Cannabidiol (also known as CBD and Epidiolex®) is one of the naturally-occurring cannabinoids found in the cannabis plant. It is one of some 113 identified cannabinoids in cannabis plants, accounting for up to 40% of the plant’s extract. It does not possess the same psychoactivity as tetrahydrocannabinol (THC), which is responsible for the euphoric and hallucinogenic aspects of cannabis, and is typically described as non-intoxicating. Cannabidiol can be administered by multiple routes, including by inhalation of cannabis smoke or vapor, as an aerosol spray into the cheek, and by mouth. It may be supplied as CBD oil containing only CBD as the active ingredient (i.e. no added THC or terpenes), a full-plant CBD-dominant hemp extract oil, capsules, dried cannabis, or as a prescription liquid solution. In the United States, the cannabidiol drug Epidiolex is approved by the Food and Drug Administration for the treatment of epilepsy disorders. The U.S. Drug Enforcement Administration has assigned Epidiolex a Schedule V classification, while non-Epidiolex CBD remains a Schedule I drug prohibited for any use. Cannabidiol is not scheduled under any United Nations drug control treaties. Subjective effects include anxiety suppression, muscle relaxation, and pain relief. Cannabidiol is generally well-tolerated with a good safety profile.However, it may have the potential to cause adverse drug-drug interactions. As a result, it is advised to use harm reduction practices if using this substance.
Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon endogenous cannabinoid receptors of the body. CBD accounts for up to 41% of the plant’s extract. Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the next to last step, where CBDA synthase performs catalysis instead of THCA synthase. At room temperature, cannabidiol is a colorless crystalline solid. It is practically insoluble in water.
The exact mechanism of action of CBD and THC is not currently fully understood. However, it is known that CBD acts on cannabinoid (CB) receptors of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems (such as the brain)). The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood. More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes. CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body. Allosteric modulators differ from receptor agonists in that they alter the activity of the receptor by binding to a functionally distinct binding site rather than directly to the receptor. In addition to the well-known activity on CB1 and CB2 receptors, there is further evidence that CBD also activates 5-HT1A/2A/3A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gamma-aminobutyric acid (GABA), and cellular uptake of anandamide, acts on mitochondria Ca2+ stores, blocks low-voltage-activated (T-type) Ca2+ channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH). The oral bioavailability of CBD is 13 to 19%, 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 and intestines by enzymes CYP2C19 and CYP3A4, and UGT1A7, UGT1A9, and UGT2B7 isoforms.