What is Orexin?

Orexin, also called hypocretin, is a neurotransmitter that regulates arousal, wakefulness, and appetite.  Narcolepsy is caused by a lack of orexin in the brain due to the destruction of the cells that produce it (R).

The brain contains about 10,000 to 20,000 neurons in the hypothalamus,  but axons from these neurons extend throughout the entire brain and spinal cord, where there are also receptors for orexin (R).

Why Should We Increase Orexin?

Orexin is not just any molecule in our body.

Brain orexin/hypocretin neurons stimulate wakefulness, alertness, eating, reward-seeking and healthy glucose balance (R).

Whenever we’re tired or fatigued, orexin is suppressed.  

It’s not like Orexin is one of the many systems that stimulate wakefulness.  It’s BY FAR the most significant stimulator of wakefulness (and it could be the only system). Histamine is also involved, but orexin activates the histamine system.

As you’ll see there are many hormones and other systems in the body that interact with orexin.  But orexin is the central player in wakefulness.  I can’t stress this enough.

Therefore, the orexin system is central to us functioning as productive human beings and being in a good mood.

Orexin also increases our metabolism and body temperature (R), so if you’re feeling cold and tired, low orexin is partly at fault. 

Orexin also increases hunger, and this works via increased neuropeptide Y expression in the arcuate nucleus of the hypothalamus (R).

This orexin system interacts with so many other systems of the body, which makes it so important.

High levels of orexin-A  cause us to be happier.  The incidence of depression is higher in narcolepsy (R).

Animal models show that low levels of orexin cause obesity -even when they consume fewer calories. (R)

This is a significant factor in why consuming sugar makes us fat.  When we eat sugar it causes our blood to spike in sugar.  This suppresses orexin, which makes us fatigued and inactive.  So instead of burning the calories, we go to sleep. (R)

Orexin and its receptors decline with age. (R)

Orexin causes us to increase oxygen consumption because it increases metabolism (R).

Local_Orexin_Activity

Narcolepsy

shutterstock_383318557

Orexin is particularly important in people with narcolepsy, which is an autoimmune condition that destroys orexin neurons.  While this isn’t a cure, if you have narcolepsy you can optimize  the orexin neurons that you have left.

Narcolepsy is significant as a result of an immune imbalance, specifically an elevated Th2 immune system. (R   Another study found elevated TNF and IL-6. (R) (Click on the links to see how to balance these out.)

Top Ways To Increase Orexin

fnbeh-07-00028-g004

1) Get Rid of Inflammation

inflammation_233859859

This is actually the most important factor in orexin being suppressed: chronic inflammation.

Elevated inflammation from cytokines like IL-1b (R) and TNF (R) cause fatigue by suppressing of orexin neurons (R, R2).

Just before the normal time of sleep onset for rats, TNF levels in brain tissue were shown to be 10-fold higher than their daily minimum (R).

There are a few main reasons why your TNF/IL-1b is significantly elevated.

  1. Food sensitivity or inflammation from food antigens.
  2. You have a chronic infection.
  3. You have a really unhealthy diet and lifestyle.
  4. You’re sleep deprived.

My favorite way to decrease inflammation is by putting a device called ICES on my head.  My second favorite way to decrease inflammation is by putting LLLT on my brain.

I also recommend exploring the following substances:

2) Use A Bright Light Device Or Get Outside

shutterstock_130218290

Bright light is used for seasonal affective disorder (SAD) and depression.

Buying a bright light device was one of the best purchases I’ve ever made.  It increases BDNF and is stimulating.

Recently it’s been demonstrated that it increases orexin and that’s the likely mechanism by which it’s effective for depression (SAD). (R)

I use this Bright light device.  It’s one of the best investments I’ve ever made.  I find it more stimulating than being outside.

3) Exercise

shutterstock_136301591

A 2007 study found acidification of our blood increases excitability of orexin, whereas alkalinization depresses it.  (R)

Anything that increases Hydrogen Ions/acidity or CO2 will increase orexin. (R)

Exercise increases both CO2 and lactate, which makes our blood more acidic.

Interval exercise especially leads to a surge in lactate, which you will read is important for exciting orexin, regardless of acidity.

Exercise can increase wakefulness even without the orexin system, so it’s good anyway. (R)

Even the increases in CO2 in the atmosphere from increased pollution can increase orexin activation, which means people have slightly more orexin activation than in the past (all other things constant) (R).

(The effects of pH involve acid-induced closure of leak-like K+ channels in the orexin cell membrane. (R))

4) ICES/PEMF

ICES is a device that I have found to potently increase wakefulness.

There is no direct research showing ICES increases Orexin, but my personal experience leads me to think that it does.

I believe the main mechanisms by which ICES increases orexin is by decreasing  inflammation and potently increasing ATP production.   It does this better than every other thing that I have tried.

ATP is the main energy-related molecule that we produce and when they’re deficient, orexin is suppressed. (R)

5) Consume Fermented Foods For Lactate (and Pyruvate)

fermented_292534334

I spoke about using lactate as a backup generator before.

Lactate is a critical energy source and a regulator of the orexin system. Lactate release from astrocytes  plays an integral part in balancing brain activity and energy supply. (R)

Supplying orexin neurons with lactate and can stop glucose from blocking orexin neurons (R).

The effect of lactate on firing activity is concentration dependent. Also, lactate disinhibits and sensitizes these orexin neurons for future excitation (R).

One study hypothesized that orexin neurons only ‘see’ glucose changes when the levels of other energy molecules are low, whereas high energy levels can stop glucose from regulating orexin cells (R).

My main source of lactate is kombucha and interval exercise.  Here are my recommendations:

6) Drink Kombucha

shutterstock_256394965

Kombucha has lactate (R), pyruvate, butyrate (R), ATP (R) and perhaps other “energy-related molecules” as a result of the fermentation process, which increases orexin (R).  I’ve found it to be the most powerful in increasing wakefulness because it has all of these in one drink.

In addition, it has tea polyphenols, which inhibit TNF-alpha.

7) Eat More Protein/Take Amino Acids

Amino acids excite orexin neurons through a few mechanisms. (R)

Nonessential amino acids were more potent in activating orexin cells than essential amino acids (R).

Amino acids blocked the glucose suppression of orexin because it tells the neurons that there’s enough energy around (R).

From most to least effective:

Glycine > aspartate > cysteine (NAC) > alanine > serine > asparagine > proline >glutamine (R).  I just recommend taking glycine and NAC, though glycine is relaxing.

A different study gave mice a dietary supplement of branched-chain amino acids (BCAAs) to brain-damaged mice, which are precursors to glutamate synthesis in the brain.  BCAA therapy reinstated activation of orexin neurons and improved wake deficits in mice with mild brain injury. (R)

(Works by inhibition of KATP channels and activation of system-A amino acid transporters. (R))

8) Restrict Glucose

Elevated glucose concentration can block or silence the activity of orexin neurons (R).

The principal way to activate orexin is by restricting glucose (R).

The  hypothesis is that under low-energy conditions such as starvation or anorexia, it could be advantageous for ingested glucose to suppress the orexin-driven net energy expenditure, thereby ensuring that more fundamental processes (such as keeping the brain alive) receive enough glucose. Conversely, when the brain has plenty of fuel (perhaps signaled by high levels of pyruvate and/or lactate), there may be little advantage in coupling glucose fluctuations to orexin activity, since under these conditions, acute changes in glucose levels would be compensated by other energy molecules (R).

The best way to do this is to eat less sugar and carbs.  This doesn’t mean to go low carb and eat less than 20g a day.  Rather, just don’t eat high carb and perhaps restrict your carbs to 200g/day, most of which should be low glycemic index carbs.

Before carbs, you can take Kidney Bean Extract, Gymnema, Chlorogenic acid or Acarbose.

9) Eat Less: Caloric Restriction

Orexin neurons are stimulated by falling glucose levels (R).

If you eat less or practice some degree of caloric restriction you will increase orexin because our body senses we’re not getting enough calories and activates this system. (R)

10) Lose Weight

obesity_348926726

Leptin inhibits orexin.  High leptin levels are characteristic of being overweight and come down as a result of weight loss (R).

(Works by presynaptic inhibition of excitatory neurotransmission and the opening of K ATP channels (R).)

11) Take Fibers and GLP-1 Agonists

GLP-1 is a gut hormone that can activate/excite orexin neurons in the hypothalamus (which increases orexin).  It’s useful in making us feel satiated as well, which will make us eat less and activate orexin even more.

It’s possible that GLP-1 could function like orexin and work instead of it.(R)  This would be good news for people with narcolepsy.

Resistant starch/prebiotics is a good way to increase GLP-1 (R, R2).

12) Take Hi-Maize

shutterstock_330564641

Hi-maize produces butyrate, which is an energy-related molecule and should, therefore, block glucose-induced suppression of orexin (R).

Also, butyric acid is acidic and increases ATP and therefore may also increase orexin in these ways.

I’ve found that it does indeed increase wakefulness after a glucose challenge or a big meal.

As discussed above, it also is a GLP-1 agonist, so it can increase orexin in multiple ways.

This is on top of the fact that it can improve memory via BDNF (R) and longevity.

13) Have Some Fun

A study found having fun or play was able to increase orexin, while the same level of exercise wasn’t able to (R).

The study concludes that motor and cardiovascular changes are not sufficient to elevate orexin, so they hypothesize that the emotional aspects of yard play account for the observed increase in orexin (R).

14) Get Into Ketosis

I haven’t seen any studies about ketosis and orexin directly, but I have some theories about how it may stimulate orexin.  I subjectively feel more awake when in ketosis.

First, if you get into ketosis, glucose levels will likely be low, which is a significant factor in activating orexin.

Second, Ketones are “energy-related molecules” that would theoretically signal to our brain that there’s not a famine, which should activate orexin (in theory).  This is thought to be the underlying logic for why lactate prevents orexin suppression.

Third, Ketones are  acidic and they increase our blood acidity, which in turn increases orexin.

Fourth, ketosis increases Ghrelin in animal studies.  Ghrelin activates orexin (R).  However, human studies show that ketosis doesn’t increase ghrelin. (R)

Fifth, Ketosis results in elevated ATP in animals (R), which activates orexin.

See my ketosis protocol.

Ketogenic diet changes

15) Increase Dopamine

A study  examined the ability of dopamine agonists to activate orexin neurons in the rat.  The study found that both D1 and D2 agonists are sufficient to activate orexin neurons. (R)

However, when dopamine binds to other receptors, it can suppress orexin(alpha-2 receptor). (R)  So it depends on the receptors.

L-Dopa, Mucuna, Amphetamines, Modafinil, Tyrosine, and SAM-e all increase dopamine in the brain.  Rhodiola specifically increases it in the hypothalamus (R– in the body of the study.)  Longvida Curcumin can also activate dopamine receptors.

Modafinil is the most powerful of these and it works by increasing LTP in Orexin neurons (via Dopamine D1). (R)

16) Forskolin

Forskolin is a well known wakeful promoter and it certainly produces a noticeable effect on me.

Forskolin increases cyclic AMP in the whole body, including in the area where orexin neurons are.   This causes these neurons to activate (long-term potentiation) and the result is we’re more wakeful. (R)

Orexin binds to orexin1 receptors to stimulate neurons by activating cAMP. (R) However, another study did not find this. (R)

17) Pregnenolone and Other GABA Antagonists

GABA antagonists or ‘negative modulators’ block the effects of GABA.

GABA (both A and B) suppresses orexin (R), so blocking GABA will help activate it.  My subjective experience validates this.

Here are a list of GABA antagonists:

18) Thyroid Releasing Hormone (TRH)

A 2009 study found TRH-stimulated orexin (R).

TRH is what commands the thyroid to make/release thyroid hormones.  TRH also powerfully suppressed Th1 and Th17 cells.

Many studies have also found that Cold exposure can also increase TRH. (R, R2, R3,R4, R5)

In rats, exposure to 4 degrees C or 39 degrees F  increased TRH release by 2 fold in the first 15 min.

Therefore you want to expose yourself to cold by going outside in the winter or taking cold showers.  This means to completely turn off the hot water.  I can only do this one minute or else it’s too annoying.

If cold exposure isn’t your thing then you can buy some TRH.  You can additionally take Hypothalamus glandular, which probably contains some minute concentrations of TRH.  I take 1500mg per a time under my tongue.

19) Ghrelin

Ghrelin increases orexin (R) and this is part of the mechanism by which ghrelin increases hunger (R).

Consuming hydrogen rich water is a potent antioxidant and also increases ghrelin (R).

20) Acetylcholine

Acetylcholine MOSTLY  increases orexin (R).  It can inhibit it simultaneously through a different mechanism, but it mostly increases it. (R)   I recommend Alpha GPC.

21) Use LLLT/Increase ATP

Increasing ATP levels can increase orexin. (R)

My favorite way to do this is to put this LLLT on my brain.  It also decreases inflammation and has a lot of other benefits.

22) Bag Breathing/CO2

CO2 is one of the methods to increase orexin (R).

You can increase CO2 by eating carbohydrates (R), but if you are trying to increase orexin you’re likely lectin sensitive, so you don’t want to have a high carb diet.

Macronutrient profile aside, you can increase CO2 by breathing into a bag for as long as comfortable a few times a day.

You can use the BreathSlim device.

23) Caffeine

Caffeine was found to activate orexin, which isn’t surprising. (R)

I recommend getting your caffeine from Tea.

24) Nicotine

Nicotine is addictive.  However, in all of the research I’ve read, nicotine is not harmful to most people.

Nicotine activates orexin neurons. (R)

Nicotine increases both Orexin A and B and ALSO increases orexin receptors.  Chronic exposure seems to have better effects.

Specifically, it increases the levels of orexin A in the dorsomedial hypothalamic nucleus (DMH) and orexin-B in the DMH and paraventricular nucleus (PVN) among the six hypothalamic regions that were examined. (R)

In addition, long-term nicotine usage increases the orexin receptors (R), which will make you more sensitive to a given amount of orexin.

In addition, nicotine and orexin excite the same synapses of the arousal pathway within the prefrontal cortex (thalamocortical). (R)  So in addition to increasing orexin, it increases wakefulness independently by activating the same neural pathways.

Nicotine addiction depends, in part, on leptin and orexin (R) and in particular orexin-1 receptors in the lateral hypothalamus.  The increase in orexin seems very significant with regard to nicotine addiction.  Withdrawal causes an increase orexin to drive you to consume nicotine.  (R)

If you’re thin and experience significant fatigue in the day, it’s likely that you have low levels of both orexin and leptin, so addiction is less likely for you – or will be less severe.

And if you do become addicted, at least it will increase wakefulness at the same time, so it’s not actually so bad.

25) Consume Fructose

Studies have found that long-term fructose consumption (bingeing)  increases orexin (R).  Also, 25% of fructose consumed turns into lactate, which has orexin increasing effects. (R)

As mentioned before, Fructose, Fructans, and FOS can also excite orexin neurons by increasing GLP-1, thereby increasing wakefulness (R, R2).

Heavy fructose consumption may not be the most healthy way to increase orexin, but based on my experience, it’s effective.

Raw honey is my preferred source.

26) Oxytocin

Oxytocin activates orexin. (R)

The structure of oxytocin is very similar to that of vasopressin.  Due to its similarity to vasopressin, it can reduce the excretion of urine slightly.

In several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and, in humans, high doses can result in hyponatremia (R).

Falling in love, having sex, nursing, and positive social encounters all of these lead to increased oxytocin. (R)

L Reuteri also increases oxytocin. (R)

27) Vasopressin (Use Caution)

Vasopressin is a hormone that makes us absorb more water and decrease urination.

Animals show increased activity when dehydrated, a behavior that improves the likelihood of locating new sources of water.

Vasopressin directly activates orexin/hypocretin neurons. (R)

I can relate to this.  When I’m really thirsty, I’m more awake.  When we haven’t drunk for a while, vasopressin is released and this activates orexin so that we look for water (R).

Vasopressin is also used as a nootropic/smart drug.

28) Neurotensin

Neurotensin is a hormone found mostly in the hypothalamus and regulates luteinizing hormone and dopamine pathways. (R)

It also decreases our body temperature and pain levels and increases our energy (‘locomotor activity).  It also has important gut functions. (R)  Neurotensin increases orexin. (R)

30) Omega 3’s?

A study found that in healthy people, there was a correlation between omega 3’s and orexin A (but not in the narcoleptics) (R).

Not Advised

CRH/CRF

CRH or Corticotrophin Releasing Hormone is released by the hypothalamus and activates orexin.  It’s released in response to stress, which is why we feel more awake at first when stressed. (R)

It stimulates the pituitary to release ACTH, which in turn stimulates the adrenals to release cortisol.

Increased CRH levels are associated with Alzheimer’s disease and major depression. (R)

Therefore we don’t want to increase orexin in this manner.

Glutamate

Glutamate is an excitatory neurotransmitter that activates orexin. (R)

Too much glutamate release is implicated in most chronic cognitive diseases. (R)

CCK

CCK is a gut hormone that causes nausea, anxiety, and satiation.  In fact, in the research, it’s used to induce panic attacks in people.  (R)

It activates orexins. (R)   However, this is the only hormone that I know of that activates orexin, but also induces sleep. (R)

A high protein diet increases CCK. (R)  Chewing gum increases it a bit. (R)

Avoid Orexin Inhibitors

The following inhibit orexin:

What Are Potential Downsides to Increasing Orexin?

Orexin plays a role in causing Alzheimer’s disease by increasing amyloid plaques (R).

In my opinion, this isn’t significant.  This is because it was found that the mechanism by which it prevented plaque was by the animals sleeping longer.   This highlights the important role of sleep in preventing Alzheimer’s, not orexin per se.

Too much orexin at night can also cause insomnia, which is no surprise. (R)

Many of the same systems in our brain that are responsible for hunger are also responsible for addiction and pleasure seeking.  Orexin is one such molecule that plays a role in both.

I have a friend who is never tired, always hungry and is addicted to pleasure – food, drugs, sex, anything.  He needs less sleep, too.  This is indicative of an overactive orexin system.

Indeed, orexin plays a role in food, drug and sex addiction.  (R)  Blocking orexin reduces cocaine-induced impulsivity. (R)

Too much orexin can also cause anxiety, panic attacks, and depression. (R)

Orexin can cause depression if there’s too much or too little.  (R)

I’ve experienced both states and I can say both cases cause worse mood, but it’s different.

One kind of depression is when you’re tired and lethargic, without much energy.  You are kind of just ‘down’.  The other is more where you experience a boredom-based depression as if nothing is stimulating enough.

The point is an overactive or underactive orexin system is not either good.

Disclaimer and Caveats

Almost all of the studies referenced in this post come from animal studies, so keep that in mind.

See Disclaimer and Caveats

Technicals

Orexins are exclusively synthesized in the Lateral hypothalamus (LH), derived from a single protein precursor named prepro-orexin. Prepro-orexin is enzymatically matured into two peptides, orexin-A, and orexin-B which bind to the G-protein coupled receptors OX1 and OX2 (HCRT1 and HCRT2) (R).

F1.large-min

Source: http://pharmrev.aspetjournals.org/content/61/2/162.long

HOW WOULD YOU RATE THIS ARTICLE?

1 Star2 Stars3 Stars4 Stars5 Stars 3 Total Votes Loading...
TWEET
0

70 COMMENTS

  • Creo

    I’ve had type 1 narcolepsy for 48 years now.
    I had no orexin at all at three months old. (after contracting whooping cough)
    I have tried many many things over the years.
    I do agree with you that Amino acids have definitely helped. But the don’t work on their own.
    I started back on provigil after ten years off, trying to find natural alternatives. I find now that Amino acids definitely put a stop to the headaches, nausea and the 4pm crash that provigil causes. However I still couldn’t stop the cataplexy or the constant brain fog and automatic behaviour which has caused many problems for me over the years (getting into debt was one of them, I have no memory of purchasing things at all but nor could I stop myself either) no antidepressants worked for me.
    After being refused baclofen by my doctor. ( it’s the new drug for cataplexy symptoms in the US apparently) I started to take Phenibut as its mechanisms were similar.
    It works brilliantly for cataplexy at a small dose. (i tried most doses but small doses work better than large ones) for me personally, anyway.
    I know about the addiction potential but it’s worth it as far as I’m concerned and I’ve never developed drug tolerance to anything. I was told as a child that no orexin means no tolerance. Though I don’t know if that’s actually true, it’s true for me, but I find myself trusting doctors less and less as I get older.
    I also agree with your point regarding gut health.
    Poor gut flora is common in narcoleptics and CFS sufferers yet it’s never suggested by doctors, ever! I found out myself from a German nutritionist.
    I starting drinking Kefir a year ago and it definitely helps. The difference is amazing.
    Some days now I forget I even have narcolepsy.
    It doesn’t rule my life like it has done previously

  • martha0114

    Joe,
    Need to read through all of this yet, but my son was given a preliminary narcolepsy diagnosis pending the longer sleep study (MSLT). Curious, we learned from MRI in February the he has a cerebral arachnoid cyst and a Rathke’s Cleft cyst. Could the latter effect the orexin issue?
    Thanks!

  • Audrey

    Can SSRI’s cause narcolepsy? I’m wondering if the increase in seratonin suppresses orexin.

  • Brooke

    The supplements I take to heal my gut and help my MTHFR polymorphisms–methyl folate, glutamine, glutathione, NAC–all of these have made me hypersomniac. And I’ve tried them over and over again. Sometimes I’m just sleepy for days for no reason. Is it possible that orexin is less my problem than just simply excess GABA? It seems like the negative effects of these “good” supplements point to that. Anyway, thank you so much for this post. The GABA-antagonists are already working–I just need to wait a little while and make sure it’s not placebo, but I actually feel AWAKE. I’ve been telling my doctor for years that I’m semi-conscious…

  • Adnan Cetin

    ATTENTION!

    It’s a good research..
    But how would you increase anything if you don’t have one?

  • julialoha

    Read here that using LLLT works in part by increasing ROS. I thought reactive oxygen species was bad for us. Is there something that mitigates the bad effects so everything comes out even in the end?

  • Olivia Coleman

    I really appreciated this article, I have been feeling so down about my weight gain, constant tiredness and never being able to get the upper hand on my narcolepsy. I only eat about once a day because I literally can’t move and don’t get hungry until its time for me to sleep again (I can only stay up for about eight hours which I save for work) Reading this gave me hope of maybe feeling better with my narcolepsy and maybe I can finally have energy and lose weight as well! I am very excited to learn this and I wanted to thank you for researching all of this and sharing it.

  • Kari

    Narcolepsy…… HLA-Qrb1 gene
    Caused by h1n1 flu vaccine.

  • Remy

    Does injectable orexin work?

    1. Joseph M. Cohen

      I doubt it

    2. cellogant

      No because it has to cross the blood brain barrier according to what I read- so they are working on a nasal spray which is in human testing right now last I read.

      Narcolepsy is no joke y’all…

  • Striker

    Chronic fatigue/tired, headaches, constant brain fog, food sensitivities, anxiety, depression, ADHD symtoms. I had all of this and more and it took me decades () to figure out it was a candida overgrowth. It’s very hard to heal yourself, but prescription drugs are not the answer imo. Fix your diet, kill it off, fix your immune system and probiotics are key. It is very difficult, good luck!

    1. Juan

      Could you elaborate on the diet and types of supplements? I feel like I suffer through the same things. Would be super helpful! Thanks

  • sen

    Hi RAFA,

    What treatment are you taking for it that gets rid of 95% of symptoms? I find myself unable to stay awake the whole day even after treatment.

  • TH

    The hi-maize source you linked for australians isn’t available anymore, would resistant starch from a potato source be ok from a lectin point of view?

    1. Joseph M. Cohen

      no

    2. John Macgregor

      Hi-Maize is available in Australia (it is grown & made there), but it is just hard to find.

  • Roderick

    Hi. Who exactly is Joseph Cohen, and his qualifications?

    1. Joseph M. Cohen

      Look at about page.

  • Gediz Gürsu

    You have described an interesting aspect beautifully. Too much wakefulness creates a Teflon mind. Nothing sticks to it. It does not remember or reunite with its past. There wont be any depth to its thinking. However it promotes anti depression effects, if there is some wrong thinking already there. So looking at it as wakefulness and logically conquering its effects and how to manipulate it and why to manipulate it, seems therefore far more important than its academical and medical aspects.

    However, if you combine concentration and wakefulness in a meaningful way, describing both neurotransmitter chains and project it to daily life. It would be not only beautiful , but also enlightening.

    Thank you.

  • Ben Peralta

    I suffer from some type of sleep issue where I can’t stay awake at work at my desk job. Been trying things and trying to find a dr to diagnosis and treat it. This article helps. Thanks

    1. Joseph M. Cohen

      🙂

    2. Rafa

      Ben,
      I too had the same unstoppable sleep urges 10 years ago which turned out to be Narcolepsy….it was hard news to take at first but there is treatment out there that get rids of 95% of the symptoms.
      I would go a “sleep clinic” at your local hospital and speak to a specialist, schedule an overnite sleep test and get the results. From my experience if you experience very vivid dreams that are often very scary and paralyzing and/or the loss of muscle tone around your knees/neck area that causes you to fall down etc..it is narcolepsy. I’ve tried taking enormous amounts of coffee, tea, nootrops…but they dont help much. That said my advice is to follow a sleep hygiene: in bed by 10pm and up st 7am. Everyday no questions ask. Zero alcoho or very little at least ( for me 2 beers and the symptoms are back the mext day)
      Eat healthy and never after 8pm i find best. No drugs obviously..cigarettes as well (although i smoke).

      Dont spend another day trying to hack this yourself because you won’t. Do NOT go to a generalist doctor or a neuro as both will only delay the cure. I was seen by 4 doctors before some suggested going to a sleep clinic directly.

      Don’t worry there is a solution out there to get back to your life as you knew it before (or very very close) 🙂
      All the best

  • Christine

    programmaticsInvestigations, please read my comments for the readers of this blog, after Joe’s response to you about his presentation of all the data he has found including anecdotal information & his own personal experiences.

    I tried to look up your information by clicking on your name to see what your background is and relationship is to orexin, but I couldn’t find anything. My information will be included in my comments. FYI

  • programmaticinvestigations

    I don’t mean this as an attack, so my apologies if it comes off that way – A lot of your posts cite a single study and then immediately advise the study’s conclusion as a cure or remedy to some problem. I just wonder how often you check whether that study was ever repeated, and if you’re ever critical of methodology.

    Even the most stringent parameters don’t guarantee that the conclusions are true or accurate for anyone outside of the context of a study. Furthermore, all studies are subject to biases, both sometimes only unconsciously so. I think it’d be good if you were more careful in your study selection, looking out to make sure there aren’t other studies that directly contradict one you’ve picked, and select among the more repeated ones.

    It’s great when you’ve tested something for months and can give your own opinion on it though.

    1. Joseph M. Cohen

      I give references so that you can look at the studies and see their quality.

      I use studies as clues, not definitives. The clues are then a template for self-experimentation. Sometimes clues are wrong or contradicted – and I do point out contradictions when I see them (You obviously haven’t read enough posts). Sometimes clues have stronger or weaker evidence. But a clue is a clue and I use the best information in a complex world, realizing that a lot of it will be wrong. Anecdotes and traditional/evolutionary ideas can also offer clues that are worth self-experimentation in my book, but they can also be wrong often.

      In my book, if you want to improve, you start experimenting with the ideas with the best evidence and you keep experimenting with clues that have less evidence behind them.

      If you don’t have this spirit of self-experimentation, this blog isn’t right for you.

      You’ve misunderstood the blog.

      1. Ditrich Redge

        Joseph, is necessary for PQQ to work to be BIOPQQ ?? Can it be this for example ??? 🙂 Thanks

        1. Joseph M. Cohen

          Don’t know, but I’d stick with biopqq

      2. Christine

        Bless you Mr. Joseph M. Cohen,

        I am so grateful to see so many things here. So much of me here. I am in my 40s, a speech pathologist with a host of ‘conditions’ that continue to require my persistent effort to live a life of some quality.

        I am a researcher by nature, and my favorite topic is what do I have (is there a name for all these symptoms), and what can I do to help it.

        From psychiatrists, neurologists, chiropractors, supplements, lifestyle changes, self-hypnosis, entrainment, homeopathy, etc, I continue to look for support for whatever causes my sleep attacks, depression, low motivation, anxiety, troubling ADHD, and corresponding executive dysfunction.

        My research & self-help has included looking at SAD and light therapy, vasopressin, Acetylcholine, oxytocin, stimulation of the vagus nerve, narcolepsy, uses of caffeine & other prescription stimulants. I am also have type 2 diabetes, and have looked into Leptin, and battle hormone-based mood issues, along with tons of sensory issues including sweet & carb cravings.

        Zinc & l-glutamate have come up & I have tried them. I currently have some probiotics & am eating lots of yogurt for the whey protein.

        At this point, I haven’t found the magic one thing that is a cure-all. I guess I am searching for the right combination of things to get me from depressed, employed part-time, with few non-familial relationships, back to employed full-time, staying awake all day & going to sleep intentionally, vibrant church life & friendships.

        But again bless you for your research & sharing. My 18 years of research in these areas are really expounded on in this article. By the way, my working diagnosis is Dysautonomia – I have some allergies, GI problems & Graves Disease (Autoimmune Thyroid disorder), so you have presented all the angles I have explored & several more. I will steer many more to your blog.

        Christine.

        1. Joseph M. Cohen

          Thanks 🙂

        2. Rafa

          Christine, please see my comment to Ben about Narcolepsy.
          Thanks

  • sjf

    Orexinergic signaling mediates light-induced neuronal activation in the dorsal raphe nucleus.
    Adidharma W1, Leach G, Yan L.
    Author information
    Abstract
    Seasonal affective disorder (SAD), a major depressive disorder recurring in the fall and winter, is caused by the reduction of light in the environment, and its depressive symptoms can be alleviated by bright light therapy. Both circadian and monoaminergic systems have been implicated in the etiology of SAD. However, the underlying neural pathways through which light regulates mood are not well understood. The present study utilized a diurnal rodent model, Arvicanthis niloticus, to explore the neural pathways mediating the effects of light on brain regions involved in mood regulation. Animals kept in constant darkness received light exposure in early subjective day, the time when light therapy is usually applied. The time course of neural activity following light exposure was assessed using Fos protein as a marker in the following brain regions/cells: the suprachiasmatic nucleus (SCN), orexin neurons in the perifornical-lateral hypothalamic area (PF-LHA) and the dorsal raphe nucleus (DRN). A light-induced increase in Fos expression was observed in orexin neurons and the DRN, but not in the SCN. As the DRN is densely innervated by orexinergic inputs, the involvement of orexinergic signaling in mediating the effects of light on the DRN was tested in the second experiment. The animals were injected with the selective orexin receptor type 1 (OXR1) antagonist SB-334867 prior to the light exposure. The treatment of SB-334867 significantly inhibited the Fos induction in the DRN. The results collectively point to the role of orexin neurons in mediating the effects of light on the mood-regulating monoaminergic areas, suggesting an orexinergic pathway that underlies light-dependent mood fluctuation and the beneficial effects of light therapy.
    Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  • Denna

    Wouldn’t increasing Pyruvate levels predispose you to tumors/cancers ?

  • Denna

    Wouldn’t an increase in lactate make you more prone to getting cancer ?

    1. Joseph M. Cohen

      Study for either of these claims?

  • Alex

    Hi Joe. Changed mind about trying nicotine. Do you know of any european (UK) analogue, and does the brand actually matter? It seems wasteful to order the one you recommend from UK.

    1. Joseph M. Cohen

      I only did well with that type…

  • Rollia

    I just got my lightening device – since I do not have much time in the morning, can I use it at night? How do you use it ideally?

  • AJT

    Fast track to TRH is a deep cold exposure like an ice bath. Not the most pleasant experience but you can adapt to it.

    1. Joseph M. Cohen

      Thanks! I added it.

  • Judd Crane

    How do you like Oxytocin? Useful for social interaction?

  • Heidi Lindborg

    Hi-
    I’m a narcoleptic and have been biohacking my orexin levels for 7 years now.
    You’ve got most of this right, but your advice for number one is lacking some critical information. If you would like to know how the inflammation really works, you can read my explanation.
    The key is oral infection control. Oropharyngeal bacteria reinfect us over and over and mess up our guts. (you should add brushing teeth with baking soda to this list of hacks.)

    The glucose part is right. I’m not so sure about the fructose.
    You should become more familiar with the long term hyperinsulinemia before you recommend that.

    I might steal some of this other stuff though…your list and presentation are really good.
    Best wishes from a fellow traveler.

    1. Joe

      I know about hyperinsulinemia.

      Oral infections can be significant for some.

      You don’t have a complete view of inflammation.

      EXCESS fructose can can inflammation, not normal amounts. If you have a reference that suggests otherwise, please do cite it.

      You seem like one of those people who talk about inflammation without understanding it in a more nuanced way, on the protein level, but you are surely over-confident of yourself.

      I don’t like to be insulting, but you seem to be more confident than your knowledge permits.

      1. KV

        I so much appreciate common ground established between many different sincere views. Fructose (for me) is one of the “seven deadly sugars” with insulin metabolism concerns. Not naturally occurring amounts (like in apples or honey,) but food industry synthesized corn (et al) syrup concentrations. Binging on that?? Yecch. Also, having finally kicked nicotine (again – the industrialized versions) …I can say I’d take almost ‘anything’ over returning to THAT addiction cycle. Great info folks! Thanks Joe!

        1. Joseph M. Cohen

          I don’t advocate concentrated fructose outside of fruits and raw honey

        2. KV

          awaiting moderation – please correct “bingeing”. thanks.

    2. Raouf

      Hi,
      I am a fellow Narcoleptic for the past 10 years and I’m wondering if you can share your “hacks” with me? i am on 250mg nuvigil daily. I hacked my way into stopping Celexa and I’d like to do the same with Nuvigil. Thank you

  • Kieron

    My god you are some guy, You know so much am jealous lol only joking, If I took cinnamon and some protein and fat with my mash potato would that lower the insulin increase?

  • MOSHE

    HI

    Here you talk about natural agonist/activate of OREXIN A

    Did you know A natural Antagonists of OREXIN A ? THANKS

    תודה ושלום

    1. Joe

      Berberine, but I don’t know how strong it is. Inhibiting orexin is the same outcome as orexin antagonists.

  • Nur Fahri Akman

    This aprroach seems ambiguous to me.Eating bread also means to eat Sugar right?How come orexin produced cells will protect theirselves by being blockaded with glucose?There must be an agent to provocate the orexin containing cell to secret more and even reproduce them.If there’ssome you know aside from kombucha I’d be happy to learn ıt.

  • Ola

    Hi Joe.
    But if there is a deeper problem – like silent inflammation which causes fatigue, I guess Kombuch will not work, right?
    Plus, I have read some articles (not studies) saying that it is very probable that home-made Kombucha may be contaminated. Do you have any thoughts on this. Is it better to buy it, or preare it on your own?

  • Joanna

    came across this today, thought it was relevant
    http://www.eurekalert.org/pub_releases/2014-02/uob-nrs021014.php

    1. Joe

      Thanks!….”Professor Sergey Kasparov, from Bristol University’s School of Physiology and Pharmacology, said: “Our findings suggest that lactate has more than one incarnation – in addition to its role as an energy source, it is also a signal to neurones to release more noradrenaline.””…….is crucial for motivation, stress responses and control of blood pressure, pain and appetite.

  • Adrian Patterson

    I’m finding your comments on this page very enlighthening guys. I don’t have narcolepsy myself but had an operation on a Third Ventricle cyst which is in the same region as the hypocretin neurons that you guys have limited amounts of. I suspect the presence of the cyst and the subsequent surgery has damaged either the number of hypocretin neurons or the connections therein. I am wondering therefore whether you guys have the following associated problems, constant anxiety, erectile dysfunction, broken sleep and I’m presuming it goes without saying problems in remaining awake? We find that within our group on Facebook group of fellow Third Ventricle cyst sufferers that this is one of the more common suite of problems our members have, though headaches and hormonal issues are also common.

    I’m going to start trying some of the recommendations you list above such as Kombucha, and the various lactates and pyruvates to see whether those have any affect on me. I note that caffeine for example can have a stimulating affect on my erectile capacity, which makes me even more convinced that we share similarities with narcoleptic sufferers, since I know caffeine has been given to narcoleptics as a possible, though I suspect limited solution to your problems. Hope you get further resolutions to your problems.

  • Sidney Phillips

    Any thoughts on this video by Dr. Greger stating that Kombucha is not safe to drink: http://nutritionfacts.org/video/is-kombucha-tea-goodfor-you/

    1. Joe

      Greger is a moron and is highly biased.

      Lactic acidosis can be caused by exercise as well. These people were sick to begin with if I recall correctly(saw that a while ago).

  • Matt

    I would like to share a couple of the methods that I use to get out of “brain fog” for your readers, I liken it to stimulating the brain cells to get out of their “Pity” state and to “jump start” them again. You should like this Joe and if you don’t, you won’t hesistate to tell me.

    1) Close your eyes and follow an imaginary pendulum moving back and forth, this uses eye muscles that you probably don’t use very regularly for this purpose, so don’t over do it, you can get a headache. Regulate your breathing where you are taking in large deep diaphragmatic breaths and holding it as long as you feel comfortable and slowly letting it out. This must be done in a stimulus free environment. This is an exercise that you will build on each day, but if your eye muscles are sore, let them rest until they are healed.

    2) Flashing light therapy. I have these blinking strobe like lights that I use to wake up in the morning or change my mood, not everyone responds to the same color, however orange seems to be best for waking up in the morning. Its as easy as staring at the flashing light, using the same breathing exercises as mentioned above. You can get the lights by visiting Amazon, I have 3, but I plan to get more, they cost me $5 a piece.

    3) Using the EFT system. You can Google EFT on the web and there are people that demonstrate it fairly well on youtube videos. Personally, I make up my own montra, the pitiful self depricating montras that they use in the videos are a little cheesy IMHO, I prefer a montra more like that of a drill seargent.

    4) Lastly there is a Fisher – Wallace stimulator that I use if alll else fails. This does require a prescription and can be fairly expensive. (They gave me one at cost because I’m a PharmD. and halfway through the NMD. program). While they recommend using it for 20 min a day, I think that it is better to start out slow.

  • Matt

    If the Orexin Neurons specifically use astracyte dirived lactate, how will calcium/magnesium lactate help?

    1. Selfhacked

      Lactate you ingest goes to the blood stream and can cross the BBB

      1. Matt

        Dude, seriously, that’s not astracyte derived What they mean from the study is the the lactic acid/lactate from glycolysis generated from within the cell. In order to have high lactic acid levels you would have to be in an oxygen deprived environment, (or someone puts you in a rear naked choke)

        1. Selfhacked

          Dude. Seriously. Astrocytes store lactate to be used by neurons. By ingesting lactate you have a direct source of it (or perhaps it could replenish the astrocytes as well.) This is theoretical, but my experience seems to support this.

  • Paul

    I take modafinil for it’s effects on wakefulness and life forefullment. I find that I am much more awake, have more energy and my anxiety and depression completely disappears on modafinil, yet brain fog stays the same. I am very interested to see if kombucha + exercise has any effect close to what modafinil has on me because modafinil is ridiculously expensive.

    Tried longvida curcumin and honestly had no resemblance to modafinil at all. I’ll let you know what happens.

    1. Steven

      Go get stung by a bee or wasp. (if your not allergic of course). It may reset autoimmune responses. Happened to me at least, my brain fog disappeared after yellow jackets stung me. Spent tons of money for 13 months dealing with brain fog and a free hike in the woods fixed it. I’m interested in amping up brain power now. So far so good. Joes tool kit is quite the power house.

  • eggdmc

    I drink store bought Green Sencha (very low caffeine) Kombucha. It gives me a cognitive boost and boost in energy but its then followed a couple of minutes later by brain fog and flare up of fight or flight. Only thing I can think of is sensitivity to caffeine.. any ideas?

    I’ve had histamine tests and they came back fine.

    1. Brin

      Hi, your case aside, such a response could be a sensitivity to the tea or other caffeine source, not to the caffeine itself. (I know this from being treated for allergies to tea and coffee among dozens of other things, but given pure caffeine pills during certain phases of the treatment.)

  • Amanda

    While I do try to treat myself naturally, as a narcoleptic, I can tell you that downing kombucha will not cause my missing neurons to reappear.

    I have done quite a bit of my own experimentation. Diet and lifestyle changes can make the disease easier to handle by fixing other underlying issues. However, parts of the disease that can be directly attributed to the missing neurotransmitter have been unchanged by the diet.

    1. Selfhacked

      I don’t disagree

  • J

    brilliant!! thank you for the post, i too find this all extremely interesting, and my first batch of kombucha is already in the ferment. Look forward to reading more, particularly in regards to natural energy.

    cheers

    1. Selfhacked

      Thanks. Let me know how it works for you.

  • Leave a Reply

    Your email address will not be published. Required fields are marked *