Author Topic: methylation genes - MAO A (monoamine oxidase) and COMT (Catechol-O-methyl transf  (Read 11517 times)

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
Well, as you may know, I began taking supplements for methylation due to getting tested positive for the mthfr mutation.  There are many other genes tested in the methylation pathway, and one of them that I had the mutation for was MAO A.  Apparently males only get one copy of this gene, and it comes from the mother's side.

Monoamine Oxidase apparently breaks down adrenaline, noradrenaline, melatonin, serotonin and also dopamine (in combination with MAO B which I was not tested for).  It gets really complicated, as I was also tested for another gene called COMT (who knows the COMT may be more relevant) which is apparently another enzyme that breaks down dopamine, epinephrine, norepinephrine.

I am heterozygous for two of the tested COMT genes, so

I should breakdown adrenaline, noradrenaline, melatonin, serotonin, and possibly dopamine slower than normal (MAO A mutation)
I should breakdown epinephrine, norepinephrine, and dopamine slower than normal (2 COMT heterozygous mutations)

Here's where I find it interesting.  I know that a lot of people get ejaculatory anhedonia after taking SSRI antidepressants.  I've had weird health problems most of my life, and on occasion I remember taking cold medicine and having strange reactions, like increased intensity of libido (don't go try it I doubt they put the same ingredients in cold medicine anymore).  Then I found out that a side effect of MAOI medications is "difficulty reaching orgasm." (monoamine oxidase inhibitors - basically people take these as antidepressants, though not used much anymore, because it keeps the neurotransmitters from breaking down so fast - but my body is doing this already due to the MAO and COMT mutations).  

I'm sure it's been noted here before, but what if our problem isn't too little neurotransmitter, but too MUCH!  What if our chemical receptors are DOWNREGULATED because they are always SWIMMING in neurotransmitters....I believe this is documented to be able to occur physiologically if I recall from my abnormal psychology class long ago.  If you have 100 molecules of serotonin in the synapse, you don't need 100 receptors, whereas someone who has 3 molecules may need 200 (made up these numbers for illustration only).

I was curious and tried to google around for things that encourage the production of monoamine oxidase, but I couldn't find anything.  My theory being that a slight reduction in these brain chemicals might spur some new process in the synapse, perhaps lead to an UPREGULATION of receptors.  Yes, basically we are talking about a sensitization process here.  Maybe one of the reasons we are not getting spontaneous cures is because there isn't a whole lot of research, much less medication that DOWNREGULATES neurotransmitters or speeds up their breakdown?

I will be getting an amino acid urine test soon, and I will be curious to see if anything is way out of balance.  Amino acids are the building blocks of the "amines" in "monoamines" by the way, and some of that stuff is in cold medicine also sometimes.  One additional thing that I found out is that smoking reduces MAO B by 40% and also reduces MAO activity.  You would think it would be good to have more of these neurotransmitters in the synapse, but maybe it is paradoxical.  

This is only one of my new theories, I have another theory simultaneously that is contradictory to this somewhat.  It involves something called BH4, and the interesting thing is it helps build neurotransmitters, and royal jelly, which is mentioned here all the time, contains some BH4 or promotes it in some way.  Some people who have the mthfr A1298C mutation (which I do) are low on BH4.  Also people who have aluminum toxicity.  I am going to be taking another test that should help me see if my BH4 is low.

The one thing I don't understand is how this (as well as all of my other health problems) started literally overnight at age 26.  I suppose I may have flipped some genetic switch.  This is also roughly the time that I began to smoke cigarettes daily (see the above note about smoking)
« Last Edit: May 05, 2014, 05:26:09 PM by no_longer_numb »

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
This just gets even more interesting. No idea if this will help me find a reliable treatment, but I'm guessing that my theory above about impaired breakdown of neurotransmitters causing fatigued receptors is a likely culprit.  I, along with many of you, have noticed that my libido and some sensation are improved after sleep deprivation and even hangovers.  Last night I couldn't sleep the entire night due to stress and all of a sudden i'm way more horny than normal and I can tell there is some increased sensation!  I don't know how this exactly relates to the quote below - but I'm guessing I may not be getting enough NREM sleep or perhaps too much REM sleep?


A noted 2002 University of California animal study indicated that non-rapid eye movement sleep (NREM) is necessary for turning off neurotransmitters and allowing their receptors to "rest" and regain sensitivity which allows monoamines (norepinephrine, serotonin and histamine) to be effective at naturally produced levels. This leads to improved regulation of mood and increased learning ability. The study also found that rapid eye movement sleep (REM) deprivation may alleviate clinical depression because it mimics selective serotonin reuptake inhibitors (SSRIs). This is because the natural decrease in monoamines during REM is not allowed to occur, which causes the concentration of neurotransmitters in the brain, that are depleted in clinically depressed persons, to increase. Sleep outside of the REM phase may allow enzymes to repair brain cell damage caused by free radicals. High metabolic activity while awake damages the enzymes themselves preventing efficient repair. This study observed the first evidence of brain damage in rats as a direct result of sleep deprivation.[25]

http://en.wikipedia.org/wiki/Sleep_deprivation

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
This is crazy...I am suspecting that my answer may be very paradoxical.

When I first got sick with many ailments at age 25, one of the first symptoms was a horrible ongoing insomnia.  This has improved a bit over the years as I have treated my gluten allergy and taken other medication (not sleep medication).  However, I still have to take a variety of herbal, melatonin, etc in order to sleep fairly normally, which I found very odd.

Well, after not having slept at all due to stress the other night, I had an unmistakable surge of libido the following two days, better sensitivity and much improved quality of erection.  Yes, not a cure, but a step in that direction.

Well, my theory at present is this.  I have abnormally high neurotransmitters due to gene mutations such as MAO A and COMT which means that my body breaks down neurotransmitters much too slowly.  Combine this with my chronic sleep problem - essentially never reaching deep sleep, and therefore the lack of NREM sleep means that NREM doesn't have a chance to break down my already high neurotransmitters. 

So, why would another random night of no sleep improve my libido and sensitivity?  This is the paradoxical part.  The answer is that it is my RECEPTORS for the neurotransmitters that are abnormally sensitized, not the neurotransmitters themselves.  Therefore, the one night lack of sleep leads to low production of neurotransmitters temporarily, which gives the RECEPTORS a partial break after chronically bathing in neurotransmitters, and allows them to partially function appropriately for a short period of time, until the neurotransmitter levels go back up and stay up.

More paradox - the cure, according to my own theory here, is to achieve deep sleep - NREM sleep.  I am considering a sleep study to try to address this component.  Also, quitting cigarette smoking, since I found articles that smoking drastically reduces the effectiveness of MAO B and perhaps MAO A which breakdown various neurotransmitters.

So essentially here is the information:  I have gene mutations which prevent my body from effectively breaking down neurotransmitters, leaving them floating around the synapse.  Secondly, I have chronic sleep problems preventing NREM deep sleep which leads to further inability to break down neurotransmitters.  The final blow is that I smoke, which further reduces the effectiveness of my MAO genes.  Therefore I am left awash in neurotransmitter levels that must be much, much higher than normal, which causes my receptors to be overly sensitized and not function.  It is as if your eye was made to stare into a spotlight until all you could see was white, and even when you closed your eyes you saw white - fatigue, neural fatigue or receptor fatigue perhaps.

If I am right the following should cure my anhedonia:

1.  Improve sleep quality, specifically acheive more NREM sleep
2.  Quit smoking

The only thing I am unsure of is how the methylation treatment will work with all of this.  Some of the methyl vitamins supposedly increase neurotransmitters.  I have an idea why royal jelly might work, at least for a short time.  Royal jelly increases something called BH4 which increases neurotransmitters.  Even though high neurotransmitters are the problem in my theory, the extra boost takes things above the baseline (a high baseline for me) enough to shake and rattle the neurotransmitter receptors into some function.  Of course, if I am correct, the relief with royal jelly would be temporary, as it would just be exacerbating the problem of too high neurotransmitters fatiguing the receptors.

Feedback welcome.


andrew_b

  • Jr. Member
  • **
  • Posts: 39
Someone way back on the old board once reported that improving his sleep resulted in a cure. This was basically discounted and ignored as being far too simple to be an actual solution, but maybe he was onto something. It does sound very possible based on what you've researched. I work shifts, intact I'm working nights as I write this, so maybe this could be a contributing factor.

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
A little bit more to report.  I have been trying numerous things now as part of my methylation treatment in addition to the EA.

First I added the regular (non DGL) licorice root I had bought some time back.  When I tried the DGL licorice, I definitely noticed an increase in precum, which had also been abnormally reduced as a symptom of my sexual dysfunction.  However, with the DGL licorice, I did not notice any benefit to my libido, sensation, orgasm, or erection.

I took one Nature's way licorice capsule at noon with lunch, and one a few hours later and I experienced some form of orgasm, some normality coming back - I didn't have to work for it, it flowed through me.  My erection was also much better the whole time and sex was much more enticing, but it wasn't a miracle cure.  However, it was something, and I have to say, Licorice root (non-DGL) has been the only supplement so far that has had any benefit on my orgasm (methylcobalamin and other things seem to help other areas, such as sensation and erection but haven't modified my orgasm).  One very noticeable improvement has been that I am ejaculating normally for the first time in years - I can feel everything going out - which makes me wonder if the reason I had been thinking I had reduced semen is because I was suffering retrograde ejaculation?

I was doing a lot of google searches about licorice root and found a lot of interesting tangents to follow up on.  Somewhere I found that it can be a MAO inhibitor - if this is true, it leads me to believe that the effect will be temporary, as it would only worsen things in the long term, although shake things up in the short term (via disturbing the recepter sensitization)

I am also considering licorice root in the following regards:

1.  It increases cortisol, the stress hormone (is this related to why libido/orgasm improves with no sleep/hangover)
2.  Phytoestrogens....I read that licorice root actually decreases testosterone, maybe it someone addresses estrogen dominance or something?
3.  non-DGL licorice can raise blood pressure
4.  Adrenal insufficiency - licorice is considered a treatment for adrenal insufficiency (this is VERY intersting to me as I am pretty sure that I have had some long term adrenal malfunction)


and perhaps MOST interesting, I found something with a google search that Licorice could be a treatment for cocaine withdrawl.  More and more I am beginning to think that this is akin to my problem - not due to drug abuse, but due to my messed up genes that don't break down neurotransmitters and therefore sensitize receptors....this genetic basis along with viewing of porn may have sensitized the receptors and licorice might be undoing this sensitization.  Like I said earlier, however, if the beneficial effect of licorice is due only to even MORE OF A REDUCTION in BREAKING DOWN neurotransmitters - then I should relapse very very hard and go back to being completely an anesthesia dick at orgasm.

Well, we will see.  I am not in a hurry to report back to the endocrinologist, because as enticing as the cortisol hypothesis is, all of my endocrinology reports were completely normal, I still think this is a neurotransmitter/receptor issue. 

I am also very intrigued by a chemical that used to be in cold medicine in the USA prior to being banned, called phenylpropanalomine.  I recall growing up that when I took certain cold medications I had a huge boost in orgasm and libido.  Several of the brands of cold medicine that I highly regarded (I never abused them only took them when I had a cold or flu) were alka seltzer plus cough and cold and I think Contact.  I found that both of these at one time (not any longer) had this PPA in them.  Apparently this PPA contains phenylalanine which believe is synthesized into tyrosine and dopamine.  In the USA, PPA is now only approved for veterinary use for incontinence in dogs, which is also ironic since I have longstanding stress urinary incontinence that is unexplained.  Cold medicine containing PPA remains legal in Europe.  It was pulled from the USA due to alleged incident of stroke in women - PPA was in those lose weight quick drugs like dexatrim etc.  I also think that I read that PPA has been looked at as a treatment for retrograde ejaculation.

Michael

  • Full Member
  • ***
  • Posts: 51

I am also very intrigued by a chemical that used to be in cold medicine in the USA prior to being banned, called phenylpropanalomine.  I recall growing up that when I took certain cold medications I had a huge boost in orgasm and libido.  Several of the brands of cold medicine that I highly regarded (I never abused them only took them when I had a cold or flu) were alka seltzer plus cough and cold and I think Contact.  I found that both of these at one time (not any longer) had this PPA in them.  Apparently this PPA contains phenylalanine which believe is synthesized into tyrosine and dopamine.  In the USA, PPA is now only approved for veterinary use for incontinence in dogs, which is also ironic since I have longstanding stress urinary incontinence that is unexplained.  Cold medicine containing PPA remains legal in Europe.  It was pulled from the USA due to alleged incident of stroke in women - PPA was in those lose weight quick drugs like dexatrim etc.  I also think that I read that PPA has been looked at as a treatment for retrograde ejaculation.

I've experienced this sexual sensory dysfunction since 1999.  Spent countless time, money and resources trying to cure it, to no avail.

The best "sexual sensations" I experience is when I take cold/flu medicine in an ultra-relaxed state.  I attributed it to the ingredient, guaifenesin.

I believe NeedHelp had his best "sexual sensations" while sick, as well


needhelpage31

  • Hero Member
  • *****
  • Posts: 270
Yes - you remind me that having a cold, or taking cold medications HAS coincided with improvement in the past.

Wish I knew why that was, or how I could repeat it.

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
I would be curious if we have any European members on this message board, if they were to try an over the counter cold medicine with phenylpropanalomine in it, since it is still apparently legal in Europe.

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
More and more I am thinking that this MAO/COMT neurotransmitter/receptor issue is the heart of my problems.  I also have had and continue to have some gnarly sleep issues that started at the same time as my EA.  I was doing some google searches and was surprised to find a study on narcolepsy of all things, specifically mentioning MAO and COMT.

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
I keep coming across the same things in my research, but I don't quit understand why.  The item I keep coming across is alpha 2 adrenergic agonist.  Because I had experimented with the licorice, and had some temporary improvement, I guess that started my searching on this.  Then I found that licorice has some kind of benefit for adrenal fatigue, and I also came across the information that licorice may help with cocaine withdrawl.  Apparently the alpha 2 adrenergic agnonists might be used for opioid withdrawal from what I am seeing on google searches.

Phenylpropanalomine is apparently listed as an a2 adrenergic agonist.  So I am wondering how it all fits together, and am also wondering if vitamin b6, or the active form known as P5P may factor in, as it too is involved with neurotransmitters and is a cofactor in a lot of reactions.  Basically, I think there is some important connection between amino acids and neurotransmitters that I am not understanding and that may somehow, genetically, be at the root of my problem.

This is why I would like to get someone around here who has studied medicine or chemistry or something because I really do think I am onto something here.

needhelpage31

  • Hero Member
  • *****
  • Posts: 270
I believe midodrine is an alpha-1 agonist. I have had mixed results on it.

Has anyone been able to try a true alpha-2 agonist? What are the options?

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
Good point needehlp - this is the kind of feedback we need from members.  At this point, I am not sure if alpha-2-adrenergic-agonists or alpha-2-adrenergic-antagonists may be the answer for me.  Everything seems to be approaching a nexus with my amateur self guided research (as I will explain later).  I suspect, like my discussion above, that the problem may be paradoxical - I may see some "change" in orgasm ability temporarily by either increasing or decreasing neurotransmitter (or adrenergic receptor) function.  I continue to think that a good hypothesis is that my body is in a deadlock, or catch-22 situation regarding neurotransmitters.  Therefore, even something that makes my genetic mutations amplified may lead to a temporary subjective feeling that it changed something with my orgasm.

To summarize my present state of mind:  I feel I have had metabolic problems my whole life. I had experiences around the year 2000 and earlier where I felt more "normal" after taking certain cold medications.  I also recall that sometimes when I was sick and taking cold medications, I would have incredible bursts of libido and orgasmic intensity.  I do recall that one of the brands of cold medicine I favored when sick was Alka Seltzer Cough and Cold.  I have found that prior to 2000, this contained phenylpropanalomine (PPA) which was later banned in the US for human use (and subsequently banned in Canada, UK, and India...conspiracy?)  It is still used in the US for a urinary incontinence treatment for dogs (which is interesting because I suffer from long term stress urinary incontinence, that is when I cough or move I am susceptible to leaking urine if I've recently urinated).  Furthermore, ever since I became ill, my semen volume has decreased.  I believe I came across information that PPA can be a possible treatment for "retrograde ejaculation" as well.

I found a website that explained that phenylpropanalomine has some agonist behavior on alpha-2-adrenergic receptors (as well as on alpha 1).  This would distinguish it from the (still legal) phenylephrine, which I found is only an alpha-1 agonist.

http://en.wikipedia.org/wiki/Phenylpropanolamine
Here is a key point, if we have any European members with late-onset ejaculatory anhedonia, who recognize their story to be similar to my own:  From wikipedia article on phenylpropanalomine "In Europe, PPA is still available in prescription decongestants such as Rinexin,[4] as well as over-the-counter medications such as Wick DayMed."

Do we have any members of this message board in Europe?  

There are other alpha-2-adrenergic receptor agonists per wikipedia:
http://en.wikipedia.org/wiki/Alpha-adrenergic_agonist

The reason that I said that things seem to be forming a nexus, is that I found out that the traditional erectile/sexual dysfunction remedy Yohimbine is an alpha-2-adrenergic antagonist (the opposite of PPA's adrenergic agonist)  I was also reading that Yohimbine is an MAO inhibitor (see my previous posts) although I don't think that science understands how and why on this topic.

So here is the nexus - everything for me is pointing to the alpha-2-adrenergic receptor, and on one side PPA as an agonist and on the other side Yohimbine (which I have not tried) as an antagonist.  And you have my genetic tests, which showed that I have an MAO A mutation which causes breakdown of certain MAO neurotransmitters as being slow, however I do not know my MAO B status, as that was not included in my test (but is included on the $99 23andme.com test).  Perhaps I have an MAO A mutation and no MAO B mutations, and this imbalance causes anhedonia?  It would be interesting to see my reaction to Yohimbine, however, I am a bit worried given that I already know that I have an MAO A mutation, and Yohimbine is said to perhaps act as an MAOI - monoamine oxidase inhibitor.  However, one possible solution to this riddle could be, in which case Yohimbine should help me, is what if Yohimbine preferentially is an MAO B inhibitor (and assuming I do not have an MAO B mutation that causes slow breakdown of the neurotransmitters for which MAO B is active, including dopamine).  In that case, perhaps this MAO A/MAO B mutation picture is at the heart of my EA.

Also interesting is that according to "Prescription for Herbal Healing" by Phyllis Balch, page 146 "Yohimbine is particularly effective for relieving sexual dysfunction caused by treatment with antidepressant drugs known as selective serotonin reuptake inhibitors SSRIs."
So somehow, with my mutated MAO A genes which cause serotonin and other MAO A neurotransmitters to be broken down too slowly, I feel that I am in a similar situation to those who have sex dysfunction as a result of SSRI's.  However, if Yohimbine did have MAO A inhibitory effects, how would it help those who had been on SSRI's?  

Even more interesting is that per the same book you should avoid taking phenylpropanalomine when using Yohimbine because Yohimbine is a "possible Monoamine Oxidase (MAO) inhibitor."


Well, that's the information that I've had in my brain for the past week.  I am of course forgetting one last important point I wanted to make, but hopefully I will remember it later.  Feedback as always is more than welcomed.  To reiterate, I have no medical knowledge or training, just a fellow EA sufferer trying to figure things out and having received some unappreciated genetic test results as detailed in my other posts.

Just remembered that last important point!  I found info on the web indicating that alpha-2-adrenergic agonists may be helpful for opioid withdrawl. Well, all I can tell you is that when I went gluten free, my EA started to get MUCH worse, and I did go through withdrawl as discussed in the book "Wheat Belly" by William Davis, MD, who in the same book discusses how wheat causes an OPIATE like ADDICTION in at least some people.  Incredible!


« Last Edit: July 23, 2014, 07:33:16 PM by no_longer_numb »

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
I am reposting this from my reply to the post-SSRI dysfunction thread because it is relevant to my thread here.  I am hoping to hear back on this topic from searchingforacure.
____________________________________

Searchingforacure - have you seen my post in the physical causes section regarding MAO?  I can't believe I found this thread of yours from 3 years ago, I feel like my research (starting from ground zero) has led up to your old post!  I actually identified Selegeline on the basis of my research and only then found your thread!

What was the verdict with selegeline or the pea?  What I am finding out is that MAO B breaks down dopamine and phenylethylamine (PEA).  The crazy thing is, if you read my other post I mentioned, I remember getting really intense orgasm sensations previously in my life when taking cold medicine.  One of the brands I favored back then was Alka Seltzer cold and cough.  I found that at one time, prior to the ingredient being banned in the US, it contained phenylpropanalomine.  After more searching, I found that phenylpropanalomine is related to phenylethylalamine!  So I feel that I have identified what could be the source of my problem, and post SSRI sex dysfunction is certainly relevant!

As you will read in my other MAO post - I have genetic test results that show that I have a MAO A mutation which causes my body to breakdown those MAO A amines (from what I read mainly serotonin) much slower than normal.  I have not had my MAO B tested (though it is tested with the $99 23andme.com test) but I am hypothesizing that my body breaks down MAO B amines normally - that is - fast (you have to understand that with MAO the "wild" or normal type of the gene breaks down neurotransmitters and the "mutated" form produces less monoamine oxidase so therefore the neurotransmitters do NOT get broken down effectively).  I think my problem is that I have too much serotonin and too little dopamine.  So I think my answer is to increase the effectiveness of Monoamine Oxidase A inhibition or decrease the effectiveness of Monoamine Oxidase B inhibition. 

I have been having success with other health problems by getting a genetic test for the mthfr mutation and supplementing accordingly, following the principles of Dr. Amy Yasko who works with autism.  I am so far getting back to normal libido and erections by supplementing with amounts of methylcobalamin, methylfolate, adenosylcobalamin, and p5p the active form of b6, and zinc piccolinate.  My orgasms are still relatively non-events, but the build up is almost satisfactory, which for me is an improvement.

It seems like to more research I do, the more questions I have.  I am still trying to find someone in Europe with EA who can try to use one of the medications which are legal there that contain phenylpropanalomine (PPA) which was banned in the US due to stroke risk for women and the fact that it was used in weight loss drugs.  I also found that there is a drug that is used for kids with autism with the MAO A mutation called Respen and in reading their materials I have so many more questions....it mentions basically every supplement I've been on or tried, including licorice.  It also said something about not taking glutamate or gaba as it interferes with the lowering of MAO A.  So I also partially wonder if my glutamate is high because I solved a lot of my sleep problems by taking gaba which is kind of in opposition to glutamate.

Anyway, I was wondering what your evaluation of Selegeline was at this time and date and whether there was any lasting improvement with your EA as a result of having tried it, or whether and what any scary side effects were. I also read that Selegeline has been looked at for smoking cessation which is interesting because smoking inhibits MAO, especially MAO B (causing slower breakdown of dopamine).  I am a cigarette smoker.

no_longer_numb

  • Full Member
  • ***
  • Posts: 84
I also wanted to add that my EA completely took over my sexual function about 6 months-1 year into going gluten free.  I am thinking this is also some clue to the cause.  Per the book Wheat Belly by William Davis, wheat has opiate like effects, and I did experience a real withdrawal when I went gluten free.  Also, I believe carbs like wheat are a building block of serotonin, and so this may factor into my situation.

Yanni

  • Jr. Member
  • **
  • Posts: 32
Yes - you remind me that having a cold, or taking cold medications HAS coincided with improvement in the past.

I find that immediately before experiencing symptoms of cold/cough/flu my libido increases substantially and I get more feeling than normal (although still not full orgasms).

I suspect this is the body's automatic reaction to potential expiry, by having a last fling at procreation, perhaps by lowering the usual thresholds.  Or it could be an elevation of the thresholds because the body is using chemicals elsewhere in preparation for fighting the illness.  Difficult to know, but I do know that it happens without the use of cold medication.

It is so annoying there aren't more definitive results that point to particular treatment.  PPA was banned in Australia because of the potential to cause strokes due to elevated blood pressure, so I can't try it myself, but even if I could would it be worth the risk of getting a stroke in exchange for experiencing a normal orgasmic feeling.

I do know that having this condition is very depressing, yet the very antidepressants that help mood can destroy orgasm.  I don't take antidepressants because I feel terrible on them:  sick and even worse mentally, give me depression any day.  Considering they mainly work by increasing Serotonin, I suspect I already have high enough Serotonin but my dopamine levels are too low.