What is the mechanism by which paracetamol improves sleep?

[mh586]

45+ old male sleep maintenance issues for couple of years resolved by fixing the basics- blacked out room, avoiding alcohol and coffee having the biggest effect. Still even if I am able to sleep 8 hours the sleep is not as restorative as I would expect.

Recently I have noted that 500mg paracetamol (tylenol, acetaminophen ) result in truly excellent restorative sleep.

My question is: what could be the mechanism involved? What hormones are affected by paracetamol that have relevance to sleep?

I would like to modify my diet/lifestyle further to get this type of sleep without the drug.
Normal weight, fighting mild gastrointestinal and dermatological issues that indicate autoimmunity and allergies, on paleo diet since 6 years if that is in any way relevant. I have no pain the drug would help me with.

[Michael R]

Hi mh,
 
Welcome to the CR Society Forums.
 

45+ old male sleep maintenance issues for couple of years ...

Recently I have noted that 500mg paracetamol (tylenol, acetaminophen ) result in truly excellent restorative sleep.

My question is: what could be the mechanism involved? ...

Normal weight, fighting mild gastrointestinal and dermatological issues that indicate autoimmunity and allergies, on paleo diet since 6 years if that is in any way relevant. I have no pain the drug would help me with.

The first thing I would say is that you've just indicated a possible mechanism. Acetaminophen is a predominantly central-acting COX inhibitor, and may be dampening down some inflammatory problem in your brain that is interfering with your sleep.

 

I would point you at PMID: 24398053, which outlines the design of a projected or ongoing clinical trial of the question for a few more tentative hypotheses:

 

 

In geriatric clinical practice, we have noticed that older patients use acetaminophen for sleep problems without having underlying pain complaints. In a survey of 176 older people, 48% stated that they used nonprescription products for sleeping problems. Of [these] ... 19% used acetaminophen [16]. Although we did not find any trials or observational studies in the literature that report the effect of acetaminophen on sleep disorders, there are some ideas as to why this medication might have a positive effect. People who sleep better on acetaminophen may have unrecognized pain complaints. Another possible hypothesis is that acetaminophen, after metabolization in the brain, reinforces the activity of the cannabinoid receptors, which in turn reinforce the activity of the serotonergic system [17, 18]. Also, there may be a relationship with body temperature [19], or its purported effect could be mainly placebo.

 

Have a look also at these papers. I note the 1969 trial that found "Paracetamol had no effect on the mean sleep interval or mean urine volume although the drug was not totally inactive since it increased the variance of the results for sleep interval and urine volume." I wonder if you have nocturnal need to urinate which is being reduced in urgency or delayed, allowing you to better complete a sleep cycle, eg.

 

Be careful, of course, about liver toxicity. In the sleep context: the full text of PMID: 19144748 is available; it summarizes and comments on a rodent study finding that acetaminophen plus intermittent hypoxia (intended to simulate obstructive sleep apena) led to liver injury, when neither alone did.

[mh586]

The first thing I would say is that you've just indicated a possible mechanism. Acetaminophen is a predominantly central-acting COX inhibitor, and may be dampening down some inflammatory problem in your brain that is interfering with your sleep.

 

Excellent answer, many thanks for that, I wonder how to start looking what the inflammatory problem could be.

 

Not the greatist thing to learn that geriatric clinical practice applies to me but that's life I gues :-)

 

I wonder if you have nocturnal need to urinate which is being reduced in urgency or delayed, allowing you to better complete a sleep cycle, eg.

Likely not my case, not drinking after 17:00 is part of my sleep improvement practice.

[mh586]

I read that all NSAID are COX inhibitors but I get this effect only from paracetamol.

[Michael R]

Yes, but that's a very broad generalization. Aspirin and ibuprofen are nonselective for COX-1 and COX2 isoforms, and active to varying degrees everywhere. Celebrex and Vioxx are selective for COX-2 and similarly largely active in all tissues. Paracetomol, as I said, is centrally-acting, which is why it's no good for peripheral inflammation, and there's some debate that it may also be selective for a CNS-specific COX-3 isoform.