Cannabidiol is the major nonpsychoactive ingredient in cannabis. Cannabidiol demonstrates a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties. Exact mechanism of action of cannabidiol is not known. GW Pharmaceuticals successfully developed the world's first prescription medicine derived from the cannabis plant, Sativex (buccal spray containing delta-9-tetrahydrocannabinol and cannabidiol) now approved in over 29 countries outside of the United States for the treatment of spasticity due to Multiple Sclerosis. GW Pharmaceuticals is developing Epidiolex (a liquid formulation of pure plant-derived cannabidiol) for certain rare and severe early-onset, drug-resistant epilepsy syndromes.

Cannabidiol:
https://drugs.ncats.io/drug/19GBJ60SN5

Cannabidiol: https://www.nonpsychotoxic.com/definition.php?term=cbd

Liver:
Cannabidiol is associated with frequent serum enzyme elevations during therapy particularly with higher doses but has not been linked to cases of clinically apparent liver injury with jaundice.

Cannabidiol Hepatotoxicity:
In prelicensure studies, serum aminotransferase elevations arose during cannabidiol therapy in 34% to 47% of patients compared to 18% of controls who were receiving other anticonvulsant medications. Elevations above 3 times ULN occurred in 13% of cannabidiol treated compared to 1% on placebo. ALT and AST elevations were more frequent with higher doses and were particularly common (and sometimes delayed) in patients who were receiving valproate and clobazam. The aminotransferase elevations typically arose within the first two months of treatment and were transient, mild-to-moderate in severity, and not associated with symptoms or jaundice. There have been no convincing reports of clinically apparent liver injury with jaundice attributable to cannabidiol, but it has had very limited general use.

E* Likelihood score: E* (unproven but suspected rare cause of clinically apparent liver injury).

Cannabidiol Overview:
https://www.ncbi.nlm.nih.gov/books/NBK548890/

Important Information:
Cannabidiol can harm your liver. Your liver function may need to be checked before and during treatment.

Call your doctor at once if you have symptoms such as:

• nausea
• vomiting
• loss of appetite
• right-sided upper stomach pain
• tiredness
• itching
• dark urine
• yellowing of the skin or eyes

Avoid driving or hazardous activity until you know how cannabidiol will affect you.

Some people have thoughts about suicide while taking cannabidiol. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

Drinking alcohol with cannabidiol can increase drowsiness.

Avoid driving or hazardous activity until you know how this medicine will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

Interactions:

Drug Interactions (536) Alcohol/Food Interactions (2) Disease Interactions (2)

What other drugs will affect Cannabidiol?
Using cannabidiol with other drugs that make you drowsy can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective. Tell your doctor about all your other medicines, especially:

• other seizure medications (especially clobazam or valproate)
• cannabis-based products

This list is not complete. Many other drugs can affect cannabidiol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.

A total of 536 drugs are known to interact with Cannabidiol.

• 9 major drug interactions
  • buprenorphine
  • leflunomide
  • levomethadyl acetate
  • lomitapide
  • mipomersen
  • pexidartinib
  • propoxyphene
  • sodium oxybate
  • teriflunomide
• 482 moderate drug interactions
• 45 minor drug interactions

Cannabidiol Drug Information:
https://www.drugs.com/mtm/cannabidiol.html

Pediatric:
Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of cannabidiol in children 1 year of age and older.

Safety and efficacy have not been established.

Geriatric:
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of cannabidiol in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Other Interactions:

• Ethanol

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol or drug abuse, history of
• Depression - Use with caution. May make these conditions worse

• Liver disease, moderate to severe - Use with caution. The effects may be increased because of the slower removal of the medicine from the body

Cannabidiol (Oral Route) (Epidiolex):
https://www.mayoclinic.org/drugs-supplements/cannabidiol-oral-route/description/drg-20443842

Breastfeeding:

Summary of Use During Lactation:
Cannabidiol is a component of cannabis.

Cannabidiol has not been studied in nursing women taking the pharmaceutical product, but it has been detected in the breastmilk of some mothers who used cannabis products.

Because no published information is available with cannabidiol use as an antiepileptic during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Alternate Drugs to Consider:

• (Seizure Disorder) Carbamazepine
• Divalproex
• Gabapentin
• Lamotrigine
• Oxcarbazepine
• Phenytoin
• Valproic Acid

Cannabidiol Drug Levels and Effects:
https://www.ncbi.nlm.nih.gov/books/NBK535598/

World Health Organization 2017:

• Cannabidiol (CBD) is one of the naturally occurring cannabinoids found in cannabis plants. It can also be produced synthetically.
• CBD can be converted totetrahydrocannabinol (THC)under experimental conditions; however, this does not appear to occur to any significant effectin patients undergoing CBD treatment.
• In experimental models of abuse liability, CBD appears to have little effect on conditioned place preference or intracranial self-stimulation. In an animal drug discrimination model CBD failed to substitute for THC. In humans, CBD exhibits no effects indicative of any abuse or dependence potential.
• CBD has been demonstrated as an effective treatment of epilepsy in several clinical trials,with one pure CBD product (Epidiolex) currently in Phase III trials.There is also preliminary evidence that CBD may be a useful treatment for a number of other medical conditions.
• There is unsanctioned medical use of CBD based products with oils, supplements, gums, and high concentration extracts available online for the treatment of many ailments.
• CBD is generally well tolerated with a good safety profile. Reported adverse effects may be as a result of drug-drug interactions between CBD and patients' existing medications.
• Several countries have modified their national controls to accommodate CBD as a medicinal product.
• To date, there is no evidence of recreational use of CBD or any public health related problems associated with the use of pure CBD.

World Health Organization Cannabidiol Pre-Review Report (PDF 27 pages):
https://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf

FDA Epidiolex (Cannabidiol) Medication Guide (PDF 30 pages):
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

Cannabidiol:

CBD does not have the same psychoactivity as THC, and may change the effects of THC on the body if both are present. Cannabidiol does not appear to have any intoxicating effects.

• A phytocannabinoid
• Discovered in 1940
• It is one of 113 identified cannabinoids in cannabis plants and accounts for up to 40% of the plant's extract.
• In the United States, the cannabidiol drug Epidiolex was approved by the Food and Drug Administration in 2018 for the treatment of two epilepsy disorders. Since cannabis is a Schedule I controlled substance in the United States, other CBD formulations remain illegal under federal law.
• Research indicates that cannabidiol may reduce adverse effects of THC, particularly those causing intoxication and sedation, but only at high doses.
• The World Anti-Doping Agency removed CBD from its banned substances list.

Cannabidiol can be taken in multiple ways, including by inhalation of cannabis smoke or vapor, as an aerosol spray into the cheek, and by mouth.

As of 2019, clinical research on CBD included studies related to anxiety, cognition, movement disorders, and pain, but there is insufficient high-quality evidence that cannabidiol is effective for these conditions.