- CBD is not likely to trigger interactions with drugs at low or moderate doses that are used by the majority of users of artisanal products. The interactions that are reported in the scientific literature typically occur at extremely large doses that are used in clinical trials for epilepsy as well as other disorders. [1]
- The most significant drug interactions can be identified by comparing CYP450 metabolic pathways utilized in the metabolism of CBD and other substances.
How Do CBD Drug Interactions Occur?
There are two kinds of interactions between drugs which alter the metabolism, absorption, and excretion of either or both of the substances (pharmacokinetic interactions) as well as those that are based upon the mechanisms of actions of the drugs (pharmacodynamic interactions). Because cannabinoids, like CBD have metabolic pathways that are shared with other drugs and share similar mechanisms of action to other drugs, the possibility for interactions is there. The majority of interactions that are clinically relevant for CBD with other medications are related to competition within the detoxification pathways of the liver. Sometimes, the combination makes each drug stronger, through slowing down metabolism and increasing the levels of the drug in the body. Alternatively, each can reduce its effects on the others, by increasing the metabolism of the other. Both can cause unwanted side effects. Of the more than 50 liver enzymes that comprise the CYP450 family of enzymes that help in the metabolisation of drugs Two enzymes are the primary ones responsible for the metabolisation of CBD: CYP3A4 and CYP2C19. Knowing these enzymes can help your health professional or you to determine the metabolic process of a drug and determine whether a CBD-drug interaction could be possible. The majority of CBD-drug interactions observed in humans, and also in rodent studies, been caused by high doses of CBD which aren’t typical for most users, however they can be utilized under medical supervision for treating seizures and other serious illnesses. The majority of the possible drug interactions are speculative and unlikely to happen in the majority of CBD users. Based on my experience in clinical practice it’s rare for CBD users to experience interactions with doses less than 100mg per day. [2]Most Common CBD Drug Interactions
CBD, Warfarin as well as various blood thinners
I’m often asked about the interactions that could be experienced with blood thinner, warfarin (also called by the brands Coumadin(r) as well as Jantoven(r)). The most important issue with warfarin’s interaction with THC since both warfarin and THC are processed through the enzyme in your liver called CYP2C9. If warfarin and THC are competing with this enzyme for processing the levels of warfarin can rise and increases the chance of bleeding. Patients taking warfarin should test their blood INR levels checked after adding cannabis containing THC to their treatment. Although it is possible that taking large quantities of CBD together with warfarin or other blood thinners could result in a negative interaction, the danger is not as significant because the enzyme responsible for metabolizing CBD (CYP2C19) can be distinct. A case report, however, was published that demonstrated the necessity of adjusting the dose of warfarin after beginning and gradually increasing CBD to a very high dosage. [3] Based on this study, those taking large doses of CBD in conjunction with warfarin must inform their physician and test their blood INR. In my practice, I’ve not seen an increase in the INR after my patients take CBD. Additionally, there is a possible connection between CBD and oral anticoagulants such as apixaban and Rivaroxaban, which are based on the CYP3A enzyme (and the P-gp efflux transporter) which could increase the chance of bleeding. Although no interaction with CBD and these medications have been documented in the scientific literature, those taking these medications and large doses of CBD must be aware of bleeding and bruising that is easy to treat. [4] The antiplatelet drug clopidogrel gets transformed to its active form via CYP2C19 and, in lesser amounts, CYP3A4. Thus that using CBD along with clopidogrel may cause a decrease in the therapeutic effects of clopidogrel. Additionally, doctors may decide to check for the appropriate response of platelets and the aggregation. This interaction is purely theoretical, and there are no case studies in the research literature. [5]CBD and Seizure Disorder Medications
Interactions between drugs and CBD are common among those suffering from seizures, particularly those who are taking high doses of CBD. When CBD is administered in conjunction in conjunction with CBD blood levels of the following medications could increase:- topiramate
- rufinamide
- N-des-methylclobazam (an active metabolite of drug clobazam)
- Zonisamide
- eslicarbazepine Patients who combine CBD along with seizure medication valproic acid must be aware of their the liver function for any potential problems.
- A recent study on animals found that, in contrast to THC, CBD actually raised the intraocular pressure. Researchers determined that the increase in pressure resulted from CBD’s effects on CBD in the CB1 receptor (negative allosteric modulation). In the same study, it was discovered that the addition of CBD in the form of THC completely prevented the effects of IOP reduction from the THC. [9]
- A study of a human subject who had elevated IOP discovered the 20mg of CBD did not have any effect however 40mg of CBD resulted in a slight increase of IOP. [10] Contrary to CBD, CBDA is not likely to have an effect on IOP because it doesn’t have the same CBD-like activity as CBD in CB1 receptor. CB1 receptor. If you suffer from glaucoma and are beginning to use CBD supplements, I suggest checking your eye pressure to determine if the CBD causes elevated pressure. Glaucoma sufferers who wish to take cannabis to reduce their IOP are likely to prefer THC-dominated products that are low in CBD. Patients with glaucoma who want to utilize hemp products to treat other ailments are likely to benefit from CBDA formulations. Glaucoma sufferers with well-controlled IOPs and are looking to take cannabis to safeguard the retina are likely to gain from the combination with CBD as well as THC.
CBD and Statin Cholesterol Medications
Statins are one of the most common families of medications to be considered to interact with CBD since they of them are processed through the enzyme CYP3A4. The combination of CBD along with statins could theoretically increase the amount of statins within the body, increasing the chance of adverse negative effects. Statins are also less compatible with CBD since statins are known to produce side symptoms that are typical and similar to symptoms we treat by using CBD. For instance, many statin medications can trigger problems with memory, muscle pain and fatigue, as well as muscle weakness. Since I see a significant number of patients suffering from chronic pain who already taking the maximum daily dosage of their statin medication I often discuss alternative treatments with their doctor, such as changing to pravastatin, which is one of the statins that is processed by different routes and reducing the dosage of the statin currently being used, or including coenzyme Q10 in order to reduce the potential adverse effects of statins.CBD and Erythromycin and Azole Antifungals
The antibiotic erythromycin as well as the antifungal azole family are commonly used drugs that block CYP enzymes that are responsible for metabolizing CBD. Combining them could theoretically increase the chance of negative consequences.CBD and Antidepressant Drugs
A variety of antidepressants and antipsychotic medications are metabolized using the same enzymes that are found in CBD and CBD, so taking these drugs together could increase the risk of adverse consequences. In six patients taking escitalopram or citalopram and CBD, the combination of CBD (200 to 800 mg per day) significantly increased blood citalopram levels. The adverse events reported by the patients were minor and included diarrhea, fatigue, and nausea. [7] In addition, as with other antidepressants, CBD increases serotonin receptors and using more than one medication that has this mechanism of action may increase the risk of developing a rare disorder called serotonin syndrome. There are no case reports of this kind of interaction have been reported in the literature of science.CBD and Immunosuppressant Medications
CBD could alter the metabolism of anti-inflammatory drugs cyclosporine and tacrolimus through liver metabolism, which could result in higher levels in the blood of these drugs and an increase in possible toxic side adverse effects. [8]CBD and Glaucoma
Glaucoma is the primary diagnosis that people tend to think of when considering cannabis as an alternative to medicine. There is evidence to suggest that THC can lower the elevated intraocular (eye) pressure (IOP) which is a characteristic of the condition. Do you think CBD aid in treating pain? Although the answer isn’t completely clear however, evidence suggests CBD does not help but could cause harm.Consult your doctor prior to using CBD
If you are taking multiple medications, visit more than one doctor or suffer from certain health issues You and your doctor must be aware of all medications you are taking to avoid possible drug interactions. An appointment with a physician who is knowledgeable about CBD and cannabis usage can assist you in establishing the best regimen for your medication and supplements in order to avoid negative interactions. Certain compounds can work in synergy with CBD So asking your physician for advice can help to maximize the benefits on your medication. Utilize online drug interaction checkers to determine which cytochrome P450 enzymes are being used. If they are found to interact with CBD (You might need to type in “Epidiolex” if it does not recognize cannabidiol) Then monitor it more closely and make certain to inform your physician. The need to be cautious is increased when you take greater dosages. Small doses carry the lowest chance of interactions with drugs.References
[1] Stout, Stephen M., and Nina M. Cimino. “Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review.” Drug metabolism reviews 46.1 (2014) (86-95).[2] Alsherbiny, Muhammad, and Chun Li. ” Medicinal Cannabis–Potential Drug Interactions.” Medicines 6.1 (2019): 3.
[3] Grayson, Leslie, et al. ” An interaction between warfarin and cannabidiol, a case report.” Epilepsy and report on behavior 9 (2018): 10.
[4] Paduch, McKenzie, and Angela R. Thomason. ” Potential Drug Interactions Between Cannabinoids and Its Derivatives and Oral Anticoagulants.” Hospital Pharmacy (2021): 0018578720985438.
[5] Greger, Jessica, et al. ” A review of cannabis and interactions with anticoagulant and antiplatelet agents.” The Journal of Clinical Pharmacology 60.4 (2020): 432-438.
[6] Gaston, Tyler E., et al. “Interactions between cannabidiol and commonly used antiepileptic drugs.” Epilepsia 58.9 (2017): 1586-1592.
[7] Anderson, Lyndsey L., et al. “Citalopram and cannabidiol: in vitro and in vivo evidence of pharmacokinetic interactions relevant to the treatment of anxiety disorders in young people.” Journal of Clinical Psychopharmacology 41.5 (2021): 525-533.
[8] Balachandran, Premalatha, Mahmoud Elsohly, and Kevin P. Hill. ” Cannabidiol interactions with medications, illicit substances, and alcohol: A comprehensive review.” Journal of general internal medicine (2021): 1-11.
[9] Miller, Sally, et al. “D9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.” Investigative ophthalmology & visual science 59.15 (2018): 5904-5911.
[10] Tomida, Ileana, et al. “Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study.” Journal of glaucoma 15.5 (2006): 349-353.
