would be that I am no more able to memorize and image or text after reading it once than I was before, however I feel that my understanding of something seems to be more concrete. Before, when trying to learn something, I often would have moments where I would understand the concept in it's entirety (or have an idea), only to feel it slip away. So I would say learning has been improved (so perhaps LTP?), though short-term memory remains roughly the same (i.e I don't find it any easier to memorize number sequences, people's names, etc, not that I have any trouble in those areas).

In terms of the social anxiety, I really don't notice any effect from any of the supplements I currently have. I suspect this is due to the fact that my minor anxiety has more to do with psychological issues than biological (neurochemical) issues. I've simply learned to feel anxiety in social situations, I wasn't always this way (I was very extroverted as a child, then flipped into an introvert).

One interesting thing in regards to memory I've noticed, is my pre-existing long term memories seem clearer. I don't know the mechanism through which memories formed before enhancing LTP could be enhanced (at least without purposely refreshing them), but I find myself looking back at childhood memories, and finding them to be much more detailed. I remember a whole ton of vague things, even large chunks of movies I haven't seen in years (one night while falling asleep, I suddenly realized I could literally "play" various scenes from a movie I watched as a child, in my mind. Sound and all). Speaking of sleep, I've also noticed that it seems easier to fall asleep, or more accurately, to just "release" and drift into a sort of meditative state. When I'm ready to go to bed, I quite literally lie down and relinquish control of my thoughts (I can still reawaken myself). Random thoughts will immidietly start to flow, I'll sort of "see" various images darting in and out of my mind, memories, concepts, random meshes of things (often bizarre dreamlike things, like one that stands out in my mind is the sudden portrait of a black man with a large coffee bean the same color as his skin tone merged with his head). It's almost like I can immidietly enter a sort of REM state, though it's not vivid enough to be hallucinations (the imagery is the same "realness" as a daydream's), it's more like a sudden flow of thoughts without any real control on my part. Then I eventually drift off.

I've been taking a lot of supps, I do plan to try each one individually (or in pairs where applicable) to determine which are helping and which aren't. What I can guess based off of the effects of each supp and the timing of their addition to my regimen, I'd say the most helpful have been the following:

-Uridine Stack (250 mg Uridine twice daily (orally), 3 g fish oil twice daily (I'm cutting back to 2 g next month though, 3gx2 is a lot in the long term)) I take this at intervals to maximize the duration of it's effects, as it's main purpose is to modulate dopamine release, preventing too much lows or highs.
-CILTEP Stack (600 mg Artichoke Extract once daily (twice during holidays), 100 mg Forskohlii Extract (which is about 20 mg forskolin)) I take this before I plan to work, as it mostly has short term benefits
-Vitamin B complex, as various B vitamins are crucial to neurotransmitter production
-L-Tyrosine (1 g twice daily), a precursor to dopamine as well as adrenal hormones. At first it will actually boost dopamine production, but the hydroxolaze will downregulate to compensate. However, the benefits will continue if you were mildly deficient prior (essentially, if you start too low, increasing it will give you an initial large boost, eventually dropping to normalish levels, but still better than dopamine levels when you were deficient). One study I mentioned earlier found large improvements when providing a few amino acid supplements to children with ADHD, especially in concert with ritalin.
-Noopept (20mg once daily, sublingually) and ALCAR (250mg once daily, I'm very sensitive to it :P). I don't get the crazy trippy effects some people seem to get with it (even when trying 40 mg in one dose, with or without fatty foods), however I'm fairly certain this contributes greatly to my ability to learn. I think it's also helped me in my efforts to restructure my sources of motivation (greater plasticity could mean responding faster to behavioral modification). It apparently works as a racetam, as well as by increasing BDNF and NGF. One thing to note is that although it doesn't come with any huge tolerance issues from long term use (at normal doses), however people have theorized that constant use over a period of months could cause noticable downregulation of BDNF/NGF activity, so withdrawal is possible. I suspect it would manifest as impaired learning until innate BDNF/NGF activity returned to normal.
-Magnesium Citrate (250 mg before bed). I take this primarily to be sure that I am not deficient in magnesium, which is apparently fairly common. I don't notice any active effects, but I'm sure that this is a good and cheap addition to any stack, regardless of it's application.

I'm still trying a lot of things, but so far the improvement I've seen using these is huge. I also have been taking Oxiracetam. However, I did not include it on this list as I have not noticed any huge effects from it, and regardless, it's less relevant to my goals. However, definitely try it, as some people have amazing reactions, while others (like me) are more meh.

How exactly does one learn to deal with rejection? I imagined that simply by having plenty of positive social experiences, one will be less likely to be shaken by rejection, as one's confidence would be increased by the "practice" in socializing. What exactly do they call a therapist who utilizes CBT/other well founded techniques for social disorders?

It's true that after you've practiced extensively with emotion regulation and socialization, your confidence will increase and your vulnerability to other people's negativity will decrease, and it'll be mostly automatic. However, there's plenty of practice to do before you get there. You have to practice these skills consciously before they become automatic, much like with any other skill.

You start by learning ways to deal with specific negative emotions. Various systems of psychotherapy emphasize different approaches -- for mainstream CBT, there are 2 main ways to deal with distress "on the fly". There's the cognitive worksheet approach of writing down your current thoughts, attitudes, and beliefs about the upsetting situation, checking them against a list of common cognitive distortions and writing down new thoughts that aren't distorted.

The other main CBT approach is applying behavioral skills, like deep breathing, muscle relaxation training, and distracting yourself temporarily. Some of these behavioral methods are suitable for use in the middle of an upsetting situation because they don't require you to leave the situation, and they can be used without anybody noticing.

Once you've learned skills for handling negative emotions as they arise, the way to deal with rejection is that you practice using those skills right when you get rejected. For example, I made a joke that nobody laughed at about an hour ago, and noticed myself scowling, hunching forward, and feeling upset. So I relaxed my face and my posture, and surreptitiously took a few deep, slow breaths. I felt mostly better after doing that, and the remaining emotional residue wore off over the next few minutes.

Since I have a lot of practice working with troublesome emotional reactions, I automatically handled that moment of social anxiety without having to think about it. But when I was first learning it, I had to intentionally bring to mind all the steps to handling the problem: "Okay, what am I supposed to do when this happens? Oh, right, muscle relaxation and deep breathing. Okay, let me check which muscles are tense... and relax them... and now take a deep breath in, and out..."

Interesting, I've basically been doing that without realizing it was part of a formal therapy standard. For example, when socializing, I observe that I'm clenching my hands, so I just consciously relax myself. I find myself doing it less nowadays. When I start panicking (which for me manifests as, my thoughts start to race, I can't seem to focus on any one thing, my heart speeds up, etc. It never gets out of hand, but it can make me jittery), I just force myself to start thinking about something that requires my full attention. For example, I'll imagine a forest, and articulate to myself various details of it, building this mental image. It doesn't have to be classic cheesy, relaxing pond type images, I just find that building mental imagery requires all of my attention, providing immediate relief to the racing thoughts, and eventually the physical symptoms (i.e within a few minutes my bp drops). These kinds of events don't happen often, usually just after an awkward situation. The good thing is that this technique I use works to relieve immediate symptoms, as well as helps me in the long term. I think a lot of the stress and negative feedback comes after the event, when I dwell excessively on it. Preventing myself from entering that loop of self-critique seems to make me less likely to avoid the situation next time.

[jadamgo]

The good thing is that this technique I use works to relieve immediate symptoms, as well as helps me in the long term. I think a lot of the stress and negative feedback comes after the event, when I dwell excessively on it. Preventing myself from entering that loop of self-critique seems to make me less likely to avoid the situation next time.

Right on target.

[GetOutOfBox]

Here's a small update. Nothing new to report in regards to my day-to-day stack, still good. I recently tried Phenibut for a convention I was going too. As I've mentioned earlier, I tend to get reserved and a little tense when meeting new people. I don't have full-blown anxiety, but I get tense.

So here's what I did. I took 1.75 g phenibut once, 3 hours prior to when I wanted the effect. I took it that early, since it's been my experience (as well as many others) that phenibut is odd in that it doesn't take effect until quite a bit after dosing. I suspect it has something to do with the requirement of cleaving the phenyl ring from the GABA. It is water soluble, so there shouldn't be a need to take it with food (and actually you shouldn't take it with fibrous food, as that can prolong absorption). Anyways, here's what I experienced, and how I presume it works. I found it reduced the scope of my nervous impulses. For example, a situation that would normally make me tense or lead to obsessive pondering of it instead only produced a mild tension. So here's what you should expect: GABA supplements like Phenibut/Picamilon will not magically make you a social demon, unless you take ridiculous doses. The goal is not to incapacitate you to the point that your inhibition dissapears, rather to make it easier to resist the anxious cascade. Another point that should be made is that all anti-anxiety drugs do not change the root of the problem, which is a pattern of thinking. People who experience social anxiety have suffered maladaptive "programming" of their neural networks; that is, their brain is physically wired to produce maladaptive responses to socializing, you have been conditioned to feel fear/tension/paranoia in response to socializing with a person. Therefore, drugs that act on neurotransmitters will not correct the cause of the anxiety. You will probably not suddenly start socializing more with people right off the bat. What drugs like Phenibut/SSRIs/benzos do is control the resulting anxiety. So although you will still feel anxious in response to socializing, the anxiety will be much reduced. Particularly in the case of GABA-substances, I find they prevent the anxiety from getting out of control.

So down to my actual experience. After taking the Phenibut, I felt it was a lot easier than normal to socialize. I was still reserved at first; I still had those instinctive impulses to avoid socializing, but as the evening went on, I slowly started warming up, talking to people, and had fun. The next day, I took the same dose again, and had even better results. I went to a dance that night, and for the first time, really loosened up. I was really relaxed and having a good time, I even danced with a few people personally and got the number of one.

The nice thing is that I've found I don't need to keep using the phenibut forever. I've found it helps to get me back on my feet. My attitude is that I'll take it before situations I think will be uncomfortable, and eventually get to the point where I don't need too. You see, the way to reverse those maladaptive behaviors is to force yourself into scenarios where your negative expectations are proven wrong. The more positive reinforcement you get, the more the behavior will be corrected. You will learn to associate socializing with pleasure rather than anxiousness, and eventually you won't need drugs to counteract the symptoms.

Now, it sounds really wonderful, but the downside is that it's potently addictive. The last day or two after those two days of dosing has created some fairly bad rebound anxiety. I didn't realize it at first, but the last day or two I've feeling really tense for no reason. Just sitting in my room constantly worrying about things. I'm certain it's rebound symptoms, though I'm glad I only took it for two days in a row. Be warned, anything acting upon the GABAergic system is very, very addictive, and the withdrawl/rebound symptoms can be insidious. You may not even make the connection between the drug and the feelings of anxiety afterwards. I highly reccomend respecting the potency of this compound, it should only be used 2 times a week at most (and even then, I would make it more of a monthly occasion, the rebound/addiction is just not worth extended use), and no more than 2 times in a row for sure. To be honest, I would stick to once unless you really need to double up. 1.5-2 grams should be enough (more than enough in many people, try with 1 gram to start), keep in mind that it takes a while to take effect. Take at least 2 hours prior to the event, it should last for a long time (some people report effects lasting more than 24 hours, though I would say a conservative estimate would be 12 hours of noticeable effects, with minor effects for another 4-5). If you can actually feel it (in the sense that you feel high/drunk), you're taking too much. It should be a lubricant, not a nitro-injection. I recommend saving it for days where you normally expect high levels of tension/anxiety, that way the more you experience them positively (with reduced symptoms), the more your behavioral patterns will change. Ideally I would combine it with some form of CBT (Cognitive Behavioral Therapy). And always remember that this will not change how you think; if you have trouble meeting people, you will still find it difficult. However, the level of anxiety experienced will be markedly reduced. Just keep in mind that you still have to muster the courage to go against your impulse to avoid those situations.

[GetOutOfBox]

Just wanted to post a recent study (double blind, placebo controlled, 36 children aged 4-14, no previous drug-treatment) that seems to show very promising benefits of Phosphatidylserine (P-Serine) in the treatment of ADHD (specifically inattention and memory symptoms). It found significant improvement in symptoms following 2 months of supplementation of 200 mg daily of P-Serine. Definitely something to look into.

J Hum Nutr Diet. 2013 Mar 17. doi: 10.1111/jhn.12090. [Epub ahead of print]
The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.

Hirayama S, Terasawa K, Rabeler R, Hirayama T, Inoue T, Tatsumi Y, Purpura M, Jäger R.

Source

Department of Early Childhood Education and Care, Kurashiki City College, Okayama, Japan; Daigokyou, Kyoto, Japan.
Abstract

BACKGROUND:

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children.
METHODS:

Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day^-1 PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task).
RESULTS:

PS supplementation resulted in significant improvements in: (i) ADHD (P < 0.01), AD (P < 0.01) and HD (P < 0.01); (ii) short-term auditory memory (P < 0.05); and (iii) inattention (differentiation and reverse differentiation, P < 0.05) and inattention and impulsivity (P < 0.05). No significant differences were observed in other measurements and in the placebo group. PS was well-tolerated and showed no adverse effects.
CONCLUSIONS:

PS significantly improved ADHD symptoms and short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD.

[Herves]

WOW!!! All those are the Exact same Symptoms i have 100% the same.

[GetOutOfBox]

Well I've been investigating other possible avenues of treating my symptoms. I've noticed other symptoms outside standard ADHD definition, most notably auditory issues. I tend to have trouble with both vocalizing and comprehending audible language. I've noticed a pattern where in situations in which I'm slightly stressed, I frequently can be mildly incoherent, such as talking incredibly fast or brokenly, but the catch is that I don't notice it myself. Customers often ask me to repeat what I've said, because apparently it was uncomprehendable, except to me it was fine. I also experience what's called a "poverty of speech", that is I sometimes feel like talking costs me energy and I respond to conversations only when directly pushed too. This combined with the major mood issues I experience including anhedonia as well as a prominent blunted affect after even mild stress (I almost fall into a stupor after being stressed out at work, just staring glassily. I'm not stuck like that, it's like my energy just spills out of me though). All of these are negative and a couple of positive symptoms of Schizophrenia. My father is diagnosed with Bipolar Disorder (originally with psychotic episodes when stupidly prescribed Tricyclic Antidepressants), which is thought to be related to schizophrenia neurologically.

I have on occasion possibly experienced mild delusions. Sometimes I have thought I'm destined to do great things, though it's not an all-consuming belief, so this may just be the occasional indulgence in narcissism on my part xD. One possible delusion is that sometimes I think or say something, only to notice it later in my surroundings and get the strangest feeling like I somehow unconciously foresaw it. Again though, I stress that in those cases I'm not possessed with the belief I have future-seeing powers, it's more that I marvel at the coincidence and wonder if there's something more to it. So I like to think think that it's just my quirky personality enjoying philosophizing, but I also have to accept the fact that if I am deluded, by definition I would not think I am. I can say that if these are delusions, they are mild in that I don't spend much time thinking about them, nor do they drive me to do irrational things (as I've said, I have a very orderly, logical mind).

So mild latent schizophrenia, or at least perhaps some dysfunction in the glutaminergic system is possible, which is why I'm investigating glutaminergic nutraceuticals. It's a bonus that these things could also benefit ADD if I have it, as NMDA/AMPA receptors have been implicated in AD(H)D. So what I've been trying so far is Sarcosine for it's effects on NMDA receptors through glycine-reuptake inhibition (so no direct NMDA action, thus less chance of excitotoxicity), and Sunifiram for it's strong AMPAkine action (aniracetam is a more common AMPAkine, though it's ridiculously short half-life makes it pretty useless). Haven't noticed a whole lot quite yet, but I'm still recovering from sleep deprivation so I'm not expecting to see benefits for a few weeks.

Another possibility I'm investigating is mild Narcolepsy. The stupor I experience after mild stress could be cataplexy, a characteristic symptom of narcolepsy in which muscles relax (in mild cases, they only relax slightly, perhaps in the form of mild facial sagging, and in extreme cases, they completely slacken causing collapse). This would account for the subjective fatigue as well as blurry vision (retinal muscles relaxing). I haven't been able to aquire things to test this hypothesis, but I intend to try modafinil to see if I benefit from it. A proactive form of treatment I'd like to look into is a short-acting SSRI immidietely before sleeping; narcolepsy is thought to be caused by dysregulation of REM sleep, not allowing sufficient NREM sleep. I recalled that SSRIs (and MAOIs) have a REM suppressing effect, so I am curious if supressing REM sleep for part of the night might actually help with the root cause of the disorder. Obviously REM sleep is still critical, which is why I'd look for an SSRI with a very short half-life, perhaps 3 hours if possible. GHB and it's derivative sodium oxybate have already been used in a similar manner, but the lesser known GHB withdrawal makes me want to stay away from chronic use (it's potently GABAergic, so no way I'd take that every night indefinitely, definitely not without an NMDA antagonist like memantine, and for all I know that might screw sleep cycles up even more).

[GetOutOfBox]

Another update: I'm moving away from Schizophrenia as a diagnosis. After some introspection I think that a diagnosis of schizophrenia would be too strong; sure I have some mild symptoms which fit the repertoire, but they are mild enough that I think they don't fit the context of the disease. My apathy has been improving a lot, I think it's the result of years of laziness during high school, I've been pushing myself to work more, and with the assistance of nootropics have started to get better at initiating work myself.

So I'm back to suspecting three possible explanations for my symptoms. Primarily ADD, possibly sleep apnea (which would explain the periods of apathy during the day, the sluggishness it causes would be more like what I experience than ADD's primarily attention-span related issues), and possibly thyroid issues. My grandmother has sleep apnea, and my mother and father show signs of it (intermittent loud snoring followed by silence), so the genetic factor is there. I tried to do a sleep study, but unfortunately was unable to fall asleep at all during the whole night, so I can't really retake it until I'm entirely confident it won't be a waste, since I doubt the province (OHIP) will cover it a third time if it's a waste (and sleep studies cost several thousands of dollars without insurance, at least). My doctor refuses to prescribe a thyroid test since I had a TSH test as a part of a routine blood panel, which came back normal according to the lab standards (2.47), but according to this blurb on wikipedia:

The National Academy of Clinical Biochemistry (NACB) stated that it expected the reference range for adults to be reduced to 0.4–2.5 µIU/mL, because research had shown that adults with an initially measured TSH level of over 2.0 µIU/mL had "an increased odds ratio of developing hypothyroidism over the [following] 20 years, especially if thyroid antibodies were elevated".^[8]

could indicate that I have mild hypothyroidism or an increased risk of it. So I want to convince my doc to do a full thyroid panel just to rule things out.

One thing I'd like to have done when I have the money is genetic testing with 23andme. They are reliable gene testers whose tests can reveal various at-risk medical conditions, including hypothyroidism. If I get a positive as a carrier of the gene(s) associated with it, I might be able to convince my doc to prescribe a full panel. The test also holds a possible use to narrow down ADHD types. Various genes are associated with various types of catecholamine dysfunctions, revealing whether say COMT or MAO is an issue (different phenotypes have different levels of said enzymes). But really, the best test that I hope to see become mainstream soon is qEEGs (Quantitative electroencephalography). qEEGs are basically analytical studies of the results of an EEG scan, correlating various results with behaviors observed in various studies. Essentially these can allow doctors to definitively determine which sub-types of ADHD the patient likely has, and adjust pharmaceutical treatment to best target the patients needs. SPECT scans also show use for mapping receptor densities in the brain, which would reveal which receptors have an abnormal density, and again, allow for specific medications to be issues (i.e patients with normal D1, D2, and D3 receptor counts but low Norepinephine receptor counts could be prescribed Atomoxetine instead of ritalin, yielding better results without months of playing around with different meds).


Anyways, I've been off Ritalin daily for several weeks, and have recently taken to taking it on specific days when I want to study, and found it works MUCH better when used this way. I consistently feel it's effects, as long as I don't take it more than 3 days in a row and take several day breaks. Despite what mainstream medical literature seems to indicate (which is based on trials that were no longer than 4 weeks), I suspect that even low-dose ritalin produces tolerance, just like any stimulant. I find it unlikely that a stimulant could avoid down-regulation no matter what the dose. Sure, down-regulation from 10 mg two times daily is likely to have negligible negative effects, it would still counteract the effectiveness of the treatment. And high dose ritalin would almost certainly produce down-regulation signifigant enough to cause crashes when the drug wears off. The only mechanism in which down-regulation could be avoided was if the drug had the effect of simaltaneously causing dopamine receptor upregulation, which as far as I'm aware, has not been observed with ritalin. NMDA-antagonists can slow down tolerance, but they have the nasty side-effect of reducing memory performance, as well as reducing arousal (the cognitive state, not sexual).

This segues into my next avenue of investigation: upregulating dopamine receptors. Several substances have been observed with this effect, most notably CDP-Choline (citicoline), and Phenylpiracetam. Of course, where this upregulation occurs has a signifigant impact on whether these substances help in the way desired, but so far with my experience using lowish average doses of CDP-Choline, it seems to increase the sensitivity of my reward system. Correlation does not equal causation of course, but I have been working much better lately. I'm awaiting Phenylpiracetam from Newstar Nootropics, but the studies demonstrating it upregulates several receptors (NMDA receptors, nicotinic acetylcholine receptors, GABA_A receptors and D₁, D₂ and D₃) is very promising. The only possible area of concern is the NMDA upregulation means one has to be careful of two things: A) Tolerance to substances will theoretically occur faster if the Glutaminergic system is sensitized. B) Excitotoxicity is more of a risk when using drugs known to have that effect (Adderall, MDMA, etc). There are benefits, especially in those with glutaminergic deficient states (theoretically some sub-types of ADHD). You just have to be careful.

I've also ordered two other very interesting Russian nootropics; Semax 0.1% nasal drops, and Afobazol, both from awakebrain. I'd like to note that despite the shady looking website, so far I've had great customer service from the guy that runs it, very fast (within the hour) responses to emails. I almost canceled my order after reading Semax (as a peptide) needs to be kept at sub 10 celcius temperatures or else it breaks down, but upon emailing him he explained that he packages it with ice-packs in insulation, and that the compounds official website states that it can withstand temperature fluctuations for short periods (about a week, so being stored at room temperature for weeks will eventually reduce it's effectiveness, but for short periods no harm is done). I also decided I wanted to add Afobazol to the order and have them shipped as one, which he was quick to do (I paid for just the cost of the pills seperately).

So anyways, these two compounds are particularly interesting. Semax presents potentially very powerful nootropic effects that seem to accumulate with time. It's been associated with a plethora of effects, including:

Strengthening the immune system (specifically by negating the negative effects stress-hormones have on immunological health).
Increasing concentrations of NGF and BDNF signifigantly (possibly producing TrKB downregulation after extended use though, so cycling might be needed).
Modulating various neurotransmitter systems (and thus rather than producing highs and lows like many stimulants, may normalize neurotransmitter output, stabilizing mood).
Anti-immflamatory effects.
Modulating the Limbic and Reticular Activating system axis (thus possibly alleviating anhedonia, brain fog, etc).

It's pretty expensive, so it can't be a regular habit, but I plan on using it during periods of intense studying.

Afobazol has shown promise as a potent anxiolytic without the common negative effects (reduced memory performance, sluggishness, EXTREME tolerance/addiction associated with benzos). My social anxiety has largely been alleviated after my efforts of exposing myself to social situations more combined with nootropics, but this could still be highly useful during stressful periods. It's also much cheaper than semax, at $30 for 60 pills.

Both of these are Russian brand-name, so it's likely they're legit. Russia tends to be much less tightly regulated when it comes to prescriptions, so obtaining such compounds is relatively easy for those in Russia, so I trust in their authenticity. I'll post back with my results.

[GetOutOfBox]

Update in regards to some of the new nootropics/novel drugs I've been trying (Afobazole, Semax, Phenylpiracetam):

I'll start with the Afobazole, since that has the most pronounced effects. So far I'm having VERY positive experiences with this novel anxiolytic. I would actually describe it as an anxiolytic/anti-depressant hybrid, as I've noticed it seems to have more of a mood stabilising effect than directly affecting anxiety. I've been taking two 10 mg doses daily (1 tab = 10 mg), one in the morning after waking up, and one at about 6 PM. I've been on it almost two weeks, and have lately noticed my mood seems much more stable; I'm less susceptible to sharp spikes in nervous tension, as well as depressive moods. There's been some issues in my romantic life for the past 6 months or so; I've mostly fixed my problems myself, but I find that when the occasional trigger enters my day, I don't experience a downward spiral of negativity. I feel as if I can just shrug depressive moods off. The Afobazole may even be useful for OCD like anti-depressants often are, as it seems to reduce obsessive thought patterns (in my case, involving a person I used to have feelings for, I spent almost a year experiencing a limerance for them, and despite giving myself credit for moving on, I strongly feel that the Afobazole helps prevent me from obsessing about "what could have been with them"). This stuff is very cheap so definitely a re-buy. I haven't noticed any addictive qualities to it, as I've skipped a dose to see what happens, and all I notice is that the positive effects diminish slightly. No compulsion to take it, or crippling re-bound anxiety. I suspect that like SSRI's it takes a week or two to begin having noticeable effects, and that it's positive effects linger even between doses (as in, it causes persistent changes in brain structure/neurochemistry). One very important thing to note about Afobazole that doesn't seem to be documented, is that you most definetly should not take it before bed, or anytime near when you'll be sleeping. One of it's primary methods of action is as a MT1 and MT3 receptor antagonist (Melatonin Receptors), and as such I highly suspect it would signifigantly reduce sleep quality if active during sleep. Melatonin is critical to regulating sleep architecture, so even if Afobazole doesn't keep you awake, it's probably reducing the quality of sleep you experience. On a side-note, I think Afobazole may have potentially very positive effects for those suffering from SAD (Seasonal Affective Disorder), which is connected to melatonin irregularities brought about by prolonged darker days in winter. Since Afobazole antagonizes the two main melatonin receptors, it could be a possible treatment alternative (or combined with) for light therapy. Just something to keep in mind.

On to Semax. I'm going to start by saying I don't think it's worth the cost. It's difficult to administer conservatively (I found trying to squirt just one drop into each nostril very difficult, the provided dropper is very sloppy, and seems to be a non-standard size, so using your own will end up using much more per drop), luckily there doesn't seem to be an LD50 (you can't overdose), and very expensive. You only get something like 10 days per bottle at best, which is between $40 and $60 usually. I did feel effects from it, I found it made me feel very "clear" and confident. I define "clear" in this context as feeling very awake (but not a stimulanty-sort of awake, very natural feeling), and filled with mental stamina. The feeling you get when you have several very good nights of sleep in a row (which is rare for me unfortunately, I usually get by on average quality sleep). I don't actually feel any profound nootropic effects in the sense of improved memory, attention span, etc. But I feel like I could handle a day of mental work. This makes sense, as it's similar in structure to ACTH (the primary hormone in the hypothalamic-pituitary-adrenal axis), but produces only neurological effects without systemic hormonal action. I suspect it primarily works by modulating the HPA and thus promoting a state ideal for handling stress. Semax probably has the most pronounced effects in those with a disrupted HPA, possibly as the result of chronic stress, hormonal issues, sleep deprivation, etc. It's a very nice feeling, but not worth the cost for me. It might be very relevant to people suffering from a disrupted HPA as an indirect effect of various disorders, such as Narcolepsy, Insomnia, and especially those with disorders like Cushings or Addisons disease (it won't treat them, but it could resolve some of their symptoms by normalizing the HPA).

Finally, Phenylpiracetam. I do notice a bit of a stimulant edge to this racetam, it's interesting but I find it's just sort of "there". It doesn't bother me, but it doesn't stimulate me in a way I feel I can channel into work. It's like a weak buzz. I'm more interested in it's long-term effects anyways, which involve upregulating several receptors, including various dopamine receptors, and GABA-A. It's fairly cheap from the right vendors, so I'm going to stick with it.

Just an update on my actual mental status; I'm definitely demonstrating some practical improvements in memory in my everyday life after the last couple of months of intensive nootropic regimens. For example, at work today on two different occasions I glanced at a customer's phone number on the screen once, and was able to remember it entirely without writing it down when I went into the back to type it into the billing computer. Sometimes I even find I recall a customer's phone number and don't need to ask them for it when they come back to pick up their product. For me, being able to keep a 10-digit number series I'm exposed to a single time, in order, in my working memory outside of a controlled environment (it's one thing to test your memory in the quiet of your home vs having to remember practical things in a loud environment) is a fairly big accomplishment. And the occasion where I actually remember said number an hour later is amazing (though I must admit this happens much less), as I have to get every customer's phone number to keep track of who's who, so that's a lot of phone numbers going in and out of my head each day.

Studying-related memory hasn't had as remarkable improvements; I find my memorization capability of complex abstract concepts (rote memory) is about the same. However I feel that my practical learning performance has improved, as I've been noticing that I'm retaining things taught to me much better. It's not really surprising rote memory isn't really improved, as it's a very inefficient way of learning (the human brain's short-term memory did not evolve to receive large quanties of abstract concepts and convert them to long-term memory in one go, repeated exposure is required to trigger Long-Term Potentiation associated with long-term memory).

Finally, of all the improvements, I'd say my emotional health has enjoyed the greatest improvement. My social-anxiety is virtually gone (I went from being a loner with one friend in high school, to a graduated adult with a network of friends in communities I'd never have dreamed I'd associate with), I find social interaction with new people much easier. I used to have a very avoidant-type personality (preferring not to take risks), and have flipped around to someone who's willing to take risks when appropriate. I face my problems directly now, rather than hiding from them, which has greatly helped my chronic (albeit minor) depression issues.

I've been using a huge variety of nootropics, which is admittedly not the best way for the wallet (it's been very expensive). I do agree with the advice to try one or two things at a time to find out what works for long-term stacks, however if you feel you have issues you'd like to fix vs simply improving yourself (i.e ADHD, social anxiety, depression, dementia, etc), a broad-spectrum approach is much more effective. There are multitudes of avenues of enhancement beyond ACh (Acetylcholine), such as targeting the glutaminergic system (i.e Sunifiram, Sarcosine), the dopaminergic system (Phenylpiracetam, Uridine, CDP-Choline, Ritalin), the seratonergic system (Bacopa, Afobazole, Tianeptine), hormonal (Selank, Semax), or even really niche areas like the immune system (Tenoten, a novel anxiolytic targeting antibodies). Without access to various extremely expensive brain imaging systems/qEEGs, there's no way to establish a direct form of treatment, so you've got to try to hit everything until something works. The one exception I do advise to this approach, is anything which is likely to have negative side-effects. I don't recommend barraging your brain with anything that has very potent acute effects, such as potent stimulants/sedatives (i.e Adderall, Ritalin, etc); combining substances that are potent agonists/neurochemical releasers could have very negative repercussions. I personally only use this approach for substances that cause gradual changes (such as upregulation), as negative side-effects can be caught as they emerge, whereas if you combine say 40 mg of Adderall with a potent MAO-A inhibitor, you'll be screwed by the time you notice side-effects.

[Mind_Paralysis]

Hey there! I've been following your progress in this thread with GREAT interest! Fantastic thread, imho. You're truly an enterprising and talented individual, when it comes to neural knowledge and experimentation.

What I have noticed, is that we have a lot of similarities in our symptoms and histories ( even down to disturbed sleep-cycle and family-history of conditions similar to Schizophrenia), and I think your treatment might work fairly well on me as well. ( I have ADD, Inattentive ADHD)

May I ask what your current regime is? What are the stacks and combo's that you have felt have helped you the most?

Also, what are your opinion on Lisdexamfetamine as an ADD-med? How does it stack, with it's delayed release of amfetamine to the body?
If you haven't heard of it, I suggest checking it out, as it's the new all-the-rage ADHD med' here in Scandinavia, seems a lot of people are hopeful about this one.
It's a combo of dextroamphetamine coupled with L-lysine, for those in the wonder, and in the know.

Edited by Stinkorninjor, 17 October 2013 - 07:55 PM.

[GetOutOfBox]

I've never tried Lisdexamphatamine (Vyvanse), however I am familiar with it. I've been on Adderall in the past, which is a racemic mixture of levoamphetamine and dextroamphetamine. In my experience, Adderall in particular has extremely potent effects on attention, as do single-salt (specifically levo or dextro) amphetamine medications (but to a lesser degree usually). However the issue I have with amphetamines and especially Adderall, is that they feel like a sledehammer approach to the problem. Sure, my attention is much more focussed, but they cause such a surge of dopamine in the brain that there are often pretty intense side-effects. I for one had minor shyness amplified to crippling social-anxiety (as I found Adderall tended to magnify my perception of tension and anxiousness). When I finally stopped, within a couple of months I found myself socializing a lot more again, after avoiding it for almost a year and a half.

The other issue is that tolerance to amphetamines develops incredibly fast. In small doses, addiction isn't really an issue, but the medication quickly reduces in effectiveness. I find the vast majority of doctors are trained to reccomend a very unsustainable dosing plan to patients, most doctors seem to try and "solve" this issue simply by perpetually raising the dose every time the patient complains they're not feeling effects, until they reach the safety limit, at which they reccomend a "holiday", which means slowly lowering the dose and repeating the same cycle.

Another issue I found with medium to higher dose amphetamines, is that no matter how good the time-release mechanism is, when the drug inevitably wears off, you crash. Some lucky people simply return to their ADHD state, that is, just unfocussed. I personally became useless once it wore off. Didn't feel like doing anything. And the issue is, a lot of the time-release mechanisms out there are very hit or miss; some days they work well, some days not so much. Adderall for one is signifigantly affected by the acidity of the GI tract, taking it with say orange juice significantly reduces absorption and increases excretion. I'm sure Vyvanse presents it's own set of issues, like some people with differing phenotypes cleaving the lysine amino acid from the d-amphetamine at different rates.

Essentially, I don't feel amphetamines are a good long-term drug. I strongly feel based on my own experience, as well as what's made very clear by the pharmacological action of amphetamines and their derivatives, that they should be reserved for acute situations, such as studying prior to a test, or for taking every now and then to have a very productive day. That way tolerance isn't an issue.

I feel the same about similar drugs like Ritalin, but to a lesser extent. I still think tolerance is a major issue that most doctors don't consider enough, but Ritalin tends to have less brutal side-effects than amphetamines, and may even have some positive effects, like being neuroprotective (whereas high dose amphetamines are neurotoxic).

TL;DR: What I've basically decided to aim for, is upregulation as a goal for long-term treatment, as it oscillates at a much slower rate than drug tolerance (once you cease taking a drug that produces upregulation, it doesn't immediately downregulate, it can take weeks to reduce again). I also think that much greater attention should be put to studying comorbid disorders in individual cases. Anxiety is frequently comorbid with AD(H)D, and I think a lot of people underestimate how much of an impact it can have on their main symptoms. Depression is also very often mistaken for attentional issues, or occurs alongside AD(H)D and exacerbates it's issues. I was skeptical of the possibility I had depression/anxiety issues, mostly because I've always rationalized my way through it. However, the Afobazole (which I noted previously, that I've observed both anxiolytic and antidepressant actions) as well as Noopept significantly helped in treating those issues, and indirectly improved my other issues. On that side-note, it's interesting to note that depression may very well be primarily an issue of hippocampal atrophy as a result of chronic stress (or other genetic predispositions). It seems SSRIs possibly increase neurogenesis in that region, which may actually be how they work instead of the very dated "Monoamine hypothesis" (summarized as: "Serotonin = happy chemical, if it's low, you're sad, so let's raise it to make you happy!!"),

There are dozens of possible factors that could cause AD(H)D like symptoms, and I suspect that like Major Depressive Disorder, what we label as "AD(H)D" may actually be several distinct conditions that respond to different treatments. Thyroid issues could cause attention difficulties, always get at least your TSH checked (standard annual blood test usually covers that) to see if there's thyroid issues. Problems with the HPA (Hypothalamic-Pituitary-Adrenal Axis) could also produce lethargy and attention issues. Such problems include Cushing's disease (Hyperadrenocorticoism), or Addison's Disease (Hypoadrenocorticoism). Cyclothymia (minor Bipolar disorder) could also severely dampen one's productivity, the mood fluctuations would be exhausting. Prodromal schizophrenia is something that should be watched for if you have a family history. I would avoid recreational psychoactive drugs if you begin manifesting schizophrenia symptoms (particularly minor delusions/hallucinations), as they likely can exacerbate dysfunctional serotonergic/dopaminergic/glutaminergic circuits. Finally, there could be as yet undefined disorders, which is why I take a broad-spectrum approach in my quest for a health mind.

[Mind_Paralysis]

Wow, that's a lot of factors you have taken into consideration! I think I really do need to check for Thyroid and HPA issues. Cyclothymia, I don't really feel seems very probable, I'd say I'm fairly emotionally stable, actually. My problems are more like yours, I have difficulty motivating myself, and focusing on longer tasks. ( I'm an artist, and there's nothing as soul-crushing as creating an intricate work of art, but also, nothing as liberating as a small, quick work of art.)

Recreational drug-use is not an issue for me, as I have so far lived a pretty dogged life of complete absolutism ( I don't even drink coffee), straight-edge so to speak.
( my parents have obvious issues handling alcohol, this has then deterred me from use of recreational drugs)

But all right, seems like you're no fan of the Amphetamine -derivatives, which surprised me, as I had seen a lot of online backlash against Ritalin and other Methylphenidates - seems like some people actually get the side-effects the other way around? I.e Meth gives them shakes and depression but Amph does not.

But tell me more about your upregulating-stacks! =) What upregulators do you take? And have you come to the conclusion that you need more dopamine than you need norepinephrine or choline? ( apparently, some ADHD patients don't have problems with dop or nor, they've got Choline transport -issues, a completely unmedicated section of the disease, it would seem)

Are you currently still on Guanfacine in some manor? I checked that drug, and it seems like a true next-gen medication when it comes to treatment. What is your final review of that drug? Did it help you?

I myself is currently only using some simple basic supplements:

240mg EPA + 200mg DHA Omega-3
120 mg of Magnesium-citrate/lactate combo
A good multivitamine

It helps a little bit, but obviously it's merely a band-aid on an oozing puss of an ADD-wound. A note about Omega-3's - it would seem as if they only help about 33% with ADHD, in the long-run. I've talked to a doctor that uses it for his patients, and he has noted that it's only 1/3 that actually get better with a good intake of Omega-3 fats.

[GetOutOfBox]

Yeah, I really feel strongly that before an AD(H)D diagnosis is made, imitator conditions that are actually curable (or partially so) should be checked. Current standard AD(H)D therapy is far from proactive or curative, it's just a band-aid that ultimately falls off. Stimulants really are not a sustainable long-term treatment, as the brain tends to adapt to them within a month at most (for me, I found Adderall was amazing for about 2 weeks, and then quickly started fading into the background until it eventually was causing more problems than it helped). The problem with prescribing stimulants to treat an AD(H)D diagnosis made primarily from a behavioral diagnosis (and not SPECT or qEEG testing, which is fairly inaccessible right now, but in the future may have more widespread use), is that they may cover up the neurological symptoms of other conditions, like hypothyroidism. Stimulants will increase attention span in ordinary healthy people, so someone who's suffering from mild cognitive impairment as a result of hormonal or other issues may actually feel an improvement, which a lot of doctors assume means they really do have AD(H)D, due to lack of widespread awareness of the nuances of stimulant treatment.

Check out the symptoms of Hypothyroidism as described by Wikipedia:

Earlier

• Appearance: thin, brittle fingernails; dry, itchy skin; weight gain, water retention,^[5][6][7] myxedema, hair loss
• Neurological: depression, rapid thoughts.
• Neuromuscular: depressed reflexes, hypotonia, muscle cramps, joint pain, mood instability, irritability, constipation^{[citation needed]}
• Constitutional: fatigue,^[8] sleepiness, cold intolerance, decreased sweating
• Cardiovascular: bradycardia, elevated serum cholesterol.
• Endocrine: female infertility, menstrual irregularities, hyperprolactinemia, and galactorrhea.

Uncommon

• Neurological: impaired memory.^[12] and inattentiveness,^[13] decreased sense of taste and smell, deafness^[14]

Mild hypothyroidism could easily be mistaken for AD(H)D, as it almost always produces fatigue issues (thyroid hormones being involved in metabolism).


Anyways, in terms of upregulating stacks, I've been taking Phenylpiracetam and CDP-Choline. Phenylpiracetam has been found to significantly increase the following receptor densities: GABA-A, D1, D2 and D3. Unfortunately it also down-regulates NMDA and Nicotinic Acetylcholine receptors (as it's an agonist of both, so in the short-term it increases nAch activity, much like nicotine, so there could be acute nootropic effects as well). I'm not so concerned about the NMDA down-regulation, as I take a few glutaminergic nootropics (Sarcosine, Sunifiram) that probably make up for the lower receptor count. I was initially concerned about possible consequences of nAch downregulation, but I haven't actually noticed any observable memory issues (I'm not really concerned about memory benchmarking, just whether or not it serves me well in practical scenarios). CDP-Choline increases dopamine receptor density as well, and does a bunch of other nice things aside from just being a choline source (improving glucose utilization and blood-flow, being neuroprotective on multiple levels, increasing SAMe production, etc).

As for my targeting dopamine, I do actually take some stuff for choline too (Oxiracetam, CDP-Choline, etc). Norepinephrine is something I'm going to look into after this phase of trials. I'm thinking of asking my doctor for a prescription of Strattera, which is primarily an NRI with little dopamine action. It effects Norepinephrine much more than Ritalin does (it's technically a DNRI, but it primarily affects the dopamine trasporter), so it'll be interesting to see how my symptoms respond to it. The reason for me looking into dopamine first, some of the D-receptors seem to be involved in regulating exploration in a laboratory sense (for rats, exploration is literally that, exploring mazes for cheese, etc. In humans, it involves more complex behaviors such as learning new things, exploring new stimuli, hence why it is applicable to seemingly unrelated conditions such as social anxiety). Other D-receptors seem to be directly involved in learning and short-term memory, so they're obviously juicy targets.

Norepinephrine may be more related to concentration at ordinary levels, which sounds like it should be the primary target for AD(H)D treatment; however I've been a little reluctant to play with it due to it's involvement in the fight-or-flight response. Elevated levels of norepinephrine often produce nervous tension, something I'm prone to in certain situations. Still, I think I'll try a low-dose of Strattera just to see how much my concentration improves.

As for Guanfacine, I was never able to obtain it. Unfortunately the AD(H)D version (an extended release delivery system, as instant-release is more beneficial to cardiological issues) Intuniv, is unavailable for standard prescription in Canada. It apparently can be obtained if you sign up for preliminary Health Canada trials, but my doctor had no idea what it was and hence really wasn't interested in filling out a bunch of forms for something he wasn't familiar with. It's been in the US for a few years now, so it'll probably make it's way into Canada without any issue. Other countries will probably also follow suit eventually. It's primarily useful for the Hyperactive sub-type, as they tend to have the most prefrontal-cortex issues (Impulsiveness is a result of the prefrontal-cortex having difficulty regulating behavior). However, I suspect it may be useful for inattentive sub-types, as they may be suffering from similar PFC issues (perhaps a minor impairment of executive function producing only mild attention issues, vs the major impairment of hyperactive sub-types, producing an almost complete inability to focus or regulate one's own behavior).

Ultimately what I'm starting to suspect, and this is based on a combination of my experience, and research in the field, is that therapy is crucial to AD(H)D regulation. Earlier in the last 9-months of my nootropic experimentation, I rehabilitated my social anxiety through a combination of Noopept and a few supporting substances, alongside forced social exposure. I took Noopept while forcing myself to attend large gatherings of people (such as anime conventions), and doing my best to talk to strangers and get to know them. At first it was really tough, but slowly, I began to find such events easier and easier and finally, here I am today. It's remarkable the change I've underwent, bizarre almost. For almost my entire high-school life, I had about 2 friends (and I held even them at a distance, only hanging out with them every now and then to maintain the friendship), and spent almost all of my time in my room playing video games, or getting by at my crappy job (where I had pretty much no friends). That's 4 years of stagnation. Now, I have a network of friends, and not only ones who are a lot like myself, but a bunch who on the surface seem completely different, but as I've gotten to know them, I find I can still enjoy being around them. I go to parties and I dance freely, without worries that people think I'm weird (and when the occasional paranoid thought emerges, I can just brush it away without shelling up). I've been in two (albeit short-lived, due to compatibility issues) relationships, whereas during elementary and high school, I only ever went on one date. I find I no longer dread going to social events, and I feel so much more socially adept.

What I'm trying to say is that I think like social anxiety, AD(H)D may have strong behavioral components as well. Perhaps negative behavioral patterns are acquired (self-defeating thought patterns, procrastinatory behaviors, etc), and then due to physical brain anomalies (i.e dopaminergic circuit defects) become near impossible to overcome. So perhaps medication restores the brain's flexibility and opens up the possibility of changing those negative behaviors, but only if you actually employ a therapeutic approach. In the case of my social anxiety, the Noopept probably counteracted the hippocampal atrophy associated with depression and anxiety disorders, and prepped my brain for exposure therapy, which I self-administered. Perhaps something similar can be achieved with AD(H)D. I am looking into a referral to a therapist who specializes in AD(H)D, I strongly suspect it would be beneficial, despite my long-running skepticism.

[MizTen]

...imitator conditions that are actually curable (or partially so) should be checked. ...
Ultimately what I'm starting to suspect, and this is based on a combination of my experience, and research in the field, is that therapy is crucial to AD(H)D regulation. ...
What I'm trying to say is that I think like social anxiety, AD(H)D may have strong behavioral components as well. Perhaps negative behavioral patterns are acquired (self-defeating thought patterns, procrastinatory behaviors, etc), and then due to physical brain anomalies (i.e dopaminergic circuit defects) become near impossible to overcome. So perhaps medication restores the brain's flexibility and opens up the possibility of changing those negative behaviors, but only if you actually employ a therapeutic approach. In the case of my social anxiety, the Noopept probably counteracted the hippocampal atrophy associated with depression and anxiety disorders, and prepped my brain for exposure therapy, which I self-administered. Perhaps something similar can be achieved with AD(H)D. I am looking into a referral to a therapist who specializes in AD(H)D, I strongly suspect it would be beneficial, despite my long-running skepticism.

This thread has been excellent. GetOutOfBox, thanks for sharing some truly insightful ideas. I think you are very correct on most, if not all, of the points you made.

I had an original dx of ADD and SAD, which later became GAD and PTSD. Adderall was helpful initially but also more harmful in the end, though very little problem for me to stop cold turkey.

This year my various nootropic experiments yielded some good, but somewhat short-lived positive effects. Then my NSI-189 trial changed the game completely for me. I noticed a few other people with ADHD dx who benefitted much more than expected from NSI-189. At the point where the positive effects of NSI-189 for me became obvious, I was able to implement the various brain-training strategies with much greater efficacy than previously. So although I was using them before, they became much more powerful and useable with the drug. So yeah, I believe that targeted therapeutic strategies can be curative with the right drugs. Some therapies can be self-taught, though a good therapy plan and therapist are preferable.

Anyway, it's a great thread.

[GetOutOfBox]

This year my various nootropic experiments yielded some good, but somewhat short-lived positive effects. Then my NSI-189 trial changed the game completely for me. I noticed a few other people with ADHD dx who benefitted much more than expected from NSI-189. At the point where the positive effects of NSI-189 for me became obvious, I was able to implement the various brain-training strategies with much greater efficacy than previously. So although I was using them before, they became much more powerful and useable with the drug. So yeah, I believe that targeted therapeutic strategies can be curative with the right drugs. Some therapies can be self-taught, though a good therapy plan and therapist are preferable.

Anyway, it's a great thread.

Wow, I had not heard of NSI-189 prior to your post. The prelinary workup is remarkable; reports of 20% gains in hippocampal volume in healthy mice, it could potentially have very practical nootropic properties as well as being a powerful (and more direct than SSRIs) treatment method for hippocampal atrophy related disorders (primarily depression and anxiety disorders, Alzheimer's/misc dementia would also greatly benefit I'm sure, if administered alongside a drug to clear amyloid plaques).

Now of course, it's easy to get excited by new compounds, as the fact they possess less studies can make positive results look fabulous, as they have no contrasting negative results. However, this compound is in end-phase clinical trials, which definitely says good things about it. Anyone interested in acquiring it should probably head to this thread that I found, for participation in a group buy.

As for your anxiety issues, I strongly advise you investigate Bacopa if you experience acute anxiety attacks. It takes about 8 weeks for positive effects to become apparent (though it has some acute effects as well), but it seems very promising in resolving serotonergic circuit aberrations. It must be taken with a fatty food for full absorption, taking Milk Thistle supplements alongside it may enhance absorption additionally (due to some effects on liver enzymes). Make sure that like all herbal supplements, you get it from a good vendor. Supplement manufacturers are not required to provide high-quality plant matter in supplements, they can legally use crappy, old useless herbs, as long as they are still what the label says they are. However if they state the percentage of active compounds on the label, I believe they are required to back it up (though obviously there's not a whole lot of enforcement unless safety is the concern). The brand I use is AOR. They're far from the cheapest, but they have a good reputation.

[chemicalambrosia]

Great thread you have here, please continue to update.

Now of course, it's easy to get excited by new compounds, as the fact they possess less studies can make positive results look fabulous, as they have no contrasting negative results. However, this compound is in end-phase clinical trials, which definitely says good things about it. Anyone interested in acquiring it should probably head to this thread that I found, for participation in a group buy.

NSI-189 is actually still in the initial human safety trials. It is not near "end-phase" trials yet.

[GetOutOfBox]

Another update, no changes in my stack this time, but I have some new insight into my results as well as some VERY interesting research I've come across. I highly suggest taking the time to read this post. Skip to the underlined part if you're only interested in the research portion.

Nothing new ADD specific, but I'm starting to suspect as a result of my stack my reaction time has improved. I'm a fan of first person shooters, particularly Team Fortress 2. However I've always been average at them, never spectacular. However, I've been noticing lately that my performance in them has improved significantly over my pre-nootropic self (and I've been an avid gamer for a large part of my life). I'm noticing that I seem to be able to process gameplay more rapidly, not only am I much more accurate with my shooting (both stationary sniping and forward-class strafe-shooting), but I automatically outwit opponents. I now often seem to anticipate my opponents actions and counter them much more effectively. It's difficult to explain without explaining the entire game's gameplay, but it can effectively be summarised as me feeling that my "reactive planning" ability has increased, as well as my visual-muscular coordination (interpolating the future position of moving objects to my advantage within the game for example). The reason I had not noticed this earlier is that for the last while I'd been playing video games significantly less often, which further makes this improvement impressive.

It's not a very rigorous scientific observation, but it was significant enough that I thought it worthwhile to post. I suspect that the combination of nootropics over the last several months has produced chronic improvements in my cognitive performance in time-limited scenarios (such as video games which require automatic thinking). This improvement in cognitive performance may actually be general, but unfortunately I still struggle with motivation issues which has been the limiting factor when it comes to abstract-concept projects such as programming. This brings me to the bit of research I've uncovered.

It seems that ADHD-Hyperactive and ADHD-Primarily Inattentive sub-types are possibly distinct disorders with separate causal factors. I've come across a couple of studies suggesting that the inattentive sub-type of ADHD may be strongly related to a polymorphism in the D4 receptor (DRD4 or Dopamine Sub-Type 4 receptor) in which it reacts less strongly to dopamine, whereas the hyperactive sub-type may be more related to a DAT (Dopamine Transporter) polymorphism. This pattern has been observed in genetic analysis of children with diagnosed with a type of ADHD, and a few studies in which various animals are genetically engineered to have either deficit also seems to produce each respective disorder. This is further supported by the very common occurence in which children and adults with the hyperactive sub-type of ADHD respond very well to Methylphenidate or Adderall, whereas the inattentive sub-types often respond less-well. If this observation is correct in that a deficit of the D4 receptor causes ADHD-Predominately Inattentive (which may or may not be the same thing as SCT, Sluggish Cognitive Tempo), it makes sense that mainstream treatments would have only small efficacy, as they target the Dopamine Transporter. They increase post-synaptic levels of dopamine, which is of some help, but ends up only indirectly treating the problem. The improvement that ADHD-PI patients may see with stimulants could simply be the marginal cognitive enhancing effect that inhibiting DAT produces in those lacking a polymorphism in that gene.

Assuming ADHD-PI is caused by the DRD4 polymorphism, Ritalin (and any other DAT-inhibitor) will not correct the dysfunction caused by the hypoactive D4 receptors. It may improve cognitive performance as a result of increasing other dopamine receptor activity, but some of the symptoms of the disorder may remain. The reasoning behind this is that all Ritalin does is increase the duration of dopamine's activity in the post-synaptic cleft. In this model of ADHD-PI, the problem is not that dopamine is being reabsorbed too rapidly, but that a specific receptor is not responding adequately to it. Thus the next best option is Adderall, which due to it's effect of both inhibiting DAT and causing elevated release of dopamine, may partially treat the problem. Greater levels of dopamine in the post-synaptic cleft may help activate the D4 receptor more, but it's still an indirect solution.

The sucky part about this model of ADHD-PI is that treating it effectively is much, much more difficult. In this case the D4 receptor itself is defective, and thus drugs which manipulate dopamine levels or even agonise the receptor will not completely resolve the issue. Two possible avenues to investigate that occur to me would be a full D4 agonist, which although still doesn't fix the issue directly, would allow for more specific treatment vs the unneeded flood of dopamine Adderall produces (which can often cause more problems than it solves). Compounds that upregulate the D4 receptor would be even better, as they could produce some long-term relief (though the receptor would still be defective, greater receptor densities could partially compensate for the problem). The bad news is that I have been unable to find an easily available D4 agonist. The few ones that exist are specifically marketed as second-line Parkinson's treatment, so good luck finding a physician willing to prescribe them for ADHD. I have been unable to find ANY compound which has confidently been observed to upregulate D4 receptors. I've seen a few "whispers" that memantine may upregulate D4 receptors, but no studies have specifically confirmed this and I have my own doubts that it would produce such an effect. I recall coming across a study that actually noted D4 receptors seem to remain static and do not upregulate or downregulate (odd exceptions to homeostasis are not unheard of, for example, for some reason nicotine seems to upregulate nAch receptors despite being a full agonist). However, there may be some hope, which I'll explain a little bit later in this post.

It also occurs to me that someone could be hit by a double-whammy and have both a DAT polymorphism and a DRD4 polymorphism, which would no doubt be crippling, though "luckily" Ritalin would still be able to cancel out the DAT side of things.

Now, what I failed to go into in earlier paragraphs is; what does the D4 receptor actually do? It seems to be less clear as to what it's function is. Some studies seem to think it may be related to novelty seeking, while others disagree. One interesting thing I observed is that it is known to REDUCE concentrations of cAMP when the receptor is activated, possibly specifically in the Prefrontal-Cortex (PFC). Elevated levels of cAMP are known to cause Prefrontal Cortex Dysfunction, as they inhibit signal propagation between neurons in the PFC and the rest of the brain. So my thinking here is that, a problem with the D4 receptor results in elevated levels of cAMP in the PFC, thus resulting in PFC dysfunction. Since the PFC is associated with higher executive processing (i.e attention regulation), it is reasonable that this could cause ADHD-PI and other disorders. Sooo, since fixing the DRD4 polymorphism is so difficult, perhaps turning our attention downstream to the cAMP problem is a possible avenue of investigation. And I have some very good news, there is a drug marketed for ADHD which could address this issue! It's Intuniv (Guanfacine), which I have mentioned earlier. It currently seems to be marketed specifically to children with hyperactivity (as the hyperactive sub-type is much more common and easily diagnosed), but I'd be VERY interested to see how effective Intuniv could be in treating the disorder.

Even better, I learned today that Intuniv (the extended release form of Guanfacine for ADHD) has finally been approved for use by Health Canada, and thus I can probable get my doctor to prescribe it. I intend to make an appointment soon to hopefully obtain some. I will post updates documenting my success.

P.S Here are links to some of the studies that inspired this post:

http://www.ncbi.nlm..../pubmed/9774775
http://www.ncbi.nlm....les/PMC1474811/
http://www.genomenew...DRD4_gene.shtml
http://www.ncbi.nlm....pubmed/15521361
http://www.scienceda...70420143324.htm

Edited by GetOutOfBox, 30 October 2013 - 02:55 AM.

[Mind_Paralysis]

Ah-HAAAH! So, this may be why Intuniv works... I've seen a lot of talk about this med', but very little about its actual function, but this post pretty much hits the nail on its head!

GetOutofBox - you da' man! I am going to ask for Intuniv when I finally get in line for the medical treatments. ( I'm currently merely going through the mental testing, and I appear to be hard to diagnose, I'm most likely ADHD-PI tho'.)

I did testing for TSH-levels for hypothyroidism btw, and it came out normal - I later checked that the testing for TSH (thyroid stimulating hormone) is often inadequate tho', since it doesn't check for the actual levels of active T3 and T4 hormone levels. ( especially the T3 is important, because the less active T4 is heavily converted to make T3, and the test can't see if you have a problem with converting T4 to T3)

I'm going to be buying a termometer and doing some body-temp testing for the next few days, as that is actually a good, effective test as well. If it's consistently below 36.5 degrees celsius, then I ( or you) might have a problem.

[chris106]

I myself have ADD-PI, and like many others have been following your thread with great interest. (In the last couple of hours that is, wish I would have found it sooner! )

Like you, I have tried various nootropics and supplements during the course of this year, with mixed results at best.
I am currently trying LLLT (see Lost Falco's massive thread about it), but I am unsure as to how beneficial upregulated ATP and mitochondrial production would be for ADD-PI, even if the PFC is targeted specifically.
My first few two sessions had an suprisingly positive effect in terms of motivation and wellbeing, though. Unluckily I ran out of PQQ and Q10, and am since waiting for my new batch to arrive, so I can continue my trial with this approach :(

Another interesting approach I recently read about is that of combining Phosphatidylserine with high doses of Omega 3,Krill Oil specifically. Some studies claim they are highly synergistic and potentiate each others effects. It's kind of a long shot with limited anecdotal reports, but then again it's kind of cheap to try, so I'll give it a shot soon. You mentioned Phospatidylserine before, I think - was it actually part of your stack at some point, and did you notice benefits?

Lastly, I recently read in another thread, that a user of this forum had unexpected success in reducing ADD-PI symptoms (specifically muscle tension) with Pycnogenol (Pine Bark extract) - so maybe that's worth a shot, too.

Anyways, sorry if my post is all over the place - but these will be the (relatively novel) approaches, which I'll try next. If anything sticks, I'll let you know.

Guanfacine seems most interesting though! Please keep us updated about your success, this thread is very inspiring and I admire how thorough you've researched your facts!

[GetOutOfBox]

Ah-HAAAH! So, this may be why Intuniv works... I've seen a lot of talk about this med', but very little about its actual function, but this post pretty much hits the nail on its head!

GetOutofBox - you da' man! I am going to ask for Intuniv when I finally get in line for the medical treatments. ( I'm currently merely going through the mental testing, and I appear to be hard to diagnose, I'm most likely ADHD-PI tho'.)

When you do get around to getting a prescription, don't let the doctor brush you off because it's marketed for hyperactivity. The bulk of ADHD studies still focus largely on the hyperactive sub-type, likely because it's more prevalently diagnosed (due to the more debilitating nature of the impulsive-hyperactive sub-type on overall quality of life, thus more people seeking medical help). Thus it's not surprising the drugs applicability to inattention hasn't been thoroughly studied. Theoretically it should have fairly profound effects in reducing common AD(H)D symptoms such as: lower attention to details, feelings of being overwhelmed by concentrated stimuli, social difficulties, short term memory dysfunction, etc. If elevated levels of cAMP are the major contributing factor to AD(H)D, essentially the Prefrontal Cortex is being disconnected from the rest of the brain, or more accurately, neurochemical "noise" prevents inputs/outputs from getting through. Thus correcting the elevated levels should essentially restore prefrontal function and possibly completely (or largely at least) treat the disease.

Now, I suspect that for the greatest benefits to be seen, an extended period of time on the drug is required. My theory on this is that with the PFC having been functionally impaired for such a long period of time (years/entire life), it will likely have atrophied, or at least the neural pathways linking it to the rest of the brain will have. Regular electrical activation is required to keep the brain from pruning synapses, so in this case it's likely the PFC is not perfectly healthy and ready to go the moment Intuniv removes the cAMP problem. The producer quotes an estimate of 2 weeks for effects to be felt I believe, though I suspect the greatest improvements could take 2-3 months to be fully realized (though this is a conservative estimate, I'm fairly confident at the very least 1 month is required for any large neural pathway adjustments to be realized).

Furthermore, the PFC of someone suffering from AD(H)D may not be in fully working order even after administration of Intuniv. I have always suspected AD(H)D is caused partially by a biological dysfunction that impedes normal development skills acquisition. So this drug may restore PFC connectivity, but it won't magically configure it so as to regulate attention and behavior properly. Those are likely learned skills, as evidenced by the effects dysfunctional parenting can have on behavior/emotional regulation. So my point is that this drug may remove the biological element of our disorder, but that still leaves it on us to take advantage of it and learn self-regulatory skills/behaviors. So in terms of a practical course of action, finding a good ADHD therapist might make all the difference in the success of Intuniv treatment. At the very least you should concentrate greatly on self-teaching yourself such skills (i.e creating and FOLLOWING lists of tasks to do, not indulging temptations to divide ones attention, etc).

I myself have ADD-PI, and like many others have been following your thread with great interest. (In the last couple of hours that is, wish I would have found it sooner! )

Like you, I have tried various nootropics and supplements during the course of this year, with mixed results at best.
I am currently trying LLLT (see Lost Falco's massive thread about it), but I am unsure as to how beneficial upregulated ATP and mitochondrial production would be for ADD-PI, even if the PFC is targeted specifically.
My first few two sessions had an suprisingly positive effect in terms of motivation and wellbeing, though. Unluckily I ran out of PQQ and Q10, and am since waiting for my new batch to arrive, so I can continue my trial with this approach :(

Another interesting approach I recently read about is that of combining Phosphatidylserine with high doses of Omega 3,Krill Oil specifically. Some studies claim they are highly synergistic and potentiate each others effects. It's kind of a long shot with limited anecdotal reports, but then again it's kind of cheap to try, so I'll give it a shot soon. You mentioned Phospatidylserine before, I think - was it actually part of your stack at some point, and did you notice benefits?

Lastly, I recently read in another thread, that a user of this forum had unexpected success in reducing ADD-PI symptoms (specifically muscle tension) with Pycnogenol (Pine Bark extract) - so maybe that's worth a shot, too.

Anyways, sorry if my post is all over the place - but these will be the (relatively novel) approaches, which I'll try next. If anything sticks, I'll let you know.

Guanfacine seems most interesting though! Please keep us updated about your success, this thread is very inspiring and I admire how thorough you've researched your facts!

Getting Omega-3s (from an animal source like salmon or krill, plant sources are terribly inefficient) is definitely a priority. They are heavily involved in brain function, a deficiency probably reduces neuroplasticity through an impact on the brain's ability to form new synapses. If you regularly eat (quality) fish in your diet, supplementation is probably redundant, but if you're like me and never/very rarely eat fish (due to an allergy in my case), supplementation is a good idea.

Yup, I still have Phospatidylserine as a part of my stack. I don't feel it's crucial, as it doesn't have acutely psychoactive effects (it doesn't have a strong effect on neurotransmitters, but rather increases cell membrane health in the long term), but I take it nonetheless as it's cheap and good for overall brain health. I cycle it every few months, as I feel the benefits are probably maintained for a while after supplementation. There seems to be some anecdotal reports it has a positive effect on ADHD, though the bulk of evidence I've seen suggests neurotransmitters are likely the main causal factors of ADHD and not underlying cell health (i.e ATP). There's a possibility of a separate disorder of cell health producing cognitive dysfunction, but likely it would not manifest as a specific neurological dysfunction but as a general cognitive dysfunction.

Pycnogenol potentially treats ADHD as a result of mild MAO inhibitory properties, which would result in increased extra-cellular dopamine levels. I doubt it has a strong enough effect to be considered a possible primary treatment though, but a potentially good thing to combine with other treatment methods (the mild MAO-activity may potentiate other dopiminergic treatments. I suspect it's safe to combine as long as you're not on medium-large doses of amphetamines).

Yeah, I'll definitely keep updating the thread! I haven't been able to get the prescription yet, haven't gotten a chance to drop into the doctors office. Will post back once I do though.

Additionally, on a whim I decided to grab some PRL-8-53 from NewStarNootropics, as it looks like a very interesting compound. Apparently one study found digit recall went from the average 7-8 digits to 21 digits, which is obviously a huge improvement. I'm highly skeptical that such large improvements could be reproducibly achieved, but a modest improvement would be nice. I'll post back on my success with this compound as well.

[abelard lindsay]

Regarding Intuiv, have you guys read these patient reviews?

http://www.addforums...ad.php?t=103704

http://www.drugs-for...94&postcount=11

http://www.medschat....iscuss/Intuniv/

http://www.drugs.com...t-disorder.html

From reading all these I don't get how this is a nootropic.

Pycnogenol potentially treats ADHD as a result of mild MAO inhibitory properties, which would result in increased extra-cellular dopamine levels. I doubt it has a strong enough effect to be considered a possible primary treatment though, but a potentially good thing to combine with other treatment methods (the mild MAO-activity may potentiate other dopiminergic treatments. I suspect it's safe to combine as long as you're not on medium-large doses of amphetamines).

Pycnogenol is a pretty solid focus supplement in my experience.

Additionally, on a whim I decided to grab some PRL-8-53 from NewStarNootropics, as it looks like a very interesting compound. Apparently one study found digit recall went from the average 7-8 digits to 21 digits, which is obviously a huge improvement. I'm highly skeptical that such large improvements could be reproducibly achieved, but a modest improvement would be nice. I'll post back on my success with this compound as well.

This one's a bit of a mystery. It had such great results but it just collected dust on a shelf for 40 years? Weird.

Edited by abelard lindsay, 06 November 2013 - 02:32 AM.

[GetOutOfBox]

UPDATE + Reply to Abelard Lindsay:

I forgot to mention, but I am starting to suspect Afobazole IS producing discontinuation effects, despite it allegedly not doing so. I finished the package at a dosing schedule of 10 mg, once in the morning and once in the evening (always spread 9-10 hours apart). I've enjoyed the mild anxiolytic effect (for me, I'd compare it to a mood stabilizer, sort of smooths things out nicely), so I'd ordered more, but it hasn't arrived yet.

Anyways, lo and behold, 2 days after the last dose I noticed some odd anxious behavior in myself. I wouldn't describe it as the general, high-strung mood benzo/phenibut withdrawal causes, it's more insidious. I actually feel decent, functional. However, at one point at work I realized I was feeling bizarrely anxious about things I shouldn't be, and had a general sort of "odd" feeling. I wasn't experiencing a panic attack or any crippling anxiety, but I was definitely overreacting to things; I'd obsess over some thought bothering me, yet feeling as if it shouldn't be bothering me as much as it was. It's hard to describe, as I'm still fully functional and relatively happy, so I only connected the fact it was day 2 of not taking Afobazole and I was feeling this way by chance.

It's possible it was just me having a bad day, but I'm definitely going to keep an eye on my mood and see if it keeps happening. As it is right now, I'd still recommend Afobazole, as the discontinuation effects if they really are present, are very tolerable as long as you know why you're feeling the way you are.

Regarding Intuiv, have you guys read these patient reviews?

http://www.addforums...ad.php?t=103704

http://www.drugs-for...94&postcount=11

http://www.medschat....iscuss/Intuniv/

http://www.drugs.com...t-disorder.html

From reading all these I don't get how this is a nootropic.

It's not. In fact, in ordinary people it would likely have a negative effect as it essentially does the opposite of the CILTEP stack. However, as I outlined in my earlier post, people with the DRD4 polymorphism (stands for Double-Repeat Dopamine 4 I believe), which is linked to ADD specifically, have impaired D4 receptors. D4 receptors have a downstream effect on reducing cAMP in the PFC. Elevated cAMP reduces activity along the neural pathways connecting the PFC to the rest of the brain. Intuniv lowers cAMP as it's method of action. So it seems like the best course of action, as there are no drugs targeting the D4 receptor specifically. Inhibiting DAT or increasing levels of dopamine won't change the fact the receptors do not activate as efficiently as they should, it would take a significant raise in dopamine to compensate, and at that level other receptors would likely be over-activated.

I am aware of the less than fanatical reception Intuniv has. It's likely due to the main side-effect being sleepiness, which most people can't tolerate. However, a lot of people do not try such drugs for as long as they should (look at the volume of people in depression forums trying an SSRI for a week and deciding it doesn't work because no relief appears right away), which can account for the less than enthusiastic response vs stimulants like Ritalin which have an immediately perceivable effect. I suspect at least a month is required to benefit from the drug.

As for the side-effect of sleepiness, if I experience it, I'll probably just toss Modafinil into the mix. Problem solved.

Pycnogenol potentially treats ADHD as a result of mild MAO inhibitory properties, which would result in increased extra-cellular dopamine levels. I doubt it has a strong enough effect to be considered a possible primary treatment though, but a potentially good thing to combine with other treatment methods (the mild MAO-activity may potentiate other dopiminergic treatments. I suspect it's safe to combine as long as you're not on medium-large doses of amphetamines).

Pycnogenol is a pretty solid focus supplement in my experience.

It's mild MAO inhibitory properties would no doubt have a nice effect on attention span and focus in healthy individuals, but in people with dopamine receptor or transport polymorphisms, a stronger effect is needed (usually). Of course it can vary between people. The bulk of studies regarding it seems to be in regards to it's antioxidant properties rather than MAO-inhibitory properties, so it's probably better suited for the aging brain (a nice combo of mild MAO-inhibition to compensate for slightly lower dopamine levels in aged brains, and antioxidant properties to prevent age-related dementia).

Additionally, on a whim I decided to grab some PRL-8-53 from NewStarNootropics, as it looks like a very interesting compound. Apparently one study found digit recall went from the average 7-8 digits to 21 digits, which is obviously a huge improvement. I'm highly skeptical that such large improvements could be reproducibly achieved, but a modest improvement would be nice. I'll post back on my success with this compound as well.

This one's a bit of a mystery. It had such great results but it just collected dust on a shelf for 40 years? Weird.

Yeah, I'm not expecting the miracles a lot of people seem to be, as the hype seems to be based off of only a couple of studies. However it has a low LD50, low side-effect profile and it's method of action doesn't sound risky like IDRA-21's does (<- an ampakine 10-30x more potent than aniracetam that can be psychoactive for 3 DAYS, that's just asking for neurotoxicity; you'd need to be verrrry careful with dosing and definitely not combine it with anything known to possibly cause excitotoxicity). So I thought I'd give it a go considering how cheap it is.

The study for it suggests that improvements as great as 200% are possible, hell, direct cranial stimulation (tDCS) doesn't produce such results, but I'm hoping for something along the lines of increasing digit recall by say, 3-4 digits.

Speaking of tDCS, that's another avenue I'd like to pursue. Theoretically it should have the most direct action of all nootropic approaches. Whereas most chemical nootropics work on neurotransmitters and thus indirectly influence neuron activity (lowering or raising activation thresholds), tDCS directly increases receptor activation and in targeted areas.

Edited by GetOutOfBox, 06 November 2013 - 03:12 AM.

[GetOutOfBox]

Followup Update:

It's starting to look like the Afobazole may not actually have been the cause of my odd symptoms, as I'm starting to get sick. Developed congested sinuses and a mild cough today, so it's very likely my anxious and foggy demeanor yesterday was fatigue caused by the rhinovirus I'm infected with.

Still, to be safe I'll keep an eye on my status following breaks in-between Afobazole dosing.

[Mind_Paralysis]

I am aware of the less than fanatical reception Intuniv has. It's likely due to the main side-effect being sleepiness, which most people can't tolerate. However, a lot of people do not try such drugs for as long as they should (look at the volume of people in depression forums trying an SSRI for a week and deciding it doesn't work because no relief appears right away), which can account for the less than enthusiastic response vs stimulants like Ritalin which have an immediately perceivable effect. I suspect at least a month is required to benefit from the drug.

As for the side-effect of sleepiness, if I experience it, I'll probably just toss Modafinil into the mix. Problem solved.

A small note on a combo of Modafinil and Guanfacine - I wouldn't take a substance with so many negative side-effects to counter the drowsiness that Intuniv gives you.

Rather, I have heard on a few ADHD -forums that some actually get good results, getting rid of irritability and drowsiness, with a bit of DMAE+B12 ( prefferably with the B12 already bound to the DMAE). This seems to work fairly well for children, who seems to be the primary consumers of Intuniv.

Not sure about the dosing tho', but the good part is that the side-effects of sleepiness and irritability that Intuniv gives, goes away in a few months, it seems, so you won't even need to pop DMAE after a while.

( a bit of DMAE now and then tho', wouldn't hurt tho, methinks. It seems to be neuroprotective, and it makes ya' feel GOOD!)

[Mind_Paralysis]

I had my first talk with a Dr a few days ago, but she was highly skeptical towards Intuniv, because she has never used it to treat people with ADD or ADHD, and isn't sure about the side-effects.

This seems to be pretty common here in Scandinavia, where the mild stimulants like Concerta seems to be the preferred weapon of choice for many Doctors. I didn't push it too much, as I want to build up her confidence in me, and get a good working relationship with her, so as to eventually ween her over to Guanfacine as the go-to drug.

Do any of you have any suggestions regarding how to charm her over to the Intuniv side tho'? I'm not sure how to proceed, because she's seems somewhat uneducated on the latest breakthroughs regarding cAMP and the PFC, and how it relates to ADD.

[GetOutOfBox]

I had my first talk with a Dr a few days ago, but she was highly skeptical towards Intuniv, because she has never used it to treat people with ADD or ADHD, and isn't sure about the side-effects.

This seems to be pretty common here in Scandinavia, where the mild stimulants like Concerta seems to be the preferred weapon of choice for many Doctors. I didn't push it too much, as I want to build up her confidence in me, and get a good working relationship with her, so as to eventually ween her over to Guanfacine as the go-to drug.

Do any of you have any suggestions regarding how to charm her over to the Intuniv side tho'? I'm not sure how to proceed, because she's seems somewhat uneducated on the latest breakthroughs regarding cAMP and the PFC, and how it relates to ADD.

It's pretty new everywhere actually, the usual first line treatment in the states and Canada is Ritalin or Ritalin SR/Concerta (time release forms). If those fail, Adderall is next up, or a non-stimulant like Strattera.

I'm not surprised she's not jumping on board right away, Docs will always err on the side of the indications in their big drug book if they aren't familiar with a compound, so it's no surprise she's not excited to prescribe it against the standard indications.

Rather than get into cAMP and the PFC, I'd just say you feel that although you don't have hyperactive tendencies, you have impulsive tendencies which perhaps impair task completion (lack of self-regulation, etc). It's a reasonable argument that fits the indications of Intuniv. You can also mention that you're interested because it's a non-stimulant that doesn't effect mood directly. The latter part of that sentence is good to deflect her likely automatic Strattera suggestion when you mention non-stimulants. Despite not being a stimulant, strattera has potent effects on mood, often negative (a lot of people, and I mean a LOT, report mild-moderate depressive tendencies on it).

As for your thoughts on Modafinil, at mild doses it's actually fairly side-effect free relative to the competition (amphetamines), and without the nasty tolerance. It's really well tolerated by most people with no serious negative effects with long term use.