Treating Insomnia With Less
Most people think of sleep as the opposite of wakefulness, a line with two poles, you slide the switch back and forth.
In fact, there are two regions in the brain, working at the same time. A wakefulness promoting region, and a sleep promoting region, battling each other, and your mind, for supremacy.
Simply as a convenience to me for the purposes of writing this post, I'll call the "wakefulness promoting region" the tuberomammillary nucleus, and the "sleep promoting region" the ventrolateral preoptic area of the hypothalamus.
Explain yourself.
The TMN sends histamine projections all over the cortex. Histamine causes arousal, increased attention, perhaps increased learning and memory. All of these are good and holy things. Antihistamines are competitive blockers of H1 receptors; they block the histamine from binding and thus prevent arousal, etc. They are thus the work of Satan.
The VLPO sends inhibitory GABA projections everywhere to turn down/off places which are aroused by projections from the TMN. It also sends projections to the TMN itself, to turn it down/off, to Dark City you.
GABA agonists-- benzodiazepines like Xanax, Ativan, Restoril, and the "non-benzo" Ambien and Sonata type, and alcohol, delicious, delicious, alcohol, all work this way.
I like Xanax.
No doubt.
Is there a difference in the quality of sleep?
No, not really, individual results may vary but the main difference is how you feel when you wake up.
The problem with these GABA agents is that no matter how aroused you try to make yourself (through the TMN, coffee, or porn) you still have the effect of the drug lingering in your body. Hence, you can be an "awake drunk" or a "caffeinated masturbator." People may feel completely refreshed after 8 hours of sleep with Ambien yet still have decreased reaction times and impaired cognition as a result of the Ambien. It probably is mild enough not to be relevant unless you get up really early to perform surgery, but such people would never dream of getting drunk the night before or taking an Ambien. Right?
And the longer the half life of the drug, the longer it is in your body, the longer the effect is there (again, even if not obviously apparent.)
If, however, you are on a pure H1 blocker, then you could simply release more histamine (e.g. wake yourself up) to displace the drug from the receptor. An H1 blocker may be the way to go if you perhaps have to get up suddenly in the middle of the night.
I tried antihistamines like Benadryl, and they don't work. In fact, they make me feel wired.
Ah, many people have this reaction. You'd be surprised to learn that this is due to, and a screen for, very low levels of testosterone.
What?!
Psyche.
The real reason is that it isn't actually an antihistamine. That's misleading.
What do you mean, misleading?
You know how I hate the FDA, and most everyone else in the world, because they use words to distort the truth, and get girls to sleep with them that would never sleep with me?
What?!
Pay attention.
Here is the affinity chart for Benadryl:
(from CNS Spectrums)
The drug has the most affinity for H1 receptors, sure, but look what else it does. M1 blockade (dry mouth, constipation, confusion.) It also has significant NE and serotonin reuptake blockade. Basically, the FDA decided to pick only one of these four properties and slap it on the box, in the same way as labeling a TV dinner as "Rice."
You'll also observe that it looks like it works the same way as Effexor or a tricyclic. You'd be right. Think about that.
So every time I take Benadryl, it's an antidepressant?
Depends on the dose.
If you eat all of this TV DINNER, you'll be getting several foods. But if you only take one single fork of the rice, then the only thing you ate was rice, even though the box says, "TV DINNER."
If you only take a low dose of Benadryl, then you are only getting H1 blockade. If you take a medium dose, then you are eating only the rice (H1 blockade) and the cogentin (M1 blockade.) A high dose gets you all of the TV DINNER and receptors blocked (and also a heart attack-- hey, the analogy holds!)
If you imagine that the drug prefers H1>M1>NET>a1>5HTT, then you see that the mistake most people make with Benadryl is that they increase the dose when if doesn't work. What you really want to do is decrease the dose, to get away from all the other things that could be stimulating (serotonin, NE, anticholinergic.)
What about Trazodone? Elavil?
Highest bar=highest affinity= "happens at lower doses."
Trazodone works best around 50, not 25, because he first thing trazodone gets you (at the lower doses) is serotonin, not H1 blockade.
Elavil is not a good choice, because there's really no way to dose low enough that you'll avoid the other stuff (serotonin.)
So what's the best?
The best is tiny doses of Remeron (3.25-7.5mg) or doxepin (1-5mg).
I took Doxepin all the way up to 200mg, it did nothing except give me dry mouth.
Doubling the dose is not twice the sleep, it is the addition of entirely new drugs (receptor systems.) 3mg of Doxepin is 3mg pure H1 blockade. 100mg of Doxepin is 6mg H1 blockade, and some Cogentin (M1), Effexor (S/N) and Hytrin (a1).
You're saying less of these sleeping pills make you sleep better?
It's not just less. It is taking only a certain kind of receptor system, and avoiding others which wake you up.
What do you use to sleep?
January 14, 2009 12:43 PM | Posted by : | Reply
So if Benadryl is as effective as say opium in getting me to sleep does that mean I have high testosterone?
I only ask because I'm a female and I've always explained the excesses hair away to being Italian.
January 14, 2009 1:10 PM | Posted by : | Reply
This is why I come to this site several times a week. Please write more of these fact-based posts and less ranting on narcissism/pop culture.
January 14, 2009 2:05 PM | Posted by : | Reply
Good stuff. Out of curiosity, how does alcohol(my sleep drug of choice) work in relation to these other drugs?
January 14, 2009 2:11 PM | Posted by : | Reply
Don't listen to him, your posts on narcissism are excellent. However, this was incredibly interesting to a former insomniac like me. Great post.
January 14, 2009 2:12 PM | Posted by : | Reply
Agreed with the poster above.
Question: what is your take on the newer drugs that tackle melatonin receptors?
January 14, 2009 2:59 PM | Posted by : | Reply
Do you have any evidence to support your belief that altering the dosage strength of Benadryl can turn a stimulant into a sedative? I would be inclined to believe that response to Benadryl has more to do with one’s individual neurotransmitter/receptor situation rather than strength of dose. People who have lots of histamine and garbage fore ne/serotonin are probably going to experience awesome sleep from it, whereas people who are the reverse will be wired up.
Yes, less of a drug will affects stimulatory receptors less, but it will also affect inhibitory receptors less. It’s possible to feel both sleepy as well as stimulated and awake. Trust me. There is a difference between type and volume. You can have blue and red together side by side, and you can have faded blue/red and you can have bold blue/red. I would think that for people who do not respond to Benadryl with sleep, less Benadryl is only going to create a faded blue/red situation, because the nature of their brain is such that they have lots of stimulation potential for Benadryl to work effectively. Using more is going to create more intensity of the symptoms, and since the complaint is insomnia all they will report is the awful keyed up feeling.
When I was suffering from really bad insomnia during my first year of RN school Benadryl was one of the only things that worked. Ambien didn’t help at all, it just made me more tired physically and wiped my memory. I am sure that I don’t have much potential to become overstimulated from serotonin and NE. At the time I was chronically depressive.
Alcohol has never worked as a sedative for me. Drinking always seems to bring me to a “baseline” state, if I am wired and energetic it can mellow me out, if I’m low and down it will wire me up in a happy way, but it never promotes sleep specifically like it does for other people. Then again my father is an alcoholic, and I suspect I am some type of bipolar so that might be why.
For my own situation I relate insomnia very strongly to cortisol levels, and possibly some dopamine dominance vs serotonin suppression thing.
Evidence for this is the fact that during the luteal phase of my menstrual cycle I will have a return of terrible insomnia, even though I feel very tired and sedated. Progesterone increases GABA (results: stable mood, lethargy, desire to sleep) but it also increases cortisol and dopamine and blocks serotonin-enhancing estrogen (result: insomnia and depression). The insomnia correlates well with the peak of progesterone (thus cortisol) … progesterone dominance basically.
So because of how progesterone increases GABA while at the same time screwing other crap up that makes you awake, it is pretty much the hormone of the devil because you’re tired and listless but are unable to fall or sustain sleep.
The exact OPPOSITE situation occurs during the follicular phase and periovulation. I can tell when I am close to ovulating because suddenly I have very easy and deep dreamful sleep (serotonin/estrogen). This is the first change I observe and it relates to an early sign of more available serotonin (which becomes melatonin, and also deals with excess cortisol)
Eventually mood becomes less stable and I experience hypomanic symptoms (e.g. getting into laughing fits, running down the block dancing, very racy thoughts and uncontrollable energy). A quick study on estrogen shows it is basically a mania-promoting hormone if there ever was one – increasing PKC, serotonin, norepinephrine, dopamine receptor sensitivity, MAO, less GABA, etc.
I find myself in a peculiar situation where I no longer need to sleep or want to sleep but my ability to sleep is actually a lot better/restful. NATURE IS FUNNY LIKE THAT.
Anyway, based on my own experiences and what I know about them I wonder why there isn’t more attention paid to cortisol in its effect on the brain to promote insomnia. Some type of cortisol blocker or modifier is probably going to be the most effective insomnia drug there is considering my insomnia predictably relates to peaks in it.
January 14, 2009 2:59 PM | Posted by : | Reply
Can you give us a histamine-blocking table? 25mg of Vistaril is how much histamine blocking compared to 25mg Seroquel or 25mg of benadryl or 5mg of Zyprexa, and so on. Most of the receptor affinitiy information compares the histamine to other receptors of that same drug, not histamine affinity compared to different drugs. Thanks.
January 14, 2009 3:35 PM | Posted by : | Reply
Excellent and very informative article, as well as the one linked to at the end.
And I too agree that the posts on narcissism are excellent. I don't understand why people read blogs and then think a) they can dictate the content, and b) just want to read things that conforms to their world view. The comfort of stagnation without having to be challenged by competing ideas is alluring I guess.
January 14, 2009 5:01 PM | Posted by : | Reply
Some people are sensing judgers, others are intuitive perceivers. The classic INTP is excited by new ideas, because those ideas lead to new questions/and ideas which lead to more.
Sensing judgers just want to know what they need to know to accomplish their goals. Like, ya know, give him the useful information about drug dosing to combat insomnia... the blatherings about narcissism and culture less so.
January 14, 2009 7:15 PM | Posted by : | Reply
and fwiw, 50mg benadryl knocks me out almost as well 3mg lunesta. which is sometimes unfortunate, as i take it most often for allergy flare-ups (of the "these sneezes are causing muscle cramps in my arms" variety), and passing out is frowned upon at work.
January 14, 2009 7:57 PM | Posted by : | Reply
Thank you for a very good article!
My sleep cycle gets screwed up very easily (e.g. by flying across 8 time zones, or by being north of the Arctic circle for a couple of days, or even just by short, dark, overcast days like we have here in the UK at the moment). It's relatively easily fixed by a burst of very bright artificial light at dawn, and avoiding bright artificial light sources (like computer screens...) after dusk.
January 14, 2009 8:56 PM | Posted by : | Reply
FWIW, I'm somewhat of an insomniac. I've read it takes the average adult 7 minutes to get to sleep. For me, it's more like 30 minutes to an hour, or even 2. But I've just had a St. Bernadus Witte, a Sierra Nevada Chico, a Bear Republic Big Black Stout, a Victory Donnybrook stout, and two shots of Knob Creek, and I'm going to recommend the alcohol.
January 14, 2009 10:16 PM | Posted by : | Reply
I gave benadryl to my dog on the recommendation of his veterinarian for his allergies. Benadryl has never made me sleep. I've taken it a couple of times after insect stings since I once had an Anaphylactic reaction to an unseen bug that bit me and never had any drowsiness, but I noticed that the vet's recommended dose for my dog was much higher than the dose for humans and tried the higher dosage for insomnia. I've done this a couple of times. Each time I get horrible foot cramps which keep me up, but then I do wake up in the morning apparently not remembering falling asleep in spite of the foot pain. The foot pain however is so bad I'm not trying this again, but I wonder, do you have any ideas on why the benadryl makes my feet hurt?
January 15, 2009 10:03 AM | Posted by : | Reply
The dog question is interesting. When I adopted my 20 lb, 10-year-old shih tzu, she was always scratching, and not from fleas. The foster-dog mom said the dog probably had undiagnosed allergies. The foster mom was giving 1 to 2 benadryls a day (typical dose 50mg - the human one, not some brand repackaged for dogs). I was astonished. But because of the incessant scratching, I was giving 1-2 per day, which helped somewhat. The dog's alertness, energy level, and time spent sleeping seemed about the same whether on zero, 1, or 2 tabs. I was afraid to go to 3.
Of course, the dog couldn't drive anyway, because she is blind, but I could not understand how a dog could handle, pound-for-pound, 7 times the dose that would make me very sleepy.
(Follow-up: I did a rotation diet and isolated wheat as the allergen. So I get wheat-free dog food, and problem solved).
The dog brain must be different. In more ways than are readily apparent (sniffing butts, licking vomit, etc.).
January 15, 2009 10:51 AM | Posted by : | Reply
A number of useful new things learned! First time I'd heard that there was a positive function to histamine; learned why dosage level is so important. Learned that a patient adjusting his/her own medication level could be a really, really bad thing.
Learned that you read your Tolkein, you don't just watch the movies. Fire, foes, AWAKE indeed! LOTR reference FTW.
January 16, 2009 1:57 AM | Posted by : | Reply
I've never understood the idea of feeding dogs wheat and corn. If there's anything the Atkins diet should apply to....
January 16, 2009 4:21 AM | Posted by : | Reply
Interesting... but I am confused by the part where you say if you take a low amount of a drug then it only does one thing, but if you take more then it does that thing plus other things... is there a minimmum dose for certain receptors? Is it the "relative selectivity" that I am confused about?
January 16, 2009 4:33 AM | Posted by : | Reply
Ah ok I found the "The Most Important Article On Psychiatry You Will Ever Read" article and I think I get the idea a bit better
January 16, 2009 9:34 AM | Posted by : | Reply
Feeding dogs: I have no idea what you should optimally feed a dog. I know that an Atkins diet would be expensive compared to dog-food from a bag. My previous dog lived to 17 years of age on Science Diet fortified with table scraps. She had surgery for doggie breast cancer (never had pups so was probably at elevated risk) when she was 10, so she was a doggie breast cancer survivor for 7 years, living on that bag dog food. I have no idea what is in science diet. I chose it mostly because the 'stool' was manageable, compared to cheaper dog food. I chose my current dog food based on the fact that it is not difficult to find, plus it has no wheat. I also have a cat (well, it is the daughter's cat) and we choose cat food because it has no wheat (the blind dog can follow the nose). Everybody is healthy and happy. What's that? Stay on topic? OK. Benadryl makes me sleepy but the same dose does not make my dog sleepy.
January 16, 2009 9:38 AM | Posted by : | Reply
"Please write more of these fact-based posts and less ranting on narcissism." Or, how about combining the sleep topic with narcissism. Like: add narcolepsy and narcissism and you get narcolepcissm. A person who sleeps in front of a mirror.
January 16, 2009 11:04 AM | Posted, in reply to , by : | Reply
I have a preference for vanilla, and I will always eat it before chocolate...but when the vanilla is gone, I will eat the chocolate.
January 16, 2009 12:11 PM | Posted by : | Reply
Interesting topic. As someone with Sleep apnea and RLS I never have problems falling asleep. My battle is to stay awake. Thank God for Provigil.
January 16, 2009 12:22 PM | Posted by : | Reply
I struggled for many years with insomnia. I tried every over-the-counter and prescpition med available. I even tried benzos and eventually opiates to cure my sleep issues. I was finally able to overcome through natural methods. Today I sleep better then I ever have without a single drug. It is possible.
January 17, 2009 1:22 PM | Posted by : | Reply
Thanks for this post ... to me, not having the background, you really lay out a perspective that makes sense. The writing is delightful ... elegant and humorous. We should always be so lucky.
My only problem with narcissism being illustrated by tv characters has to do with my antipathy towards television and my feeling that your (excellent) approach is better illustrated writing "from the ground up." No need to resort to TV characters. In addition, it's just too popular-culture tacky. And, as this opinion comes from me, it obviously is true. So please take heed.
January 17, 2009 2:06 PM | Posted by : | Reply
Timely article for me. I took 10mgs Doxepin over the past week and it did nothing. After I took it at night it was as though I had taken nothing, or maybe even worse than nothing. I was wide awake most of the night all week.
Prior to that I was taking 100mgs Trazadone to no avail...still was wide awake most of the night. The only thing that seems to help me sleep is 15-20mgs Valium along with 1000mgs Tegretol, but even the Valium stops working after a while...so I went off it once again and have been trying to find something else...very frustrating.
January 21, 2009 10:07 AM | Posted by : | Reply
Spot on about the Remeron. Whether you want it or not, it's lights out, often quite suddenly. Fun to try waking up from, too, given its half-life.
January 21, 2009 1:38 PM | Posted by : | Reply
This article (and the linked article) have changed my life. I was never taught these concepts and to have them so clearly and entertainingly presented was a thoroughly enjoyable revelation. Please keep doing what you're doing! THANKS!
March 1, 2009 7:32 AM | Posted by : | Reply
Though previously well acquainted with the sleep hygiene bull this cardiologist/sleep doc was convinced was my problem, zolpidem changed my life.
When you lie awake in bed until 4 and get up at 6, spend your classes trying not to fall asleep and end up with projectile eraser marks on the side of your head (I repeat, no sleep hygiene suggestions helped), become severely depressed because your interminable waking moments are all miserable and your mood is miserable due to lack of sleep as well as humiliation in class and academic failings, and can't remember to take your thyroid drugs because you'd be considered low-functioning even if you were an eggplant...
I personally would suffer through decreased reaction times and impaired cognition. Or perhaps, less than maximum reaction times and cognition, as they were all greatly increased. I'm actually one of the living these days. Instead of being a drooling zombie, I can hold down an 8-7 thinking-intensive job. (I don't take it on weekends and end up lying awake until 3 even with my normalized 12-7 sleep schedule during the week.)
I do feel like there could be some significant memory effects, but it's all really muddy since the doc who finally prescribed me zolpidem also made my thyroid go away around the same time. And up until that point it had been mostly taken over by tumor, so I don't have a freakin clue how my baseline "normal" is supposed to feel.
The zolpidem already once stopped being effective after 2 years and I fear it will happen again (temazepam was totally ineffective), so I'll try to remember this post. Until then, you'd have to wait until I'm drugged before you could pry it from me, and even then I'll likely have a death grip.
May 12, 2009 4:22 PM | Posted by : | Reply
"The dog brain must be different. In more ways than are readily apparent (sniffing butts, licking vomit, etc.)."
The drug was developed for human HT1 receptors. It probably has a lower affinity for canine receptors. The activity against the other receptors probably tracks with that. Hence a higher dose being required and tolerated.
September 28, 2011 12:15 AM | Posted by : | Reply
Going to try some of the other ideas in this forum. Shoulder replacement pain wakes me or keeps me up most nights. Ambien has been a godsend for years first 5s then 10s. Most recently I am taking CRs 12.5 I think. For me, it's much more difficult to fall asleep with CRs but once asleep, the quality of rest seems good. No doubt I am loosing cognative and other upper (lower?) brain functionalities but a good nights sleep is tops for me. I plan on trying some other therapies after studying up a bit but for now, the most effective ambien dose for me is a half of a regular ambien and a whole CR taken together at bedtime. When i don't fall a sleep quickly, i get to read interesting and embarrassing emails and facebook posts in the morningwhich I have no recollection writing. Sometimes I sleepwalk and have no knowlege of doing it but only while taking CR. Good luck all with the zzzzz's and I hope to learn a lot in this forum
November 18, 2011 1:32 AM | Posted, in reply to , by : | Reply
I just stumbled onto this article, so I apologize for responding out of the blue!
When talking to my vet, I found out that dogs require a higher dose per pound of body weight than humans. The proper Benadryl dosage for a 40-lb human child is 1/2 a capsule (12.5-mg), whereas the dosage the vet recommended for my 37-lb dog was 1 1/2 to 2 capsules (37.5 to 50-mg).
So a human upping their dose to match that of an equivalent-weight dog would get a much higher dose than needed, and that would likely exacerbate the insomnia and the other side-effects.
June 12, 2013 12:20 PM | Posted by : | Reply
I realize this is a couple of years after these postings but thought I would ask about tolerance development. I develop a tolerance to all of the BZD effectors within 5-7 days and have to increase the dosage - for antihistamines tolerance to the sleep effects occurs within 2-4 days. I have almost no tolerance at the beginning of the drug intake and usually cut it back to 1-2 mgs and then within 3-4 days I am at the prescribed dosage and after 7 they stop working. I convinced my sleep Dr. to allow me to give me several BZD, Z and sedating ADs and it is always the same for each. I developed a rotationary strategy of taking 1 of each per day per week and it stretched the tolerance development to 4-5 months. I am in the middle of a Gaba effector vacation and taking the antihistamines and ADs (doxepin and mirtazapine) but the sedating effects drop fast. I have read about cell down regulation but really do not understand such fast tolerance development. Unfortunately many of the older classes of drugs are falling off the market and limiting choices for this type of rotational strategy. I am living in hope that the orexin effectors will help - or at least add something to the rotation if I develop tolerance to this as well. But the first is still 6 months away from approval.
July 14, 2013 5:10 PM | Posted by : | Reply
It seems like maybe you don't respond to comments... and this was posted a long time ago... nevertheless, I feel compelled to ask - you seem to advise Doxepin and Mirtazapine but both drugs are listed with rather long half-lives. Are they actually a practical solution, or just an armchair solution to pounding on the H1 receptor?
December 19, 2013 2:26 AM | Posted by : | Reply
Way to take information you don't even understand and just start tenuously connecting bits and pieces together to look like you know what you're talking about.
It IS an antihistamine because that is the only effect it has at the recommended therapeutic dose because there is a required minimum blood serum concentration for the given chemical to exert its effects at a receptor.
"thelastpsychiatrist", christ you're thick...
December 19, 2013 9:11 AM | Posted, in reply to , by : | Reply
"When you find yourself hating someone (who did not directly hurt you) with blinding rage, know for certain that it is not the person you hate at all, but rather something about them that threatens your identity."
Don't get so worked up over something so silly, silly.
April 15, 2014 10:17 PM | Posted by : | Reply
BENADRYL IS THE ONLY HELPFUL MEDICATION FOR SLEEP.
40 YEARS TAKING THIS ITEM IS PROOF ENOUGH FOR ME.
MY CARDIOLOGIST TOLD ME THAT HE TAKES BENADRYL 25 MG AND AN HERB FOR SLEEP. HOW CAN I GO WRONG.
July 14, 2014 9:39 PM | Posted by : | Reply
Question for the lat psychiatrist..I read that it is acting like antihistamines at small dosage being strong H1 and 5 HT receptor antagonist ...can it stop to be effective after a while? Then is there is any concern that these receptor may take long time to return to normal?
Thanks for your answer
January 16, 2015 3:10 PM | Posted by : | Reply
I have been battling insomnia for years...
I have tried mirtazapine at low dosages of 3,25mg and I got side effects! Twitching muscles falling asleep. Something like PLMD.
I have tried doxepin low dosage and I got exactly the same.
I have tried 25mg trazodone and I don't have this problem (neither at higher dosages such as 75mg).
I have tried Hydroxyzine at 12,5mg, today will be my 3rd night only, and I seem not to have this problem, or if i have its such a low intensity that it doesn't bother me.
Would this side effect be connected to H1 blocking?! Or Muscarinic 1 or higher serotonin/lower dopamine ?
Also, how can I find the binding affinities for Hydroxyzine?
Thanks a lot! I loved these articles, they gave me lots of insight on how it works...



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