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Cbd oil and methotrexate for ra

Does CBD Interact or Interfere with Medication? What Arthritis Patients Must Know Now

CBD (cannabidiol) is seemingly everywhere, with oils, tinctures, pills, chocolates, gummy bears, and creams available all over the internet, at national drugstore chains, and perhaps at your local farmer’s market — even if you don’t live in a state where medical or recreational marijuana is legal.

CBD, a type of chemical known as a cannabinoid, is a mainingredient in hemp, one type of cannabis plant. Marijuana, another type of cannabis plant, also has some CBD but an abundance of THC (tetrahydrocannabinol), an intoxicating cannabinoid known for making users feel “stoned” or “high.” While CBD won’t get you high, it interacts with cannabinoid receptors in your body and may have effects that are sought by people with arthritis, such as pain relief, reduced inflammation, and improvements in sleep and anxiety.

According to CreakyJoints research presented at the 2019 Annual European Congress of Rheumatology meeting earlier this year, 52 percent of respondents reported having tried CBD for a medical reason. Of those who did, 93 percent said it helped. More than half said they wanted more information on CBD from their doctor, but 58 percent of those who told their doctors about their CBD use did not get the information on safety, effectiveness, and dosing they were looking for.

One common concern among people with chronic illness who use CBD is whether CBD can interfere with prescription drugs you may take for arthritis or other conditions.

We put commonly asked questions to Nina M. Bemben, PharmD, BCPS, a specialist in drug interactions who is trying to educate other pharmacists about possible drug-drug interactions with CBD, as well as Rachna Patel, DO, a physician who does consultations about medical marijuana and CBD and sells her own line of CBD products.

What kind of drug interactions can happen with CBD?

A huge number of medications, including CBD, are broken down by the same large family of liver enzymes, called CYP450.

CBD inhibits some enzymes in this family. This makes them break down certain drugs more slowly, which could potentially increase side effects unless your doctor adjusts the dose. On the other hand, CBD induces other enzymes in this family, which speeds the breakdown of certain drugs so they may potentially be less effective unless the dose is increased.

As examples, you may experience increased side effects if CBD is used along with these drugs:

  • Antidepressants (such as fluoxetine, or Prozac)
  • Medications that can cause drowsiness (antipsychotics, benzodiazepines)
  • Macrolide antibiotics (erythromycin, clarithromycin)
  • Heart medications (some calcium channel blockers)

“There is still a lot of uncertainty about how CBD interacts with drug-metabolizing enzymes in the body. We know that there are some drug-metabolizing enzymes that are affected by CBD, some that are not, and many others where we just don’t have any information yet,” says Dr. Bemben.

What do we know for sure about CBD’s interactions with other drugs?

The most direct information comes from studies on the only FDA-approved CBD product, Epidiolex, which is used to treat rare forms of epilepsy. Epidiolex has been found to increase blood levels of the blood thinner warfarin about 30 percent, which raises the risk of bleeding. It also interacts with other medications used for epilepsy.

“The manufacturer of Epidiolex was asked by the FDA to conduct more drug-drug interaction studies, so we will learn more about CBD’s interactions with other drugs in the future,” says Dr. Bemben.

Can CBD interact with medications I take specifically for arthritis?

“Based on what we know now about the way CBD is metabolized, I would not expect significant drug-drug interactions with drugs commonly used in arthritis treatment, such as methotrexate, and most nonsteroidal anti-inflammatory drugs (NSAIDs). I would advise caution on one NSAID, diclofenac, because there isn’t information on how CBD affects — if at all — the enzyme that metabolizes it,” says Dr. Bemben.

Rheumatologists are always on the alert for liver problems that may result from arthritis medications, and that includes CBD as well as NSAIDs and methotrexate.

Are older people more at risk of CBD drug interactions?

Yes, for several reasons. “As we age, our livers and kidneys may be slower to eliminate drugs from the body. In addition, older patients and those with chronic health problems are more likely to be using multiple medications, so the risk for drug interactions increases,” says Dr. Bemben.

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Dr. Patel worries in particular about any side effects or interactions that result in dizziness and may increase the risk of falls in the elderly. For example, using the antidepressant fluoxetine together with cannabis products can increase dizziness and drowsiness.

Are there some people who should stay away from CBD?

Hold off if you have known liver damage, says Dr. Patel. In a study done on mice published earlier this year, the dose of CBD used to protect against seizures was found to induce liver damage. According to other animal research, CBD may increase levels of liver enzymes, raising concerns about liver toxicity in patients taking methotrexate.

“We use other therapies that cause liver injury, like nonsteroidal anti-inflammatories (NSAIDs). If liver enzymes go up in someone on methotrexate, we would generally hold the drug other than methotrexate [for example, CBD or an NSAID] to see if the enzyme levels normalize,” says Michael Weinblatt, MD, professor of medicine at Harvard Medical School in Boston.

People who take Epidiolex for epilepsy are more likely to develop abnormal liver enzymes, as well as sleepiness and other symptoms, if they are also using valproic acid to control seizures.

“This is important for people with arthritis to know because valproic acid is sometimes used for pain that isn’t controlled by other medications,” says Dr. Patel.

If I stick with a CBD cream, does that reduce the risk of drug interactions?

Probably, since little if any of a topical product is likely to be absorbed into your system. “Unfortunately, we just don’t have good information about how much of a topical CBD product gets absorbed. This can be influenced by the inactive ingredients in the product, where on the body it’s applied, and whether you apply a bandage over the area after applying it,” says Dr. Bemben.

While topical CBD products may not be absorbed deeply enough to raise concerns about drug interactions, that also means they may not be as effective for arthritis pain. “If you just have one joint hurting and it’s close to the surface, using a topical would be appropriate. It’s not as likely to help a hip or other deep joint,” says Dr. Patel.

Which health professionals need to know I’m trying CBD?

Tell your rheumatologist and anyone else who prescribes medication for you. If you need surgery, an anesthesiologist may choose a different dose or type of anesthesia if you’re using CBD.

“If you fill all of your medications at the same pharmacy, your pharmacist will be able to assess for drug interactions for all of them, regardless of who prescribed them. You should still let the pharmacist know about over-the-counter medications, herbs, and supplements — including CBD — that you don’t get through the pharmacy. It is important to bring the CBD product to your doctor and pharmacist so they can check the amount of CBD and other ingredients it contains,” says Dr. Bemben.

“While patients may be wary of stigma surrounding CBD products, I believe most health care providers understand this is a growing area and one strategy patients are trying in hopes of getting relief,” she says.

Is there an online source I can use to figure out which of my medications might interact with CBD?

Online databases are available to help health professionals evaluate potential drug-drug interactions, at a price. “Freely available resources tend to be less reliable, and this highlights the importance of discussing all your medications, including CBD, with your doctor and pharmacist,” says Dr. Bemben.

One source available to patients is, where you can plug in either cannabidiol (which will give you the FDA-approved oral product Epidiolex) or cannabis (which will give you both THC and CBD) and check for possible interactions with other medications you take.

Has anyone had a life-threatening drug interaction with CBD?

“There haven’t been reports of serious drug-drug interactions with over-the-counter CBD products. However, these products are relatively new and it typically takes time for reports to be published. We have very little information about over-the-counter CBD products and how they may interact with other drugs,” says Dr. Bemben.

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What You Should Know About CBD and Methotrexate

Michelle Pugle is an expert health writer with nearly a decade of experience contributing accurate and accessible health information to authority publications.

Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.

Anita Chandrasekaran, MD, MPH, is board-certified in internal medicine and rheumatology and currently works as a rheumatologist at Hartford Healthcare Medical Group in Connecticut.

Cannabidiol, also known as CBD, is a non-psychoactive cannabinoid produced by the Cannabis sativa L. plant. It has garnered attention as a natural alternative for treating chronic pain and inflammation for arthritis. However, it can interact with medications that people with conditions like rheumatoid arthritis (RA) are already taking, namely methotrexate. Those taking methotrexate need to know how also using CBD to manage their symptoms can impact their liver functioning.

How CBD Helps Arthritis

CBD has shown therapeutic properties that are potentially useful in the treatment of different forms of arthritis, including anti-inflammatory effects, pain-relieving (analgesic) effects, and possible anti-insomnia effects. These benefits, however, have only been demonstrated in animal studies, not human ones, meaning these findings may not apply to people.

A medical literature review found that some of the evidence supporting the use of CBD is of low quality. The authors concluded that there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.

A more recent study in 2019 showed that CBD can potentially help with RA, but highlights the importance of targeting the right cannabinoid receptors in the right place. Even so, the study authors suggested that further research based on their findings to pinpoint the exact mechanism through which CBD works for people with RA is needed.

The current evidence supporting the use of CBD for arthritis pain is largely anecdotal and derives from animal research. More well-designed, scientifically valid, and rigorous clinical trials are needed to answer the question of how helpful CBD is to people with chronic arthritis pain.

How CBD Works For Pain

Cannabinoids, like non-psychoactive CBD, are said to reduce pain by activating central and peripheral cannabinoid type 1 (CBD1) receptors, peripheral cannabinoid type 2 receptors (CB2) receptors, and CBD-sensitive non-cannabinoid receptor targets.

Cannabinoids show anti-inflammatory effects by activating cannabinoid type 2 receptors (CB2), which decrease cytokine (protein secreted by immune system cells) production and immune cell mobilization. Cannabinoid type 1 receptor (CB1) activation on immune cells is pro-inflammatory, while CB1 antagonism provides anti-inflammatory effects.

Potential Interactions

CBD is a chemical substance metabolized in the liver with the help of cytochrome P450 enzymes, namely the CYP3A4 enzyme. It is estimated that 60% of clinically prescribed drugs, including methotrexate, are also metabolized via CYP3A4. This means some medications can either inhibit CBD’s therapeutic potential or lead to slower substance degradation, leading to higher CBD doses that are active in the body longer.

Animal studies have linked the use of CBD to increased liver enzyme levels, which raise the risk of liver toxicity in people taking methotrexate, which has also been associated with elevated liver enzyme levels. Increased liver enzyme levels indicate problems with the liver. This is why it’s crucial to be transparent with your healthcare provider about any medications (including over-the-counter drugs), supplements, vitamins, or herbs you may be consuming to reduce risk of negative interactions. Never begin, alter, or stop the use of CBD without consulting your healthcare provider.

CBD, Methotrexate, and Alcohol

While using CBD or taking methotrexate, you should limit or avoid consumption of alcohol. Alcohol is a known toxic substance that adds stress to your liver—the organ responsible for detoxifying and removing alcohol from your bloodstream. Increasing the toxic load on your liver can increase your risk of liver damage since CBD and methotrexate are tied to a higher risk of liver toxicity.

Any amount of alcohol in your system will take metabolic priority, which interferes with your ability to effectively metabolize medications like CBD and methotrexate.

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When to Call Your Healthcare Provider

You should call your healthcare provider if you have any of the following symptoms of liver damage:

  • Fever
  • Chills
  • Joint pain or swelling
  • Unusual bleeding or bruising
  • Skin rash or itching
  • Loss of appetite
  • Fatigue
  • Nausea or vomiting
  • Abdominal pain
  • Dark urine
  • Pale stools
  • Yellowing of the skin or eyes

Monitoring Liver Function

If your healthcare provider decides CBD and methotrexate are appropriate for your arthritis, they will also recommend liver function monitoring. Your healthcare provider will order periodic liver panels, which are a group of lab tests that will check everything from your liver enzyme levels to the rate at which your liver metabolizes certain substances.

These tests offer early detection of liver problems and toxicity to prevent further issues and potential damage as well as preserve optimal functioning. You can also have individual tests conducted to monitor specific liver enzymes such as AST and ASL.

The elderly needs to take extra precautions because the liver’s ability to metabolize many substances decreases with aging.

How to Use CBD Safely

Taking CBD and methotrexate together should only ever be done under the supervision of a medical professional who knows your current list of prescriptions, vitamins, supplements, and over-the-counter medications.

Tips for safely using CBD when you have arthritis:

  • Do not use CBD as a substitute for disease-modifying treatment for inflammatory arthritis
  • Always talk to your prescribing healthcare provider or rheumatologist before starting or stopping CBD treatment
  • As with any cannabis product, start low (dose) and go slow (when titrating)
  • Avoid vaping CBD because the inhalation of vapor oils and chemical byproducts carry unknown risks, particularly for people with inflammatory arthritis
  • If you experience negative side effects like drowsiness or nausea when using any CBD product, contact your healthcare provider

Tips for safely using CBD and methotrexate:

  • Talk to your healthcare provider about recommended dosing times
  • Keep a diary of symptoms and responses to your medications
  • Avoid taking CBD edibles like gummies and chocolates because onset and dosing is unreliable
  • Do try topical CBD creams and salves on the skin area over painful joints, but know that more research is needed to confirm how CBD is delivered through the skin barrier

What to Look For

CBD products exist outside the regulations that ensure safe handling, processing, and administering of prescription drugs. This means you can find CBD products everywhere from online to farmer’s markets, so there may be concerns about purity and potency of the products you purchase.

According to one study on currently available CBD products, nearly 43% were under-labeled, meaning their cannabinoid content was higher than the label claimed, around 26% were over-labeled, meaning they contained more CBD than claimed, and just 30% were accurate.

Other considerations include THC content and the presence of additional ingredients, preservatives, and contaminants.

When looking for a CBD product:

  • Look for products manufactured in the United States with ingredients grown domestically
  • Choose products made by companies that follow good manufacturing practices established by the FDA for pharmaceuticals or dietary supplements or required by the state where they are manufactured
  • Buy from companies that test each batch and provide a certificate of analysis from an independent lab that uses validated standardized testing methods approved by the American Herbal Pharmacopoeia (AHP), the U.S. Pharmacopeia (USP), or the Association of Official Agricultural Chemists (AOAC)
  • Avoid companies that claim their products have disease benefits
  • Be aware that marketers and people behind retail counters are not health professionals; they are salespeople

A Word From Verywell

Taking CBD along with methotrexate increases your risk of liver toxicity and requires periodic liver monitoring to preserve overall health and function. While the CBD market expands and continues to go unregulated, claims of all kinds are repeated by manufacturers looking to sell products to people who care about their health. Put your healthcare provider’s professional opinion above any company’s claims and remember human studies are still needed to understand the full potential and risks of using CBD for RA.