Cannabidiol and drug-drug interactions

The accumulating body of evidence explaining cannabis-drug interaction indicates that CBD’s inhibitory or enhancing effect is dose-dependent and is not necessarily harmful. In essence, the clinical effect of the cannabis-drug interaction depends on many factors, including the extent of inhibition, the therapeutic window of the affected medication, and the adverse effects of the drug metabolites. For drugs with toxic metabolites, a cytochrome P450 enzyme-enhancing effect increases the metabolism of the drug and, consequently, increases the circulating metabolites’ level. The adverse effects of the affected drug become pronounced momentarily. In drug combinations with potential severe harmful effects, expert recommendation requires dosage modification and drug spacing under medical supervision.


Cannabidiol interaction with common drugs

Currently, there is no official classification for cannabis-drug interactions. Research inquiries on this subject are insufficient and, as such inadequate to formulate a uniform, generally acceptable catalog of drugs to be avoided by patients managed with cannabidiol. As a proposed guideline, some studies have classified cannabis-drug interaction into three categories: (1) Major—a combination with a highly significant risk, to be avoided in patients; (2) Moderate—a combination with a moderate significant risk recommended only when benefits outweighs the risk; and (3) Minor—a combination with minimal risk and such poses no significant health risk under expert supervision. The medical recommendations concerning these interactions are at best derived from anecdotal or self-assessed accounts. 


  • CBD’s interaction with antidepressants

 Antidepressants are becoming increasingly popular in the population. In the U.S., an estimated 12% of the young population is documented to have used an antidepressant in recent times. Prozac and Sarafem are the most popular brands of this drug class. These selective serotonin reuptake inhibitors increase the neurotransmitters’ levels to treat depression, anxiety, and bulimia. 

Antidepressants are common medications prescribed for the aged and young population currently experimenting with cannabis-derived products. As such, experts have observed the effects of CBD on the pharmacokinetic parameters of antidepressants. The CBD-drug interactions, as observed for these classes of drugs, have been beneficial. The anti-anxiety effects of CBD have been studied extensively. By co-administering CBD with antidepressants, this cannabinoid enhances the effects of antidepressants in a synergistic relationship. 


  • CBD’s interaction with warfarin

Warfarin is a blood thinner primarily indicated for venous thrombosis, stroke, and thromboembolism. As with other anticoagulants, warfarin interferes with the hepatic synthesis of the clotting factors and prevents abnormal blood coagulation. The condition for which warfarin is prescribed is common in aged patients who might need CBD for pain management or as an appetite stimulant. 

In 2017, Epilepsy and Behavior Case Reports published the details of a research study investigating the interaction between warfarin and CBD. As indicated by this research, warfarin, and CBD are metabolized by about five enzymes directly involved in the metabolism of warfarin. The CBD metabolic pathway competes for these enzymes, and most importantly, CBD has long been demonstrated to inhibit the activities of these enzymes. Resultantly, such impairs the degradation of warfarin by these enzymes is impaired, and the level of circulating warfarin is increased. Patients combining these two drugs can suffer from hemorrhage as adverse effects of excessive blood thinning.



  • CBD’s interaction with antiretroviral drugs

In advanced stages of HIV/AIDS, the clinical manifestations are many and can include pain, nausea, anxiety, and inflammation. This disease is a global burden affecting over 40 million people who are sometimes managed with CBD as complementary medicine for symptoms management. Research studies have suggested that CBD boosts the immune system and effectively manages anxiety and pain. When co-administered, clinicians have observed that CBD offers lasting relief for symptoms presented in patients on antiretroviral medications. There is currently no conclusive evidence of this observation. However, The BMJ published a proposal outline for a study aimed at investigating the interaction between oral cannabinoids and antiretroviral drugs in people living with HIV/AIDS. 


  • CBD’s interaction with anti-epileptic drugs

The interaction between cannabidiol and anti-epileptic drugs (AEDs) has been studied extensively. These studies were conducted following clinical reports of significant adverse effects noticed in patients treated with the common anti-epileptic drugs Clobazam and Valproate. Popular research examining the pharmacokinetic interaction between cannabidiol and serum level of AEDs was published in 2018 by Epilepsy Currents. According to the findings, with the exemption of clobazam, topiramate, zonisamide and eslicarbazepine, the pharmacokinetic parameter of most AEDs remains unaltered when co-administered with CBD (Gatson et al., 2018).

Participants in this study have diagnosed cases of refractory epilepsy and received cannabidiol in gradually increasing doses. The levels of serum AEDs were also checked periodically. The results of this research indicated that the serum levels of clobazam metabolites are noticeably increased. This result agrees with earlier studies suggesting that CBD and clobazam administration increases the risk of hepatotoxicity and sedation in patients. 


  • CBD’s interaction with alcohol

Alcohol is not expressly classified as a drug; however, its use has increased noticeably over the decades. Binge drinking is now a common practice among millennials—a demographic also likely abuse cannabis-derived products. This observation has fueled different research studies investigating the interaction between CBD and alcohol consumption. Alcohol is metabolized primarily by three different enzymes: alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P450 E21 (CYP2E1). Cannabinoid affects the activity of almost all these enzymes and, as such, is expected to alter the metabolism of alcohol. Different researches have studied the CBD-alcohol interaction with different submissions suggesting no significant harmful effects. According to these studies, CBD significantly lowers blood alcohol levels, reduces alcohol consumption, motivation, and relapse. In addition, CBD also attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation, and alcohol-induced neurodegeneration. 


Generally, cannabidiol and other cannabis-derived products interact with almost all the drugs metabolized by cytochrome P450 enzymes. It is recommended that patients consult a pharmacist or a physician for adequate information regarding CBD’s potential effects on their medication before co-administration. 



Anthony Tribunella

Having experienced the benefits of CBD first hand when it was starting to gain popularity, Anthony decided to spend his working life championing it to the public and his peers in the wider CBD community. As a CBD innovator himself, Anthony likes to remain at the leading edge of scientific and product development to ensure that the potential of CBD has every chance of being fully realized.

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