Tylenol Versus CBD - The Pain Connection

by Indigo Naturals February 09, 2019

It started with a question...can CBD be taken with Tylenol?

It's a common one we get.

While investigating what NIH research had to say on the matter, we fell down the veritable rabbit hole.

We found so much more about the two!

Just in time.

An estimated 23% of Americans take Tylenol at least once a week.

That's 74 million people!

You're not going to believe the connection between Tylenol and CBD.

It's going to have you asking an entirely different question altogether.

Why this isn't the biggest health story is beyond us.

Let's look at what research has to say about acetaminophen (such as brand-name Tylenol) and CBD oil.

The reason people are taking the two is pretty obvious.

Pain!

We'll look at the effectiveness of both as well as any negatives.

Most importantly, we'll see what research says about how they may interact.

We're going to dive into the science behind how both CBD and Tylenol work in the body.

You may be surprised!

Not a second too early.

In 2015, it was estimated by NIH that 25 million Americans suffer from chronic pain (pain once a day for the last 3 months).

In 2018, the CDC estimated it at 50 million!

Is the opioid crisis so surprising?

We're also going to look at the lady who can't feel pain EVER because of a genetic mutation in a chemical CBD directly affects. More later.

We'll cover these different topics:

How Tylenol and CBD work for pain (so exciting!)
Health concerns of either Tylenol or CBD
The liver and Tylenol and CBD
Can you mix Tylenol and CBD
Long term use of Tylenol or CBD
The weird sleep effect of Tylenol PM and CBD

How Tylenol and CBD work for pain

We'll start with CBD for a very specific reason (becomes clear later)

We have a massive review of CBD and pain here with a focus on NSAIDs.

The mechanisms of CBD for pain are pretty well established.

It helps to boost the endocannabinoid system which we all have in our body.

There are receptors on almost every type of cell that make up this system.

They come in two flavors:

CB1- mainly in the brain
CB2- mainly in the body with a focus on the immune and endocrine system (hormones)

CBD causes it's pain reduction effects in two ways:

It is a powerful anti-inflammatory
It reduces the "feeling" of pain

Inflammation is a definite source of pain in the body.

The obvious results of inflammation are such things as swelling, irritation, and localized pain (such as a site of injury).

That's not all though.

Arthritic pain (and other sources of pain where the immune system attacks us) is also governed by inflammation.

Keep in mind that our immune system really manages inflammation and pain response.

Finally, what does inflammation of our nerves or nervous system feel like?

It can run from obvious discomfort all the way to neuropathy and even effects such as anxiety or depression (inflammation in the brain!)

The endocannabinoid system helps to manage ALL these pathways of pain.

CBD directly supports this system.

You can learn all about CBD and pain here.

Just a few examples of how CBD addresses all the facets of pain...

First, it reduces the sensation of pain (the nociceptive pathway)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/

Secondly, it reduces inflammatory pain:

Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration and thickening of the synovial membrane in a dose-dependent manner.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/

Finally, it lessens neurological pain:

CBD significantly suppressed chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371734/

That's CBD.

It works through the endocannabinoid system which governs our pain threshold, pain sensation, and inflammatory response (think arthritis, IBS, Crohn's, MS, etc).

What about Tylenol?

The search for Tylenol's effect on pain has been long, confusing, and in the end...very interesting.

If you really want to geek out on Tylenol's history and effect in the body:

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2710.2009.01143.x

By mistake, researchers eventually stumbled on its anti-fever effects.

Conflicting results and different theories of how it works then followed.

There are some effects on the COX pathway which creates inflammation in the body.

You've heard of Cox inhibitors by their brand names:

OTC - Motrin, Aleve, Advil
Prescription - Celebrex

Tylenol shows conflicting effects on the COX pathway (1,2, and 3).

Some different pathways showed similarly mixed results in research.

Finally...the endocannabinoid system.

Yes, the very one that CBD boosts above!

The endocannabinoid system has recently been proposed to be involved in the mechanism of analgesic action of paracetamol.

Paracetamol is just another name for Tylenol.

The piece de la resistance (sorry, my mom's French):

Acetaminophen’s analgesic properties are blocked by the administration of CB1 receptor antagonists at doses that inhibit known CB1 receptor agonists.

This basically says that Tylenol was unable to affect pain in mice where their endocannabinoid receptor was knocked out genetically!

Don't you feel like Sherlock right about now!

As for that COX connection below (throw Celebrex in there), it turns out that they may also use the endocannabinoid system to reduce pain:

All the NSAIDs that inhibit COX2 can influence the cannabinoid system

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056416/

Basically, they block FAAH which itself, increases potential pain sensation.

Okay...this is getting crazy.

FAAH breaks down our two principle endocannabinoids! Guess what CBD does to it?

It inhibits or blocks it!

CBD inhibits FAAH more potently than the (+)-enantiomer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573017/#bib8

All the Tylenol and Advils and even Celebrex's of the world may cause their effects via this one system.

Leave it to scientist to zoom in closer and closer:

Acetaminophen Relieves Inflammatory Pain through CB1 Cannabinoid Receptors in the Rostral Ventromedial Medulla

https://www.ncbi.nlm.nih.gov/pubmed/29167401

First, at your next dinner party, drop the old "Rostral Ventromedial Medulla" on them.

Next, explain to them what they do.

They are characterized by their response to nociceptive input.

So, it's where pain is processed in the brain. Via a CB1 (endocannabinoid receptor).

We rest our case.

We promised to talk about the woman who can't feel pain (or anxiety or depression).

She has a very uncommon mutation on her FAAH gene where she doesn't make much of it.

This allows her anandamide levels (the so-called "bliss" molecule) to rise very high.

You can learn all about her here but the net-net is this...

CBD reduces levels of FAAH!

Back to Tylenol.

The problem is that this class of pain relievers has lots of very serious knock effects.

CBD doesn't!

It's not a hammer on a given pathway.

Let's see how this avoids very serious consequences.

Health concerns of either Tylenol or CBD

Again, we'll start with CBD since it's such a simpler list.

The safety profile for CBD is very strong.

You can learn all about CBD's safety here.

The common side effects are:

Dry mouth
Lower blood pressure
Drowsiness (dependent on sleep/wake cycle - more here)
Lightheadedness (likely due to lower blood pressure if you already have low blood pressure)

The research shows it is well-tolerated especially compared to the alternatives:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/

Read below on the interaction with CBD and other medications (including Tylenol).

What about Tylenol?

Oh, it's just the leading cause of liver failure and ER visits in the US.

SO there's THAT.

Tylenol basically exhausts a pathway in the liver (uses up glutathione) which creates a toxin in the liver.

https://www.ncbi.nlm.nih.gov/books/NBK441917/

In fact, check out what CBD does for glutathione or CBD on oxidative stress.

If anything, CBD may help to protect from damage of Tylenol in the liver. We looked at CBD and gut damage for aspirin here.

If anything, CBD isolate is a tool to protect the gut from damage by Tylenol and NSAIDs.

That's just the start.

Many studies have looked at the impact of taking Tylenol while pregnant on the babies.

Tylenol has been shown to affect hormones in the bodies.

In fact, in one Danish study, boys born to mothers who used Tylenol and other NSAID"s had a 43% higher chance of having undescended testicles.

Another study found that children born to mothers who used these medications during pregnancy had a higher risk of ADHD and autism.

This was further explored by another study:

Acetaminophen disrupts memory in object recognition and increases extracellular signal-regulated kinase phosphorylation in male mice.

https://ehp.niehs.nih.gov/doi/full/10.1289/EHP2478

We need more research but impacts on hormones are showing in the research.

That's just the beginning.

The real issue is with the chronic use of Tylenol and other NSAIDs.

There, the issue is with increased blood pressure, gastrointestinal bleeding, and more.

The body is complicated. The brain, even more so!

In a rat study, Tylenol was shown to reduce empathy responses:

In this study, we also showed that acetaminophen decreased oxytocin and vasopressin levels in the prefrontal cortex and amygdala.

https://www.ncbi.nlm.nih.gov/pubmed/30359628

Oxytocin is our social bonding chemical in the brain!

Vasopressin is very important for blood pressure and sexual response (among other things).

These are both powerful hormones.

Check out CBD and orgasm as an example

By the way, the endocannabinoid system above helps to balance the endocrine system (responsible for hormones).

We'll leave you with this on Tylenol's risks for cardiovascular, gastrointestinal tract, and other issues.

https://sciencebasedmedicine.org/tylenol-may-not-be-as-safe-and-effective-as-we-thought/

Look, the gut issues alone are critical since all new roads in medicine are pointing to the gut biome as a critical player in our health.

See CBD and the gut here.

We haven't even listed the side effects of Tylenol.

More on that here:

https://www.livescience.com/42785-acetaminophen.html

The liver and Tylenol and CBD

We need to take a quick detour...to the liver!

Both CBD and Tylenol use a similar pathway in the liver to be metabolized.

It's called the P450 pathway.

It's a pretty busy thoroughfare. Almost 60% of common drugs use this same interchange.

If we take CBD and/or Tylenol, it will use up some resources in this pathway and affect how much of each gets processed.

CBD does not have the issue that Tylenol has in terms of leading to liver failure.

As we mentioned above, Tylenol can exhaust glutathione in the liver and cause a toxic build-up.

We're starting to get research on CBD and the liver slowly.

The first signs are positive:

Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice, were normalized following cannabidiol administration.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057300/

This is not surprising since the endocannabinoid is intimately linked to proper liver function.

CBD was even found the reverse liver disease markers:

Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation, and neutrophil-mediated injury

https://www.nature.com/articles/s41598-017-10924-8

CBD will affect how medications are metabolized (either more or less depending on medicine).

We'll need another article on CBD and the liver.

The key point is this.

It's best to take CBD at least 2 hours away from other medications and ideally after your fattiest food.

Also, work with your doctor, assuming he or she knows CBD.

Can you mix Tylenol and CBD

Yes... you can.

The question after reading above is why would you.

Yes, Tylenol might have a fast response on pain (depending on CBD delivery option) but with many knock-on effects.

Other than the liver pathway traffic jam posed by the two, research doesn't show a conflict.

Long term, chronic use of Tylenol can serious effects on the gut, hormones, and cardiovascular systems.

These same risks do not appear with CBD in research.

CBD may have a protective role in offsetting some of the effects of Tylenol.

That being said since it's shown that Tylenol actually reduces the sensation of pain via the CB1 receptor, why not impact that receptor directly with CBD.

CB is literally short for "CannaBinoid".

CBD is a cannabinoid.

We just didn't have a way to directly affect it until CBD could be extracted from the plant.

Again, 2 hours away from other medications, consult doctors, and hopefully replace Tylenol with CBD for a stronger safety profile.

Best CBD to replace Tylenol

The same rules appear here:

3rd party tested
THC free (roughly 24-36% of people are allergic to THC which will increase inflammation)
Pesticide-free
Heavy metal-free
Organically grown in the US
Bacteria and Mold free

We also need enough CBD to actually help.

Check out our article on How Much CBD to Take

See what works for your system.

Finally, a great deal of our pain and more importantly, pain sensitivity, is from our nervous system state and even our hormonal balance.

Inflammation in the nervous system and brain can make us more susceptible to pain.

I found this out the hard way with perimenopause (that story is here).

The last thing we want to do in create a histamine response which is just a different pathway for inflammation.

It directly causes pain (swelling, redness, irritation) but histamine in the brain is a different deal altogether.

For this reason, we only deal with CBD Isolate.

Everyone's pushing full spectrum but roughly 40-60% of the population may have a bad response to this!

That's the wrong direction.

If you need a powerful example of histamine, look no further than Tylenol PM.

It's very popular not for pain but for sleep!

Many women in their late 40's during perimenopause and menopause take it for sleep alone.

Why?

We'll leave it Harvard medical to explain:

The sleep-inducing ingredient in Tylenol PM is diphenhydramine, an antihistamine.

https://www.health.harvard.edu/staying-healthy/going-safety-of-over-the-counter-sleeping-pills

Yes, histamine is in charge of wakefulness and an antihistamine is helping people sleep!

That alone is an argument for CBD Isolate!

Check out why only CBD Isolate works for histamine and allergy-sensitive people.

Until we see research to back all the other claims, it's just marketing.

CBD is the real deal based on 100's of articles.