Categories
Nootropics Phenylpiracetam Racetams

Phenylpiracetam — Stimulant Nootropic: Effects, Dosage & Experiences

Those who spend any amount of time looking into nootropics will be very familiar with the racetam class of nootropics, a group of drugs that are structural derivatives of piracetam. These drugs display variance in the details of their effects, but they all exhibit neuroprotectant and cognitive-enhancing properties.
One of these piracetam derivatives, phenylpiracetam, is appealing to many nootropic users due to its many purported benefits.

Background and Benefits

phenylpiracetam nootropicPhenylpiracetam is frequently cited to display the following effects:[1][2]

  • Memory enhancement
  • Anti-amnesia
  • Antidepressant
  • Anticonvulsant
  • Antipsychotic
  • Anxiolytic

If phenylpiracetam does indeed have these listed properties, its appeal extends beyond just the sphere of nootropics. Any drug with that kind of resume is certainly impressive. Here we will examine this unique substance and its purported effects.

Phenylpiracetam, also known by its Russian pharmaceutical names Phenotropil and Carphedon, was developed in Russia in the 1980s as a piracetam derivative, with the hopes that it would display and expand upon the nootropic properties that make piracetam such a popular drug. Specifically, phenylpiracetam is a phenylated analog of piracetam, meaning that it is essentially a piracetam molecule with a phenyl group attached. Interestingly, some have theorized that phenylpiracetam’s purported stimulant effects may be due to the molecule’s similarity to phenethylamine (and, by extension, amphetamine).

These potential stimulant properties, along with phenylpiracetam’s ability to improve physical stamina, has led to the drug being banned from use in Olympic competitions.[3]

phenylpiracetam-nootropic-stimulant

Dosage, Mechanism, and Effects

Phenylpiracetam is typically sold by online vendors in its pure powder form or as pharmaceutical tablets. Most of these sources sell a racemic mixture of the molecule, but some of the studies done on the effects of phenylpiracetam were conducted using only the R-isomer.

Phenylpiracetam Phenotropil Nootropic
Original Russian Phenylpiracetam (Phenotropil)

A single dose of phenylpiracetam typically ranges from 100200 mg. Most prescription guidelines state that phenylpiracetam can be taken 2-3 times per day, as the drug will exert effects on the body for about 4-6 hours before receding. It should be noted that most anecdotal reports from users indicate that phenylpiracetam builds up a tolerance rather quickly, so it might not be wise to use it for days in a row. That being said, the drug appears to be relatively safe to use regardless of tolerance buildup.

Phenylpiracetam’s mechanism of action still remains largely uncertain. While various studies have been conducted on its effects, few have dealt with the specifics of its pharmacology. However, one study performed on rats found that phenylpiracetam decreased the density of nACh and NMDA receptors in the hippocampus when they had previously been given scopolamine, an anticholinergic drug.

Phenylpiracetam was also found to increase the density of the D1, D2, and D3 dopamine receptors[4]. Dopamine receptors are important for motivation, arousal, pleasure, and memory.

It also appears that phenylpiracetam’s enantiomers have unique effects and properties. Most notably, studies indicate that the R-enantiomer is mostly responsible for its stimulating and cognition-enhancing effects while the S-enantiomer may be more responsible for stopping cognitive decline.[5]

One of the drug’s biggest potential uses is for treating cognitive decline brought on by diseases like Alzheimer’s. Various studies have been conducted in Russia studying the effect of phenylpiracetam on cognitive decline caused by organic causes. These studies found that phenylpiracetam improved the cognition of those with Alzheimer’s disease, and showed minor effectiveness in improving the cognition of patients afflicted with epilepsy. The drug did not, however, appear to improve cognition for those whose cognitive decline was brought on by traumatic brain injury.[6] In a study conducted on 400 patients with ischemic stroke, phenylpiracetam was able to improve cognition when taken at a dose of 400 mg per day for one year.[7]

There is currently no research conducted on phenylpiracetam’s effect on cognition in young, healthy subjects, although anecdotal reports throughout the internet suggest that it does improve cognition among those with no cognitive disorders. One study conducted on rats found that the R-enantiomer of phenylpiracetam was able to enhance cognition, but this result has not been replicated in any study using the racemic mixture.[8]

Zhiliuk, Mamchur & Pavlov[9] found that Phenylpiracetam improves the processes of learning and storing conditional skills when studying cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats.[10]

Gustov, Smirnov, Korshunova IuA and Andrianova argue that Phenylpiracetam is beneficial to people who develop cognitive deficits and/or depression after encephalopathy and brain injuries.[11] It increased quality of life in patients with encephalopathy after acute lesions (30 people), brain traumas (33 people) and glioma surgery (36 people). The average Mini Mental State Examination (MMSE) scores (a 30-point questionnaire) from baseline improved in all groups. Anxiety improved and depression declined substantially, resulting in less discomfort and better ability to execute everyday activities.[12]

phenylpiracetam memorySome preliminary studies have found phenylpiracetam to have antidepressant properties. However, this area of effect has not seen as much research as the area of cognitive enhancement. A study performed on rats found that when phenylpiracetam was administered to rats, it significantly reduced depression symptoms caused by a forced-swim test.[13] A study conducted on human patients with cognitive decline concluded that phenylpiracetam is able to alleviate symptoms of depression.[14]

Perhaps one of the most unique and attractive benefits of phenylpiracetam is its ability to act as a psychostimulant. However, this effect is not very well researched, although one experiment conducted on rats found that phenylpiracetam increases locomotor activity for upwards of 2 hours.[15]

Anecdotal Reports

As with any nootropic drug that has not seen as much clinical research as one might hope, it is useful to look at anecdotal reports from users to give a fuller picture of the drug’s effects. Obviously, individual user reports are especially prone to the placebo effect and should be weighed and judged by the reader with caution.

Reddit user The_Antagonist said –

At the peak of it’s effects (about an hour in) I feel intense focus, not especially jittery, unless stacked with something else, just pure attention, and a complete abolishment of any lethargy I would have been feeling previously. It’s not really a euphoric compound, but I’ve noticed it seems to make me significantly happier when I’m accomplishing something on it. It might be the racetam effects rearing their head, but solving mathematical problems, or gaining a more complete understanding of a concept just feels plain good. This attribute [in particular], for me at least, makes it a hell of a study drug.[16]

Reddit user Notlambda

I’m not a social butterfly. I’m retarded when it comes to explaining a concept or defending an argument.
On phenylpiracetam (or daily doses of piracetam), I’m a social genius. What it feels like is that I’m not the one saying the words that I’m saying. It’s like I feed a “command” into a register in my brain that is then picked up by whatever part of my cortex deals with speech, and then I find myself just saying the perfect words to explain everything concisely.
It’s like I’m watching somebody else be awesome, but that somebody else is me. It’s really nice because I can free the rest of my mind to think about concepts while the “other” me is doing all the talking.
It’s also very subtle. I’m explaining this like it’s a dissociative experience or something like that. It’s not.[17]

From user le_unknown

I’ve had great results with phenylpiracetam. Without a doubt, it has been the nootropic that works best for me. Gives me alertness (but no jitteriness, I just feel awake and normal – kills all drowsiness), focus, and a tiny mood elevation. I’m surprised I don’t see more people talking about it…[18]

Conclusion

Phenylpiracetam’s seemingly wide array of effects and benefits makes it well worth looking into. Most notably, phenylpiracetam seems to provide many of the benefits of piracetam, while seemingly being more potent or effective in certain areas. Phenylpiracetam seems to noticeably provide cognitive capacity improvement, mood elevation, and stimulation. Experiences will vary widely among individual users, so we would highly recommend you try phenylpiracetam for yourself to see how it works for you.

You can buy Phenylpiracetam in powder form as well as in capsules at NootropicsDepot.

Phenylpiracetam
8
Focus
8
Mood
7
Memory
9
Stimulation
6
Relaxation
8.5
Safety
Reviewer 9

References   [ + ]

Categories
Biohacking Coluracetam Nootropics PRL-8-53 Tutorials

Photographic Memory: Nootropics and Mnemonic Devices 101

Photographic memory, or eidetic memory, is the ability to vividly recall images after seeing them for a short period of time. A Google search shows over 16.000 results for “photographic memory nootropics”. Of all the articles I read, no one of them answer the fundamental question: Does photographic memory exist, and is it possible to achieve with a combination of mnemonic techniques, training, and nootropics?

What is Photographic Memory?

According to the Merriam-Webster dictionary[1]

Eidetic is the technical adjective used to describe what we more commonly call a photographic memory. The word ultimately derives from the Greek noun eidos, meaning “form.” The ability of certain individuals to recall images, sounds, or events with uncanny accuracy is a subject of fascination for researchers in the field of psychology. Among notable people who were reputed to have eidetic memories is the late television comic Jackie Gleason, who reportedly was able to memorize an entire half-hour script in a single read-through.[2]

There are only two case studies of eidetic memory in scientific research. Let’s take a quick look at them.

Case 1: The Mind of a Mnemonist

The first case study of a subject with an “incredible” (photographic?) memory was published in a Russian medical journal in the 1960s by psychologist Alexander Luria.

Alexander Luria was a famous Russian psychologist active in the mid-1900s. In the early days of his career, he met a young man named Solomon Shereshevsky. Shereshevky, — or simply ‘S.’, the acronym used in Luria’s writings — was a Russian reporter working for a local newspaper. Each morning the editor would meet with the staff to hand them a rather long list of assignments. Solomon was able to memorize the entire list by looking at the sheet of paper just once.

Solomon Shereshevsky Photographic Memory Nootropics
Solomon Shereshevsky

Even though he was not a brilliant student due to his shy nature, when S. was a schoolboy he could memorize every single thing he read without ever taking notes. Intrigued, Luria took S. to his lab and, over the course of several months, tested his memory using all kinds of complex mathematical formulas and rare languages. Once, he read him the first four lines of Dante’s La Divina Commedia in Italian, a language he could not understand, and he was able to recite it in a matter of seconds.

On the basis of the research’s findings, Luria diagnosed S. with a rare form of synesthesia, called ideasthesia.

Ideasthesia is a phenomenon in which letters, numbers, and other visual objects evoke a “perception”-like experience. Since humans are hardwired to memorize visual concepts more efficiently than letters or numbers, an individual with ideasthesia can memorize characters, numbers, and symbols after viewing them for a couple seconds

The theory of this phenomenon closely resembles the idea behind the Method of Loci (more on that later), a technique used by mnemonists to memorize many different chunks of information that would otherwise be difficult to memorize.

So what kind of visual perceptions did the Divine Comedy evoke?

The first line, Nel mezzo del cammin di nostra vita, he rendered into images this way: Nel, Nel’skaya, a ballerina; mezzo, she is together with (Russian vmeste) a man; del, there is a pack of Deli cigarettes near them; cammin, a fireplace (Russian kamin) is also close by; di, a hand is pointing toward a door (Russian dver); nos, a man has fallen and gotten his nose (Russian nos) pinched in a doorway (Russian tra); vita, the man steps over a child, a sign of life — vitalism; and so on, for 48 syllables.[3]

In 1968, after S.’s death, Luria published a book of his findings, The Mind of a Mnemonist. He wrote it for a non-scientific audience and I recommend it to anyone. The translated version can be easily found on the web with a quick Google search.

Case 2: The Girl with Eidetic Memory

Fast forward to the 1970s. A Harvard scientist named Charles Stromeyer III publishes a paper about a girl with an incredible ability. He gave her a sheet of paper with a pattern of 10,000 random dots, and the next day another random pattern with a different layout.

The girl was able to fuse the pattern in his mind and form a stereogram, which she saw as a three-dimensional image floating above the surface. A couple of days later, when questioned by the researcher, she could draw each pattern with astonishing accuracy.

The case study of Elizabeth – this is the name of the girl – was published in Nature. However, in a comical turn of events, the researcher later married the girl, and she was never tested again.

dot pattern photographic memory
A random dot pattern like the one given to Elizabeth

A couple of years later, in 1979, a researcher named John Merrit published the results of an eidetic memory test he had placed in magazines all over the country. After seeing Elizabeth results, he had hoped that someone might come forward and prove, once and for all, the existence of photographic memory. He figured that over 1 million people had tried the test. However, of the 30 people that were able to correctly figure it out, he went on to visit 15 of them, and nobody could repeat the experiment with the scientist looking over his/her shoulders.

So how was Elizabeth able to succeed in the test? Did she have some weird memory superpower?
Some say that the Elizabeth study was not real, but rather a silly prank between friends that got out of hand. nthomas from the Straight Dope forum explains it:[4]

When I was in a graduate seminar on the psychology of memory (about 16 years ago, at a major university) I was told by the professor, an expert in the field, that the “discovery” was, in fact, a hoax. As he told the story, “Elizabeth” was actually the girlfriend of the researcher, who had been talking to her about his interest in eidetic imagery. He had a reputation, however, for being rather gullible, and, for a joke, she, and a group of his other friends, cooked up a fake demonstration of her amazing eidetic powers. He was completely taken in, and became very excited at his amazing “discovery”. But before “Elizabeth” and her friends had the time (or maybe the heart) to let the victim in on the joke, things had got out of hand, and the discovery was already well known, and, before long, published.
The etiquette of scientific publication would make it difficult to get a story like this into the formal record, and, anyway, psychologists probably do not want it too widely known how easily they can be taken in. (Perhaps, also, people were reluctant to ruin the career of the poor, duped but not dishonest, researcher.)
[…]I got the impression from my professor that the hoax story was quite well known amongst memory researchers. Furthermore, my impression is that psychological opinion over whether eidetic imagery (as distinct from the ordinary, relatively unreliable, memory imagery, that nearly everyone experiences) really exists, is still much more divided than Cecil seems to believe. It may be the majority opinion that it is real, but a respectable minority of researchers have their doubts. The amazing abilities of “Elizabeth” do still occasionally get mentioned in the reputable psychological literature, however. Some serious scientists do seem to believe it. I myself am no longer sufficiently close to the “in group” of memory psychologists to have heard the hoax story again, or to check out how widely it is known or believed.

So there you have it: the only recorded case of a genuine photographic memory among ordinary human beings is, very likely, a hoax.

Kim Peek Super Memory
Kim Peek

That’s not to said that there aren’t folks with a really good memory. Kim Peek, the famous savant who was the inspiration behind Rain Man, could supposedly memorize each page of a 9,000+ page book, reading at a rate of 8 to 12 seconds per page (with each eye reading its own page). This has not been thoroughly tested, however.

The American actress and author Marilu Henner, on the other hand, can supposedly remember every day of his life. Again, this has not been tested in a clinical setting, and may just be a symptom of an obsessive-compulsive disorder.

Another savant, Stephen Wiltshire, has been called the “human camera” for his ability to draw objects around him several minutes (to hours) after having seen them for the first time. However, again, as precise he is, he takes liberties, so it is not clear if he truly has a “photographic” memory, but he’s the closest to it.

Stephen Wiltshire Eidetic Memory
Stephen Wiltshire

How to Develop Photographic Memory

Solomon, Kim, and Stephen are truly fascinating cases, but they are not normal guys – they have very rare abilities. So, can a normal human being develop photographic memory or the closest thing to it?

The answer is No. Photographic memory can’t be achieved, not even with nootropics. However, by taking nootropics and learning a few techniques, we can develop an exceptional memory. Let’s see how.

Memory: What is It, How to Improve it

There are several stages of memory formation: memory acquisition/encoding, working memory/short-term memory, long-term memory/consolidation, memory retrieval, and reconsolidation.

Five major pathways are essential for the formation, retrieval and reconsolidation of memory: dopamine, choline,AMPA, norepinephrine and adrenergic receptors, and neurotrophic factors (BDNF, GDNF, NGF).

  • Choline is essential for short-term memory and memory consolidation
  • Dopamine helps focus, motivation and general cognition[5]
  • Norepinephrine is a memory modulator[6] and it’s essential for memory retrieval[7]
  • AMPA improves synaptic plasticity and strengthen synapses
  • BDNF is important for long-term memory[8], learning, and synaptogenesis[9]

NGF is also important for neurons health and memory — but only in old subjects, as it actually impaired memory when given to young rats[10], so we’re not going to focus on it too much. Same for norepinephrine and adrenergic receptors, GDNF, Sigma, cAMP, PKA, CRE, CREBs and other minor neurotransmitters/neuromodulators.

References   [ + ]

Categories
Nootropics NSI-189 Recovery

NSI-189: A Nootropic Antidepressant That Promotes Neurogenesis

The use of antidepressant medications in America is a rapidly growing portion of the pharmaceutical industry. The number of people who take antidepressants has increased by almost 400% from 1990 through 2008.[1] In addition, eleven percent of Americans aged 12 years and older take some form of antidepressant medication.

Antidepressants have long been a troubled group of drugs in terms of side-effects, with even the most recent class of antidepressants (SSRIs) exhibiting potential side-effects like insomnia, sexual dysfunction, or even worsened depression. These troublesome side-effects have displayed a clear need for more effective treatment options.

Prozac capsules and packaging anti depression medication

Despite the apparent need for a more effective class of antidepressants, no new major milestones have occurred regarding antidepressants since 1987, the year fluoxetine (Prozac) was approved by the FDA.[2] Since the beginning of Prozac’s use to treat depression, SSRIs have dominated the area of medical treatment for depression. This era of depression treatment has been going on for about 29 years. However, some progress is being made in the development of new antidepressants. One of the newest experimental drugs for depression, NSI-189, also displays nootropic properties. Here we will be examining some of the claims surrounding the purported benefits of NSI-189.

Origins of NSI-189

NSI-189 is an experimental drug currently being developed and studied by Neuralstem Inc., a biotechnology company that commercially produces neural stem cells for therapy.[3] The research and development of NSI-189 began in the 1990s, during the years of Bill Clinton’s presidency.

The Clinton administration contracted Neuralstem to research the possibilities of creating a “super soldier,” one that was able to stay awake and alert for extended periods of time.[4] The researchers at Neuralstem recognized that a drug targeting the hippocampus could possibly alleviate the effects of sleep deprivation and exhaustion, and set out to find a drug that could induce neurogenesis. Neuralstem, finding their prospects to be promising, continued research in this vein even after the government program was canceled.

This preliminary research would eventually result in the drug NSI-189. Clinical research on NSI-189 has been in the works since 2011, and a phase 1b trial was completed in July of 2014.[5] Clinical phase 1 trials typically focus on finding the correct dosage range of the drug, which has been placed around 40 to 80 mg per day in the treatment of Major Depressive Disorder (MDD) and cognitive decline.

NSI-189 structure

Chemically speaking, NSI-189 is classified as a small-molecule benzylpiperazine-aminopyridine drug, making it structurally unique among other antidepressants. However, the drug has also seen increased interest in terms of its ability to stimulate nerve growth in the hippocampus.

According to the official Neuralstem, Inc. press release concerning the phase 1b trial, “[NSI-189] is a proprietary new chemical entity that stimulates new neuron growth in the hippocampus, a region of the brain believed to be implicated in MDD, as well as other diseases and conditions such as traumatic brain injury (TBI), Alzheimer’s disease, and post-traumatic stress disorder (PTSD).”[6]

The phase 1b trial of NSI-189 was “a randomized, double-blind, placebo-controlled, multiple-dose escalating trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamic effect of NSI-189 in the treatment of MDD.” Now that the trial has been completed, the results have been released, and they appear quite promising.

The study, which was conducted on 24 patients over the course of 28 days, found that NSI-189 administration reduced the symptoms of depression and cognitive decline significantly more than placebo. The drug was tolerated well by the subjects, and it “may also exhibit pro-cognitive properties associated with increases in prefrontal alpha coherence.” [7] [8]

Mechanism of Action

Selective serotonin reuptake inhibitors (SSRIs) attempt to treat depression by increasing levels of serotonin in the brain. This model of depression, known as the “monoamine hypothesis,” states that depression is caused by a shortage or imbalance of certain neurotransmitters in the depressed patient, mainly serotonin. However, this model has been quite drastically debunked in recent years.[9] Many researchers and psychiatrists now recognize that depression is far more complex than a simple chemical imbalance. New theories have emerged that recognize factors such as emotional trauma, environmental factors, glutamatergic dysfunction, and inflammation as potential causes of depression.

In short, depression is a complex web of interweaving causes and effects, both psychological and physiological. While scientists know from research that SSRIs and other antidepressants certainly have an effect in alleviating depression, the actual pharmacology behind the medications is far more unclear. Why do some respond to medication negatively? Why do some not respond at all? Because these questions are so intimately tied with genetic and biochemical factors, they are very difficult to address in a comprehensive manner.

These observations lead to two important points: First, depression is such a complex disorder that we don’t yet know the best way to treat it with medication. Second, SSRIs may be somewhat effective in alleviating depression, but we don’t completely understand why they work the way they do. Because the root causes of depression are still somewhat uncharted territory, exploration of new treatments that work differently than SSRIs is very important. By pioneering these treatments and observing their effects, the puzzle pieces that make up the full picture of depression can be pieced together into a comprehensive model.

NSI-189 vs Placebo Hippocampus
Topographs of average amplitude at 10-12 Hz showing increased high-frequency alpha in patients receiving NSI-189 at Day 28. Differences scores comparing conditions show most significant differences between total subjects receiving NSI-189 (left) vs. Placebo (right) in the left posterior temporal and parietal regions.

Some researchers, like those at Neuralstem, have noticed a correlation between reduced hippocampal volume and increased incidence of Major Depressive Disorder.[10] According to this theory, NSI-189 could potentially be a remedy to those suffering from depression by contributing to the growth of the patient’s hippocampus. Because the hippocampus is also so closely associated with memory, NSI-189 also has the potential to impact cognition.

This “hippocampal” model of depression is still in its infancy, and NSI-189 is one of the first drugs being researched that uses this specific form of treatment. Although it is known that NSI-189 increases hippocampal volume, the exact mechanism underlying this effect is still unsure. The results of the phase 1b trial even suggested that NSI-189s effect on hippocampal volume was not as drastic as that which was seen in animal studies.[11] Whether or not the increase of hippocampal volume persists after ceasing the medication remains to be determined. As the research and experimentation with NSI-189 continue, new research will shed light on this model for depression, and the medical community will be better able to understand the correlation between depression and hippocampal volume.

Purported Benefits

As mentioned above, the potential benefits of NSI-189 are:

    1. Improvement in behavioral responses associated with depression.[12]
    2. Reversal of hippocampal atrophy.[13]
    3. May enhance memory and cognition through increase neurogenesis, particularly in depressed subjects.
    4. Positive effects may persist after treatment ceases.[14]

    Subjective Experiences

    Because NSI-189 is still in its infancy as a clinical treatment for MDD and cognitive disorders, anecdotal information is important for those determining if they want to try NSI-189. This community poll conducted by /u/MisterYouAreSoDumb on /r/nootropics is useful for seeing various users’ experiences with NSI-189

    A Reddit user, Code_of_Error, relayed his experience with NSI-189 in a post on reddit[15]:

    I have been on NSI-189 Phosphate for three weeks now. I take 40mg orally once per day. I used to take it sublingually, but I learned that doing so may be counterproductive due to the possibility that too much is absorbed. Apparently, 40mg-80mg ORALLY was the sweet spot in clinical trials, so sublingual administration has too many unknowns to be worth it. Albeit, the freebase form is a different story.
    Anyway, I started exploring this substance in hopes of counteracting my chronic brain fog, slight depersonalization, anhedonia, general feelings of haziness, and slow cognition.
    Most notably, I have noticed an intensification of emotions, as well as pleasure. The first few days, I felt the inclination to tear up at every positive emotion. It felt ridiculous, but that has mostly leveled out. Although I am only three weeks in, I notice I am more inclined to look forward to plans. I am quicker to laugh and socialize.
    Prior to NSI-189, every emotion I experienced felt like nothing more than background noise. Now a days, all of my emotions feel more genuine, as if they’re at the forefront of my brain. When I experience anxiety, I no longer feel so dissociated from it. When I feel joy, it tends to last longer. Although these new perspectives are scary, I welcome the change. My default state of mind tends to be slightly perkier as well.
    I will admit that I am more guided by my emotions than I have been in years, and I am totally enabling it. I don’t recommend falling in love while on this substance. However, this substance is bringing me closer to my long-lost inner feelings. The effects aren’t perfect, and I still often feel that irritating haze (i.e., brain fog/dulled-out sensation/whatever ambiguous symptoms) to a degree, but I hope that my mental issues continue to improve as I stay on this. I’ve certainly made strides.
    Interestingly, I have noticed that I better able to “feel” the effects of nootropics while on this as well. Caffeine has a much more profound effect on me (comparable to when I first started using it), and the effects of tianeptine are as potent as ever. Again, I feel as if this speaks MORE to NSI-189’s ability to make you feel and less to its ability to reduce tolerance.
    Lastly, I would venture to say I am bit sharper mentally, and less likely to experience “cluttering” when I go to speak.
    Side effect wise, I only experience a mild fluttering (almost like a twitch) directly behind the inner half of my right eyebrow. Other than that, no headaches. I may have a mild reduction in sex drive, but nothing too troubling.
    Overall, I am looking forward to staying on this drug for a while. My mental symptoms are nowhere near gone, but I see enough benefits to keep going. Like many people who try an under-researched compound intended for depression, I feel as if I have little to lose.

    This is the experience of flare1028us, another reddit user:[16]

    Personally, I’ve found NSI-189 to be very useful. I’m taking 50mg freebase once daily in the morning. The acute effects for me are a gentle wave of calmness, improved long-term memory, and notably improved vision.
    The improved vision, as another redditor put it, is like my vision being “zoomed out” by 5%, like having a slightly larger field of view. Improved memory is the strong point of this substance. I find myself having vivid recollection of memories going back to my single digit ages. This has also allowed me to remember times when I encountered some of the same struggles I have to this day, and how I handled them – I feel better equipped to tackle them with better memory of what did and didn’t work in the past.
    As far as side effects, child-like emotions are coming on fairly strong. This is both good and bad. The good is that the sense of wonderment that we experience as children has come forth again, the bad being somewhat immature initial emotional responses. For example, jealousy – on a very childish level. It’s not debilitating, but it’s something to be mindful of.
    Speaking of being mindful, it has gotten a whole lot easier to practice mindfulness meditation and commit experiences I’ve gained through it to long(er) term memory.
    Interactions: Cannabis now gives me a mild headache, but if the high is balanced well (sometimes I’ll add some sublingual CBD), it is a very useful state of mind – for me it’s like being high with a better ability to remember the observations I make about my decisions and behavior that I may not come to so quickly in other states of mind. I tried taking piracetam once on NSI, and I’m never doing it again. Total dysphoria for most of the day from 3.5g piracetam in the morning. This stuff is supposed to reset piracetam tolerance, but I won’t be testing that until I’m off NSI-189 for a while.
    Tianeptine (sodium and sulfate) feels like it meshes really well with NSI-189, along with neurogenic peptides – took 200ug NA-Semax Amidate (sub-q) with NSI and went to yoga class (pretty intense class too). That was a level of control I would love to be able to gain every time I exercise in general.
    Hope this helps, I’m still waking up – I’ll answer questions if you have them

    Conclusion

    If NSI-189 proves to be an effective treatment for Major Depressive Disorder, it could have a potentially large impact on the direction of depression medication in the upcoming years. The long-standing dominance of SSRI drugs in the treatment of depression has left many wondering just how much longer it will be before the next major breakthrough occurs in depression treatment.

    A novel drug like NSI-189 could be the answer, and the studies concerning NSI-189 also give us a useful glimpse into the correlations between depression, hippocampal volume, and cognition. As we move further into the 21st century, the scientific community will undoubtedly continue to map more accurately the territory that is the human mind.

    References   [ + ]

    Categories
    Biohacking Tutorials

    The Ultimate Guide To Hair Loss: A Scientific Approach

    Male-pattern hair loss, also known as androgenic alopecia, or male-pattern baldness (MPB), is a very common condition, affecting 70% of males and an ever-increasing number of females at some point in their life. A British research poll conducted on males ages 18 to 30 asked the question, “what do you fear the most?” The number one answer was hair loss,[1], surpassing erectile dysfunction, sexually transmitted disease and a number of other rather worrying conditions. All over the web, we find remedies — frequently without any scientific basis — on how to “cure” ourselves of this annoying condition. This is the reason why I’ve decided to take a scientific approach to treating hair loss.

    What is Androgenic Alopecia?

    hair areas regions hair lossAndrogenic alopecia (AGA) is a condition in which the hair follicles progressively miniaturize due to the effects of androgenic hormones. The reason why it is more frequent in males is that the male scalp has regions that are highly sensitive to DHT (dihydrotestosterone), a potent androgenic hormone that has an adverse effect on hair. These sensitive areas are the vertex (crown) and the frontal regions. While hair recession on the temples is a normal part of the aging process of men, recession of the vertex and the midscalp is caused by androgenic alopecia.

    Thinning Hair Treatments

    Before we venture into the wild world of MPB treatments, it is important to point out that growing back completely miniaturized hair follicles (i.e. totally bald areas) is extremely unlikely and that treatment should be started as soon as possible.

    That said, I don’t recommend taking DHT inhibitors (e.g. finasteride, dutasteride) if you are less than 23 years old, as DHT is important for developing the male body. If that’s the case, I recommend taking natural DHT inhibitors such as saw palmetto together with minoxidil until you feel safe about taking a heavy-duty DHT inhibitor. We’ll talk more about that later.

    norwood hamilton hair loss scale
    The Hamilton-Norwood scale, introduced by Dr. James Hamilton and revised by Dr. O’Tar Norwood, is used as a measurement scale in male pattern baldness.

    Minoxidil

    Since its introduction in the 1980s, Minoxidil has been used by millions of people all around the world. Everything that could be said on Minoxidil has been talked about many times over throughout the internet. However, it is worth summarizing the vast amount of info we can find on the web in a small recap.

    Minoxidil is a drug that was developed as a blood pressure medication due to its vasodilating properties. The drug was effective but had a number of side effects. One of these effects was unexpected hair growth. The increase of hair growth became so obvious that dermatologists began prescribing minoxidil for androgenic alopecia without it having been approved by the FDA. The researchers thus quickly repurposed minoxidil as a hair loss treatment, and the rest is history.

    Minoxidil is, as of today, the most effective drug to stimulate hair growth and it is frequently used by transgenders to stimulate beard hair growth. You can buy a 6 months supply for around 26$, which is slightly more than 4$ a month. Side effects may include black circles, body hair growth, wrinkles and faster skin aging. The last two can be prevented with retinoids (more on that later).

    Finasteride

    Finasteride (Proscar) is a 5-alpha reductase inhibitor (5-ARI). Basically, it inhibits 5-AR, an enzyme that converts excess testosterone into its more androgenic brother, dihydrotestosterone (DHT). As we’ve seen already, DHT — plus other factors, including elevated sebum production, stress, inflammation, and diet — is the ultimate hair killer, so we don’t want that.

    Unfortunately, DHT is involved in many bodily processes and functions, such as muscle building, depression and anxiety, body hair (generally people with a lot of body hair are more susceptible to androgenic alopecia), height and so on. finasteride dht inhibitionThat said, the incidence of side effects in Proscar (finasteride) patients is very low and around the same rate as a placebo (sugar) pill. So, why there are people all over the internet screaming about how finasteride “shrunk their balls” or destroyed their life forever? As usual, I think the truth is somewhere in the middle. In my experience, yes, finasteride slightly lowers libido. However, the effect is not as bad as some people say, and it gets better with time.

    Some of the complaints may come from the fact that doctors are prescribing a higher dose than needed. The dose for hair loss is 1 mg a day (and 5 mg for prostatic hyperplasia), but according to several studies, a single dose of finasteride will lower DHT for almost a week. In fact, one study demonstrated that 0.05 mg of finasteride was nearly 50% as effective as 100 times the dose of 5 mg in reducing serum DHT after a single dose. Not only that but with daily dosing it was almost 90% effective as 1 mg!

    My recommendation thus is — if you choose the oral route — to take between 0.25 to 0.5 mg every other day (or every day if your DHT levels are really high).

    Topical Finasteride

    One question that always struck my mind about finasteride is why the scientists that were developing it never thought about going by the topical route. I’m not a scientist but it just seems more logical to me to apply a hair loss drug directly on the hair follicle rather than taking it orally, don’t you think?

    Clinical Studies

    Fortunately, in the last decade, we’ve seen more and more studies being done with topical finasteride. In a study conducted in India last year[2], the researcher switched patients aged 20 to 40 years old from oral finasteride to a solution of 5% minoxidil and 0.1% finasteride. Of the 45 patients that underwent treatment, 84.44% of them maintained a good hair density with the minoxidil-finasteride combination.[3] Five of them stopped the treatment for a period of 8-12 months and then resumed it. Of those five that stopped the treatment, 4 of them had a good improvement when they resumed treatment.[4]

    A Swiss study[5] compared the efficacy of topical vs oral finasteride. The results were clear: 1 mg of topical finasteride once a day reduced DHT levels in the scalp more effectively than 1 mg of oral finasteride.[6] The former reduced DHT levels by 71% while the oral finasteride only reduced them by 51%. Both administrations reduced DHT blood levels, so if you get side effects with Propecia, you will likely get side effects with topical finasteride. They also tried 0.5 mg of topical finasteride twice a day, but that only reduced scalp DHT levels by 47%.




    To obtain a topical finasteride solution you need to crush Proscar (or generic finasteride) tablets in your Minoxidil solution. You should try to obtain between 0.05 and 0.1% of finasteride. Start at 0.05% twice a day and work your way up.

    Black Castor Oil + Peppermint Oil

    Castor oil has been used as hair growth tool since early times, but only recently has it been rediscovered as a scientifically-proven hair growth oil.

    Prostaglandin D2
    Prostaglandin D2

    Before we go any further, we need to point out the discovery in 2012 by dermatologist Luis A. Garza and his team, that men with androgenic alopecia have high levels on the scalp of the enzyme prostaglandin D2 synthase (PTGDS) and its product prostaglandin D2.

    Yin & Yang: Prostaglandin D2/E2

    Prostaglandin E2
    Prostaglandin E2

    During a normal hair cycle, the levels of PTGDS increase immediately before a regression phase. The researchers thus assume that PTGDS and PD2 have an inhibitory effect on hair growth and that prostaglandin D2 inhibitors can, therefore, be used to stimulate hair growth.

    On the other hand, we have prostaglandin E2 (PGE2) that stimulates hair growth.[7] Bimatoprost, a PGE2 analog, is currently being researched as a hair loss treatment.

    “That’s cool and everything,” you may say, “but what does it have to do with Castor or Peppermint oil?”

    • Castor oil contains ricinoleic acid, a fatty acid with anti-inflammatory and analgesic activity that activates the EP3 prostanoid receptor for prostaglandin E2.[8] Unfortunately, it is terribly understudied, which is quite strange since castor oil has been a popular hair treatment for years, particularly in Jamaica.
    • Peppermint oil in a 3% solution stimulated hair growth in mice[9] through an increase in IGF-1 mRNA expression. The results were similar to those obtained with Minoxidil.
    • By combining these two oils with Minoxidil and topical finasteride, we can achieve incredible hair growth. I personally have achieved hair growth in remarkably “difficult” areas such as the temples. It’s important to start as early as possible before the hair follicles miniaturize completely.
      I personally use June Milnrow Peppermint Jamaican Black Castor Oil which combines flaxseed, peppermint, and black castor oil together, but it can be a bit expensive to buy it in the US, so here’s another one manufactured in the USA.
    • There are other oils that may aid hair growth. One of these is pumpkin seed oil (PSO), which is a well-known 5-AR. A 2013 study compared the effect of pumpkin seed oil to placebo in 76 patients suffering from mild to moderate androgenic alopecia. Half of them were assigned to the treatment group (400 mg of pumpkin seed oil capsules) and the other to the placebo group. The patients were instructed to not take any hair loss treatments (both topical and oral) for the 3 months prior to the study. The Mean Hair Count in the treatment group increased by 40%, whereas in the placebo group it increased by 10%. The study did not address the topical use of PSO nor the (common) combination of pumpkin seed oil with other natural 5-alpha reductase inhibitors (like in saw palmetto complex).

    Dermaroller and Dermapen™

    dermaroller
    Dermaroller

    A dermaroller is a skin needling device. The concept behind it is that by penetrating the skin with small needles, you can stimulate collagen production without leaving scars. A dermapen is pretty much the same; the only difference is that by removing the rolling process it is more gentle on the skin, which should theoretically heal faster and have better results. It is also a hundred times more expensive, so unless you have a lot of money to throw away, I recommend going with the dermaroller.

    Which Dermaroller Should I Use?

    There are dermarollers of all (needle) lengths, ranging from 0.2 to 3 mm. Generally, the lengths used to stimulate hair growth are between 0.2 to 1.5 mm. So which one should you buy? The answer is: it depends.
    There are two ways of doing this:

    • If you’re a minoxidil user, I recommend a 0.25 mm dermaroller to be used every other day (or every day if your skin tolerates it) before applying minoxidil. This will increase minoxidil absorption — and thus, efficacy — a lot. At this length, however, it is not able to stimulate collagen production, and its only purpose is to boost the absorption of topical products.
    • If you do not use minoxidil, or you use it but are willing to go the extra mile to regrow hair, then choose with a 1 to 1.5 mm dermaroller to be used once a week.
    dermaroller-skin-penetration
    Skin penetration of different dermaroller needle lengths

    A 2013 study[10] compared a group of patients taking 5% minoxidil twice a day to another group taking 5% minoxidil and using a weekly dermarolling regimen (the dermaroller chosen had 1.5 mm needles). The mean change in hair count after twelve weeks was significantly better in the dermaroller group compared to the minoxidil only group (91.4 vs. 22.2 respectively).[11].

    Tretinoin

    Tretinoin (Retin-A), is a vitamin A (retinol) derivative. Retinoids are terribly understudied as hair loss treatments, but according to a clinical review,[12] they are important for hair growth, especially when paired with minoxidil[13] and used on females.[14] A study showed that tretinoin and 5% minoxidil once a day was as effective as 5% minoxidil twice a day.[15]

    I think tretinoin 0.025% (or even just retinol itself), is a good addition to my hair loss regimen but it is not as important as the other compounds. They are important, however, to make once a day dosing of minoxidil/topical finasteride possible. So, in the end, I’ll probably keep using it (or resort to retinol should tretinoin get too expensive).

    Putting It All Together

    Now that we have discussed some of the most effective and convenient treatments for combating hair loss, we can use this information to develop a treatment regimen.

    Regimen A

    Morning

    1. wake up
    2. do a 0.25 dermaroller routine on the scalp alternating a day on and one off (or 1.5 mm once a week)
      go back and forth each roll
      dermaroller technique
    3. apply minoxidil-finasteride 5%/0.1% solution on dry hair
    4. apply a thin film of tretinoin or retinol on the hair line and vertex

    Afternoon

    1. apply castor oil on the hair line, vertex and other balding areas

    Regimen B

    Morning

    1. wake up
    2. split a 1 mg tablet of finasteride and take half of it (every other day)
    3. do a 0.25 dermaroller routine alternating a day on and one off (or 1.5 mm once a week)
      go back and forth each roll
      dermaroller technique
    4. if the skin is not bleeding, apply 5% minoxidil solution, otherwise wait for it to stop bleeding

    Afternoon

    1. apply 5% minoxidil
    2. apply castor oil on hairline and vertex

    Do not dermaroll if skin if hasn’t healed yet and follow the instructions on the box closely.

    Other Useful Tips for Thinning Hair

    • I recommend a complete head shave when starting the regimen. The reason is simple: doing so will allow the dermaroller (and thus the minoxidil/finasteride) to penetrate deep into the skin and strengthen the hair follicle significantly. After that you can grow your hair normally.
    • Avoid wearing hats or other constrictive headwear, they will speed up hair loss and cause more problems such as traction alopecia or scalp folliculitis.
    • To stimulate hair growth, use shampoos or creams containing caffeine[16] [17], copper peptides or miconazole (the -azoles have a synergistic effect with minoxidil).
    • Supplementing Biotin, Copper, Zinc, MSM and the amino acids L-Cysteine, L-Methionine, and L-Lysine will also stimulate hair growth. A good overall supplement is Country Life Maxi-Hair Plus
    • In my experience, N-Acetylcysteine (NAC), a more bioavailable form of the amino acid Cysteine in high doses (600 mg twice a day) will significantly stimulate hair and beard growth.
    • Blocking DHT with finasteride will increase estradiol (estrogen), a female hormone. To avoid that, consider buying a diindolylmethane supplement, which is a compound found in cruciferous vegetables that reduces the levels of estrogen.
    • Other supplements to help reduce or eliminate Propecia’s side effects are zinc and grape seed extract. The latter is a strong aromatase inhibitor, a substance that inhibits the conversion of testosterone to estrogen.
    • Aromatase inhibitors may reduce finasteride efficacy — particularly the pharmaceutical ones — so keep that in mind should you consider taking one.

    So that’s it for now, folks! For any questions or suggestions leave us a comment and we’ll get back to you!

    References   [ + ]

    Categories
    Coluracetam Nootropics Racetams Reviews

    Coluracetam Review: A Nootropic With Antidepressant Properties

    The drug piracetam is often regarded as the first truly nootropic drug, due to its ability to promote healthy brain function and cognition without potentially debilitating side effects. The family of nootropics that are structurally related to piracetam, known as racetams, have also been held in high esteem by the nootropics community. Coluracetam is one of the many members of this nootropic drug class, but it has some unique properties that set it apart from the rest.

    Introduction

    ColuracetamColuracetam is a fairly new addition to the racetam category of nootropics, being developed and initially researched in the mid-1990s.[1] Coluracetam, known also by its research names of MKC-231 and BCI-540, was initially developed and researched by the Mitsubishi Tanabe Pharma Corporation in Japan as a potential treatment for Alzheimer’s disease. Coluracetam has also seen some limited research concerning its potential use for treating Major Depressive Disorder and Generalized Anxiety Disorder.[2]

    Mechanism of Action

    When ingested, coluracetam becomes present in nerve tissue within 30 minutes of administration. The concentration in the body begins to decrease about 3 hours after ingestion.[3]
    The most definitive mechanism through which coluracetam works is high-affinity choline uptake (HACU). HACU is a crucial step in the process of the body’s converting of choline into acetylcholine, a vital neurotransmitter for cognition processes. [4] In essence, this means that an increase in HACU (caused by coluracetam) will also increase the activity level of acetylcholine in the nervous system. This is the basis for coluracetam’s ability to enhance cognition

    My Experience with Coluracetam

    My trial run for NootropicsDepot’s coluracetam lasted for one week, due to the fact that coluracetam’s effects seem to all take place rather quickly. In other words, the effects do not appear to be cumulative like some other nootropics. Typically, I took 30 mg orally in the morning, along with another 30 mg in the afternoon. If necessary, I took another dose later on in the day. Dosage recommendations for coluracetam range anywhere from 3 mg up to 100 mg or more, but this dose seemed to work just fine. Having experimented with coluracetam briefly a few months ago, I had a general feel for what dose might work.

    Coluracetam powder nootropicDuring the time of this trial, I was not taking any prescription medications. In the morning, I was taking Vitamin B12, Vitamin D, potassium gluconate, fish oil, and turmeric. The effects I experienced from taking coluracetam have been very positive. However, bear in mind that this is only a subjective experience. The placebo effects cannot be ruled out (although I am convinced it was the coluracetam I felt), and experiences will vary between individuals. That being said, I will now go into what I felt are the major benefits of coluracetam:

    1. Motivation enhancement
      Right off the bat, coluracetam seems to provide a decent increase in motivation to engage in productive work. I felt a stronger desire to work on school work that I don’t find very interesting. It made it much easier to push through to get things done, leaving a very satisfactory feeling when things were accomplished.
    2. Stimulation
      This effect goes somewhat hand-in-hand with motivation enhancement. Coluracetam has the effect of making me feel more awake and alert. It seems to help me feel more ready and able to get work done. It didn’t make me feel “jittery” either – I felt quite relaxed the whole time.
    3. Reduction in fatigue
      Coluracetam appears to help alleviate both physical and mental fatigue. There were a few instances when taking it where I went from being exhausted and drained to energized and ready to go.
    4. Enhanced cognition
      This effect is very important for any nootropic compound. After all, it is the main thing that nootropics are purported to influence. Within half an hour of taking coluracetam, I felt much more able to formulate thoughts and translate them into writing. I also felt more able to connect ideas in my mind and get a better idea of the “bigger picture.” I also felt more naturally able to hold conversations with others, feeling much more engaged and fluent.
    5. Music enhancement
      While this is mostly unrelated to the topic of cognitive enhancement, listening to music while on coluracetam was very pleasant. The music itself felt more full, interwoven, and immersive than usual. Individual pieces of melody and minor details became more distinguishable than usual.
    6. Mood Boost
      After taking coluracetam, I can understand why it is being researched as a treatment for depression. It helped me remain more positive and upbeat throughout the day. I also seemed to make things more enjoyable in general.

    Drawbacks

    Coluracetam seems to be a very promising nootropic in terms of its multiple benefits and few side-effects. I did not experience any apparent increase in tolerance during the week I was taking it, even with multiple doses in one day. Experiments in which rats were given coluracetam for 14 days at a time seems to reinforce this.[5] The only possible side-effect I experience was mild to moderate headaches, which occurred throughout the week. This should be taken with a grain of salt because I am normally fairly prone to headaches in the first place. I’ve also heard that taking choline can alleviate headaches that come with racetam supplementation, so that could be a potential remedy.

    Conclusion

    All things considered, I was very pleased with the effects of coluracetam. I will certainly be implementing it into my nootropic stacks, as it is one of the most noticeable and useful nootropics I have personally taken. It seemed to have a real impact on my motivation, energy, and cognition. Everyone is bound to react differently to coluracetam, but I strongly encourage nootropics users to give it a try.

    You can buy Coluracetam powder and capsules at NootropicsDepot.

    Coluracetam
    7.5
    Focus
    8.5
    Mood
    8
    Memory
    7.5
    Stimulation
    7
    Relaxation
    8
    Safety
    Reviewer 8.4
    Summary
    I highly recommend coluracetam for anyone who needs to spend extended periods of time working on demanding mental tasks. The cognitive boost and mental stimulation was extremely useful.

    References   [ + ]

    Categories
    Biohacking

    Improve Sleep Quality With This Sleep Optimization Checklist

    Sleep quality naturally declines during aging. For example, sleep duration and sleep consolidation both deteriorate as we age. (Less consolidated sleep is more fragmented, with shorter mean sleep bout duration). Moreover, impaired sleep quality is a sensitive prodromal sign of future cognitive decline and Alzheimer’s disease (AD).

    Improving sleep quality often translates to improved mood, enhanced cognitive function, and general well-being. We’ve cataloged ten of the most relevant ways to improve sleep quality. The first few tips apply more to healthy subjects; the latter suggestions are aimed at individuals struggling with clinically significant insomnia.

    1. Circadian rhythm is coupled to light cues from the environment. Individuals who sleep in an environment that is not dark enough will have a blunted circadian rhythm (e.g., impaired expression of the proteins that regulate sleep/wake oscillations). To maximize sleep quality, use black electrical tape to cover all light sources (e.g., blinking electronics).
    2. f.lux-iphone-comparisonThis tip is an extension of the previous one. Download the f.lux app, which calibrates the wavelength of the light emitted by your laptop screen (or monitor) according to the time of day.Screens normally emit high-energy/low wavelength blue light which interferes with the biological block. With flux activated, at night your laptop will emit warm, red/orange light (like a sunset), which is less likely to cause the “circadian rhythm phase delay” that impairs sleep onset.
    3. Turn the thermostat down at night to slightly chilly temperatures. Internal body temperature drops to a trough at around 4 AM. Low temperatures at night are considered an environmental cue that entrains the biological clock and helps facilitate sleep initiation.
    4. Vigorous exercise before bed has been consistently noted to improve sleep quality.
    5. Practice good sleep hygiene by going to bed and waking up at the same time. Humans are creatures of habit, and following a regular schedule can help synchronize your body clock. Limit stimulating activities in the evening. For years, I played computer games until 2 am right before going to bed. Suffice it to say, I had vivid dreams and sleep quality was not ideal.
    6. Nutraceuticals that show promise in alleviating (mild) insomnia
      • Magnesium (bioavailable such as glycinate, aspartate or taurate are recommended)
      • Melatonin (low doses, e.g. <1 mg are paradoxically more effective than higher doses)
      • Glycine (an inhibitory neurotransmitter and co-agonist at NMDA receptors)
      • L-Theanine
      • Herbal tea with lemon balm, passionflower, and chamomile
    7. If you have clinically significant insomnia, do not be deterred from using prescription drugs to manage your symptoms. Long-term sleep loss is extremely taxing on the body and mental health. Often primary insomnia will not respond to tips #1-6. It is tempting to dismiss patients with clinically significant insomnia with soft-core interventions like “get more exercise” but that just won’t cut it for this patient population.

      sleep aids how they work

      Unfortunately, when it comes to sleep aids, there is an inverse relationship between long-term safety and efficacy. The most effective sleep aids are more likely to adversely affect brain health. This cost/benefits analysis and the trade-offs of different medications should be weighed by your clinician. When shopping for sleep aids, start with the safest, most suitable agents for long-term use:

      • Ramelteon (Rozarem)
      • Suvorexant (Belsomra)
      • Trazodone (Desyrel)
      • Mirtazapine (Remeron)
      • Hydroxyzine (this antihistamine has a long half-life but has negligible anticholinergic activity)
      • Other antihistamines and sedatives

      Higher-risk options:

      • Phenibut
      • Z-drugs (e.g., Ambien)
      • Benzodiazepines (e.g., Xanax)
      • Ibutamoren (aka MK-677)
    8. Resolve/treat contributory diseases. The most important disorders that can exacerbate sleep disorders are:
      • Sleep apnea
      • Hyperthyroidism/hypothyroidism
      • Disorders of hyperarousal (Anxiety disorders, PTSD, depression)
      • ADHD
      • Restless leg syndrome
      • Delayed sleep phase syndrome/other circadian rhythm disorder
    9. scumbag brain on waking up earylSometimes, chronic insomnia develops from a self-reinforcing psychological process. Let’s say a major life event disrupts your sleep and mood for a short period of time. Many people will recover the lost sleep quality, but some people will begin to obsess about their inability to get a proper night’s rest. This results in a positive feedback loop where as you become more worried about fixing your broken sleep, your sleep quality deteriorates further.Panic disorders often arise from a similar process, where the object of your anxiety is the anxiety itself. For example, you might be concerned that heightened anxiety will cause a heart attack (because your heart is palpitating), which adds more fuel to the fire, culminating in a full-blown panic. Harvard has devised some behavioral interventions that can be helpful for this kind of self-perpetuating neurotic sleep disorder. They suggest taking a sabbatical from work (if you can afford it), and instead of trying to go to bed, trying to stay up as long as possible. Chronically restricting the total amount of time in bed may be one of the most robust behavioral interventions for treating sleep-onset insomnia.
    10. A promising sleep enhancement strategy worth mentioning is the pharmacologic augmentation of slow-wave-sleep (SWS) using selective 5-HT2A antagonists.
    Categories
    Reviews Stacks

    Axon Labs’ NEXUS Nootropic Stack, My Experience (Review)

    Formulating nootropic stacks can sometimes be a difficult or time-consuming process. While the research that goes into drug combinations and synergy can be rewarding and even enjoyable, sometimes it’s difficult to find the right information on specific nootropics. Even when the right ratios are figured out, making multiple capsules of a certain stack can be even more time-consuming than the research.

    Although pre-made nootropic stacks can be more expensive than buying bulk powder, they are sometimes well worth the price. Nootropic blends can be specially formulated by individuals with a deep understanding of neuroscience, giving the best cognitive benefits possible. Axon Labs’ NEXUS Nootropic Stack is an encapsulated blend of aniracetam, CDP-choline, phosphatidylserine, and Pycnogenol. The serving size is two capsules, and each serving contains 1.250 mg of this nootropic blend. Although the amounts of each component are not specifically listed, we can make a plausible assumption based on standard dosages for these compounds.

    nexus-facts_large.jpg

    The key component to this blend is aniracetam, a well-respected nootropic that is gaining popularity for its unique ability to improve cognition and reduce anxiety at the same time. A more detailed look at aniracetam’s mechanism can be found here on our site. Essentially, aniracetam modulates the action of glutamate (an excitatory neurotransmitter) by reducing glutamate receptor desensitization. [1] This, in theory, would improve memory and strengthen the connections between neurons. Aniracetam is also unique among racetams in the fact that it has the ability to reduce feelings of anxiety and depression. It most likely accomplishes this by means of serotonergic, dopaminergic, and cholinergic mediation. [2]

    CDP-choline (also known as citicoline) is a source of choline that also serves as a prodrug to uridine, another nootropic supplement. Choline is essential for the production of the neurotransmitter acetylcholine in the body, which is the neurotransmitter thought to be closely involved with the regulation of cognitive processes. Aniracetam is partially cholinergic in its mechanism of action, as it potentiates the action of nicotinic acetylcholine receptors.[3] When aniracetam is paired with a choline source, the increase in acetylcholine will theoretically potentiate the cholinergic effects of aniracetam.

    Phosphatidylserine is a naturally-occurring fatty acid derivative that helps comprise cell membranes. In 2003, the Food and Drug Administration (FDA) authorized sellers of phosphatidylserine to label their products with the claim that “consumption of phosphatidylserine may reduce the risk of dementia and cognitive dysfunction in the elderly.” [4] Various studies have indeed confirmed that supplementation of phosphatidylserine can improve cognition[5], memory[6], and processing speed[7], among other factors. Phosphatidylserine also has the potential to increase levels of acetylcholine in the brain, an effect that would work synergistically with aniracetam’s cholinergic mechanisms. [8]

    Pycnogenol is a patented extract of pine bark, containing a number of antioxidant flavonoids known as procyanidins. Pycnogenol’s most notable effects include its ability to increase blood flow[9], while also improving attention and cognition.[10] Pycnogenol’s main mechanism seems to be its ability to increase concentrations of nitric oxide (NO). It does this by preventing NO from oxidizing while also inducing the Nitric Oxide Synthase (NOS) enzyme, which catalyzes the production of NO.[11]

    My Experience

    Note: When dealing with anecdotal experiences, it is difficult to completely rule out the placebo effect as the cause of certain perceived changes in cognition and mood. This is simply my own experience, and it is likely that every individual’s experience with these nootropics will vary. These are simply the effects I perceived.
    Previous to this experience, I had taken aniracetam on a few occasions with modest success, taking it with a choline source.

    My dosing regimen of Nexus consisted of taking 2 capsules in the morning after I woke up. I took another dose in the afternoon or evening if I was working on tasks that benefit from boosts in cognition (i.e. writing, analysis). During this time period, I was also taking fish oil, bacopa monnieri, and centrophenoxine, which I have been taking regularly for at least a month. I was thus familiar with their effects and would be able to perceive any changes brought on by adding this stack. I took Nexus regularly for about one month.
    One of the most marked improvements I noticed was a modest reduction in anxiety that set in about an hour after taking Nexus. I am typically a fairly anxious person, both in general and in social situations. I felt more able to focus on important tasks, rather than focusing on anxious thoughts I was having. I also felt a noticeable clear-headedness and ability to think straight.

    There was also a subtle improvement in being able to pick up on new concepts more easily. During college courses, I felt very engaged in the materials being presented, even in the classes, I do not normally find very interesting. I also found it easier to contribute to the discussion.
    Taking another dose before working on writing essays and papers seemed to help a great deal with my cognition. Aniracetam has anecdotally been touted to improve holistic and collective thinking, and that seemed to be the case in my experience. It was much easier to weave different concepts and themes together in a way that presented a coherent bigger picture.

    Again, when it comes to nootropics, it can be difficult to differentiate legitimate effects from placebo. However, many of the effects I experienced were extreme enough that I am fairly convinced that they were effects of this stack.

    Conclusion

    Everyone is likely to react differently to a nootropic like aniracetam. There are some people I know who experience little to no effect from taking it. For others, the effects seem to be almost life-changing. However, I do feel like the additional ingredients in Nexus’s blend contribute a good deal to its effects. It seemed to have greater effects than just aniracetam alone.

    This being said I can definitely recommend trying Nexus out. It is a good stack for those who are fairly new to nootropics and aren’t sure how to formulate their own stacks, but for the expert nootropic user, it is definitely overpriced. That said, I would definitely like to use it again in the future.

    Axon Labs' NEXUS
    7.5
    Focus
    7
    Mood
    6
    Memory
    6
    Stimulation
    7
    Relaxation
    9
    Safety
    Reviewer 7.1
    Summary
    I would recommend this stack to anyone who is into experimenting with nootropics. It gave me a clear cognitive boost while simultaneously reducing anxiety.

    References   [ + ]

    Categories
    Nootropics Tutorials

    Nootropics: A Beginner’s Guide To Cognitive Enhancers

    The realm of nootropic substances (aka cognitive enhancers or smart drugs), at the time around its conception, was reserved for the very select few who had access to these novel cognition-enhancing drugs. In recent years, nootropics have gained more widespread recognition, and are more accessible to average individuals than ever before, thanks to the rising number of online vendors and communities who make these substances accessible for all.

    The term “nootropic” has been consistently more and more searched on google ever since 2011 (the year when the film Limitless was released) , and people’s interest in the subject will certainly continue to rise. Although nootropics still maintain a type of “fringe” status in the world of drugs, their infiltration into the mainstream is undeniable.

    Nootropic Trend - Google searches of keyword "nootropics"

    What is a Nootropic?

    nootropic brainCorneliu E. Giurgea, the Romanian chemist who first synthesized piracetam, developed the concept of nootropic substance in 1972.[1] It is a combination of the Greek words “νους” (nous) meaning “mind”, and “τρoπoς” (tropos) meaning “bend” or “change”. This is what nootropics do. Essentially, they positively alter the way in which your mind works.

    Nootropic drugs are a specific subtype of psychoactive substances. According to Giurgea, in order for a drug or supplement to be considered a nootropic, it must adhere to the following criteria:[2]

    1. Enhances learning and memory
    2. Enhances resistance of learned behaviors to conditions that will disrupt them
    3. Protects the brain against physical of chemical injuries (such as concussions or neurotoxic drugs)
    4. Increases the efficacy of cortical/subcortical control mechanisms of the brain (such as improving reaction time)
    5. Typically lacks negative side-effects (i.e. sedation), and possesses low toxicity

    Though these criteria lay out the foundation for what a nootropic is, most modern definitions are much more general. As a more common definition, nootropics are chemical substances or herbal supplements that enhance cognition and mental function.

    Caffeine
    Caffeine

    If we think in terms of this general definition, there is about a 90% chance you use a pseudo-nootropic substance regularly. Caffeine, the most popular drug in the world, is commonly classified as a nootropic, due to the fact that it is stimulatory and enhances attentiveness linked to cognition, learning, and memory. [3] [4]

    Certain substances that don’t explicitly enhance cognition are still sometimes grouped in with nootropics. This would include substances that improve mood, reduce anxiety, or promote an overall feeling of wellbeing. Some examples of these substances are phenibut, sulbutiamine, and ashwagandha. Even if these supplements don’t have mechanisms that directly improve cognition, their mood-improving capabilities will tend to lead to an enhanced ability to focus and think clearly.

    Who Uses Them?

    Giurgea coined the term “nootropic” after he synthesized piracetam, which is, under Giurgea’s definition, the first substance to display purely nootropic properties. Piracetam has cognitive enhancing and neuroprotective capabilities while also possessing relatively few side effects. [5] Because of this, piracetam is commonly used to improve cognition in individuals who are experiencing the cognitive decline that comes with old age, dementia, or Alzheimer’s.

    With the development of piracetam, other nootropic substances were investigated and researched for their applications in those who experience cognitive decline. Many drugs derived from piracetam (referred to as racetams) have been developed in hopes that they would yield even more benefits than piracetam. For instance, phenylpiracetam displays stimulant properties in addition to cognitive enhancement. [6] Likewise, aniracetam works as an anxiolytic. [7]

    Modafinil is wakefulness-enhancing nootropic used by college students as a safer alternative to Ritalin and Adderall

    Up until the past decade, these kinds of cognitive-enhancing drugs were only used extensively in clinical applications, such as treating cognitive illnesses. However, the past few years have seen tremendous growth in the use of nootropics among younger healthy individuals in hopes that they could improve their performance in work or academic studies. For example – modafinil (Provigil), a wakefulness-promoting nootropic substance, has seen increased usage among college students as an alternative to Adderall, due to the fact that it aids the brain in focusing on tasks for extended periods of time without fatigue. [8]

    Many nootropic substances, such as the racetams and tianeptine (an antidepressant nootropic), are prescription drugs in Europe but are unscheduled in the United States. This has led to many of them being sold online by nootropic vendors, making them readily available for those who wish to purchase them.

    Not surprisingly, Russia, the country that has developed a large number of nootropics (including Phenibut, Picamilon, Phenylpiracetam, Selank, Semax, Cerebrolysin, Emoxypine and so on), it’s the place where the keyword “nootropic(s)” is most popular in 2016[9], according to Google.

    The increasing number and growth of online communities, such as the nootropics subreddit, has attracted the attention of younger individuals who seek to improve their cognitive performance and preserve their youthful cognitive capabilities. These online communities are extremely valuable sources of information on all things related to nootropics. They are open forums where anyone can ask questions about smart drugs and cognitive enhancement and engage in valuable discussion. Many newer nootropic substances have not been extensively tested in clinical settings, but anecdotal user reports can be found within these online communities.

    Where Do I Begin?

    If you are determined to make a go at nootropic supplementation, then logically the smart thing to do is implement the smartest ways to use smart drugs. You do not have to be a brain surgeon to begin effectively supplementing with nootropics, but understanding at least the bare bones of the foundations of a few related fields like neuroscience, neurology, and drug metabolism, is vital to getting the most out of them.

    Ideally, you want a good working understanding of all the major mechanisms of action, including receptor systems involved in memory, mood and cognition (dopamine, GABAacetylcholineserotonin, etc).learning memory nootropics Attempting anything other could end up as catastrophically as fiddling with the kernel of your operating system without knowing how it works. The best way to go about it is to learn what happens to drugs inside the body, how the classic nootropics work (like Piracetam and Aniracetam), and what are some of the basic nootropic stacks.

    Even though it can be a bit daunting at first, you will also want to learn how to access & read scientific researchwhat is acetylcholine (the learning and memory neurotransmitter), how it works, how the brain produces it and what is a choline precursor. Learning the major neurotransmitters, understanding the difference between excitatory and inhibitory neurotransmitters, all these are great places to start.

    When first getting into the world of cognitive enhancement, the sheer number of substances out there can be very intimidating. Here is a short list that outlines some of the most popular and proven nootropics for beginners.

    Wakefulness and Motivation

    • Caffeine and L-Theanine – Promotes wakefulness and is stimulating in general. The addition of L-theanine helps reduce the negative side effects of caffeine, such as anxiety. Additionally, L-theanine also improves cognition.
    • Modafinil, Armodafinil, and Adrafinil – These three compounds are chemically related. Armodafinil is the active isomer of modafinil and is thus generally more potent. Adrafinil is a prodrug to modafinil. In other words, it is metabolized into modafinil by the body. All three of these are used to promote wakefulness and reduce fatigue.
    • Rhodiola Rosea – A herb that acts as an adaptogen, meaning it aids the body in reacting positively to stressful stimuli. It typically reduces feelings of fatigue and is slightly stimulatory. It is also sometimes used to lessen the effects of caffeine withdrawal.

    Note: Prescription drugs such as Adderall (amphetamine) and Ritalin (methylphenidate) are especially effective at increasing feelings of motivation. However, they carry additional side effects and risks of dependency, and should be used with caution.

    General Cognition

    piracetam nootropic adhd

    • Piracetam – The original racetam, was originally developed as a sleep-aid because of it’s GABA structure, when given to rats it improved their memory and cognition.
    • Noopept – Is chemically similar to piracetam but is active at a fraction of the dose (10 mg vs 1000 mg), and also increases the production of NGF and BDNF, two neurotrophic factors that promote the survival and differentiation of neurons. It typically provides an increase in cognitive ability along with mild stimulation.
    • Aniracetam – Provides cognitive effects that are similar to Noopept, but is also anxiolytic in nature. It is especially helpful in helping the brain associate different thoughts and piecing them together to form the “bigger picture.”
    • Phenylpiracetam – Similarly aids cognition like noopept and aniracetam, but it noticeably more stimulatory. It is also known to be more neuroprotective, and aids in preventing cognitive decline. It is a good alternative to Modafinil.

    Note: Because racetams and noopept work through modulation of acetylcholine, they should be supplemented alongside a choline source, such as alpha-GPC or CDP-choline.

    Mood Improvement

    • Tianeptine – Chemically a tricyclic antidepressant, tianeptine is novel in the fact that it improves mood while also serving as a neuroprotectant and cognitive enhancer.
    • Phenibut – an anxiolytic compound that may enhance cognition in stressful situations (like exams or a public presentation) through means of reduced anxiety.

    Memory

    • Bacopa monnieri – Bacopa has been found to improve the formation, retention, and acquisition of memory. It is an adaptogen and is often taken for its anxiolytic properties
    • Huperzine A – an acetylcholinesterase inhibitor (a compound that prevents the breakdown of the neurotransmitter acetylcholine) extracted from the plant Huperzia Serrata.

    What To Expect

    Most nootropics rarely display immediate or noticeable acute effects on cognition and well-being (the only exception being stimulant nootropics like Modafinil and Phenylpiracetam) . In fact, they are typically used for long-term neuroprotection, and may not display immediate or noticeable results from use. The psychoactive effects of nootropics are more subtle than the effects of recreational drugs but are ultimately more beneficial. By definition, the daily use of nootropic substances should be far more sustainable than that of recreational drugs.

    Nootropics are meant to be safe to use indefinitely though not all drugs sometimes referred to as “nootropics” will meet these criteria. For instance, phenibut, a GABAergic anxiolytic, is sometimes discussed as having nootropic capabilities related to anxiety reduction. However, phenibut has a fairly high risk of causing dependency or withdrawal, and should not be used on a daily basis.

    coffe and modafinil pure nootropics
    Modafinil is used by college students as a safer alternative to Ritalin and Adderall

    Many people supplement multiple nootropics at once to maximize their cognitive benefits. These combinations of substances are referred to as “stacks”. For instance, one might stack caffeine and L-theanine because L-theanine is known to reduce the jitters and anxiety that come with caffeine. [10] When taking multiple nootropics, it is extremely important to research any potential negative interactions between substances. Examine.com is an invaluable resource for researching nootropics and their possible interactions.

    Nootropics can certainly be of great benefit to those who wish to improve their cognitive function and protect their minds from degradation. However, nootropics will likely be far more beneficial when they are used in combination with exercise, a proper diet, and meditation.[11] Nootropics can only do so much, and are certainly not an excuse to neglect these other primary health factors.
    In addition to this, nootropics should not be used to treat mental disorders unless under the direction of a trained health professional. It may seem tempting to use promising and novel nootropics to treat something like depression, but there is still some amount of risk involved with doing so, especially given the fact that many of the newest nootropics still require a great deal of research before they can be used clinically.

    Even if “old” nootropics like racetams are totally safe, it is still a good idea to check out interactions if you’re taking prescription medications.

    Up Next

    References   [ + ]

    Categories
    Modafinil Nootropics

    Modafinil is the New Ritalin© — Where To Buy It

    Modafinil, also known as Provigil, is a drug used to treat chronic daytime sleepiness. An entire generation of students and entrepreneurs, however, certify its use as a study aid. It is a prescription medication, but generic Modafinil can be bought on the internet without issues as long as it is for personal use. Let’s have a look at some of the basic things you need to know before you buy Modafinil online.

    What is Modafinil?

    ModafinilModafinil is a “eugeroic”, aka a wakefulness-promoting agent – that is, a drug used to enhance wakefulness among individuals suffering from excessive daytime sleepiness. It is clinically used in narcolepsy, to treat shift pattern sleep disorders, sleepiness induced by sleep apnea and so forth. The drug boosts wakefulness in individuals, but obviously, it does not make up for the loss of sleep one may experience. Modafinil works by relieving individuals from the symptoms related to lack of sleep or fatigue. It works on various parts of the brain that play a pivotal role in the wake and attention process.

    Modafinil is also used off-label to treat fatigue and sedation in a number of conditions, including fibromyalgia, depression, Parkinson’s disease, myotonic dystrophy and opioid-induced sleepiness. A study done on 72 patients with multiple sclerosis showed that modafinil improves the symptoms of fatigue related to MS. [1] Modafinil also improved mood and relieved sleepiness and fatigue when used as an adjunct to antidepressants, in particular, SSRIs. [2] [3]

    Modafinil as a Learning Tool

    Modafinil Use Ranking UK UniversitiesFrom what we gathered so far, Modafinil seems to be an excellent stimulant and fatigue-relieving drug in some medical conditions. If you are reading this article, however, it is likely that you are interested in using Modalert as a cognitive-enhancing nootropic.

    A 2014 online survey by the students website The Tab[4] showed that 1 in 5 students[5] (out of a sample of almost 2000 UK students)[6], has taken Modafinil to enhance their study sessions. Topping that list, the University of Oxford, one of the most prestigious schools in the world, with 26% of Oxonians who participated in the survey being Modafinil users. Another interesting find of the survey is that 9% of those who use Modafinil think it of it as cheating (but they keep on taking it).[7]

    Sounds too good to be true? It isn’t.

    A systematic review of 24 studies on Modafinil done last year[8] concluded that Modafinil improves learning —particularly in long and complex tasks—, as well as enhancing decision-making and planning, while also having at the same time an excellent safety profile.[9] Some of those studies also showed an improvement in flexible thinking and concepts association, as well as other cognitive benefits.

    Adrafinil vs Modafinil

    Adrafinil is the oldest of the afinil drug family. It is a pro-drug of modafinil: when the liver metabolizes Adrafinil, it converts it into Modafinil. The main difference between Modafinil and Adrafinil are efficacy (Adrafinil is a lot less efficient compared to Modafinil) and side effects profile. Adrafinil can cause pain, anxiety, skin irritation and increased liver enzymes with long-term use It has been abandoned in clinical practices due to less desirable pharmacological profile.

    modafinil liver metabolization modafinil

    Modafinil vs Armodafinil

    Technically speaking, Armodafinil consist of solely the (R) enantiomer of Modafinil. There are subjective differences between how these two drugs affect your brain. Armodafinil appears to be cleaner and more effective, but it is also a lot more expensive. Some say that Armodafinil was developed by Cephalon — the company that owns the rights of -afinil drugs — simply because the Modafinil patent expired and they did not want to lose their primary source of income. But this, of course, is only a speculation.

    Where to Buy Modafinil

    Modafinil requires a prescription, but because of affordability and quality of the generic equivalents Modalert and Modvigil, in the past years, it has turned be the brand of choice for millions of students and entrepreneurs around the globe. We recommend ModafinilXL as a legit and reliable supplier of Modafinil and Armodafinil for the USA, and RUPharma for the EU and UK markets.

    Conclusion

    Modafinil is a one-of-a-kind drug. Not only that but its safety profile and its nootropic potential has been used by students all over the world to boost their grades and learning abilities with excellent results. That said, there is a minority of individuals that are non-responders: they are naturally immune to Modafinil (and other -afinils). The majority of people that try it, however, has a positive experience.

    Modafinil
    10
    Focus
    8
    Mood
    8.5
    Memory
    9
    Stimulation
    6.5
    Relaxation
    8.5
    Safety
    Reviewer 9.5

    References   [ + ]

    Categories
    Health

    10 Conditions That Cause Chronic Fatigue

    With our hectic lifestyles and less than optimal health habits, feeling like you have no energy is a modern day epidemic. For an ever-increasing number of individuals, however, feeling tired

    Sleep

    Sleep is essential to our body. It allows the brain to consolidate memories and thoughts, and to work more efficently. Poor or inadequate sleep can wreak havoc on your mental health by disrupting your circadian rhythm, and this, in turn, causes fatigue and brain fog just like chronic fatigue syndrome.

    Check out our Sleep Optimization Checklist for a list of useful tips on how to improve your sleep quality.

    Diet

    The most common cause of fatigue is a poor diet. A good diet is not necessarily about losing weight, it’s about eating healthy food and feeling better. In this highly advanced and globalized society where you can buy and eat all kinds of delicious foods from all over the world, we are getting fatter and sicker compared to previous generations. Here’s why…

    a. Nutritional deficiencies

    Iron deficiency (often found with vegetarians and vegans) and lack of vitamin B12 can cause anemia, a common pathology where the blood cannot supply enough oxygen to the body due to a lack of important nutrients.

    High-potassium-foodLow potassium and magnesium levels are also associated with low energy and fatigue. Low potassium can be easily treated by eating bananas: one banana contains around 425 mg of potassium [1], so eating two bananas a day for a week can easily replenish the potassium stores of the body.

    Magnesium is a key nutrient. Over 300 enzymes require the presence of magnesium ions, including all enzymes synthesizing ATP (the primary source of energy in cells) as well as DNA and RNA. It is, unfortunately, becoming harder and harder to find in today’s highly-processed food. Because of this, the only method to replenish the magnesium ions in the body is to use a magnesium supplement. It’s essential to get a good magnesium supplement – most of the commercial magnesium brands contain “cheap” inorganic forms for economic reasons. These are usually magnesium oxide, magnesium chloride or sulfate, which have very low bioavailability and are often used as laxatives. The most effective magnesium forms are malate, glycinate, orotate, and taurate. We recommend the malate salt which is especially effective for pain and fatigue. A less expensive option is magnesium citrate.

    b. Excessive carb intake

    99carbsOther than nutritional deficiency, an excessive intake of carbohydrates is a very common cause of chronic fatigue.

    First of all, we need to remember that the “modern” Western diet is full of carbohydrates, particularly refined carbs such as sugar, corn syrup, fructose, as well as refined flours, grains, and starches. Not all carbs are immediately used by the body. Excessive glucose (sugar) gets stored in the body for future use as glycogen and fat. However, there is one thing that all carbs do: they make the body secrete insulin, and insulin decreases plasma levels of large amino acids that would ordinarily compete with tryptophan for transport (particularly in the blood-brain barrier), therefore increasing tryptophan availability.

    Tryptophan and its metabolite, serotonin, have a complex role in the brain, but the two things they are most known for is regulating mood and hunger. Low levels of serotonin[2] have been associated with depression (even though this is recently being disputed) while high levels (especially its precursor, tryptophan[3]) have been correlated with fibromyalgia and chronic fatigue.

    It should also be noted that an insulin spike is followed by a crash, which can further exacerbate symptoms of mental fatigue and depression. And that’s not all!

    A group of researchers at the University of Bordeaux found that when rats were given a choice between a sugar substitute and intravenous cocaine, 94% of them chose the sugar substitute.[4]

    While the research on cardiovascular disease in the last fifty years has been focusing mainly on the dangers of fats, new research reveals that carbs are actually more dangerous to health than fats. A study showed that a high-carb diet increased blood fats level more than a high-fat diet![5]

    If you crave carbohydrates as your primary source of energy, it’s time to cut them back. But the brain needs glucose to function, how can glucose be produced without carbs?

    Luckily, this is not really a problem for the human body. If you think about it, the early human diet was made almost entirely of protein and fats. As a matter of fact, the body can produce glucose from proteins through a process called gluconeogenesis. [6]

    low-carb-foods

    While this idea of a low carb diet [7] may seem a crazy, it actually goes back to the 1920s [8]. Originally developed to reduce symptoms of epilepsy, (back when anticonvulsant drugs did not exist), the ketogenic diet has helped millions people all over the world lose weight and overcome their chronic fatigue as of today.

    Without getting too technical, the ketogenic diet forces the body to burn fats rather than carbohydrates. In this process, ketone bodies are created, and they replace glucose as the body’s primary source of energy. When there is a high blood level of ketones the body goes into a ketosis state, which leads to a reduction of the frequency of epileptic seizures.

    But that’s not all! Without carbs to get in the way, the body starts burning fats at a much higher rate, and this helps those in overweight in shedding excessive fats and reach the desired weight.
    For more information check the keto subreddit.

    Parasites

    Even though parasites may make you think of Third World countries, they are still fairly common in civilized nations. Tapeworms, hookworms, pin worms, liver flukes, giardia, these are just a few of the parasites that cause disease in humans.

    intestinal parasites

    Symptoms of parasitic infestation include:

    • fatigue and lethargy
    • abdominal pain and swelling
    • fever
    • vomiting
    • diarrhea
    • malnutrition and anemia
    • loss of appetite and blood

    The severity of these symptoms depends on the type of parasite, the number of parasites, and the site of the infestation. Most infections are asymptomatic, especially in the early stages. Parasitic infections are usually treated with benzimidazoline drugs like mebendazole (Vermox) and albendazole (Albenza) while protozoan parasites (like giardia) are treated with nitroimidazole antibiotics like metronidazole (Flagyl) and tinidazole (Tindamax).

    “Colon cleanse” supplements have never been proved to work, and they should not be used as a primary treatment but only to augment the efficacy of antiparasitic drugs.

    Eating good amounts of garlic, papaya, and black pepper, and taking a zinc supplement, may reduce the severity of the infestation.

    Thyroid

    thyroidHypothyroidism is a common condition caused by the thyroid not producing enough thyroid hormones (T4 and T3). This generally happens for two reasons: Iodine deficiency or Hashimoto’s thyroiditis.

    Iodine deficiency is the most common form, and it is caused by an inadequate amount of iodine in the diet. This type of hypothyroidism is fairly widespread in second and third world countries. One of the ways in which governments have tried to prevent this is by promoting the use of iodized salt (table salt with additional potassium iodide).

    Hashimoto’s thyroiditis, on the other hand, is an autoimmune disease in which the immune system sees the thyroid cells as an enemy and attacks them. It is one of the most common causes of hypothyroidism in the United States.

    But fatigue is not only a symptom of hypothyroidism: it can, (even though it’s less prevalent), also be a symptom of hyperthyroidism, the opposite of hypothyroidism.

    If your metabolism is too slow (or too fast), or if you can’t stand hot (or cold) temperatures, you should check TSH, T4, and T3 levels through a blood test.

    It is a good idea to supplement the building blocks of thyroid cells: iodine and selenium (200 mcg each). Iodine can be supplemented with a potassium iodide supplement or Lugol’s iodine. Selenium should be supplemented in the selenomethionine form since sodium selenite is a pro-oxidant, which is not something we generally want (unless you have cancer).[9]

    Medications

    A fairly common side effect of some medications (especially those that act on the brain) is fatigue. If you are taking supplements, it’s also a good idea to stop taking them one at a time for a couple days and see if there is an improvement.

    In general, the worst offenders are antidepressants, antipsychotics, antihistamines, and beta blockers. Please consult a medical professional before you stop taking a psychiatric medication.

    That being said said, here is a list of medications commonly associated with fatigue, sedation and brain fog:

    • Antidepressants: mirtazapine (Remeron), citalopram (Celexa), paroxetine (Paxil), trazodone (Desyrel), mianserin (Norval), amitriptyline (Elavil), imipramine (Tofranil), clomipramine (Anafranil) etc.
    • Antipsychotics: all of them
    • Antihistamines: diphenhydramine (Benadryl), promethazine (Phenergan), hydroxyzine (Atarax)
    • Beta-blockers: all of them
    • Benzodiazepines: alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), clonazepam (Klonopin)

    Adrenals

    adrenal-hormonesThe adrenal glands are two small glands that sit on top of the kidneys. They produce a variety of hormones, including cortisol, adrenaline, and aldosterone, through a process called steroidogenesis.

    The adrenals produce three types of hormones: mineralocorticoids, glucocorticoids, and androgens.
    Mineralocorticoids help blood pressure regulation and electrolyte balance.
    Glucocorticoids — including cortisol and corticosterone — regulate the immune system as well as metabolism.
    Androgens are steroids that get converted to fully functional sex hormones in the gonads and other target organs.

    There are a number of diseases that affect the adrenal glands. An overproduction of cortisol causes Cushing’s syndrome and a deficiency of cortisol causes Addison’s disease. Cortisol and adrenaline are implicated in the stress response (“fight-or-flight response“). Too much cortisol promotes stress and anxiety and not enough cortisol causes chronic fatigue.

    But why do the adrenals stop working properly? Two common reasons are either stress or a over-consumption of drugs that affect the adrenal glands, like caffeine and amphetamines.

    About caffeine and stimulants…

    Seriously, who doesn’t love a cup of coffee in the morning? It tastes great, helps you wake up and stay focused, it’s full of antioxidants, and protects your liver — this “liquid gold” can truly be a lifesaver when used correctly. But an excessive or poorly timed use of coffee and other caffeine sources, on the other hand, can stress your adrenal glands and disrupt your sleep cycle (which by itself increases cortisol).

    As a rule of thumb:

    • avoid taking caffeine after 5 pm
    • limit intake of caffeine to no more than 300 mg a day (a cup of coffee usually contains between 60 to 100 mg of caffeine)
    • do not mix caffeine p0wder or coffee with other stimulants

    The same principles more or less apply to stimulants. They may seem like a good idea when you’re feeling exhausted and unmotivated, but if the fatigue is a symptom of a chronic condition they end up doing more harm than good.

    Excessive use of stimulants may lead to burn-out, psychosis, and neurotoxicity.

    Inflammation

    disease caused by chronic inflammationInflammation is part of the process that begins as a response of the body to harmful stimuli. Inflammation is usually caused by an infection, but that is not always the case – in some cases, the harm done by years of an unhealthy lifestyle (through smoking, drug abuse, over-consumption of alcohol, or an inadequate diet), can produce a chronic inflammatory state.

    Chronic inflammation – whether caused by infection or a bad lifestyle – is associated with heart disease, muscle loss, cancer, depression (and other mood disorders), shortened lifespan, and autoimmune diseases.

    Methylation cycle

    The methylation cycle is a biochemical pathway that regulates a number of bodily functions, including detoxification, the immune system, energy production, and mood. Explaining the methylation cycle is a bit out of the scope of this article, and I’ll address it in a future one.

    What is important to know is that individuals generally fall into two categories: under-methylators and over-methylators. Typically these genetic differences in methylation are discovered by genome testing, like 23andme.

    Here you can read more about the methylation cycle, how it works and how is it linked to chronic fatigue and poor mental performance.

    Conclusion

    In the end, there are many conditions that cause or mimic chronic fatigue. As chronic fatigue is a relatively complex and still pretty unknown syndrome, it is a good idea to test for all the conditions we just explained, before giving up to the diagnosis.

    As a matter of fact, there are other conditions that may cause this syndrome – like hypogonadism (low testosterone levels), or high blood ammonia – but we left those out to cover them in detail in future articles.

    Have you enjoyed the article? Do you feel like you may have one of this conditions? Leave us a comment!

    References   [ + ]