Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of some 113 identified cannabinoids in cannabis plants, accounting for up to 40% of the plant's extract. As of 2018, preliminary clinical research on cannabidiol included studies of anxiety, cognition, movement disorders, and pain.
|Trade names||Sativex (with THC), Epidiolex|
|Synonyms||CBD, cannabidiolum, (−)-cannabidiol|
|AHFS/Drugs.com||International Drug Names|
|Inhalation (smoking, vaping), buccal (aerosol spray), oral (solution)|
|Bioavailability||• Oral: 13–19%|
• Inhaled: 31% (11–45%)
|Elimination half-life||18–32 hours|
|Chemical and physical data|
|Molar mass||314.464 g/mol g·mol−1|
|3D model (JSmol)|
|Melting point||66 °C (151 °F)|
Cannabidiol can be taken into the body in multiple ways, 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 (no added tetrahydrocannabinol [THC] or terpenes), a full-plant CBD-dominant hemp extract oil, capsules, dried cannabis, or as a prescription liquid solution. CBD does not have the same psychoactivity as THC, and may affect the actions of THC. Although in vitro studies indicate CBD may interact with different biological targets, including cannabinoid receptors and other neurotransmitter receptors, as of 2018 the mechanism of action for its biological effects has not been determined.
In the United States, the cannabidiol drug Epidiolex has been approved by the Food and Drug Administration for treatment of two epilepsy disorders. The side effects of long-term use of the drug include somnolence, decreased appetite, diarrhea, fatigue, malaise, weakness, sleeping problems.
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, and in 2018 the World Health Organization recommended that it remain unscheduled.
There has been little high-quality research into the use of cannabidiol for epilepsy, and what there is is limited to refractory epilepsy in children. While the results of using medical-grade cannabidiol in combination with conventional medication shows some promise, they did not lead to seizures being eliminated, and were associated with some minor adverse effects.
An orally administered cannabidiol solution (brand name Epidiolex) was approved by the US Food and Drug Administration in June 2018 as a treatment for two rare forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome.
Preliminary research on other possible therapeutic uses for cannabidiol include several neurological disorders, but the findings have not been confirmed by sufficient high-quality clinical research to establish such uses in clinical practice.
Preliminary research indicates that cannabidiol may reduce adverse effects of THC, particularly those causing intoxication and sedation, but only at high doses. Safety studies of cannabidiol showed it is well-tolerated, but may cause tiredness, diarrhea, or changes in appetite as common adverse effects. Epidiolex documentation lists sleepiness, insomnia and poor quality sleep, decreased appetite, diarrhea, and fatigue.
Laboratory evidence indicated that cannabidiol may reduce THC clearance, increasing plasma concentrations which may raise THC availability to receptors and enhance its effect in a dose-dependent manner. In vitro, cannabidiol inhibited receptors affecting the activity of voltage-dependent sodium and potassium channels, which may affect neural activity. A small clinical trial reported that CBD partially inhibited the CYP2C-catalyzed hydroxylation of THC to 11-OH-THC. Little is known about potential drug interactions but CBD-mediates decrease in clobazam metabolism.
Cannabidiol has low affinity for the cannabinoid CB1 and CB2 receptors. 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, and this action may be involved in its antidepressant, anxiolytic, and neuroprotective effects. 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.
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 as well as in the intestines by CYP2C19 and CYP3A4 enzymes, and UGT1A7, UGT1A9, and UGT2B7 isoforms. CBD may have a wide margin in dosing.
Nabiximols (brand name Sativex) is a patented medicine containing CBD and THC in equal proportions. The drug was approved by Health Canada in 2005 for prescription to treat central neuropathic pain in multiple sclerosis, and in 2007 for cancer related pain. 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."
Cannabidiol is insoluble in water but soluble in organic solvents such as pentane. At room temperature, it is a colorless crystalline solid. In strongly basic media and the presence of air, it is oxidized to a quinone. Under acidic conditions it cyclizes to THC, which also occurs during pyrolysis (smoking). The synthesis of cannabidiol has been accomplished by several research groups.
|Formal numbering||Terpenoid numbering||Number of stereoisomers||Natural occurrence||Convention on Psychotropic Substances Schedule||Structure|
|Short name||Chiral centers||Full name||Short name||Chiral centers|
|Δ5-Cannabidiol||1 and 3||2-(6-isopropenyl-3-methyl-5-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol||Δ4-Cannabidiol||1 and 3||4||No||Unscheduled|
|Δ4-Cannabidiol||1, 3 and 6||2-(6-isopropenyl-3-methyl-4-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol||Δ5-Cannabidiol||1, 3 and 4||8||No||Unscheduled|
|Δ3-Cannabidiol||1 and 6||2-(6-isopropenyl-3-methyl-3-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol||Δ6-Cannabidiol||3 and 4||4||?||Unscheduled|
|Δ3,7-Cannabidiol||1 and 6||2-(6-isopropenyl-3-methylenecyclohex-1-yl)-5-pentyl-1,3-benzenediol||Δ1,7-Cannabidiol||3 and 4||4||No||Unscheduled|
|Δ2-Cannabidiol||1 and 6||2-(6-isopropenyl-3-methyl-2-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol||Δ1-Cannabidiol||3 and 4||4||Yes||Unscheduled|
|Δ1-Cannabidiol||3 and 6||2-(6-isopropenyl-3-methyl-1-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol||Δ2-Cannabidiol||1 and 4||4||No||Unscheduled|
Society and cultureEdit
Food and beverageEdit
Food and beverage products containing CBD were introduced in the United States in 2017. Similar to energy drinks and protein bars which may contain vitamin or herbal additives, food and beverage items can be infused with CBD as an alternative means of ingesting the substance. In the United States, numerous products are marketed as containing CBD, but in reality contain little or none. Some companies marketing CBD-infused food products with claims that are similar to the effects of prescription drugs have received warning letters from the Food and Drug Administration for making unsubstantiated health claims. In February 2019, the New York City Department of Health announced plans to fine restaurants that sell food or drinks containing CBD, beginning in October 2019.
Selective breeding of cannabis plants has expanded and diversified as commercial and therapeutic markets develop. Some growers in the U.S. 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 USA, 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.
CBD does not appear to have any psychotropic ("high") effects such as those caused by ∆9-THC in marijuana, but may have anti-anxiety and anti-psychotic effects. As the legal landscape and understanding about the differences in medical cannabinoids unfolds, experts are working to distinguish "medical marijuana" (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.
Various strains of "medical marijuana" are found to have a significant variation in the ratios of CBD-to-THC, and are known to contain other non-psychotropic cannabinoids. Any psychoactive marijuana, regardless of its CBD content, is derived from the flower (or bud) of the genus Cannabis. 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. Certain standards are required for legal growing, cultivating, and producing the hemp plant. 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%.
In the United States, CBD's legal status depends on the source from which it is derived. When derived from marijuana it is a schedule 1 controlled substance under the federal Controlled Substances Act (CSA). This is because the CSA's definition of marijuana (spelled "marihuana") includes "all parts" of the cannabis plant. When it is the investigative new drug Epidiolex it is schedule 5 (see below). However, when CBD is derived from hemp or some other lawful source it is not a controlled substance. Section 10113 of the Agricultural Improvement Act of 2018 defines "hemp" as "the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis." Hemp is excluded from the definition of marijuana under the Controlled Substances Act (CSA). CBD is not specifically scheduled in the CSA. It is therefore lawful when derived from hemp, which is not a controlled substance and the definition of which includes "cannabinoids". CBD is a cannabinoid.
In September 2018, following its approval by the FDA for rare types of childhood epilepsy, Epidiolex was rescheduled (by the Drug Enforcement Administration) as a Schedule V drug to allow for its prescription use. This change applies only to FDA-approved products containing no more than 0.1 percent THC. This allows GW Pharmaceuticals to sell Epidiolex, but it does not apply broadly and all other CBD-containing products remain Schedule I drugs. Epidiolex still requires rescheduling in some states before it can be prescribed in those states.
A CNN program that featured Charlotte's Web cannabis in 2013 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 doctor's recommendation (instead of a prescription) for treatment of certain medical conditions. This is in addition to the 30 states that have passed comprehensive medical cannabis laws, which allow for the use of cannabis products with no restrictions on THC content. Of these 30 states, eight have legalized the use and sale of cannabis products without requirement for a doctor's recommendation.
Some manufacturers ship CBD products nationally, an illegal action which the FDA has not enforced in 2018, with CBD remaining the subject of an FDA investigational new drug evaluation, and is not considered legal as a dietary supplement or food ingredient as of December 2018[update]. Federal illegality has made it difficult historically to conduct research on CBD. CBD is openly sold in head shops and health food stores in some states where such sales have not been explicitly legalized.
The 2014 Farm Bill legalized the sale of "non-viable hemp material" grown within states participating in the Hemp Pilot Program. This legislation defined hemp as cannabis containing less than 0.3% of THC delta-9, grown within the regulatory framework of the Hemp Pilot Program. The 2018 Farm Bill allowed for interstate commerce of hemp derived products, though these products still fall under the purview of the FDA.
Prescription medicine (Schedule 4) for therapeutic use containing 2 per cent (2.0%) or less of other cannabinoids commonly found in cannabis (such as ∆9-THC). A schedule 4 drug under the SUSMP is Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription.
Following a change in legislation in 2017, CBD was changed from a schedule 9 drug to a schedule 4 drug, meaning that it is legally available in Australia.
The passing of the Misuse of Drugs (Medicinal Cannabis) Amendment Act in December 2018 means some products containing cannabidiol (CBD) are now prescription medicines only.
Cannabidiol is no longer a controlled drug in New Zealand under the Misuse of Drugs Act. It is a prescription medicine under the Medicines Act provided the product contains no more than two percent THC of total CBD.
In 2017 under the previous government, Associate Health Minister Peter Dunne had made changes to the regulations so that restrictions would be removed, which meant a doctor was able to prescribe cannabidiol to patients.
In 2019, the European Commission announced that CBD and other cannabinoids would be classified as "novel foods", meaning that CBD products would require authorization under the EU Novel Food Regulation stating: because "this product was not used as a food or food ingredient before 15 May 1997, before it may be placed on the market in the EU as a food or food ingredient, a safety assessment under the Novel Food Regulation is required." The recommendation – applying to CBD extracts, synthesized CBD, and all CBD products, including CBD oil – was scheduled for a final ruling by the European Commission in March 2019. If approved, manufacturers of CBD products would be required to conduct safety tests and prove safe consumption, indicating that CBD products would not be eligible for legal commerce until at least 2021.
Cannabidiol is listed in the EU Cosmetics Ingredient Database (CosIng). However, the listing of an ingredient, assigned with an INCI name, in CosIng does not mean it is to be used in cosmetic products or is approved for such use.
CBD is classified as a medical product in Sweden.
Cannabidiol, in an oral-mucosal spray formulation combined with delta-9-tetrahydrocannabinol, is a product available (by prescription only until 2017) for relief of severe spasticity due to multiple sclerosis (where other anti-spasmodics have not been effective).
Until 2017, products containing cannabidiol marketed for medical purposes were classed as medicines by the UK regulatory body, the Medicines and Healthcare products Regulatory Agency (MHRA) and could not be marketed without regulatory approval for the medical claims. As of 2018[update], cannabis oil is legal to possess, buy, and sell in the UK, providing the product does not contain more than 0.2% THC and is not advertised as providing a medicinal benefit.
In January 2019, the UK Food Standards Agency indicated it would regard CBD products, including CBD oil, as a novel food in the UK, having no history of use before May 1997, and indicating such products must have authorization and proven safety before being marketed.
While THC remains illegal, CBD is not subject to the Swiss Narcotic Acts because this substance does not produce a comparable psychoactive effect. Cannabis products containing less than 1% THC can be sold and purchased legally.
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