Ibuprofen and Weed: How Ibuprofen Interacts with THC and CBD

Ibuprofen is a widely used, FDA-approved drug for anti-inflammation, rheumatoid disorders, and pain. Pain and inflammation are two of the top reasons that individuals may choose to begin using cannabis, especially if they are seeking to get away from over-the-counter and prescription medication. Within the United States, 38 states have medical cannabis programs, all of which include pain as a qualifying condition in one way or another.

Current research indicates that the concurrent use of ibuprofen and weed may provide more significant pain relief for individuals than just using ibuprofen and weed. However, it is essential to note that research is still ongoing, and there may still be risks when it comes to combining ibuprofen and cannabis.

What is Ibuprofen?

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) intended to treat inflammatory diseases and rheumatoid disorders. Used in hospitals and also available over the counter, Ibuprofen is the most commonly used NSAID, with roughly 16.5 million prescriptions and over 8.8 million patients in 2020.

Many people use ibuprofen for headaches, cramps, dental pain, fever, pain from an injury, chronic pain, or other inflammatory conditions such as arthritis.

Ibuprofen works by inhibiting the prostaglandin precursors, which mediate pain and inflammatory responses in the body and are created by cyclooxygenase-1 (COX -1) and cyclooxygenase-2 (COX-2) enzymes. Ibuprofen can be given in a liquid, pill, chewable tablet, liquid capsule, or IV form. Ibuprofen is found in name-brand over the counter drugs such as Advil, Midol, Motrin, Neurfen.

Common side effects of ibuprofen overuse can include:

• Diminished kidney function
• Gastrointestinal bleeding
• Rashes.

Other side effects individuals may experience from taking ibuprofen at average doses include:

• Dizziness
• Headaches
• Indigestion
• Nausea
• Vomiting

In addition, topical ibuprofen use – and even when ingested – can result in sensitivity to sunlight, putting some individuals at increased risk for sunburns. Individuals can experience immediate phototoxicity or delayed photoallergy and should use sunscreen and monitor for side effects when exposed to the sun.

Individuals with prescription ibuprofen can take a maximum of 3200 mg per 24-hour period, while over-the-counter ibuprofen users can take a maximum of 1200 mg per 24-hour period. Prescription ibuprofen doses are typically for individuals experiencing severe pain, such as those coming from surgery or tooth extraction. Over-the-counter doses of ibuprofen are for individuals with mild to moderate pain and are intended to prevent adverse effects and overdose. Ibuprofen is available under various brand names, including Advil, Midol, Motrin, and Neurofin. 

It is always recommended to consult a healthcare professional to ensure proper and safe medication use.

Ibuprofen and Weed: Interactions and Risks

When used correctly, both ibuprofen and cannabis are considered safe to use when taken independently. To date, no research indicates the concurrent use of cannabis and ibuprofen is unsafe. Individuals taking ibuprofen may experience side effects such as dizziness, headaches, indigestion, nausea, and vomiting. Likewise, cannabis can also cause side effects, particularly at higher doses, including anxiety, drowsiness, coughing, dry mouth, short-term memory loss, and increased appetite.

Research from 2011 by Paunescu et al. indicates that the body’s ability to metabolize anandamide could be affected by taking therapeutic doses of ibuprofen because it inhibits fatty acid amide hydrolase (FAAH)¹. In turn, the use of ibuprofen could boost the endocannabinoid system's ability to relieve pain through the increase of anandamide. Since anandamide is the closest endocannabinoid, chemically, to THC and binds to the same CB1 receptors, there may be implications for cannabis as well, especially since there’s reason to believe THC also helps relieve pain and inflammation.

Research demonstrates that certain cannabinoids inhibit CYP2C9 metabolism, one of the enzymes responsible for metabolizing ibuprofen². These cannabinoids include: 

• CBC
• CBD
• CBDa
• CBDV
• CBDVa
• CBG
• CBGa
• THC
• THCa
• THCV
• THCVa

Of these cannabinoids, CBDa was the only one to demonstrate inhibition at clinically relevant doses. However, further research is necessary to determine if other cannabinoids affect CYP2C9 metabolism at clinically relevant doses, and it is advised to space the dosing of cannabinoids and ibuprofen by two hours after taking either compound. Interestingly, the same study indicates that taking ibuprofen may reduce the psychotropic effects of high-THC cannabis. However, this has not been proven in clinical trials.

Are There Any Benefits to Taking Weed and Ibuprofen?

Research demonstrates that combining ibuprofen and weed may be beneficial to the consumer in several ways.

The number one potential benefit of choosing to use ibuprofen and cannabis concurrently is greater pain relief than if just ibuprofen was used. A 2022 analysis from Nutt et al. found that cannabinoid-based medicines with a 1:1 ratio of THC to CBD (as well as just THC or CBD) are safer and more effective than other pharmaceutical medications, including ibuprofen³. Other research looking at synthetic cannabinoids, such as nabilone, also demonstrates effectiveness in reducing neuropathic pain and improving the patient's quality of life.

Another potential benefit is the reduction of unwanted side effects. One study from 2013 by Chen et al. hypothesized that the learning and memory impairment caused by delta-9 THC might be linked to the activation of COX-2, an enzyme involved in the inflammatory response⁴. The researchers analyzed whether inhibiting COX-2 production using ibuprofen could alleviate learning and memory impairment induced by delta-9 THC. It is important to note that this study was conducted in a laboratory using mice, and further research is necessary to validate and expand upon these findings in human subjects. 

In addition to inhalable and ingestible CBD products, research from Bruni et al. (2018) states that CBD topicals can relieve pain in more localized areas of the body, such as in individuals with arthritis in the hands or knee pain³. By interacting with the cannabinoid receptors in the skin, including the CB2 receptors and TRPV channels, cannabinoids like CBD can help mediate pain response by supplementing the use of ibuprofen.

What About Ibuprofen and CBD?

A study published in December 2022 by Krajka-Kuźniak et al. found that using a combination of CBD and ibuprofen can inhibit the activation of NF-kB signaling and reduce the expression of COX-2 in vulvar squamous cell carcinoma (VSCC)⁶. However, more clinical research is needed to determine CBD's efficacy and safety in treating or potentially preventing vulvar squamous cell carcinoma when used in combination with antiviral agents, HPV vaccination, and NSAIDs such as ibuprofen.

In 2021, Henshaw et al. published a systematic review looking at the effects of cannabinoids on pro- and anti-inflammatory cytokines⁷. Researchers found that CBD, CBG, and the combination of THC and CBD resulted in lower pro-inflammatory cytokines and increased production of anti-inflammatory cytokines. It is important to note that this systematic review focused on articles using cell lines and not clinical trials. Clinical trials are an important step in determining the efficacy of these cannabinoid blends on pro- and anti-inflammatory cytokines in humans.

While these initial findings show promising results for combining CBD and ibuprofen, there are potential risks consumers should consider.

The use of CBD could potentially inhibit the metabolization of ibuprofen, resulting in an increased concentration of the drug⁸. This occurs due to the secondary metabolic pathways of CBD, specifically by the UGT1A9 and UGT2B7 enzymes found in the liver, kidneys, epithelial cells of the lower gastrointestinal tract, and brain. 

It is recommended that individuals using both CBD and ibuprofen for pain relief should space out the intake of either compound by two hours to avoid any adverse side effects unless using a cannabis topical product. 

Safety Precautions When Taking Ibuprofen and Medical Marijuana

When using medical marijuana, an individual should be aware of and monitor for adverse side effects. These side effects of cannabis can include but are not limited to:

• Anxiety
• Coughing
• Drowsiness
• Dry mouth
• Increased appetite
• Temporary short-term memory loss

Cannabis overdose is not fatal and can be remedied through rest and hydration. Some reports suggest eating black peppercorns or using CBD to help alleviate overwhelming effects. It is not typical that an individual would need medical assistance after ingesting too much THC, although feelings of paranoia may lead to such a reaction.

In addition, overuse of ibuprofen can lead to the following symptoms:

• Blurred Vision
• Diarrhea
• Dizziness
• Headaches
• Indigestion
• Nausea
• Ulcers and bleeding in the stomach
• Seizures
• Vomiting

If an individual believes they have ingested too much ibuprofen (more than 1200 mg per 24 hours for OTC and 3200 mg per 24 hours for prescription), they should seek medical attention immediately.

If seeking medical attention for either cannabis or ibuprofen overuse, it is important to be honest with your doctor or medic so they can treat you accordingly.

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How long should I wait to use cannabis after taking Ibuprofen?

It is advised to wait two hours after taking ibuprofen to consume cannabis.

Is there a cannabis consumption method that’s safer to use when taking Ibuprofen?

No scientific evidence suggests that any method is safer than another when taking ibuprofen. It is advised, however, to avoid the combustion of plant material via pipes, bongs, joints, etc.

Can cannabis be a substitute for Ibuprofen for pain relief?

Yes, there is both clinical and anecdotal evidence that THC, CBD, and other cannabinoids can help relieve pain. Likewise, studies are revealing the potential role of terpenes in pain relief. However, you should consider speaking with your doctor before changing your medication regimen, especially if you have been treating severe or chronic pain.

Is CBD or high-THC cannabis safer to use with ibuprofen?

Both high-THC and high-CBD products are generally considered safe to use with ibuprofen, with THC demonstrating a lower risk of adverse effects than CBD due to its secondary metabolic pathways. However, consulting with a qualified medical practitioner before combining medications is worth it.

References

1. Paunescu H, Coman OA, Coman L, et al. Cannabinoid system and cyclooxygenases inhibitors. Journal of Medicine and Life. 2011;4(1):11-20.
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2. Doohan PT, Oldfield LD, Arnold JC, Anderson LL. Cannabinoid Interactions with Cytochrome P450 Drug Metabolism: a Full-Spectrum Characterization. The AAPS journal. 2021;23(4):91. doi:https://doi.org/10.1208/s12248-021-00616-75.
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3. Nutt DJ, Phillips LD, Barnes MP, et al. A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products. Cannabis and Cannabinoid Research. 2021;7(4). doi:https://doi.org/10.1089/can.2020.0129
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4. Chen R, Zhang J, Fan N, et al. Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling. Cell. 2013;155(5):1154-1165. doi:https://doi.org/10.1016/j.cell.2013.10.042
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5. Bruni N, Della Pepa C, Oliaro-Bosso S, Pessione E, Gastaldi D, Dosio F. Cannabinoid Delivery Systems for Pain and Inflammation Treatment. Molecules. 2018; 23(10):2478. https://doi.org/10.3390/molecules23102478
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6. Violetta Krajka-Kuźniak, Katarzyna Papierska, Narożna M, Jelińska A, Aleksandra Majchrzak-Celińska. Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma. Molecules. 2022;27(24):8779-8779. doi:https://doi.org/10.3390/molecules27248779
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7. Henshaw FR, Dewsbury LS, Lim CK, Steiner GZ. The Effects of Cannabinoids on Pro- and Anti-Inflammatory Cytokines: A Systematic Review of In Vivo Studies. Cannabis Cannabinoid Res. 2021;6(3):177-195. doi:10.1089/can.2020.0105
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8. Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Journal of Clinical Medicine. 2019;8(7):989. doi:https://doi.org/10.3390/jcm8070989
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The information in this article and any included images or charts are for educational purposes only. This information is neither a substitute for, nor does it replace, professional legal advice or medical advice, diagnosis, or treatment. If you have any concerns or questions about laws, regulations, or your health, you should always consult with an attorney, physician or other licensed professional.