In the United States, the Food and Drug Administration (FDA) has indicated only one brand of prescription cannabidiol, sold under the brand name Epidiolex, for the treatment of seizures associated with Dravet syndrome, Lennox–Gastaut syndrome, or tuberous sclerosis complex in people one year of age and older.^[31][32][33] While Epidiolex treatment is generally well tolerated, it is associated with minor adverse effects, such as gastrointestinal upset, decreased appetite, lethargy, sleepiness, and poor sleep quality.^{[4][32][34][33]}

In the European Union, Epidyolex is indicated for use as adjunctive therapy of seizures associated with Lennox–Gastaut syndrome or Dravet syndrome, in conjunction with clobazam, for people aged two years of age and older.^[11] In 2020, the label for Epidiolex in the US was expanded to include seizures associated with tuberous sclerosis complex. Epidiolex/Epidyolex is the first prescription formulation of plant-derived cannabidiol approved by regulatory bodies in the US and Europe.^[35]

CBD demonstrates potent antimicrobial properties primarily against Gram-positive bacteria, including several ESKAPE pathogens, by disrupting their cell membrane.^[36] While generally ineffective against Gram-negative bacteria due to their protective outer membrane, CBD has shown some activity against specific Gram-negative pathogens like Legionella pneumophila, Moraxella catarrhalis, and Neisseria species. The efficacy of CBD has been demonstrated in topical applications using ex vivo pig skin and mouse models, highlighting its potential as a therapeutic agent.^[37][36]

Health benefits for CBD beyond its approved medical uses are unproven; there are potential risks like liver damage and drug interactions if used during pregnancy or breastfeeding.^[38][21]

CBD may help with pain, sleep, and addiction, potentially serving as a non-intoxicating alternative to opioids, but clinical evidence is limited and legal regulations are complex.^[20][39]

There is very limited evidence on CBD use in mental disorders, and current studies do not show clear benefits for treating any mental illness or disorder.^[19]

CBD is strongly advised against during pregnancy or breastfeeding due to unknown effects on fetal and infant development.^[38]

Cannabidiol does not appear to have any intoxicating effects^[40] such as those caused by ∆⁹-THC in cannabis, but it is under preliminary research for its possible anxiolytic and antipsychotic effects.^[19][20][25] As the legal landscape and understanding about the differences in medical cannabinoids unfolds, experts are working to distinguish “medical cannabis” (with varying degrees of psychotropic effects and deficits in executive function) from “medical CBD therapies”, which would commonly present as having a reduced or non-psychoactive side-effect profile.^[20][25][41]

Various strains of “medical cannabis” are found to have a significant variation in the ratios of CBD-to-THC and are known to contain other non-psychotropic cannabinoids.^[42] Any psychoactive cannabis, regardless of its CBD content, is derived from the flower (or bud) of the genus Cannabis. As defined by US federal law, non-psychoactive hemp (also commonly termed “industrial hemp“), regardless of its CBD content, is any part of the cannabis plant, whether growing or not, containing a ∆⁹–tetrahydrocannabinol concentration of no more than 0.3% on a dry-weight basis.^[43] In the United States, certain standards are required for legal growing, cultivating, and producing the hemp plant, but there are no federal standards for quality being enforced in the hemp industry. Certain state regulations are in place, but vary state to state.^[44] For instance, the Colorado Industrial Hemp Program registers growers of industrial hemp and samples crops to verify that the dry-weight THC concentration does not exceed 0.3%.^[43]

Nabiximols (brand name Sativex), an oromucosal spray made of a complex botanical mixture containing cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), and additional cannabinoid and non-cannabinoid constituents from cannabis sativa plants, was approved by Health Canada in 2005, to treat central neuropathic pain in multiple sclerosis, and in 2007, for cancer-related pain.^[45] In New Zealand, Sativex is “approved for use as an add-on treatment for symptom improvement in people with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication.”^[46]

Epidiolex (Epidyolex in Europe) is an orally administered cannabidiol solution.^[4][11] It was approved in 2018 for treatment of two rare forms of childhood epilepsy, Lennox–Gastaut syndrome and Dravet syndrome, and seizures associated with tuberous sclerosis complex.^[4][11] In the US, it is approved in these indications for people one year of age and older.^[4]

In vitro, cannabidiol has low affinity for, and acts as a negative allosteric modulator of the CB₁ cannabinoid receptor^[63][64]

Cannabidiol may be an antagonist of GPR55, a G protein-coupled receptor and putative non-homologous CB₃ cannabinoid receptor shown by in vitro studies to be widely distributed in the brain.^[65][66][67] Cannabidiol may interact with various neurotransmitters, such as serotonin, dopamine, and GABA.^[65][66][68]

As of 2024, the cellular effects and mechanisms of cannabidiol in vivo are unknown,^[4][11] as research to date has been inconclusive and based on laboratory studies.^[65] The anticonvulsant effects provided by cannabidiol (Epidiolex) in people with certain forms of epilepsy do not appear to involve cannabinoid receptors.^[4] A possible mechanism for the effects of cannabidiol on seizures is by affecting the neuronal movement of calcium in brain structures involved in the excessive electrical activity of seizures.^[11]

The oral bioavailability of cannabidiol is approximately 6% in fasting state and 36.5–57.3% in fed-state^[69] in humans, while its bioavailability via inhalation is 11–45% (mean 31%).^{[12][13][69][70]} The oral bioavailability of cannabidiol varies based on several factors such as formulation,^[70] dose, and food intake.^[69] The sublingual bioavailability of cannabidiol is approximately 12–35%.^[14] The elimination half-life of cannabidiol in blood is 56–61 hours after oral doses twice per day over 7 days.^[4] Based on the pharmacokinetic analysis of long-term dosing of cannabidiol in humans, the terminal elimination half-life is estimated to be >134 hours.^[69] Cannabidiol is metabolized in the liver as well as in the intestines by cytochrome P450 enzymes.^[4][66]