Cannabidiol may be an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain. It also may act as an inverse agonist of GPR3, GPR6, and GPR12. CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist. At higher concentrations, CBD acts as an inverse agonist of 5-HT1A receptors. It is an allosteric modulator of the μ- and δ-opioid receptors as well. The pharmacological effects of CBD may involve PPARγ agonism, inhibition of voltage-gated cation channels, and intracellular calcium release. Pharmacokinetics
The oral bioavailability of cannabidiol is approximately 6% in humans, while its bioavailability via inhalation is 11 to 45% (mean 31%). The elimination half-life of CBD is 18–32 hours. Cannabidiol is metabolized in the liver as well as in the intestines by the cytochrome P450 enzymes CYP2B6, CYP2C19, CYP2D6, CYP2J2, and CYP3A4, and by the isoenzymes UGT1A7, UGT1A9, and UGT2B7, forming a variety of metabolites such as 7-hydroxycannabidiol as well as the 6α- and 6β-hydroxy isomers and derivatives hydroxylated on the alkyl side chain, followed by glucuronidation. CYP3A4 facilitates decarbonylation of CBD to liberate carbon monoxide, a bioactive gasotransmitter and pharmaceutical candidate. CBD may have a wide margin in dosing. Pharmaceutical preparations
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.
United Nations
Cannabidiol is not scheduled under the Convention on Psychotropic Substances or any other UN drug treaties. In 2018, the World Health Organization recommended that CBD remain unscheduled. United States
As of 2021, cannabidiol extracted from marijuana remains a Schedule I Controlled Substance, and is not approved as a prescription drug or dietary supplement or allowed for interstate commerce in the United States. CBD derived from hemp (with 0.3% THC or lower) is legal to sell as a cosmetics ingredient or for other purposes not regulated by the FDA, but cannot be sold under federal law as an ingredient in food, dietary supplement, or animal feed. It is a common misconception that the legal ability to sell hemp (which may contain CBD), and hemp extracts and derivatives (including CBD), makes CBD legal for sale as a supplement or medicine.In September 2018, following its approval by the FDA for rare types of childhood epilepsy, the GW Pharmaceuticals drug Epidiolex was rescheduled (by the Drug Enforcement Administration) as a Schedule V drug to allow for its prescription use. Epidiolex still requires rescheduling in some states before it can be prescribed in those states.In 2013, a CNN program that featured Charlottes Web cannabis brought increased attention to the use of CBD in the treatment of seizure disorders. Since then, 16 states have passed laws to allow the use of CBD products with a physicians recommendation (instead of a prescription) for treatment of certain medical conditions.