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Important Medical Cannabis and Drug Interactions: What Every Patient Needs to Know
Important Medical Cannabis and Drug Interactions: What Every Patient Needs to Know
Medical Cannabis and Drug Interactions: What Every Patient Needs to Know
Cannabis has made broad strides in gaining social acceptance and legal status in the last several years. Now, in 2025, cannabis can legally be prescribed for medical use in 40 of 50 states, and 24 states have legalized recreational use. While more than 70% of Americans now have legal access to cannabis, which is great news, it also means that now is the time for education.
More people with access to cannabis means that more people are finally able to reap its benefits, from calming their nerves or enhancing creativity to easing the physical discomfort of nausea, headaches, and more. However, increased usage also means additional opportunities for interactions with other medications.
Pharmacists and physicians are getting up to speed on the research to stay ahead of any possible contraindications, but building up a full knowledge profile can take years. Here’s what we know so far, to help you stay safe.
Understanding Drug Interactions
Pharmacokinetic interactions occur as the body undergoes the natural process of absorbing, distributing, metabolizing, and eventually excreting a particular drug. Your body’s pharmacokinetics can change with age or as a result of a medical condition, so doctors will take your medical history and current physiological state into consideration when evaluating the possibility of adverse pharmacokinetic interactions.
Pharmacodynamic interactions describe the way in which the body responds to a particular drug or a combination of drugs and foods. When the interaction is the result of a combination of drugs or foods, the pharmacodynamic interactions can be inductive, which means one substance works in a similar way and can increase the effects of another drug. They can also be inhibitive, meaning one substance acts in a way that antagonizes or lessens the effect of another.
The latest research efforts have focused on identifying the ways in which cannabis may impact the body’s pharmacokinetic interaction with other medications. Researchers are particularly interested in how the cannabinoids THC and CBD are metabolized by the cytochrome P450 enzyme, the enzyme responsible for the metabolism of many common prescription medications.
Cannabinoids and the Cytochrome P450 System
The metabolism of the cannabinoids THC and CBD is facilitated by specific liver enzymes, including CYP3A4, CYP2C9, and CYP2C19, which are all part of the cytochrome P450 system. Because these are the same enzymes responsible for metabolizing common prescription medications, researchers need to understand what happens when the cytochrome P450 is tasked with metabolizing a cannabinoid and another drug simultaneously.
When drugs compete for the same enzymes, one or both may be inhibited, leading to reduced therapeutic effect, or induced, resulting in overdose and other unintended harms. To prevent these harms, researchers need to understand the interaction between cannabinoids and cytochrome P450.
Common Medications with Potential Interactions
The rising concern regarding medical cannabis drug interactions stems from the shared reliance on the cytochrome P450 system and the lack of robust evidence-based research and case studies.
With the widespread state legalization of cannabis, it’s easy to forget that federal regulations still classify cannabis as a Schedule 1 controlled substance, which limits scientists’ ability to study THC and CBD metabolism. The rising concern regarding medical cannabis drug interactions stems from this lack of robust evidence-based research and case studies.
Antiepileptics
The cannabinoid CBD has been proven to be effective at reducing the severity of epileptic symptoms for patients with treatment-resistant seizures. This beneficial use put the study of antiepileptic and cannabis interaction at the top of the priority list.
Early studies of concomitant CBD and antiepileptic medication use found that CBD increased serum levels of the antiepileptic drug, clobazam, increasing reported adverse events like diarrhea, vomiting, and fatigue, with increased drowsiness being the most frequent complaint.
CBD’s seizure-reducing activity continues to make it a beneficial addition to the therapeutic protocol for specific patients. In these cases, doctors can reduce adverse events by starting with a low dose of CBD and building up slowly while carefully monitoring serum levels of antiepileptic drugs.
Anticoagulants
While most studies of anticoagulants and cannabis have shown little evidence of increased adverse effects, there is some indication of a potential Warfarin and cannabis bleeding risk. Warfarin is a popular anticoagulant metabolized by the same CYP2C9 enzyme responsible for the metabolism of THC.
Studies have shown that THC inhibits the metabolism of Warfarin, increasing bleeding risk. Currently, patients taking Warfarin are advised to avoid cannabis use.
Immunosuppressants
There is anecdotal evidence that immunosuppressants and cannabinoids may increase the risk of elevated drug concentrations and toxicity. Both THC and CBD cannabinoids have been shown to inhibit the CYP3A4 enzyme, which is a key factor in the metabolism of the immunosuppressant drug, tacrolimus.
Tacrolimus is commonly used as an immunosuppressant following an organ transplant procedure. Elevated blood concentration of tacrolimus can result in slowed recovery post-transplant surgery and may lead to more serious adverse events, including neurotoxicity and increased morbidity risk.
Central nervous system depressants
Central nervous system (CNS) depressants like opioids and benzodiazepines have a potent sedative effect. Cannabis, particularly THC, can produce CNS depressant effects as well. When taken together, cannabis and CNS depressants may produce an additive drug-drug interaction that amplifies the sedative effects of both drugs.
Antidepressants
The CYP2D6 enzyme is involved in the metabolism of many SSRIs, tricyclic antidepressants, and antipsychotics. Because cannabis inhibits CYP2D6, antidepressants and cannabis use could result in increased side effects due to elevated blood concentrations of antidepressant medications.
On a positive note, there has been some indication that cannabis interaction with dopamine receptors may allow for the reduction of certain antidepressants, like opioids.
Factors Influencing Drug Interactions
The frequency and severity of adverse reactions resulting from the use of cannabis with prescription medications are often mitigated by several factors.
Frequency of cannabis use
More frequent use of cannabis, or high doses, can lead to increased inhibition of the cytochrome P450 system, leading to increased levels of prescription medications in the bloodstream. The most significant interactions are likely to result in patients who consume more than 30mg of THC per day, or more than 300mg of daily CBD.
Individual metabolic differences
The normally occurring differences in individual metabolic function can impact the likelihood of adverse cannabis and prescription medication interactions. Patients with slower metabolic function due to disease or age may have increased blood concentrations of cannabinoids and prescription medications, increasing the risk of adverse effects like drug toxicity.
Polypharmacy
Polypharmacy, or taking five or more medications at one time, along with cannabis, can lead to an increased risk of adverse reactions. This risk increases as the number of medications consumed rises.
Recognizing and Managing Potential Interactions
The symptoms of a potential adverse interaction may be significant or subtle, depending on the individual and the specific drugs involved in the interaction. While some patients have reported notable symptoms like dry mouth, dizziness, nausea, and diarrhea, other potentially serious interactions were only identified after lab tests revealed an anomaly.
This variability in symptom expression highlights the importance of consulting with your physician before using cannabis with prescription medications and scheduling regular lab testing during use.
Special Considerations for Older Adults
As we age, organ function declines. This physical fact of life happens to even the healthiest and most active seniors. As organs become less efficient at breaking down and processing medications, the risk of adverse reactions increases.
Older adults may experience greater susceptibility to, and increased impact of the cognitive impacts of certain drugs, including cannabis.
Additionally, older adults are more likely to require prescription medications, increasing their opportunities for experiencing an adverse interaction between cannabis and one or more prescription drugs.
An estimated 85% of seniors have used at least one prescription drug in the past month. Considering the fact that adults between 45 and 65 years old were among the most likely to have tried cannabis, educating this cohort on the beneficial effects and potential risks of cannabis use is particularly important.
Resources for Patients and Healthcare Providers
For the time being, scientific data on polypharmacy and cannabis remains scarce. The Pennsylvania State University, College of Medicine, Department of Pharmacology maintains a publicly accessible list of cannabinoid interactions with prescription medications. European database, EudraVigilance, logs reports of adverse events associated with the concomitant use of prescription drugs and cannabis. Frontiers in Pharmacology offers a free online tool designed to identify potential drug-drug interactions between cannabis and prescription medications.
Physicians can turn to tools like the EBM Consult, an online system containing 16 different databases of free medical education information for use by healthcare teams.
Recent advances in DNA testing, which enable the practice of truly personalized medicine, should become the future gold standard in assessing an individual’s risk of adverse drug interactions.
Conclusion
While there is still a significant lack of peer-reviewed scientific research on the pharmacokinetic effects of cannabis, the known interactions discussed in this article provide a solid baseline understanding of the risks associated with using cannabis with several common prescription medications.
As the federal government moves toward legalization, the knowledge base surrounding cannabis interactions with other medications is expected to expand rapidly. However, the gold standard of care remains the personalized medical advice provided by your primary care physician.
Despite the interactions described here, serious adverse effects are actually pretty rare, and most people tolerate cannabis use well. You can increase your safety and reduce risk even further by consulting with your doctor before considering cannabis for symptom management or recreational use.
If you are interested in exploring cannabis medicine for the treatments and would like to understand more about potential drug interactions, reach out to us to book your telemedicine appointment.
