Studies have shown CBD to be a safe substance, but as with any new drug, you must make sure it doesn’t negatively interact with other medications.
Cannabidiol (CBD) is a well-known component of hemp with health benefits such as reducing pain and inflammation after physical activity, relief from occasional sleeplessness, as well as improvements in focus, mood and resilience to stress.
Numerous studies have shown that CBD is a safe, non-impairing, and non-habit-forming substance. The safety profile of CBD has been acknowledged by major health agencies, such as the World Health Organization (WHO), showing that it’s well-tolerated by animals and humans and rarely produces any dangerous side effects.
However, while CBD is safe to take with many medications, it has the potential to produce problematic interactions with others. Most often, CBD interacts with other drugs via liver metabolism.
It is important to know how and why these interactions occur and describe the classes of medications that are processed by the same liver enzymes the body uses to process CBD.
The key takeaways for you to remember are:
- CBD is unlikely to cause drug interactions at low and moderate doses used by most consumers of artisanal products. Drug interactions reported in the scientific literature most often occur at very high doses used in clinical trials of epilepsy and other conditions.
- The most important drug interactions can be predicted by comparing the CYP450 metabolic pathways used by CBD and other drugs. Cytochrome P450 (CYP) is a protein in the blood that plays a key role in the metabolism of drugs.
There are two main types of drug interactions: those that change the absorption, metabolism, and excretion of one or both drugs (pharmacokinetic interactions), and those based on the mechanism of action of the drugs (pharmacodynamic interactions). Since cannabinoids, including CBD, share metabolic pathways with other drugs, and have similar mechanisms of action with other drugs, the potential for interaction exists.
Most of the clinically relevant interactions of CBD with other drugs are related to competition in the liver’s detoxification pathways. Sometimes the combination can make each substance stronger, by slowing metabolism and increasing the levels of the drugs in the body, or one can weaken the effects of the other by speeding up its metabolism. Either can lead to unintended side effects.
Of the 50+ liver enzymes that make up the CYP450 family of drug-metabolising enzymes, two are primarily responsible for metabolizing CBD: CYP3A4 and CYP2C19. Knowing these can allow you or your healthcare provider to look up the metabolism of a pharmaceutical drug and determine if a CBD-drug interaction is possible.
Most of the documented CBD-drug interactions in humans, as well as in rodent studies, have resulted from high doses of CBD that are not typical of most users, but may be used under medical supervision in the treatment of seizures or other serious conditions. So, most of the potential drug interactions are theoretical and unlikely to occur in most CBD users. It is rare for people to experience CBD-drug interactions at doses below 100mg daily.
CBD and Warfarin and other blood thinners
The blood thinner warfarin is also known as by the brand names Coumadin® and Jantoven®. The concern with warfarin is its interaction with THC because both warfarin and THC are metabolized by the liver enzyme CYP2C9. When warfarin and THC compete for processing by this enzyme, warfarin levels can increase and thereby increase the risk of bleeding. Patients using warfarin need to have their blood INR level tested after adding THC-containing cannabis to their regimen.
While it is possible that taking large amounts of CBD with warfarin or other blood thinners can cause a harmful interaction, the risk is less concerning because the enzyme that metabolizes CBD (CYP2C19) is different. One case report was published demonstrating the need to adjust warfarin dosage after starting and titrating CBD to a very high dose. Based on this one report, individuals using high doses of CBD concurrently with warfarin should also notify their medical provider and have their blood INR tested.
There is also a theoretical interaction between CBD and the direct-acting oral anticoagulants like apixaban and rivaroxaban, based on the CYP3A enzyme, potentially increasing the risk of bleeding. While no cases of interactions between CBD and these drugs have been reported in the scientific literature, people using these drugs and high doses of CBD should monitor for signs of easy bruising and bleeding.
The antiplatelet drug clopidogrel is metabolized into its active metabolite by CYP2C19, and to a lesser extent, CYP3A4. Therefore, taking CBD with clopidogrel could result in decreased therapeutic effects of the clopidogrel.
CBD and Seizure Disorder Medications
Drug interactions with CBD are most common in patients with seizures, especially those using high doses of CBD. When administered with CBD, the blood levels of the following drugs may increase:
- n-des-methylclobazam (an active metabolite of the drug clobazam)
Patients combining CBD with the seizure drug valproic acid should monitor liver function for potential abnormalities.
CBD and Statin Cholesterol Medications
Statins are a common family of drugs to consider for interaction with CBD because most are processed by the CYP3A4 enzyme. Taking CBD with statins can theoretically raise the levels of statins in the body, increasing the risk of side effects. Additionally, statins are less compatible with CBD because statins tend to cause side effects that are common and similar to the symptoms we tend to treat with CBD. For example, most statin drugs can cause memory issues, muscle pain, fatigue and muscle weakness. Pravastatin is a statin that is metabolized by other routes or talk to your doctor about reducing the amount of the current statin, or adding coenzyme Q10 to mitigate potential statin-related adverse effects.
CBD and Erythromycin and Azole Antifungals
The antibiotic erythromycin and the azole family of antifungals are common medications that inhibit CYP enzymes that metabolize CBD. Taking them together could theoretically increase the risk of adverse effects.
CBD and Antidepressant Drugs
Several antidepressant and antipsychotic drugs are metabolized by the same enzymes as CBD, and taking them in combination could increase the likelihood of adverse effects. In six patients on citalopram or escitalopram, the addition of CBD (200 – 800 mg daily) significantly increased citalopram blood concentrations. Adverse events reported for these participants were mild and included fatigue, diarrhea, and nausea.
CBD stimulates serotonin receptors, and taking more than one drug with this mechanism of action could increase the risk of a rare condition called serotonin syndrome. No case reports of this interaction have been described in the scientific literature.
CBD and Immunosuppressant Medications
CBD has the potential to affect the metabolism of the immunosuppressant drugs cyclosporine and tacrolimus via liver metabolism, which may result in increased blood levels of these drugs and an increase in the potential toxic side effects.
CBD and Glaucoma
Glaucoma is still the first condition many people think of when they consider cannabis as a medicine. The evidence is clear that THC can reduce elevated intraocular (eye) pressure (IOP), a hallmark of the condition. Be careful, research indicates otherwise:
- A recent animal study found that, unlike THC, CBD actually raised intraocular pressure. The researchers determined the pressure elevation was caused by the effects of CBD on the CB1 receptor (negative allosteric modulation). The same study found that adding CBD to THC completely blocked the IOP-lowering effects of the THC.
- One human study on patients with elevated IOP found that 20 mg of CBD had no effect, but 40mg caused a slight increase in IOP.
Unlike CBD, CBDA is not likely to have any impact on IOP since it does not share CBD’s activity on the CB1 receptor.
If you have glaucoma and start using CBD products, have your eye pressures checked to determine if the CBD is causing elevated pressure.
People with glaucoma who want to use cannabis to lower their IOP will do better with THC-dominant, low-CBD preparations. People with glaucoma might do best with CBDA formulas. People with glaucoma who have well-controlled IOPs wishing to use cannabis to protect the retina are most likely to benefit from a combination of CBD and THC.
Talk with Your Doctor Before CBD Use
If you take several different medicines, see more than one doctor, or have certain health conditions, you and your doctors need to be aware of all the medicines you take to avoid potential drug interactions.
A consultation with a doctor experienced in CBD and cannabis use can help you establish the right routine for your medications and supplements to avoid potentially negative interactions. Some compounds work synergistically with CBD, so asking your doctor can help you maximize the effect of your treatment.
Use online drug interaction checkers to see which cytochrome p450 enzymes are used. If they overlap with CBD (You may have to enter “Epidiolex” if it does not recognize cannabidiol), then monitor more closely and be sure to tell your medical provider, especially with higher doses. Using small amounts poses a very low risk of drug interactions.
Black pepper is one of the most commonly used spices worldwide. It is made by grinding peppercorns, which are dried berries from the vine Piper nigrum. It has a sharp and mildly spicy flavor that goes well with many dishes.
But black pepper is called the “king of spices”. It was used in ancient Ayurvedic medicine for thousands of years due to its high concentration of potent, beneficial plant compounds.
Free radicals are molecules that can damage your cells They are created naturally, such as when you exercise and digest food. However, excessive free radicals can be formed with exposure to things like pollution, cigarette smoke, and sun rays. Excess free radical damage may lead to major health problems.
Black pepper is rich in a plant compound called piperine, which studies have found to have potent antioxidant properties. Ground black pepper and piperine supplements may reduce free radical damage.In animal studies, those fed a high-fat diet plus either black pepper or a concentrated black pepper extract had significantly fewer markers of free radical damage in their cells after 10 weeks compared to rats fed a high-fat diet alone.
Chronic inflammation may be an underlying factor in many conditions, such as arthritis, heart disease, diabetes, and cancer. Laboratory studies suggest that piperine fights inflammation. In studies with animals with arthritis, treatment with piperine resulted in less joint swelling and fewer blood markers of inflammation. Piperine also suppressed inflammation in airways caused by asthma and seasonal allergies.
Piperine has been shown to improve brain function in animal studies. In particular, it has demonstrated benefits for symptoms related to degenerative brain conditions like Alzheimer’s and Parkinson’s disease. In animals with Alzheimer’s disease, piperine improved memory, as the distribution of piperine enabled the animals to repeatedly run a maze more efficiently than those not given the compound.
Piperine extract decreases the formation of amyloid plaques, which are dense clumps of damaging protein fragments in the brain that have been linked to Alzheimer’s disease.
Studies suggest that piperine may help improve blood sugar metabolism. In one study, rats fed a black pepper extract had a smaller spike in blood sugar levels after consuming glucose compared to rats in the control group.
Additionally, 86 overweight people taking a supplement containing piperine and other compounds for 8 weeks experienced significant improvements in insulin sensitivity, which measures how well the hormone insulin removes glucose from the bloodstream.
Black pepper extract has been studied in animals for its potential to reduce cholesterol levels. In one 42-day study, rats fed a high-fat diet and a black pepper extract had decreased blood cholesterol levels. The same effects were not seen in the control group.
Back pepper and piperine are believed to boost the absorption of dietary supplements that have potential cholesterol-lowering effects like turmeric and red yeast rice. Black pepper may increase the absorption of the active component of turmeric, curcumin, by up to 2,000%.
Researchers hypothesize that the active compound in black pepper, piperine, may have cancer-fighting properties. Though no human trials have been performed, researchers a discovering that pipeline may have cancer fighting properties. Test-tube studies found that piperine slowed the replication of breast, prostate, and colon cancer cells and induced cancer cell death.
Another test-tube study screened 55 compounds from spices and observed that piperine from black pepper was the most effective at enhancing the efficacy of traditional treatment for triple-negative breast cancer, the most aggressive cancer type. Piperine has shown promising effects in laboratory studies for reversing multidrug resistance in cancer cells which is an issue that interferes with the efficacy of chemotherapy treatment.
Black pepper may benefit health in many other ways according to preliminary research:
- Boosts absorption of nutrients. Black pepper may increase the absorption of essential nutrients like calcium and selenium, as well some beneficial plant compounds, such as those found in green tea and turmeric.
- May promote gut health. The makeup of your gut bacteria has been linked to immune function, mood, chronic diseases, and more. Preliminary research suggests that black pepper may increase the good bacteria in your gut.
- May offer pain relief. Though it has yet to be studied in humans, studies in rodents suggest that the piperine in black pepper may be a natural pain reliever.
- May reduce appetite. In a small study, 16 adults reported reduced appetite after drinking a black-pepper-based beverage compared to flavored water. However, other studies did not show the same effects.
How to Buy
Pepper is available ground, coarsely-ground, cracked and as whole peppercorns. The whole peppercorns are the best choice as they hold their freshness, flavor, and essential oils longer. Ground pepper deteriorates with time and can take on a bitter flavor. Freshly ground pepper is the best option for full flavor benefit.
How to Store
- Store whole peppercorns in a sealed container in a cool, dry place up to one year. Some sources claim that properly stored, sealed peppercorns can still be viable for up to three years.
- Ground pepper begins to lose flavor after about four months, so if you do not use a lot of pepper, avoid those huge cans.
- Brined peppercorns need to be refrigerated after opening and used within a month.
- Water-packed peppercorns have the shortest shelf life after opening—they should be refrigerated and used within one week.
How to Cook
Black pepper pairs well with other seasonings, including turmeric, cardamom, cumin, garlic, and lemon zest.
Spicy Black Pepper Tofu
Adapted from Kristen Miglore's, “Black Pepper Tofu from Yotam Ottolenghi” from Food 52 Genius Recipes
For the Tofu:
- Olive oil, for sautéeing
- 1 12.3-ounce package of firm tofu packed in water, cut into 3/4-inch cubes
- 2 tablespoons cornstarch
- 6 small shallots, thinly sliced
- 1 fresh red chili (go for milder ones), thinly sliced
- 6 cloves garlic, crushed or very thinly sliced
- 1 tablespoon freshly ground ginger
- 3 1/2 tablespoons tamari
- 1-2 tablespoons maple syrup
- 1 tablespoon blackening spice – see below
- 5-6 green onions cut into 1 1/4-inch lengths
For the Blackening Spice:
- 1/2 tablespoon paprika
- 1 tablespoon garlic powder
- 1 tablespoon onion powder
- 1/2 tablespoon dried thyme
- 1 tablespoon dried oregano
- 1/2 tablespoon salt
- 1/2 tablespoon freshly ground black pepper
- Combine all ingredients for the blackening spice in an airtight jar.
- In a large bowl, toss the tofu cubes with the cornstarch.
- Heat a thin layer of oil into a large frying pan or wok over medium heat and fry half the cubed tofu at a time to prevent overcrowding.
- Fry for about 6-8 minutes or until golden brown, stirring frequently.
- When they are done transfer the tofu to paper towels and complete your second batch adding oil first if needed.
- Remove any sediment from your pan and heat another tablespoon of oil in the same pan.
- Add your shallots, chili, ginger, and garlic and sauté for about 5 minutes or until all the ingredients are soft.
- Add tamari sauce and blackening spice mixing well.
- Add 1 tablespoon of maple syrup.
- Add the tofu to the sauce and mix well to incorporate and warm.
- Add more syrup (1 tablespoon) if needed.
- Finally, stir in the green onions and serve.