Meloxicam And CBD Oil Interaction

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Are you thinking of combining CBD and Mobic? Learn about their side effects and interactions at CBD Education Online. It can’t be emphasized enough that patients must be honest with their doctors about their cannabis use, particularly if CBD is involved, given its modulating effects on various CYP enzymes. A case report suggests that CBD oil contributed to someone's death. Some scientists—and the weed industry—aren’t so sure.

CBD and Mobic

CBD and Mobic explained. Mobic (meloxicam) is a prescription drug often given to patients suffering from conditions like osteoarthritis or rheumatoid arthritis. However, given the possible side effects of Mobic, and other prescription drugs, many patients look into more natural alternatives like CBD to augment their current treatment. But, one must ask, is it safe to mix the two?

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Is it Safe to Mix CBD and Mobic?

It is potentially unsafe to mix Mobic and CBD. CBD can change the way that your body metabolizes certain drugs. It can also cause your body to eliminate drugs from your system more slowly. This could increase the risk of unwanted side effects. CBD and Mobic should not be combined without the express knowledge, consent and supervision of your healthcare team.

What is Mobic?

Mobic is a prescription strength non-steroidal anti-inflammatory (NSAID) drug that is prescribed to treat symptoms of painful chronic conditions. It can reduce joint pain, stiffness and swelling. It works by suppressing the production of prostaglandins, hormones that cause inflammation.

Cytochrome P450 Enzymes

Throughout your body, thousands of chemical reactions are needed to sustain homeostasis. Enzymes are naturally occuring chemicals, usually protein chains. Their function is to speed up these chemical reactions in your body. The enzymes that metabolize most medications are known as cytochrome P450 enzymes (CYP450). There are over 50,000 different CYP450s. They metabolize over 60% of prescription medications. CYP450 enzymes can be found throughout your body, however, this discussion will focus on the ones found in your gut and liver.

Drug Metabolism Basics

When you swallow a medication it first travels to your stomach. Most medications pass through your stomach chemically unchanged and move on to your small intestine. Once there, CYP450 enzymes begin to break the medication down. The medication is then absorbed into your bloodstream and immediately travels to your liver through the hepatic portal vein. Inside your liver, more CYP450 enzymes break down the medication further before it enters the systemic bloodstream that circulates throughout the rest of your body. Then, as blood circulates through your systemic bloodstream it eventually goes back through your liver where CYP450s break down more and more of the medication each time until eventually all of the medication is cleared from your body completely.

The First Pass Effect

The first pass effect refers to how much of a drug is destroyed during its first trip through your liver before entering your systemic bloodstream. Typically, at least some of the active ingredients of a drug are destroyed by gut and liver enzymes before they ever reach your systemic bloodstream. The measure of how much of a medication makes it into the systemic bloodstream is known as the bioavailability. The bioavailability of drugs varies. Some might have a bioavailability of 80%, meaning 20% is destroyed and the other 80% makes its way into the rest of your body.

CBD and Drug Metabolism

CBD, coming from either the cannabis, or hemp plant, can have a profound effect on drug metabolism. In studies, CBD has been shown to inhibit the activity of several CYP450 enzymes. The mechanism of how CBD does this is not yet fully understood, but it’s thought that CBD binds to the enzymes. Enzymes have what is known as an active site. This is the end of the enzyme that attaches to a substrate, in this case a drug, and carries out its chemical reaction. When CBD comes into contact with certain CYP450 enzymes, it may bind to the active site. If the active sites of the enzymes are bound up by CBD, they’re not free to bind to the molecules of a medication and break them down.

This effect does not just wear off after a few hours. The enzymes are permanently bound to the CBD. In order for your body to go back to metabolizing drugs normally, you have to wait for a new batch of enzymes to be produced. The amount of time it takes for enzymatic function to return to normal after taking CBD is not yet known. However, compounds in grapefruit can also permanently bind certain CYP450 enzymes in the gut. It’s been shown that it takes as long as 72 hours for enzymatic function to normalize after eating grapefruit or drinking grapefruit juice. So simply spacing out taking medications a few hours apart from CBD may not be helpful.

Mobic Metabolism

Mobic is primarily metabolized by the CYP450 enzyme CYP2C9, although CYP3A4 does play a minor role as well. A 2012 study found that CBD, and other cannabinoids, can inhibit the actions of CYP2C9. Another study, published in 2011, found that CBD also inhibits CYP3A4.

Bioavailability of Mobic

Mobic has a relatively high bioavailability, about 89%. Normally, only 11% is lost before it reaches the systemic bloodstream. However, the greater concern in regards to Mobic is the possibility that CBD could slow clearance of the drug from your body. As each subsequent dose of Mobic is taken, if enough of the drug has not been cleared from the body, this could lead to unsafe levels of the drug in your bloodstream. This increases the chances of side effects like:

  • Increased blood pressure
  • Severe headaches
  • Increased bleeding, including internal bleeding
  • Unexplained bruising
  • Symptoms of heart failure
    • Swelling ankles or feet
    • Extreme fatigue
    • Unusual weight gain
    • Abdominal pain
    • Persistent nausea and vomiting
    • Yellowing of the skin and/or eyes

    Liver problems caused by Mobic are of great concern because they could be fatal. For these reasons, combining CBD and Mobic should not be attempted unless under the strict supervision of your healthcare team.

    CBD for Inflammation

    Unfortunately, science is still catching up when it comes to research on CBD for pain in humans. However, in 2008, a comprehensive review of animal studies about using cannabinoids for managing chronic pain was compiled. Overall, the consensus was that CBD showed great potential to alleviate symptoms like pain and inflammation and possibly a lower risk of side effects than NSAIDs.

    Anecdotal accounts point to the potential positives of using CBD for chronic pain conditions. Some users state that they have been able to reduce or eliminate their NSAIDs by using CBD. Many claim that a topical application of CBD can help with joint swelling, pain and stiffness. Using CBD topically may help to bypass enzymatic inhibition.

    Conclusions

    It could be unsafe to mix CBD and Mobic. CBD might change how your body metabolizes this drug, causing a higher percentage to enter your bloodstream and causing it to take longer for your body to clear the drug from your system. You should not combine CBD and Mobic without going over the possible risks and benefits with your healthcare team and you should follow their recommendations. However, CBD may be able to help relieve symptoms like joint pain, swelling and stiffness in its own right.

    Did CBD Kill This Woman?

    On February 20, 2020, the journal Case Reports in Ophthalmogical Medicine published an article about a 56-year-old woman who died two days after ingesting a sublingual CBD tincture in addition to a cocktail of drugs prescribed to manage her pre-existing conditions. 1

    Sensationalized accounts of this report quickly circulated online, which misrepresented the incident as the “first death caused by CBD .”

    The actual report, entitled “Commercial Cannabinoid Oil-Induced Stevens-Johnson Syndrome,” does not validate this alarming claim. That, however, won’t stop CBD cynics and drug war diehards from brandishing this case report as proof that cannabidiol is a dangerous substance.

    Written by a team of researchers affiliated with the SUNY Upstate Medical University in Syracuse, New York, the case report describes a 56-year-old woman with “a medical history of herniated disc with chronic pain, hypertension, and coronary artery disease.” She had been taking three pharmaceuticals – famotidine, lisinopril-hydrochlorothiazide, and meloxicam – under a doctor’s supervision to treat her ailments.

    In an effort to improve her health, the unidentified woman also had been using various CBD products for five years without ill effect. But a week after switching to a new CBD product called “Natural Native,” she was admitted to her local emergency room with a hideous rash and skin ulcers. She was diagnosed with Stevens-Johnson syndrome, which is usually triggered by a bad reaction to medications, causing skin tissue to die and detach. The mucous membranes of the eyes, mouth, and/or genitals are also adversely affected. 2

    She ultimately died of septic shock while hospitalized.

    What are Liposomes & What Is Their Role in This?

    The case report notes the patient had previously used commercial CBD products “without side effects or associated allergic reactions [which] suggests involvement of other ingredients in this non- FDA -regulated product as the causative agent.”

    What other ingredients may have been involved?

    Shortly before she died, she had started taking a CBD tincture that utilized a liposomal delivery method. 3 This may have been a key factor in her untimely demise.

    Liposomes, composed of natural or synthetic lipid bilayers, are small spherical vesicles that can be used in product formulation as a means of enhancing the bioavailability of the active ingredient(s). Employed as a vehicle for administering drugs and nutraceuticals, this type of delivery system can facilitate a 10 to 100-fold increase in bioavailability depending on the compound in question. Sounds impressive, but that’s not always a good thing.

    It’s worth noting that the pharmaceutical cocktail prescribed by her doctor included meloxicam, a non-steroidal anti-inflammatory drug, which reduces inflammatory pain by inhibiting COX enzymes that produce compounds, known as prostaglandins, that regulate the body’s inflammatory response.

    When the liposomal CBD product was administered in conjunction with meloxicam and two other pharmaceuticals, the combination proved to be fatal.

    Mechanisms at Play—It’s Not Just the CBD

    How and why did this fatality occur?

    Similar to grapefruit juice, CBD can cause drug-drug interactions due to its inhibitory or inductive actions on cytochrome P450 enzymes ( CYP s). In particular, CBD inhibits both CYP2C9 and CYP3A4 , the latter of which is responsible for metabolizing nearly 30 percent of prescribed pharmaceutical drugs. 4-8 Significantly, the aforementioned meloxicam is also metabolized by CYP2C9 and CYP3A4 . 9

    Unfortunately, this information was not included in the case report, which also neglected to indicate that grapeseed oil was one of the components of the CBD -infused liposomal formulation consumed by the patient. Grapeseed oil contains retinoids, which are Vitamin A derivatives that have many important functions throughout the body, including roles in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes. 10 But these compounds must be carefully dosed to avoid potential toxicity.

    Product manufacturers should be cognizant of the chemical make-up of all the ingredients in their formulations, especially when using delivery methods designed to enhance bioavailabiity. Liposomal delivery likely enhanced not only the level of CBD in the patient but also the level of retinoid compounds found in the grapeseed oil. This, in turn, could lead to enhanced inhibition of CYP3A4 and CYP2C9 , which would slow the metabolism of the meloxicam, further elevating its levels in the blood. Enhanced retinoid delivery likely exacerbated the situation by triggering the Stevens-Johnson syndrome.

    Furthermore, the case report notes “complete chemical analysis from the patient’s commercial CBD oil was not performed.” Additionally, a certificate of analysis was not avilable on the website purveying this product, and we don’t know the dose of CBD that was administered or if other contaminants were also present.

    To summarize: The problematic interaction between CBD , meloxicam, and retinoids was heightened due to the liposomal delivery of retinoid-containing grapeseed oil.

    A Cautionary Tale

    CBD skeptics and click-bait confabulators on the internet jumped to the conclusion that cannabidiol caused this woman’s death. But those who read the case report know that the actual cause of death was septic shock. While CBD ’s inhibitory activity on CYP enzymes may have contributed to this, the chance combination of all these factors is what ultimately led to the woman’s death.

    Let this be a lesson for CBD consumers, product formulators, and physicians alike – be careful!

    Although cannabis is still federally illegal, it is essential that health professionals be well informed about potentially catastrophic drug-drug interactions. And it can’t be emphasized enough that patients must be honest with their doctors about their cannabis use, particularly if CBD is involved, given its modulating effects on various CYP enzymes.

    Education and honest discourse are paramount if we are to prevent more tragedies such as this from occurring in the future.

    The diagram above depicts the proposed interaction between CBD , meloxicam, and retinoids. This interaction would be heightened due to the liposomal delivery of retinoid containing grapeseed oil. Source: Mawson AR , Eriator I, Karre S. Stevens-Johnson syndrome and toxic epidermal necrolysis ( SJS / TEN ): could retinoids play a causative role?. Med Sci Monit. 2015;21:133–143. Published 2015 Jan 12. doi:10.12659/ MSM .891043.”

    The diagram above depicts the proposed interaction between CBD , meloxicam, and retinoids. This interaction would be heightened due to the liposomal delivery of retinoid containing grapeseed oil. Source: Mawson AR , Eriator I, Karre S. Stevens-Johnson syndrome and toxic epidermal necrolysis ( SJS / TEN ): could retinoids play a causative role?. Med Sci Monit. 2015;21:133–143. Published 2015 Jan 12. doi:10.12659/ MSM .891043.”

    Footnotes

    1. Yin, Han Yang & Hadjokas, Nicholas & Mirchia, Kanish & Swan, Robert & Alpert, Samuel. (2020). Commercial Cannabinoid Oil-Induced Stevens-Johnson Syndrome. Case Reports in Ophthalmological Medicine. 2020. 1-5. 10.1155/2020/6760272.
    2. Dodiuk-gad RP , Chung WH , Valeyrie-allanore L, Shear NH . Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An Update. Am J Clin Dermatol. 2015;16(6):475-93.
    3. Enhanced CBD Oil Extract Spray https://www.exspose.com/index.php?route=product/product&product_id=58 A… 3/9/20
    4. Zanger UM , Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103-41.
    5. Michiru Nagao, Yukako Nakano, Masataka Tajima, Erika Sugiyama, Vilasinee Hirunpanich Sato, Makoto Inada, and Hitoshi Sato.Cannabis and Cannabinoid Research.ahead of print http://doi.org/10.1089/can.2019.0098
    6. Yamaori S, Ebisawa J, Okushima Y, Yamamoto I, Watanabe K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011;88(15-16):730-6.
    7. World Health Organization Expert Committee on Drug Dependence. Cannabidiol ( CBD ) Pre-review Report Agenda Item 5.2 and Peer Review. World Health Organization: Geneva, Switzerland, 2017. Google Scholar
    8. Yamaori, S., Koeda, K., Kushihara, M., Hada, Y., Yamamoto, I., & Watanabe, K. (2012). Comparison in the In Vitro Inhibitory Effects of Major Phytocannabinoids and Polycyclic Aromatic Hydrocarbons Contained in Marijuana Smoke on Cytochrome P450 2C9 Activity. Drug Metabolism and Pharmacokinetics, 27(3), 294–300. doi:10.2133/dmpk.dmpk-11-rg-107
    9. Ludwig E, Schmid J, Beschke K, Ebner T. Activation of human cytochrome P-450 3A4 -catalyzed meloxicam 5’-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999;290(1):1-8.
    10. Garavaglia J, Markoski MM , Oliveira A, Marcadenti A. Grape Seed Oil Compounds: Biological and Chemical Actions for Health. Nutr Metab Insights. 2016;9:59-64.
    11. Mawson AR , Eriator I, Karre S. Stevens-Johnson syndrome and toxic epidermal necrolysis ( SJS / TEN ): could retinoids play a causative role?. Med Sci Monit. 2015;21:133–143. Published 2015 Jan 12. doi:10.12659/ MSM .891043.

    Kyle Boyar is a cannabis scientist with a background in neurobiology, microbiology, and analytical chemistry. He is currently employed as the Director of Product Science at Tagleaf. Additionally, he also serves as the Vice Chair and Scholarship Committee Chair for the American Chemical Society’s Cannabis Chemistry Subdivision ( CANN ).

    Copyright, Project CBD . May not be reprinted without permission.

    The Bizarre Case of a Death Allegedly Caused by CBD Oil

    A case report suggests that CBD oil contributed to someone’s death. Some scientists—and the weed industry—aren’t so sure.

    Two days after trying a new CBD oil extract to treat her chronic pain, a 56-year-old woman developed an awful rash.

    Her primary care physician prescribed antihistamines and prednisone, a common steroid used to treat inflammation. She went home. The rash got worse. From a local emergency room, she went to a hospital burn unit. There, the rash went out of control.

    Angry red lesions broke out over 30 percent of her body, including her eyes and groin. Skin peeled from her arms and back. Doctors administered more antibiotics, more anti-inflammatory steroids. They didn’t work. After a month of suffering, she was dead from septic shock, the final result of a rare and extremely serious allergic reaction called Stevens-Johnson Syndrome (SJS), according to an account published February in Case Reports in Ophthalmological Medicine.

    Companies Making CBD Gummies, Vapes, and Lube Got Millions In Bailout Loans

    Described by the Mayo Clinic as both “rare and unpredictable,” Stevens-Johnson Syndrome is typically triggered by “a medication, an infection or both.” According to the British NHS, among the “medicines that most commonly cause” the affliction is the “oxicam” family of anti-inflammatory drugs. The woman had been taking meloxicam for arthritis, but that’s not what killed her, according to the case report, written by a group of eye doctors from SUNY Upstate Medical University in Syracuse, New York. She had already been on meloxicam without any reported complications, after all.

    What set off the fatal allergic reaction, they claim, was the product she had tried. It was a new brand of cannabidiol (CBD) oil she was taking for back pain; she had previously taken other CBD brands without issue. Though the new CBD oil she used was not tested for impurities, either some unknown ingredient in the oil or some reaction triggered by the CBD was the most likely cause of the allergic reaction and subsequent death, the doctors wrote, published under the title “Commercial Cannabis Oil–Induced Stevens-Johnson Syndrome.”

    If true, the news that a cannabis product killed someone would amount to the upending of a longstanding claim from weed legalization advocates that the drug is so safe no one has ever died from it. And this wasn’t a case of high-THC cannabis allegedly causing psychosis—it was a possible reaction to CBD oil, an increasingly popular and widely available wellness product in the United States.

    Physicians and medical professionals with expertise in cannabis consulted by VICE were divided on the merits of the medical journal article. But though they argued over the value of the case study and what (if anything) it means, one common theme emerged: it’s still the Wild West days for CBD, a drug that is still poorly studied, poorly understood and—with products of wildly varying potency and purity available online in all 50 states, at gas stations and novelty shops and corner bodegas—almost entirely unregulated.

    News of the “first death caused by CBD” made ripples in the weed world and on social media. Project CBD, a cannabidiol advocacy organization, published a rebuttal that criticized “CBD skeptics and click-bait confabulators” rushing to blame a cannabis product, while raising the possibility that the oil could have reacted with the woman’s medications to fatal effect.

    Peter Grinspoon is a physician on staff at Massachusetts General Hospital in Boston and a professor at Harvard Medical School who frequently blogs about cannabis and other drugs on Harvard’s website (his father is Lester Grinspoon, the Harvard psychiatrist who authored Marihuana Reconsidered, one of the bibles of cannabis-policy reform, in the 1960s). Grinspoon was skeptical that the death had much to do with CBD.

    “It’s unlikely that this is the first case in 5,000 years of a cannabinoid causing Stevens-Johnson Syndrome (SJS), but it is certainly possible,” he said.

    Grinspoon allowed that CBD could have inhibited liver enzymes metabolizing the meloxicam, raising its potency and lowering the body’s defenses, thus triggering the allergic reaction. It’s possible that the CBD, the meloxicam and the other pharmaceuticals the woman was taking could have set off a sort of perfect storm.

    But since the SUNY ophthalmologists did not analyze the CBD oil—and offered up theoretical adulterants as a cause, apparently without knowing whether they were in the CBD product or not—“they have no idea, really, what this patient consumed, and it seems sort of intellectually reckless to pin the death on CBD,” Grinspoon said.

    “Researchers are always eager to try to be the first ones to tie a death to a cannabinoid as this gets you in the news,” he added.

    Some experts were even more dismissive of the case study. “I think the paper is shite,” Jeffrey Hergenrather, a physician and former president of the Society of Cannabis Clinicians, wrote in an email. “Regarding CBD and the association with SJS, I’ve never heard of such a thing.”

    The case report did not address what possible contaminant in the offending CBD oil might have been and what it might have done. Nor did it state the size and frequency of the CBD dose taken or any of the patient’s genetic factors that might have been an equal or greater risk factor for Stevens-Johnson Syndrome, he said. Instead, the authors went straight to the CBD—and that, he pointed out, is a classic tell of anti-cannabis bias. “As usual it is easy to publish a case report implicating harm with a cannabis product,” he said. “Cannabis is an easy target for assertions of harm.”

    Other researchers similarly pointed to gaps in the knowledge.

    “I don’t remember seeing any other case reports associated with cannabidiol, but that being said, we don’t know what else was in the cannabidiol products that might be associated with this type of disorder,” said Ziva Cooper, a pharmacologist and the research director at the University of California, Los Angeles’s Cannabis Research Initiative.

    Side effects of drugs like meloxicam are known because “thousands of people” using it “have been tracked. And this has not been the case with cannabidiol,” she said.

    How to Get Into Weed While You’re Self-Isolating

    The case report notes that the “new liposomal CBD extract spray” came from Natural Native, a CBD company based in Oklahoma. Last November, the company received a warning letter from the Food and Drug Administration. On Facebook and on its website, Natural Native broke several FDA rules for marketing CBD water, marketing CBD products intended for infants and otherwise making scientific claims that suggested CBD was a drug that could help with health conditions ranging from acne to chronic pain to cancer. (CBD is a “drug” in the taxonomical sense, but in the legal sense, a drug needs FDA approval to be marketed as such.)

    In this, the company is hardly unique. Making unsubstantiated claims about CBD’s medical benefits or marketing CBD products as medicines or food products in violation of FDA rules is unscrupulous, but also happens often enough that it’s almost become a cannabis industry standard.

    In interviews with VICE, Danny Bannister, one of Natural Native’s owners, did not deny crossing the line with the FDA. But nonetheless, he said, the case report could baselessly damage his business. He has been trying, to no avail, to get the title of the paper changed.

    Bannister first heard about the case report in late February, when one of his competitors emailed the story to a retail client of his. The title, Bannister pointed out, is “Commercial Cannabis Oil-Induced Stevens-Johnson Syndrome,” which sounds conclusive. Only toward the end of the report’s discussion section do the authors admit that it’s still “unclear if marijuana-derived/CBD products can induce” SJS, and that it’s a subject that requires more study as well as general clinical awareness.

    “He should take that assertive assumption out of the title,” Bannister said. “Even turning it into a question. It would be that simple.”

    Bannister said he’s been unable to get a response from either the SUNY Upstate doctors who wrote the case study or the editors at Case Reports in Ophthalmological Medicine. (The report’s authors also did not respond to repeated requests for comment from VICE.)

    Underlying all this is a lot of uncertainty, and the stark truth that CBD is widely available, poorly understood, and also poorly regulated. Under former FDA Commissioner Scott Gottlieb, the Trump Administration seemed interested in getting a stronger handle on CBD regulation. But Gottlieb stepped down last year, and with COVID-19 seizing the attention of both the agency and the public, the nature of the industry seems unlikely to change anytime soon.

    It’s true that a woman did die after taking CBD oil, but that doesn’t mean that CBD killed her. CBD is safe for the vast majority of people, but that doesn’t mean it’s safe for everyone. We simply don’t know enough about how CBD interacts with other drugs.

    “Drugs kill people all the time. The safety profile of CBD is pretty good, but it is a drug,” said Michael Backes, a Southern California cannabis consultant and author of Cannabis Pharmacy, one of the leading compendiums of the plant’s medical and scientific effects. “There may be a person out there who takes a particular preparation of CBD, and it could kill them. That could happen.”

    Follow Chris Roberts on Twitter.

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