Support for Those Who React Badly to Diazepam

I recently happened on a thread where the OP was suffering from what she felt was severe allergy symptoms after being switched from Klonopin to Valium, and mentioned that she had found validation that Valium itself could very well be the cause. This immediately got my attention!

I too was suffering from multiple, increasingly intense allergic symptoms the further I progressed in the Ashton Schedule for tapering from xanax to valium:  more and more severe congestion (ultimately totally blocked nasal passages on waking); agitated insomnia or at best unrestful fragmented sleep (could not stay asleep longer than 3 or 4 hours); waking up feeling hot in a cool bedroom; deep, intense itching, especially my scalp and eyes; eyelids feeling like they were scalded; later on, iincreasingly bad bouts of lumpy hives - painful itchy welts on my legs and buttocks; sneezing fits (I would sometimes sneeze a dozen times or more in a row, tears streaming out of my eyes and mucus flowing out of my nostrils).

I had never suffered severe symptoms like these in the twenty years I've been on Xanax. And it was becoming clear as I kept careful records of my increasing diazepam dosage (strictly per the Ashton schedule) that the symptoms were definitely increasing in intensity as my diazepam dosage increased.

I quickly started searching for the information that the OP had mentioned, and discovered just a bit of online evidence (to which I have links below) that my ever-increasing doses of diazepam (Valium) could definitely be the cause of my increasing misery. The explanation I found was that diazepam (unlike the other benzos) can inhibit DAO (diamine oxidase), an absolutely essential enzyme in our bodies for metabolizing histamine. And it seemed likely to me that this would probably be a major problem for the few of us "histaminics" who are prone to allergy anyway.

I have been histaminic all my life - prone to allergic reactions ever since I can remember. Various allergists have referred to my metabolism as histadelic, histaminic, or histamine sensitive. However, by avoiding all foods and medications known to increase systemic histamine, as well as moving away from an area where my worst air-borne allergens thrive (such as Russian thistle), I have been able to achieve a much less allergy-impaired life for a long time.

Based on the scant information that diazepam (unlike the other benzos) may be a root cause of allergy due to it inhibiting DAO (an idea hotly disputed by some), I stopped using it (and unfortunately had to reinstate the equivalent alprazolam), and was finally able to sleep through the night and wake with clear nasal passages - instead of sleeping fitfully for only a few hours and waking totally congested. My skin didn't feel "sunburned" and I was not itching anywhere! Eureka!

But I found in further researching that Benadryl (diphenhydramine), which is used to block histamine (and the resulting allergic symptoms) as well as induce sleep, and is proven to slightly increase DAO in medical research - thus seeming to be the "cure" for diazepam woes - ironically also blocks HNMT (histamine N-methyltransferase) the other absolutely essential enzyme in metabolizing excess histamine.

So now I'm "between a rock and a hard place", as my grandfather used to say.

But at least, I now know a bit more that could explain why I was suffering with diazepam - and I've regained definite relief from intensifying allergy, as well as warm support from several benzo buddies.

I would like to offer what little I have gleaned about "diazepam allergy" with those still mystified by why they can't tolerate diazepam - the benzo which is the ideal way to taper off benzos for most people. Unfortunately, I have no solution. But perhaps a grief shared is half a grief...or misery loves company.

Links to three pages to be considered regarding this issue:

https://www.histaminintoleranz.ch/en/therapy_medicaments.html#dao

https://www.adrianaduelo.com/wp-content/uploads/2015/10/Histamine-histamine-intoxication-and-intolerance.pdf  Scroll to Table 1, or search (CTRL+F) the page for "diazepam" (without the quotes).

https://en.wikipedia.org/wiki/Histamine_intolerance Histamine intolerance is real and has been accepted by much of the medical world.

Dave

I also believe the DAO inhibition is true. I understand other people don't believe it because there is not proof. I don't have proof either, so I can't guarantee it's true. I just have an inner feeling that it is true, it's like my subconscious mind cough something my conscious mind didn't.

I don't have an histamine health problem like you, but I feel like diazepam is messing with my histamine. And I've read many other people saying the same, so there should be something. Maybe there is not empirical proof from scientific tests just because no scientist has tried but it doesn't mean it isn't true. Neither mean it is.

I also believe the DAO inhibition is true. I understand other people don't believe it because there is not proof. I don't have proof either, so I can't guarantee it's true. I just have an inner feeling that it is true, it's like my subconscious mind cough something my conscious mind didn't.

 

I don't have an histamine health problem like you, but I feel like diazepam is messing with my histamine. And I've read many other people saying the same, so there should be something. Maybe there is not empirical proof from scientific tests just because no scientist has tried but it doesn't mean it isn't true. Neither mean it is.

I very much appreciate your input LQTYS! I had mentioned links to webpages regarding our issue, but they were somehow lost - I've restored them, so you might like to check them out.

I'm not sure if I understand the situation, but if you're referring to Libertas skepticism about diazepam DAO blocking, I think they're just a stickler for medical studies and they were sharing that they couldn't find anything except a study about dogs intestines.

DAO operates throughout the ENTIRE BODY; that's why it's so important, and why diazepam, if it does interfere with DAO, could be causing so many problems. DAO levels outside the gut can't be directly improved or replaced with any current supplements, to my knowledge.

I remember when Libertas started posting studies and their concerns about my liquid clonazepam experiments (back when I had some really wild ideas). I think Libertas really means well. We're a diverse group, and that's a good thing. 

Hi, SlowNSteady!

No, I wasn't disturbed by Libertas' post at all. The post was backed by actual medical research on dogs. That appeals and interests me. It's also important to note that human-safe doses of Tylenol, Advil, alcoholic beverages, and even chocolate can be fatal to dogs, so there's a big difference between canine and human metabolisms. The findings that diazepam didn't inhibit dogs' DAO doesn't necessarily transfer to human biology.

Actually, my leaving the original thread was brought about by blunt, close-minded contention posted earlier on that thread. The last straw was the harsh refusal to even examine the links about diazepam inhibiting DAO (links which I've moved here).

Closed minds claimed (and were believed) for centuries that the earth was the center of the universe, tectonic plates were a myth, that DDT was harmless to humans, smoking tobacco was glamorous - not dangerous, and opioids were a blessing to people in pain.

Both my doctor and a psychiatrist 20 years ago said that benzos were necessary for a lot of people, who should take them "for the rest of their lives" [and I quote verbatim], "like insulin for a diabetic", despite my reluctance about being addicted to an unnatural chemical. In response to my reluctance, I was told not to neurotically resist what was necessary medication for me. Now the opposite of what my "highly trained" doctors insisted on - like the opposite of everything in the previous paragraph - is the actual truth. And along with most of you, I'm still struggling to overcome the results of that old "truth" - but I have also been made conscious of a new possible fact for the few who encounter a major tragic snag in the process, namely an unsuccessful or unbearable transition to diazepam.

Despite the paltry supporting evidence, I have my own personal physical reactions to diazepam and the relief after stopping diazepam - as I described above - to keep me pursuing this possible DAO-histamine connection. I declare nothing as proven, but I would like to keep this possibility open for more evidence - laboratory or empirical - without the arrogant disdain that I encountered in the other thread.

My hope at this point is that this thread can give some support, can point to alternate solutions for those who keep struggling to taper with Valium and end up miserable every time. Because that's what I've done at least three times in the past few years.

I also want to keep this thread open to provide a place for any official research info about the Valium vs DAO issue that anyone has found and can post here, as well as personal experiences, i.e., empirical or anecdotal info that maintains the possibility that for many people Valium really is the problem and it's not their fault if they fail at completing an Ashton taper (which offers only Valium as a solution) - and encourage them to stop struggling with Valium and pursue other ways to taper, which they can find in this forum.

Okay Dave! I think it's anecdotally a very clear correlation.

I can't offer any further resources besides the ones you've linked to. But I will say that I was discouraged from taking Valium initially by intuitive information and spirit guides, who insisted that it would be too harmful to my gut. When I found the same resources that you mention, AND numerous other benzo buddies who were suffering histamine problems on Valium or who had needed to crossover to another benzo because of similar effects... I figured my gut concerns might have some basis.

I'm tapering K, and I'm grateful that it can be done. I'm trying to put more resources together so that other people can taper K successfully (link in my signature); V is not the only long-acting benzo to taper, and it seems for many, it's the worst of the two.

Then there's folks that taper Xanax; I don't know how they do that... 

Okay Dave! I think it's anecdotally a very clear correlation.

Thank you for the confirmation, SlowNSteady!

I can't offer any further resources besides the ones you've linked to. But I will say that I was discouraged from taking Valium initially by intuitive information and spirit guides, who insisted that it would be too harmful to my gut.

I'm intrigued that you were guided by intuition and the spiritual!

When I found the same resources that you mention, AND numerous other benzo buddies who were suffering histamine problems on Valium or who had needed to crossover to another benzo because of similar effects... I figured my gut concerns might have some basis.

Interestingly, I worked through this in practically the opposite direction! First, I started by having problems with diazepam; second, other benzo buddies suggested that increasing histamine in my system due to the inhibition of DAO by diazepam might be the problem; third, I found the resources online that supported that notion; and lastly, I felt a growing urgency inside that I had to stop diazepam right away to catch up on my sleep before I burn out!

I'm tapering K, and I'm grateful that it can be done. I'm trying to put more resources together so that other people can taper K successfully (link in my signature); V is not the only long-acting benzo to taper, and it seems for many, it's the worst of the two.

I desperately wish I could join your group in planning tapers with Klonopin, but as if cursed, I develop 100% insomnia when I take Klonopin - no itching, no rash, no headache, no congestion, but also, NO SLEEP. So in the case of K., it doesn't have any of the array of histaminic symptoms - it's only like I'm drinking the strongest espresso all day and night without getting coffee nerves - just growing exhaustion from no sleep. My pharmacist refers to it as a "rare paradoxical reaction" that occurs with maybe 1% of people who try Klonopin. Of course, I would be in the 1% - I often am.

Then there's folks that taper Xanax; I don't know how they do that... 

Unfortunately, that's exactly what I am having to do. I micro-dose Xanax several times a day, cutting each dose down little by little - and it gets more "micro" as I go - the time is fast approaching for me to start a liquid tapering method. But I won't quit until I can get off benzos forever.

Blessings to you! I'll pay your group a visit soon.

Dave

Thank you so much to Dave for starting this support group! I think it will be informative to hear of other's experiences.  Of course we all wish there were top-notch scientific studies looking at this issue, but, sadly, like many things benzo recovery related, there are not. 

I am another who has potentially experienced what seems to be histamine reactions with D.  My benz history is short, but it does include C/T of K and another gaba-ergic, baclo.  So, it is possible that the C/T is more the cause of my symptoms.

However, since I was "stabilized" on 10mg D. four weeks ago, I have felt anything but stable, and many reactions seem to be histamine-related.  My main symptoms are nausea resulting in alarming weight loss, intense shaking in the mornings (oh how I dread waking up!); red, itchy patches that appear randomly; a few hives; anxiety;  and a definitely worsening of all these symptoms when I consume histamine-high foods.  For a couple mornings I last week I tried the "adrenal coctail" that floats around (OJ, water, salts, cream of tartar).  Within minutes, all symptoms mentioned above were 10/10.  I also noticed this a few weeks ago when I ate some tomato soup.  I am new to the ideas of histamine intolerance, but it seems to me I have had a few strong experiences in the past weeks with such.

I know that many of the symptoms I listed above and "common" taper symptoms.  However, I have also learned that, along with cortisol, our bodies release histamine in the mornings as part of our awakening response.  If my histamine cannot be cleared due to DAO inhibition, it makes sense to me why my mornings would be absolutely horrendous like they are. 

My Dr. would like me to try a 1 mg. taper over the next few weeks from V. and see if it helps any of the above symptoms, and, also, just because it's time to get on the tapering path.  However, she did say that she would be open to considering a switch back to K. if symptoms continue to be unbearable.

I am also considering the Genesight test.

Looking forward to continuing this discussion with all of you.

Best Wishes!

This is a very interesting thread for me.  A few years back when I was tapering Xanax and was switched to liquid Valium, I went thru hell.  It was horrible.  I had every withdrawal symptom in the book.

Fast forward to now.... I am tapering off of Ativan liquid and it is going very smoothly so far ....  Had a little hiccup at the beginning with the liquid, but after I stabilized it got better.    So now I have a feeling that maybe I could not tolerate the Valium...... and I almost switched at the beginning of this to Valium again

Luckily Badsocref kinda stopped me from doing that, and for that I am grateful.... Just my 2 cents..... 

This is a very interesting thread for me.  A few years back when I was tapering Xanax and was switched to liquid Valium, I went thru hell.  It was horrible.  I had every withdrawal symptom in the book.

I'm so sorry you had to suffer that excruciation! If you were just switched and not transitioned to liquid Valium, that was very likely the reason it was a horrible hell for you. (I actually tried that one time and I KNOW the nightmare of a sudden switch from Xanax to Valium!) Anecdotally, people who are suddenly switched from one benzo to another experience varying degrees of awful withdrawal from the original one despite the new benzo being taken - it's a sudden shock to your nervous system - the chemistry of each benzo is different. The long transitions involved in the Ashton method show that Dr. Ashton was well aware of this. Most medical practitioners apparently are not. The inhibition of DAO and an increase in histamine was probably not a major factor in your misery in this case at all - I believe that would involve more time to develop.

Fast forward to now.... I am tapering off of Ativan liquid and it is going very smoothly so far ....  Had a little hiccup at the beginning with the liquid, but after I stabilized it got better.  So now I have a feeling that maybe I could not tolerate the Valium...... and I almost switched at the beginning of this to Valium again

Happy to hear your Ativan tapering is going well! Your thought of returning to Valium was not - I think it's what most benzo taperers would do.  But I feel that you were fortunate that Badsocref persuaded you not to do that! Another big change to your biochemistry AND the possibility of allergic reaction posed by Valium (which we can't know if you would've had or not) have both been avoided completely. And your tapering seems to be going just right for you! Congratulations!

Hello all,

I fit into this group.  When I crossed over to Valium I experienced some pretty big issues immediately.  Except for the depression and severe constipation, I didn’t think it was anything other than Klonopin wds at the time.  I developed food allergies and got eczema rashes, blisters, just awful.  Then I got repeated sty infections in my eyes.  One swelled so bad into a boil that I still have a little scar tissue in my lower lid.  That was back in early 2019.  Had no clue about diazepam and the DAO enzyme issue back then.  I’m already histamine sensitive and have been since I was a child.  So this drug has done a number on me.  Oddly, as I’ve tapered down the histamine issues are only worse.  You’d think they would get better, but maybe those DAO receptors need to heal.  I’ve become super sensitive to the fillers in the drug itself, and having allergic reactions to them even.  This was not the case when I was on Klonopin.  I’m now limited to only a dozen foods, maybe less.  The most recent allergy I’ve developed is to the sun 😭  I cannot tolerate the sun for the histamine issues go savage!  My throat closes and I get covered in hives and it flares up my rashes, get worse agitation and akathisia, anxiety goes through the roof, get worse flushes, and even less sleep.  It has seriously made my world so limited and much smaller.  Heartbroken. 

Uni,

I just want to tell you that I am truly sorry.  All of that, every little bit, is awful.  You've walked through so much.  I'm sure you are weary.  It doesn't seem fair that some people seem to walk through taper relatively easily and many of us suffer so much.  I just wanted to send you love and a supportive hug.

I fit into this group.  When I crossed over to Valium I experienced some pretty big issues immediately.  Except for the depression and severe constipation, I didn’t think it was anything other than Klonopin wds at the time.  I developed food allergies and got eczema rashes, blisters, just awful.  Then I got repeated sty infections in my eyes.  One swelled so bad into a boil that I still have a little scar tissue in my lower lid.  That was back in early 2019.  Had no clue about diazepam and the DAO enzyme issue back then.  I’m already histamine sensitive and have been since I was a child.  So this drug has done a number on me.  Oddly, as I’ve tapered down the histamine issues are only worse.  You’d think they would get better, but maybe those DAO receptors need to heal.  I’ve become super sensitive to the fillers in the drug itself, and having allergic reactions to them even.  This was not the case when I was on Klonopin.  I’m now limited to only a dozen foods, maybe less.  The most recent allergy I’ve developed is to the sun 😭  I cannot tolerate the sun for the histamine issues go savage!  My throat closes and I get covered in hives and it flares up my rashes, get worse agitation and akathisia, anxiety goes through the roof, get worse flushes, and even less sleep.  It has seriously made my world so limited and much smaller.  Heartbroken.

Welcome, my poor Unicorn! You certainly have deep empathy here, especially from me.

Let me apologize for not responding to your post sooner. I'm so glad that "Butterflies" did! She is the one who first mentioned the Valium vs DAO possibility, making me suspect that I was suffering more and more for that very reason as I continued to increase Valium intake during my transition from Xanax, following Ashton's Schedule very faithfully. This got me researching this whole issue and starting this thread.

Ironically, the reason I haven't posted anything yet is that I have been suffering from an experimental retry with Valium. Just to be absolutely sure that I wasn't misleading people in this thread. I backed up to a much lower dose than the one where allergic symptoms had become unbearable before, decreasing my xanax dose in proportion.

Well, shortly after midnight - after taking Valium the preceding day, I woke up having horrible reactions - dreadful nausea; painful, lumpy hives on my legs; intense itching (especially in my scalp); burning eyes; total nasal congestion; and a piercing headache. But all this after an even lower substitution of valium than before when I had stopped taking Valium because such symptoms had become unbearable.

After that pretty clear indication that Valium indeed causes a histamine surge in me (apparently I'm more sensitized to it than ever) - I've been too exhausted and foggy brained to function. Better now - the miserable symptoms have subsided. But now you have my total empathy and share your despair about this.

I would guess that symptoms getting worse the lower you taper could be because Valium has such a long half-life (up to 200 hours!) that it accumulates in your body as you continue to take more - but that is only a guess. I am no expert about this.

You mention that you were on Klonopin before. The only solution I can suggest is to seek help at SlowNSteady's thread and blog - he has worked out careful plans to taper directly from Klonopin and is quite a nice person to work with:

Instructions for homebrew liquid K, liquid/tablet hybrids, DMT, etc...

http://www.benzobuddies.org/forum/index.php?topic=254653

I'm happy to share more personal details on my blog...

http://www.benzobuddies.org/forum/index.php?topic=252027.0

Unfortunately, I can't tolerate Klonopin for a different reason - it causes a "paradoxical reaction" in me - 100% insomnia - but without any other symptoms - nothing allergic/histaminic like Valium.

Unicorn, I wish you all the luck in the world, and a quick escape from this benzo torture chamber we're all struggling to get out of!

Dave

Benzos are mast cell stabilisers.

Many ppl develop histamine probs when they come off.

I started a thread on MCAS on here if anyone is interested.

Ajusta,

Was K. better for you?  I hate V.  I am depressed, no motivation to do anything, and feel so drugged up.  Being on it 6 weeks now, I'm hesitant to make a change and think I should just push through.  I know all of my symptoms are common withdrawl symptoms to any benzo.

Does an antihistamine work for this?

Yes, in the short term, Benadryl worked for me as far as quelling the allergic (histamine) reactions - it got rid of my serious nasal congestion, sneezing fits, and painful hives after I reinstated Valium experimentally. However, it's not a great solution in the long term - for me, at least.

One, used along with Valium, Benadryl only increases feeling "drugged out", lethargic, foggy brained, etc.

And two, it can eventually block too much histamine N-methyltransferase (HNMT), the other enzyme besides DAO (which Valium may suppress in many of us) that is essential in metabolically reducing histamine in the body, thus letting systemic histamine levels accumulate for another reason - causing a sufferer to take more and more Benadryl, the very thing that is blocking HNMT and raising their histamine levels. The one positive thing is that diphenhydramine (Benadryl) is not physically addictive like benzos. Once the allergen is eliminated, Benadryl can be stopped immediately without any major withdrawal that I know of.

I got no relief from other types of anti-histamines. However, other people may! As is often said, our metabolisms can be very different.

Some people suffer NO discomfort whatsoever from taking Valium, whereas others simply cannot tolerate it. I'm suggesting that histamine build-up is one potential explanation - this really seems to explain my own idiopathic reactions to Valium.

Was K. better for you?  I hate V.  I am depressed, no motivation to do anything, and feel so drugged up.  Being on it 6 weeks now, I'm hesitant to make a change and think I should just push through.  I know all of my symptoms are common withdrawal symptoms to any benzo.

These links might be of interest to you in regard to histamine and depression: 

https://www.low-histamine.com/blog/depression-histamine-connection

https://www.huffingtonpost.co.uk/kiran-ram/causes-of-anxiety-and-depression_b_6327486.html (#5)

https://drruscio.com/wp-content/uploads/2019/04/HistamineHandout.pdf

Many other testimonies of histaminic allergy causing depression can be found online. I myself have suffered severe, incapacitating depression during the worst allergy seasons (it may not have been the antihistamines after all!), along with all the more typical allergy symptoms of itching, congestion, hives, poor sleep, etc.

VERY similarly, taking more and more Valium as I followed the Ashton protocol in transitioning from Xanax to Valium, I couldn't overcome an ever-increasing lethargy (feeling more and more "drugged up"), brain fog, and eventually a total absence of motivation or interest in anything (i.e., depression), while also experiencing increasingly severe itching all over, congestion, burning eyes and nasal passages - more typical symptoms of excess histamine. In the dead of winter! No other allergen present.

Here is a very technical report indicating that a form of the essential amino acid methionine is involved in the maintenance of HNMT (which may be reduced by antihistamines) - HNMT is one of the two enzymes that lower histamine levels in the body (the other being DAO, which Benadryl has proven in laboratory research to actually increase slightly):

https://academic.oup.com/ajcn/article/85/5/1185/4633007#110960408 - Figure 2.

I have read many other less technical articles recommending methionine to moderate histamine levels, but never saw the metabolic process involved as shown in this report. Methionine can be purchased in most health food stores. When I was living in an area where I was especially allergic every summer, I took as much as 1000mg of methionine a day without any side effects.

However, in order to prevent it from degrading into homocysteine (a potentially harmful by-product of high-dose [500mg+] methionine metabolism), I have read in a number of articles that a combination of B6 (esp. as P5P), methyl-folate, and B12, or just TMG (trimethylglycine or "betaine" - also found in most health food stores) will convert homocysteine BACK into methionine (so intake of methionine can then be decreased).

I take no more than 250mg of TMG every other day at most - the tablets are usually 500mg, which I find way too much as that much makes me sleep all day (a moderate level of histamine is necessary for wakefulness, while ironically, too much may make you apathetic and depressed, and even fall into a miserable sleep). Though TMG is quite effective, the vitamins are probably much better nutritionally, and don't cause sleepiness.

And finally, lots of vitamin C acts as a good natural antihistamine.

I'm sad to see Ailuron, aka Dave, is gone from the forum. I lost track of this thread, but I hope that his work here will be support for diazepam users who are noticing DAO/histamine issues; the problem is well supported anecdotally, and in this tapering business, I think anecdote might be all we have to work with sometimes. From anecdote to self-investigation to self-understanding.

Farewell Dave; thanks for your hard work.