10 Medications That Interact Negatively with CBD

There are 562 drugs known to interact with cannabidiol (CBD) — 13 have significant drug interactions, 499 moderate, and 50 are minor potential interactions.

Most major and moderate negative interactions are with drugs that are opioids or sedatives, e.g., benzodiazepines and sodium oxybate. Some of these are cancer medications used in immunotherapy or hormone treatments, e.g., pexidartinib (Turalio) and relugolix (Orgovyx, Relumina). In some instances, CBD products and medical cannabis may be utilized to reduce reliance on some drugs it interacts with.

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How CBD Can Affect Medications

There are three main ways CBD can affect the way other drugs behave:

1. It can interfere with metabolization in the liver. This could be due to an increased risk of hepatic impairment when combined with some drugs (e.g., teriflunomide, an immunomodulatory drug for multiple sclerosis) or CBD’s ability to desensitize the liver enzyme cytochrome P450 (CYP450). This can increase the level of other drugs in the body, as they are not being metabolized and broken down entirely, leading to an increased risk of negative side effects.
2. The sedative effects of high doses of CBD can increase the sedative effects of other drugs that affect the central nervous system (CNS), dopamine receptors, or serotonin receptors. This includes opioids, benzodiazepines, barbiturates, antidepressants, and alcohol.
3. CBD’s anti-inflammatory and immunomodulatory properties (i.e., its ability to suppress or stimulate the immune system) can interfere with other drugs with similar effects.

Many drugs that interact with CBD also interact with medical cannabis in similar ways.

Medications That Interact with CBD

Opioids, Particularly Propoxyphene, Morphine, and Buprenorphine

Using buprenorphine with CBD can increase the likelihood of suffering severe side effects such as respiratory distress (including respiratory depression, coma, and even death).

Cannabinoids like CBD can help reduce the need for opioid-based painkillers.

Immunosuppressives Such as Leflunomide and Teriflunomide

Some immunosuppressives like Leflunomide may cause liver problems. Using it with other medications that can also affect the liver, such as cannabidiol, may increase that risk.

Corticosteroids Like Hydrocortisone and Prednisolone

Corticosteroids can inhibit the cytochrome P450 enzyme CYP3A, and so can CBD. Concomitant use may decrease glucocorticoid clearance and increase the risk of side effects.

Hormones Like Levothyroxine

A 2017 study found that if a patient takes the thyroid medication levothyroxine and CBD simultaneously, levothyroxine is not metabolized properly. This leads to a buildup of thyroxine, which can lead to hyperthyroidism and troubles with digestion, the heart, and muscle function.

Antidepressants Such as Fluoxetine (Prozac)

Like corticosteroids, using CBD interferes with the enzymes in the liver that break down many drugs, including antidepressants. Their interactions may lead to insufficient concentrations of the drug in the body (or the opposite: too much, leading to an increased chance of overdose), resulting in subtherapeutic effects. Using the two together may also increase the likelihood of sedation and dizziness. CBD may also alleviate depression and decrease antidepressant and sedative intake.

Some Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Like Ibuprofen and Diclofenac

Using CBD and diclofenac (Voltaren) together may increase the likelihood of suffering from liver problems, stomach bleeding, or GI upset. Regular use of high doses of CBD and high amounts of NSAIDs like ibuprofen, diclofenac, and other stronger NSAIDs are more often associated with such complications.

Anticoagulants and Anti-platelets Like Warfarin and Clopidogrel

Using CBD together with warfarin (Coumadin) may increase the blood levels and effects of warfarin. As warfarin is an anticoagulant, this can thin the blood to dangerous levels, and this can cause clotting, wound-healing, and bruising problems and potentially affect heart rate.

CBD also inhibits the enzyme CYP2C19, an isoenzyme responsible for the transformation of clopidogrel to its active thiol metabolite. This can lead to “subtherapeutic levels of the active metabolite and possibly increased stroke risk.”

Benzodiazepines Such as Alprazolam and Lorazepam

Using CBD with benzodiazepines can increase the likelihood of suffering from side effects such as dizziness, drowsiness, confusion, and difficulty concentrating.

Many benzodiazepines, including alprazolam, triazolam, brotizolam, and midazolam, are mainly metabolized by CYP3A4. CBD desensitizes this enzyme, interfering with how the liver metabolizes benzodiazepines. This also increases the chances of negative and subtherapeutic effects.

Benzodiazepines may be prescribed for the short-term treatment of anxiety and PTSD or the long-term treatment of seizures, including those caused by epilepsy. CBD is effective for Lennox-Gastaut and Dravet syndrome, forms of epilepsy that are often managed by addictive sedatives. CBD could be used to reduce benzodiazepine intake.

Antipsychotics Such as Aripiprazole

Interestingly, CBD has antipsychotic properties and could be used on its own or in combination with other antipsychotics for managing psychosis in schizophrenia or bipolar disorder. However, concomitant use can also lead to increased sleepiness, fatigue, and possible accidental falls. CBD may also interfere with the metabolization of some types of antipsychotic medications.

Antihistamines Such as Diphenhydramine (Benadryl)

Using CBD with antihistamines like diphenhydramine can increase their sedative properties.

Does the Type of CBD and Dose Matter?

Broad-spectrum and full-spectrum CBD oils contain other cannabinoids and terpenes, which can also interact with any other medications you are taking. CBD isolates mean it is just the CBD (and possibly other non-cannabis or hemp ingredients) that interact with the medication.

Inhaled CBD acts fastest (peaking within 30 minutes) and may increase the risk of immediate (acute) side effects. Edibles can take a longer time to reach their high concentration point, but their potency can drastically increase the sedative effects of other medications. Topical creams and salves do not tend to penetrate past the first few layers of skin, so they are unlikely to get into the bloodstream and react with other medications. Transdermal patches release cannabinoids slowly into the bloodstream and do not necessarily reach a high concentration peak, but their potency and long-lasting effects may cause negative drug-drug interactions.

CBD also has biphasic effects, meaning it has two different effects at different dosages. In low doses, CBD is stimulating, and in higher doses, it is more sedative. Higher doses of CBD may be more likely to interfere with a sedative, antidepressant, and NSAID metabolization than lower doses.

So yes, CBD’s type, form, and dose do matter.

The Bottom Line

Although CBD is a well-tolerated compound with few severe or adverse side effects, there are some potential complications. Those suffering from serious health problems would be well advised to speak to a medical marijuana doctor first if they intend to start using CBD in addition to taking over-the-counter and prescription medications.

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