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?