Drug interactions can be influenced by a number of factors, including your health, weight, and general tolerance. When CBD oil is combined with blood thinners, several considerations must be made.
Warfarin treatment can increase your chances of bleeding during the first three months. The risk is even greater for older adults. You may also be at risk if you use other blood-thinning medications.
Can CBD Replace Warfarin?
CYP450 is predominantly responsible for the metabolism of warfarin. CBD inhibits this enzyme class. CBD competes with warfarin on the same metabolic pathway, according to a US National Library of Medicine study published in 2017.
What Can Increase the Risk of Bleeding?
Other medical conditions that increase your risk of bleeding are:
INR Trend over time.
A 44-year-old Caucasian male with Marfan Syndrome, mechanical mitral valve replacement, warfarin therapy, and post-stroke epilepsy was enrolled in the University of Alabama at Birmingham open-label program for compassionate use of cannabidiol for the management of treatment-resistant epilepsy ( <"type":"clinical-trial","attrs":<"text":"NCT02700412","term_id":"NCT02700412">> NCT02700412). His seizures began at age 27 concurrent with diagnosis of stroke during the post-operative period from cardiac surgery. Despite initial control of seizures on monotherapy, events returned in 2011 prompting adjustment of anti-seizure medications and eventual consideration of epilepsy surgery. Following video EEG monitoring, he was determined to be a poor surgical candidate due to non-localized seizure onset. Additionally, the need for anticoagulation due to mechanical valve limited more invasive testing for localization of seizure focus as well as posed a challenge for completion of any surgical resection. He was subsequently referred to the UAB CBD program.
At the time of study enrolment, the patient was taking lamotrigine 400 mg and levetiracetam 1500 mg, both twice daily. He was also taking warfarin 7.5 mg daily with a goal International Normalized Ratio (INR) of 2–3. Prior to study entry, his INR had been stable for at least 6 months with levels ranging from 2.0 to 2.6 ( Fig. 1 ). At the initial study visit, his baseline INR was obtained and he was placed on the starting dose of CBD at 5 mg/kg/day divided twice daily. Per study protocol (www.uab.edu/cbd) CBD dose was increased in 5 mg/kg/day increments every two weeks.
The metabolism of CBD is also by way of the hepatic P450 enzyme system. To date there are seven major isoforms identified that contribute to this process: CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5, with CYP3A4 and CYP2C19 being the dominant contributors . Five of the seven isoforms are also involved with metabolism of warfarin, including CYP2C9, which is the dominant enzyme for S-warfarin, and CYP3A4, which is the dominant enzyme for R-warfarin , . In addition to competing for enzymes in same metabolic pathway as warfarin, CBD has been demonstrated to act as a potent competitive inhibitor of all seven of its own CYP enzymes and as such could further impair the degradation of warfarin , . It is this combination of factors that presumably constitutes the observed rise in INR values with concomitant warfarin and CBD administration.
2. Case report
With up-titration of CBD oil, a non-linear increase in the INR was noted ( Table 1 , Fig. 1 ). Warfarin dosage adjustments were made by primary care physician in effort to maintain an INR within his therapeutic range. At the most recent study visit his warfarin dose had been reduced by approximately 30%. The patient was followed clinically without bleeding complications.
Absolutely. Inhaled CBD gets into the blood the fastest, reaching high concentration within 30 minutes and increasing the risk of acute side effects. Edibles require longer time to absorb and are less likely to produce a high concentration peak, although they may eventually reach high enough levels to cause an issue or interact with other medications. Topical formulations, such as creams and lotions, may not absorb and get into the blood in sufficient amount to interact with other medications, although there is very little information on how much of CBD gets into the blood eventually. All of this is further complicated by the fact that none of these products are regulated or checked for purity, concentration, or safety.
Products containing cannabidiol (CBD) seem to be all the rage these days, promising relief from a wide range of maladies, from insomnia and hot flashes to chronic pain and seizures. Some of these claims have merit to them, while some of them are just hype. But it won’t hurt to try, right? Well, not so fast. CBD is a biologically active compound, and as such, it may also have unintended consequences. These include known side effects of CBD, but also unintended interactions with supplements, herbal products, and over-the-counter (OTC) and prescription medications.
Researchers from Penn State College of Medicine evaluated existing information on five prescription CBD and delta-9-tetrahydrocannabinol (THC) cannabinoid medications: antinausea medications used during cancer treatment (Marinol, Syndros, Cesamet); a medication used primarily for muscle spasms in multiple sclerosis (Sativex, which is not currently available in the US, but available in other countries); and an antiseizure medication (Epidiolex). Overall, the researchers identified 139 medications that may be affected by cannabinoids. This list was further narrowed to 57 medications, for which altered concentration can be dangerous. The list contains a variety of drugs from heart medications to antibiotics, although not all the drugs on the list may be affected by CBD-only products (some are only affected by THC). Potentially serious drug interactions with CBD included
Many drugs are broken down by enzymes in the liver, and CBD may compete for or interfere with these enzymes, leading to too much or not enough of the drug in the body, called altered concentration. The altered concentration, in turn, may lead to the medication not working, or an increased risk of side effects. Such drug interactions are usually hard to predict but can cause unpleasant and sometimes serious problems.
Does the form of CBD matter?
The researchers further warned that while the list may be used as a starting point to identify potential drug interactions with marijuana or CBD oil, plant-derived cannabinoid products may deliver highly variable cannabinoid concentrations (unlike the FDA-regulated prescription cannabinoid medications previously mentioned), and may contain many other compounds that can increase the risk of unintended drug interactions.
While generally considered safe, CBD may cause drowsiness, lightheadedness, nausea, diarrhea, dry mouth, and, in rare instances, damage to the liver. Taking CBD with other medications that have similar side effects may increase the risk of unwanted symptoms or toxicity. In other words, taking CBD at the same time with OTC or prescription medications and substances that cause sleepiness, such as opioids, benzodiazepines (such as Xanax or Ativan), antipsychotics, antidepressants, antihistamines (such as Benadryl), or alcohol may lead to increased sleepiness, fatigue, and possibly accidental falls and accidents when driving. Increased sedation and tiredness may also happen when using certain herbal supplements, such as kava, melatonin, and St. John’s wort. Taking CBD with stimulants (such as Adderall) may lead to decreased appetite, while taking it with the diabetes drug metformin or certain heartburn drugs (such as Prilosec) may increase the risk of diarrhea.
CBD has the potential to interact with many other products, including over-the-counter medications, herbal products, and prescription medications. Some medications should never be taken with CBD; the use of other medications may need to be modified or reduced to prevent serious issues. The consequences of drug interactions also depend on many other factors, including the dose of CBD, the dose of another medication, and a person’s underlying health condition. Older adults are more susceptible to drug interactions because they often take multiple medications, and because of age-related physiological changes that affect how our bodies process medications.
Doubling up on side effects
People considering or taking CBD products should always mention their use to their doctor, particularly if they are taking other medications or have underlying medical conditions, such as liver disease, kidney disease, epilepsy, heart issues, a weakened immune system, or are on medications that can weaken the immune system (such as cancer medications). A pharmacist is a great resource to help you learn about a potential interaction with a supplement, an herbal product (many of which have their own drug interactions), or an over-the-counter or prescription medication. Don’t assume that just because something is natural, it is safe and trying it won’t hurt. It very well might.