Cannabidiol (CBD)

Prescription CBD is used for treatment of certain seizure disorders.

Some people use CBD to treat many other health problems, including the following:

• Bipolar disorder

• Pain

• Anxiety

• Crohn disease

• Diabetes

• Sleep problems

• Multiple sclerosis

• Symptoms of withdrawal from heroin, morphine, and other opioid drugsSymptoms of withdrawal from heroin, morphine, and other opioid drugs

Oral CBD has been approved by the US Food and Drug Administration (FDA) for the treatment of seizures associated with two epileptic encephalopathies: Lennox-Gastaut syndrome and Dravet syndrome. These epileptic encephalopathies start in childhood and involve frequent seizures along with severe impairments in cognitive development. Two clinical studies have reported on the effectiveness of CBD in these patients and other patients with treatment-resistant epilepsies (2, 3). However, not enough research has been done on cannabinoids for other, more common forms of epilepsy to determine if they are helpful for these conditions.

A 2018 Cochrane systematic review on cannabis‐based medicines for chronic neuropathic pain in adults included 16 studies with 1750 participants (4). The analysis showed that cannabis‐based medications may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%). Cannabis-based medications probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%). The authors concluded that this small improvement in neuropathic pain might be outweighed by the potential harms.

There are numerous clinical studies regarding the uses of CBD for various symptoms and disorders summarized on the National Institutes of Health (NIH) website.

CBD can have adverse effects such as dry mouth, low blood pressure, diarrhea, decreased appetite, mood changes, light-headedness, fatigue, rash, insomnia and poor quality sleep, and sleepiness.

CBD can cause increased transaminases and liver injury.

CBD is metabolized by the cytochrome p450 (CYP) enzymes CYP3A4 and CYP2C19. Coadministration with medications that are metabolized by or inhibit CYP3A4 or CYP2C19 can increase plasma concentrations of these medications or of CBD, which may result in increasing their effects and a greater risk of adverse reactions (5).

CBD may increase the serum concentration and effects of a number of drugs including the following:

• Antiseizure medications (eg, brivaracetam, carbamazepine, clobazam, topiramate)Antiseizure medications (eg, brivaracetam, carbamazepine, clobazam, topiramate)

• Immunosuppressants used to prevent rejection after an organ transplant (eg, cyclosporine, tacrolimus)Immunosuppressants used to prevent rejection after an organ transplant (eg, cyclosporine, tacrolimus)

• Anticoagulants (eg, warfarin)Anticoagulants (eg, warfarin)

• Tricyclic antidepressants

• Proton pump inhibitors (eg, omeprazole); diarrhea may occurProton pump inhibitors (eg, omeprazole); diarrhea may occur

• Nicotine, prolonging duration of action of nicotineNicotine, prolonging duration of action of nicotine

• Lithium, causing or increasing lithium toxicityLithium, causing or increasing lithium toxicity

• Ketamine, possibly enhancing antidepressant effectsKetamine, possibly enhancing antidepressant effects

• MethadoneMethadone

• LevothyroxineLevothyroxine

CBD can cause sleepiness and drowsiness, so taking both CBD and sedatives (eg, benzodiazepines, phenobarbital, morphine, alcohol) may make people too drowsy.CBD can cause sleepiness and drowsiness, so taking both CBD and sedatives (eg, benzodiazepines, phenobarbital, morphine, alcohol) may make people too drowsy.

Information on interactions is emerging. Any medication that has a narrow therapeutic index (eg, amiodarone) warrants caution and close monitoring with CBD use due to the possibility of drug interactions.Information on interactions is emerging. Any medication that has a narrow therapeutic index (eg, amiodarone) warrants caution and close monitoring with CBD use due to the possibility of drug interactions.

Acetaminophen, valproic acid, and CBD can cause liver injury, so the combination of CBD and acetaminophen or valproic acid might increase the chance of liver injury.Acetaminophen, valproic acid, and CBD can cause liver injury, so the combination of CBD and acetaminophen or valproic acid might increase the chance of liver injury.

A number of drugs, including antiseizure medications and rifampin, may lower the serum concentration of CBD.A number of drugs, including antiseizure medications and rifampin, may lower the serum concentration of CBD.

Tricyclic antidepressants may increase serum concentrations of CBD and thus may increase adverse effects of CBD.

(See also table Some Possible Dietary Supplement–Drug Interactions.)

1. 1. Bonn-Miller MO, Loflin MJE, Thomas BF, et al: Labeling accuracy of cannabidiol extracts sold online. : Labeling accuracy of cannabidiol extracts sold online.JAMA 318(17):1708-1709, 2017. doi:10.1001/jama.2017.11909

2. 2. Szaflarski JP, Bebin EM, Comi AM, et al: Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. : Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results.Epilepsia 59(8):1540-1548, 2018. doi:10.1111/epi.14477

3. 3. Szaflarski JP, Bebin EM, Cutter G, et al: Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. : Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study.Epilepsy Behav 87:131-136, 2018. doi:10.1016/j.yebeh.2018.07.020

4. 4. Mucke M, Phillips T, Radbruch L, Petzke F, Hauser W: Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 3(3):CD012182, 2018. Published 2018 Mar 7. doi:10.1002/14651858.CD012182.pub2

5. 5. Balachandran P, Elsohly M, Hill KP: Cannabidiol interactions with medications, illicit substances, and alcohol: a comprehensive review. : Cannabidiol interactions with medications, illicit substances, and alcohol: a comprehensive review.J Gen Intern Med 36(7):2074-2084, 2021. doi:10.1007/s11606-020-06504-8

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

1. National Institutes of Health (NIH), National Center for Complementary and Integrative Health: Cannabis (Marijuana) and Cannabinoids: What You Need To Know