When taken by mouth: Cannabidiol is POSSIBLY SAFE when taken by mouth or sprayed under the tongue appropriately. Cannabidiol in doses of up to 300 mg daily have been taken by mouth safely for up to 6 months. Higher doses of 1200-1500 mg daily have been taken by mouth safely for up to 4 weeks. A prescription cannabidiol product (Epidiolex) is approved to be taken by mouth in doses of up to 10-20 mg/kg daily. Cannabidiol sprays that are applied under the tongue have been used in doses of 2.5 mg for up to 2 weeks.
Selective breeding of cannabis plants has expanded and diversified as commercial and therapeutic markets develop. Some growers in the US succeeded in lowering the proportion of CBD-to-THC to accommodate customers who preferred varietals that were more mind-altering due to the higher THC and lower CBD content. In the US, hemp is classified by the federal government as cannabis containing no more than 0.3% THC by dry weight. This classification was established in the 2018 Farm Bill and was refined to include hemp-sourced extracts, cannabinoids, and derivatives in the definition of hemp.
Cannabidiol has low affinity for the cannabinoid CB1 and CB2 receptors, although it can act as an antagonist of CB1/CB2 agonists despite this low affinity. 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. It is an allosteric modulator of the μ- and δ-opioid receptors as well. The pharmacological effects of CBD may involve PPARγ agonism and intracellular calcium release.
However, when cannabinoids are taken externally, it’s difficult to distinguish between the clinically desirable effects and the therapeutically undesirable effects of various phytocannabinoids. This is because cannabinoid receptors send a variety of signals that often interconnect to coordinate the body’s functions, so it’s hard to tell them apart.
In the United States, the cannabidiol drug Epidiolex was approved by the Food and Drug Administration in 2018 for treatment of two epilepsy disorders. Since cannabis is a Schedule I controlled substance in the United States, other CBD formulations remain illegal to prescribe for medical use or to use as an ingredient in foods or dietary supplements. cannabidiol oil