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Does CBD Interact With Acetaminophen (Tylenol)?

CBD can interact mildly with the analgesic and antipyretic acetaminophen, enhancing analgesic effects but causing potentially severe side effects too.

Article By
Daily CBD , last updated on April 15, 2022

Acetaminophen is an analgesic and antipyretic drug used to treat fever and pain. It can be used alone or combined with other analgesics. Cannabidiol (CBD) can be an agonist for acetaminophen.

Taking them together may cause some unwanted side effects. CBD’s analgesic and antioxidant characteristics may contribute to acetaminophen’s analgesic qualities.

Long-term use, however, may result in drug accumulation and side effects.

Acetaminophen illustration

Does CBD Interact With Acetaminophen (Tylenol)?

Yes. CBD can interact with acetaminophen, though the interaction is mostly mild.

There are two ways by which CBD can interact with acetaminophen.

A) CBD Can Increase Acetaminophen’s Effects (Agonistic Interaction)

Two substances that have the same effects on the body and cause it to operate in the same direction is an antagonistic interaction.

CBD works by interacting with the body’s endocannabinoid system. It possesses antioxidant and pain-relieving effects, which may help reduce inflammation and reduce pain.

 On the other hand, it’s unclear exactly how acetaminophen works, but it could be by lowering prostaglandin production in the brain and spinal cord. The body produces prostaglandins in reaction to injury and certain disorders. Decreasing its production may relieve pain as well. It inhibits cyclooxygenase (COX) pathways in the central nervous system and is often categorized with NSAIDs for this reason. 

Recent studies have shown that acetaminophen may even affect the endocannabinoid system to produce analgesic effects [1].

B) CBD May Slow Down Acetaminophen’s Metabolization (Metabolic Competition)

Most medications in the body are metabolized by the cytochrome P450 enzymes. Two medications that are both metabolized by the same enzyme can sometimes end up fighting for the same enzyme. This could lead to slowed medication removal and an overabundance of one or both medicines.

The liver enzymes cytochrome P450 (CYP) 1A2, 2E1, and 3A4 metabolize acetaminophen.

CBD’s metabolization is also aided by these enzymes.

As a result, consuming them together for an extended period may result in elevated acetaminophen plasma levels in the body. It could produce extra negative effects, such as stomach trouble, vomiting, tiredness, and so on, by slowing down its elimination.

Similar Medications: CBD & Acetaminophen (Tylenol)

Acetaminophen is classified as an analgesic and antipyretic. CBD and analgesics all share similar risks for interaction and side effects.

Here’s a list of similar medications that share a similar level of risk when combined with CBD:

  • Abenol
  • Acephen
  • Actamin
  • Actimol
  • Paracetamol
  • Altenol

Is It Safe to Take CBD & Acetaminophen (Tylenol) Together?

In small amounts, combining acetaminophen and CBD is relatively safe, but they may interact mildly to moderately. However, long-term use may cause negative effects due to acetaminophen accumulating in the body.

Too much acetaminophen in the body can have negative consequences, such as liver failure. If you want to start using CBD while taking acetaminophen, always consult your physician first.

Only take these two medications together as directed by your physician, and never take more than the recommended dose. Low doses of both medications, spaced properly, may assist in reducing side effects. Any negative effects from taking these two drugs warrant a visit to your medical practitioner immediately.

Is CBD a Viable Alternative to Acetaminophen (Tylenol)?

Cannabidiol (CBD) is a powerful pain reliever, particularly for mild to moderate conditions.

CBD works in the same way as the neurotransmitter adenosine in that it inhibits pain sensations. CBD may also aid in relieving pain and inflammation by binding to transient receptor potential (TRP) channels, which help to block pain signals from the brain [2]. CBD may be more effective and have fewer adverse effects than acetaminophen in moderate circumstances.

CBD’s antioxidant property may help relieve inflammation and help to treat the conditions that cause pain [3].

However, there are no studies that prove CBD’s effectiveness in treating fever.

Because of these reasons, while CBD may be an effective painkiller in mild conditions, it probably won’t help bring down a fever.

What is Acetaminophen (Tylenol)?

Acetaminophen is an analgesic and antipyretic drug. Tylenol is one of its common brands. It is used to treat mild to moderate pain and to decrease fever. It is often sold in combination with other analgesics like ibuprofen.

It is sold as an over-the-counter medication. 

 Acetaminophen (Tylenol) Specs:

Drug Name Acetaminophen
Trade Name Tylenol, Acephen, Actamin, Altenol, Aminofen, Feverall, Genapap Genebs, Infantaire, Mapap, Pyrecot, Pyregesic, Q-Pap, Redutemp, Silapap, T-Painol, Tycolene
Other Names (other generics) N-acetyl-para-aminophenol (APAP), paracetamol
Classification   Analgesics, Antipyretics
CYP Metabolism Cytochrome P450 (CYP) 1A2, 2E1, and 3A4  
Interaction With CBD Metabolic Competition, Agonistic
Risk of Interaction Mild to Moderate

Other Names For Acetaminophen (Tylenol)

Acetaminophen is sold under many different names. All share the same risk and potential interactions.

Other names for acetaminophen include:

  • Acephen
  • Actamin
  • Altenol
  •  Aminofen
  • Feverall
  • Genapap
  • Genebs
  • Infantaire
  • Mapap
  • Pyrecot
  • Pyrigesic
  • Q-Pap
  • Redytemp
  • Silapap
  • T-Painol
  • Tycolene
  • Tylenol

What Does Acetaminophen (Tylenol) Do?

Acetaminophen works through two mechanisms: cyclooxygenase (COX) inhibition and activities of its metabolite N-arachidonoylaminophenol (AM404).

1. COX Inhibitor

Acetaminophen is pharmacologically similar to nonsteroidal anti-inflammatory medications (NSAIDs) that work by inhibiting COX-1 and COX-2 enzymes and is especially selective to COX-2 inhibitors. By lowering the active form of COX-1 and COX-2 enzymes, acetaminophen decreases prostaglandin production.

This occurs only when the levels of arachidonic acid and peroxides are low. In these settings, COX-2 is the main form of cyclooxygenase. Peroxide levels are high in inflammatory circumstances, which counteracts paracetamol’s calming effect. Hence, acetaminophen does not have any anti-inflammatory abilities.

2. AM404 Action

The second mechanism occurs through the action of AM404 metabolite of acetaminophen l. This metabolite has been found in the brains of animals and the cerebrospinal fluid of people who take acetaminophen. It appears to be generated in the brain by the action of fatty acid amide hydrolase from another acetaminophen metabolite, 4-aminophenol.

AM404 is a powerful activator of the transient receptor potential vanilloid subtype 1 (TRPV1) receptor and a modest agonist of the CB1 and CB2 cannabinoid receptors. It also inhibits the endocannabinoid transporter.

Hence, it is believed that acetaminophen’s actions on the cannabinoid system and TRPV1 receptor may cause its analgesic effects.

The half-life of acetaminophen is 5.4 hours.

Because acetaminophen is so easily available as an OTC drug, it is also more liable to be misused and cause overdose and liver failure.

Side Effects of Acetaminophen (Tylenol)

Acetaminophen should not be used in those with acetaminophen hypersensitivity.

It should be used with caution in users with:

  • Severe hepatic impairment
  • Severe renal impairment
  • With G6PD deficiency

Many people think acetaminophen can be taken without consequence, but it’s easy to take too much, which can lead to severe complications.

The most common side effects include:

  • Abdominal pain
  • Agranulocytosis
  • Angioedema
  • Disorientation
  • Dizziness
  • Gastrointestinal hemorrhage
  • Hepatotoxicity Liver failure
  • Hyperammonemia
  • Laryngeal edema
  • Leukopenia
  • Nausea
  • Nephrotoxicity
  • Neutropenia
  • Pancytopenia
  • Pneumonitis
  • Rash
  • Thrombocytopenia
  • Toxic epidermal necrolysis
  • Urticaria
  • Vomiting

Key Takeaways: Is it Safe to Take Acetaminophen (Tylenol) With CBD?

Both CBD and acetaminophen reduce pain; however, CBD has no antipyretic properties.

They can interact moderately, but low doses of these two medications are usually safe to use as long as it’s not daily. Still, it’s always best to talk to your doctor to avoid any possible problems. Large doses and long-term use can exacerbate acetaminophen’s negative effects by accumulating in the body and delaying metabolism.


References

  1. Klinger-Gratz, P. P., Ralvenius, W. T., Neumann, E., Kato, A., Nyilas, R., Lele, Z., … & Zeilhofer, H. U. (2018). Acetaminophen relieves inflammatory pain through CB1 cannabinoid receptors in the rostral ventromedial medulla. Journal of Neuroscience, 38(2), 322-334.
  2. De Petrocellis, L., Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., … & Di Marzo, V. (2011). Effects of cannabinoids and cannabinoid‐enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British journal of pharmacology, 163(7), 1479-1494.
  3. Atalay, S., Jarocka-Karpowicz, I., & Skrzydlewska, E. (2020). Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants, 9(1), 21.

Learn More About CBD-Drug Interactions

Learn More About CBD-Drug Interactions

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