19 replies to this topic

[penisbreath]

probably a long-shot, but trying to rule out anything that might be contributing to my current anxiety/irritability ..

i occasionally use doxylamine succinate (25-50mg) for insomnia and, after reviewing my journal, realized that I've been using it every night since beginning Riluzole

I know rebound insomnia can be an issue, particularly with longterm use, but is there any risk of next-day anxiety?

[protoject]

I would say yes. This is the reason that I do not use diphenhydramine for insomnia, because I do get rebound anxiety the next day, and it gets worse the more I use it.

(I forgot to mention that in my eplivanserin thread when someone asked why I don't use it... )

[penisbreath]

Interesting. I was using it continually last month and feeling awful the next day; however, I was doing a detox with high-dose Milk Thistle at the same time and figured it was the Milk Thistle (more anxious, alert, twitchy, hyperactive). I cut out the Milk Thistle and the Doxylamine at the same time and suddenly felt a lot better over the next 4 days (though sleeping was worse, and thought sleep-deprivation might be having a slight AD effect).

I began the Riluzole immediately after, couldn't sleep the first night and resumed the Doxylamine. I'll try cutting it out tonight -- though predict I won't sleep -- and will see what happens.

FWIW, all benzos and short-acting z-drugs give me awful rebound anxiety.

[BlueCloud]

I've been using antihistaminics for years ( doxylamine, diphenhydramine, cyproheptadine ), it's the only thing that ever worked for my chronic insomnia ( wich i had for almost the last 15 years ). Can't really say it makes my anxiety worse for the next day, in fact it's often the opposite... But then anytime i get a real good night sleep, my anxiety is lower the next day.

Edited by BlueCloud, 27 August 2013 - 07:37 PM.

[protoject]

I've been using antihistaminics for years ( doxylamine, diphenhydramine, cyproheptadine ), it's the only thing that ever worked for my chronic insomnia ( wich i had for almost the last 15 years ). Can't really say it makes my anxiety worse for the next day, in fact it's often the opposite... But then anytime i get a real good night sleep, my anxiety is lower the next day.

Just out of curiosity would you say that you got any side effects while on these? also if so, would you give any order of priority to these meds you've tried in terms of therepeutic value and side effects?

[extroverinstinct]

I'm not sure if this is selective to a particular chemical, but don't antihistamines upregulate adrenergic receptors?

[BlueCloud]

I've been using antihistaminics for years ( doxylamine, diphenhydramine, cyproheptadine ), it's the only thing that ever worked for my chronic insomnia ( wich i had for almost the last 15 years ). Can't really say it makes my anxiety worse for the next day, in fact it's often the opposite... But then anytime i get a real good night sleep, my anxiety is lower the next day.

Just out of curiosity would you say that you got any side effects while on these? also if so, would you give any order of priority to these meds you've tried in terms of therepeutic value and side effects?

The only side-effects I get from them are the usual anticholinergic effects, and I only really feel them during the winter. Mostly dry mouth, dry sinuses. It's disturbing for me during winter because the heater in my appartment makes the air very dry already . I usually try to always use a humidifier in my room during the whole night, otherwise the mouth dryness can constantly wakes me up.
That's about it for short-time side effects. I have no idea about long-term effects (I've been taking these quite regularly for almost a decade) , I did lots of research and couldn't find any studies concerning that...

As for therapeutic value, their effects iare a a bit different on some aspects, while being similar overall in terms of sleep quality:
- Diphenhydramine and Doxylamine have similar latency before the sleeping effect hits (depending on whether you're stomach is full or not. I usually always take them on empty stomach. Or one hour after dinner) I start to feel the effect strongly after half an hour, sometimes up to an hour.
Diphenhydramine seems a bit shorter acting than Doxylamine. The last one tends to linger on a few hours upon awakening ( 2 or 3 hours), whereis Diphehydramine's effect is sometimes a bit too short ( I would wake up after 7 hours instead of the 8 or 9 hours i usually need).
Potency is similar ( I take 25 to 50mg of Diphenhydramine, or 7.5 to 15mg of Doxylamine ) . Sometimes my insomnia is so strong that I would still awake many times during night, or my sleep would still be very superficial, but usually this dosage would work 80% of the time.

- Cyproheptadine is a bit different. It has a much longer latency. The effect hits almost invariably 4 hours after dosing. So, If I want to fall asleep at midnight, I take a dose around 8pm, usually on empty stomach.
And when it hits you my friend, it hits you like a truck. It's by far the most powerful thing I ever tried for insomnia, and definitely surpasses the other two antihistaminics. My dose is usually 2mg. The full pill (4mg) is way too powerful and makes sleep almost 10 to 12 hours.

The quality of sleep on it is really great too , deep and restful. And if I need to wake up during night to go to the bathroom, once i'm in my bed again I'll fall back to sleep in a matter of a few seconds, whereis it can take me a few minutes (or much more) with the other two AH.
There a few studies on Pubmed that confirm Cyproheptadine increases sleep quality and quantity ( especially slow wave sleep ).
The only caveat with Cyproheptadine is that its effect lingers on much longer than the other two. Waking up is quite difficult, and I feel somewhat groggy for half a day.
Technically its half-life is supposed to be between 6 to 9 hours, but the clearance of the substance is not necessarily the same length as the antagonism of 5-HT2a+c ( it's also often used to counter serotonin syndrome ) wich probably lasts much longer.
I never use Cypro more than once or twice a week, and usually alternate between the others. I avoid taking many days in a row as it was shown to suppress growth hormone is taken more than 5 days in a row at doses of 8 to 12 mg. Granted, you'll probably never need more than 4mg ( usually no more than 2mg) but Iprefer to cycle it.

Edited by BlueCloud, 28 August 2013 - 08:45 AM.

[protoject]

The only... etc

Thanks for that. I think it's important for anyone considering these options for insomnia to know about the possible differences. I'm wondering also which products you got these medicines in. I know here in canada I commonly see Diphenhydramine in Gravol and other "otc sleep meds". Doxylamine and Cyproheptadine I haven't seen on the shelves though. Maybe I'm missing it?

I'm already using a med that I consider superior for sleep purposes (for me), but, in terms of sleep initiation I may consider one of these OTC as I do believe sleep initiation is one thing I could do better with. Really helps to control that window of time that you have IN and OUT of bed

I'm not sure if this is selective to a particular chemical, but don't antihistamines upregulate adrenergic receptors?

That's what I was thinking, I anecdotally experience some kind of adrenergic rebound; and , if Im not mistaken I thought I saw some paper on what you said but Id have to look into it... (doing thatnow)

[penisbreath]

I'm not sure if this is selective to a particular chemical, but don't antihistamines upregulate adrenergic receptors?

yes, I mentioned this in my Riluzole thread, but as soon as I d/c the doxylamine last night, a lot of my agitation, dysphoria and anxiety disappeared today. Wish I'd known earlier since I've been using the stuff on and off (sometimes weeks at a time) over the past year.

unfortunately, my sleep is still awful and I can't use z-aids or benzos due to rebound. I've ordered mangosteen (5-ht antagonist), but it doesn't really help with onset

Cyproheptadine I haven't seen on the shelves though. Maybe I'm missing it?

it might be called Periactin. I can also vouch for Periactin providing far deeper sleep than the other antihistamines, but it does a number on my anxiety/mood the next day

[nowayout]

I don't get rebound anxiety from doxylamine, while I do get it from benzos.

(I like your username. I was that once. Unforgettable night.)

[penisbreath]

haha thanks. I can't remember where I came across it -- might've been mentioned in a movie. I've never been a 'lucky pierre' though, for the record

[penisbreath]

I'm not sure if this is selective to a particular chemical, but don't antihistamines upregulate adrenergic receptors?

would this be the case with all antihistamines including something like Mirtazapine?

[RJ23_1989]

It's interesting you'd bring that observation up. For years I took claratin and I always thought that when I took it my mood was better but never understood why.

Probably about a year ago I happened to look up some information on it and came across this:

Loratadine (INN) is a second-generation[1]H1histamine antagonist drug used to treat allergies. In terms of structure, it is closely related to tricyclic antidepressants, such as imipramine, and is distantly related to the atypical antipsychoticquetiapine.[2]

Sent from my SCH-I605 using Tapatalk 2

[extroverinstinct]

I'm not sure if this is selective to a particular chemical, but don't antihistamines upregulate adrenergic receptors?

would this be the case with all antihistamines including something like Mirtazapine?

Yes, mirtazapine is centrally acting so to a degree. It really depends on how strong it hits those receptors. Why are you on Mirtazapine?

The only... etc

Thanks for that. I think it's important for anyone considering these options for insomnia to know about the possible differences. I'm wondering also which products you got these medicines in. I know here in canada I commonly see Diphenhydramine in Gravol and other "otc sleep meds". Doxylamine and Cyproheptadine I haven't seen on the shelves though. Maybe I'm missing it?

I'm already using a med that I consider superior for sleep purposes (for me), but, in terms of sleep initiation I may consider one of these OTC as I do believe sleep initiation is one thing I could do better with. Really helps to control that window of time that you have IN and OUT of bed

I'm not sure if this is selective to a particular chemical, but don't antihistamines upregulate adrenergic receptors?

That's what I was thinking, I anecdotally experience some kind of adrenergic rebound; and , if Im not mistaken I thought I saw some paper on what you said but Id have to look into it... (doing thatnow)

Dieters use potent anti-histamine to upregulate beta receptors following clenbuterol usage. I used benedryl as a child and noticed this, I think it's why I was diagnosed with ADHD, i was just too damn wild and could never sleep.

[BlueCloud]

Dieters use potent anti-histamine to upregulate beta receptors following clenbuterol usage. I used benedryl as a child and noticed this, I think it's why I was diagnosed with ADHD, i was just too damn wild and could never sleep.

You mean Diphenhydramine can upregulate noradrenergic receptors ? Do you have a source for that ?

[BlueCloud]

After doing some quick research, all I could find is that some anthistamines ( the H-1 antagonists , like the ones we're mentionning here for insomnia ) have some antagonist action at the alpha-1 adrenergic receptors. Now, being antagonists doesn't necessarily imply that upregulation of those receptors will follow, does it ? Anyone can confirm or deny this ?

I'd really love to get to the heart of this issue, because if it's true, it could explain a lot of things in my case. I've been using antihistamines almost daily for years to this day for my insomnia, and concurently during these years I've constantly failed to find something that gets my chronic anxiety under control ( outside of benzos ). Could it be because of all these years of almost daily upregulation of adrenergic receptors....

[extroverinstinct]

After doing some quick research, all I could find is that some anthistamines ( the H-1 antagonists , like the ones we're mentionning here for insomnia ) have some antagonist action at the alpha-1 adrenergic receptors. Now, being antagonists doesn't necessarily imply that upregulation of those receptors will follow, does it ? Anyone can confirm or deny this ?

I'd really love to get to the heart of this issue, because if it's true, it could explain a lot of things in my case. I've been using antihistamines almost daily for years to this day for my insomnia, and concurently during these years I've constantly failed to find something that gets my chronic anxiety under control ( outside of benzos ). Could it be because of all these years of almost daily upregulation of adrenergic receptors....

Obviously this is anecdotal, but considering the context and considering my prior experience.....well you can come to your own conclusion.

http://forums.steroi...works-clen.html

These are bodybuilders, and as we all know they are serious about their stuff lol.

"These are the oldest H₁-antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic acetylcholine receptor (anticholinergic) antagonists as well. These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor selectivity is the basis of the poor tolerability profile of some of these agents, especially compared with the second-generation H₁-antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes." Thats from wiki, obviously its very ambiguous offering no specifics whatsoever.

"Cationic ampiphylic drugs are known for their ability to inhibit phospholipase A2. Benadryl (diphenhydramine) is a cationic ampiphylic drug.
Ergo, Benadryl slows desensitization of Beta receptors (i.e. Upgrades them) by inhibiting phospholipase A2, which is the enzyme that breaks down methylated phospholipids, and this action in turn keeps the phospholipid membrane stable, and thus keeps the receptors functioning properly. (7). This will allow you to use clen for much longer and it´ll still have the same effects. Also, since Benadryl is an anti-histamine, and histamines have a direct effect on beta-adrenoreceptors (not just Beta-2´s but all of them), using an anti-histamine will have a direct effect on reducing beta-receptor stimulation (16), and thus upregulating your beta-receptors." Another bodybuilder site that doesn't reference statement

BEST THING I FOUND SO FAR

"You must remember that benadryl has anticholinergic properties. It can block the binding of Ach to M2 receptors found in the heart. This would most likely increase the heart rate, which would be detrementalfor a person recently diagnosed with CHF. In addition to this, there could be a drug drug interaction with beta blockers, which are commonly prescribed after a MI.

Beta receptors are embedded in the cell's outer phospholipid membrane. The stability of the membrane has a lot to do with the functionality of the receptors. It turns out that methylation of the phospholipids is stimulated by the binding of beta agonists to their receptors. The body recognizes these methylated phospholipids as foreign, and breaks them down with an enzyme called phospholipase A2. This alters the structure of the outer membrane and results in desensitizaton of the beta receptors (1). Conversely, agents that inhibit phospholipase A2 slow desensitization.

It turns out that cationic ampiphylic drugs are well known for their ability to inhibit phospholipase A2. Ketotifen is a cationic ampiphylic drug, so is diphenhydramine (Benadryl)

Max


(1) Prog Clin Biol Res. 1981;63:383-8.
Phospholipid methylation: a possible mechanism of signal transduction across biomembranes.
Hirata F, Tallman JF, Henneberry RC, Mallorga P, Strittmatter WJ, Axelrod J
http://forums.studen...p/t-244952.html
"

I know many poo poo on anecdotal evidence, I don't when it is reported in large quantities, especially as concerns bodybuilding since there is an actual visibly noticeable effects. If benedryl didn't upregulate beta receptors so some degree the clenbuterol wouldn't work for cutting. All anecdotal reports I have come across so far say that it isn't as effective as ketotifen, which naturally shouldn't suprise us. The last report I posted links benedryl to high blood pressure, something I noticed the morning after using benedryl along with agitation and increased urination.

Sorry if this isn't good enough. I hope the last post is.

As far as your insomnia is concerned have you tried Hesperidin?
Here is a cheap source, for horses, but it is a large quantity for less than buying encapsulated.
http://www.cheshireh...wder-P3090.aspx

Edited by extroverinstinct, 26 October 2013 - 07:44 AM.

[penisbreath]

I'd really love to get to the heart of this issue, because if it's true, it could explain a lot of things in my case. I've been using antihistamines almost daily for years to this day for my insomnia, and concurently during these years I've constantly failed to find something that gets my chronic anxiety under control ( outside of benzos ). Could it be because of all these years of almost daily upregulation of adrenergic receptors....

Yeah, I'm starting to think I might be trapped in a bad cycle of insomnia --> antihistamine --> rebound anxiety/irritability --> exacerbated insomnia --> antihistamine etc.

[BlueCloud]

I know many poo poo on anecdotal evidence, I don't when it is reported in large quantities, especially as concerns bodybuilding since there is an actual visibly noticeable effects. If benedryl didn't upregulate beta receptors so some degree the clenbuterol wouldn't work for cutting. All anecdotal reports I have come across so far say that it isn't as effective as ketotifen, which naturally shouldn't suprise us. The last report I posted links benedryl to high blood pressure, something I noticed the morning after using benedryl along with agitation and increased urination.

It's plausible. I'm still kind of surprised that there aren't any studies linking them directly to upregulation of beta-adrenergic receptors, considering that antihistamines are old substances, and have been extensively studied. But it remains a plausible thing. I guess all I can do is completely stop taking them for a while and see if it has any impact on my anxiety issues.
At the moment I'm taking buspirone at night and it's a decent help for sleep, albeit not as efficient as the antihistamines.

As far as your insomnia is concerned have you tried Hesperidin?
Here is a cheap source, for horses, but it is a large quantity for less than buying encapsulated.
http://www.cheshireh...wder-P3090.aspx

mmm... I'm not sure about the purity of that for human consumption, but anyways, I've tried hesperidine in the past ( it's sold OTC here for hemorroids bouts ) and haven't noticed any sedative aspect.

[extroverinstinct]

I know many poo poo on anecdotal evidence, I don't when it is reported in large quantities, especially as concerns bodybuilding since there is an actual visibly noticeable effects. If benedryl didn't upregulate beta receptors so some degree the clenbuterol wouldn't work for cutting. All anecdotal reports I have come across so far say that it isn't as effective as ketotifen, which naturally shouldn't suprise us. The last report I posted links benedryl to high blood pressure, something I noticed the morning after using benedryl along with agitation and increased urination.

It's plausible. I'm still kind of surprised that there aren't any studies linking them directly to upregulation of beta-adrenergic receptors, considering that antihistamines are old substances, and have been extensively studied. But it remains a plausible thing. I guess all I can do is completely stop taking them for a while and see if it has any impact on my anxiety issues.
At the moment I'm taking buspirone at night and it's a decent help for sleep, albeit not as efficient as the antihistamines.

As far as your insomnia is concerned have you tried Hesperidin?
Here is a cheap source, for horses, but it is a large quantity for less than buying encapsulated.
http://www.cheshireh...wder-P3090.aspx

mmm... I'm not sure about the purity of that for human consumption, but anyways, I've tried hesperidine in the past ( it's sold OTC here for hemorroids bouts ) and haven't noticed any sedative aspect.

Equine products are pretty straigtforward, and expensive. Imagine making a "dirty" product and getting sued for millions because a race horse just kicked the bucket lol. I checked ingredients on other sites and it is pure, whether that is a lie.....I can't tell you. I use a few "made for pet" prodcuts and have been happy with them so far although they have all been on the more expensive end of the spectrum.

I'm not surprised there aren't any long term studies on anti-histamine BECAUSE they are old. My guess is some are so old they were grandfathered in, not sure though. I do know, after having seen them used in clinical setting, they can seriously screw with memory and causes agigatation the day after in Elderly. I would steer clear of them if I were you. There are tons of natural or safe anti-histamines on the market that don't cause those side effects.

The fact that you noticed no sedation from Hesperidin makes me wonder if maybe you have a problem with your serotonin receptors or production.

I know some people have serious issues with Idenone orally, I'm wondering if you might be a candidate for my method of administration. Figure out your dose then find some jojoba oil and measure mg idebenone for about 30ml oil., then mix idebenone in Jojoba oil, put in a warm car for about a week at which time it should be fully dissolved and clear orange. Rub 1ml on over jugular vein semi roughly.

If you are sure you are producing enough serotonin and /or don't think you have any issues with serotonin this isn't really necessary.