There's a community of us that have ADHD-I, disassociation & major depressive disorder but everything disappears during a hangover.

quijonido · 2016-02-20T00:07:48+00:00

I'm a medical student who has spent years trying to figure out the exact mechanism behind this. I started a thread a few years ago at Longecity (http://www.longecity.org/forum/topic/64835-chronic-dopamine-deficiency-consistently-disappearing-during-alcohol-hangovers/page-1) about this phenomenon - my username there is Chadwick.

These days I'm basically free from initial symtoms (mainly lack of sociability) thanks to a tetrahydrobiopterin supplement I'm taking.

EDIT: 5-MTHF (methylfolate) has helped me a lot in the last couple of years but nowadays I use tetrahydrobiopterin instead.

My theory is that variations in the MTHFR and DHFR enzymes reduce folate metabolism which in turn leads to high peroxynitrite, as methylfolate is a peroxynitrite scavenger. The high peroxynitrite then leads to low tetrahydrobiopterin which is a cofactor for monomaine (dopamine, norepinephrine, serotonin) synthesis.

Acetaldehyde, a waste product of alcohol, blocks the enzyme methionine synthase during hangovers and raises the levels of available methylfolate, which can be used for peroxynitrite scavenging. This leads to higher tetrahydrobiopterin.

Alcohol consumption also leads to higher NADH which in turn increases tetrahydrobiopterin formation.

Mqrius · 2016-02-19T15:05:35+00:00

There are actually a bunch of threads out there on similar things. Here's some links:

That last one eventually found he got the same effect from taking 10 mg sublingual NADH, but you said that doesn't work for you. He also tested 5-MTHF on the idea that it may be caused by MTHFR mutations, which seemed to work for him as well. There's lots more in-depth discussion about biochemistry and neurochemistry in that thread, so there might be other interesting ideas there.

kanooker · 2016-02-19T14:42:01+00:00

[deleted]

TomSawyer83 · 2016-02-19T15:12:05+00:00

Woah, this is me. Have told this to several mental health professionals and they just shrug it off.

raven105x · 2016-02-19T21:35:19+00:00

This is a fascinating thread, I also share this experience - extreme lucidity, heightened color sensitivity, motivation, cognition, social acuity - things feel perfectly "right" after a night of getting pretty drunk (hard liquor) Whether this is actually true or subjective, however, I can't say - although my performance at work, when reviewed on a completely sober mind, does seem outstanding from when I was hung over. My lifts in the gym (tracked) don't go down either.

On reddit for four years, this is the first time I've seen something so significant it warrants participation.

grimeMuted · 2016-02-19T14:59:47+00:00

Try comparing the effects of an equal amount of ethanol ingested from vodka, red wine, and brandy. Congeners/polyphenols/fusels may be important.

bikramdrugsbikram · 2016-02-19T16:10:40+00:00

I have found personally that sleep deprivation significantly helps my depression and adhd, and there have been some studies backing this up (on mobile but will try to link later). Could it be that it's the sleep deprivation and not the hangover that's resulting in decreased symptoms? Even when you sleep after a night of drinking, it's not the type of restful sleep one would get sober.

Guacomaco · 2016-02-19T13:35:57+00:00

Do you exercise daily? Have you tried meditation? Do you breath deeply or is your breathing usually shallow?

postscarce · 2016-02-19T15:58:51+00:00

One theory is that hangovers are caused by alcohol's effects on the GABA neurotransmitter system, so it seems like you could try to find nootropics that have similar effects.

BelievesItsNotButter · 2016-02-19T18:35:33+00:00

I definitely can't relate to this. Hangovers turn my ADHD symptoms up to 11 and crank up my depression / anxiety. All day I have to keep telling myself "It's just the hangover. You'll feel better tomorrow". I've even had them last 48 hours before.

funkbawks · 2016-02-19T13:39:17+00:00

[deleted]

Nootist · 2016-02-19T17:03:15+00:00

Finally someone said it. I can strongly relate to everything OP said!!! it's awesome :)

SlightlyStoopkid · 2016-02-19T18:15:54+00:00

I've struggled with all those disorders in the past and have also noticed a strange kind of mood lift during hangovers, where I'd feel a bit giggly and uninhibited, but also calm and peaceful. I've always assumed it was somehow related to 5-ht because the feeling reminded me of SSRIs and serotonergic psychedelics, but I've never investigated it seriously.

If you're desperate to feel better though, OP, I saw below that you have some belly fat and that you only exercise about an hour a week, and I think that addressing those issues are going to take you a lot farther when it comes to your mental health than trying a bunch of random experimental supplements. I took SSRIs and spent a couple years in therapy, but upping my exercise to 3 or 4 hours a week helped more than both of those put together. Just food for thought.

SoFlo421 · 2016-02-19T21:56:23+00:00

Kava may be all you need to drink to solve your depression and ADHD issues. Much like alcohol it inhibits Monoamine Oxidase enzymes in your liver which are responsible for breaking down serotonin, dopamine, noradrenalin as well as other neurotransmitters. This inhibition boosts the levels of these neurotransmitters in your blood effectively enhancing your mood and ability to focus on the task at hand. As alcohol is a depressant in large doses, it can exacerbate your depression disorder and further complicate your life. Take a few moments to read this for some more information. Hope this helps!

[deleted] · 2016-02-20T02:01:18+00:00

The immune system and microglia functioning likely change the day after drinking, lowering glutamate sensitivity, creating an anti-depressive effect similar to ketamine whilst reducing brain inflammation, allowing the brain to finally relax.

When I smoked cannabis and took ketamine at the same time, the day after is similar to what you experience. This combination reduces glutamate and microglia.

Microglia activity lacks control in the presence of certain toxins (so test for toxins) as well as viruses (so tests for viruses via PCR and CSA test). This can also affect the immune system leasing to auto-immunity.

Try low dose naltrexone. This reduces microglia and increases endorphins. I imagine you also feel much better after intense fitness or sport, particularly when you got really engaged with it? This is due to endorphins- they're great at reducing brain inflammation, which is the cause of nearly all brain related problems. You have to find our what's causing it. As I said, the answer is often toxins (often acquired over years of stress which reduces methylation, so continue to take B12 + folate to increase methylation again) or viruses.

EDIT: Oh and you may want to try this, as like me you most likely have much too high acetylcholine levels, which drags down dopamine levels (as the two have a see-saw effect with one another)- https://www.reddit.com/r/Drugs/comments/34ex06/the_intermittent_use_of_low_doses_of_amphetamine/

Also try the Thync device. Personally helps all my high acetylcholine symptoms (I use the calm vibes only). Buy it from Amazon and send it back if it doesn't help you at all.

Would also recommend taking a daily diary of your symptoms, and experiment smoking high CBD cannabis (ideally with a 1:1 ratio of CBD to THC) for a week a few hours before bed, and note if you have improved (I expect you will).

Lastly, read the book Chronotherapy, by Michael Terman. Circadian rhythms affect nearly every biochemical pathway in our body. It may be you need to change your sleep cycle as your body is in some sort of mild jet lag state.

Whatever the answer is, there's a reason. Might not be easy but the answer is attainable. The more things you try the more clues it gives you, and eventually you'll find out the root cause. You really should do some tests if you can. The MAP test would be worth doing in addition also.

dkz999 · 2016-02-22T06:41:13+00:00

I have been looking into this a bit since it first popped up Friday.

I think a good route to test would be glycine supplements. Its widely available and seems safe to use with negligible side-effects.

Drinking increases the amount of available glycine in the body, because it decreases liver and kidney function. I was lead to glycine by the fact that its availability is also increased by Sarcosine. Glycine co-agonizes NMDA receptors along with glutamate, the primary excitatory neurotransmitter.

A hangover involves tons of neurological functions. There is a bit of hyper-excitability the day after drinking as your body rebounds from the depressant (GABAnergic) effects of drinking (even though it is often still feeling these effects). Some of this may be due to increased glycine available to bond, activating post-synaptic neurons in higher proportions than "baseline".

Given the fact that glycine plays a direct role as an inhibitory transmitter in some parts of the CNS, this double combination could well be responsible for the effects you feel the day after. Its interesting to note that an analogous co-agonist, d-Serine, has been used to treat depression. All of this makes me think we have a good candidate for the possible MoA of this "treatment" for most of the symptoms described.

The only way to know would be to test both glycine and d-serine. If greater effects are felt from glycine than the serine, it would likely point to another function of glycine (not co-agonism of NMDA receptors), whereas with d-serine it seems like the primary effect would be due to this co-agonism.

voyaging · 2016-02-19T16:04:48+00:00

I'm sure there's more to it, but the increased extroversion and heightened emotions sounds like it may just be residual drunkenness.

funkbawks · 2016-02-19T13:54:31+00:00

[deleted]

dbbo · 2016-02-19T15:44:58+00:00

Might seem like a stretch, but what types of diets have you tried, and do you have any other known diseases or any family history thereof?

The reason I ask is that I wonder if there is a metabolic component. I can give more details if needed, but to give an overview: one of the effects of high EtOH consumption is an increase in NADH since both ADH and ALDH reduce NAD+, which essentially leads to increased TAG, lactate, and ketone formation, and decreased gluconeogenesis (of course in severe cases this can result in acidosis and/or hypoglycemia, among others. However, NADH/niacin supplements most likely won't cause such a shift in a healthy, well-nourished individual.

smadan · 2016-02-19T17:07:15+00:00

I've also had times where I feel really happy, emotional and clear when waking up after a night of drinking. I remember walking through a park one morning and I nearly started crying because the trees were so beautiful. My assumption is that it must be serotonin related. ADD/ADHD is usually due to a deficiency of some sort. The hyperactivity is a way for the mind to get more satisfaction and stimulation because it naturally produces so little dopamine, serotonin, norepinephrine. The reason why some stimulants work to treat these 'disorders' is because they essentially increase the amount of the otherwise low-leveled neurotransmitters. Alcohol (perhaps certain types) must have a lasting effect of increased serotonin during a hangover. That's my understanding anyhow. I also found a kind of similar thread that you might be interested in: http://www.longecity.org/forum/topic/64835-chronic-dopamine-deficiency-consistently-disappearing-during-alcohol-hangovers/

KlusterBoy · 2016-02-19T17:52:19+00:00

Have you had a hormone panel done?

I'd be interested in seeing your Luteinizing and FS hormone levels (and testosterone by extension.). Pure curiosity at this point, but some strange stuff happens with the HPT axis on a hangover.

Pyryn · 2016-02-19T18:56:38+00:00

Wow. Very weird reading this, I experience pretty much all of this as well. Extreme ADHD-PI, depression, then depersonalization. Goes away after a night of drinking-->hangover, until the hangover goes away and I sober up....

I can say, couple things that have helped me the most: Cerebrolysin and meditation. These two make a world of difference for me.

dkz999 · 2016-02-19T19:50:20+00:00

You should try taking sleep out of the equation. If you drink and get a hangover without sleeping, does it have the same effect?

This is super interesting. I'll check out some literature when I am home in a bit.

Update: Have you tried any glycine supplements? Elevated levels seem to be a common factor between hangovers and Sarcosine.

gaucho_max · 2016-02-19T20:08:57+00:00

The way I understand it, alcohol temporarily negates the effect of chronic subclinical inflammation (through the numerous pathways mentioned in this thread.)

Gastrointestinal yeast infections, for instance, are massively underdiagnosed because of [a] unreliable blood tests and [b] the poor reputation of the topic among the scientific community (no one wants to be associated to the "candida crowd", resulting in an irrational negative prejudice.)

AstronautRob · 2016-02-19T23:15:18+00:00

How much exercise do you get?

eeksy · 2016-02-19T23:43:37+00:00

wow, how serendipitous. I was thinking about this very thing this morning after having consumed a fifth of hornitos last night and going through the usual hangover. The difference I feel, although always accompanied by a somewhat debilitating headache, is like walking through a dreamscape; more vivid colors, softer hues, softer aspects of just about everything...I'm glad there is some attention being given to it, since using alcohol to achieve the effect is not an option most of us would consider making a habit of. By the amount of people chiming in saying "wow I can't believe someone posted this finally", I would say this effect is actually common, albeit more pronounced for individuals suffering ADHD or MD disorders.

gojuugo · 2016-02-19T23:50:39+00:00

I am in the EXACT same boat as you and feel the EXACT way you do during a hangover. I thought it was just coincidence, but time and time again the fog is temporarily lifted and like you I feel very social, normally being an introvert it's extremely noticeable.

I didn't know others experienced the same thing, I will keep a close eye on this project, thanks for your interest and serious attempt at making sense of it.

EnIdiot · 2016-02-20T00:06:16+00:00

I think ADHD-I is a completely different beast than some of the other ADHD subtypes. I have the exact experience of being hung over and having a clarity that just isn't what most my friends report. I also get infrequent (but violently vertigo inducing) migraines and experience something like it afterwards (also synesthesia in the area of taste in relation to light).

I'm taking The methylfolate while my genetic tests come in and it is seeming to help. I hope that the answers are forthcoming.

sudoku_apt-get_rekt · 2016-02-19T13:31:36+00:00

Denationalization much later.

Who is your doctor, Donald Trump?

ExtrinsicFalsehood · 2016-02-19T18:37:51+00:00

Hey I saw that someone posted my thread, I as well resonated the same feelings and I still continue to have this as well. I still haven't experimented with anything and have no clue what to try yet. I heard a NMDA agonist is my best bet at this point. I'm just still pretty weary to say the least.

To be honest the best bet at this point is for anyone to read the longecity, me and many others have posted our thoughts into that thread and it's interesting to see everyones different takes on the subject matter.

Thanks for bringing this to light again!

EDIT: To OP, do you feel exactly like my post? If not how do you feel different and with what feeling? Thanks.

Also maybe you should list some common habits you have to create a correlation, like do you always go to sleep late? Is it hard for you to get out of bed, is it easier to come up with suggestions for answers in lets say a business setting when you are feeling good from a hangover?

goesagainstflow · 2016-02-19T19:11:16+00:00

Hm. What's your blood pressure like?

redguardnugz · 2016-02-19T20:33:18+00:00

Wow that's crazy that you feel positive effect. Hangovers tend to make me the absolute worst imaginable version of myself.

ThizzelleBundchen · 2016-02-20T07:12:06+00:00

You know what, you guys are right. I don't know what other people are experiencing, so you may get some relief that I don't actually understand. My bad. I hope you guys find the solution that you're looking for.

dondebouzzedondon · 2016-02-20T10:35:42+00:00

NDMA-upregulation?

kensalmighty · 2016-02-20T10:57:24+00:00

I have a very unscientific, broad theory. Any kind of major experience has the ability to knock the brain out of previous patterns, and can be beneficial. Drinking heavily, exercise, psychedelic drugs, ECT, any of these can do this, and achieve the same results, sort of.

phenidoot · 2016-02-20T16:09:27+00:00

i have experienced exactly the same. what ive noticed is that ketamine gives me exactly the same feeling in low doses. might be worth looking into. its currently in clinical trials for depression treatment.

[deleted] · 2016-02-20T17:24:34+00:00

This is a really tricky case. I have a hunch that NMDA and monamine imbalance, on two different levels such as a COMT mutation causing dopamine downregulation and insensitivity, plays a key role, but I'm not sure what's exactly going on in your case. Possibly a chronic case of low stimulation, resolved by messing around with the excitotory processes of the glutamatergic systems, which can be further improved by improved by regulating monoamine imbalance? I also think that the VTA signaling might also play a role, but I'm going to have to do some more research.

However, CDP-choline doesn't seem to do much for you, so I'm not sure if dopamine upregulation would solve it...

I feel that I'm somewhat similar, but my genetic profile only suggests a slight problem, and I think my issues are about a notch less severe than yours, and I don't always have the same symptoms, though I definitely feel new and improved whenever I get a drug afterglow. Ever consider getting a 23andme test and putting it through genetic genie and promethease?

Have you ever done a 23andme profile?

FuckitGimmeSome · 2016-02-20T17:29:28+00:00

I'm sure this has mentioned but this thread is getting long... Have you tried supplements/drugs isolating each aspect of alcohol. So if alcohol does x, y, and z, try a drug that does only x and see what happens then try something that only does y and so on. You could also try things that do the opposite of alcohol and see if it makes your symptoms worse. Or before you do that actually, what are things that make your symptoms worse?

russdr · 2016-02-25T15:10:41+00:00

You know I had always been so preoccupied by nausea and headache, which is present during 95% of my hangovers, to even think about the benefits they provide to my ADHD. But seeing yours and others explanations in writing makes it all click together.

I've tried so many different nootropics to no avail... but that correlation is the first step in hopefully understanding my problem and finding a solution. Thank you!

ThizzelleBundchen · 2016-02-20T00:43:55+00:00

Dude, this is silly. I think a wide variety of people experience this, even those who don't suffer from the afflictions you noted. I remember in high school, my favorite thing after a night of partying was driving home in the morning, because it was just awesome to feel the wind come through my window and I felt so alive. This is a symptom of being sleep deprived and still having alcohol in your system. This phenomena doesn't seem to be that mysterious, I always thought it was pretty straightforward...

meatball4u · 2016-02-19T15:58:47+00:00

I have mitochondrial cytopathy, a far more common issue than is currently realized. Mitochondrial dysregulation = dysregulation of energy usage in many processes especially in the brain as it's the most energy hungry organ. My brother struggles with ADHD and other issues that point towards mito issues.

If your problems do stem from mito, it would explain partly why its so damn difficult to treat. I've learned a lot from podcasts from MitoAction, a foundation set up to help educate about the disease. Most intriguing to me was one regarding psychiatry and mito. My major depressive disorder was about to kill me, I was hospitalized for the 10th time, and finally I tried lithium and after 7 years of living a depressed, anxious life I finally got over it. And it turns out lithium is a modulator of mitochondrial function. And has been studied in relation to energy modulation in the brain. I'd post the link but I'm on my phone and don't have the podcast handy.

Hope this helps, I understand what it's like to have a rare disease. I'm currently on my way to see a neurologist 4 hours away and hope he doesn't brush me off immediately after telling him I have Post Orgasmic Illness Syndrome...!

EscapeFromFlorida · 2016-02-19T15:59:20+00:00

Try taking nyquil or something with dextromethorphan in it before bed. Just the normal dose. I have this same problem, and it's one of the only things that has helped.

Does your mood also improve greatly with sleep deprivation?

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